@article {pmid41646110, year = {2024}, author = {Kennedy, J and Iyer, K and Grinspan, A and Lai, J}, title = {Safe and successful fecal microbiota transplantation for recurrent Clostridioides difficile infection in a child with an intestinal transplant.}, journal = {Intestinal Failure (New York, N.Y.)}, volume = {4}, number = {}, pages = {100046}, pmid = {41646110}, issn = {2950-4562}, abstract = {Fecal microbiota transplantation (FMT) treats patients with recurrent Clostridioides difficile infections (CDI) by restoring the colonic flora with a balanced microbiome. There are currently no reports of safe and successful FMT in pediatric patients with history of intestinal transplant on immunosuppression. Our case report describes a 6-year-old boy with a multi-visceral transplant (including: stomach, small bowel, colon, liver, pancreas, and en-bloc bilateral kidneys) who had recurrent CDI episodes treated with antibiotics (including prolonged tapers). After multiple recurrences, he had a FMT via colonoscopy. The fecal preparation was inserted in the transplanted cecum without complication. The patient did well without any adverse events or need for hospitalization and the FMT was a success, as he had no recurrent symptoms in the 3 months following FMT.}, } @article {pmid41646037, year = {2026}, author = {Syllaios, A and Papadakos, SP and Ioannou, A and Frountzas, M and Michelakis, D and Patsouras, D and Dritsas, S and Pramateftakis, MG and Schizas, D}, title = {Slow Transit Constipation: Pathophysiological Perspectives and Management Updates.}, journal = {Journal of digestive diseases}, volume = {}, number = {}, pages = {}, doi = {10.1111/1751-2980.70030}, pmid = {41646037}, issn = {1751-2980}, abstract = {Slow transit constipation (STC) is a chronic colonic motility disorder characterized by markedly delayed transit, leading to reduced bowel movements, abdominal discomfort, and significant quality-of-life impairment. It predominantly affects women and is associated with abnormalities in enteric neuronal signaling, smooth muscle contractility, interstitial cells of Cajal, gut peptides, bile acid homeostasis, and autonomic regulation. Secondary causes of constipation and structural lesions must be excluded before the diagnosis of STC, with colonic transit studies serving as the gold standard. Complementary investigations such as anorectal manometry and defecography help detect coexisting outlet obstruction, which can alter management. The treatment of STC should follow a stepwise approach, beginning with dietary and lifestyle modification, osmotic and stimulant laxatives, and prokinetics such as prucalopride. Secretagogues and bile acid modulators may offer additional benefit. Biofeedback therapy is primarily indicated for overlapping dyssynergic defecation. For refractory STC, interventional therapies, such as fecal microbiota transplantation, acupuncture, sacral nerve stimulation, and transanal irrigation, are found to have equivocal outcomes. Antegrade continence enema procedures can be an alternative for patients unsuitable for colectomy. Surgical options, including subtotal colectomy with ileosigmoid or cecorectal anastomosis, and total colectomy with ileorectal anastomosis, are reserved for carefully selected patients with medically intractable symptoms, following thorough physiological evaluation. Although advances in understanding STC pathophysiology are guiding novel therapeutic development, robust randomized controlled trials remain scarce. Optimal care requires multidisciplinary collaboration between gastroenterologists, colorectal surgeons, and pelvic floor specialists to ensure accurate diagnosis, tailored treatment, and improved long-term outcomes.}, } @article {pmid41645327, year = {2026}, author = {Zubair, A and Alkahtani, AM and Shahani, MY and Afghan, N}, title = {Gut microbiome-based strategies for HIV prevention and therapy, current challenges and future prospects.}, journal = {Gut pathogens}, volume = {18}, number = {1}, pages = {11}, pmid = {41645327}, issn = {1757-4749}, abstract = {The gut microbiome has become a primary controller of host immunity as well as the pathogenesis of human immunodeficiency virus (HIV) infection. Commensal microbes in healthy persons keep the intestinal and other body barriers intact and regulate mucosal and systemic immune responses and generate metabolites, including short-chain fatty acids and indole derivatives that suppress inflammation and stimulate epithelial healing. These functions are impaired by HIV infection via depletion of gut CD4 + T cells, damage caused to epithelium, microbial translocation, and microbiota disruption. In this review article, we summarize recent studies suggesting that a balanced microbiome can mitigate HIV susceptibility and progression by preserving mucosal defenses, limiting systemic immune activation, and generating antiviral compounds. Other interventions, including probiotics, prebiotics, dietary modulation, and fecal microbiota transplantation (FMT), have been trialed with mixed outcomes in most cases, showing small but significant changes in the gut microbial composition and/or inflammatory markers. Current evidence highlights the potential of microbiome-targeted strategies to support HIV management; however, substantial gaps remain. Future research should focus on defining protective microbial signatures, developing next-generation live biotherapeutics, exploring metabolite-based therapies, and conducting large, mechanistically driven clinical trials. Harnessing the microbiome's protective functions could offer novel approaches to reducing HIV transmission, mitigating inflammation, and improving immune reconstitution in infected individuals.}, } @article {pmid41645047, year = {2026}, author = {Thalib, HI and Fatima, N and Fakruddin, FH and Ali, HH and Khan, S and Zubair, MTM and Pereira, M and Sayed Hassan, FE}, title = {Modulating the Gut Microbiome as a Therapeutic Approach in Multiple Sclerosis: Implications for Gut-Brain Interactions and Immune Pathways: A Narrative Review.}, journal = {Brain and behavior}, volume = {16}, number = {2}, pages = {e71254}, doi = {10.1002/brb3.71254}, pmid = {41645047}, issn = {2162-3279}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/immunology ; *Multiple Sclerosis/immunology/microbiology/therapy/metabolism ; Animals ; *Dysbiosis/immunology ; *Brain-Gut Axis ; Probiotics ; Brain/immunology ; }, abstract = {PURPOSE: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by progressive disability. Emerging evidence has implicated gut microbiome dysbiosis, characterized by decreased short-chain fatty acids (SCFAs)-producing taxa and increased pro-inflammatory species, in disturbed immune signaling, T-helper17/T-regulatory cells imbalance, disturbed tryptophan metabolism, and disrupted integrity of the blood-brain barrier. In this review, we summarize the mechanistic and therapeutic insights from studies that have explored the gut microbiome in MS.

METHOD: We performed a literature search in PubMed, Scopus, Web of Science, and ClinicalTrials.gov from database inception to January 2025; only English-language articles were included, comprising human MS cohorts and preclinical experimental autoimmune encephalomyelitis models. Of these, approximately 95 human and preclinical studies fulfilled the inclusion criteria. Evidence synthesis was narrative, without meta-analysis.

FINDING: There has been a consistent depletion of beneficial genera such as Faecalibacterium and Roseburia, expansion of Akkermansia muciniphila, and reduction in microbial metabolites such as butyrate, propionate, and neuroactive indole derivatives in MS patients across studies. These changes promote intestinal permeability, exaggerated pro-inflammatory cytokine responses, and microglial activation. The therapeutic approach of restoring microbial balance includes therapies such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and dietary interventions. Early trials have shown modest improvements in relapse rates, fatigue, immune profiles, and microbiome composition. Results across randomized studies are heterogeneous, with no significant clinical benefit in several. Pilot trials report modest reductions in relapse rate (RR ≈ 0.85) and fatigue (Cohen's d ≈ 0.3), but several double‑blind RCTs showed no significant benefit (p  >  0.05) in up to 40% of participants, highlighting variable effect sizes.

CONCLUSION: Interventions aimed at the microbiome are promising as adjunct approaches to the treatment of MS, acting principally through the restoration of SCFAs, immune modulation, and strengthening of the gut-brain axis. Larger, longer-term randomized trials are required to confirm clinical efficacy, define responder phenotypes, and inform personalized microbiome-based therapies.}, } @article {pmid41644796, year = {2026}, author = {Krukowski, H and Valkenburg, S and Vich Vila, A and Maciel, LF and Vázquez-Castellanos, JF and Gryp, T and Joossens, M and Van Biesen, W and Verbeke, F and Derrien, M and Huys, GRB and Glorieux, G and Raes, J}, title = {Host factors dictate gut microbiome alterations in chronic kidney disease more strongly than kidney function.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {41644796}, issn = {2058-5276}, support = {860329//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 860329//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 860329//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 860329//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 860329//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 101149152//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; G017815N//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; G017815N//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; G017815N//Fonds Wetenschappelijk Onderzoek (Research Foundation Flanders)/ ; }, abstract = {Despite recent progress, microbial associations reported in chronic kidney disease (CKD) remain inconsistent. Here we combined quantitative faecal metagenomics (n = 130) and cross-study biomarker comparisons (ntotal = 4,420) to study microbiome associations with estimated glomerular filtration rate (eGFR; kidney function) and 4-year CKD progression. Intestinal transit time (ITT) and medications significantly explained microbiome variation, surpassing eGFR-related effects. Lower eGFR was associated with increased p-cresol and indole biosynthetic potential and reduced plant-to-animal CAZyme ratios. This was consistent with community-wide saccharolytic-to-proteolytic microbiome transitions linked to dietary guidelines and slowed-down ITT. Peritoneal dialysis patients showed distinct microbiome dysbiosis accompanied by increased intestinal inflammation. Only Escherichia coli, an unnamed Alistipes species and Bifidobacterium adolescentis were covariate-independent markers for eGFR, but neither these nor previous microbial markers convincingly replicated across 11 studies. No predictors for CKD progression were found. Nevertheless, our study adds insight into plausible ITT and nutrition-related effects, highlighting their potential in CKD interventions.}, } @article {pmid41644742, year = {2026}, author = {Ziogas, DC and Theocharopoulos, C and Martinos, A and Lyrarakis, G and Stefanou, D and Anastasopoulou, A and Gogas, H}, title = {Toward Microbiome-Informed Melanoma Care: The Gut Microbiota in Melanoma Evolution, Immunotherapy Response and Immune-Related Toxicity.}, journal = {Current oncology reports}, volume = {28}, number = {1}, pages = {10}, pmid = {41644742}, issn = {1534-6269}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/drug effects ; *Melanoma/immunology/therapy/microbiology/pathology ; *Immunotherapy/adverse effects/methods ; *Immune Checkpoint Inhibitors/adverse effects/therapeutic use ; }, abstract = {PURPOSE OF REVIEW: The gut microbiome (GM) has emerged as a pivotal modulator of melanoma pathogenesis and progression through its influence on systemic inflammation, immune surveillance, and antitumor immunity. Inter-individual variability in GM composition may underlie differences in immune checkpoint inhibitor (ICI) responsiveness and the development of immune-related adverse events (irAEs). This review aims to synthesize current knowledge on the complex interplay between the GM, host immunity, and melanoma, emphasizing its relevance to disease development, therapeutic response, and toxicity.

RECENT FINDINGS: Both preclinical and clinical evidence have demonstrated that alterations in microbial diversity and composition can affect melanoma outcomes. Depletion or imbalance of specific microbial taxa has been linked to an increased risk of melanoma development or, conversely, to reduced tumor burden. In patients treated with ICIs, distinct taxonomic GM signatures have been correlated with therapeutic efficacy and the likelihood of developing irAEs. Emerging studies have also explored strategies to modulate the GM-including diet, antibiotics, probiotics, and fecal microbiota transplantation-to restore gut "eubiosis" and enhance antitumor immune responses. The intricate crosstalk between the gut microbiome, host immunity, and melanoma significantly influences disease biology and treatment outcomes. A deeper understanding of these interactions will be critical to the development of microbiome-informed, personalized approaches to melanoma management and immunotherapy optimization.}, } @article {pmid41644553, year = {2026}, author = {Wen, R and Xin, Y and Bao, S and Zhang, X and Wang, Q and Dang, Z and Zhou, Z and Wu, J and Song, D and Fu, L and Li, W and Niu, J and Wen, Y and Zhou, X and Han, M and Zhao, J}, title = {The gut microbiota mediates depression-like behaviors in mice with chronic Echinococcus multilocularis infection.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-026-00929-5}, pmid = {41644553}, issn = {2055-5008}, support = {NO. 32160181//National Natural Science Foundation of China/ ; 2022AAC02076//Ningxia Natural Science Found Project/ ; 2024BEG02028//Key research and development projects of the Ningxia Hui Autonomous Region/ ; }, abstract = {Alveolar echinococcosis (AE), a chronic parasitic disease caused by Echinococcus multilocularis (E. multilocularis), remains poorly characterized with respect to central nervous system (CNS) involvement, and its long-term effects on mental health have not been systematically investigated. In this study, we established a BALB/c mouse model of chronic E. multilocularis infection and applied an integrative framework combining behavioral assessments, histomorphological analyses (hematoxylin-eosin staining, Nissl staining, and transmission electron microscopy), cytometric bead array (CBA), and multi-omics approaches (16S rRNA sequencing, metagenomics, and untargeted metabolomics) to investigate infection-induced neuroimmune-gut microbiota interactions. Chronically infected mice exhibited pronounced depression-like behavioral phenotypes, accompanied by hippocampal neuronal nuclear membrane atrophy and disrupted microglial homeostasis. Both peripheral and central inflammatory profiling revealed elevated levels of pro-inflammatory mediators, particularly IL-6 and MCP-1, suggesting coordinated systemic immune activation and neuroimmune alterations. Notably, fecal microbiota transplantation (FMT) from infected donors was sufficient to induce depression-like behaviors in recipient mice, supporting a contributory role of infection-associated gut microbiota alterations in behavioral abnormalities. Integrated multi-omics analyses further revealed a marked reduction in Lactobacillus abundance in infected mice, which was positively correlated with decreased levels of key metabolites within the tryptophan/5-hydroxytryptamine (5-HT) metabolic pathway. Collectively, these findings suggest that chronic E. multilocularis infection may be associated with depression-like behaviors through gut microbiota dysbiosis and related metabolic perturbations. This study provides initial insights into the potential mechanisms underlying neuropsychiatric complications in AE and proposes a conceptual framework for future investigations into early intervention and microbiota-targeted therapeutic strategies.}, } @article {pmid41643874, year = {2026}, author = {Liu, K and Ren, Y and Liu, Y and Zhang, Y}, title = {Scutellaria baicalensis Georgi and Its Active Component Scutellarin Alleviate Asthma in Rats by Modulating the Gut Microbiota-Bile Acid Axis.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {121304}, doi = {10.1016/j.jep.2026.121304}, pmid = {41643874}, issn = {1872-7573}, abstract = {The Complete Works of Jingyue recorded that Scutellaria baicalensis Georgi (SBG, Huangqin) cleared heat and relieved asthma from Ming Dynasty. SBG possess a long history of medicinal use and have demonstrated efficacy in treating respiratory diseases. Building on these traditional applications, recent studies have reported its anti-asthmatic. Yet, it's unclear whether SBG improves asthma via gut microbiota modulation or which component is key.

AIM OF THE STUDY: This study established an asthma model and employed 16S rRNA sequencing and metabolomics approaches to investigate the active components and underlying mechanisms of SBG in the treatment of bronchial asthma through gut-lung axis.

MATERIALS AND METHODS: An innovative combined approach was employed, utilizing Ultra-high-performance liquid chromatography/Q/Q/Q Exactive HFX mass spectrometry (UHPLC-QE-MS), 16S rRNA sequencing, metabolomics, and molecular biology to analyze the effective components of SBG, the changes in gut microbiota, and the endogenous metabolic mechanisms involved in the improvement of bronchial asthma.

RESULTS: SBG and scutellarin reduced airway (Rrs) and elastic resistance (Ers) (P<0.05) in asthmatic rats, alleviated lung inflammation, and decreased serum IL-2 levels (P<0.05). They also mitigated mucosal damage and inflammatory infiltration, restoring colonic homeostasis and increasing beneficial gut bacteria. Multi-omics analysis suggested SBG acts through the bile acid pathway, modulating bile salt transformation, biosynthesis, and transport. Fecal microbiota transplantation (FMT) from treated rats to germ-free rats partially replicated the anti-asthma effects, indicating SBG and scutellarin inhibit asthma by up-regulating Bifidobacterium animalis. This bacterium produced cholic acid, especially when treated with SBG or scutellarin, showing anti-inflammatory and anti-allergic properties.

CONCLUSION: SBG and its core blood-absorbed component scutellarin augment Bifidobacterium animalis, stimulate cholic acid production, modulate the bile acid pathway, and alleviate pulmonary inflammation and allergic reactions, exerting anti-asthma effects.}, } @article {pmid41642539, year = {2026}, author = {Shenthilvel, RK and Umashankar, TA and Uvarajan, D and Mathuraj, M and Ravikumar, M}, title = {"Unfolding Parkinson's Disease Through the Microbiome-Gut-Brain Axis".}, journal = {Journal of molecular neuroscience : MN}, volume = {76}, number = {1}, pages = {25}, pmid = {41642539}, issn = {1559-1166}, mesh = {Humans ; *Parkinson Disease/microbiology/therapy/metabolism ; *Gastrointestinal Microbiome ; Animals ; *Brain/metabolism ; *Brain-Gut Axis ; }, abstract = {Parkinson's disease (PD) is a progressive and multifactorial neurodegenerative disorder primarily caused by the loss of dopaminergic neurons in the substantia nigra. This neuronal loss leads to characteristic motor symptoms such as tremors, rigidity, and slowness of movement. Although PD has long been regarded as a disorder originating in the brain, recent findings suggest that the gut-brain axis, the intricate communication network between the gastrointestinal tract and the central nervous system also plays an important role in the development and progression of PD. Interestingly, early non-motor symptoms such as constipation and other bowel irregularities often appear several years before the onset of motor symptoms, indicating that changes in gut function may precede and even contribute to neurodegeneration. The gut microbiota influences neuronal signaling, immune activity, and metabolic balance through neuroactive molecules such as neurotransmitters, short-chain fatty acids (SCFAs), and cytokines. In PD, microbial imbalance, intestinal barrier dysfunction, and chronic inflammation are closely linked to the misfolding and accumulation of α-synuclein (α-syn), which can spread from the gut to the brain through the vagus nerve in a prion-like manner. Current therapeutic approaches are increasingly exploring ways to restore gut microbial balance using probiotics, prebiotics, dietary interventions, fecal microbiota transplantation (FMT), and SCFA supplementation. These strategies not only aim to relieve symptoms but may also have the potential to slow disease progression. This review discusses the mechanisms through which the gut-brain axis contributes to PD, summarizes key clinical and preclinical findings, and highlights emerging gut-targeted therapeutic approaches.}, } @article {pmid41642500, year = {2026}, author = {Wang, J and Xie, S and Li, Z and Jiang, S and Wang, Q and Qi, R}, title = {Dynamic changes in gut microbiota and identification of inflammation-associated biomarkers in high-fat diet-induced obese mice.}, journal = {Antonie van Leeuwenhoek}, volume = {119}, number = {3}, pages = {50}, pmid = {41642500}, issn = {1572-9699}, support = {U21A20245//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Diet, High-Fat/adverse effects ; *Obesity/microbiology/etiology ; Mice ; *Inflammation/microbiology/metabolism ; Biomarkers ; Male ; Feces/microbiology ; Mice, Inbred C57BL ; Bacteria/classification/genetics/isolation & purification ; Fecal Microbiota Transplantation ; Mice, Obese ; }, abstract = {This study aimed to analyze the dynamic changes in gut microbiota during high-fat diet (HFD)-induced obesity in mice, investigate the transmissibility of obesity-associated inflammation via fecal microbiota transplantation (FMT), and identify key bacterial genera linked to inflammation. In experiment 1, 8 control group mice and 12 obese group mice were fed a normal diet (ND) and a HFD, respectively, and fecal samples were collected from six mice in each group at weeks 4, 8, and 12. The results showed that long-term HFD (12 weeks) significantly reduced the diversity and richness of the gut microbiota (p < 0.05). HFD significantly affected the composition of the gut microbiota during the experimental period, with an increase in the relative abundance of harmful bacteria genera such as Escherichia-Shigella and Proteus (p < 0.05). In experiment 2, the transmissibility of obesity-associated inflammation was validated through a fecal FMT experiment. The results indicated that the intestinal microbiota of obese mice increased the inflammation level of recipient mice (p < 0.05), and the composition of the intestinal microbiota in the obese recipient group was significantly affected by that in the obese donor group. Furthermore, correlation analysis revealed that the relative abundances of Proteus and Escherichia-Shigella were positively correlated with the levels of inflammatory factors in the serum and ileal tissue (p < 0.05), suggesting that these two bacterial genera may serve as potential pro-inflammatory biomarkers. This study revealed the dynamic changes in the gut microbiota during HFD-induced obesity, confirmed the critical role of the gut microbiota in the transmission of inflammation, and provided a new theoretical basis for the intervention of obesity-related diseases.}, } @article {pmid41642353, year = {2026}, author = {Gholizadeh, P and Faghfuri, E}, title = {Reprogramming Gastric Cancer Therapy: A Microbiome-Guided Approach to Precision Oncology.}, journal = {Current microbiology}, volume = {83}, number = {3}, pages = {150}, pmid = {41642353}, issn = {1432-0991}, } @article {pmid41641458, year = {2025}, author = {Bai, H and Xu, Y and Qu, S and Li, B and Wang, X}, title = {The influence of the maternal microbiome on offspring neurodevelopment: a critical review of associations, controversies, and challenges.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1737795}, pmid = {41641458}, issn = {1662-4548}, abstract = {The role of the maternal microbiome in offspring neurodevelopment has become a prominent topic in neuroscience, yet its true causal status is under intense scrutiny. This critical review moves beyond conventional deconstructions of popular hypotheses in the field (e.g., "prenatal programming" "windows of opportunity") to challenge a more fundamental premise. We systematically argue that the currently observed associations along the "microbiota-gut-brain axis" may reflect complex confounding, with macroscopic social factors such as socioeconomic status (SES) being the true underlying drivers. The core thesis of this paper is that the maternal microbiome is, to a great extent, a "biological imprint" of the mother's living environment, diet, and stress levels-a highly sensitive "proxy" indicator acting as a biological mediator heavily shaped by the environment, rather than solely as an independent driver. By integrating evidence from social epidemiology, we contend that positioning the microbiome alongside factors like SES in a "flattened" network model is misleading. Instead, we propose a Hierarchical Causal Model where socioeconomic factors act as top-level "master regulators," systematically shaping all downstream biological processes, including the microbiome. Through a critical analysis of interventions such as Fecal Microbiota Transplantation (FMT) and vaginal seeding, this review further exposes the translational predicaments that arise from neglecting this hierarchical structure. Ultimately, this review advocates for a paradigm shift: from searching for a single "microbial panacea" to understanding the microbiome's true position within the socio-biological system, and proposes a conceptual framework for future research that is more aligned with real-world complexity and endowed with greater sociological imagination.}, } @article {pmid41641369, year = {2026}, author = {Wang, N and Luo, L and Yang, X}, title = {The gut-eye axis in age-related macular degeneration: from microbial dysbiosis to targeted intervention strategies.}, journal = {Experimental biology and medicine (Maywood, N.J.)}, volume = {251}, number = {}, pages = {10876}, pmid = {41641369}, issn = {1535-3699}, mesh = {Humans ; *Macular Degeneration/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology/complications/therapy ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; Prebiotics ; }, abstract = {Age-related macular degeneration (AMD) represents a leading cause of irreversible blindness among the older persons. Characterized by a complex pathogenesis and multiple risk factors, AMD poses substantial challenges for treatment and has emerged as a significant public health concern. The gut microbiota constitutes a vast and dynamically evolving ecosystem, with a healthy microbial community playing an essential role in maintaining host homeostasis through its involvement in digestion and immune defense. However, alterations in microbial composition or function can compromise intestinal barrier integrity, trigger systemic inflammation, and contribute to disease pathogenesis. Evidence now underscores the influence of gut microbiota on the development and progression of AMD. This review examines the mechanisms by which gut microbes may contribute to AMD pathogenesis and evaluates the therapeutic potential of interventions targeting the gut microbiome-including dietary modifications, Pharmacological and Biological Agents, probiotics, prebiotics, and fecal microbiota transplantation-for AMD management.}, } @article {pmid41641127, year = {2025}, author = {Rogalidou, M}, title = {Clostridioides difficile infection in pediatric inflammatory bowel disease: current understanding and clinical challenges.}, journal = {Frontiers in pediatrics}, volume = {13}, number = {}, pages = {1753289}, pmid = {41641127}, issn = {2296-2360}, abstract = {Clostridioides difficile infection (CDI) represents a significant and increasingly recognized complication in children with inflammatory bowel disease (IBD), contributing to prolonged hospitalization and risk of adverse outcomes. Children with IBD are particularly susceptible due to frequent antibiotic exposure, healthcare system contact, immunosuppressive therapy, and underlying gut dysbiosis, all of which promote colonization and toxin-mediated intestinal injury. Distinguishing CDI from an IBD flare is challenging, as gastrointestinal symptoms and systemic inflammation overlap, and asymptomatic toxigenic colonization is common. Management recommendations for pediatric IBD-associated CDI are largely extrapolated from adult studies, with prompt initiation of targeted antibiotics being critical. Immunosuppressive therapy is generally continued, with escalation considered if diarrhea persists despite CDI-directed therapy. Fecal microbiota transplantation (FMT) has emerged as a safe and promising option for recurrent CDI in children with IBD, although careful patient selection, donor choice, and timing remain crucial. Key challenges persist in differentiating true CDI from IBD flares, understanding the clinical impact of asymptomatic colonization, and optimizing microbiome-targeted interventions. Future research should prioritize biomarker-driven diagnosis, individualized therapeutic strategies, and longitudinal evaluation of microbiome-based treatments to improve outcomes in pediatric patients with concurrent CDI and IBD.}, } @article {pmid41640872, year = {2026}, author = {Chen, YX and Sun, NQ and Mo, SJ}, title = {Rhapontin activating nuclear factor erythroid 2-related factor 2 to ameliorate Parkinson's disease-associated gastrointestinal dysfunction.}, journal = {World journal of gastroenterology}, volume = {32}, number = {4}, pages = {114468}, pmid = {41640872}, issn = {2219-2840}, mesh = {*NF-E2-Related Factor 2/metabolism ; Gastrointestinal Microbiome/drug effects ; Animals ; Humans ; *Parkinson Disease/complications ; *Gastrointestinal Diseases/etiology/therapy/microbiology ; Mice ; Disease Models, Animal ; Kelch-Like ECH-Associated Protein 1/metabolism ; Signal Transduction/drug effects ; Fecal Microbiota Transplantation ; Brain-Gut Axis/drug effects ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; }, abstract = {This commentary provides a critical evaluation of the study by Wang et al, which focuses on rhapontin activating colonic nuclear factor erythroid 2-related factor 2 (NRF2) to explore its therapeutic potential for Parkinson's disease (PD)-associated gastrointestinal dysfunction. The commentary acknowledges the academic value of the study: It has not only validated intestinal NRF2 as a therapeutic target for PD but also provided experimental support for the "enteric pathology hypothesis". However, several key gaps remain unresolved in the study. At the gut microbiota level, the exploration of the causal relationship of the microbiota is insufficient, with no validation conducted via methods such as fecal microbiota transplantation; additionally, it fails to systematically integrate the gut-brain axis with PD and does not assess the impact of rhapontin on the composition or function of the gut microbiota. At the pathway mechanism level, it lacks an analysis of the crosstalk between NRF2 and other rhapontin-targeted pathways, including nuclear factor kappa-B, mitogen-activated protein kinase, adenosine monophosphate-activated protein kinase, and sirtuin 1. At the experimental method level, the behavioral testing methods for PD mouse models and the limitations of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse models need attention. Additionally, certain flaws exist in some experimental result figures. Furthermore, this commentary puts forward improvement suggestions for the study. Future research should prioritize multi-omics analysis, encompassing combined metabolomics and metagenomics detection, while conducting mechanistic validation of NRF2-interacting molecules (KEAP1 and p62). In addition, it is necessary to improve refined behavioral tests, focusing on incorporating cognitive function and anxiety-related assessment items.}, } @article {pmid41640608, year = {2026}, author = {Velikova, T and Ali, H and Batselova, H and Chervenkov, L and Miteva, D and Peruhova, M and Gulinac, M and Tomov, L and Mitova-Mineva, Y and Velev, V}, title = {Interplay between viral infections and gut microbiota dysbiosis: Mechanisms and therapeutic potential.}, journal = {World journal of gastroenterology}, volume = {32}, number = {3}, pages = {112437}, pmid = {41640608}, issn = {2219-2840}, mesh = {Humans ; *Dysbiosis/therapy/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; *COVID-19/immunology/microbiology/complications/therapy ; SARS-CoV-2 ; Prebiotics/administration & dosage ; *Virus Diseases/immunology/microbiology/therapy ; Animals ; }, abstract = {Viral infections, particularly those triggered by emerging pathogens like severe acute respiratory syndrome coronavirus 2, are increasingly recognized for their profound impact on the gut microbiota, causing dysbiosis, a condition characterized by an imbalance in microbial communities. Recent studies suggest that alterations in gut microbiota can influence disease progression, immune responses, and clinical outcomes. The bidirectional relationship between the gut microbiota and the host immune system is crucial in shaping responses to infection. Furthermore, dysbiosis has been linked to exacerbated inflammation, impaired mucosal barrier function, and altered drug metabolism, thereby complicating both disease pathogenesis and treatment efficacy. This review examines the interplay between viral infections and gut microbiota dysbiosis, with a focus on the underlying mechanisms and potential therapeutic strategies to modulate host immunity. We also evaluate the potential of microbiome-based interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, as therapeutic strategies for restoring microbial balance and mitigating the severity of infections. The paper underscores the need for further research to optimize microbiota-targeted therapies and integrate them into clinical practice, offering a comprehensive approach to managing dysbiosis in viral infectious diseases.}, } @article {pmid41639673, year = {2026}, author = {Wu, H and Pang, MM and Li, YL and Huang, JJ and Geng, SZ and Hong, JH and Liu, PM and Yang, JJ}, title = {Flos sophorae immaturus exosome-like nanovesicles alleviate ulcerative colitis by attenuating intestinal oxidative stress and inflammation through activating Aryl hydrocarbon receptor via gut microbiota and tryptophan metabolism regulation.}, journal = {Journal of nanobiotechnology}, volume = {24}, number = {1}, pages = {132}, pmid = {41639673}, issn = {1477-3155}, support = {82501460, U23A20421//National Natural Science Foundation of China/ ; }, abstract = {Ulcerative colitis (UC) is an inflammatory bowel disease that significantly impacts patients' quality of life. The pathogenesis of UC remains incompletely understood, with oxidative stress and inflammation emerging as novel research targets. This study first isolated Flos Sophorae immaturus exosome-like nanovesicles (FSIEVs), demonstrating high purity, uniform particle size, and excellent biocompatibility and biosafety, with potential for treating UC. In vivo, FSIEVs improve the overall condition of a dextran sodium sulfate-induced murine model of UC, reduce intestinal inflammation and oxidative stress, and repair intestinal barrier integrity. Moreover, FSIEVs exhibit anti-UC effects by modulating the gut microbiota (enhancing Lactobacillus species), promoting tryptophan metabolism, and increasing the production of indole-3-acetic acid (IAA). Findings from antibiotic treatment, fecal microbiota transplantation (FMT), and intestinal organoid models confirmed that IAA is a key metabolite mediating the anti-UC effects of FSIEVs, and all these approaches significantly activated the aryl hydrocarbon receptor (AhR). The role of AhR in the anti-UC effects of FSIEVs was further validated using AhR antagonists. Notably, FSIEVs alleviated UC symptoms involving the enrichment of beneficial anti-UC Lactobacillus species, L. paracasei by mono-colonization. In summary, FSIEVs improve UC by regulating the gut microbiota and tryptophan metabolites, enhancing IAA production, activating AhR, and suppressing NLRP3 inflammasome activation and ROS production.}, } @article {pmid41639396, year = {2026}, author = {Weber, D and Tariq, M and Hazenberg, M and Poeck, H and Malard, F}, title = {Microbiome, GvHD, and immune reconstitution in allogeneic hematopoietic cell transplantation.}, journal = {Bone marrow transplantation}, volume = {}, number = {}, pages = {}, pmid = {41639396}, issn = {1476-5365}, abstract = {The gut microbiota has emerged as a critical factor influencing outcomes following allogeneic hematopoietic cell transplantation (alloHCT). Notably, disruptions to the intestinal microbiome-referred to as dysbiosis-have been strongly linked to the development of acute graft-versus-host disease (aGVHD). The gut microbiome interacts closely with the host immune system, influencing both immune reconstitution and alloHCT complications. As a result, microbiome-targeted strategies are being investigated to improve outcomes and include antibiotic stewardship, prebiotic and diet intervention, probiotics including fecal microbiota transfer (FMT) and postbiotics. These approaches are being investigated not only as a therapeutic intervention in particular for aGVHD, but also as preventive strategies.}, } @article {pmid41639119, year = {2026}, author = {Xu, Q and Lv, Q and Yang, Z and Yang, Y and Li, Z and Zhang, Y and Chen, L and Zhan, S and Che, H and Wang, G and Wu, J and Han, J}, title = {Polygonatum cyrtonema Hua fructan ameliorates ulcerative colitis via gut microbiota modulation and follistatin targeting.}, journal = {NPJ science of food}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41538-026-00729-3}, pmid = {41639119}, issn = {2396-8370}, support = {2024AH051923//the Natural Science Research Initiative of the Anhui Provincial Department of Education/ ; 2024AH051934//the Natural Science Research Initiative of the Anhui Provincial Department of Education/ ; 2024AH040169//the Natural Science Research Initiative of the Anhui Provincial Department of Education/ ; 82270879//the National Natural Science Foundation of China/ ; 2508085QH341//the Natural Science Foundation of Anhui Province/ ; 2024CCCX260//the TCM Innovation and Inheritance Project of Anhui Province/ ; HKDCCM2024008//the Open Fund of the High-level Key Discipline of Chemistry of Chinese Medicine of the State Administration of Traditional Chinese Medicine, Anhui University of Chinese Medicine/ ; 2023yjsmsgzs037//he Anhui Provincial Postgraduate Education Quality Project (Han Jun Distinguished Mentor Studio)/ ; 2023yjsdstd053//the Anhui Provincial Pharmacy Graduate Supervisor Team/ ; 2023CXMMTCM011//the Research Funding for the Center of Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM/ ; 2023zc06//The "Chi Zhu Zhi Guang" Major Scientific and Technological Achievements Engineering Project of Wuhu City/ ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease with persistent colonic inflammation and inadequate therapeutic options. The medicinal and edible plant Polygonatum cyrtonema Hua from Jiuhua Mountain contains polysaccharides with potent anti-inflammatory activities. In this study, a low-molecular-weight fructan (Mw = 2087 Da), designated PCP2, was isolated and purified from its rhizome. Biologically, PCP2 administration markedly alleviated disease severity in dextran sulfate sodium (DSS)-induced colitis mice, as shown by the improvement in multiple indicators of colon injury and inflammation. Fecal microbiota transplantation and antibiotic depletion experiments revealed that the protective effects of PCP2 are mediated through both modulation of the gut microbiota and additional microbiota-independent pathways. Importantly, through molecular dynamics simulations, microscale thermophoresis, and surface plasmon resonance assays, follistatin (Fst) is identified as a direct binding target of PCP2. Functional validation using siRNA-mediated Fst knockdown in Caco-2 cells, combined with adenovirus-mediated knockdown in the murine colon, confirmed that PCP2 exerts its therapeutic effect by directly interacting with Fst and suppressing the BMP4/Smad1/ID1 signaling axis. In summary, PCP2 ameliorates ulcerative colitis via dual mechanisms involving restoration of gut microbiota homeostasis and direct targeting of Fst. These findings establish a novel therapeutic strategy and support the clinical development of P. cyrtonema Hua from Jiuhua Mountain as a functional food for intestinal health.}, } @article {pmid41636306, year = {2026}, author = {Luan, M and Bao, S and Zhang, X and Huang, Y and Yuan, R and Zhong, P and Liu, M and Li, J and Liu, X and Chen, L and Huang, Q and Wu, R}, title = {Sinensetin Ameliorates Metabolic Syndrome via Regulating Gut Microbiota and Bile Acid Metabolism.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c12920}, pmid = {41636306}, issn = {1520-5118}, abstract = {The exact mechanism through which dietary flavonoids alleviate metabolic syndrome (MetS) via the gut microbiota remains fully unclear. This study demonstrates that sinensetin markedly impeded the development of MetS and altered hepatic transcriptomic profiles by activating alternative bile acid biosynthesis signaling cascades both in vivo and in vitro. Importantly, sinensetin administration induced significant shifts in hepatic bile acid composition, notably increasing the relative abundance of non-12-hydroxy bile acids (non-12-OH BAs) in high-fat diet (HFD)-fed mice. Additionally, oral administration of sinensetin significantly relieved intestinal dysbiosis caused by HFD by altering the composition of gut microbiota in mice. The therapeutic efficacy of sinensetin against MetS was microbiota-dependent, as antibiotic-mediated depletion of gut microbiota abolished its beneficial effects, and fecal microbiota transplantation transmited this metabolic improvement. These findings suggest that sinensetin alleviated MetS by reshaping the gut microbiota to enhance non-12-OH BAs synthesis, offering novel mechanistic insights and promising avenues for therapeutic intervention.}, } @article {pmid41635847, year = {2025}, author = {Sun, Q and Gao, J and Zhao, X and Wang, T and Pan, W and Yu, J}, title = {The gut-lung axis in severe pneumonia-related lung injury: mechanisms and therapeutic strategies.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1700534}, pmid = {41635847}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Lung/immunology/microbiology ; Animals ; *Pneumonia/microbiology/therapy/immunology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; *Lung Injury/therapy/microbiology ; *Acute Lung Injury/therapy/microbiology ; Prebiotics/administration & dosage ; }, abstract = {Severe pneumonia-related lung injury is a life-threatening condition associated with high morbidity and mortality. Recent advances in research on the gut-lung axis have provided novel insights into its pathophysiology and revealed potential therapeutic targets. Within the conceptual framework of the microorganism-immunity-metabolism network, modulation of the gut microbiota has emerged as a promising strategy for intervention. Therapeutic approaches such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation aim to enhance microbial diversity and alter metabolite profiles, thereby optimizing immune responses and attenuating systemic and pulmonary inflammation. This review explores the mechanistic underpinnings of the gut-lung axis in the context of severe pneumonia-related lung injury, with a particular focus on microbiota-targeted interventions. Our goal is to provide a theoretical foundation for the clinical application of gut microbiota modulation in the prevention and treatment of severe pneumonia-related lung injury.}, } @article {pmid41634704, year = {2026}, author = {Bao, L and Jin, L and Yang, Y and Zhao, Y and Wu, K and Shan, R and Liu, Y and Han, Y and Shang, S and Zhang, N and Hu, X and Fu, Y and Zhao, C and Jiang, H and Bian, W}, title = {Hexadecanamide alleviates experimental colitis in mice and modifies the gut microbiome.}, journal = {BMC biology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12915-026-02530-w}, pmid = {41634704}, issn = {1741-7007}, abstract = {BACKGROUND: Hexadecanamide (HEX) has been recognized for its significant anti-inflammatory properties. However, its specific role and underlying mechanisms in the context of colitis remain poorly understood.

RESULTS: Herein, we first determined the effect of oral HEX on DSS-induced colitis in mice. Our results showed that HEX alleviated DSS-induced colitis in mice, which was related to the improvement of intestinal barrier integrity and the reduction of colonic inflammatory responses. Interestingly, HEX suppressed the initiation of DSS-induced ferroptosis. In detail, HEX inhibited autophagy and ferritinophagy, which subsequently blocked lipid peroxidation. 16S rRNA sequencing revealed that HEX intervention regulated the gut microbial composition, characterized by an increased relative abundance of Actinobacteriota and Patescibacteria and a decreased the relative abundance of Firmicutes. To validate these findings, fecal microbiota transplantation (FMT) was performed in DSS-treated mice. The microbiota derived from HEX-treated mice exhibited greater efficacy in alleviating colitis compared to that from control-treated mice, as evidenced by prominent anti-inflammatory effects and colonic barrier repair, and consistent alterations in the gut microbial community, which were further confirmed by FMT.

CONCLUSIONS: Overall, our findings suggest that HEX markedly ameliorates DSS-induced colitis by limiting inflammation, improving barrier integrity and regulating gut microbial composition. These results highlight the critical role of HEX in maintaining intestinal homeostasis and suggest its potential as a novel preventive and therapeutic strategy.}, } @article {pmid41633775, year = {2026}, author = {Kang, KS and Choi, GH and Kim, YJ and Lee, WS and Lee, DE and Kim, MY and Yoon, H and Lee, DH}, title = {Analysis of gut microbiota in super donors for fecal microbiota transplantation and isolated gut commensal bacteria of inhibition against Clostridioides difficile.}, journal = {Intestinal research}, volume = {}, number = {}, pages = {}, doi = {10.5217/ir.2025.00179}, pmid = {41633775}, issn = {1598-9100}, abstract = {BACKGROUND/AIMS: Fecal microbiota transplantation (FMT) is increasingly recognized as an alternative to antibiotics for treating recurrent Clostridioides difficile infection. The success of FMT heavily depends on the appropriate selection of donors, encompassing factors such as diet patterns, lifestyle, environmental exposures, and intestinal microbiota diversity.

METHODS: A potential super donor was identified from 5 healthy adults and provided stool samples periodically over 2 years (2021-2022). The samples underwent 16S rRNA sequencing via the Illumina MiSeq platform, and microbial diversity was analyzed using QIIME 2 in comparison with 152 healthy individuals.

RESULTS: The stool microbiome composition of the potential super donor remained stable without significant changes over a 2-year period. Both alpha and beta diversity analyses revealed significant differences between the super donor and the 152 healthy individuals. The super donor exhibited significantly higher microbial diversity based on alpha diversity metrics (P< 0.0001) and distinct compositional profiles as shown by beta diversity. Linear discriminant analysis effect size (LEfSe) analysis indicated that Faecalibacterium and Prevotella strains comprised a significant proportion, with notable differences in relative abundance patterns (P< 0.05). Furthermore, 7 bacterial species were isolated from the super donor, all of which demonstrated inhibitory effects on the growth of C. difficile in vitro.

CONCLUSIONS: These findings suggest that selecting donors with specific microbiota profiles, particularly those exhibiting higher microbial diversity, may potentially contribute to the inhibition of C. difficile, and further clinical studies are warranted to validate these findings.}, } @article {pmid41632629, year = {2026}, author = {Runaas, L and Fank, S and Palen, K and Szabo, A and Rein, L and Ying, G and Salzman, N and Samanas, L and Abedin, SM and Chhabra, S and Hamadani, M and Longo, W and Shah, NN and Haber, J and Gradissimo, A and Waters, NR and Peled, JU and Johnson, B and Kearl, T and Drobyski, WR}, title = {TIDRAKIZUMAB FOR THE PROPHYLAXIS OF GRAFT VERSUS HOST DISEASE AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION.}, journal = {Blood advances}, volume = {}, number = {}, pages = {}, doi = {10.1182/bloodadvances.2025019065}, pmid = {41632629}, issn = {2473-9537}, abstract = {We conducted a phase 1-2 study in which patients undergoing allogeneic hematopoietic stem cell transplantation received tildrakizumab in addition to standard immune suppression with tacrolimus and methotrexate for graft versus host disease (GVHD) prophylaxis. Fifty patients were enrolled between March 2020 and June 2023 with a median age of 56 (range 19-64). All patients received myeloablative busulfan-based conditioning and were transplanted with HLA-matched related or unrelated peripheral blood stem cell grafts. Patients were treated with tildrakizumab on an extended subcutaneous administration schedule for five doses which was well tolerated. The cumulative incidences of grades II-IV and III-IV acute graft versus host disease were 14% (95% CI 7-28) and 4% (95% CI 1-16) at day 100, respectively. The incidence of chronic GVHD requiring systemic immune suppression was 52.7% (95% CI 40.4-68.9) at twelve months. The one-year probabilities of overall, disease-free, and GVHD-free relapse-free survival were 80% (95% CI 70-92), 78% (95% CI 67-90), and 19.3% (90% CI 11.8-31.4), respectively. Pharmacokinetic analysis revealed that the half-life of tildrakizumab approximated 28 days without formation of detectable anti-tildrakizumab neutralizing antibodies. Comparative examination of fecal microbial composition in tildrakizumab and a similarly transplanted cohort treated with tocilizumab prophylaxis demonstrated that both cytokine blockade strategies had a low frequency of enterococcal dominance. We conclude that tildrakizumab resulted in a low incidence of acute GVHD and attenuation of microbiome dominance with potentially pathogenic organisms but did not mitigate the emergence of chronic GVHD as administered on this dosing schedule. NCT04112810.}, } @article {pmid41632104, year = {2026}, author = {Li, J and Song, L and Liang, X and Zhou, J and Luo, J and Sun, X and Jin, R and Zhang, Z}, title = {Lactobacillus plantarum TY-S8 ameliorates hyperuricemia through the regulation of gut microbiota and tryptophan metabolism in mice.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d5fo04423e}, pmid = {41632104}, issn = {2042-650X}, abstract = {Hyperuricemia (HUA) has become a worldwide metabolic disease, which can lead to acute gout attacks, renal dysfunction, uric acid (UA) urolithiasis, and cardiovascular damage. Probiotics, known for their cost-effectiveness, minimal toxic side effects, and high safety profile, have shown potential in alleviating HUA. In the present study, the beneficial function of Lactobacillus plantarum TY-S8 on HUA and related mechanisms were comprehensively investigated by constructing a mice model of hyperuricaemia, combined with the use of microbiomics and metabolomics. Our results demonstrated that L. plantarum TY-S8 markedly lowered serum UA (SUA) concentrations by 22.41%, suppressed xanthine oxidase (XOD) activity and modulated the level of key transporters, including GLUT9, ABCG2, and NTP1. Furthermore, the pathological damage in the liver, kidney and colon of hyperuricemic mice was alleviated by the probiotics. Meanwhile, the strain upregulated the levels of occludin, a key tight junction protein, and promoted the synthesis of short-chain fatty acids (SCFAs), with a notable increase in butyric acid. Microbiome sequencing and analysis revealed that L. plantarum TY-S8 significantly increased the proportions of Lactobacillus johnsonii and Limosilactobacillus reuteri. Additionally, metabolomic analysis of fecal and blood samples indicated that the differential metabolites among the three groups were primarily indole derivatives, such as indole-3-acetic acid (IAA), indole-3-lactic acid (ILA), and indole-3-acetaldehyde (IAAld), which are involved in the tryptophan metabolism pathway. Notably, there is a clear correlation between the key bacterial strains and these differential metabolites. At last, fecal microbiota transplantation (FMT) was performed to confirm that the ameliorative effect of L. plantarum TY-S8 on the hyperuricemic mice is primarily mediated by the regulation of gut microbiota and tryptophan metabolites. In conclusion, L. plantarum TY-S8 exerts probiotic effects on hyperuricemic mice through multiple pathways. In particular, it alleviates intestinal inflammation by regulating tryptophan metabolism, thereby effectively promoting uric acid metabolism, which highlights its potential value in the intervention of HUA.}, } @article {pmid41632030, year = {2026}, author = {Zhang, H and Li, Z and Xiao, Y and Bian, J and He, C and Liu, C and Gong, L and Han, L and Liu, Z and Wang, M}, title = {Gut Microbiota-Derived Anandamide Mediates the Therapeutic Effects of Urolithin A on Alcohol-Induced Cognitive and Social Dysfunction via CB1R-DRD2-RAP1 Signaling Axis.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e08048}, doi = {10.1002/advs.202508048}, pmid = {41632030}, issn = {2198-3844}, support = {CARS-07-E-2//financial support provided by the China Agriculture Research System/ ; 32001701//Natural Science Foundation of China/ ; }, abstract = {Chronic alcohol consumption disrupts the gut microbiome, exacerbating alcohol-induced cognitive and social dysfunction (AICSD), which constitutes a primary etiology of early-onset dementia. Urolithin A (UA) has been well-reported as an effective intervention for neurodegenerative diseases. However, the protective efficacy of UA against AICSD, and its underlying mechanisms remain largely elusive. First, our study demonstrates that UA significantly enhances work memory (60.43%), short-term memory (12-fold), long-term memory (50.32%), social ability (10-fold), and social novelty (12-fold), while concurrently reducing synaptic impairments and neuroinflammation. Moreover, UA restores AICSD by upregulating the dopamine D2 receptor (DRD2) via RAP1 signaling. Furthermore, antibiotic treatment and fecal microbiota transplantation experiments confirm the causality between the host microbiota and behavioral alterations. Treatment with UA-enriched Bacteroids sartorii and Parabacteroids distasonis, or their derived endocannabinoid-anandamide (AEA), also ameliorates AICSD. Finally, AEA inhibits the Rap1 signaling through cannabinoid receptor 1 (CB1R) and DRD2 interaction, eventually ameliorating AICSD. Collectively, our study elucidates that microbiota-derived AEA mediates the therapeutic effects of UA on AICSD through the CB1R-DRD2-RAP1 signaling axis, providing valuable insights for UA and microbiome-targeted endocannabinoid interventions against AICSD.}, } @article {pmid41630697, year = {2026}, author = {Olasunkanmi, OI and Zheng, L and Zheng, P}, title = {Gut-brain axis in health and brain disease.}, journal = {Chinese medical journal}, volume = {}, number = {}, pages = {}, pmid = {41630697}, issn = {2542-5641}, abstract = {The gut-brain axis is a complex, bidirectional network of communication systems that integrates neural, endocrine, and immune pathways, as well as metabolic processes, to regulate homeostasis and maintain physiological and cognitive equilibrium. Central to this axis is the gut microbiota, which exerts a profound influence on brain function through microbial metabolites, including short-chain fatty acids, tryptophan metabolites, and bile acids. Disruption of this microbial balance, known as dysbiosis, has been implicated in the onset and progression of major neuropsychiatric and neurodegenerative disorders, including depression, Alzheimer's disease, and Parkinson's disease. This review critically examines the mechanistic underpinnings of the gut-brain axis, emphasizing metabolic, immunological, and neuroendocrine signaling as key mediators. Furthermore, it explores how dietary components, particularly fiber, polyphenols, and fermented foods, modulate gut microbial composition and function to influence brain health. Emerging therapeutic strategies, such as probiotics, prebiotics, and fecal microbiota transplantation, are discussed, along with the potential of personalized targeted intervention. By integrating current findings, this review underscores the gut-brain axis as a dynamic interface that not only influences neurological and psychiatric outcomes but also represents a promising target for therapeutic intervention.}, } @article {pmid41629813, year = {2026}, author = {Astudillo-Guerrero, C and Garrido, Á and Masferrer, D and Sepúlveda, C and Olavarría, L and Del Campo, R and Bravo-Sagua, R and Cubero, FJ and Salech, F and Thumala-Dockendorff, D and Urrutia, PJ and Quera, R and Bunout, D and Espinoza, R and Jorquera, G}, title = {Randomized, double-blind, placebo-controlled trial of fecal microbiota transplantation from young physically active donors to promote resilient aging: clinical trial protocol (ARMOR study).}, journal = {BMC geriatrics}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12877-025-06920-7}, pmid = {41629813}, issn = {1471-2318}, } @article {pmid41629271, year = {2026}, author = {Yao, Y and Zhu, Y and Chen, K and Chen, J and Li, Y and Li, D and Wei, P}, title = {Microbiota in cancer: current understandings and future perspectives.}, journal = {Signal transduction and targeted therapy}, volume = {11}, number = {1}, pages = {39}, pmid = {41629271}, issn = {2059-3635}, support = {82273240, 82473078//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82273240, 82473078//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82273240, 82473078//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82273240, 82473078//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Humans ; *Neoplasms/microbiology/therapy/immunology/pathology ; *Microbiota/immunology ; Immunotherapy ; *Gastrointestinal Microbiome/immunology ; *Carcinogenesis/immunology/genetics ; Animals ; Probiotics/therapeutic use ; }, abstract = {The intricate relationship between the microbiota and cancer has recently emerged as a pivotal area of research, highlighting their critical roles in carcinogenesis, progression, and prognosis. With the increasing recognition of the therapeutic potential of the microbiota in cancer, there is an urgent need to understand the diverse impacts of different microbiota on tumors and explore innovative strategies to harness their benefits. For the first time, this review traces the historical evolution of microbiota-cancer studies, from early observations of microbial presence in cancers to landmark discoveries linking specific microorganisms to carcinogenesis. Furthermore, this study delves into the molecular mechanisms underlying microbiota-mediated cancer progression to elucidate the modulatory roles of oncogenic pathways, immune responses, and tumor metabolism. We also discuss the dual roles of the microbiota in promoting and inhibiting cancer, highlighting its potential as both a facilitator of tumor growth and a target for therapeutic intervention. In addition, this review highlights the mechanism by which the microbiota mediates the response to anticancer immunotherapy, chemotherapy, and radiotherapy. Simultaneously, emerging anticancer strategies targeting microbiota (e.g., probiotics, antibiotics, and fecal microbiota transplantation) have been explored alongside U.S. Food and Drug Administration-approved drugs and ongoing clinical trials. Finally, this review outlines future directions in this field, emphasizing the need for personalized approaches to harness the anticancer potential of the microbiota. The interpretations in this review are expected to establish a stereoscopic, comprehensive framework for advancing research and clinical applications in microbiota-targeted oncology.}, } @article {pmid41628870, year = {2026}, author = {Zhang, A and Li, S and Qiao, J and Zhong, C and Zhang, Z and Ye, X and Jin, J and Shang, S and Wu, S and Zhang, Q and Yang, G}, title = {Isopsoralen alleviates osteoarthritis by modulating the MAPK/NF-κB signaling pathway and regulating the structure of gut microbiota.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {121257}, doi = {10.1016/j.jep.2026.121257}, pmid = {41628870}, issn = {1872-7573}, abstract = {The therapeutic effect of Psoralea corylifolia L. on knee joint pain was recorded as early as the Ming Dynasty in the Compendium of Materia Medica, which notes its actions of tonifying the kidney, strengthening tendons, and bones. Isopsoralen (ISO), derived from the Psoralea corylifolia L., has shown efficacy in improving osteoarthritis (OA) in both traditional use and our previous screening, demonstrating effects in alleviating joint inflammation and protecting cartilage.

AIM OF THE STUDY: OA is a common disabling disease. Its progression connects local joint pathology to systemic metabolic and inflammatory states, extending to gut microbiota and metabolites. This study examines the therapeutic mechanism of isopsoralen against OA using a DMM-induced model.

MATERIALS AND METHODS: ISO's targets were predicted by network pharmacology approaches. Therapeutic effects were evaluated through behavioral tests, micro-CT, histology, Western blot, and PCR, while safety was assessed via liver/kidney staining. 16S rDNA sequencing and targeted metabolomics were employed to analyze gut microbiota structure and short-chain fatty acids (SCFAs). Pseudo germ-free mice and fecal microbiota transplantation (FMT) were used to validate the role of gut microbiota.

RESULTS: Network pharmacology indicated ISO's multi-target action against OA. ISO downregulated the MAPK/NF-κB pathway, attenuated subchondral bone abnormalities, and alleviated joint degeneration in DMM mice. It also modulated gut microbiota composition and SCFA levels. FMT confirmed the essential role of gut microbiota in ISO's efficacy. Furthermore, no hepatorenal toxicity was observed.

CONCLUSION: ISO alleviates OA by modulating gut microbiota/SCFAs and inhibiting the MAPK/NF-κB pathway, thereby reducing inflammation and improving bone abnormalities, without hepatorenal toxicity.}, } @article {pmid41628815, year = {2026}, author = {Nowicka, A and Gil, L}, title = {Fecal microbiota transplantation for carbapenem-resistant Pseudomonas spp. colonization in hematology patients: long-term real-world data.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {}, number = {}, pages = {108447}, doi = {10.1016/j.ijid.2026.108447}, pmid = {41628815}, issn = {1878-3511}, abstract = {OBJECTIVES: Colonization with carbapenem-resistant Pseudomonas spp (CRP) contributes to infections and high mortality. Fecal microbiota transplantation (FMT) offers a strategy for eradicating multidrug-resistant organisms, but experience on CRP decolonization in immunocompromised patients is meagre.

DESIGNS AND METHODS: A single-center retrospective study of gastroscopic FMT in CRP-positive hematological patients. The primary objective was decolonization. Short and long-term post-FMT CRP-related infectious complications were evaluated.

RESULTS: By April 30, 2025, 14 patients (5 ALL, 5 AML, 2 MDS, 1 APL, 1 NHL) were enrolled; 8 had received allo-HCT. With a median follow-up of 16 months (1,45-26), decolonization was achieved in 10 in a median of 14 days (9-34) and was durable in 6. Eradication failure occurred in 4 due to persistence and 4 due to recurrence. Median time to recolonization was 83 (32-173). 9 patients experienced CRP-related infections following FMT: bloodstream infections (BSI) 67%, soft tissue 56%, gastrointestinal 56%, urinary tract 33%, pneumonia 22%, septic shock 22%. A total of 7 died; due to infections in 6, with CRP responsible in 5. No severe adverse events of FMT were reported.

CONCLUSIONS: FMT demonstrates safety and efficacy in early decolonization of CRP. In failure, CRP-related infections remain a leading cause of mortality.}, } @article {pmid41627354, year = {2026}, author = {Blonk, L and Straatman, J and Wierdsma, NJ and Gisbertz, SS and van der Peet, DL and Kazemier, G and van Berge Henegouwen, MI}, title = {Nutritional aspects and quality of life in gastroesophageal cancer patients that underwent colonic interposition.}, journal = {Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus}, volume = {39}, number = {1}, pages = {}, doi = {10.1093/dote/doaf126}, pmid = {41627354}, issn = {1442-2050}, mesh = {Humans ; *Quality of Life ; Male ; Female ; Retrospective Studies ; Middle Aged ; *Colon/surgery/transplantation ; Aged ; *Esophageal Neoplasms/surgery ; *Nutritional Status ; Intestinal Absorption ; Energy Intake ; *Postoperative Complications/etiology ; *Stomach Neoplasms/surgery ; *Esophagectomy/methods/adverse effects ; Anastomosis, Surgical ; }, abstract = {The use of a colonic interposition after major esophageal surgery leads to substantial anatomical changes, but information regarding the effects of these changes on functional outcomes is limited. Objective of this study was to evaluate the presence of gastrointestinal symptoms, nutritional aspects, intestinal absorption capacity, and health-related quality of life (HR-QoL) in adult patients after colon interposition. This single-center study consisted of three parts. Part 1 involved a retrospective review of anthropometric data, dietary patterns, and gastrointestinal symptoms in all consecutive patients who underwent colonic interposition between 2010 and 2021 and in whom at least 6 months of follow-up were available. Patients from part 1 who were still alive in 2021 were invited for an in-depth evaluation of dietary intake and intestinal absorption capacity. This included measuring daily fecal losses of energy (kcal), fat (g), and protein (g) over a 72-hour period. The coefficients of fat and protein absorption (CFA and CNA) were calculated. Energy balance (kcal/day) was determined by subtracting fecal energy loss (kcal/day) and daily estimated total energy expenditure (eTEE) from the dietary energy intake (kcal/day). Part 3 assessed HR-QoL prospectively using the EORTC QLQ-C30 and OG-25 questionnaires. All consecutive patients presenting to the outpatient clinic between 2014 and 2021 were asked to complete these questionnaires. In part 1 of this study, 30 patients were included. Symptoms of steatorrhea/diarrhea (65%) and dysphagia (42%) were most frequently reported, and 31% could not cease enteral nutrition via jejunostomy or nasal tube due to weight loss or gastrointestinal symptoms. Ten patients were included in part 2 of this study. Intestinal malabsorption of fat and protein (CFA and CNA <85%) was found in 70% of patients, and 60% of patients had a negative energy balance. HR-QoL was measured in 20 patients. Median global QoL score (EORTC QLQ-C30) was 63 (IQR 50-83) and the OG-25 symptom score 19 (IQR 6.9-36). In conclusion a colonic interposition after esophagectomy is accompanied by gastrointestinal symptoms, intestinal malabsorption, and an impaired QoL. Adequate counseling of patients and follow-up with a multidisciplinary approach to treat gastrointestinal symptoms and correct for intestinal malabsorption is recommended.}, } @article {pmid41626790, year = {2026}, author = {Barati, S and Ghoflchi, S and Nakhaei, A and Yazdi, MP and Hosseinzadeh, P and Hosseini, H and Jalili-Nik, M}, title = {Gut Microbiome Strategies for Enhancing ICI Delivery Across the BBB in Glioblastoma.}, journal = {BioFactors (Oxford, England)}, volume = {52}, number = {1}, pages = {e70077}, doi = {10.1002/biof.70077}, pmid = {41626790}, issn = {1872-8081}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/immunology ; *Glioblastoma/drug therapy/immunology/microbiology/pathology ; *Blood-Brain Barrier/drug effects/metabolism/immunology ; *Immune Checkpoint Inhibitors/administration & dosage/therapeutic use ; *Brain Neoplasms/drug therapy/immunology/microbiology/pathology ; Animals ; Tumor Microenvironment/drug effects ; Fecal Microbiota Transplantation ; }, abstract = {Glioblastoma (GB) is highly malignant with a median survival of 14 months despite conventional treatments like surgery, radiotherapy, and temozolomide. Resistance to these therapies necessitates innovative approaches, such as immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed death ligand 1 (PD-L1) to enhance T-cell-mediated tumor destruction. However, clinical trials have shown limited ICI efficacy in GB due to its immunosuppressive microenvironment and the blood-brain tumor barrier (BBTB), which impairs drug delivery. Emerging evidence highlights the gut microbiota as a pivotal modulator of ICI response, enhancing CD8[+] and CD4[+] T-cell function, antigen presentation, and immune modulation via the gut-brain axis in cancers. In addition, studies showed that gut-derived metabolites, including short-chain fatty acids, modulate immune responses and support blood-brain barrier integrity by regulating inflammatory signaling and tight junction proteins. Future GB research should prioritize clinical trials, mechanistic studies, and interventional strategies like fecal microbiota transplantation and probiotics to enhance ICI efficacy.}, } @article {pmid41626654, year = {2026}, author = {Guo, YY and Xue, KJ and Wang, L and Wang, GG and Zhang, TT and Hou, SL}, title = {Alterations in Gut Microbiota and Metabolic Profiles in Relapsed or Refractory Lymphoma.}, journal = {MicrobiologyOpen}, volume = {15}, number = {1}, pages = {e70225}, pmid = {41626654}, issn = {2045-8827}, support = {20241201//Shanxi Province Applied Basic Research Program Project/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Male ; Female ; Middle Aged ; *Metabolome ; *Lymphoma/microbiology/metabolism ; Aged ; Feces/microbiology ; Metabolomics ; *Bacteria/classification/genetics/isolation & purification/metabolism ; Adult ; RNA, Ribosomal, 16S/genetics ; }, abstract = {To identify potential therapeutic strategies for relapsed or refractory lymphoma (R/RL) by examining differences in gut microbiota composition and metabolic profiles between patients with R/RL and those with primary, treatment-naïve lymphoma (PL), using fecal microbiota analysis and metabolomics. A total of 21 patients with lymphoma were enrolled at the Department of Lymphoma and Oncology, Shanxi Bethune Hospital, between November 2023 and December 2024. The cohort included 14 patients with R/RL and 7 with PL, who served as the control group. Pretreatment fecal samples and clinical data were collected from all participants. Gut microbiota profiling was conducted using 16S rDNA sequencing, including alpha diversity, beta diversity, species composition, and differential abundance. Untargeted metabolomics was employed to identify and analyze differentially expressed metabolites between the groups. Patients with R/RL exhibited increased relative abundances of Actinobacteriota and Alphaproteobacteria and decreased levels of Erysipelotrichales, Morganellaceae, Faecalibacterium, Clostridium, Klebsiella, and Ruminococcus. Seven metabolites were significantly upregulated in the R/RL group (p < 0.05): 3-amino-4-methylpentanoic acid (p = 0.028), 2-hydroxybutyric acid (p = 0.020), UDP-N-acetylglucosamine (UDP-N-AG) (p = 0.011), pantothenic acid (p = 0.037), isoleucine (p = 0.028), glycine (p = 0.044), and alanine (p = 0.025). Literature review and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated enhanced central carbon metabolism and amino acid metabolism in cancer. Alterations in gut microbiota and metabolic activity may contribute to the pathophysiology of R/RL. Therapeutic modulation of the gut microbiota, including the use of fecal microbiota transplantation, may improve the intestinal immune microenvironment in this patient population. The present work is hypothesis-generating and requires large-scale validation.}, } @article {pmid41455033, year = {2025}, author = {Liu, Y and Eirin, A and Lerman, LO}, title = {Novel Therapeutic Strategies for Obesity-Related Glomerulopathy.}, journal = {Current hypertension reports}, volume = {28}, number = {1}, pages = {3}, pmid = {41455033}, issn = {1534-3111}, support = {DK122734/DK/NIDDK NIH HHS/United States ; HL158691/HL/NHLBI NIH HHS/United States ; AG062104/AG/NIA NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW:: Conventional management primarily focuses on weight reduction and renin-angiotensin-aldosterone blockade; however, these approaches are often insufficient to halt disease progression.

RECENT FINDINGS:: Recent advances have identified novel therapeutic targets and strategies aimed at addressing the metabolic, inflammatory, and hemodynamic abnormalities, as well as gut microbiome dysbiosis, driving obesity-related glomerulopathy (ORG). Pharmacological agents like sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, finerenone, mitochondrial transfer, and fecal microbiota transplantation have demonstrated renoprotective effects through improving weight, insulin sensitivity, blood pressure, inflammation, and gut microbiome. The potential direct renoprotective effects of these medications in ORG, independent of weight loss, warrant further investigation. Additionally, artificial intelligence and emerging biomarkers represent promising strategies for personalized and precise management, early non-invasive diagnosis, and prognostic evaluation of ORG.}, } @article {pmid41625766, year = {2025}, author = {Zhao, H and Liu, Y and Su, L and Cui, P and Sai, J and Li, S and Wang, N and He, P}, title = {Gut-liver-muscle axis: linking gut microbiota dysbiosis to malnutrition and sarcopenia in liver disease.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1727270}, pmid = {41625766}, issn = {2296-858X}, abstract = {Nutritional disorders and muscle wasting associated with liver disease are key determinants of poor prognosis in patients with chronic liver disease. The formation of these conditions involves multiple factors, including impaired energy metabolism, enhanced protein degradation, and gut microbiota imbalance. In recent years, with the deepening of microbiome research, the concept of the "gut-liver-muscle axis" has gradually emerged to explain the more systematic interaction between gut microbiota, liver metabolism, and skeletal muscle homeostasis. Gut dysbiosis can promote liver inflammation and metabolic disorders through various pathways, further weakening muscle energy utilization and protein synthesis, ultimately leading to malnutrition and sarcopenia. This review systematically explores the crucial role of gut microbiota in liver disease-related malnutrition and muscle wasting, elucidates its potential mechanisms in influencing host metabolism and nutritional status through the "gut-liver-muscle axis," and discusses the prospects of microbiome interventions in improving nutritional outcomes in liver disease.}, } @article {pmid41623601, year = {2026}, author = {Koda, K and Mimura, T and Yamana, T and Ishizuka, M and Takahashi, T and Takano, S and Abe, T and Nishizawa, Y and Katsuno, H and Sato, M and Nishimura, K and Yoshida, M and Maeda, K}, title = {The Japan Society of Coloproctology Practice Guidelines for Fecal Incontinence 2024 (Revised Second Edition).}, journal = {Journal of the anus, rectum and colon}, volume = {10}, number = {1}, pages = {64-134}, pmid = {41623601}, issn = {2432-3853}, abstract = {In 2024, the second edition of the Japan Society of Coloproctology (JSCP) Practice Guidelines for Fecal Incontinence was published in Japan, followed by the release of this English version. This marks the first major revision in 7 years since the publication of the first edition. The second edition was completed over a span of 3 years, and its overview and key features are summarized below. This guideline begins with a clinical flowchart outlining the general diagnostic and therapeutic approach. A notable update is the inclusion of insertable anal and vaginal continence devices, which are now considered a form of conservative therapy under clinical research frameworks. In Chapter I-B (Epidemiology), the prevalence of anal incontinence was newly reported: among a Japanese population with an average age of 35 years, 15.5% of men and 42.7% of women were affected. In Chapter II (Diagnosis), the utility of a bowel diary for patient assessment is discussed for the first time. The guideline also provides a detailed description of the evaluation method for digital rectal examination. Additionally, a new section was added addressing incontinence-associated dermatitis (IAD), including its risks and methods of assessment. In Chapter III (Diagnostic Testing), the guideline expands upon previously established diagnostic tests by newly including detailed descriptions of ultrasound techniques-specifically, endoanal ultrasound, transperineal ultrasound, and transvaginal ultrasound. Chapter IV (Treatment) outlines conservative treatment strategies, including dietary guidance, bowel habit instruction, and care for fecal incontinence. Pharmacologic therapies are presented with itemized explanations by drug type. Pelvic floor muscle training, biofeedback therapy, and transanal irrigation are classified under "specialized conservative therapies" and discussed in detail. For surgical treatment, a new Clinical Question (CQ) addresses postpartum fecal incontinence. It recommends early referral to a specialized center when a sphincter injury is present to be repaired, whereas observation for one year may be appropriate when no injury is identified. Another new CQ discusses the mode of delivery in subsequent pregnancies following obstetric anal sphincter injuries (OASIS), emphasizing the need to evaluate fecal incontinence severity, anal sphincter function, and its integrity before making clinical decisions. Stoma creation is described in detail as one of the surgical treatment options, including its implications for improved postoperative quality of life. For the first time, regenerative therapy for the anal sphincter is introduced as a novel surgical option, reporting promising long-term outcomes from trials involving the transplantation of autologous cultured myoblasts into the external anal sphincter. Finally, Chapter V addresses special clinical scenarios in detail, including fecal incontinence associated with neurological and spinal disorders, dementia, frailty, and bedridden elderly patients.}, } @article {pmid41622997, year = {2026}, author = {Li, Y and Wang, J and Wang, H and Ma, X and Ren, D and Wang, B}, title = {A novel exopolysaccharide from Lactiplantibacillus plantarum H6 improves cholesterol metabolism via Muribaculum-mediated activation of the enterohepatic FXR-FGF15 axis.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2623578}, doi = {10.1080/19490976.2026.2623578}, pmid = {41622997}, issn = {1949-0984}, mesh = {Animals ; *Cholesterol/metabolism ; Mice ; *Fibroblast Growth Factors/metabolism/genetics ; Gastrointestinal Microbiome/drug effects ; Male ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; *Polysaccharides, Bacterial/pharmacology/chemistry/administration & dosage ; Mice, Inbred C57BL ; Liver/metabolism/drug effects ; Hypercholesterolemia/metabolism/drug therapy ; Probiotics/administration & dosage ; Bile Acids and Salts/metabolism ; Humans ; }, abstract = {Hypercholesterolemia is a major risk factor for atherosclerotic cardiovascular disease; however, current therapeutic options such as statins are limited by issues including hepatotoxicity and patient intolerance. Probiotics and their metabolites show promise in modulating cholesterol metabolism through the gut‒liver axis, yet the specific commensal bacteria and molecular mechanisms underlying these effects remain poorly understood. In this study, we isolated and characterized EPS-D1, a novel exopolysaccharide (15.003 kDa) derived from Lactiplantibacillus plantarum H6, which is composed primarily of mannose (46.10%) and glucose (33.98%) and features a highly branched structure (branching degree of 29.5%). The administration of EPS-D1 significantly reduced the serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) by 40.31%, 37.55%, and 43.15%, respectively, in high-cholesterol diet (HCD) mice. Additionally, it improved hepatic steatosis and reduced markers of liver injury. Through 16S rRNA sequencing and fecal microbiota transplantation (FMT), we identified Muribaculum as the key commensal bacterium enriched by EPS-D1. Direct administration of Muribaculum (Muribaculum intestinale) replicated the cholesterol-lowering effects, decreasing ileal and fecal cholesterol levels by 74.79% and 53.16%, respectively. Mechanistically, both EPS-D1 and M. intestinale activated the enterohepatic FXR‒FGF15 axis, which resulted in the upregulation of hepatic cholesterol 7α-hydroxylase (CYP7A1) expression and the downregulation of ileal ASBT and NPC1L1, thereby promoting bile acid synthesis and inhibiting cholesterol absorption. Furthermore, M. intestinale increased intestinal short-chain fatty acids (SCFAs), particularly acetic acid and caproic acid, by 37.88% while also modulating the composition of the bile acid pool. These findings establish M. intestinale as a precise microbial target for cholesterol management and demonstrate that EPS-D1 from L. plantarum H6 enhances cholesterol metabolism through microbiota-mediated activation of the enterohepatic FXR‒FGF15 axis, providing a novel therapeutic strategy for managing hypercholesterolemia.}, } @article {pmid41622931, year = {2025}, author = {Hong, X and Deng, Y and Feng, J and Bao, C and Zhang, Y and Gao, N and Shen, H}, title = {[Fecal Microbiota Transplantation: A Promising Avenue for Lung Cancer Therapy].}, journal = {Zhongguo fei ai za zhi = Chinese journal of lung cancer}, volume = {28}, number = {11}, pages = {841-848}, doi = {10.3779/j.issn.1009-3419.2025.101.21}, pmid = {41622931}, issn = {1999-6187}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Lung Neoplasms/therapy/immunology/microbiology ; Gastrointestinal Microbiome ; Animals ; }, abstract = {As lung cancer treatment continues to advance, mainstream approaches such as surgery, radiotherapy, chemotherapy, neoadjuvant therapy, targeted therapy and immunotherapy have become widely adopted in clinical practice. However, the efficacy of these methods is still limited and they are associated with significant side effects. In recent years, the pivotal role of the gut microbiota in tumor immune regulation has become increasingly recognized, with its potential impact on tumor immunotherapy emerging as a novel therapeutic focus in lung cancer management. Against this backdrop, fecal microbiota transplantation (FMT) has been proposed as a potential immunomodulatory strategy. It enhances host immune responses and improves the tumor immune microenvironment by regulating the gut microbiota. This paper provides a systematic review of the latest research advances in FMT for lung cancer treatment. Focusing on the relationship between gut microbiota and lung cancer, the therapeutic mechanisms of FMT and clinical application studies, it provides a comprehensive exploration of the challenges and prospects for the use of FMT in lung cancer therapy. .}, } @article {pmid41621641, year = {2026}, author = {Chen, L and Yang, Y and Zhang, Y and Yang, X and Zhang, X and Chen, L and Li, W and Zhang, S and Xiong, R and Wang, J and Xu, Z and Zhang, ZY and Pan, C and Ji, M}, title = {Tuft cells in the gut limit cognitive disorders by regulating gut homeostasis.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {}, number = {}, pages = {101747}, doi = {10.1016/j.jcmgh.2026.101747}, pmid = {41621641}, issn = {2352-345X}, abstract = {BACKGROUND & AIMS: Tuft cells, a type of epithelial cell in the gut, play a pivotal role in regulating type 2 immunity and maintaining the gut barrier. However, their role in cognitive impairments remains unclear.

METHODS: We compared behavioral performance between male tuft cell-absent mice (Pou2f3[-/-]) and their wild-type littermates (WT). We analyzed gut microbiota using fecal 16S rRNA, measured gut permeability via FITC-dextran assay, and detected CD4[+]-T cells and type 2 innate lymphoid cells by flow cytometry in both genotypes. Co-housing and fecal microbiota transplantation (FMT) experiments were conducted to explore the role of gut microbiota in cognitive diseases. Single-cell RNA sequencing and fluorescence imaging were used to examine tuft cell changes in the colon of WT and Alzheimer's disease (AD) model mice. Colonic organoids were used to assess the effect of β-amyloid on tuft cell differentiation. Succinic acid, a promoter of tuft cells, was administered, and tuft cell-deficient AD mice were generated to evaluate its impact on behavior and gut homeostasis.

RESULTS: Increased gut permeability, immune imbalance, neuroinflammation, and cognitive dysfunction occurred in 10-month-old mice lacking tuft cells. These alterations were mediated by gut microbiota, evidenced by shifts in microbiota composition and abundance, and supported by co-housing and FMT experiments. AD model mice had fewer tuft cells and impaired type 2 immunity in the gut, potentially because of β-amyloid inhibiting tuft cell differentiation. Succinic acid, a tuft cell activator, restored cognitive function and gut homeostasis in AD mice.

CONCLUSION: Tuft cells may be necessary for maintaining gut homeostasis in cognitive disorders.}, } @article {pmid41620567, year = {2026}, author = {Yang, S and Song, J and Wang, Z and Peng, G and Tong, L and Li, X and Yang, K and Chen, Y and Zhang, H and Zhang, Q and Chen, R}, title = {eIF6 deficiency alleviates colorectal cancer by modulating the gut microbiota and related metabolites.}, journal = {Cell death and differentiation}, volume = {}, number = {}, pages = {}, pmid = {41620567}, issn = {1476-5403}, abstract = {eIF6 is overexpressed in multiple cancers. Previous work has showed that deficiency alters the gut microbiota. This study investigated the mechanism linking eIF6 deficiency, microbial dysbiosis, and colorectal cancer (CRC). eIF6 expression was assessed in human and mouse CRC samples. Functional assays were conducted in mice with AOM/DSS-induced CRC. Antibiotic treatment and faecal microbiota transplantation (FMT) were applied to evaluate microbiota-mediated effects. 16S rDNA sequencing and Dubosiella newyorkensis (D. newyorkensis) supplementation were used to identify key bacteria. Metabolites from the bacterial supernatant were analysed via targeted mass spectrometry. The effect of indole-3-carboxaldehyde (3-ICA) was tested in murine models. eIF6 expression was upregulated in CRC. Its deficiency reduced the tumour incidence and proliferation of tumours in mice and increased the abundance of beneficial bacteria such as Akkermansia and Dubosiella. FMT from eIF6 deficient mice and D. newyorkensis administration attenuated tumorigenesis and enhanced barrier function. 3-ICA, a metabolite of D. newyorkensis, also suppressed CRC progression. eIF6 deficiency exerts protective effects against CRC through the enrichment of D. newyorkensis and its metabolite 3-ICA, revealing a novel mechanism and potential therapeutic strategy for CRC.}, } @article {pmid41620444, year = {2026}, author = {Zhou, X and Liu, X and Peng, B and Yang, Y and Lu, H and Li, D and Deng, Y and Jiang, Z and Wu, C and Fang, W and You, Y and Kwan, HY and Zhao, X and Liu, Y}, title = {Simiao Decoction alleviates hyperuricemia-induced renal injury through regulating gut dysbiosis and decreasing gut-derived uremic toxins.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-026-00923-x}, pmid = {41620444}, issn = {2055-5008}, support = {2023A1515110757//National Natural Science Foundation of China-Guangdong Joint Fund/ ; 20231800913372//Science and Technology Program of Dongguan, China/ ; U22A20365//Joint Funds of National Natural Science Foundation of China/ ; T2341019//National Natural Science Foundation of China/ ; 81830117//the Key Project of National Natural Science Foundation of China/ ; 2024B03J1343//Guangzhou Science and Technology Plan Project/ ; 20252D003//The Major scientific and technological project of Guangzhou Municipal Health Commission/ ; }, abstract = {Renal injury is a common complication of hyperuricemia (HUA), which has been recognized as an independent risk factor for chronic kidney disease (CKD). The gut-kidney axis theory suggests that targeting the gut microbiota may be a potential treatment option for kidney disease. In this study, we utilized a spontaneous HUA rat model to demonstrate that Simiao decoction (SMD), a traditional Chinese medicine formula, can effectively alleviate HUA-induced renal injury by modulating gut microbiota and bacterial metabolism of tryptophan and tyrosine, thereby reducing gut-derived uremic toxins such as indoxyl sulfate (IS) and p-Cresol (PC). Fecal microbiota transplantation (FMT) further confirmed that the therapeutic effect of SMD was mediated by gut microbiota. Finally, in vitro studies revealed that IS promotes epithelial-mesenchymal transition (EMT) while PC induces cellular senescence in tubular cells. Collectively, our findings suggest that SMD can effectively alleviate HUA-induced renal injury through regulating gut dysbiosis and decreasing gut-derived uremic toxins. This study sheds light on a novel mechanism by which SMD exerts its effects on HUA-induced renal injury.}, } @article {pmid41618858, year = {2026}, author = {Yang, T and Gao, Z and Huang, H and Zhang, C and Tang, Y and Qu, Q and Li, H and Ke, J and Chen, Z and Feng, M and Zhou, H and Shu, Y and Yuan, W}, title = {Gut-Metabolome-Proteome Interactions in Age-Related Hearing Loss: Insights from Fecal Microbiota Transplantation and Multi-Omics Analyses.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e14269}, doi = {10.1002/advs.202514269}, pmid = {41618858}, issn = {2198-3844}, support = {81873702//National Natural Science Foundation of China/ ; 81470694//National Natural Science Foundation of China/ ; 82225014//National Natural Science Foundation of China/ ; 82171114//National Natural Science Foundation of China/ ; 2024NF008//National Clinical Research Center for Otolaryngologic Diseases/ ; CSTB2023TIAD-KPX0059//Chongqing Technology Innovation and Application Development Special Project/ ; 2022DBXM006//Major Programs of Chongqing Science and Health Union/ ; cstc2022ycjh-bgzxm0126//Chongqing Talent Project/ ; CSTB2022NSCQ-MSX0553//Chongqing Natural Science Foundation/ ; }, abstract = {Age-related hearing loss (ARHL) is a prevalent sensory disorder lacking disease-modifying interventions. The biological drivers, particularly the contribution of the gut microbiota and gut-inner ear crosstalk, remain poorly defined. Here, we utilize germ-free (GF) mice and fecal microbiota transplantation (FMT) to isolate microbiota-dependent effects on ARHL progression. Through integrated metagenomic, metabolomic, and proteomic profiling, we map molecular signatures of auditory aging and uncover functional gut-inner ear network, prioritizing 5-hydroxytryptophan (5-HTP) as a key intermediate metabolite within this network. Furthermore, in an aging-like House Ear Institute-Organ of Corti 1 (HEI-OC1) model, 5-HTP exhibits protective effects, potentially mediated through the PI3K/Akt-antioxidant signaling axis. Collectively, this study provides a valuable multi-omics resource and highlights microbiota-derived metabolic regulation as a promising avenue for biomarker discovery and therapeutic development in ARHL.}, } @article {pmid41618133, year = {2026}, author = {Wang, S and Fan, X and Zheng, Z and Gu, Q and Xu, S and Zhu, Y and Zhang, F and Diao, M and Hu, W}, title = {Multi-omics characterized the effects of Akkermansia muciniphila and fecal microbiota transplant on the microglial activation after traumatic brain injury.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-026-04775-5}, pmid = {41618133}, issn = {1471-2180}, support = {2024ZL718//Science and Technology Program of Traditional Chinese Medicine in Zhejiang Province/ ; 2025KY1055//The medical and healthresearch project of Zhejiang province/ ; 2025KY1091//The medical and healthresearch project of Zhejiang province/ ; A20250077//Hangzhou Health Science and Technology Program/ ; 20220919Y006//Hangzhou Science and Technology guide project/ ; 2025HZZD04//The Construction Fund of Key Medical Disciplines of Hangzhou/ ; }, } @article {pmid41618079, year = {2026}, author = {Cheng, C and Li, Y and Lv, W and Zhao, J and Zhang, Y and Lu, H}, title = {A dual pathway intervention of tES and FMT enhances emotion regulation in stressed military personnel.}, journal = {Discover mental health}, volume = {}, number = {}, pages = {}, doi = {10.1007/s44192-026-00375-x}, pmid = {41618079}, issn = {2731-4383}, support = {LHJJ24XL08//The Project of Psychological Interdisciplinary Integration/ ; LHJJ24XL08//The Project of Psychological Interdisciplinary Integration/ ; LHJJ24XL08//The Project of Psychological Interdisciplinary Integration/ ; LHJJ24XL08//The Project of Psychological Interdisciplinary Integration/ ; LHJJ24XL08//The Project of Psychological Interdisciplinary Integration/ ; LHJJ24XL08//The Project of Psychological Interdisciplinary Integration/ ; }, abstract = {This review explores novel strategies for enhancing emotion regulation in military personal under stress, based on the interaction mechanisms of the microbiota-brain-gut axis. Military stress often triggers emotional fluctuations, cognitive decline, and physiological dysregulation, significantly impairing both mental health and combat performance. Existing research has primarily focused on psychological remediation, with insufficient attention paid to physiological mechanisms-particularly brain-gut interactions in emotion regulation. This paper proposes a dual-mode intervention strategy combining "top-down" and "bottom-up" approaches. On one hand, non-invasive neuromodulation techniques such as transcranial electrical stimulation (tES) are used to precisely regulate emotion-related brain regions, enabling immediate mitigation of negative emotions. On the other hand, fecal microbiota transplantation (FMT) is employed to restore gut microbial balance, thereby modulating neurotransmitter production and central nervous function via the gut-brain axis to enhance long-term emotional stability. Ultimately, we propose an integrated intervention combining tES and FMT, which addresses both acute emotional control and sustained regulation. This approach offers a promising theoretical and practical framework for enhancing emotion regulation, safeguarding psychological health, and maintaining combat effectiveness in high-stress military environments.}, } @article {pmid41623954, year = {2025}, author = {Abtahi Froushani, SM and Hasani, SJ and Ghaderi, M and Mahmoudzadeh, L}, title = {A review of inflammatory bowel diseases in humans and pets: treatment strategies.}, journal = {Veterinary research forum : an international quarterly journal}, volume = {16}, number = {11}, pages = {601-610}, pmid = {41623954}, issn = {2008-8140}, abstract = {Inflammatory bowel disease (IBD) encompasses a group of chronic inflammatory conditions that primarily impact the gastrointestinal system. While ulcerative colitis and Crohn's disease are the principal manifestations in humans, animals frequently exhibit lymphocytic-plasmacytic enteritis/colitis and eosinophilic enteritis/colitis. Growing evidence suggests a complex interplay among genetic predisposition, gut microbiota imbalance and abnormal immune responses to intestinal microbes in susceptible individuals. This intricate involvement results in remarkably similar clinical presentations across species. Patients often experience symptoms such as diarrhea, vomiting, weight loss and anemia. Extraintestinal manifestations including uveitis, skin rash and arthritis may also occur. Endoscopy and biopsy typically serve as the gold standard for confirming the diagnosis and differentiating it from other gastrointestinal disorders in humans and animals. The treatment approach generally focuses on managing disease activity through immunosuppressive medications such as glucocorticoids, administered at appropriate dosages. However, the precise cause of IBD remains a topic of ongoing research. With the emergence of additional treatment options like herbal compounds and fecal microbiota transplantation, which have demonstrated effectiveness in restoring gut health in IBD patients, there is optimism for novel therapeutic strategies. Ultimately, conclusion is that chronic gastrointestinal conditions like IBD are complex in both human and veterinary medicine. These diseases share numerous common pathophysiological features, yet, diagnostic and treatment challenges continue to exist.}, } @article {pmid41617714, year = {2026}, author = {Du, Q and Li, Q and Ullah, H and Wei, Y and Liao, G and Xiao, X and Yao, J and Li, K}, title = {Harnessing gut microbiota for brain health: protective role of Hungatella hathewayi for post-mTBI cognitive impairment.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-026-00922-y}, pmid = {41617714}, issn = {2055-5008}, support = {2024NSFSC0592//Sichuan Province Science and Technology Support Program/ ; U22A20334//National Natural Science Foundation of China/ ; }, abstract = {Cognitive impairment (CI) following mild traumatic brain injury (mTBI) poses a clinical challenge, with emerging evidence implicating gut microbiota. This study found that mTBI patients who developed CI exhibited decreased Hungatella hathewayi, while those without CI showed an increase. Microbiota transplantation in mTBI rats revealed that higher Hungatella hathewayi levels enriched beneficial, short-chain fatty acid (SCFA) -producing bacteria and reduced harmful ones. Elevated Hungatella hathewayi improved performance in the Morris water maze and novel object recognition tests, indicating enhanced spatial learning and memory. It also reduced gut and brain inflammation, shown by lower TNF-α and IL-6 mRNA expression, and promoted M2 microglia polarization in the peri-lesional cortex. Metabolomics identified increased fecal and serum butyrate, a SCFA with anti-neuroinflammatory properties. Thus, Hungatella hathewayi may mitigate Post-mTBI CI by boosting butyrate production, which alleviates intestinal inflammation, shifts microglia toward the protective M2 phenotype, reduces neuroinflammation, and supports neuroprotection, ultimately lowering CI risk after mTBI. This study was registered with the Chinese Clinical Trial Registry (ChiCTR) on May 31, 2023 (Registration number: ChiCTR2300072000, URL: https://www.chictr.org.cn/showproj.html?proj=197867).}, } @article {pmid41617211, year = {2026}, author = {Sang, X and Zheng, Q and Qin, M and Chen, M and Wan, X and Hao, M and Yang, Q and Cao, G}, title = {Pentagalloylglucose, a limited oral bioavailability polyphenol, improves allergic asthma through regulating gut microbiota and modulating enteritis.}, journal = {British journal of pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bph.70345}, pmid = {41617211}, issn = {1476-5381}, support = {82274101//National Natural Science Foundation of China/ ; 82374123//National Natural Science Foundation of China/ ; LY24H280002//Natural Science Foundation of Zhejiang Province/ ; LQ23H280004//Natural Science Foundation of Zhejiang Province/ ; 2025JKZKTS23//Research Project of Zhejiang Chinese Medical University/ ; 2024R410A033//Students Science and Technology Innovation Activity Plan of Zhejiang Province/ ; }, abstract = {BACKGROUND AND PURPOSE: Pentagalloylglucose (PGG), a natural hydrolysable gall tannin, has limited bioavailability, and its biological activities are concentrated in the digestive system. However, our study discovered that this nonabsorbable compound can improve allergic asthma. This study focuses on elucidating the mechanisms underlying PGG's anti-allergic asthma effects.

METHODS: PGG serum metabolites were analyzed by UPLC/Q-TOF MS. To further explore its mechanisms, 16S rRNA sequencing, qPCR, and UPLC/Q-TOF MS were used to assess gut microbiota and metabolites. Fecal microbiota transplantation from PGG-treated mice into antibiotic-treated asthmatic mice evaluated its microbiota-dependent effects. Flow cytometry analyzed PGG's modulation of pulmonary ILC2s in a murine asthma‑colitis comorbid model.

KEY RESULTS: PGG's serum metabolites were below the quantification limit. PGG administration improved colonic injury and modulated L. reuteri; notably, exogenous L. reuteri alleviated asthma via increasing I3A from Trp metabolism. However, fecal microbiota transplantation from PGG-treated mice did not alleviate asthma, and PGG remained effective in microbiota-depleted mice, suggesting its action is microbiota-independent. Furthermore, PGG alleviated intestinal inflammation in both normal and antibiotic-treated asthmatic mice. In a comorbid colitis-asthma model, PGG counteracted colitis-aggravated asthma symptoms by modulating lung ILC2s.

CONCLUSION AND IMPLICATIONS: Although PGG modulates the gut microbiota and related metabolites, its anti-asthmatic effect is not primarily dependent on this pathway. Notably, it can ameliorate lung ILC2 dysregulation by alleviating enteritis.}, } @article {pmid41616125, year = {2026}, author = {Zhu, S and Bian, S and Lu, J and Wang, Y and Iqbal, M and Kiani, FA and Dong, H and Zhang, X and Yuan, Z and Liu, F and Li, A}, title = {Pathogenesis of Bovine Mastitis and Influence of the Gut Microbiota: A Review.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c13667}, pmid = {41616125}, issn = {1520-5118}, abstract = {Bovine mastitis (BM) is a highly prevalent bacterial infection that causes significant economic losses in the dairy industry. Its pathogenesis involves the recognition of pathogen-associated molecular patterns by Toll-like receptors (TLRs, primarily TLR2 and TLR4) and the subsequent activation of the NF-κB signaling pathway. Emerging evidence highlights the critical role of the gut microbiota in regulating BM through the "gut-mammary axis." Gut dysbiosis reduces microbial diversity, impairs the intestinal barrier, and promotes endotoxemia or translocation of metabolites, such as LPS (lipopolysaccharide) and short-chain fatty acids (SCFAs), which modulate mammary inflammation. Traditional antibiotic therapy is increasingly limited by resistance and residues, necessitating alternative approaches: targeting the gut microbiota through probiotics, fecal microbiota transplantation (FMT), or plant-derived active components offers promising strategies to restore microbial balance, enhance intestinal barrier function, and suppress excessive inflammation, thereby providing novel avenues for the prevention and treatment of BM.}, } @article {pmid41614917, year = {2026}, author = {Zhan, M and Chen, H and Fu, X and Tang, S and Song, X and Li, H and Zhu, L and Wang, B}, title = {TUDCA Ameliorates Cognitive Impairment in APP/PS1 Mice by Modulating the Microbiota-Gut-Brain Axis.}, journal = {Current issues in molecular biology}, volume = {48}, number = {1}, pages = {}, doi = {10.3390/cimb48010087}, pmid = {41614917}, issn = {1467-3045}, support = {2020ZY013802//Chongqing Municipal Health Commission and Chongqing Science and Technology Bureau/ ; }, abstract = {Tauroursodeoxycholic acid (TUDCA), a bile acid conjugate, has been suggested to improve cognition in models of Alzheimer's disease (AD), although its underlying mechanisms remain unclear. This study aimed to evaluate the effects of TUDCA and its potential pathways in APP/PS1 mice. Behavioral tests, assessments of amyloid-β (Aβ) deposition, neuroinflammation, peripheral inflammatory responses, intestinal barrier integrity, and gut microbiota composition were performed, along with pseudo-sterile mouse experiments and fecal microbiota transplantation (FMT). The expression of genes related to the TLR4/NF-κB/NLRP3 pathway was also examined. TUDCA significantly ameliorated cognitive impairments, reduced Aβ accumulation, and suppressed inflammatory responses in both the central nervous system and peripheral tissues. It improved intestinal barrier function and reshaped gut microbial composition by reducing pro-inflammatory taxa. FMT demonstrated that TUDCA-modulated microbiota contributed to improved learning and memory in AD mice, whereas antibiotic-induced pseudo-sterility indicated that TUDCA also exerted cognitive benefits independent of gut flora. Moreover, TUDCA inhibited the activation of the TLR4/NF-κB/NLRP3 pathway. In conclusion, TUDCA alleviates AD-related cognitive deficits partly through modulation of the microbiota-gut-brain axis while also acting via microbiota-independent mechanisms, supporting its potential as a promising therapeutic strategy for AD.}, } @article {pmid41614846, year = {2025}, author = {Montoya Montoya, J and Gómez, EC and Tabares Guevara, JH and Arango Rincón, JC and Naranjo Preciado, TW}, title = {Effect of Gut Microbiota Alteration on Colorectal Cancer Progression in an In Vivo Model: Histopathological and Immunological Evaluation.}, journal = {Current issues in molecular biology}, volume = {48}, number = {1}, pages = {}, doi = {10.3390/cimb48010015}, pmid = {41614846}, issn = {1467-3045}, support = {646-2021//Ministerio de Ciencia, Tecnología e Innovación/ ; }, abstract = {Background/Objectives: Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide, with its development influenced by diet, obesity, and gut microbiota (GM) alterations. This study aimed to evaluate the impact of human fecal microbiota transplantation (FMT) on the progression of CRC in a murine model. Methods: CRC was chemically induced in BALB/c mice using azoxymethane/dextran sulfate sodium (AOM/DSS). Mice were transferred with GM via FMT and divided into two experimental groups according to the microbiota source (healthy donors or CRC patients). A positive control group (AOM/DSS without FMT) and a negative control group (no CRC induction or FMT) were included. Clinical parameters, histopathological analyses, and cytokine profiling were performed. Results: Mice receiving FMT, particularly from CRC patients, exhibited increased mitotic activity, dysplasia, neoplastic proliferation, structural alterations in the colon, and more pronounced GALT hyperplasia. At the immunological level, both FMT groups (healthy and CRC-derived) showed modulation of IL-1β, IL-4, IL-6, IL-10, IL-17A, and TNF-α compared to the positive control. Conclusions: Human GM transplantation modulated the colonic microenvironment through histopathological and immunological changes, influencing CRC progression in this murine model. These findings highlight the role of GM in shaping CRC development and suggest that human-derived microbiota may significantly impact tumor dynamics.}, } @article {pmid41614677, year = {2026}, author = {Pettersson, M and La Sala, G and Gunnarsson, A and Vildhede, A and Sparklin, B and Holm, B and Petrović, D and Lasky, G and Turick, S and Szydlowska, M and Gopalakrishnan, V and Bake, T and Petersen, J and Brånalt, J and Westerlund, K and Taillefer, M and Henricsson, M and Ek, M and Warrener, P and Roth, R and Cohen, T and Sjögren, T and Fahlander, U and Jurva, U and Morias, Y and Liddle, J}, title = {Discovery of a Highly Potent and Selective Small-Molecule Inhibitor of In Vivo Anaerobic Choline Metabolism by Human Gut Bacteria.}, journal = {Journal of medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jmedchem.5c01451}, pmid = {41614677}, issn = {1520-4804}, abstract = {Trimethylamine (TMA) Lyase is an enzyme expressed in human gut bacteria that plays a pivotal role in the formation of trimethylamine oxide (TMAO), a metabolite implicated in the development of heart failure. Here, we describe a strategy to design covalent inhibitors targeting the active site thiyl radical involved in the catalytic cycle of the enzyme under anaerobic conditions. This strategy led to the discovery of 7, a previously unreported highly potent and selective inhibitor of TMA Lyase. When dosed orally to rats, 7 shows a significant reduction of circulating TMAO levels and, importantly, demonstrates inhibition of TMAO generated from a human microbiome when profiled in a human fecal mouse transplant model.}, } @article {pmid41613791, year = {2026}, author = {Mozga, K and Synowiecka, O and Rydzyk, I and Marek, A and Wieczorek, E and Petniak, A and Gil-Kulik, P}, title = {The Frontier of Melanoma Treatment: Defeating Immunotherapy Resistance-A Systematic Review.}, journal = {Oncology research}, volume = {34}, number = {2}, pages = {4}, pmid = {41613791}, issn = {1555-3906}, mesh = {Humans ; *Melanoma/therapy/immunology/pathology/drug therapy ; *Immunotherapy/methods ; *Drug Resistance, Neoplasm/immunology ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {OBJECTIVES: Immunotherapy based on immune checkpoint blockade (ICB) has become a key treatment for melanoma. However, the increasing number of cases of melanoma resistant to immunotherapy highlights the need to develop methods to overcome this resistance. This study aims to collect the most recent information on melanoma immunotherapy, discuss potential strategies to overcome resistance to immunotherapy, and identify areas that require further analysis.

METHODS: To achieve this goal, scientific publications from 2021-2024 available in PubMed and Google Scholar databases were analyzed. The databases were searched using the following terms: "melanoma", "immunotherapy", "Immune Checkpoint Blockade", and "immunoresistance".

RESULTS: The results of preclinical and early-stage clinical research indicate the potential application of tank-binding kinase 1 (TBK-1), fecal microbiota transplant (FMT), Toll-like Receptor 9 (TLR9), lipid nanoparticles (LNPs) containing a stimulator of an interferon gene agonist (STING), BRAF inhibitors, Lymphocyte Activation Gene (LAG-3), T-Cell Immunoglobulin and ITIM Domain (TIGIT), and oncolytic viruses (OVs) as potential methods to enhance melanoma sensitivity to ICB.

DISCUSSION: To optimize immunotherapy, further research is needed to determine the detailed mechanisms of action, safety profiles, tolerability, and precise patient selection criteria for methods capable of overcoming melanoma's immunoresistance.}, } @article {pmid41613143, year = {2025}, author = {Liu, L and Zhang, X and Wang, C and Zhou, K and Bao, J and Cheng, Z and Sun, H and Zhu, C and Yu, G and Xiao, W and Wan, R}, title = {Dysregulation of the microbiota-gut-brain axis induced by chronic pancreatitis mediates anxiety- and depression-like behaviors in mice.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1753424}, pmid = {41613143}, issn = {1664-3224}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Depression/etiology/microbiology ; *Anxiety/etiology/microbiology ; Mice ; *Pancreatitis, Chronic/microbiology/psychology/complications/chemically induced ; Mice, Inbred C57BL ; Male ; *Behavior, Animal ; Disease Models, Animal ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; *Brain-Gut Axis ; *Brain/metabolism ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Anxiety and depression are common psychological complications in patients with chronic pancreatitis (CP). This study aims to investigate the dysregulation of microbiota-gut-brain axis induced by CP in driving anxiety- and depression-like behaviors in mice.

METHODS: C57BL/6J mice injected with caerulein (Cae) were used to establish an experimental CP model. Behavioral tests were performed to assess anxiety- and depression-like behaviors. The gut microbiota composition and serum metabolites were analyzed via 16S rRNA sequencing and liquid chromatography-mass spectrometry, respectively. Antibiotic cocktail (ABX) and fecal microbiota transplantation (FMT) models were employed to validate the direct role of the gut microbiota, while mixed probiotic gavage was used for intervention evaluation.

RESULTS: Cae-injected mice presented typical CP symptoms and significant anxiety- and depression-like behaviors. 16S rRNA sequencing revealed altered gut microbiota composition in CP mice, with a reduced abundance of Lactobacillus and enrichment of Helicobacter. ABX and FMT experiments confirmed that the CP-derived gut microbiota can independently induce anxiety/depression-like behaviors. In CP mice, Serum corticosterone and its metabolite levels were significantly increased in CP mice. CP-induced microbiota dysbiosis can induce the downregulation of intestinal barrier and blood-brain barrier functions, increase inflammatory levels, and extensively dysregulate neurotransmitter transmission in the brain. Treatment with mixed probiotics improved anxiety- and depression-like behaviors in CP mice.

CONCLUSIONS: CP promotes anxiety- and depression-like behaviors in mice by inducing gut microbiota dysbiosis. This study provides experimental evidence for the use of microbiota-targeted interventions for treating the psychological complications of CP.}, } @article {pmid41613006, year = {2025}, author = {Wang, ZQ and Zheng, HD and Li, LJ and Cao, LL and Shen, L and Qiao, Y and Chen, YY and Wu, LY and Li, GN and Wu, HG}, title = {Electroacupuncture alleviates Parkinson's disease by targeting HDAC/SIRT-mediated deacetylation of 14-3-3.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1719326}, pmid = {41613006}, issn = {1663-4365}, abstract = {INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and the accumulation of pathological α-synuclein. Although current treatments can alleviate symptoms, they do not modify disease progression. Growing evidence implicates gut microbiota dysbiosis and aberrant protein acetylation in PD pathogenesis. Electroacupuncture (EA) has shown therapeutic potential in PD; however, its effects on protein acetylation remain unclear.

METHODS: A PD mouse model was established through MPTP induction and fecal microbiota transplantation (FMT) from PD patients. Mice received EA stimulation at Baihui (GV20) and Yanglingquan (GB34) acupoints for 14 days. Behavioral tests, immunohistochemistry, Western blot, qPCR, and 4D label-free acetyl proteomics were employed to assess motor function, neuronal integrity, protein expression, and acetylation profiles.

RESULTS: EA significantly improved motor coordination, enhanced sensorimotor function in the adhesive removal test, and increased open-field activity in PD mice. It attenuated the loss of tyrosine hydroxylase-positive neurons and decreased α-synuclein accumulation in the substantia nigra. Proteomic analysis revealed hyperacetylation of Ywhaq (14-3-3) in PD mice, which was reversed by EA. Mechanistically, EA upregulated the expression of deacetylases HDAC1/2/3 and SIRT1/2 at both protein and mRNA levels, restoring acetylation homeostasis.

CONCLUSION: Electroacupuncture ameliorates behavioral and neuropathological phenotypes in a PD mouse model by restoring deacetylase expression and normalizing protein acetylation, particularly of 14-3-3. Our results underscore the therapeutic potential of EA and highlight acetylation modulation as a promising strategy for PD treatment.}, } @article {pmid41612728, year = {2026}, author = {Li, S and Che, C and Zhou, Y and Fan, D and Bai, X and Lu, Y and Zhao, X}, title = {Gut microecology empowers cancer immunotherapy: commensal microbiota-mediated mechanisms and translational prospects of PD-1/PD-L1 therapy.}, journal = {Cancer biology & medicine}, volume = {}, number = {}, pages = {}, doi = {10.20892/j.issn.2095-3941.2025.0347}, pmid = {41612728}, issn = {2095-3941}, support = {82222058//National Natural Science Foundation of China/ ; 82425046//National Natural Science Foundation of China/ ; 82273142//National Natural Science Foundation of China/ ; }, abstract = {Anti-programmed cell death protein 1 (PD-1) or its ligand (PD-L1) are immune checkpoint inhibitors (ICIs) that have revolutionized cancer therapy. However, the efficacy of anti-PD-1 and anti-PD-L1 is limited by resistance and inter-individual variability. In recent years increasing evidence has highlighted the pivotal role of the gut microbiota in modulating the response to PD-1/PD-L1 immunotherapy. Extensive preclinical studies have demonstrated that commensal microbes can increase the efficacy of PD-1/PD-L1 blockade through multiple mechanisms, including the production of metabolites, such as short-chain fatty acids (SCFAs), tryptophan derivatives, and extracellular polysaccharides that remodel the tumor microenvironment, as well as the activation of immune pathways involving dendritic cells, CD8[+] T cells, and M1 macrophages to increase antitumor immunity. Moreover, clinical studies have shown that fecal microbiota transplantation (FMT) and targeted probiotic interventions show promise for improving the response to PD-1/PD-L1 therapy, while reducing the risk of immune-related adverse events (irAEs). This review systematically explores the multifaceted regulatory roles of the commensal microbiota in PD-1/PD-L1 therapy and examines the preclinical prospects of microbiota-based personalized immunotherapeutic strategies. The integration of multiomics technologies, synthetic biology, and precise microbiota interventions may further optimize PD-1/PD-L1 immunotherapy and offer novel insights into antitumor immune modulation.}, } @article {pmid41611085, year = {2026}, author = {Vullierme, PN and Galperine, T and Benech, N and Alric, L and Mosca, A and Joly, AC and Kapel, N and Scanzi, J and Landman, C and Sokol, H and Bleibtreu, A}, title = {Fecal microbiota transplantation in compassionate indications: French experience from 2019 to 2022.}, journal = {Infectious diseases now}, volume = {}, number = {}, pages = {105247}, doi = {10.1016/j.idnow.2026.105247}, pmid = {41611085}, issn = {2666-9919}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is validated for recurrent Clostridioides difficile infections but is increasingly considered for compassionate indications: steroid-refractory graft-versus-host disease (GVHD), multidrug-resistant organism (MDRO) eradication, severe inflammatory or infectious colitis. Evidence remains limited outside clinical trials.

METHODS: Retrospective multicenter analysis of requests submitted to the French National Commission for compassionate FMT between 2019 and 2022. Approved cases were evaluated for feasibility, safety, and clinical outcomes.

RESULTS: Among 67 requests, 54 were approved and 40 FMT procedures were performed. The main indications were severe steroid-resistant GVHD (35%), MDRO carriage (28%), and inflammatory/infectious colitis (12%). Overall success was 37.5%. The response rate for GVHD was 53% and 31% for MDRO eradication. Adverse events were mostly mild.

CONCLUSIONS: Compassionate FMT in France is feasible through a centralized process but shows variable efficacy depending on the indication. GVHD seems to be the most promising target, while MDRO eradication and colitis require further evaluation.}, } @article {pmid41608653, year = {2026}, author = {Yang, RL and Lu, Q and Liang, EM and Luo, HC}, title = {Strengthening causal inference and analytical rigor in the Wumei Pills-Lactobacillus reuteri-intestinal stem cell axis for chemotherapy-induced mucositis.}, journal = {World journal of stem cells}, volume = {18}, number = {1}, pages = {114114}, pmid = {41608653}, issn = {1948-0210}, abstract = {A recent preclinical study reported that Wumei Pills (WMP) and Lactobacillus reuteri (L. reuteri) mitigate 5-fluorouracil-induced intestinal mucositis by promoting intestinal stem cell (ISC)-mediated repair via Wnt/β-catenin signaling. The mechanistic interpretation rests largely on systemic inflammation readouts, correlative microbiota changes, and immunohistochemistry of pathway markers. From a clinical standpoint, chemotherapy-induced mucositis remains a common and burdensome toxicity that leads to dose reductions, treatment delays, and infection risk; current care is largely supportive and does not directly restore ISC-mediated repair. This unmet need motivates rigorous appraisal of the proposed "WMP → L. reuteri → ISC/Wnt" axis. To highlight key methodological considerations that may affect causal inference and analytical rigor in the proposed "WMP → L. reuteri → ISC/Wnt" pathway. This letter critically appraises the study's design, endpoints, and analyses against current best practices in mucositis biology, microbiome causality testing, Wnt/β-catenin pathway validation, and preclinical statistics, and synthesizes concrete, literature-grounded remedies. Six issues with potential impact on interpretation were identified: (1) Reliance on serum cytokines/lipopolysaccharide to infer local mucosal inflammation, with limited tissue-level indices (e.g., myeloperoxidase, interleukin-1β, immune-cell infiltration); (2) Absence of necessity/sufficiency tests to verify microbiota mediation (e.g., L. reuteri depletion, WMP-donor fecal microbiota transplantation, probiotic add-back); (3) Pathway evidence tiering - Wnt/β-catenin activation not confirmed by β-catenin nuclear translocation or downstream targets (Axin2, c-Myc, cyclin D1), and Lgr5 quantification/specificity insufficient; (4) Statistical design under-specified (power justification, blinded assessment, control of multiple comparisons) and potential cage effects unmodeled; (5) Limited dose-response and safety profiling for WMP/L. reuteri; and (6) Constrained generalizability (single sex/strain/age, lack of ABX-only controls, single time-point). The reported benefits of WMP and L. reuteri in chemotherapy-induced mucositis are promising, but stronger causal and analytical foundations are needed. Incorporating tissue-level inflammation readouts, microbiota loss-/gain-of-function designs, definitive Wnt/β-catenin activation assays, rigorous statistical practices (including mixed-effects models for cage clustering and multiplicity control), dose-response/safety evaluation, and broader experimental scope (sex/age/strain, ABX-only controls, time-course) will yield more robust and translationally relevant conclusions.}, } @article {pmid41608641, year = {2026}, author = {Sun, ZH and Gong, Q and Wang, ZL and Li, C and Wang, JN and Yu, JT and Ji, ML and Zhang, DF and Wei, J and Xie, SS and Zhou, FJ and Li, XY and Suo, XG and Zhu, Q and Jin, J and Shao, W and Pan, P and Meng, XM}, title = {Microbiota-Gut-Kidney Axis and Targeted Therapeutic Strategies in Kidney Diseases.}, journal = {International journal of biological sciences}, volume = {22}, number = {3}, pages = {1142-1161}, pmid = {41608641}, issn = {1449-2288}, mesh = {Humans ; Animals ; *Gastrointestinal Microbiome ; *Kidney Diseases/microbiology/therapy ; Fecal Microbiota Transplantation ; Synbiotics ; Diet, Protein-Restricted ; Precision Medicine ; }, abstract = {The gut microbiota, as a source of profound genetic and metabolic capacity, affects every aspect of human biology including health, development and aging, as well as disease. Studies have demonstrated the crosstalk between the gut microbiota and the kidney, which is directly referred to as the "microbiota-gut-kidney axis". Most gut microbiota metabolites are associated with metabolic, immune, and inflammatory pathways. Disruption of gut microbiota homeostasis in patients with kidney disease contributes to further loss of kidney function, forming a vicious cycle. This discovery may provide a potential avenue of treatment for kidney diseases, creating a new therapeutic paradigm. Moreover, new therapeutic strategies seem to be beneficial for kidney health via the modulation of the gut microbiota. Although these strategies show early beneficial results, their long-term effectiveness and safety require further investigation and confirmation. In this review, we discuss the interactions between the gut microbiota and kidney diseases and explore related therapeutic strategies. A comprehensive understanding of the microbiota-gut-kidney axis will facilitate the development of efficient therapeutic measures for kidney diseases.}, } @article {pmid41608475, year = {2025}, author = {Xu, G and Luo, R and Wu, Z and Liu, C and Liao, H and Wu, J and Li, Z and Wang, Y and Chen, X and Li, Y and Xu, R}, title = {IgG/IgM-coated gut microbiota in schizophrenia: associations with inflammation disease activity.}, journal = {Frontiers in psychiatry}, volume = {16}, number = {}, pages = {1689069}, pmid = {41608475}, issn = {1664-0640}, abstract = {BACKGROUND: While immunoblobulin A(IgA) dominates gut mucosal immunity, the roles of immunoglobulin M (IgM) and immunoglobulin G (IgG) in host-microbiota interactions remain poorly characterized, particularly in schizophrenia (SCZ). Although gut dysbiosis and immune activation have been implicated in SCZ,the contribution of IgG/IgM-coated gut microbiota to disease associated inflammation and behavioral alterations remains unknown.

METHODS: We recruited six patients with SCZ, six with other psychiatric disorders (OPD) and six age- and sex- matched healthy controls. IgG/IgM-coated gut microbiota were isolated from 100 mg fecal samples via magnetic-activated cell sorting (MACS) and profiled by 16S rRNA sequencing. A pilot an IgG/IgM-coated fecal microbiota transplantation (FMT) using anaerobically cultured human intestinal microbiota was conducted in mice to assess the effects on gut pathology, peripheral immunity, and behavior. The percentage of neutrophil granulocyte in peripheral blood was quantified microscopically, and statistical analyses were performed using one-way ANOVA in GraphPad Prism 8, with (p < 0.05.

RESULTS: The proportions of IgM-coated bacteria was significantly higher in patients with SCZ than in healthy controls (p<0.05), with enrichment of Rhodococcuss, Shigella, Clostridium and Streptococcus. Mice receiving a mixture of high-IgM-coated intestinal bacteria mixture showed reduced depletion of peripheral neutrophils, mild colon shortening, and mucosal inflammation compared with those receiving low IgM-coated or uncoated bacteria. In contrast, high IgG-coated bacteria, enriched in Rhodococcuss, Acinetobater and Pseudomonas, decreased in SCZ, but induced similar inflammatory gut changes. No IgG- nor IgM- induced anxiety-like behavior were detect in the mice.

CONCLUSIONS: Our findings reveal that IgG/IgM-coated intestinal microbiota display distinct immunoreactive microbiota signatures associated with SCZ. These coated communities promote gut inflammation without inducing anxiety-like behavior, highlighting their potential as novel biomarkers of SCZ-associated immune dysregulation and as targets for personalized therapeutic strategies.}, } @article {pmid41607755, year = {2026}, author = {Chen, ZK and Zhao, JW and Wang, YG and Wang, C and Shi, M}, title = {Gut microbiota and the colorectal cancer tumor microenvironment: From carcinogenic mechanisms to therapeutic opportunities.}, journal = {World journal of gastrointestinal oncology}, volume = {18}, number = {1}, pages = {115309}, pmid = {41607755}, issn = {1948-5204}, abstract = {Colorectal cancer (CRC) is ranked as the third most common tumor globally, representing approximately 10% of all cancer cases, and is the second primary cause of cancer-associated mortality. Existing therapeutic approaches demonstrate limited efficacy against CRC, partially due to the immunosuppressive tumor microenvironment (TME). In recent years, substantial evidence indicates that dysbiosis of the gut microbiota and its metabolic products is closely associated with the initiation, progression, and prognostic outcomes of CRC. In this minireview, we systematically elaborate on how these microbes and their metabolites directly impair intestinal epithelial integrity, activate cancer-associated fibroblasts, remodel tumor vasculature, and critically, sculpt an immunosuppressive landscape by modulating T cells, dendritic cells, and tumor-associated macrophages. We highlight the translational potential of targeting the gut microbiota, including fecal microbiota transplantation, probiotics, and engineered microbial systems, to reprogram the TME and overcome resistance to immunotherapy and chemotherapy. A deeper understanding of the microbiota-TME axis is essential for developing novel diagnostic and therapeutic paradigms for CRC.}, } @article {pmid41607395, year = {2026}, author = {Uppala, PK and Karanam, SK and Maddi, R}, title = {Science of fecal microbiota transplant: From history to cutting-edge clinical practice.}, journal = {World journal of gastrointestinal endoscopy}, volume = {18}, number = {1}, pages = {113133}, pmid = {41607395}, issn = {1948-5190}, abstract = {Fecal microbiota transplantation (FMT) is a pioneering medical technique designed to re-establish a balanced gut microbiome by transferring processed stool from a rigorously screened donor into the gastrointestinal tract of a recipient. Initially conceived as a last-resort therapy for recurrent Clostridioides difficile (C. difficile) infections - a challenging condition frequently resistant to conventional antibiotics - FMT has achieved impressive clinical response rates, often surpassing 80% in resolving recurrent C. difficile infections. This remarkable success has generated significant enthusiasm for its potential use in addressing a broader spectrum of disorders linked to disrupted gut microbial populations, including inflammatory bowel disease, irritable bowel syndrome, metabolic syndrome, and various autoimmune and neurological conditions. However, the wider clinical integration of FMT is accompanied by several notable challenges. These include the need for optimal donor selection, comprehensive long-term follow-up of recipients, standardization of stool processing and delivery methods, and thorough economic evaluation to establish cost-effectiveness. Safety remains a top priority, with particular attention paid to minimizing the risk of infectious disease transmission and preventing unwanted immune responses. Regulatory standards for FMT vary internationally, with some nations categorizing it as a biologic therapy or experimental treatment, while others have established more formalized approval processes. This article offers a comprehensive examination of FMT, covering its historical evolution, underlying mechanisms, current clinical applications, safety protocols, and regulatory landscape. By consolidating the latest research and clinical guidelines, it aims to educate clinicians, researchers, and policymakers on the expanding role of FMT in modern healthcare.}, } @article {pmid41607157, year = {2025}, author = {Janowski, WM and Kaczmarczyk, GM and Tarasiuk-Zawadzka, A and Fichna, J}, title = {Therapeutic strategies in irritable bowel syndrome: current standards, emerging options and future challenges.}, journal = {Folia medica Cracoviensia}, volume = {65}, number = {4}, pages = {5-29}, doi = {10.24425/fmc.2025.156694}, pmid = {41607157}, issn = {0015-5616}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/diagnosis ; }, abstract = {The development of safe and efficient therapeutic interventions in irritable bowel syndrome (IBS) is challenged by the complexity of its pathophysiology and a wide range of symptoms. On the other hand, with the progress in design of diagnostic and analytical tools (including software and artificial intelligence), we understand more about the disease what brings us closer to its successful treatment. In this review we discuss currently available and potential future pharmacological and non-pharmacological treatments, focusing mainly on clinical proof of their efficiency. Moreover, we aim at identifying risk and challenges that need to be overcome to obtain a marketed drug.}, } @article {pmid41606514, year = {2026}, author = {Hu, S and Luo, C and Wan, S and Zhang, S and Li, N and Liu, G and Zhao, LY}, title = {Modulating the gut microbiome to enhance cancer immunotherapy: a systematic review and Meta-Analysis of probiotics and FMT as adjuncts.}, journal = {BMC cancer}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12885-026-15655-6}, pmid = {41606514}, issn = {1471-2407}, } @article {pmid41606381, year = {2026}, author = {Baillieu, V and Delannoy, J and Kapel, N and Barbut, F and Mosca, A and Joly, AC and Waligora-Dupriet, AJ and Sintes, R}, title = {Evaluation of the efficacy of inactivated fecal transplants against Clostridioides difficile: an in vitro study.}, journal = {World journal of microbiology & biotechnology}, volume = {42}, number = {2}, pages = {66}, pmid = {41606381}, issn = {1573-0972}, } @article {pmid41606121, year = {2026}, author = {Duttagupta, S and Messaoudene, M and Hunter, S and Desilets, A and Jamal, R and Mihalcioiu, C and Belkaid, W and Marcoux, N and Fidelle, M and Suissa, D and Ponce, M and Geiger, M and Malo, J and Piccinno, G and Punčochář, M and Filin, A and Heidrich, V and Rusu, D and Mbaye, B and Durand, S and Ben Aissa, I and Puller, V and de Lahondès, R and Blais, N and Tehfe, M and Owen, S and Bélanger, K and Parvathy, SN and Shieh, B and Raphael, J and Lenehan, J and Breadner, D and Rothenstein, J and Rozza, N and Maillou, J and Nili, S and Prifti, DK and Pinto, F and Armanini, F and Kim-Schulze, S and Marron, TU and Kroemer, G and Derosa, L and Zitvogel, L and Silverman, M and Segata, N and Vareki, SM and Routy, B and Elkrief, A}, title = {Fecal microbiota transplantation plus immunotherapy in non-small cell lung cancer and melanoma: the phase 2 FMT-LUMINate trial.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, pmid = {41606121}, issn = {1546-170X}, abstract = {Immune checkpoint inhibitors (ICI) have improved outcomes for patients with non-small cell lung cancer (NSCLC) and melanoma, yet over half of patients exhibit primary resistance. Fecal microbiota transplantation (FMT) may overcome resistance to anti-programmed cell death protein 1 (PD-1) therapy. The clinical activity and safety of FMT plus anti-PD-1 in NSCLC or anti-PD-1 plus anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) therapy in melanoma have not been evaluated. Here we report results from FMT-LUMINate, a multicenter, open-label, phase 2 trial assessing healthy donor FMT plus anti-PD-1 in NSCLC (n = 20) or anti-PD-1 plus anti-CTLA-4 (dual ICI) in melanoma (n = 20), in the first-line setting. Eligible patients received a single FMT via oral capsules prior to ICI initiation. The primary endpoint was objective response rate (ORR) in NSCLC. Secondary endpoints included ORR in melanoma, safety and donor-host microbiome similarity. In NSCLC, the ORR was 80% (16/20), meeting the study primary endpoint. In melanoma, the ORR was 75% (15/20). FMT was deemed safe in both cohorts by an independent data and safety monitoring committee, with no grade 3 or higher adverse events (AEs) in NSCLC and 13 (65%) patients experiencing grade 3 or higher AEs in melanoma. Shotgun metagenomic sequencing revealed that responders developed a distinct post-FMT gut microbiome composition, independent of acquired donor-recipient similarity or strain-level engraftment. Responders exhibited significantly greater loss of baseline bacterial species compared to non-responders, with frequent depletion of Enterocloster citroniae, E. lavalensis and Clostridium innocuum. This finding was reproduced across three published FMT oncology trials. We recolonized antibiotic-treated, tumor-bearing mice with post-FMT stool from two responder patients, and reintroduction of the specific bacterial species that were lost after FMT abrogated the antitumor effect of ICI. Taken together, these findings confirm the clinical activity of FMT in combination with ICI and suggest that the elimination of deleterious taxa is required for FMT-mediated therapeutic benefit. ClinicalTrials.gov identifier: NCT04951583 .}, } @article {pmid41606120, year = {2026}, author = {Fernandes, R and Jabbarizadeh, B and Rajeh, A and Hong, MMY and Baines, KJ and Ernst, S and Winquist, E and Ali, AS and Penny, S and Figueredo, R and Parvathy, SN and Lenehan, JG and Pinto, DM and Silverman, MS and Maleki Vareki, S}, title = {Fecal microbiota transplantation plus immunotherapy in metastatic renal cell carcinoma: the phase 1 PERFORM trial.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, pmid = {41606120}, issn = {1546-170X}, support = {1-MR_2022_4884//Lotte and John Hecht Memorial Foundation (Lotte & John Hecht Memorial Foundation)/ ; 203745/WT_/Wellcome Trust/United Kingdom ; }, abstract = {Immune checkpoint inhibitors (ICIs) improve outcomes in metastatic renal cell carcinoma (mRCC) but are hindered by immune-related adverse events (irAEs). Modulation of the gut microbiome may enhance efficacy and mitigate toxicity, yet the safety and mechanisms of healthy donor fecal microbiota transplantation (FMT) in mRCC remain unexplored. In this phase 1 trial, 20 treatment-naive patients with mRCC received encapsulated healthy donor FMT (LND101) combined with ipilimumab/nivolumab (n = 16), pembrolizumab/axitinib (n = 3) or pembrolizumab/lenvatinib (n = 1). The primary endpoint was safety, defined by the incidence and severity of irAEs. Secondary endpoints included clinical response (Response Evaluation Criteria in Solid Tumors version 1.1), gut microbiome and immune correlates and patient-reported quality of life. The safety endpoint was met with 50% (10/20) of patients experiencing grade 3 irAEs and no serious FMT-related toxicities or grade 4 or 5 irAEs. Among evaluable patients, the objective response rate was 50% (9/18), including two complete responses (11%, 2/18). Notably, most treatment responders did not develop any grade 3 or higher irAEs. Alpha (α) diversity improvement and durable engraftment of taxa and metabolic functions associated with anti-inflammatory properties correlated with reduced toxicity and improved response. Conversely, patients experiencing grade 3 irAEs exhibited expansion of Segatella copri, particularly with ipilimumab/nivolumab, and elevated levels of donor-derived microbial enzymes previously linked to pro-inflammatory activity. Resilience to toxicity correlated with the maintenance of protective metabolites and increased levels of immune regulatory cells, whereas the presence of grade 3 irAEs and S. copri enrichment was associated with high immune dysregulation. These findings demonstrate the safety and potential for functional microbiome engraftment to optimize response and minimize toxicity in ICI-treated mRCC. ClinicalTrials.gov identifier: NCT04163289 .}, } @article {pmid41606119, year = {2026}, author = {Porcari, S and Ciccarese, C and Heidrich, V and Rondinella, D and Quaranta, G and Severino, A and Arduini, D and Buti, S and Fornarini, G and Primi, F and Stumbo, L and Giannarelli, D and Giudice, GC and Damassi, A and Giron Berríos, JR and Punčochář, M and Barbazuk, TB and Piccinno, G and Pinto, F and Armanini, F and Asnicar, F and Schinzari, G and Derosa, L and Kroemer, G and Sanguinetti, M and Masucci, L and Gasbarrini, A and Tortora, G and Cammarota, G and Zitvogel, L and Segata, N and Iacovelli, R and Ianiro, G}, title = {Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, pmid = {41606119}, issn = {1546-170X}, support = {GR-2018-12365734//Ministero della Salute (Ministry of Health, Italy)/ ; PNRR-POC-2023-12377319//Ministero della Salute (Ministry of Health, Italy)/ ; PNRR-POC-2023-12377319//Ministero della Salute (Ministry of Health, Italy)/ ; 30203//Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)/ ; FIS00001711//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; ERC-StG MicroRestore-101221279//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; 101052444//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; microTOUCH-101045015//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; 101168810//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; ONCOBIOME-825410//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; IHMCSA-964590//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 1U01CA230551//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; }, abstract = {Renal cell carcinoma (RCC) is a common malignancy with limited durable responses to first-line immune checkpoint inhibitor (ICI)-based therapies. Emerging evidence implicates the gut microbiome in modulating ICI efficacy. In the investigator-initiated, randomized, double-blind placebo-controlled phase 2a TACITO trial, we evaluated whether fecal microbiota transplantation (FMT) from complete ICI responders enhances clinical outcomes in treatment-naive patients with metastatic RCC (mRCC) receiving pembrolizumab + axitinib. The primary endpoint was the rate of patients free from disease progression at 12 months after randomization (12-month progression-free survival (PFS)). Secondary endpoints were median PFS and median overall survival, objective response rate (ORR), safety and microbiome changes, after randomization. Forty-five patients randomly received donor FMT (d-FMT) or placebo FMT (p-FMT). Although the primary endpoint was not met (70% versus 41% for d-FMT versus p-FMT, respectively, P = 0.053), the secondary endpoint of median PFS was significantly longer with d-FMT (24.0 months in the d-FMT arm versus 9.0 months in the p-FMT arm; hazard ratio = 0.50, P = 0.035). The ORR was 52% of patients in the d-FMT arm and 32% of patients receiving placebo. Microbiome analysis confirmed donor strain engraftment and increased α-diversity and larger microbiome shifts (β-diversity) compared with baseline composition in the d-FMT treatment group. Acquisition or loss of specific strains, but not total engraftment, was associated with the primary endpoint. Our findings support the safety and potential efficacy of selected donor FMT to enhance ICI-based treatment in mRCC, which deserves further investigations. ClinicalTrials.gov identifier: NCT04758507 .}, } @article {pmid41601624, year = {2025}, author = {Yang, J and Song, X and Yan, S and Li, Q and Yang, W}, title = {The gut microbiota influences neurodegenerative diseases through the gut-brain axis: molecular mechanisms and effects on immune function.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1739329}, pmid = {41601624}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Neurodegenerative Diseases/immunology/microbiology/therapy/metabolism/etiology ; Animals ; *Brain/immunology/metabolism ; *Brain-Gut Axis/immunology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Prebiotics ; }, abstract = {The pathogenesis of neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), is complex and multifactorial. Recent studies indicate that the microbiota-gut-brain axis (MGBA) plays a crucial role in the development and progression of NDDs. The MGBA concept reveals a complex bidirectional regulatory network between the gut microbiota and the central nervous system (CNS), linking them through immune, neural, endocrine, and metabolic pathways. This review summarizes the components of the MGBA, communication pathways between gut microbiota and the brain, and mechanisms by which gut microbiota influence the onset and progression of NDDs. Finally, preclinical therapeutic approaches for NDDs are discussed, evaluating preclinical trial data for probiotics, prebiotics, and fecal microbiota transplantation.}, } @article {pmid41454342, year = {2025}, author = {Song, H and Ma, Y and Peng, L and Gao, F and Fan, X and Yang, M and Hua, T and Yang, Y and Fan, R and Li, Z and Yuan, H}, title = {Platinum-doped emodin carbon dots mitigate sepsis-induced lung injury by targeting the gut-lung axis.}, journal = {Journal of nanobiotechnology}, volume = {24}, number = {1}, pages = {84}, pmid = {41454342}, issn = {1477-3155}, support = {82471239//National Natural Science Foundation of China/ ; JDLCZDZK//Military clinical key specialty project fund/ ; }, abstract = {UNLABELLED: Sepsis-induced acute lung injury is a life-threatening complication with limited therapeutic options. Although the gut-lung axis is crucial in sepsis pathogenesis, effective interventions targeting this pathway remain scarce. Here, we developed multi-enzymatic platinum-doped emodin carbon dots (Pt-ECDs) via a hydrothermal method. Pt-ECDs exhibited superior catalase, superoxide dismutase, glutathione peroxidase and peroxidase-like activities, enabling potent reactive oxygen species (ROS) scavenging. In a murine sepsis model, oral Pt-ECDs significantly improved survival, reduced systemic inflammation, and ameliorated lung injury. Transcriptomic analysis revealed that Pt-ECDs suppressed oxidative stress and macrophage pyroptosis in lung tissues. Mechanistically, integrated metabolomic and microbiome analyses demonstrated that Pt-ECDs modulated the gut microbiota, specifically inhibiting g_Bacteroides-derived palmitic acid (PA) production. We further confirmed that PA exacerbates macrophage pyroptosis and pro-inflammatory polarization by directly binding to NOX2 and NLRP3. Crucially, fecal microbiota transplantation from Pt-ECDs-treated mice attenuated septic lung injury, whereas microbiota depletion abolished the therapeutic benefits. Collectively, our findings identify Pt-ECDs as a promising nanotherapeutic that alleviates septic lung injury by targeting the gut microbiota-palmitic acid-pyroptosis axis.

GRAPHICAL ABSTRACT: [Image: see text]

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-025-03972-0.}, } @article {pmid41444511, year = {2025}, author = {Tang, M and Li, H and Tang, F and Shu, Y and Meng, B and Zhang, Q and Li, C and Xu, Y and Xu, Y and Pan, J and Liu, Y and Hu, L and Wang, C and Wu, T and Li, J}, title = {GPR43 deficiency aggravates sepsis by promoting gut microbiota-dependent barrier disruption and HIF-1α-ENO1 axis-mediated M1 polarization of macrophages.}, journal = {Cellular & molecular biology letters}, volume = {31}, number = {1}, pages = {12}, pmid = {41444511}, issn = {1689-1392}, support = {82400132//National Natural Science Foundation of China/ ; 82470108//National Natural Science Foundation of China/ ; U24A20643//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: GPR43, a receptor for short-chain fatty acids (SCFAs), is broadly expressed in intestinal epithelial and immune cells and is essential for preserving barrier integrity and immune homeostasis. Nevertheless, how GPR43 influences gut microbiota composition and intestinal barrier integrity while also regulating macrophage immunometabolism in the context of sepsis remains poorly understood.

METHODS: A cecal ligation and puncture model was used to induce sepsis in mice. Survival, histopathology, and immune responses were compared between Gpr43[−/−] and wild-type mice; 16S ribosomal RNA (rRNA) sequencing and untargeted metabolomics were performed to evaluate gut microbiota composition and metabolic profiles. Antibiotic-mediated microbiota depletion and fecal microbiota transplantation were used to assess functional impacts. Bone marrow-derived macrophages were employed to investigate the effects of GPR43 deficiency on macrophage polarization. RNA sequencing, metabolic flux analysis, and Western blotting were conducted to explore the molecular mechanisms involved. Peripheral blood mononuclear cell samples from patients with sepsis were analyzed for clinical correlation.

RESULTS: Gpr43[−/−] mice exhibited significantly reduced survival following CLP, along with impaired intestinal barrier function and elevated proinflammatory cytokine levels. Microbiota diversity and SCFA-producing bacteria were markedly decreased, accompanied by reduced SCFA levels in fecal metabolites. Fecal microbiota transplantation (FMT) partially restored gut function and survival in Gpr43[−/−] mice. GPR43-deficient macrophages displayed a strong M1-polarized phenotype with the upregulation of the glycolytic enzyme ENO1 and its upstream regulator HIF-1α. The inhibition of either ENO1 or HIF-1α reversed the proinflammatory phenotype. A clinical data analysis revealed that GPR43 expression was negatively correlated with IL-6, ENO1, and lactate levels.

CONCLUSIONS: GPR43 exerts a dual protective role in sepsis by maintaining gut microbiota homeostasis and barrier integrity and by modulating macrophage metabolism and polarization via the HIF-1α–ENO1 axis. This study provides novel insights into the GPR43 in pathogenesis of sepsis and suggests potential therapeutic targets for intervention.

GRAPHICAL ABSTRACT: [Image: see text]

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s11658-025-00833-4.}, } @article {pmid41601518, year = {2025}, author = {Sgarbossa, C and Chinna Meyyappan, A and Forth, E and Bromley, H and Milev, R}, title = {Assessing the long-term effects of microbial therapeutics as treatment within psychiatry: a systematic review.}, journal = {Frontiers in psychiatry}, volume = {16}, number = {}, pages = {1663719}, pmid = {41601518}, issn = {1664-0640}, abstract = {BACKGROUND: The management and treatment of psychiatric disorders by manipulating the gut microbiome and utilizing microbial therapeutics, via modulation of the gut-brain-axis, has been a rapidly growing field of research. Given the novelty of using microbial therapeutics within psychiatry, a growing number of studies have investigated their use as treatment for various psychiatric disorders and symptoms. However, few studies have explored the longitudinal efficacy of these treatments. This review aims to summarize the findings of any studies assessing the long-term effects of gut-related interventions on mood and psychiatric symptoms.

METHODS: A systematic search of 4 databases (Embase, PsycINFO, Medline, Web of Science) from inception to May 28, 2025, informed by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and using key words relating to microbial therapeutics, psychiatric disorders, and long-term effects was conducted. Findings were included or excluded using pre-determined eligibility criteria such as being been written in English and published by a peer-reviewed journal, assessed for quality using the Cochrane Handbook for Systematic Reviews of Interventions Risk of Bias tool, and qualitatively evaluated.

RESULTS: The search yielded 4175 studies, of which 1274 duplicates were removed. All remaining studies underwent abstract screening, from which 70 records were full-text screened and a total of ten clinical studies (n = 10) met eligibility criteria and were included in the review. The majority of studies explored the effects of microbial therapeutics such as fecal microbiota transplant and probiotics, as treatment for disorders of the gastrointestinal tract as the primary scope, with additional outcome measures assessing psychiatric well-being. The review presented with mixed findings: many studies reported a sustained improvement in symptoms of depression and anxiety ranging from 3- to 18-months post-treatment, while others reported the opposite with no sustained long-term improvement in mood-related symptoms. There was also a lack of consistency across follow-up duration between studies, making it difficult to compare findings.

CONCLUSIONS: Overall, this review highlighted the need for more placebo-controlled studies with larger sample sizes to effectively evaluate the longitudinal potential of microbial therapeutics as treatment for mood-disturbances and psychiatric symptoms. With consideration for the limitations of this field, these results provide evidence that there may be long-term benefits of targeting the gut microbiome as treatment for mood-related disturbances.}, } @article {pmid41601294, year = {2026}, author = {Song, CH and Kim, N and Nam, RH and Choi, H and Jin, I and Kim, EH and Ha, S and Kang, K and Lee, W and Choi, H and Kim, YR and Seok, YJ and Lee, HK and Shin, CM and Lee, DH}, title = {Sex-Dependent Microbial and Host Profiles Following Fecal Microbiota and Bifidobacterium longum Treatment in Stress-Induced Gut Dysbiosis.}, journal = {Gut and liver}, volume = {}, number = {}, pages = {}, doi = {10.5009/gnl250440}, pmid = {41601294}, issn = {2005-1212}, abstract = {BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder influenced by stress, microbial dysbiosis, and immune activation. Microbiota-directed therapies, including fecal microbiota transplantation and probiotics, show promise, but their sex-specific effects remain unclear. We compared the therapeutic effects of lyophilized fecal microbiota (LFM) with Bifidobacterium longum BBH016 in male and female Wistar rats subjected to repeated water avoidance stress.

METHODS: Fecal pellet output (FPO), colonic mast cell infiltration, and fecal short-chain fatty acids were measured. Gut microbial composition and function were analyzed by 16S rRNA sequencing and Kyoto Encyclopedia of Genes and Genomes pathway prediction.

RESULTS: Both interventions significantly reduced FPO and mast cell infiltration in males but had less pronounced effects in females. Microbiota analyses revealed sex-dependent responses, with distinct microbial trajectories in each treatment group. Using linear discriminant analysis effect size, we identified seven key taxa with treatment- or sex-specific enrichment. Alistipes onderdonkii and Bacteroides uniformis consistently increased in both LFM- and B. longum-treated groups, regardless of sex. Bacteroides finegoldii and Barnesiella intestinihominis were specifically enriched in the LFM group. In males, Blautia faecis and Fusicatenibacter saccharivorans were enriched following the interventions, whereas Parabacteroides goldsteinii appeared exclusively in stressed males. Functional predictions revealed the enrichment of estrogen signaling and bile acid pathways in males and the attenuation of proinflammatory pathways in females following LFM. Correlations between microbial taxa and host outcomes were predominantly observed in male rats.

CONCLUSIONS: These findings highlight sex-specific microbial and host responses to microbiota-targeted therapies in a stress-induced IBS model, emphasizing sex as a biological variable in designing personalized microbiome-based treatments.}, } @article {pmid41599902, year = {2026}, author = {Plaza-Diaz, J and Herrera-Quintana, L and Olivares-Arancibia, J and Vázquez-Lorente, H}, title = {Personalized Nutrition Through the Gut Microbiome in Metabolic Syndrome and Related Comorbidities.}, journal = {Nutrients}, volume = {18}, number = {2}, pages = {}, doi = {10.3390/nu18020290}, pmid = {41599902}, issn = {2072-6643}, mesh = {Humans ; *Metabolic Syndrome/microbiology/prevention & control/diet therapy/therapy ; *Gastrointestinal Microbiome/physiology ; Exercise ; *Precision Medicine/methods ; Comorbidity ; Diet ; }, abstract = {Background: Metabolic syndrome, a clinical condition defined by central obesity, impaired glucose regulation, elevated blood pressure, hypertriglyceridemia, and low high-density lipoprotein cholesterol across the lifespan, is now a major public health issue typically managed with lifestyle, behavioral, and dietary recommendations. However, "one-size-fits-all" recommendations often yield modest, heterogeneous responses and poor long-term adherence, creating a clinical need for more targeted and implementable preventive and therapeutic strategies. Objective: To synthesize evidence on how the gut microbiome can inform precision nutrition and exercise approaches for metabolic syndrome prevention and management, and to evaluate readiness for clinical translation. Key findings: The gut microbiome may influence cardiometabolic risk through microbe-derived metabolites and pathways involving short-chain fatty acids, bile acid signaling, gut barrier integrity, and low-grade systemic inflammation. Diet quality (e.g., Mediterranean-style patterns, higher fermentable fiber, or lower ultra-processed food intake) consistently relates to more favorable microbial functions, and intervention studies show that high-fiber/prebiotic strategies can improve glycemic control alongside microbiome shifts. Physical exercise can also modulate microbial diversity and metabolic outputs, although effects are typically subtle and may depend on baseline adiposity and sustained adherence. Emerging "microbiome-informed" personalization, especially algorithms predicting postprandial glycemic responses, has improved short-term glycemic outcomes compared with standard advice in controlled trials. Targeted microbiome-directed approaches (e.g., Akkermansia muciniphila-based supplementation and fecal microbiota transplantation) provide proof-of-concept signals, but durability and scalability remain key limitations. Conclusions: Microbiome-informed personalization is a promising next step beyond generic guidelines, with potential to improve adherence and durable metabolic outcomes. Clinical implementation will require standardized measurement, rigorous external validation on clinically meaningful endpoints, interpretable decision support, and equity-focused evaluation across diverse populations.}, } @article {pmid41599716, year = {2026}, author = {Krynicka, P and Cortegoso Valdivia, P and Morawski, M and Marlicz, W and Skonieczna-Żydecka, K and Koulaouzidis, A}, title = {Microbiota-Driven Strategies for Managing IBD-Associated Risks: From Infections to Mental Health.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {19}, number = {1}, pages = {}, doi = {10.3390/ph19010118}, pmid = {41599716}, issn = {1424-8247}, abstract = {Inflammatory bowel diseases (IBD) are increasingly acknowledged not merely as confined gastrointestinal disorders but as systemic immunometabolic syndromes. Central to this paradigm is the gut microbiota including non-bacterial components such as the virome, whose functional disruption marked by reduced short-chain fatty acids (SCFAs), increasingly implicated in pathogenic processes extending beyond intestinal mucosa. This review outlines how these alternations compromise the epithelial barrier and immune regulation, increasing the risk of recurrent Clostridioides difficile infections to anemia, neuropsychiatric comorbidities, and extraintestinal manifestations. We critically evaluate emerging microbiota-targeted strategies, including fecal microbiota transplantation (FMT), live biotherapeutic products (LBPs), and precision postbiotics, positioning them as potential adjuncts to conventional immunosuppression. Finally, we discuss the current barriers to clinical translation, such as safety and heterogeneity, and propose a future framework for personalized, functionally integrated IBD care aimed at restoring long-term microbiota homeostasis.}, } @article {pmid41599127, year = {2025}, author = {Zhou, Y and Zhang, Y and Li, Y and Chen, Y and Chi, X and You, Z and Zhang, H and Li, Y and Wu, L}, title = {Bile Derivative T3K Ameliorates Colitis by Regulating the Intestinal Microbiota-Bile Acid Axis.}, journal = {Pharmaceutics}, volume = {18}, number = {1}, pages = {}, doi = {10.3390/pharmaceutics18010020}, pmid = {41599127}, issn = {1999-4923}, support = {2023-I2M-2-009//CAMS Innovation Fund for Medical Sciences/ ; }, abstract = {Background/Objectives: The pathogenesis of ulcerative colitis (UC) is complex, and there is an urgent need for effective therapeutic agents with low side effects. Recent studies highlight the critical roles of abnormal bile acid (BA) metabolism and gut microbiota dysbiosis in UC progression. However, there is a significant knowledge gap about the relation between BA and gut microbiota. The BA derivative T3K exerts good anti-UC effect, and its mechanism is still unknown. In this study, we investigate how its anti-UC mechanism is involved in the modulation of the gut microbiota-BA axis and BA metabolism. Methods: Gene expression microarray GSE92415 of UC from the Gene Expression Omnibus was used to analyze BA metabolism. DSS-induced colitis mouse model, Caco-2 and IEC6 cells were used to confirm the anti-UC of T3K using intestinal permeability assay with FITC, Western-blot, immunohistochemical staining, immunofluorescenc and so on in vitro and in vivo. The changes in bile acid and microbiota were measured by 16S rRNA sequencing and bile acid analysis combined with pseudo-germ-free (PGF) models and fecal microbiota transplantation (FMT). Results: T3K demonstrated strong therapeutic effects, including reduced weight loss, lower disease activity index (DAI), and increased colon length. T3K also enhanced the expression of Occludin and Mucin2, and restored gut barrier integrity. Furthermore, T3K improved intestinal dysbiosis and abnormal BA metabolism in colitis mice. Through PGF models and FMT, we confirmed that T3K modulates BA metabolism via the gut microbiota. T3K specifically promotes the growth of beneficial bacteria, such as Akkermansia muciniphila, increases levels of hydrophilic BAs like muricholic acid (MCA), lithocholic acid (LCA) and its derivatives isoLCA and then repairs damaged intestinal mucosa. Conclusions: Bile acid derivative T3K, as a potential anti-UC candidate, effectively restores gut barrier integrity and then ameliorates colitis by improving gut microbiota composition and regulating BA metabolism, including increasing hydrophilic BAs.}, } @article {pmid41597735, year = {2026}, author = {Moser, K and Ballif, A and Pillonel, T and Concu, M and Montenegro-Borbolla, E and Nickel, B and Stampfli, C and Ruf, MT and Audry, M and Kapel, N and Gerber, S and Jacot, D and Bertelli, C and Galpérine, T}, title = {Fecal Microbiota Transplantation Donor Screening: Is Dientamoeba fragilis a Valid Criterion for Donor Exclusion? A Longitudinal Study of a Swiss Cohort.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010217}, pmid = {41597735}, issn = {2076-2607}, support = {//internal funding at the Lausanne University Hospital (CHUV)/ ; grant number 51NF40 180575//he salaries of K.M. and E.M.-B. were supported as a part of NCCR Microbiomes, a National Centre of Competence in Research, funded by the Swiss National Science Foundation/ ; }, abstract = {Dientamoeba fragilis is a protozoan of the human digestive tract, yet its transmission and pathogenic role remain poorly understood. This study aimed to evaluate its impact on the efficacy and safety of fecal microbiota transplantation (FMT) in treating recurrent Clostridioides difficile infection (rCDI). This longitudinal cohort study analyzed stool samples from FMT donors and recipients pre-treatment and at 2 and 8 weeks post-FMT. All samples were retrospectively tested using real-time PCR. Shotgun metagenomics was also performed on selected donor-recipient pairs to explore transmission. CDI cure rates, gastrointestinal adverse events (AEs), and serious adverse events (SAEs) were assessed prospectively. A total of 53 FMT were analyzed (179 samples), with 23 (43%) derived from D. fragilis-positive donor stool (4 of 10 donors, 40%). Four of 52 recipients (18.2%), initially negative and who received treatment from positive donors, tested positive post-FMT. Shotgun metagenomics could not definitely confirm transmission due to the lack of a good reference genome. No significant differences in efficacy, AE, or SAE were observed between FMT from D. fragilis-positive versus -negative donors, even in immunocompromised patients. No SAEs were attributed to FMT. D. fragilis may be transmitted via FMT without evidence of short-term clinical impact. Consequently, RT-PCR detection should be interpreted cautiously in the context of donor exclusion decisions.}, } @article {pmid41597728, year = {2026}, author = {de Groen, P and Gouw, SC and Hanssen, NMJ and Nieuwdorp, M and Rampanelli, E}, title = {Early-Life Gut Microbiota: Education of the Immune System and Links to Autoimmune Diseases.}, journal = {Microorganisms}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/microorganisms14010210}, pmid = {41597728}, issn = {2076-2607}, support = {09150182010020//NWO-VICI grant 2020/ ; 101141346//ERC Advanced grant/ ; 4-SRA-2025-1766-M-B//BREAKTHROUGH T1D Grant/ ; 09150172210050//ZonMw-VIDI grant 2023/ ; }, abstract = {Early life is a critical window for immune system development, during which the gut microbiome shapes innate immunity, antigen presentation, and adaptive immune maturation. Disruptions in microbial colonization-driven by factors such as cesarean delivery, antibiotic exposure, and formula feeding-deplete beneficial early-life taxa (e.g., Bifidobacterium, Bacteroides, and Enterococcus) and impair key microbial functions, including short-chain fatty acid (SCFA) production by these keystone species, alongside regulatory T cell induction. These dysbiosis patterns are associated with an increased risk of pediatric autoimmune diseases, notably type 1 diabetes, inflammatory bowel disease, celiac disease, and juvenile idiopathic arthritis. This review synthesizes current evidence on how the early-life microbiota influences immune maturation, with potential effects on the development of autoimmune diseases later in life. We specifically focus on human observational and intervention studies, where treatments with probiotics, synbiotics, vaginal microbial transfer, or maternal fecal microbiota transplantations have been shown to partially restore a disrupted microbiome. While restoration of the gut microbiome composition and function is the main reported outcome of these studies, to date, no reports have disclosed direct prevention of autoimmune disease development by targeting the early-life gut microbiome. In this regard, a better understanding of the early-life microbiome-immune axis is essential for developing targeted preventive strategies. Future research must prioritize longitudinal evaluation of autoimmune outcomes after microbiome modulation to reduce the burden of chronic immune-mediated diseases.}, } @article {pmid41597349, year = {2025}, author = {Varnas, D and Kunevičius, A and Burokas, A and Urbonas, V}, title = {Fecal Microbiota Transplantation for Autism Spectrum Disorder in Children: Results from a Prospective Open-Label Controlled Observational Study.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {62}, number = {1}, pages = {}, doi = {10.3390/medicina62010065}, pmid = {41597349}, issn = {1648-9144}, support = {01.2.2-LMT-K-718-03-0099//Lietuvos Mokslo Taryba/ ; }, mesh = {Humans ; *Autism Spectrum Disorder/therapy/complications ; Male ; Female ; Prospective Studies ; *Fecal Microbiota Transplantation/methods/standards ; Child ; Child, Preschool ; Treatment Outcome ; }, abstract = {Background and Objectives: Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with an increasing global incidence. Gut microbiota dysbiosis is believed to be playing a role in ASD pathogenesis. Fecal microbiota transplantation (FMT) is emerging as a potential therapeutic strategy to alleviate ASD-related and gastrointestinal symptoms, but data in pediatric ASD populations remain limited. Materials and Methods: We conducted a prospective, single-center, open-label controlled study to evaluate the efficacy of colonoscopic FMT in children with ASD. Participants were allocated to two groups: an intervention group that underwent a single FMT procedure and a control group. Gastrointestinal Symptoms Rating Scale (GSRS), Autism Diagnostic Observation Schedule (ADOS), Childhood Autism Rating Scale (CARS), Child Behavior Checklist (CBCL), and Parent Global Impression (PGI-R) scales were assessed for both groups at baseline and at set time points. Results: 30 participants were enrolled, with 15 in each group. At 8 weeks, no significant between-group differences were observed for the prespecified primary endpoint, change in ADOS scores. The intervention group showed significantly greater improvements in CARS (p < 0.001), PGI-R (p < 0.001), CBCL Internalizing Problems (p = 0.001), and GSRS (p = 0.037) compared with controls; CARS and PGI-R improvements persisted at 6 months. Within the intervention group, sustained improvements were noted in CARS, GSRS, and PGI-R up to 18 months. No serious adverse events were observed; three mild, self-limited adverse events were recorded following FMT. Conclusions: Colonoscopic FMT was associated with significant short-term improvements in gastrointestinal and caregiver-reported ASD symptoms (CARS), but not in ADOS scores. Some effects persisted long-term. However, due to a lack of blinding and possible selection bias, these findings should be interpreted as exploratory. Larger randomized controlled trials are needed to confirm efficacy and optimize protocols.}, } @article {pmid41596802, year = {2026}, author = {Qin, T and Wei, Y and Zheng, W and Li, S and Song, S and Ai, C}, title = {Bacteroidesfinegoldii and Parabacteroides goldsteinii Mediate Fucoidan-Induced Attenuation of Intestinal Inflammation in Mice Through Betaine- and Spermidine-Related Pathways.}, journal = {Foods (Basel, Switzerland)}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/foods15020203}, pmid = {41596802}, issn = {2304-8158}, abstract = {Fucoidan improves host health by enriching beneficial taxa such as Bacteroides and Parabacteroides, yet the underlying mechanisms remain unclear. This study validated the association between these two genera and fucoidan-mediated mitigation of intestinal inflammation in mice. Subsequently, the effects of Parabacteroides goldsteinii and Bacteroides finegoldii were evaluated in colitis mice, and the contributions of microbiota-associated metabolites spermidine and betaine were investigated in vitro. Both strains reduced IL-6 (32-36%), TNF-α (30-37%), and IL-1β (40-45%) levels and increased levels of catalase (25-35%) and glutathione peroxidase (31-45%) in the colon. Mechanically, these strains suppressed activation of the NF-κB and MAPK pathways and preserved tight junction integrity by inhibiting myosin light chain kinase activation. These effects were associated with alterations of gut microbiota, characterized by decreased Proteobacteria and increased Bacteroidota, resulting in increased betaine (45-60%) and spermidine (90-112%). In vitro, betaine and spermidine alleviated LPS-induced inflammation and oxidative damage by regulating macrophage polarization. These results suggest that Bacteroides and Parabacteroides contribute to fucoidan-induced improvement of host health through betaine- and spermidine-related pathways. Future studies should clarify the origins of key metabolites and validate their causality and translational relevance using approaches such as fecal microbiota transplantation, metabolite tracing, and human-relevant systems.}, } @article {pmid41595645, year = {2026}, author = {Rusu, M and Ichim, C and Anderco, P and Pălăștea, A and Boicean, A}, title = {Gut-Kidney Axis: Unraveling the Role of the Microbiome in Chronic Kidney Disease.}, journal = {Biomedicines}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/biomedicines14010109}, pmid = {41595645}, issn = {2227-9059}, abstract = {Chronic kidney disease (CKD), which affects over 850 million individuals globally, is increasingly regarded as a systemic condition in which the gut microbiota represents a key pathogenic node. This review provides an integrated overview of mechanistic, translational and clinical data implicating the gut-kidney axis in CKD. The CKD-associated microbiota displays a characteristic dysbiosis, marked by depletion of short-chain fatty acid-producing commensals, overgrowth of proteolytic and urease-expressing taxa and disruption of epithelial barrier integrity. These disturbances favor the generation and systemic accumulation of gut-derived uremic toxins, most notably indoxyl sulfate, p-cresyl sulfate, indole-3-acetic acid and trimethylamine-N-oxide, which promote endothelial dysfunction, vascular calcification, fibrosis and chronic inflammation, thereby hastening renal function loss and heightening cardiovascular risk. Microbiome-directed interventions, including dietary modification, prebiotics, probiotics, synbiotics, intestinal dialysis, fecal microbiota transplantation, gut-acting sorbents and nephroprotective phytochemicals, are summarized with emphasis on their effects on uremic toxin burden and clinical surrogates. System-level implications of the gut-kidney axis for cardiovascular disease, immunosenescence and sarcopenia are discussed, together with future priorities for integrating multi-omics profiling and precision microbiome-based strategies into nephrology practice.}, } @article {pmid41594368, year = {2026}, author = {Han, L and Zhou, F and Zhang, C and Li, H and Zheng, Y and Tian, Y and Liu, Y and Yin, J and Huang, X}, title = {Lean DLY Pig-Derived Fecal Microbiota Promotes Growth Performance by Modulating Gut Microbiota: Serum Metabolic Profiles in Obese Ningxiang Pigs.}, journal = {Animals : an open access journal from MDPI}, volume = {16}, number = {2}, pages = {}, doi = {10.3390/ani16020177}, pmid = {41594368}, issn = {2076-2615}, support = {U20A2055//National Natural Science Foundation of China/ ; CX20230714//Graduate Research Innovation Project of Hunan Province/ ; }, abstract = {Fecal microbiota transplantation (FMT) has demonstrated potential in reshaping gut microbiota to improve animal phenotypes, yet its application in lean-type to obese-type pigs like Ningxiang (NX) pigs remains unclear. To address this, we investigated the effects of Lean Duroc × Landrace × Yorkshire (DLY) pig-derived fecal microbiota on the growth, gut microbiota composition, and serum metabolism of obese NX pigs. Thirty-six 50-day-old castrated male NX pigs of similar initial body weight were randomly assigned to either a control group or FMT group. The trial lasted for 35 days. Results indicated that FMT significantly improved the average daily gain and increased nutrient digestibility. Serum biochemical analysis revealed elevated levels of globulin and total protein and reduced low-density lipoprotein cholesterol in the FMT group. In addition, 16S rRNA sequencing demonstrated that FMT modified gut microbiota composition and diversity, enriching beneficial genera such as Blautia, Agathobacter, Faecalibacterium, and Eubacterium_coprostanoligenes_group. Untargeted serum metabolomics further revealed altered metabolite profiles linked to lipid and amino acid metabolism. Correlation analysis further revealed a link between these enriched bacteria and metabolites changes. Overall, these findings demonstrate that transplantation of the fecal microbiota from lean DLY pigs significantly improved the growth performance of obese NX pigs by improving nutrient digestibility and modulating the gut microbiota-host metabolic axis.}, } @article {pmid41593440, year = {2026}, author = {Lv, J and Liu, R and Sun, Z and Zhang, J and Zhang, Y and Zhao, X and Liu, J and Zhou, X and Zhang, M and Liu, Q and Gao, F}, title = {Gut Microbiota as Neuroimmune Modulators in Myasthenia Gravis: Mechanistic Insights from the Gut-Brain Axis to Therapeutic Innovations.}, journal = {The American journal of Chinese medicine}, volume = {}, number = {}, pages = {1-21}, doi = {10.1142/S0192415X26500023}, pmid = {41593440}, issn = {1793-6853}, abstract = {Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by an immune-mediated attack on neuromuscular junction acetylcholine receptors (AChRs), and its pathogenesis is closely linked to immune dysregulation. Emerging evidence has highlighted the pivotal role of the gut microbiota in the pathophysiology of MG through immunomodulation, microbial metabolite signaling, and gut-brain axis interactions. This review combines 16S rRNA sequencing, metagenomic, and metabolomic data to reveal distinct gut microbial signatures in patients with MG. These signatures include reduced α-diversity, depletion of beneficial taxa like Bacteroides and Bifidobacterium, enrichment of pathobionts such as Escherichia and Enterococcus, and diminished levels of the short-chain fatty acids (SCFA), which were inversely correlated with disease severity. Experimental models have demonstrated that fecal microbiota transplantation (FMT) and probiotic supplementation with strains like Bifidobacterium ameliorate symptoms by restoring Th17/Treg equilibrium, suppressing the expression of pro-inflammatory cytokines including IL-6 and TNF-α, and enhancing intestinal barrier integrity. Mechanistically, gut dysbiosis exacerbates autoimmunity via NF-αB pathway activation, disrupts tryptophan metabolism and impairs gut-brain signaling. While existing studies have established microbiota-MG associations, further causal validation, personalized therapeutic strategies, and multi-omics integration remain critical priorities. Microbiota-targeted interventions, including precision FMT and metabolite delivery, hold translational potential, but their validation via large-scale randomized controlled trials and interdisciplinary approaches like AI-driven microbiota profiling is essential if they are to advance precision medicine for MG management.}, } @article {pmid41589673, year = {2026}, author = {Rosa, A and Gargari, M and Martelli, M}, title = {Gut-Brain-Jaw Axis: The Emerging Role of Gut Microbiota in Temporomandibular Disorders and Orofacial Pain-A Narrative Review.}, journal = {Journal of oral rehabilitation}, volume = {}, number = {}, pages = {}, doi = {10.1111/joor.70156}, pmid = {41589673}, issn = {1365-2842}, abstract = {BACKGROUND: Temporomandibular disorders (TMDs) and chronic orofacial pain are multifactorial conditions influenced by complex neurobiological and systemic mechanisms. Recent findings emphasise the gut-brain axis as a central modulator of pain, neuroinflammation, and immune signalling. Nevertheless, the role of the gut microbiota in TMD pathogenesis and oral rehabilitation remains insufficiently characterised.

METHODS: A structured literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science up to December 2024 using combinations of keywords including "gut microbiota," "temporomandibular disorder," and "orofacial pain." Eligible publications included clinical studies, systematic and narrative reviews, meta-analyses, and theoretical works addressing microbiota-pain relationships.

RESULTS: Recent Mendelian randomization studies reveal causal associations between specific bacterial genera and TMD risk. Experimental models demonstrate that gut dysbiosis exacerbates temporomandibular joint inflammation and neuroinflammatory responses, while restoring microbial balance through probiotics or faecal microbiota transplantation alleviates pain hypersensitivity. Mechanistic studies suggest that microbial metabolites such as short-chain fatty acids, GABA, and serotonin modulate trigeminal pain pathways via vagal and immune signalling.

CONCLUSION: Current evidence supports a bidirectional gut-brain-jaw communication system influencing both peripheral and central pain mechanisms. Incorporating microbiome-targeted approaches-such as dietary modulation, probiotics, and microbial therapy-may enhance TMD management and promote a more holistic, personalised model of oral rehabilitation.}, } @article {pmid41589431, year = {2025}, author = {Şahin, N and Salbaş, E}, title = {The Gut-Joint Connection: Microbiome's Role in Rheumatic Disease.}, journal = {Archives of rheumatology}, volume = {40}, number = {4}, pages = {413-421}, doi = {10.5152/ArchRheumatol.2025.25192}, pmid = {41589431}, issn = {2618-6500}, abstract = {The human gut microbiome is a pivotal regulator of systemic immunity and a central factor in the pathogenesis of rheumatic diseases. An imbalance in this microbial community, known as "dysbiosis," can trigger and perpetuate autoimmune responses through the "gut-joint axis." A key mechanism underpinning this connection is increased intestinal permeability ("leaky gut"), which facilitates the translocation of microbial products like lipopolysaccharide into the systemic circulation, thereby provoking chronic inflammation. Concurrently, dysbiosis disrupts the critical homeostatic balance between pro-inflammatory Th17 cells and regulatory T cells, an immunological hallmark of conditions such as rheumatoid arthritis (RA), ankylosing spondylitis, and systemic lupus erythematosus (SLE). Specific microbial signatures, including the expansion of Prevotella copri in RA and Ruminococcus gnavus in SLE, are emerging as potential diagnostic biomarkers. This deeper understanding is paving the way for innovative therapeutic strategies. Interventions aimed at modulating the gut microbiota, such as targeted diets, probiotics, prebiotics and fecal microbiota transplantation, represent a promising frontier for the personalized management of rheumatic diseases. This review explores the foundational mechanisms linking the microbiome to autoimmunity and discusses the clinical potential of harnessing the gut-joint axis to improve patient outcomes.}, } @article {pmid41587946, year = {2026}, author = {Quraishi, MN and Moakes, CA and Yalchin, M and Blackwell, C and Segal, J and Ives, NJ and Magill, L and Manzoor, SE and Gerasimidis, K and McMullan, C and Mathers, J and Horniblow, R and Loi, S and Kaur, M and Loman, NJ and Sharma, N and Hawkey, P and McCune, V and Quick, J and Nicholls, S and McMurray, C and Nichols, B and Svolos, V and Raguideau, S and Kerbiriou, C and Oo, YH and Beggs, AD and Crees, N and Hansen, R and Hart, AL and Gaya, DR and Quince, C and Iqbal, TH}, title = {Mechanistic insights into FMT for the treatment of ulcerative colitis: analysis of the STOP-Colitis trial.}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjag006}, pmid = {41587946}, issn = {1876-4479}, abstract = {BACKGROUND AND AIMS: Faecal microbiota transplantation (FMT) is a promising therapy for ulcerative colitis, but variable responses and unclear mechanisms limit its efficacy. We aimed to compare nasogastric versus colonic FMT delivery and define the microbial and immunological changes associated with clinical response.

METHODS: In this prospective, open-label, randomised pilot trial (STOP-Colitis), 30 adults with active ulcerative colitis were randomised to receive multi-dose FMT via nasogastric tube or colonoscopy with subsequent enemas. Key endpoints were clinical outcomes at week 8 and longitudinal multi-omic analyses of stool and biopsies to define changes in microbial composition (16S rRNA and shotgun metagenomics), short-chain fatty acids, mucosal T-cells, and host gene expression.

RESULTS: Colonic FMT was superior to nasogastric delivery, with a higher clinical response rate at week 8 (75% [9/12] vs 25% [2/8]; RR 2·94, 95% CI 0·84-10·30-per protocol analysis). Response was underpinned by successful microbial engraftment, leading to significantly increased faecal microbial diversity and enrichment of SCFA-producing taxa, including Oscillospiraceae and Christensenellaceae. This correlated with reduced faecal calprotectin. Responders showed a significant increase in mucosal regulatory T cells (P = 0·01), with a concurrent decrease in Th17 (P = 0·03) and CD8 + T cells. This anti-inflammatory shift was confirmed by mucosal transcriptomics, which revealed upregulation of metabolic pathways and downregulation of proinflammatory defence pathways in responders. (Trial registration: ISRCTN13636129).

CONCLUSION: Colonic FMT is a more effective delivery route than nasogastric administration. Clinical response is driven by the engraftment of immunomodulatory bacteria that restore a healthy host-microbe dialogue, providing rationale for developing targeted microbial therapeutics.}, } @article {pmid41586375, year = {2025}, author = {Zhao, Z and Wu, B}, title = {Gut microbiota dysbiosis aggravates sepsis-induced lung injury by promoting neutrophil extracellular traps and suppressing host integrin defense.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1699748}, pmid = {41586375}, issn = {1664-302X}, abstract = {BACKGROUND: The gut-lung axis is central to systemic inflammatory regulation, but the mechanisms by which gut microbiota dysbiosis aggravates sepsis-induced acute lung injury (ALI), particularly through neutrophil extracellular traps (NETs) and integrin signaling, remain unclear. Given the critical need for microbiota-based therapeutic strategies, this study investigates the mechanistic link between gut microbiota, NET formation, and pulmonary endothelial barrier dysfunction.

METHODS: Using a cecal ligation and puncture (CLP) sepsis model, control, sepsis, and fecal microbiota transplantation (FMT) groups were compared. Lung injury was assessed via histopathology, wet/dry weight ratios, and bronchoalveolar lavage fluid (BALF) analysis. High-throughput RNA sequencing (GO/KEGG/PPI) identified key targets, validated by lentiviral knockdown/overexpression of ITGAM and ITGB2 in vivo and in vitro [mouse pulmonary microvascular endothelial cells (MPMECs) and neutrophil co-cultures]. NETs were quantified by MPO-DNA ELISA and immunofluorescence.

RESULTS: CLP-induced sepsis triggered severe pulmonary edema, neutrophil infiltration, and NET accumulation, alongside downregulation of ITGAM/ITGB2 and tight junction proteins (β-catenin/ZO-1/VE-cadherin). FMT reduced NETs by 58% (p < 0.001) and restored endothelial barrier integrity. Transcriptomics revealed ITGAM/ITGB2 as central nodes in neutrophil activation and integrin pathways. In vitro, NET exposure increased endothelial permeability (3.1-fold FITC-dextran flux, p < 0.01) and IL-6/TNF-α secretion, while ITGAM/ITGB2 overexpression reversed these effects. Conversely, integrin silencing abolished FMT's protection, exacerbating ALI.

CONCLUSION: We unveil a novel gut microbiota-NET-integrin axis in sepsis-induced ALI, where microbial dysbiosis promotes NET-mediated suppression of ITGAM/ITGB2, leading to endothelial barrier failure. Our findings position FMT and integrin modulation as promising strategies to mitigate pulmonary vascular dysfunction, advancing the therapeutic potential of microbiota-targeted interventions in critical care.}, } @article {pmid41585577, year = {2026}, author = {Benterkia, S and Blythe, J}, title = {Brief Report: Can Fecal Microbiota Transplantation Treat Depression?.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {10}, number = {1}, pages = {e70336}, pmid = {41585577}, issn = {2397-9070}, } @article {pmid41585498, year = {2026}, author = {Jin, X and Wei, J and Min, X and Fan, Y and Yuan, Z and Du, Z and Su, Z and Xun, T and Du, Q and Liang, T and He, X and Tang, W}, title = {Gut microbiota and Parkinson's disease: exploring pathogenesis and potential therapeutic strategies from a gut-brain axis perspective.}, journal = {iScience}, volume = {29}, number = {2}, pages = {114185}, pmid = {41585498}, issn = {2589-0042}, abstract = {Parkinson's disease (PD) is a prevalent neurodegenerative disorder with a global prevalence exceeding 1‰, posing a significant public health challenge. Although the pathogenesis of PD is not yet fully elucidated, accumulating evidence suggests that it results from the interplay between genetic and environmental factors, highlighting its multifactorial nature. With advances in translational medicine, the gut has emerged as a critical participant in PD onset and progression. This review systematically summarizes the role of the gut in PD, particularly emphasizing potential mechanisms involving neuroinflammation in the central nervous system (CNS), pathological aggregation of α-synuclein (α-syn), and mitochondrial dysfunction. Furthermore, gut-targeted therapeutic strategies for PD are discussed, including fecal microbiota transplantation (FMT), gut-directed anti-inflammatory therapies, supplementation with gut microbiota-derived metabolites such as short-chain fatty acids (SCFAs), and interventions targeting α-syn aggregation. A deeper understanding of these mechanisms not only advances the pathological knowledge of PD but also provides theoretical foundations for the early diagnosis and innovative treatment of the disease.}, } @article {pmid41585029, year = {2026}, author = {Hecker, MT and Rosero, C and Mendo-Lopez, R and Wilson, BM and Torres-Teran, MM and Donskey, CJ}, title = {Long-Term Follow-Up After Fecal Microbiota Transplantation via Freeze-Dried Capsules for Recurrent Clostridioides difficile Infection.}, journal = {Pathogens & immunity}, volume = {11}, number = {1}, pages = {1-13}, pmid = {41585029}, issn = {2469-2964}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a standard therapy for recurrent Clostridioides difficile infection (CDI). Limited information is available on the durability of response after FMT via freeze-dried oral capsules and on whether patients who fail an initial FMT can be successfully managed with repeated FMT.

METHODS: We conducted a retrospective cohort study of all patients undergoing initial FMT for recurrent CDI via freeze-dried capsules from March 2015 through June 2022 at 2 acute-care hospitals. Information on response to FMT during the initial management period (ie, 3 months after the initial FMT) and long-term durability of response was collected through direct communication with patients and medical record review. Episodes occurring within 90 days of the initial FMT were defined as recurrences, whereas those occurring more than 90 days after the initial FMT were defined as additional CDI episodes.

RESULTS: Of 129 patients with recurrent CDI treated with FMT via freeze-dried capsules, 114 (89%) had experienced 3 or more prior episodes of CDI. At 3 months after the initial FMT, 103 (80%) patients had no recurrence, 26 (20%) patients had 1 or more recurrences managed with 1 (n=21) or 2 (n=2) additional FMTs, and 3 (12%) were transitioned to CDI suppressive therapy. During subsequent long-term follow-up (median 182 weeks), 21 of the 126 patients (17%) who did not transition to suppressive therapy had additional episodes managed with CDI therapy only (n=9), CDI therapy and additional FMT (n=10), or suppressive CDI therapy (n=2).

CONCLUSIONS: In a real-world setting with long-term follow-up, FMT via freeze-dried capsules was effective for the management of recurrent CDI. Repeated FMT procedures were effective for the management of patients with early failure after initial FMT and with additional episodes during long-term follow-up.}, } @article {pmid41584842, year = {2025}, author = {Ruchko, E and Chernysheva, M and Sokolov, V and Starinnov, Z and Sabirov, M and Vasiliev, A}, title = {β-cell heterogeneity and molecular plasticity in type 2 diabetes: multi-omics perspectives and the role of gut microbiota.}, journal = {Frontiers in cell and developmental biology}, volume = {13}, number = {}, pages = {1698296}, pmid = {41584842}, issn = {2296-634X}, abstract = {Type 2 diabetes (T2D) is a complex metabolic disorder characterized by systemic insulin resistance and progressive deterioration of pancreatic β-cell function. Advances in single-cell transcriptomics, epigenomics, and spatial transcriptomics have delineated marked β-cell heterogeneity, revealing subpopulations with differential secretory capacity, stress resilience, and vulnerability to metabolic and immune-mediated insults. These high-resolution approaches have further identified disease-associated alterations in other islet endocrine cells, as well as in immune, stromal, and exocrine pancreatic compartments, highlighting the central role of intercellular signaling in T2D pathogenesis. Concurrently, microbiome research has elucidated mechanisms by which gut microbial composition and metabolic activity modulate glucose homeostasis and β-cell function through immunoregulatory pathways, maintenance of epithelial barrier integrity, and enteroendocrine signaling, notably via glucagon-like peptide-1 (GLP-1). Therapeutic strategies targeting the gut microbiota include conventional probiotics, prebiotics, and fecal microbiota transplantation, alongside emerging synthetic biology approaches employing genetically engineered probiotic strains to deliver bioactive molecules, including GLP-1, directly in the gut microenvironment. This review integrates current multi-omics and experimental evidence to provide a comprehensive framework for understanding β-cell molecular plasticity, microbiota-mediated metabolic regulation, and their intersection as potential therapeutic targets. Such integrative approaches offer prospects for the development of precision interventions aimed at preserving or restoring β-cell function in T2D.}, } @article {pmid41584685, year = {2026}, author = {Li, W and Wang, X and Zhang, Y and Yang, H and Wang, X and Meng, W and Hu, T and Zhang, W and Zhu, Y and Wang, J and Yang, G}, title = {Engineered Bacillus subtilis WB600/ZD reduces post-weaning diarrhea in piglets by modulating gut microbiota and aryl hydrocarbon receptor (AHR) signaling.}, journal = {Animal nutrition (Zhongguo xu mu shou yi xue hui)}, volume = {24}, number = {}, pages = {46-60}, pmid = {41584685}, issn = {2405-6383}, abstract = {Post-weaning diarrhea (PWD) causes significant economic losses to the pig industry. A previous study demonstrated that engineered Bacillus subtilis WB600 expressing Zophobas atratus defensin (ZD), termed WB600/ZD, alleviates intestinal inflammation, modulates gut microbiota, and maintains redox homeostasis in Salmonella-challenged mice; however, the precise mechanisms remain unclear. In this study, a total of 50 weaned Landrace × Large White piglets at 21 d of age were assigned to four groups: healthy piglets fed standard diet (H group; 6.60 ± 0.48 kg, n = 15) or 2 × 10[9] CFU/mL WB600/ZD (H + WB600/ZD group; 6.00 ± 0.68 kg, n = 15), and diarrheic piglets fed standard diet (PWD group; 6.51 ± 1.16 kg, n = 10) or 2 × 10[9] CFU/mL WB600/ZD (PWD + WB600/ZD group; 6.91 ± 0.57 kg, n = 10). All groups received 7 d of treatment followed by 3 d of post-treatment monitoring. During the 10-d trial period, the body weight, feed intake per group, and diarrhea incidence were recorded. Results demonstrated that WB600/ZD reduced diarrhea incidence in both healthy (P < 0.001) and diarrheic piglets (P = 0.040). Additionally, WB600/ZD improved the growth performance, including final body weight (P = 0.017) and average daily gain (ADG; P = 0.007), without affecting average daily feed intake (ADFI; P = 0.907). Mechanistically, WB600/ZD increased the levels of serum glutathione peroxidase (GSH-Px; P = 0.014) and reduced myeloperoxidase (MPO; P < 0.001) and malondialdehyde (MDA; P < 0.001). Integrated fecal microbiota and metabolites showed that this protective effect of WB600/ZD was associated with gut microbiota-dependent tryptophan metabolism (P < 0.001). Furthermore, antibiotic-treated (pseudo-germ-free) mice receiving fecal microbiota transplantation (FMT) from WB600/ZD-treated piglets or administered the aryl hydrocarbon receptor (AHR) agonist 6-formylindolo[3,2-b]carbazole (FICZ) before Salmonella enterica subsp. enterica serovar Infantis (S. Infantis) challenge exhibited activation of the AHR/cytochrome P450 family 1 subfamily A member 1 (CYP1A1) signaling pathway (P = 0.022) and increased interleukin (IL)-22 secretion (P < 0.001), thereby alleviating S. Infantis infection. Overall, this study provides strong evidence that WB600/ZD is a promising antibiotic alternative for preventing PWD in newly weaned piglets.}, } @article {pmid41584317, year = {2026}, author = {Jawed, F and Aziz, R and Mir, SUI and Khan, SA}, title = {Gut microbiota, sarcopenia, and type 2 diabetes: a triangular pathophysiological network.}, journal = {Journal of diabetes and metabolic disorders}, volume = {25}, number = {1}, pages = {41}, pmid = {41584317}, issn = {2251-6581}, abstract = {PURPOSE: Type 2 diabetes mellitus (T2DM), sarcopenia, and gut microbiota dysbiosis are increasingly recognized as interrelated conditions. T2DM accelerates muscle wasting through insulin resistance, inflammation, and oxidative stress, while sarcopenia worsens metabolic dysfunction. This review explores the interconnected conditions of Type 2 Diabetes, sarcopenia, and gut microbiota dysbiosis, highlighting their therapeutic potential and the need for interventions targeting these conditions for metabolic and musculoskeletal health.

METHODS: An extensive literature search was performed in PubMed, EMBASE, Scopus, and Web of Science up to July 2025 using terms related to gut microbiota, sarcopenia, and T2DM. Both preclinical and human studies were included if they addressed microbial composition, metabolites, inflammation, insulin resistance, or muscle protein turnover.

RESULTS: Evidence indicates bidirectional relationships: T2DM patients show higher prevalence of sarcopenia, while reduced muscle mass increases T2DM risk. Gut dysbiosis in T2DM is characterized by depletion of SCFA-producing taxa (e.g., Faecalibacterium prausnitzii) and enrichment of endotoxin-producing bacteria, leading to systemic inflammation and impaired insulin signaling. Germ-free and antibiotic-treated rodent models demonstrate muscle atrophy, whereas probiotic or prebiotic supplementation restores muscle mass and improves glucose metabolism. Limited clinical trials suggest dietary fibre, probiotics, and fecal microbiota transplantation improve glycemic control and inflammatory markers, with potential secondary benefits on muscle function.

CONCLUSION: T2DM, sarcopenia, and gut microbiota are linked through insulin resistance, inflammation, and altered signaling. Targeting gut-muscle-metabolism axis through diet, microbiota modulation, and exercise is promising. Future longitudinal and interventional studies are needed to establish causality and develop precision microbiome-based therapies.

SUMMARY: Type 2 diabetes mellitus (T2DM), sarcopenia, and gut microbiota dysbiosis are interconnected in a triangular pathophysiological network. T2DM accelerates muscle loss through insulin resistance, inflammation, and oxidative stress, while sarcopenia worsens glycaemic control. Gut dysbiosis reduces beneficial short-chain fatty acid (SCFA) production and increases pro-inflammatory metabolites such as lipopolysaccharides, further impairing muscle metabolism and glucose regulation. Preclinical and emerging clinical evidence shows that dietary fibre, probiotics, and fecal microbiota transplantation can modulate this axis. Targeting the gut-muscle-metabolism triad offers promising integrative strategies for preventing and managing diabetic sarcopenia.}, } @article {pmid41583842, year = {2025}, author = {Sandblom, G and Koishibayeva, LM and Poskus, T and Koishibayev, ZM}, title = {Editorial: Microflora and bacterial translocation in intestinal obstruction.}, journal = {Frontiers in surgery}, volume = {12}, number = {}, pages = {1760588}, pmid = {41583842}, issn = {2296-875X}, } @article {pmid41583463, year = {2025}, author = {Zha, T and Ding, Y and Xu, X and Zhang, Y and Guo, J and Ge, H and Xu, L}, title = {The oral-gut axis in chronic atrophic gastritis: current perspectives and integrated strategies.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1699501}, pmid = {41583463}, issn = {1664-3224}, mesh = {Humans ; *Gastritis, Atrophic/microbiology/therapy/immunology/metabolism/etiology ; *Gastrointestinal Microbiome/immunology ; Helicobacter Infections/microbiology/immunology/complications ; Dysbiosis ; Helicobacter pylori ; *Mouth/microbiology/immunology ; Chronic Disease ; Animals ; }, abstract = {Chronic atrophic gastritis (CAG) is a key precursor to gastric cancer, characterized by progressive mucosal atrophy, inflammation, and microbial dysbiosis. The Correa cascade model highlights Helicobacter pylori as a primary driver, progressing from gastritis to atrophy, intestinal metaplasia (IM), dysplasia, and malignancy. However, 20%-30% of CAG cases lack H. pylori involvement, emphasizing the roles of non-H. pylori microbial dysbiosis, environmental factors, and the oral-gut axis in disease progression. Oral microbes, such as Porphyromonas gingivalis, translocate to the stomach, amplifying inflammation through NF-κB and Wnt/β-catenin pathways and altering metabolites like short-chain fatty acids and trimethylamine N-oxide. Pro-inflammatory cytokines, including IL-1β, IL-6, and IL-17, alongside Th17-driven immune dysregulation, further accelerate carcinogenesis. This perspective integrates multi-omics data to elucidate microbiome shifts, metabolic changes, and immune responses across CAG subtypes. Advanced diagnostics, such as endoscopic imaging, serum biomarkers, and oral microbiota profiling, enable precise risk stratification. Management strategies extend beyond H. pylori eradication to include probiotics, fecal microbiota transplantation, periodontal interventions, and herbal compounds, targeting the oral-gut axis to restore microbial balance and halt carcinogenesis. This framework offers novel avenues for prevention and therapy in high-burden regions.}, } @article {pmid41583462, year = {2025}, author = {Bong, H and Min, J and Kim, S and Lim, W and Lim, D and Eom, H and Her, Y and Jeon, M}, title = {ATOMIC: a graph attention network for atopic dermatitis prediction using human gut microbiome.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1670993}, pmid = {41583462}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Dermatitis, Atopic/microbiology/diagnosis/etiology ; Adult ; Dysbiosis ; Female ; Computational Biology/methods ; Male ; }, abstract = {INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease driven by complex interactions among genetic, environmental, and microbial factors; however, its etiology remains unclear. Recent studies have reported the role of gut microbiota dysbiosis in AD pathogenesis, leading to increased interest in microbiome-targeted therapeutic strategies such as probiotics and fecal microbiota transplantation. Building on these findings, recent advances in computational modeling have introduced machine learning and deep learning-based approaches to capture the nonlinear relationships between gut microbiota and diseases. However, these models focus on diseases other than AD and often fail to capture complex microbial interactions or incorporate microbial genomic information, thereby offering limited interpretability.

METHODS: To address these limitations, we propose ATOMIC, an interpretable graph attention network-based model that incorporates microbial co-expression networks to predict AD. Microbial co-expression networks incorporate microbial genomic information as a node feature, thereby enhancing their ability to capture functionally relevant microbial patterns. To train and test our model, we collected and processed 99 gut microbiome samples from adult patients with AD and healthy controls at Kangwon National University Hospital (KNUH).

RESULTS: ATOMIC outperformed baseline models, achieving an AUROC of 0.810 and an AUPRC of 0.927 for KNUH dataset. Furthermore, ATOMIC identified microbes potentially associated with AD prediction and proposed candidate microbial biomarkers that may inform future therapeutic strategies.

DISCUSSION: By identifying key microbial taxa that contributed to the AD classification through its interpretable attention mechanism, ATOMIC provides a foundation for personalized microbiome-based interventions and biomarker discovery. Additionally, to facilitate future research, we publicly released a gut microbial abundance dataset from KNUH. The source code and processed abundance data are available from ATOMIC GitHub repository at https://www.github.com/KU-MedAI/ATOMIC.}, } @article {pmid41583434, year = {2025}, author = {Zhang, Y and Zhang, H and Miao, T and Wang, X and Zuo, Y and Zhang, R and Zhang, L and Cheng, Y and Liu, D and Chen, X and Li, L and Xie, X and Li, N}, title = {Advances in the study of gut microecology and mechanisms of hyperuricemia and gouty arthritis.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1738716}, pmid = {41583434}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Hyperuricemia/microbiology/immunology/therapy/metabolism/etiology ; *Arthritis, Gouty/microbiology/immunology/therapy/metabolism/etiology ; Animals ; Dysbiosis/immunology ; Uric Acid/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {Gouty arthritis is a metabolic disorder caused by purine metabolism dysregulation, characterized by monosodium urate crystal deposition in and around joints, triggering acute articular inflammation via NLRP3 inflammasome activation and IL-1β-mediated inflammatory cascades. While hyperuricemia represents a critical biochemical prerequisite for gouty arthritis development, elevated serum urate levels do not invariably lead to the disease. Mounting evidence suggests a significant relationship between gut microbiota and the pathogenesis of both gouty arthritis and hyperuricemia. The gut microbial ecosystem influences host health through metabolic and immune function modulation, performing essential roles in digestion, energy harvesting, and short-chain fatty acid production. Intestinal dysbiosis can damage epithelial integrity, compromise immune tolerance, and activate immune cells, thus contributing to disease onset and progression. Elucidating the complex interactions between gut microbiota and the mechanisms underlying gouty arthritis and hyperuricemia presents promising opportunities for developing novel preventative and therapeutic interventions. This review synthesizes recent advances in understanding the gut-joint axis and evaluates emerging therapeutic strategies including probiotics, dietary interventions, and fecal microbiota transplantation.}, } @article {pmid41582062, year = {2026}, author = {Hartman, V and Bracke, B and Chapelle, T and Hendrikx, B and Huysentruyt, F and Liekens, E and Roelant, E and Roeyen, E and Ysebaert, D and Roeyen, G}, title = {Comparing faecal Elastase-1 and [13]C mixed triglyceride breath test in patients undergoing pancreatic surgery.}, journal = {HPB : the official journal of the International Hepato Pancreato Biliary Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.hpb.2026.01.001}, pmid = {41582062}, issn = {1477-2574}, abstract = {BACKGROUND: The optimal test for diagnosing pancreatic exocrine insufficiency (PEI) remains debated. This study compares the diagnostic accuracy of faecal elastase-1 (FE-1) and the [13]C Mixed Triglyceride Breath Test (MTGT) in patients undergoing pancreatic surgery.

METHODS: Patients undergoing pancreatic resection at Antwerp University Hospital (2016-2023) had FE-1 and MTGT testing before and after surgery. The MTGT was used as the reference standard. Agreement between both tests was evaluated using Cohen's kappa.

RESULTS: Preoperatively, in a patient cohort of 249 patients, PEI was detected in 25.3 % using MTGT and 39.6 % using FE-1 (cutoff <200 μg/g). The sensitivity and specificity of FE-1 were 63.5 % and 68.3 %, respectively. Agreement was fair (κ = 0.27). After pancreatoduodenectomy, the prevalence of PEI increased to 60 % (MTGT) and 92.2 % (FE-1), with only slight agreement between tests (κ = 0.17). Although FE-1 demonstrated high sensitivity (98.1 %), its specificity was poor (16.7 %), resulting in an 83.5 % false-positive rate.

CONCLUSIONS: In patients undergoing pancreatic surgery, especially after pancreatoduodenectomy, the agreement between MTGT and FE-1 is substantially lower than expected. FE-1 demostrates low specificity and a high false-positive rate, resulting in overdiagnosis and unnecessary economic and patient burden.}, } @article {pmid41580820, year = {2026}, author = {Ding, M and Xiao, Z and Hou, X and Luo, Z and Zhang, Z and Guo, M and Xu, C and Xu, R and Shan, J and Peng, H}, title = {Targeting G-protein-coupled receptors and gut microbiota: Ge-Lian Qi-Shen decoction elevates GLP-1 to combat non-alcoholic fatty liver disease.}, journal = {Chinese medicine}, volume = {21}, number = {1}, pages = {51}, pmid = {41580820}, issn = {1749-8546}, support = {KZYY2209//Kunshan Traditional Chinese Medicine Science and Technology Development Fund Project/ ; XZR2024193//Nanjing University of Chinese Medicine Natural Science Foundation Project/ ; KS2233//Kunshan Social Development Project/ ; ZD202425//Key Projects of Jiangsu Provincial Science/ ; LCZX202229//Suzhou Clinical Key Disease Diagnosis and Treatment Project/ ; }, abstract = {BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), often accompanied by insulin resistance, obesity, and hyperlipidemia, is a challenging metabolic disorder to treat. Ge-Lian Qi-Shen Decoction, a traditional Chinese herbal formula, has been clinically used to alleviate symptoms associated with NAFLD, but its underlying mechanisms remain unclear.

METHODS: A NAFLD model was established in C57BL/6J mice using a high-fat diet (HFD). The effects of 4-week GQD intervention at different doses on NAFLD-related symptoms were assessed using biochemical analyses, pathological sections, and oral glucose tolerance tests. ELISA and qPCR were employed to investigate the impact of GQD on serum GLP-1 levels and intestinal Gcg gene expression in NAFLD mice. The direct stimulatory effects of GQD on GLP-1 secretion were examined in NCI-H716 cells and HFD-fed mice. UPLC-MS/MS was used to analyze the composition of ileal contents in GQD-treated mice, and the regulatory effects of 24 identified compounds on GLP-1 secretion were evaluated. Additionally, 16S rDNA sequencing, metabolomics and fecal microbiota transplantation were utilized to explore the role of gut microbiota in GQD's anti-NAFLD effect.

RESULTS: GQD improved HFD-induced hepatic steatosis, impaired glucose tolerance, and elevated blood lipid levels in a dose-dependent manner. It increased serum GLP-1 levels, reduced energy intake, and enhanced glucose tolerance in mice. A single dose of GQD directly elevated serum GLP-1 levels in HFD-fed mice and improved glucose tolerance in a GLP-1-dependent manner. In NCI-H716 cells, GQD promoted intracellular calcium influx and GLP-1 release by activating two G-protein-coupled receptors (GPCRs): bitter taste receptors and TGR5. Compounds such as berberine, coptisine, nuciferine, liensinine, higenamine, aurantio-obtusin, and obtusifolin in GQD activated bitter taste receptors, while maslinic acid and cycloastragenol activated TGR5, facilitating GLP-1 secretion. Furthermore, GQD gavage increased the levels of Muribaculaceae and Akkermansia in mouse feces, leading to elevated concentrations of short-chain fatty acids (SCFAs) such as acetate, propionate, butyrate, and valerate. These SCFAs potentially activated fatty acid-related GPCRs, such as GPR41, in the colon, thereby enhancing colonic Gcg expression. FMT experiment showed that gut microbiota can partially mediate the effect of GQD in increasing GLP-1 levels thus alleviating NAFLD.

CONCLUSION: Some alkaloids, anthraquinones, and triterpenoids in GQD can activate GPCRs, including bitter taste receptors and TGR5, in intestinal endocrine cells, promoting GLP-1 secretion. Simultaneously, GQD regulates gut microbiota composition and metabolism, increasing SCFA levels and Gcg gene expression, leading to sustained elevation of GLP-1 levels. These combined effects contribute to the alleviation of NAFLD symptoms.}, } @article {pmid41580778, year = {2026}, author = {Bai, Y and Kong, X and Wang, J}, title = {Targeting microbiome-driven epigenetic modifications: a new frontier in breast cancer treatment.}, journal = {Clinical epigenetics}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13148-025-02046-0}, pmid = {41580778}, issn = {1868-7083}, abstract = {Breast cancer remains a leading cause of morbidity and mortality among women worldwide, with significant heterogeneity in its development and treatment response. Recent advances in understanding the roles of the microbiome and epigenetic regulation have opened new avenues for addressing the complexities of breast cancer progression and therapeutic resistance. This review explores the intricate relationship between the gut and intratumoral microbiomes and epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNAs. Specifically, we examine how microbial metabolites, particularly short-chain fatty acids (SCFAs), regulate gene expression via epigenetic mechanisms, influencing tumor growth, metastasis, and treatment response. The impact of metabolic diseases, including obesity and type 2 diabetes mellitus (T2DM), on breast cancer risk through microbiome-mediated epigenetic changes is also discussed. Furthermore, the review highlights emerging therapeutic strategies that integrate microbiome modulation with epigenetic therapies, including the use of probiotics, dietary interventions, and fecal microbiota transplantation (FMT), as well as DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors. These innovative approaches hold promise for overcoming treatment resistance and improving clinical outcomes in breast cancer patients. Future research should focus on elucidating the molecular pathways through which the microbiome influences epigenetic regulation and developing personalized, microbiome-targeted therapies that enhance the efficacy of existing treatments. By targeting both the genetic and epigenetic drivers of breast cancer, microbiome-based interventions represent a novel frontier in the fight against this challenging disease.}, } @article {pmid41580690, year = {2026}, author = {Zhu, B and Huang, J and Zhang, H and Lin, H and Chen, T and Min, L and Yang, Y and Liu, Y and Guo, S}, title = {Akkermansia muciniphila vesicles attenuate smoking-induced cognitive decline via ILA-mediated AhR-dependent microglial reprogramming.}, journal = {Journal of nanobiotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12951-026-04044-7}, pmid = {41580690}, issn = {1477-3155}, support = {A2402014//Shenzhen Medical Research Fund/ ; 2023B110008//Guangdong Provincial Clinical Research Center for Laboratory Medicine/ ; 32300761//Youth Foundation of the National Natural Science Foundation of China/ ; }, abstract = {Chronic cigarette smoking accelerates age-related cognitive decline, yet the underlying mechanism remains elusive. Here, we elucidate a pathway through which smoking-induced gut dysbiosis contributes to cognitive impairment. This dysbiosis is marked by reductions in the abundances of Akkermansia muciniphila (A. muciniphila) and its metabolite indole-3-lactic acid (ILA), which correlate with cognitive deficits in older adult smokers. Using fecal microbiota transplantation, we demonstrate that the microbiota from smoke-exposed donors recapitulates cognitive impairment and microglial dysfunction in recipient mice. Importantly, these deficits were mitigated by treatment with either A. muciniphila-derived outer membrane vesicles (OMVs) or exogenous ILA, which restore synaptic integrity. Mechanistically, we demonstrate that both OMVs and ILA exert their neuroprotective effects via aryl hydrocarbon receptor (AhR) signaling. This AhR-dependent activation reprograms microglial metabolism toward oxidative phosphorylation, thereby suppressing neuroinflammation and restoring cellular bioenergetics. These findings suggest a mechanism through which smoking influences brain function via specific gut microbial metabolites and highlight the A. muciniphila-ILA-AhR axis as a promising target for preventing cognitive decline.}, } @article {pmid41580415, year = {2026}, author = {Song, M and Zhou, W and Fan, J and Cai, D and Wei, H and Tao, S}, title = {Dietary fiber deficiency exacerbates intestinal inflammation via miR-6240-enriched gut extracellular vesicles.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-026-00918-8}, pmid = {41580415}, issn = {2055-5008}, support = {2022YFA1304104//National Key Research and Development Program/ ; 32272898//National Nature Science Foundation of China/ ; }, abstract = {Emerging evidence underscores the critical role of dietary fiber in maintaining gut homeostasis. While extracellular vesicles (EVs) have recently gained attention as key mediators of host-microbe communication, their functional contribution to fiber deficiency-associated pathologies remains largely unexplored. In this study, we revealed that a fiber-free diet induces significant intestinal inflammatory damage in mice, an effect that can be faithfully reproduced through fecal microbiota transplantation. Importantly, we demonstrated that intestinal epithelial cells-derived EVs from fiber-deprived mice are sufficient to recapitulate the detrimental effects of fiber deficiency. Mechanistic studies revealed enrichment of miR-6240 in these EVs, which targeted the 3'UTR of STAT6 mRNA to suppress its expression. This impairment of STAT6 signaling inhibited M2 macrophage polarization, exacerbating intestinal inflammation. This novel pathway is further validated in primary macrophage adoptive transfer experiments. Our work unveils a previously unrecognized mechanism by which fiber deficiency exacerbates intestinal inflammation through IECs-derived EVs and miR-6240/STAT6-mediated macrophage dysfunction.}, } @article {pmid41580145, year = {2026}, author = {Merrick, B and Cooper, R and Davido, B and Goldenberg, S}, title = {The role of the gut microbiome in MDRO colonisation and infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2026.01.009}, pmid = {41580145}, issn = {1469-0691}, abstract = {BACKGROUND: Colonisation of the gastrointestinal tract by multidrug-resistant organisms (MDROs) is a precursor to endogenous infection and onward transmission. The gut microbiome provides colonisation resistance (CR) - the ability to prevent or limit the establishment of pathogens, including MDROs - through nutrient and niche competition, production of inhibitory metabolites, and immune modulation. However, its integrity is threatened by antibiotics, adverse diet, and healthcare exposures.

OBJECTIVES: To describe mechanistic, epidemiological, and interventional evidence on the role of the gut microbiome in MDRO colonisation and infection, and to highlight implications for clinical practice, policy, and research.

SOURCES: PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from 1 January 2000 to 30 September 2025, supplemented by hand-searching of key international guidelines (EUCIC/ESCMID, WHO, CDC/ECDC, NICE/UKHSA) and reference lists.

CONTENT: CR is shaped by microbial and host factors, including metabolic interactions, immune responses, and environmental exposures. Antimicrobials, non-antimicrobial drugs, diet, travel, and healthcare contact can disrupt the microbiota, predisposing to MDRO acquisition and infection. Observational data link gut microbial composition to risk of colonisation and infection outcomes, but predictive models are imperfect. Interventions to preserve or restore CR - such as diet-based strategies, probiotics, and faecal microbiota transplant - show promise but require robust and repeated, context-specific evaluation.

IMPLICATIONS: Protecting the microbiome must be a clinical and policy priority. Short-course, microbiome-sparing antimicrobial regimens, microbiome-aware diagnostics, and public health measures that support microbiome resilience could reduce MDRO burden and infections. Rigorous trials of microbiota-based therapies and integration of microbiome stewardship into antimicrobial resistance strategies are essential for translating mechanistic insights into patient benefit.}, } @article {pmid41577348, year = {2026}, author = {Liu, Y and Yan, X and Yang, J and Zhang, D and Fang, Y and Huang, J and Zhu, M and Li, L and Zhang, T and Zhang, Q and Jiang, F}, title = {Efficacy and safety of non-pharmacological therapies for irritable bowel syndrome with diarrhoea: protocol for systematic review and network meta-analysis.}, journal = {BMJ open}, volume = {16}, number = {1}, pages = {e105579}, doi = {10.1136/bmjopen-2025-105579}, pmid = {41577348}, issn = {2044-6055}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/complications ; Systematic Reviews as Topic ; *Diarrhea/therapy/etiology ; Network Meta-Analysis as Topic ; Quality of Life ; Research Design ; Probiotics/therapeutic use ; Meta-Analysis as Topic ; Cognitive Behavioral Therapy ; Acupuncture Therapy ; Randomized Controlled Trials as Topic ; }, abstract = {INTRODUCTION: Irritable bowel syndrome with diarrhoea (IBS-D) significantly impairs patients' quality of life. Although various non-pharmacological interventions show promise, evidence on their comparative effectiveness remains limited. This protocol outlines a systematic review and network meta-analysis designed to comprehensively evaluate and rank the efficacy and safety of guideline-recommended non-pharmacological therapies.

METHODS AND ANALYSIS: We will systematically search PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure, Chinese Biomedical Database, Wanfang Data and VIP Database from inception to January 2025. Eligible studies will include randomised controlled trials assessing guideline-recommended non-pharmacological interventions, probiotics, acupuncture, cognitive-behavioural therapy, dietary modifications and faecal microbiota transplantation in adults diagnosed with IBS-D based on Rome III or IV criteria. The primary outcome is the Irritable Bowel Syndrome Symptom Severity Score. Secondary outcomes include the Irritable Bowel Syndrome Quality of Life Scale and Hospital Anxiety and Depression Scale. Two independent reviewers will screen studies, extract data and evaluate risk of bias using the Cochrane Risk of Bias 2.0 tool. Network meta-analysis will be performed using frequentist methods with Stata and R software. Transitivity, heterogeneity, consistency and publication bias will be assessed. Certainty of evidence will be graded using the Grading of Recommendations, Assessment, Development and Evaluations methodology, supplemented with trial sequential analysis to determine the required information size.

ETHICS AND DISSEMINATION: Ethical approval is not required for this secondary analysis as it uses published data. The results will be disseminated via peer-reviewed journals and conference presentations to inform clinical practice and guideline development.

REGISTRATION: INPLASY202470112.}, } @article {pmid41575675, year = {2026}, author = {Kopalli, SR and Wankhede, N and Rahangdale, SR and Sammeta, S and Aglawe, M and Koppula, S and Taksande, B and Upaganlawar, A and Umekar, M and Kale, M}, title = {Age-driven dysbiosis: gut microbiota in the pathogenesis and treatment of aging disorders.}, journal = {Biogerontology}, volume = {27}, number = {1}, pages = {42}, pmid = {41575675}, issn = {1573-6768}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/therapy/microbiology ; *Aging/physiology ; Animals ; Probiotics/therapeutic use ; }, abstract = {Aging, a complex physiological and molecular process, has undergone significant changes, of which gut microbiome composition has surfaced as an important key in the maintenance of neurological health. Recent studies have revealed the significant impact of age-related gut dysbiosis in the induction of neuroinflammation, metabolic syndrome, disruptions in gut-brain axis, and age-related neurological decline. Although significant studies have revealed the impact of the microbiome-gut-brain axis in individual neurological diseases, an aging-focused holistic synthesis has not yet been adequately developed. This review provides a critical assessment of the involvement of age-related dysbiosis of gut microbiota in the development and progression of neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and cognitive aging of the elderly, and to focus on age-related microbial patterns and mechanisms of dysbiosis related to neurological aging, including inflammation and immune system dysregulation, metabolic changes, oxidative stress, barrier dysfunction, and gut-brain communication through enteroendocrine, enteric neural, and vagal mechanisms, and to emphasize disease-specific and common microbial patterns of dysbiosis and beneficial and harmful microbial roles in aging diseases. This review assesses some of the latest promising therapies aimed at the microbiota, such as probiotics, prebiotics, dietary therapies, fecal microbiota transplantation, as well as pharmacological therapies, and critically discusses their limitations in terms of interindividual variability and their generalisation and applicability. Focusing on mechanistic, comparative, and translation aspects, this review offers a comprehensive approach to neurological aging due to gut microbiota and identifies gaps for future precision microbiome-based interventions.}, } @article {pmid41575201, year = {2026}, author = {Kleinhans, M and Lissen, A and Hewitson, L and Rijkers, GT}, title = {From fecal microbiota transplants to targeted intervention for improvement of immune checkpoint inhibition therapy: how far down the road are we?.}, journal = {Expert review of anticancer therapy}, volume = {}, number = {}, pages = {}, doi = {10.1080/14737140.2026.2621240}, pmid = {41575201}, issn = {1744-8328}, abstract = {INTRODUCTION: The outcome of immune checkpoint inhibition (ICI) therapy of cancer appears to be influenced by the gut microbiota composition of the patient. Microbiome-based therapy by fecal microbiota transplantation (FMT) appears to improve the outcome of ICI therapy. The ideal composition of the microbiota as well as treatment schedule are not yet established.

AREAS COVERED: The most recent published studies are reviewed, as well as the study designs of registered clinical trials which are ongoing. The effect of pretreatment of patients with antibiotics, aimed to improve engraftment of the transplant, is evaluated.

EXPERT OPINION: The optimal treatment schedule would be to start with FMT, followed by ICI, implying FMT should be given to ICI naive patients. Rather than donor derived FMT, defined consortia of microbiota could be preferred.}, } @article {pmid41574864, year = {2026}, author = {Gao, Y and Shahbaz, S and Elahi, S and Monaghan, TM and , and Kao, D}, title = {Distinct T and innate-like lymphocyte reprogramming following lyophilized fecal microbiota transplantation in recurrent C. difficile infection.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2620127}, doi = {10.1080/19490976.2026.2620127}, pmid = {41574864}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Clostridium Infections/immunology/therapy/microbiology ; Clostridioides difficile/physiology/immunology ; Male ; Female ; Middle Aged ; Immunity, Innate ; Adult ; }, abstract = {Fecal microbiota transplantation (FMT) is highly effective in preventing recurrent Clostridioides difficile infection (rCDI), yet its immunological mechanisms remain poorly defined. While bacterial engraftment and recovery of microbial diversity are central to FMT efficacy, accumulating evidence suggests that host immune reprogramming is involved. In murine models, regulatory CD4[+] T cells are indispensable for clearing C. difficile. To address this mechanistic gap, we examined systemic immune reprogramming following FMT by performing flow cytometry and single-cell RNA sequencing (scRNA-seq) on a subset of successfully treated participants from a clinical trial comparing lyophilized FMT (LFMT) with lyophilized sterile fecal filtrate (LSFF, no live bacteria) for preventing rCDI. Flow cytometry was performed on peripheral mononuclear cells from 19 LFMT recipients and 18 LSFF recipients, and scRNA-seq analysis was performed on two LFMT recipients. Although flow cytometry results did not show significant changes in the assessed markers after rCDI resolution in either treatment group, exploratory scRNA-seq in the two LFMT recipients revealed distinct LFMT-associated transcriptional signatures across adaptive and innate-like lymphocyte populations. LFMT was associated with upregulated activation and regulatory genes (CD69, STAT1, TOX, RORA, FOXP3) in CD4[+] and CD8[+] T cells, suggesting enhanced immune regulation with reduced cytotoxic gene expression (GZMB, PRF1, GNLY). Innate-like lymphocytes displayed broad activation, with natural killer cells showing increased KLRD1, PRF1, and IL2RB and mucosal-associated invariant T cells (MAIT cells) upregulating STAT1, JUN, and RORA while downregulating KLRB1 and STAT3. These transcriptional programs are consistent with recalibration of T cell homeostasis and innate-like lymphocyte activation, potentially driven by microbial restoration. Collectively, this exploratory study provides the first single-cell immune atlas of LFMT in rCDI, identifying coordinated activation of regulatory, effector, and innate immune pathways. Given the small sample size, these findings should be considered hypothesis-generating, requiring validation in larger cohorts.}, } @article {pmid41574548, year = {2026}, author = {Li, C and Ma, J and Huang, G and Chen, B and He, C and Wu, R}, title = {Lactobacillus Regulates the Specificity of Polysaccharides Derived From Pericarpium Citri Reticulatae "Chachiensis" to Alleviate High-Fat Diet-Induced Depression-Like Behavior.}, journal = {Molecular nutrition & food research}, volume = {70}, number = {2}, pages = {e70388}, doi = {10.1002/mnfr.70388}, pmid = {41574548}, issn = {1613-4133}, support = {2024A0505090024//Guangdong and Macao cooperation project from Department of Science and Technology of Guangdong Province and Jiangmen Science and Technology Bureau/ ; 0077/2024/AGJ//Macao Science and Technology Development Fund/ ; 2520002000138//Jiangmen Key Project of Fundamental and Applied Basic Research/ ; 2024ZDJS035//Guangdong Provincial Key Disciplines Scientific Research Capacity Enhancement Project/ ; 2024ZDZX4015//Department of Education of Guangdong Province/ ; }, mesh = {Animals ; *Diet, High-Fat/adverse effects ; *Depression/etiology/drug therapy ; Gastrointestinal Microbiome/drug effects ; Male ; *Polysaccharides/pharmacology/chemistry ; *Lactobacillus/physiology ; Mice, Inbred C57BL ; Mice ; Fecal Microbiota Transplantation ; Antidepressive Agents/pharmacology ; Behavior, Animal/drug effects ; }, abstract = {Gut microbiota dysbiosis is closely linked to depression and can be modulated by dietary polysaccharides. This study aimed to characterize three polysaccharide fractions from Pericarpium Citri Reticulatae "Chachiensis" (PCRCP)-PCRCPI, PCRCPII, and PCRCPIII-and evaluate their antidepressant effects in a high-fat diet-induced mouse model. Their average molecular weights were approximately 48.9 kDa (PCRCPI), 13.7 kDa (PCRCPII), and 34.8 kDa (PCRCPIII), with a composition primarily of galacturonic acid, arabinose, galactose, and rhamnose. PCRCPI most effectively mitigated depression-like behaviors, as indicated by improved behavioral performance and neurotransmitter levels and reduced neuronal damage. The antidepressant effect of PCRCPI was contingent upon the gut microbiota, as demonstrated by the fact that fecal microbiota transplantation (FMT) from donors treated with PCRCPI conferred behavioral improvements. Mechanistically, PCRCPI treatment selectively increased the abundance of Lactobacillus species and elevated fecal levels of metabolites associated with retrograde endocannabinoid signaling, particularly 2-arachidonoylglycerol (2-AG). Subsequent colonization experiments with specific Lactobacillus strains, either alone or in combination with PCRCPI, activated hippocampal retrograde endocannabinoid signaling as revealed by transcriptomic analysis, and ameliorated depression-like phenotypes. These findings demonstrate the potential of PCRCPI as a prebiotic for alleviating diet-associated depression, through a novel microbiota-gut-brain axis mechanism targeting the endocannabinoid system.}, } @article {pmid41574027, year = {2026}, author = {Lin, A and Xiong, M and Jiang, A and Chen, L and Huang, L and Li, K and Wong, HZH and Zhang, J and Liu, Z and Cheng, Q and Tang, B and Zhang, P and Luo, P}, title = {Tumor Immunotherapy and Microbiome: From Bench-to-Bedside Applications.}, journal = {MedComm}, volume = {7}, number = {2}, pages = {e70454}, pmid = {41574027}, issn = {2688-2663}, abstract = {Cancer immunotherapy has emerged as a transformative therapeutic strategy that harnesses the immune system to combat malignant tumors, overcoming critical limitations such as the nonspecific cytotoxicity of conventional chemotherapy and radiotherapy and drug resistance arising from target mutations in targeted therapies. Growing evidence demonstrates that the human microbiome plays a pivotal role in modulating immune responses and influencing the efficacy of immunotherapeutic interventions. Although the impact is increasingly recognized, the molecular mechanisms and translational potential of microbiome-based strategies remain incompletely explored. This review systematically elucidates how microorganisms from distinct anatomical sites (including bacteria, fungi, and viruses residing in the gut, oral cavity, skin, respiratory tract, and urogenital tract) and intratumoral microbes modulate the tumor immune microenvironment through metabolites, immune cell priming, and antigen mimicry. Furthermore, we discuss how specific microbial signatures predict responses to immune checkpoint inhibitors (ICIs) and CAR-T cell therapy, and highlight emerging interventional strategies, including fecal microbiome transplantation (FMT), probiotics, and engineered bacteria, that demonstrate synergistic effects with immunotherapy in preclinical and clinical settings. By integrating mechanistic insights with translational advances, this review provides a comprehensive scientific foundation for microbiome-based precision immunotherapy, aimed at improving patient survival outcomes and reducing treatment-related adverse events.}, } @article {pmid41573337, year = {2026}, author = {Liu, J and Chen, Y and Wang, Y and Li, D and Xu, Z and Zhang, J and Qin, L and Han, B and Jing, Y and Cui, D and Zhu, Y and Xia, S and Jiang, C}, title = {Diversity of Gut Microbiota and Metabolites in Benign Prostatic Hyperplasia with Different Prostate Volumes.}, journal = {European urology open science}, volume = {84}, number = {}, pages = {40-49}, pmid = {41573337}, issn = {2666-1683}, abstract = {BACKGROUND AND OBJECTIVE: The gut microbiota, influenced by age and sex hormones, may correlate with the development and progression of benign prostatic hyperplasia (BPH). This study aims to characterize gut microbiota and metabolite profiles in BPH patients with varying prostate volumes.

METHODS: Fecal samples from BPH patients were analyzed using 16S rDNA sequencing and untargeted metabolomics. Microbial and metabolic differences were assessed via the Linear discriminant analysis Effect Size, KEGG pathway enrichment, and a mediation analysis.

KEY FINDINGS AND LIMITATIONS: We identified 26 differential amplicon sequence variants (ASVs) and 70 metabolites, with 18 microbes correlating significantly with clinical BPH indicators. The key pathways included unsaturated fatty acid and steroid hormone biosynthesis. Akkermansia (ASV549) may affect prostate volume through the regulation of intestinal amino acid metabolism and may negatively affect prostate-specific antigen levels by inhibiting heat shock protein (HSP) 90 (luminespib). Limitations include sample size and unmeasured confounders.

Gut microbiota and metabolite diversity are associated with prostate volume; further studies are warranted to elucidate the potential interventions via microbiome modulation or metabolic targeting for BPH management.

PATIENT SUMMARY: In this study, we identified the potential associations between gut and both prostate volume and benign prostatic hyperplasia symptoms. These findings suggest that dietary interventions or fecal microbiota transplantation may represent potential strategies for modulating prostate health in the future.}, } @article {pmid41572749, year = {2026}, author = {Ding, L and Xi, Z and Zou, Y and Li, S and Chen, D and Liu, Y and Zhao, J}, title = {Targeting the Gut Microbiota in the Treatment of Type 2 Diabetes: Dietary Interventions, Microbial Preparations, and Fecal Transplantation.}, journal = {Current diabetes reviews}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115733998411102251127094217}, pmid = {41572749}, issn = {1875-6417}, abstract = {Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disease worldwide, characterized by hyperglycemia and insulin resistance (IR). Its escalating global prevalence and the associated morbidity and mortality render it a major public health concern. Conventional glucose- lowering therapies frequently entail adverse effects, hypoglycaemia risk, and fail to arrest disease progression. Emerging evidence positions the gut microbiota as a central regulator of glucose homeostasis and insulin sensitivity, suggesting that gut microbiota might be a promising target for T2DM. This review synthesizes current knowledge of microbiota-driven mechanisms, particularly those of the gut microbiota and their metabolites, that precipitate or exacerbate T2DM. It then critically evaluates microbiota-targeted interventions (dietary modulation, probiotics, prebiotics, antibiotic therapy, and fecal microbiota transplantation) as emerging therapeutic or adjunctive strategies to restore glycaemic control by modulating the gut microbial ecosystem. While clinical validation is incomplete, targeting the gut microbiota represents a promising avenue for both prevention and treatment of T2DM.}, } @article {pmid41572742, year = {2026}, author = {Patil, S and Doshi, G}, title = {Gut Microbiota in the Hepato-Cardiorenal Axis: Microbial Metabolites, Inflammation, and Emerging Therapeutic Targets.}, journal = {Current pharmaceutical design}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113816128413464251209115653}, pmid = {41572742}, issn = {1873-4286}, abstract = {INTRODUCTION: To sustain systemic homeostasis, the gut microbiota manages immunological, metabolic, and inflammatory processes. Multiorgan diseases, especially those impacting the liver, kidney, and cardiovascular system through the hepato-cardiorenal axis, have been strongly associated with dysbiosis.

METHODS: A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, Science Direct, and Google Scholar, with the focus on articles till 2025. Eligible sources included clinical trials, systematic reviews, and peer-reviewed academic publications that discussed metabolites, gut microbiota, and treatment approaches for diseases of the liver, kidney, and heart. A qualitative synthesis of the data indicated important mechanisms and potential treatments.

RESULTS: SCFAs have anti-inflammatory and intestinal barrier integrity-enhancing qualities, whereas uremic toxins and TMAO promote oxidative stress, fibrosis, and vascular dysfunction. Hepatic steatosis, insulin resistance, and systemic inflammation are all affected by the dysbiosis-induced bile acid imbalance. Microbiotatargeted therapies include fecal microbiota transplantation, fiber- or polyphenol-rich diets, probiotics, prebiotics, synbiotics, and pharmacological modification of bile acid or TMAO pathways, which have potential but need more comprehensive validation.

DISCUSSION: The findings show that, among other factors, gut metabolites-such as uremic toxins, bile acids, TMAO, and SCFAs - are key players in mediating inflammation and metabolic dysregulation across the hepato-cardiorenal axis. However, the lack of consistent treatment protocols and differences in microbiome composition limit the practical application of preclinical research that has clearly demonstrated the existence of mechanistic links. Future research should focus on long-term clinical outcomes, biomarker identification, and precise microbiome modifications to establish causation and improve therapy effectiveness.

CONCLUSION: The gut microbiota significantly influences the hepato-cardiorenal axis through metabolitemediated signalling. While therapeutic modulation shows promise, precision medicine approaches and highquality randomized trials are essential to tackle multi-organ metabolic and inflammatory diseases.}, } @article {pmid41572325, year = {2026}, author = {Su, SH and Lu, DD and Wu, YF and Huang, XS and Zhang, L}, title = {Fecal microbiota transplantation promotes Wnt3a-mediated hippocampal neurogenesis in a rat model of chronic cerebral hypoperfusion.}, journal = {Journal of translational medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12967-025-07631-8}, pmid = {41572325}, issn = {1479-5876}, support = {81974209//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Limited data support the beneficial effects of fecal microbiota transplantation (FMT) against intracranial ischemic injury under chronic cerebral hypoperfusion (CCH). However, a comprehensive understanding is lacking, hindering its clinical translation. In the present study, we evaluated microbial, metabolic, cellular, and behavioral alterations to explore the roles and mechanisms of FMT in hippocampal neurogenesis under CCH.

METHODS: Rats underwent bilateral common carotid artery occlusion to induce CCH. Intestinal microbiota (IM) and fecal/hippocampal metabolites were assessed by 16S ribosomal RNA sequencing and untargeted liquid chromatography-mass spectrometry, respectively. Potential molecular pathways and differentially expressed genes in the hippocampus were identified by RNA sequencing and verified by western blot, immunofluorescence, and dual-luciferase reporter assays. Neurogenesis was quantified by BrdU/DCX, BrdU/nestin, BrdU/GFAP, and BrdU/NeuN labeling. Cognitive function was evaluated with the Morris water maze.

RESULTS: FMT altered IM composition by enriching Verrucomicrobiae, Ruminococcaceae, Akkermansiaceae, Turicibacter, Akkermansia, Verrucomicrobiales, Oscillospirales, Verrucomicrobiota, and Akkermansia_muciniphila. These shifts were associated with significantly elevated metabolites in tryptophan- and arginine-related pathways, including fecal L-tryptophan and hippocampal L-arginine, L-glutamine, indolepyruvate, indoleacetaldehyde, and kynurenic acid. Furthermore, FMT potentiated the Wnt3a/β-catenin/Neurog2/BDNF pathway, promoting hippocampal neurogenesis. FMT-induced activation of Wnt3a/β-catenin/Neurog2 signaling also up-regulated hippocampal C3 expression, contributing to neurogenesis and cognitive recovery under CCH.

CONCLUSION: These findings provide evidence that FMT exerts protective effects against CCH insult through Wnt3a-mediated neurogenesis.}, } @article {pmid41571673, year = {2026}, author = {Bautista, J and Lamas-Maceiras, M and Hidalgo-Tinoco, C and Guerra-Guerrero, A and Betancourt-Velarde, A and López-Cortés, A}, title = {Gut microbiome-driven colorectal cancer via immune, metabolic, neural, and endocrine axes reprogramming.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-025-00883-8}, pmid = {41571673}, issn = {2055-5008}, abstract = {Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide and is increasingly recognized as the outcome of complex host-microbe interactions. Beyond established genetic and environmental drivers, the gut microbiome has emerged as a causal and mechanistic contributor to CRC initiation, progression, and therapy response. This review synthesizes current molecular, ecological, and translational evidence to explain how gut microbial communities reprogram immune, metabolic, neural, and endocrine networks within the tumor microenvironment. CRC-associated dysbiosis is characterized by enrichment of pathobionts such as Fusobacterium nucleatum, pks[+] Escherichia coli, and enterotoxigenic Bacteroides fragilis, and by loss of protective, short-chain-fatty-acid-producing commensals. These microbes promote carcinogenesis through genotoxin-induced DNA damage, epithelial barrier disruption, metabolic rewiring, and chronic inflammation that collectively sustain immune suppression and tumor growth. Defined mutational signatures from bacterial metabolites, including colibactin, cytolethal distending toxin, and indolimines, now directly link microbial exposures to human cancer genomes. By integrating these findings, this review conceptualizes CRC as a biofilm-structured, microbiome-driven ecosystem disease, where polymicrobial consortia coordinate barrier breakdown, immune evasion, and metabolic cooperation. Finally, we highlight emerging microbiota-targeted strategies, including dietary modulation, pre- and probiotics, postbiotics, bacteriophage therapy, engineered live biotherapeutics, and fecal microbiota transplantation, that translate these insights into precision prevention and therapy. Through this integrative framework, the review aims to reposition the microbiome from a correlative feature to a tractable determinant of CRC pathogenesis and treatment response.}, } @article {pmid41571448, year = {2026}, author = {Cakir, RC and Belen, NH and Yildirim, S and Avci, S and Dincer, A and Kazan, MK and Celik, O and Aslaner, A and Eyvaz, K and Cakir, T}, title = {Effect of Ileal Feces Transplantation in Preventing Diversion Colitis and Its Complications Due to Protective Loop Ileostomy in Rectal Cancer Cases.}, journal = {Journal of investigative surgery : the official journal of the Academy of Surgical Research}, volume = {39}, number = {1}, pages = {2609429}, doi = {10.1080/08941939.2025.2609429}, pmid = {41571448}, issn = {1521-0553}, mesh = {Humans ; *Ileostomy/adverse effects/methods ; Male ; Middle Aged ; Female ; *Rectal Neoplasms/surgery ; Prospective Studies ; Aged ; *Colitis/prevention & control/etiology/pathology ; Ileum/surgery ; *Postoperative Complications/prevention & control/etiology ; Treatment Outcome ; *Fecal Microbiota Transplantation/methods ; Adult ; Feces ; }, abstract = {To evaluate the effectiveness of fecal transplantation (FT) in preventing the development of diversion colitis (DC) and reducing its complications in patients who underwent protective loop ileostomy (PLI) following low anterior resection for rectal cancer. The study was prospectively conducted at Tertiary Hospital. Seventeen patients who underwent PLI were assigned to the FT group (FT+), and 19 patients served as the control group (FT-). In the FT+ group, ileal content was delivered to the efferent loop via a catheter placed during surgery. Both groups were evaluated postoperatively through biopsies taken for histopathological examination. In the FT+ group, significant reductions were observed in parameters specific to DC, such as the severity of inflammation, ulceration, goblet cell loss, and crypt abscesses, compared to the FT- group (p < 0.05). The epithelial structure and crypt organization in the FT+ group were closer to normal. FT is an effective and easily applicable method for preventing DC development and reducing the severity of inflammatory changes in patients undergoing PLI. The technique is low-cost, has high patient compliance, and aligns with methods reported in the literature for DC prevention.}, } @article {pmid41571367, year = {2026}, author = {Lin, Y and Jiang, Z and Yu, Z and Huang, T and Gui, W and Wang, Z and Li, F and Xiao, P and Li, C and Liu, E}, title = {Honokiol attenuates diabetes by enriching Akkermansia muciniphila andregulating tryptophan metabolism in mice.}, journal = {Chinese journal of natural medicines}, volume = {24}, number = {1}, pages = {59-72}, doi = {10.1016/S1875-5364(26)61077-1}, pmid = {41571367}, issn = {1875-5364}, mesh = {Animals ; *Lignans/administration & dosage/pharmacology ; *Tryptophan/metabolism ; Gastrointestinal Microbiome/drug effects ; Mice ; *Biphenyl Compounds/administration & dosage/pharmacology ; Male ; Mice, Inbred C57BL ; *Hypoglycemic Agents/administration & dosage ; Glucagon-Like Peptide 1/metabolism ; *Akkermansia/drug effects ; Receptors, Aryl Hydrocarbon/metabolism ; *Diabetes Mellitus, Experimental/drug therapy/metabolism/microbiology ; Humans ; *Diabetes Mellitus/drug therapy/metabolism/microbiology ; Fecal Microbiota Transplantation ; Allyl Compounds ; Phenols ; }, abstract = {Diabetes mellitus (DM) is a chronic disease influenced by gut microbiome disturbances. Honokiol (HON), a low oral bioavailability compound from Magnolia officinalis bark, has demonstrated potential as a treatment for DM. This research investigates the effects of HON on gut microbiota and host metabolism to elucidate its mechanism of action in DM. After 8 weeks of intervention through fecal microbiota transplantation (FMT) or antibiotic treatment, HON improved glucose tolerance and lipid metabolism in a gut microbiota-dependent manner. Specifically, HON administration significantly increased Akkermansia muciniphila (AKK) abundance and modulated tryptophan (TRP) metabolism, as evidenced by 16S ribosomal ribonucleic acid (rRNA) gene sequencing and untargeted/targeted metabolomics analysis. Notably, research revealed that AKK metabolized TRP into tryptamine (TA) and other metabolites in vitro. Both AKK and TA activated the aryl hydrocarbon receptor (AHR) pathway, increasing circulating glucagon-like peptide-1 (GLP-1) levels and ameliorating diabetes-related symptoms in DM mice. These findings indicate that HON's hypoglycemic effect primarily stems from AHR-GLP-1 pathway activation through targeted modulation of AKK and microbial TRP metabolite TA, potentially enhancing HON's clinical applications.}, } @article {pmid41570877, year = {2026}, author = {Wang, Y and Wang, X and Gan, B and Jia, T and Xu, T and Xu, H}, title = {Ferroptosis and Hepatic Fibrosis induced by Cooperative Exposure to Polylactic Acid Nanoplastics and Copper: Emphasis on Gut Microbiota Dysbiosis.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {}, number = {}, pages = {127698}, doi = {10.1016/j.envpol.2026.127698}, pmid = {41570877}, issn = {1873-6424}, abstract = {Co-exposure to polylactic acid nanoplastics (PLA-NPs) and copper (Cu) in the environment poses a health risk, yet their combined toxic effects remain poorly understood. This study investigated the synergistic hepatotoxicity and underlying mechanisms, focusing on the gut-liver axis, in a mouse model of subacute exposure. Results demonstrated that co-exposure caused significant synergistic effects, including exacerbated changes in body weight (BW), increased hepatic index ratio, and severe liver injury marked by elevated Aspartate Aminotransferase/Alanine Aminotransferase/Alkaline Phosphatase (AST/ALT/AKP) activities and histopathological damage. Crucially, co-exposure synergistically induced hepatic ferroptosis (evidenced by dysregulated Glutathione (GSH), Malondialdehyde (MDA), and iron homeostasis), disrupted lipid metabolism, and promoted oxidative stress. These hepatic injuries were indeced by intestinal barrier damage and gut microbiota dysbiosis, characterized by reduced beneficial Lactobacillus murinus. The fecal microbiota transplantation (FMT) experiment definitively confirmed the causal role of gut microbiota, as transferring microbiota from donor mice to healthy recipients recapitulated the key hepatointestinal injuries. This study demonstrates that co-exposure to PLA-NPs and Cu induces synergistic hepatotoxicity primarily mediated through gut microbiota disruption and gut-liver axis dysfunction, leading to hepatic ferroptosis and fibrosis. These findings highlight the critical role of the gut microbiome in modulating the synergistic toxicity of environmental contaminants and provide new insights into the health risks of mixed pollutant exposure.}, } @article {pmid41570815, year = {2026}, author = {Tong, T and Huang, X and Li, L and Hu, M and Zhu, X and Zhu, B and Ma, Y and Ning, L and Jiang, Y and Zhang, Y and Zhou, Y and Wang, Z and Ding, J and Zhao, Y and Xuan, B and Zhang, Y and Xiao, X and Fang, JY and Hong, J and Yin, Y and Liu, F and Chen, H}, title = {Microbial metabolite FAD mobilizes adipocyte lipid remodeling to enhance cancer immunotherapy efficacy.}, journal = {Cell metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmet.2025.12.012}, pmid = {41570815}, issn = {1932-7420}, abstract = {Crosstalk between gut microbiota and adipose tissue critically shapes immunotherapy responses in patients with cancer. An obesity-associated microbial signature enriched in riboflavin-producing taxa was identified, along with increased microbial riboflavin biosynthesis pathway and elevated levels of flavin adenine dinucleotide (FAD), in obese responders to immune checkpoint blockade (ICB). In diet-induced obese (DIO) mice, fecal microbiota transplantation (FMT), administration of Lachnospiraceae bacterium, or FAD supplementation significantly enhanced the therapeutic efficacy of anti-PD-1 therapy. These interventions increased the cytotoxicity of tumor-infiltrating CD8[+] T cells via mesenteric adipocyte-driven synthesis of polyunsaturated fatty acids (PUFAs). Inhibiting fatty acid desaturase 2 (FADS2) eliminated the benefits of FAD, underscoring a critical role for adipocyte-intrinsic lipid remodeling in mediating immune responses. Clinically, elevated systemic levels of PUFAs, particularly docosahexaenoic acid (DHA), were positively correlated with intratumoral CD8[+] T cell infiltration and favorable immunotherapy outcomes. Dietary DHA supplementation improved ICB responses in lean mice. This study highlights that a microbiota-adipose axis shapes antitumor immunity, enabling potential personalized metabolic and microbial immunotherapy strategies.}, } @article {pmid41570783, year = {2026}, author = {Ding, J and Xu, F and Chen, D and Xi, J and Gao, F and Chen, L and Wang, B and Dou, X and Qiu, J and He, G}, title = {Qing Hua Yu Du formula ameliorates alcoholic hepatic fibrosis by regulating MAPK/TLR4-MyD88 inflammatory pathways, restoring hepatic metabolism and modulating gut microbiota.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {152}, number = {}, pages = {157830}, doi = {10.1016/j.phymed.2026.157830}, pmid = {41570783}, issn = {1618-095X}, abstract = {BACKGROUND: Alcohol-induced liver injury (ALI) and subsequent hepatic fibrosis pose significant global health burdens, with limited effective therapeutic options. Traditional Chinese Medicine (TCM) formulas, such as Qing Hua Yu Du (QHYD) formula, have shown potential in treating alcoholic hepatic fibrosis in clinical, but their therapeutic effects, and underlying mechanisms remain incompletely characterized. Additionally, the interplay between hepatic inflammation, metabolic disorders, and gut-liver axis dysregulation in ALI-related fibrosis necessitates comprehensive validation across multiple models.

PURPOSE: This study aimed to evaluate the therapeutic effects of QHYD formula on alcohol-CCl₄-induced alcoholic hepatic fibrosis in diverse models (alcohol-CCl₄, acute binge alcohol, and cell models), explore its mechanisms involving inflammatory signaling, hepatic metabolism, and gut microbiota, validate the key metabolite l-histidine's role, and assess its safety profile.

METHODS: The QHYD formula's chemical composition was characterized using advanced high-performance liquid chromatography (HPLC) fingerprinting for quality control and ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS) for constituent identification. Male C57BL/6 mice were assigned to normal, model, QHYD (2.7, 4.05, 5.4 g/kg/day), and fecal microbiota transplantation (FMT) groups. Acute binge alcohol and AML-12 cell models were used for supplementary validation. Liver injury was evaluated by plasma biochemical markers (ALT/AST/GGT/TC/TG) and histological staining (H&E/Masson). Inflammatory pathways (MAPK/TLR4-MyD88), metabolic changes, and gut microbiota were analyzed via Western blot, ELISA, transcriptomics, metabolomics, and 16S rRNA sequencing. l-histidine's mechanism was validated in LX-2 cells using qRT-PCR and immunofluorescence. Acute/chronic toxicity assays were conducted to assess safety.

RESULTS: HPLC confirmed QHYD's batch consistency, and UHPLC-Q/TOF-MS identified 82 constituents. QHYD significantly ameliorated liver injury and fibrosis in alcohol-CCl₄ and acute binge alcohol models, reduced plasma TC/TG, and inhibited Col1a1/α-SMA expression. It suppressed MAPK/TLR4-MyD88 signaling, restored protein digestion/absorption pathway (upregulating l-histidine), and modulated gut microbiota richness/composition. FMT experiments confirmed QHYD-modulated gut microbiota directly mediated anti-fibrotic effects. l-histidine dose-dependently inhibited HSC activation via the NF-κB-TIMP1 axis.

CONCLUSION: QHYD ameliorates alcoholic hepatic fibrosis through multi-targeted mechanisms: inhibiting MAPK/TLR4-MyD88 inflammatory pathways, restoring hepatic metabolism via l-histidine, and modulating gut microbiota. Its favorable safety profile and efficacy across diverse models support QHYD as a promising therapeutic candidate, with l-histidine serving as a key mediating metabolite.}, } @article {pmid41569851, year = {2026}, author = {Kabil, AK and Cait, A and Reynolds, LA and Chopra, S and Bilenky, M and Moksa, M and Li, Y and Cait, J and Hernaez, DC and Scott, RW and Fogarty, E and Finlay, BB and Mohn, WW and Hirst, M and Hughes, MR and McNagny, KM}, title = {Early-life microbiota skews long-term gene expression and chromatin states of bone marrow hematopoietic precursors.}, journal = {Cell reports}, volume = {45}, number = {2}, pages = {116871}, doi = {10.1016/j.celrep.2025.116871}, pmid = {41569851}, issn = {2211-1247}, abstract = {Early life is a critical window during which the gut microbiota sculpts immunity and long-term susceptibility to allergic disease. Using neonatal antibiotic administration and bone marrow transplantation assays, we show that depletion of short-chain fatty acid (SCFA)-producing bacteria alters gene expression in hematopoietic stem and progenitor cells (HSPCs) and imprints a persistent, transplantable atopic immune phenotype. Bone marrow transplants from exposed mice generate recipients with elevated serum immunoglobulin E (IgE), downstream increased IgE bound to basophils, and exacerbated allergic lung inflammation following papain challenge. Depletion of SCFA-producing bacteria also impairs recovery from chemotherapy-induced myelosuppression and increases DNA damage in long-term HSPCs in an antibiotic-specific manner. Histone 3 lysine 27 (H3K27) chromatin immunoprecipitation sequencing (ChIP-seq) analyses further reveal differential histone acetylation in HSPCs, consistent with an SCFA-mediated epigenetic regulatory mechanism. Collectively, these findings establish a link between gut microbiota composition, hematopoiesis, and long-term immune function, offering a mechanistic explanation for microbiota-driven susceptibility to atopic disease and hematopoietic dysfunction.}, } @article {pmid41569045, year = {2026}, author = {Yao, G and Zhang, T and Qin, Z and Wang, Y and Gu, J and He, C and Jin, J}, title = {Corn silk extract as a prebiotic exerts antihypertensive effects via gut microbiota modulation in hypertensive rats.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0144225}, doi = {10.1128/spectrum.01442-25}, pmid = {41569045}, issn = {2165-0497}, abstract = {UNLABELLED: Corn silk extract (CSE), a traditional medicinal food rich in polysaccharides, flavonoids, and saponins, has been used as a natural antihypertensive agent, but its mechanism remains unclear. This study aimed to evaluate whether CSE can lower blood pressure through gut microbiota modulation. Spontaneously hypertensive rats received oral CSE for 4 weeks, followed by a 4-week drug-free observation. The treatment significantly reduced blood pressure, increased microbial diversity, decreased the Firmicutes/Bacteroidetes ratio, and enriched beneficial genera, such as Akkermansia and Lactobacillus. These changes were accompanied by reduced serum lipopolysaccharide and pro-inflammatory cytokines, elevated nitric oxide (NO) levels, and restored endothelial function. Permutational multivariate analysis of variance (PERMANOVA) and correlation analyses showed that microbiota and inflammatory markers were more strongly associated with blood pressure improvements than urinary indices. Structural equation modeling suggested a potential mechanistic pathway involving gut microbiota-inflammation-NO regulation. Importantly, fecal microbiota transplantation using post-treatment donor samples reproduced the antihypertensive and anti-inflammatory effects, confirming the microbiota's critical mediating role. These findings provide the first experimental evidence that CSE functions as a prebiotic to improve gut microbial balance and vascular health, offering a promising natural strategy for microbiota-targeted blood pressure control.

IMPORTANCE: This study identifies corn silk extract (CSE) as a novel plant-derived prebiotic with antihypertensive effects mediated through gut microbiota modulation. Using a spontaneously hypertensive rat model, we demonstrated that CSE reshapes gut microbial composition, enhances microbial diversity, and promotes beneficial genera while reducing systemic inflammation and restoring nitric oxide (NO)-mediated vascular function. Importantly, fecal microbiota transplantation confirmed the causal role of gut microbiota in mediating these effects. These findings highlight a gut microbiota-inflammation-NO axis as a key pathway through which CSE regulates blood pressure. As a safe, accessible, and food-compatible intervention, CSE represents a promising strategy for non-pharmacological blood pressure management and broadens the application scope of prebiotics in cardiovascular health.}, } @article {pmid41568946, year = {2026}, author = {Huang, P and Cao, L and Cao, T and Wang, X and Cui, S and Jiang, S and Chen, H and Di, L and Li, S and Huang, L}, title = {Intermittent Fasting Alleviates Anesthesia/Surgery-Induced Delirium-Like Behavior in Aged Mice by Remodeling Gut Microbiota.}, journal = {CNS neuroscience & therapeutics}, volume = {32}, number = {1}, pages = {e70748}, pmid = {41568946}, issn = {1755-5949}, support = {//Hebei Medical University Postdoctoral Fund/ ; PD2025007//Postdoctoral Research Support Program for Clinical Medicine of Hebei Medical University/ ; H2022206586//the S&T Program of Hebei/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Fasting/physiology ; Mice ; Mice, Inbred C57BL ; Male ; *Delirium/prevention & control/etiology ; Hippocampus/ultrastructure/metabolism ; Fecal Microbiota Transplantation ; *Anesthesia/adverse effects ; Aging ; Mitochondria/metabolism ; Fatty Acids, Volatile/metabolism ; *Postoperative Complications/prevention & control ; Intermittent Fasting ; }, abstract = {BACKGROUND: Postoperative delirium (POD) is a serious complication in elderly patients, associated with prolonged recovery and adverse outcomes. Recent evidence links POD to mitochondrial dysfunction. While intermittent fasting (IF) has been shown to enhance mitochondrial function and exert neuroprotective effects, potentially through gut microbiota modulation, its ability to prevent POD and the underlying mechanisms remain unclear.

METHODS: We examined the effects of preoperative IF on delirium-like behavior in aged mice following anesthesia/surgery. Assessments included neurobehavioral tests, gut microbiota composition, fecal shortchain fatty acids (SCFAs), hippocampal synaptic and mitochondrial ultrastructure via transmission electron microscopy, mitochondrial function, and related molecular markers. To establish causality, fecal microbiota transplantation and SCFA supplementation experiments were conducted.

RESULTS: Preoperative IF significantly attenuated anesthesia/surgery-induced delirium-like behaviors. Mechanistically, IF reshaped the gut microbiota and preserved SCFA levels, which collectively maintained hippocampal mitochondrial homeostasis. Both fecal microbiota transplantation and SCFA supplementation replicated the protective effects of IF, confirming the causal role of gut microbiota and its metabolites.

CONCLUSION: These findings demonstrate that preoperative intermittent fasting mitigates delirium-like behavior by modulating the gut microbiota-SCFA-mitochondrial axis, highlighting its potential as a non-pharmacological strategy to enhance neurocognitive resilience and prevent POD in elderly surgical patients.}, } @article {pmid41568321, year = {2026}, author = {Yahyapour, A and Najafi, A and Ahmadi, A and Salarizadeh, N}, title = {Immunoprotective and neuroprotective properties of gut microbiome in psoriasis.}, journal = {Journal of translational autoimmunity}, volume = {12}, number = {}, pages = {100348}, pmid = {41568321}, issn = {2589-9090}, abstract = {Psoriasis impacts nearly 100 million people globally and is associated with neuropsychiatric comorbidities such as depression and anxiety. With gut microbiome dysbiosis serving as a primary pathophysiological factor, the gut-brain-skin axis provides a crucial framework for understanding this relationship. This review evaluates the mechanisms of the gut-brain-skin axis in psoriasis pathophysiology and assesses the therapeutic potential of microbiome-based treatments, combining preclinical, clinical, and multi-omics data. Patients with psoriasis show specific gut dysbiosis patterns, including reduced microbial diversity, lower SCFA-producing bacteria (especially Faecalibacterium and Akkermansia), and increased pro-inflammatory bacteria. This microbial imbalance damages intestinal barrier integrity, triggers systemic inflammation, activates cutaneous Th17 pathways, and induces neuroinflammation through blood-brain barrier disruption. Axis communication occurs through immune-inflammatory mechanisms mediated by SCFAs and neuroendocrine pathways involving microbially-derived neurotransmitters (GABA, serotonin, dopamine). Metagenomic research indicates functional deficiencies in neurotransmitter and SCFA synthesis pathways are more significant than taxonomic alterations. Machine learning models can utilize these functional features to identify patients at risk for neuropsychiatric comorbidities and predict treatment response. Recent randomized controlled trials demonstrate that targeted interventions (probiotics, prebiotics, postbiotics, fecal microbiota transplantation) significantly improve Psoriasis Area and Severity Index scores, inflammatory markers, and microbiota composition. The evidence supports a shift toward integrated microbiome strategies, emphasizing functional approaches including mitochondrial therapies, psychobiotics, precision nutrition, and multi-omics-guided therapies.}, } @article {pmid41568320, year = {2025}, author = {Perry, S and Pillarisetti, L and Gelfman, T and Agrawal, DK}, title = {Gut-Brain Axis in Inflammatory Bowel Disease: Pathogenesis and Therapeutics.}, journal = {Archives of internal medicine research}, volume = {8}, number = {4}, pages = {339-345}, pmid = {41568320}, issn = {2688-5654}, support = {R25 AI179582/AI/NIAID NIH HHS/United States ; }, abstract = {Inflammatory Bowel Disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a chronic inflammatory disorder of the gastrointestinal tract driven by complex interactions between genetic susceptibility, environmental triggers, microbial dysbiosis, and immune dysregulation. The gut microbiome, composed primarily of Firmicutes and Bacteroidetes, plays a crucial role in maintaining intestinal barrier integrity, immune balance, and neuroimmune signaling. Disruption of this microbial ecosystem is characterized by loss of beneficial short chain fatty acid producing bacteria and expansion of pathogenic species which promotes mucosal inflammation, cytokine release, and neuroimmune signaling that can disrupt mental health through the gut-brain axis. Emerging evidence links microbial metabolites, vagal tone, and the hypothalamic-pituitary-adrenal axis in a feedback loop that perpetuates inflammation and alters mood regulation. Current therapeutic approaches include diet modification, osteopathic manipulative treatments, fecal microbiota transplantation and phage therapy. This article focuses on understanding mechanisms linking dysbiosis, immune activation, and neuroinflammation to guide future interventions. A holistic model addressing the gut-brain axis holds the greatest promise for improving outcomes and personalizing care for IBD.}, } @article {pmid41568166, year = {2026}, author = {Lu, M and Guo, S and Nie, Z and Ji, J and Wang, Y and Jiang, X and Zhang, L and Xiang, B and Wu, W and Ji, J and Zou, J and Ding, X and Yu, X}, title = {Differences in gut microbiota composition are an important reason for lower serum p-cresol sulfate levels in anuric peritoneal dialysis patients compared to hemodialysis patients.}, journal = {Current research in microbial sciences}, volume = {10}, number = {}, pages = {100548}, pmid = {41568166}, issn = {2666-5174}, abstract = {BACKGROUND: Patients with end-stage kidney disease (ESKD) accumulate toxic metabolites that contribute to severe clinical complications. Peritoneal dialysis (PD) and hemodialysis (HD) exhibit distinct capacites for toxin clearance. Furthermore, the gut microbiota plays a significant role in toxin generation and is modulated by dialysis modality. This study aimed to compare gut microbiota composition and serum metabolite profiles between PD and HD patients, and to investigate their association with uremic toxin production.

METHODS: This single-center, cross-sectional study included 100 anuric ESKD patients (50 PD and 50 HD) matched for age, gender, and dialysis duration. Fecal and serum samples were collected and analyzed using 16S rRNA gene sequencing and non-targeted metabolomics. To validate the gut microbiota-serum metabolite relationship, fecal microbiota transplantation (FMT) was performed in germ-free CKD mice.

RESULTS: No significant differences in alpha diversity were observed between PD and HD groups (all indices P > 0.05), but beta diversity analysis revealed distinct gut microbial compositions (ANOSIM R = 0.093, P = 0.001), with PD patients showing higher abundance of opportunistic pathogens and lower abundance of beneficial bacteria. Non-targeted metabolomics identified 314 significantly different metabolites between the two groups, including significantly lower levels of p-cresyl sulfate (PCS) in PD patients (PD:19.16(7.24,53.83), HD:70.21(26.75,96.79), P < 0.001), with altered metabolic pathways such as tyrosine, tryptophan, and phenylalanine metabolism. FMT experiments in CKD germ-free mice confirmed higher serum PCS levels in HD recipients than in PD recipients (PD:30,456.02±4598.39, HD:45,025.00±4513.59, P < 0.05), supporting the role of gut microbiota in toxin production.

CONCLUSION: PD and HD patients show distinct gut microbiota and serum metabolite profiles, with notably lower PCS levels in PD patients. These differences are associated with variations in gut microbiota. Animal experiments provide additional evidence suggesting a potential causal relationship. Modulating gut microbiota may represent a promising therapeutic approach to decrease uremic toxin production in dialysis patients.}, } @article {pmid41567684, year = {2025}, author = {Lanas, A and Alvarez-Mercado, AI}, title = {Editorial: Improving the gut microbiome: applications of fecal transplantation in disease, volume II.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1758943}, doi = {10.3389/fmed.2025.1758943}, pmid = {41567684}, issn = {2296-858X}, } @article {pmid41566359, year = {2026}, author = {Ko, H and Kim, CJ and Choi, S and Noh, J and Kim, SW and Lee, J and Byun, S and Lee, H and Park, JC and Park, HE and Sharma, A and Park, M and Park, J and Lee, CG and Cha, KH and Im, SH}, title = {Commensal microbe-derived butyrate enhances T follicular helper cell function to boost mucosal vaccine efficacy.}, journal = {Microbiome}, volume = {14}, number = {1}, pages = {37}, pmid = {41566359}, issn = {2049-2618}, support = {RS-2024-00414820//Ministry of Education, Science and Technology/ ; 2Z07251//Korea Institute of Science and Technology/ ; RS-2024-00345575//Ministry of Science and ICT, South Korea/ ; }, mesh = {Animals ; Mice ; *T Follicular Helper Cells/immunology/drug effects ; *Gastrointestinal Microbiome/immunology ; *Butyrates/metabolism ; Peyer's Patches/immunology ; *Immunity, Mucosal ; Mice, Inbred C57BL ; Immunoglobulin A, Secretory/immunology ; Cell Differentiation ; Immunoglobulin A/immunology ; *T-Lymphocytes, Helper-Inducer/immunology ; Female ; B-Lymphocytes/immunology ; }, abstract = {BACKGROUND: The gut microbiota plays an essential role in mucosal immunity, with secretory immunoglobulin A (IgA) acting as a key effector in neutralizing pathogens and maintaining host-microbiota homeostasis. IgA production occurs via T cell-dependent (TD) and -independent pathways, with T follicular helper (Tfh) cells driving high-affinity, antigen-specific IgA responses. However, the specific microbial taxa and metabolites that regulate Tfh-mediated IgA responses under steady-state conditions remain poorly understood. This study investigated how gut microbiota-derived signals shape Tfh responses and IgA production, with implications for enhancing mucosal vaccine efficacy.

RESULTS: We demonstrate that Peyer's patches (PP)-derived Tfh cells exhibit superior IgA-inducing capacity compared to splenic Tfh cells. RNA sequencing revealed distinct transcriptional profiles in PP-Tfh cells, including upregulation of the genes associated with Tfh differentiation and activation (Bcl6, Cd40lg, Maf), T-B cell interactions (Il21, Sh2d1a, Fyn), and migration (Ccr6, Cxcr5). Functionally, PP-Tfh cells formed larger T-B cell contact areas and induced significantly higher IgA secretion in co-culture than their splenic counterparts. Microbiota depletion experiments revealed that eliminating neomycin-depleted bacteria reduced fecal IgA levels and diminished PP-Tfh cell frequencies. Fecal microbiota transplantation from neomycin-treated mice restored both IgA production and Tfh responses in germ-free (GF) mice. Bioinformatic analysis (PICRUSt2 and LEfSe) identified butyrate-producing Lachnospiraceae and Ruminococcaceae as key drivers of the Tfh-IgA axis. Butyrate supplementation enhanced Tfh differentiation and IgA⁺ germinal center B cell development in vitro and increased fecal IgA levels in vivo. Mechanistically, butyrate promoted IgA production via GPR43 signaling, as its effect was lost in co-cultures with Gpr43[⁻/⁻] Tfh cells. Moreover, treatment with tributyrin, a butyrate prodrug, enhanced vaccine-induced IgA and protected mice against Salmonella Typhimurium infection, reducing bacterial burden and tissue damage. These findings define a functional microbiota-Tfh-IgA axis sustained by neomycin-depleted, butyrate-producing bacteria.

CONCLUSIONS: Our study underscores the crucial role of the gut microbiota, particularly neomycin-depleted butyrate producing taxa, in regulating PP-Tfh cell function and IgA production. Butyrate emerges as a metabolite linking microbial metabolism to Tfh differentiation and IgA class switching. Together, these findings establish a microbiota-metabolite-Tfh cell axis essential for mucosal immune homeostasis and suggest novel strategies for enhancing vaccine efficacy and protection against enteric infections. Video Abstract.}, } @article {pmid41564102, year = {2026}, author = {Pu, X and Liu, B and Dong, L and Yuan, M and Jin, S and Jiang, X}, title = {Fecal microbiota transplantation ameliorates radiation-induced lung injury by reshaping gut metabolic homeostasis to activate FAM134B-mediated ER-phagy.}, journal = {PLoS pathogens}, volume = {22}, number = {1}, pages = {e1013786}, pmid = {41564102}, issn = {1553-7374}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Mice ; *Gastrointestinal Microbiome/physiology ; *Endoplasmic Reticulum/metabolism ; *Lung Injury/therapy/metabolism/etiology/microbiology ; Homeostasis ; Mice, Inbred C57BL ; Male ; Pancreatitis-Associated Proteins/metabolism ; *Membrane Proteins/metabolism ; }, abstract = {Radiation-induced lung injury (RILI) is a serious complication of thoracic radiotherapy, with limited effective treatment options. This study demonstrates that fecal microbiota transplantation (FMT) confers protection against RILI through modulation of the gut-lung axis. In a total lung irradiation (TLI) mouse model, FMT significantly alleviated pulmonary histopathological injury, inflammatory responses, oxidative stress, and collagen deposition during fibrogenesis. Concurrently, FMT improved intestinal motility, enhanced mucosal barrier integrity, and restored TLI-induced dysbiosis in gut microbiota diversity and community structure. Metabolomic analysis revealed that TLI significantly disrupted the metabolism of unsaturated fatty acids and arachidonic acid (AA), whereas FMT partially restored these metabolic networks. Transcriptomic and ultrastructural analyses indicated that RILI suppressed endoplasmic reticulum (ER) protein processing and induced ER swelling, while FMT promoted protective ER-phagy and facilitated restoration of ER morphology. Integrated multi-omics analysis further identified the AA metabolism as a key component of FMT-mediated protection, with its alterations closely associated with pulmonary tissue repair. Further in vivo and in vitro experiments demonstrated that AA binds to and activates the nuclear receptor PPARγ, leading to transcriptional upregulation of FAM134B, promoting protective ER-phagy and ameliorating RILI. In summary, this study highlights the bidirectional gut-lung axis as a therapeutic target in RILI progression and intervention, and reveals that FMT confers protection through metabolic remodeling and activation of the PPARγ-FAM134B-mediated ER-phagy pathway, providing a mechanistic basis for potential clinical translation.}, } @article {pmid41562083, year = {2025}, author = {Liu, J and Hong, W and Sun, Z and Zhang, S and Xue, C and Dong, N}, title = {The gut-lung axis: effects and mechanisms of gut microbiota on pulmonary diseases.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1693964}, pmid = {41562083}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; Animals ; *Lung/immunology/metabolism/microbiology ; Dysbiosis/immunology ; *Lung Diseases/microbiology/immunology/metabolism/therapy/etiology ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {The proposal of the gut-lung axis has profoundly reshaped our understanding of the mechanisms underlying respiratory diseases. As a crucial component of this axis, the gut microbiota plays a central role in pulmonary immune regulation through inter-organ communication mediated by metabolic products. However, a systematic integration of mechanisms explaining how gut microbes achieve precise cross-organ immune regulation remains elusive. Existing research predominantly focuses on descriptive observations, such as the association between early-life microbiota dysbiosis and an increased risk of asthma and chronic obstructive pulmonary disease (COPD), as well as the frequent occurrence of acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF), often accompanied by gut microbiome disruption. This paper focuses on three key gut microbial metabolites-short-chain fatty acids (SCFAs), tryptophan metabolites, and polyamines (PAs)-to examine their roles in immune regulation, maintenance of barrier function, and modulation of metabolic signaling networks. Based on the latest experimental and clinical evidence, this study systematically elucidates how dysbiosis of the gut microbiota, a key component of the gut-lung axis, crosses physiological barriers to exacerbate pulmonary inflammation. Regarding intervention strategies, probiotics, fecal microbiota transplantation (FMT), and CRISPR-Cas systems have demonstrated significant therapeutic potential in restoring gut microbial balance. Finally, this paper outlines future research directions, emphasizing the need to further explore non-invasive microbial sampling techniques, molecular interaction mechanisms of the gut-lung axis, and personalized microbiome-based diagnostic and therapeutic strategies to provide new insights for the prevention and treatment of respiratory diseases involving gut microbiota.}, } @article {pmid41561086, year = {2025}, author = {Zhang, MY and Chen, SY and Lin, YH and Yuan, XX}, title = {Gut microbiota modulation in gastrointestinal disorders: current evidence and therapeutic perspectives.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1740322}, pmid = {41561086}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Gastrointestinal Diseases/therapy/microbiology ; Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; Gastrointestinal Tract/microbiology ; Phage Therapy ; Dysbiosis/therapy ; }, abstract = {Gut microbiome medicine is a promising field in functional medicine, offering personalized treatment strategies for gastrointestinal disorders. Advanced metagenomic and metabolomic technologies have revealed the gut microbiome's systemic influence, extending to distant organs like the brain and lungs. While small molecules and genes facilitate these effects, the gut microbiota's greatest abundance and activity are concentrated in the gastrointestinal tract, particularly in the distal regions. The balance of microbial communities in the small and large intestines is crucial for gastrointestinal health. However, the dominance of pathogenic bacteria can disrupt this balance, leading to tissue damage and contributing to gastrointestinal disorders. Emerging interventions, such as probiotics, fecal microbiota transplantation, and dietary enrichment with short-chain fatty acids, show potential in restoring microbial balance, enhancing immune function, and potentially protecting against carcinogenesis. Current evidence from clinical trials and animal models supports the therapeutic role of gut microbiome modulation in reversing gastrointestinal disorders. However, variability in study outcomes highlights the need for further research to standardize these approaches for clinical practice. This review underscores the gut microbiome's pivotal role in gastrointestinal health and the therapeutic promise of functional medicine in addressing these disorders. This review also explores emerging interventions, such as phage therapy and engineered microbes, and provides comparative analyses of microbiota signatures and therapeutic approaches across different gastrointestinal disorders.}, } @article {pmid41561085, year = {2025}, author = {Bu, W and Chen, Z and Liu, B and Jia, X}, title = {Gut microbiota and its metabolism in autism spectrum disorder: from pathogenesis to therapy.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1687691}, pmid = {41561085}, issn = {2235-2988}, mesh = {Humans ; *Autism Spectrum Disorder/therapy/microbiology/metabolism ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation ; Dysbiosis/microbiology ; Probiotics ; Animals ; Brain-Gut Axis ; Prebiotics/administration & dosage ; }, abstract = {Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by social communication deficits and repetitive behaviors. Studies show that nearly half of ASD patients have gastrointestinal symptoms such as abdominal pain and diarrhea, indicating the important role of gut microbiota in its pathogenesis. This review finds that ASD patients exhibit reduced gut microbiota diversity and imbalanced Bacteroidetes/Firmicutes ratio, with abnormal microbial structure affecting neurobehavior through the gut-brain axis. Abnormalities in gut microbiota metabolites (short-chain fatty acids, phenolic compounds, bile acids, amino acids, etc.) are key mediators, which can exacerbate symptoms by affecting BBB permeability, neuroinflammation, and neurotransmitter balance. The gut-brain axis regulates ASD through mechanisms including the HPA axis, vagus nerve, immune pathways, and barrier functions. Gut microbiota-targeted interventions (exercise, dietary intervention, fecal microbiota transplantation, prebiotics/probiotics, etc.) can alleviate gastrointestinal and behavioral symptoms of ASD by regulating microbiota balance and improving metabolic environment. However, there are still issues such as unclear metabolite regulation mechanisms and significant individual differences in interventions. Future studies should combine multi-omics and artificial intelligence to identify core targets, develop personalized plans, and promote clinical translation.}, } @article {pmid41491103, year = {2026}, author = {Bryant, JA and Vulić, M and Walsh, EA and Allen, EG and Beauchemin, NJ and Chafee, ME and Diao, L and Fenn, K and Ford, KA and Hasson, BR and Litcofsky, KD and Lombardo, MJ and Martinez, A and O'Brien, EJ and Straub, TJ and Sykes, SM and Marshall, LF and Winkler, JA and McGovern, BH and Ford, CB and Wortman, JR and Henn, MR}, title = {The impact of an oral purified microbiome therapeutic on the gastrointestinal microbiome.}, journal = {Nature medicine}, volume = {32}, number = {1}, pages = {186-196}, pmid = {41491103}, issn = {1546-170X}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Clostridium Infections/microbiology/therapy/prevention & control ; Clostridioides difficile/pathogenicity ; Administration, Oral ; Male ; Female ; Double-Blind Method ; Feces/microbiology ; Middle Aged ; Bacillota ; Adult ; *Fecal Microbiota Transplantation/methods ; Aged ; }, abstract = {VOWST (VOWST oral spores, VOS; fecal microbiota spores, live-brpk, formerly SER-109) is an FDA-approved, orally administered consortium of purified Firmicutes spores developed to prevent recurrent Clostridioides difficile infection (CDI). Although 86.7% (26/30) of patients with recurrent CDI did not experience a subsequent recurrence over 8 weeks in an open-label phase 1b study, a subsequent double-blind phase 2 study (NCT02437487) did not demonstrate a significant benefit over placebo (rate of recurrence at 8 weeks in SER-109 versus placebo: 44.1% versus 53.3%). These discordant outcomes were hypothesized to be due to suboptimal dosing. This hypothesis was addressed in a pivotal phase 3 trial (NCT03183128) using an approximately tenfold higher dose. In phase 3, only 12% of VOS-treated patients versus 40% of placebo patients recurred by week 8 (relative risk 0.32, P < 0.001). Here in this follow-up post hoc analysis, across-trial comparisons confirmed that the higher, efficacious phase 3 dose is associated with improved pharmacokinetics, assessed by VOS engraftment (patients with available samples: phase 1b: 28, phase 2: 79, phase 3: 170). In-depth phase 3 analyses revealed that VOS significantly altered microbial composition, significantly enriching the diversity and abundance of Firmicutes species and reducing the prevalence and abundance of C. difficile and opportunistic pathogens (for example, Enterobacteriaceae species). Consistent with these taxonomic changes, significant changes in key bioactive metabolites were observed, including depletion of conjugated and deconjugated primary bile acids, enrichment of secondary bile acids and increases in short-chain and medium-chain fatty acids. In vitro, VOS batches produced these C. difficile-inhibiting metabolites. These findings on the pharmacology of VOS underscore the importance of rapidly restoring key protective functions of the microbiome in patients with recurrent CDI to achieve durable prevention of recurrence, as observed in the phase 3 study; they also highlight the need to include the microbiome in the clinical management of CDI. ClinicalTrials.gov registrations: NCT02437487 and NCT03183128 .}, } @article {pmid41398688, year = {2025}, author = {Zhong, W and Feng, R and Liang, H and Hu, J and Zhou, S and Liu, D and Li, S and Liao, G and Liao, J and Yang, S and Zhang, Y and Xiao, X and Qian, J and Chen, H and Fan, L and Li, M and Zhao, M and Chen, J and Liu, Y}, title = {Longitudinal profiling of gut microbiota dynamics in kidney transplant recipients.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {91}, pmid = {41398688}, issn = {1479-5876}, support = {No. 2022A1515012304 & 2023A1515110205//Basic and Applied Basic Research Foundation of Guangdong Province/ ; No. 82170764 & 82403882//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: The gut microbiota undergoes substantial alterations in kidney transplant recipients, which are linked to postoperative complications and renal function recovery. However, the underlying mechanisms of these associations remain unclear.

METHODS: We conducted a prospective, longitudinal cohort study at our center. Fecal samples were collected from 88 kidney transplant recipients at multiple time points before and after surgery. The gut microbiota dynamics were profiled using 16S rRNA sequencing.

RESULTS: Significant shifts in gut microbiota diversity and composition were observed following transplantation. At 30 days post-surgery, a significant enrichment of Enterobacteriaceae was associated with an increased risk of urinary tract infections (UTIs) and a concomitant reduction in multiple peripheral blood lymphocyte subsets. While Enterobacteriaceae enrichment was not correlated with renal function, patients with an estimated glomerular filtration rate (eGFR) greater than 30 mL/min/1.73 m² at 30 days post-transplantation exhibited a marked increase in Bifidobacterium.

CONCLUSIONS: Our findings suggest that post-transplant enrichment of Enterobacteriaceae may be associated with an increased incidence of UTIs and immune dysregulation. In contrast, Bifidobacterium may play a beneficial role in supporting renal function recovery. These results highlight specific gut microbiota taxa as potential biomarkers or targets for improving outcomes in kidney transplant recipients.

GRAPHICAL ABSTRACT: [Image: see text]

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-025-07465-4.}, } @article {pmid41561048, year = {2025}, author = {Wang, L and Chen, S and Cai, X and Zheng, Y and Zheng, C and Yao, Y}, title = {The influence of immune regulation mediated by intestinal microbiota on postmenopausal osteoporosis and intervention strategies.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1720484}, pmid = {41561048}, issn = {1664-2392}, mesh = {Humans ; *Osteoporosis, Postmenopausal/immunology/microbiology/therapy ; *Gastrointestinal Microbiome/immunology ; Female ; Animals ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Postmenopausal osteoporosis (PMO) is a common metabolic bone disease characterized by reduced bone mass and deteriorated bone microarchitecture, leading to an increased risk of fractures. In recent years, growing evidence has highlighted the role of gut microbiota and its immune-mediated regulation in the pathogenesis and progression of PMO. The gut microbiota modulates host immune responses, influencing the balance between bone resorption and bone formation. Estrogen deficiency after menopause disrupts gut microbiota composition, induces systemic inflammation, and promotes osteoclast activation, accelerating bone loss. Moreover, specific microbial communities and their metabolites, such as short-chain fatty acids (SCFAs), regulate bone metabolism by modulating immune cells, including T cells, B cells, and macrophages. Various microbiota-targeted interventions, such as probiotics, prebiotics, and fecal microbiota transplantation (FMT), have shown potential in improving bone health. However, several challenges remain, including individual variability in microbiota composition, the long-term effects of interventions, and their clinical applicability. Further investigations into the gut microbiota-mediated immune regulation of PMO may provide novel insights and therapeutic strategies for osteoporosis prevention and treatment.}, } @article {pmid41560593, year = {2026}, author = {Reddy, N and Lau, K and Naman, J and Lu, K and McGillivary, E and Salmasi, A and Liss, M and Stewart, T}, title = {Killing cancer takes guts: lessons learned from the manipulation of gut microbiome and immunotherapy for the future of urothelial carcinoma.}, journal = {Oncoimmunology}, volume = {15}, number = {1}, pages = {2611458}, doi = {10.1080/2162402X.2025.2611458}, pmid = {41560593}, issn = {2162-402X}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/drug effects ; *Immunotherapy/methods ; Immune Checkpoint Inhibitors/therapeutic use ; Fecal Microbiota Transplantation ; Animals ; Probiotics/therapeutic use ; *Carcinoma, Transitional Cell/therapy/immunology/microbiology ; *Urinary Bladder Neoplasms/therapy/immunology/microbiology ; }, abstract = {Urothelial carcinoma (UC) remains a common cancer with significant morbidity and mortality worldwide. Immune checkpoint inhibitors (ICIs) have helped revolutionize the treatment of UC, and there is growing evidence suggesting the crucial role of the gut microbiome in immune system function influences immunotherapy outcomes in this disease. Herein, we review the preclinical basis for how manipulation of the gut microbiome may alter the efficacy of immunotherapy for patients with cancer, highlight interventions optimizing gut microbiome diversity currently in use, review recent and ongoing clinical trials supporting the role of the gut microbiome in improving immunotherapy outcomes, and discuss clinical implications to improve outcomes for UC patients with immunotherapy in the real world. There is growing evidence that suggests that specific gut microbiome compositions significantly modulate the host immune system and response to ICIs. Early studies have shown that certain microbial taxa enhance antitumor immunity by influencing T cell priming, dendritic cell activation, and cytokine production. Fecal microbiota transplantation (FMT), probiotic supplementation, and dietary modulation have emerged as promising methods to alter microbiomes to improve immunotherapy outcomes. Taxa from positive immunotherapy responders across a variety of cancers demonstrate beneficial effects when transplanted into both treatment-naive or prior nonresponders. Increasing evidence suggests that the gut microbiome plays a crucial role in cancer care, particularly when patients are treated with immunotherapy. Future studies are needed to better understand the underlying mechanisms. While some studies are currently underway to explore gut manipulation for patients with UC, more studies are needed to investigate the potential to convert nonresponders into responders through microbiome manipulation.}, } @article {pmid41560360, year = {2026}, author = {Zhang, J and Wang, Z and Li, S and Luo, C and Li, H and Ma, S and Wang, P and Liu, H and Sun, L and Yin, Y and Zhang, W and Wang, Q}, title = {Phocaeicola coprophilus-Derived 6-Methyluracil Attenuates Radiation-Induced Intestinal Fibrosis by Suppressing the IDO1-Kynurenine-AHR Axis.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e18502}, doi = {10.1002/advs.202518502}, pmid = {41560360}, issn = {2198-3844}, support = {JDYY15202429//Youth Development Fund of the First Hospital of Jilin University/ ; JDYY-DEP-2022006//Doctor of Excellence Program (DEP), The First Hospital of Jilin University/ ; YDZJ202402012CXJD//Department of Science and Technology of Jilin Province/ ; 82330017//National Natural Science Foundation of China/ ; 82270610//National Natural Science Foundation of China/ ; 20240484505//Beijing Nova Program/ ; 2024ZD0530100//Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; }, abstract = {Therapeutic options for radiation-induced intestinal fibrosis (RIF) remain limited. This study reveals that intestinal kynurenine (Kyn) is persistently elevated after radiation and correlates with fibrosis severity in both murine models and human rectal cancer samples. Exogenous Kyn exacerbated RIF, whereas inhibition of indoleamine 2,3-dioxygenase 1 (IDO1) attenuated fibrotic progression. Mechanistically, Kyn activates the aryl hydrocarbon receptor (AHR) to promote fibroblast activation and fibrosis. Antibiotic depletion of gut microbiota abrogates radiation-induced IDO1-Kyn upregulation and protects against RIF. Conversely, fecal microbiota transplantation from irradiated mice recapitulates the elevated IDO1-Kyn phenotype. Metagenomic analysis identify radiation-induced depletion of Phocaeicola coprophilus (P. coprophilus), whose abundance inversely correlates with Kyn levels. Supplementation with live P. coprophilus suppresses IDO1-Kyn signaling and ameliorates RIF. Untargeted metabolomics further show that radiation reduces 6-methyluracil, a metabolite derived from P. coprophilus. Exogenous 6-methyluracil replenishment inhibits repression of the IDO1-Kyn axis and mitigates fibrosis. Together, these findings define a microbiota-metabolite-host pathway in which radiation depletes P. coprophilus, leading to loss of 6-methyluracil and derepression of the IDO1-Kyn-AHR axis, thereby driving fibrogenesis. Restoration of either P. coprophilus or its metabolite 6-methyluracil represents a promising therapeutic strategy against RIF.}, } @article {pmid41558030, year = {2026}, author = {Fan, C and Hayase, T and Chang, CC and Glover, IK and Flores, II and McDaniel, LK and Ortega, MR and Sanchez, CA and El-Himri, RK and Brown, AN and Karmouch, JL and Jamal, MA and Ahmed, SS and Halsey, TM and Jin, Y and Tsai, WB and Prasad, R and Enkhbayar, A and Mohammed, A and Schmiester, M and Damania, AV and Ajami, NJ and Wargo, JA and Peterson, CB and Rondon, G and Al-Juhaishi, T and Alousi, AM and Molldrem, JJ and Champlin, RE and Shpall, EJ and Martens, E and Arias, CA and Jenq, RR and Hayase, E}, title = {Fecal carbohydrate-degrading bacteria are associated with reduced incidence of lower gastrointestinal GVHD.}, journal = {Blood advances}, volume = {}, number = {}, pages = {}, doi = {10.1182/bloodadvances.2025016780}, pmid = {41558030}, issn = {2473-9537}, abstract = {Lower gastrointestinal graft-versus-host disease (LGI-GVHD) carries morbidity and mortality for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), with critical contributions from the intestinal microbiome. In a retrospective cohort of metagenomic sequencing of allo-HSCT patient stool (n = 90), we found that a reduction in specific Parabacteroides and Bacteroides species around the time of engraftment contributes to LGI-GVHD risk. Given the known diverse carbohydrate degrading functionality of these bacteria, we investigated gene abundances for Carbohydrate-Active enZyme (CAZyme) and found that Parabacteroides merdae, Parabacteroides distasonis and Bacteroides ovatus abundances were significantly correlated with CAZymes in patients who did not develop LGI-GVHD compared to those who did. The specific gene abundances of xylosidase, which contribute to the degradation of xylose-containing polysaccharides, were significantly associated with reduced risk of LGI-GVHD. Together, these findings show the importance of carbohydrate degrading functionality of putative beneficial bacteria in mediating risk of LGI-GVHD.}, } @article {pmid41557194, year = {2026}, author = {Hayashi, A and Okamoto, T and Takahashi, T and Sato, Y and Ueda, Y}, title = {Pitfalls in the differential diagnosis of diarrhea after kidney transplantation: challenges in identifying Yersinia enterocolitica infection.}, journal = {CEN case reports}, volume = {15}, number = {1}, pages = {25}, pmid = {41557194}, issn = {2192-4449}, mesh = {Humans ; *Kidney Transplantation/adverse effects ; Male ; *Yersinia enterocolitica/isolation & purification ; *Yersinia Infections/diagnosis/drug therapy ; Diagnosis, Differential ; Adolescent ; *Diarrhea/diagnosis/etiology/microbiology ; Anti-Bacterial Agents/therapeutic use ; Feces/microbiology ; Colonoscopy ; Immunocompromised Host ; Abdominal Pain/etiology ; }, abstract = {We present the case of a 14-year-old boy with a history of kidney transplantation due to focal segmental glomerulosclerosis who developed severe diarrhea and abdominal pain following an episode of antibody-mediated rejection. Despite stable kidney function, the patient required increased immunosuppressive therapy, raising concerns regarding possible drug-induced enteritis or infections. Initial investigations, including stool tests for common pathogens and imaging, failed to identify the causative agent. Colonoscopy revealed thickening of the terminal ileum and aphthae in the colon; however, common infections, such as cytomegalovirus and Epstein-Barr virus, were excluded. Given the persistence of symptoms and worsening ultrasound findings showing enlarged lymph nodes and mucosal thickening, Yersinia enterocolitica infection was suspected. Special stool culture media for Yersinia spp. confirmed the infection, and the patient responded well to antibiotic therapy. Our case highlights several challenges in diagnosing gastrointestinal infections in kidney transplant recipients, including the non-specific nature of symptoms and the difficulty in distinguishing between drug-induced enteritis, viral or bacterial infections, and other transplant-related complications. This underscores the importance of considering rare pathogens, such as Yersinia, in the differential diagnosis of gastrointestinal symptoms in immunocompromised transplant patients, including pediatric patients, and emphasizes the need for specialized diagnostic techniques, such as stool culture on selective media, to confirm the diagnosis.}, } @article {pmid41557025, year = {2026}, author = {Alnaggar, M and Chen, Y and Wang, C and Wang, S and Zhu, F and Lin, Y and Abdu, FA and Gong, L}, title = {Synergistic Effect of Fecal Microbiota Transplantation, γδT Cell Immunotherapy, and Pembrolizumab in Refractory Advanced Pancreatic Cancer: A Case Report.}, journal = {Journal of gastrointestinal cancer}, volume = {57}, number = {1}, pages = {23}, pmid = {41557025}, issn = {1941-6636}, support = {KJZD20230923115110020//Shenzhen Major Scientific and Technological Project./ ; }, mesh = {Humans ; Male ; *Antibodies, Monoclonal, Humanized/therapeutic use/pharmacology ; Aged ; *Pancreatic Neoplasms/therapy/pathology/immunology ; *Fecal Microbiota Transplantation/methods ; *Antineoplastic Agents, Immunological/therapeutic use ; *Immunotherapy/methods ; Combined Modality Therapy ; }, abstract = {BACKGROUND: Pancreatic cancer (PC) remains one of the most lethal malignancies with limited treatment options, particularly in advanced stages. Emerging immunotherapeutic strategies, such as Gamma Delta (γδ) T cell therapy paired with microbiota management, have demonstrated promise.

CASE PRESENTATION: We report a case of a 75-year-old male diagnosed with advanced-stage and poorly differentiated PC who demonstrated significant clinical improvement following a novel therapeutic approach combining fecal microbiota transplantation (FMT), γδ T cell therapy, and pembrolizumab. Initial chemotherapy and radiotherapy were discontinued due to adverse effects. Pre-treatment the CA19-9 (1206 U/mL), tumor markers were significantly elevated with CEA, CA15-3 and CA125 all within normal limits. No pathogenic mutations (e.g., BRCA1/2, PALB2) were identified. A comprehensive assessment revealed tumor progression, immunosuppression, and gut microbiota dysbiosis, resulting in FMT and γδ T cell therapy being introduced alongside pembrolizumab.

OUTCOMES: The combination therapy resulted in the clearance of circulating tumor cells (CTCs), normalization of CA19-9 to 72 U/mL, improved clinical symptoms, and a marked reduction in tumor size, as confirmed by CT. Tolerability was excellent with no serious adverse events occurred.

CONCLUSION: This case suggests that FMT combined with γδ T cell therapy may be a promising immunotherapeutic strategy for advanced PC. Further studies are needed to validate these findings.}, } @article {pmid41556761, year = {2026}, author = {Xu, J and Han, Z and Xue, Q and Wang, H and Song, J and Li, Y and Zhang, Y and Wang, D and Hu, M}, title = {Limosilactobacillus mucosae attenuates hyperlipidemic periodontitis via the gut-oral axis.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2617699}, doi = {10.1080/19490976.2026.2617699}, pmid = {41556761}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Periodontitis/microbiology/therapy ; Mice ; Humans ; *Hyperlipidemias/microbiology/complications/therapy ; Male ; Mice, Inbred C57BL ; Dysbiosis/microbiology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Claudin-1/metabolism/genetics ; *Probiotics/administration & dosage ; }, abstract = {The link between hyperlipidemia and periodontitis is well-established, but the underlying mechanisms remain incompletely understood. Here, we reveal a critical role for a 'gut-oral' axis in mediating this interaction. Integrating multi-omics analyses of clinical samples and mouse models, we identified that a significant reduction of intestinal Limosilactobacillus mucosae is a key feature of hyperlipidemic periodontitis (HPD). Fecal microbiota transplantation established a causal link between this gut dysbiosis and exacerbated periodontitis. Mechanistically, oral administration of live L. mucosae ameliorates HPD by restoring intestinal levels of the key metabolite, glycerophosphocholine (α-GPC). Notably, supplementation with α-GPC alone recapitulated this protective effect by upregulating the tight junction protein Claudin-1 (CLDN1) in periodontal tissue. This reinforcement of the epithelial barrier curtailed inflammatory infiltration and restored bone homeostasis. Our findings uncover a protective ' L. mucosae-α-GPC-CLDN1' axis, providing mechanistic insight into how gut microbiota mediates metabolism-associated inflammation and proposing a potential therapeutic strategy for HPD.}, } @article {pmid41555858, year = {2026}, author = {Wu, Z and Yang, Z and Lyu, C and Sun, B and Zhang, R and Li, H and Chen, J}, title = {Gut microbiota and neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a review of current evidence and emerging insights.}, journal = {Therapeutic advances in medical oncology}, volume = {18}, number = {}, pages = {17588359251413948}, pmid = {41555858}, issn = {1758-8340}, abstract = {Locally advanced rectal cancer (LARC) presents a significant burden on lower gastrointestinal diseases, with current treatment strategies primarily involving neoadjuvant chemoradiotherapy (nCRT) followed by radical surgery. However, patient responses to nCRT exhibit significant variability, highlighting the need for personalized therapeutic approaches. Emerging evidence suggests that the gut microbiota plays a critical role in influencing both treatment outcomes and toxicity in LARC patients. Intestinal dysbiosis has been linked to LARC progression and may affect the efficacy and adverse effects of nCRT. This narrative review critically evaluates the current literature on the relationship between gut microbiota and nCRT in LARC. Certain microbial taxa, such as Alistipes spp., Akkermansia muciniphila, and Faecalibacterium prausnitzii, have been associated with enhanced therapeutic responses, while others, such as Fusobacterium nucleatum and Enterotoxigenic Bacteroides fragilis, may contribute to treatment resistance and exacerbate adverse effects. We also discuss novel mechanisms by which specific gut microbiota and their metabolites modulate nCRT response distinct from conventional immune regulation, alongside emerging strategies for microbiota modulation, including dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation. Despite challenges in standardizing microbiota analysis and fully understanding the precise mechanisms, microbiota-targeted interventions offer a promising avenue for personalized treatment in LARC, with the potential to improve patient outcomes and quality of life.}, } @article {pmid41382117, year = {2025}, author = {Wang, Y and Bai, Z and Sun, J and Gong, Q and Miao, W and Niu, Z and Li, X and Xu, J and Lai, Z}, title = {Intestinal congestion-driven gut dysbiosis: a cross-disease hemodynamic mechanism in liver cirrhosis and heart failure.}, journal = {Journal of translational medicine}, volume = {24}, number = {1}, pages = {79}, pmid = {41382117}, issn = {1479-5876}, support = {SYYYRC-2022006//First Hospital of Shanxi Medical University/ ; 202103021224408//Natural Science Foundation of Shanxi Province/ ; 202203021221248//Natural Science Foundation of Shanxi Province/ ; 202204010931008//Shanxi Provincial Science and Technology Department/ ; YDZJSX2021B012//Shanxi Provincial Science and Technology Department/ ; 82470693//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 2023065//Health Commission of Shanxi Province/ ; }, abstract = {BACKGROUND: Intestinal congestion is a common pathophysiological feature of both liver cirrhosis and heart failure (HF). This study aimed to investigate whether intestinal congestion induces similar gut microbiota and metabolite alterations under both conditions, and to identify key microbial and metabolic signatures.

METHODS: We analyzed 117 cirrhosis patients (uncomplicated cirrhosis, cirrhosis with hepatocellular carcinoma, transjugular intrahepatic portosystemic shunt, and liver transplantation), 75 HF patients, and 31 healthy controls (CG). We performed 16S rRNA sequencing on all samples to assess gut microbial diversity, and subjected six representative samples per group to metagenomic sequencing. We conducted untargeted metabolomics on 30 fecal samples each from the uncomplicated cirrhosis, HF with reduced ejection fraction (HFrEF), and CG groups to profile intestinal metabolites, followed by correlation analyses among representative taxa, clinical characteristics, and key metabolites.

RESULTS: Intestinal congestion of different etiologies exhibits similar alterations in the gut microbiota, particularly in patients with uncomplicated cirrhosis and HFrEF. Alterations in Bacteroides were closely associated with the severity of congestion. Veillonella and Lactobacillales were enriched in cirrhotic patients, whereas Coprococcus was uniquely abundant in HFs. Metabolomic analysis revealed significant reductions in tripeptides, anti-inflammatory compounds, and prostaglandin analogs in patients with intestinal congestion. Musacin D and neopterin may serve as potential noninvasive biomarkers for HF and cirrhosis, respectively.

CONCLUSION: Intestinal congestion is associated with gut microbiota dysbiosis and metabolic disturbances in cirrhosis and HFs, with specific microbes and metabolites showing potential predictive value for distinguishing underlying diseases.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-025-07547-3.}, } @article {pmid41344924, year = {2026}, author = {Raso, T and D'Arcangelo, G and Renzo, S and Strisciuglio, C and Colucci, A and Saccomani, MD and Bramuzzo, M and Bravin, F and Sansotta, N and Russo, G and Lionetti, P and Zullo, A and Oliva, S}, title = {Diagnostic accuracy of non-invasive tests for helicobacter pylori infection in children: A multicenter retrospective study by SIGENP.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {58}, number = {1}, pages = {82-87}, doi = {10.1016/j.dld.2025.11.013}, pmid = {41344924}, issn = {1878-3562}, mesh = {Humans ; *Helicobacter Infections/diagnosis ; Retrospective Studies ; Female ; Male ; *Helicobacter pylori/isolation & purification ; Child ; Breath Tests ; Child, Preschool ; Sensitivity and Specificity ; Adolescent ; Italy ; *Feces/chemistry/microbiology ; *Antigens, Bacterial/analysis ; Predictive Value of Tests ; Urea/analysis ; Infant ; }, abstract = {BACKGROUND: Helicobacter pylori (H. pylori) infection remains prevalent in children, with significant clinical implications. While endoscopy with biopsy is the gold standard for diagnosis, non-invasive tests such as the stool antigen test (SAT) and urea breath test (UBT) may offer alternatives.

OBJECTIVES: To assess the diagnostic accuracy of SAT and UBT in children with suspected H. pylori infection and identify clinical predictors of infection.

METHODS: This retrospective multicenter study included pediatric patients undergoing endoscopy for suspected H. pylori across six Italian centers. Histological analysis served as the reference standard. Diagnostic metrics of SAT and UBT were calculated. Demographic and clinical factors were analyzed to identify independent predictors.

RESULTS: Of 256 patients, 150 (58.6 %) had confirmed infection. SAT showed higher sensitivity [94 % (95 % CI: 0.87-0.97)] than UBT [87 % (CI: 0.64-0.98)] but lower specificity [55 % vs 67 %], with lower PPV (64 % vs 78 %) and higher NPV (91 % vs 80 %). Independent predictors for H. pylori infection included family history [OR 4.4], positive SAT [OR 16.29], and non-Caucasian ethnicity [OR 4.3].

CONCLUSIONS: SAT demonstrates high sensitivity and NPV, supporting its role as a screening tool. In children without alarm symptoms, a negative SAT may safely exclude infection and help avoid unnecessary endoscopy.}, } @article {pmid41555353, year = {2026}, author = {Yu, C and Qian, Y and Zhou, Y and Sang, Y and Huang, W and Yang, L and Lu, L and Rong, X and Wu, H and Shi, Y and Kong, X}, title = {Deficiency of osteopontin in gut epithelial cells enhances intestinal integrity by promoting gut renewal through the JAK3/STAT4 pathway in acetaminophen (APAP)-induced acute liver injury.}, journal = {Cell communication and signaling : CCS}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12964-026-02675-9}, pmid = {41555353}, issn = {1478-811X}, support = {82405136//National Natural Science Foundation of China/ ; 82370582//National Natural Science Foundation of China/ ; PKJ2022-Y42//Shanghai Pudong New Area Science and Technology Development Fund Institutional Public Welfare Research Special Program Healthcare Project/ ; 201940352//The Scientific Program of Shanghai Municipal Health Commission/ ; 22ZR1428100//the Science and Technology Commission of Shanghai Municipality/ ; }, abstract = {Gut barrier dysfunction is a key feature of acute liver injury (ALI) and leads to systemic immune responses (SIRS). Our previous studies have demonstrated that knockout of osteopontin (OPN) modulates antimicrobial peptide expression and reduces intestinal flora, thereby ameliorating sepsis. In this study, we employed an acetaminophen (APAP)-induced hepatotoxicity model, the leading cause of acute liver failure (ALF) worldwide, to investigate the role of intestinal epithelial-derived OPN in gut barrier integrity during ALF. We found that intestinal epithelial-specific OPN knockout mice (Opn[△][IEC]) exhibited significant protection against APAP-induced liver injury and reduced gut barrier leakage. Fecal transplantation experiments revealed that mice receiving feces from Opn[△][IEC] mice showed increased resistance to APAP-induced liver injury and enhanced immune defense. Mechanistically, transcriptome analysis of the gut barrier indicated that OPN exacerbated gut barrier damage by inhibiting gut self-renewal via the JAK3/STAT4 signaling pathway. Epithelial-derived OPN may play a critical role in compromising gut barrier integrity and may be a target for suppressing inflammation and ameliorating ALI.}, } @article {pmid41554975, year = {2026}, author = {Garzón, E and Galindo, V and Harary, Y and Teman, A and Yavits, L}, title = {Integrated BSI bacteria identifier-on-chip using approximate k-mer matching.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-026-36497-z}, pmid = {41554975}, issn = {2045-2322}, abstract = {Acute graft-versus-host (GVHD) is a deadly disease that can be treated through fecal microbiota transplantation. However, such treatment is often followed by life-threatening bloodstream infections (BSI). Rapid detection of BSI-causing bacteria is critical in preventing BSI-related deaths. PC-CAM is a pathogen identification system-on-chip designed to assist in avoiding BSI by real-time detection of pathogen bacterial genomes using k-mer matching. The core of PC-CAM is an Approximate search-capable (Hamming distance tolerant) Content Addressable Memory (ACAM). PC-CAM was designed and manufactured in a commercial 65nm process. We use PC-CAM for real-time detection of bacteria in blood and stool samples of GVHD patients and evaluate PC-CAM bacteria identification efficiency, performance, silicon area, and power consumption based on silicon measurements. PC-CAM is capable of classifying 960K short DNA reads/sec within a silicon area of 2.38mm[Formula: see text] consuming about 1.27mW. We envision PC-CAM as a platform deployed at points of care to provide real-time, accurate, privacy-preserving, easy-to-operate, and energy-efficient pathogen classification.}, } @article {pmid41553256, year = {2026}, author = {Linn, A and Boton, N and Beekmann, SE and Kociolek, L and Sandora, TJ and Polgreen, PM and Lee, MSL and Mehrotra, P}, title = {Pediatric Infectious Diseases Physicians' Preferences for Management of Clostridioides difficile Infection: An Emerging Infections Network (EIN) Survey.}, journal = {Journal of the Pediatric Infectious Diseases Society}, volume = {}, number = {}, pages = {}, doi = {10.1093/jpids/piag004}, pmid = {41553256}, issn = {2048-7207}, abstract = {We queried pediatric infectious diseases physicians via the Emerging Infections Network regarding management preferences for Clostridioides difficile infection (CDI). We explored use of vancomycin, fidaxomicin, bezlotoxumab and fecal microbiota transplantation and found that physicians are increasingly considering newer and adjunctive therapies for pediatric CDI, highlighting the need for updated guidelines.}, } @article {pmid41550945, year = {2025}, author = {Bibbò, S and De Maio, F and Capone, F and Quaranta, G and Rondinella, D and Rosato, R and Minelli, M and De Lorenzis, D and Sanguinetti, M and Cammarota, G and Di Lazzaro, V and Masucci, L}, title = {Correction: Case Report: Fecal microbiota transplantation via capsules ameliorated clinical outcomes in a patient with multiple sclerosis.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1768227}, doi = {10.3389/fimmu.2025.1768227}, pmid = {41550945}, issn = {1664-3224}, abstract = {[This corrects the article DOI: 10.3389/fimmu.2025.1678759.].}, } @article {pmid41548987, year = {2026}, author = {Wang, A and Miao, Z and Huang, B and Zeng, J and Yuan, M and Yan, D}, title = {Baicalin Restores the Hypoglycemic Effect of Metformin by Regulating the Microbial Imidazole Propionate and Short-Chain Fatty Acids.}, journal = {Phytotherapy research : PTR}, volume = {}, number = {}, pages = {}, doi = {10.1002/ptr.70186}, pmid = {41548987}, issn = {1099-1573}, support = {82204699//National Natural Science Foundation of China/ ; 82130112//National Natural Science Foundation of China/ ; U24A20789//National Natural Science Foundation of China/ ; 2022-4-20218//Capital's Funds for Health Improvement and Research/ ; 2022-051//Youth Beijing Scholar/ ; 320.6750.2023-03-16//Clinical Research Project of Wu Jieping Medical Foundation/ ; }, abstract = {Gut microbiota dysbiosis is implicated in metformin non-response. This study aimed to investigate whether baicalin, a microbiota-modulating flavonoid derived from Radix Scutellariae, could restore metformin sensitivity and explored the underlying mechanisms. Fecal samples from metformin-treated responders and non-responders were collected and used to establish mouse models via fecal microbiota transplantation (FMT). The hypoglycemic efficacy of baicalin in combination with metformin was then evaluated. Serum levels of imidazole propionate (ImP) and the expression of downstream signaling proteins were assessed. Gut microbiota analysis identified ImP-producing bacteria modulated by baicalin, which was further validated in vitro. The roles of these bacteria and short-chain fatty acids (SCFAs) in metformin responsiveness were also examined. In vitro experiments were conducted to investigate the mechanism of SCFAs affect the production of ImP. Metformin responder and non-responder mouse models were successfully established. Baicalin co-administration significantly ameliorated insulin resistance in non-responder mice, reduced serum ImP levels, suppressed p38γ/Akt/AMPK (S485) signaling, and restored AMPK (T172) phosphorylation. Baicalin markedly suppressed key ImP-producing bacteria-Staphylococcus epidermidis and Streptococcus mutans. Notably, colonization with S. epidermidis induced metformin non-response in previously responsive mice. Furthermore, baicalin increased the abundance of SCFA-producing bacteria and elevated colonic SCFAs levels. SCFAs reduced ImP production by inhibiting the growth of ImP-producing bacteria, thereby enhancing metformin responsiveness. These findings indicate that baicalin restores metformin sensitivity by enriching SCFAs, suppressing ImP-producing bacteria, and lowering serum ImP, thereby reinstating metformin's hypoglycemic action. This study supports the potential of baicalin as an adjunct therapy for overcoming metformin non-response.}, } @article {pmid41547475, year = {2026}, author = {González, CA and Suárez, BG and Moreno, MB and Puig-Asensio, M and Alonso, VR and Marín, GS and Martí, CS and Ramón Santos, J and Alonso, LR}, title = {Clostridioides difficile infection: Position paper of the Catalan Society of Gastroenterology.}, journal = {Gastroenterologia y hepatologia}, volume = {}, number = {}, pages = {502634}, doi = {10.1016/j.gastrohep.2025.502634}, pmid = {41547475}, issn = {0210-5705}, abstract = {INTRODUCTION: Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated infectious diarrhea and is associated with significant morbidity and mortality, primarily due to its high recurrence rate. For this reason, the Catalan Society of Gastroenterology commissioned the development of a position paper aimed at providing practical recommendations, grounded in scientific evidence and expert consensus, on the diagnosis and management of CDI.

METHODS: This position paper was developed by specialists in Gastroenterology, Infectious Diseases and Microbiology. It was based on a non-systematic review of the scientific evidence. Recommendations were formulated through expert consensus.

RESULTS: The document presents a structured approach to the diagnosis and treatment of CDI, emphasizing individualized management and strategies to reduce recurrence rates. Key components include the role of fecal microbiota transplantation and a therapeutic algorithm informed by disease severity and by whether the episode is initial or recurrent.

CONCLUSIONS: This position paper aims to serve as a practical, evidence-based guide for healthcare professionals involved in the clinical management of CDI, promoting the implementation of optimal therapeutic strategies and addressing the main challenges associated with this infection.}, } @article {pmid41547302, year = {2026}, author = {Zhang, W and Zhang, K and Xu, W and Sun, X and Xue, Y}, title = {Microbiota-targeted modulation of the gut-kidney axis in diabetic kidney disease: Therapeutic advances and future perspectives.}, journal = {Biochemical and biophysical research communications}, volume = {800}, number = {}, pages = {153294}, doi = {10.1016/j.bbrc.2026.153294}, pmid = {41547302}, issn = {1090-2104}, abstract = {Diabetic kidney disease (DKD) is increasingly recognized as a systemic disorder driven by immune-metabolic dysfunction, in which the gut microbiota plays a pivotal role. Dysbiosis of the intestinal microbiota disrupts epithelial barrier integrity, promotes endotoxemia, and triggers chronic low-grade inflammation, contributing to renal injury and fibrosis. Conversely, declining kidney function exacerbates gut microbial imbalance and uremic toxin accumulation, forming a bidirectional pathological loop. Beyond the classical gut-kidney axis, recent findings highlight the existence of a multi-organ signaling network-encompassing immune, metabolic, and hematopoietic pathways-that mediates cross-talk between the gut and kidneys. Microbial metabolites such as short-chain fatty acids, indoxyl sulfate, and bile acids act as endocrine-like regulators modulating renal inflammation, fibrosis, and metabolic stress. This review outlines the mechanistic underpinnings of gut-derived renal injury, including gut-immune-kidney, gut-metabolism-kidney, and gut-bone marrow-kidney axes. We also discuss emerging microbiota-targeted therapies, including probiotics, engineered bacteria, fecal microbiota transplantation, and AI-based personalized interventions. Together, these insights support a systems-level redefinition of DKD and underscore the therapeutic potential of restoring gut microbial homeostasis.}, } @article {pmid41547071, year = {2026}, author = {Xu, X and Fang, H and Liu, F and Zhou, Y and Wen, Y and Wang, X and Du, D and Lu, L and Yin, J and Sun, T and He, F and He, J and Zhou, M}, title = {Akebia saponin D attenuates ulcerative colitis via targeting EGFR and remodeling gut microbiota homeostasis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {151}, number = {}, pages = {157829}, doi = {10.1016/j.phymed.2026.157829}, pmid = {41547071}, issn = {1618-095X}, abstract = {BACKGROUND: Ulcerative colitis (UC), a refractory subtype of inflammatory bowel disease (IBD), is clinically characterized by chronic abdominal pain and bloody hematochezia. Although therapeutic interventions have advanced significantly in recent years, existing treatment modalities remain limited. Akebia saponin D (ASD), a bioactive triterpenoid saponin extracted from the traditional medicinal herb Dipsacus asper, has been demonstrated potent multimodal bioactivity.

PURPOSE: This study systematically evaluates the therapeutic potential of ASD in UC treatment and elucidates its underlying molecular mechanisms.

METHODS: A dextran sulfate sodium (DSS)-induced UC mouse model was established, and ASD treatment was administered to observe its effects on colitis and organ toxicity. Inflammation was induced in NCM460 and HT29 cells using lipopolysaccharide (LPS), and ASD treatment was applied to evaluate its anti-inflammatory effects. To assess the involvement of the gut microbiota and metabolite landscape, fecal microbiota transplantation (FMT), 16S rRNA sequencing, and untargeted metabolomics were conducted. Single-cell RNA sequencing (scRNA-seq) was performed using the MGISEQ-2000 platform to characterize the ASD-induced cellular landscape of the colon. Additionally, network pharmacology approaches were employed to predict and validate potential molecular targets of ASD.

RESULTS: ASD demonstrated significant therapeutic efficacy in UC, as evidenced by attenuated body weight loss, restored colonic length, and improved mucosal barrier integrity. Treatment with ASD substantially remodeled the gut microbiota composition and metabolic profiles, notably elevating the abundance of Akkermansia muciniphila (A. muciniphila) and levels of indole-3-carbinol (I3C). Single-cell resolution analysis revealed that ASD promoted the expansion of Hmgb2[+] transit-amplifying cells (TACs) and Muc2[+] goblet cells (GCs) in colonic tissues. Mechanistically, we demonstrated that EGFR is a key molecular target of ASD upstream of the MEK/ERK/AP-1 signaling cascade.

CONCLUSION: Our study demonstrates that ASD, as a microbiota-modulating therapeutic agent, alleviates intestinal inflammation by inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway.}, } @article {pmid41546540, year = {2026}, author = {Thelen, AC and Korten, NM and Blischke, L and Voelz, C and Beyer, C and Seitz, J and Trinh, S}, title = {Faecal Microbiota Transplantation in Anorexia Nervosa: A Systematic Review of Methodologies, Outcomes, and Challenges With Recommendations for Future Studies.}, journal = {European eating disorders review : the journal of the Eating Disorders Association}, volume = {}, number = {}, pages = {}, doi = {10.1002/erv.70080}, pmid = {41546540}, issn = {1099-0968}, support = {//Doktor Robert Pfleger-Stiftung/ ; START (101/23)//RWTH Aachen University/ ; START (16/22)//RWTH Aachen University/ ; }, abstract = {OBJECTIVE: Anorexia nervosa (AN) is a severe psychiatric disorder displaying an altered gut microbiome. Faecal microbiome transplantation (FMT) has emerged as a powerful research tool and potential treatment option in AN due to the microbiome-gut-brain axis. Current studies are limited and reveal variable FMT protocols. This leads to heterogeneous outcomes and complicates drawing definitive conclusions from existing literature. This review aims to compile and assess the different protocols and develop recommendations on ideal donors, handling of faeces, recipients, duration/frequency of FMT, and measuring transfer success for future FMT studies regarding AN.

METHODS: We systematically screened three databases (Pubmed, Embase, Web of Science), identifying 13 studies, including two human case reports, one human study protocol, and 10 animal studies.

RESULTS: While all studies demonstrated microbial alterations in the recipients, not all animal studies successfully induced an AN/underweight phenotype, suggesting that precise coordination of study protocol components to allow further refinement is essential.

CONCLUSION: Researchers should prioritise clear, comprehensive, and transparent documentation to ensure the interpretability and reproducibility of FMT procedures. Detailed reporting will enable more meaningful comparisons across studies, deepen our understanding of the microbiome's role in AN, and help identify methodological factors that influence outcomes. Ultimately, completeness of documentation in FMT studies in AN has substantial potential to support future clinical applications and improve patient care.}, } @article {pmid41545905, year = {2026}, author = {Ma, J and Liu, M and Xu, J and Liu, B and Cui, Y and Shi, Y}, title = {Fecal microbiota transplantation mitigates lipopolysaccharide-induced oxidative stress in weaned piglets by modulating gut microbiota and enhancing riboflavin metabolism.}, journal = {Journal of animal science and biotechnology}, volume = {17}, number = {1}, pages = {9}, pmid = {41545905}, issn = {1674-9782}, support = {CARS-34//Modern Agro-industry Technology Research System of China/ ; No. 244200510010//the Science and Technology Innovation Leading Talent in Central Plains/ ; No.30500636//the Outstanding Talents of Henan Agricultural University/ ; }, abstract = {BACKGROUND: During the weaning phase, piglets are exposed to significant physiological and environmental stressors, which disrupt the balance of their intestinal microbiota and often lead to severe diarrhea. Previous studies have demonstrated that alfalfa fiber, derived from the stems and leaves of alfalfa, can effectively alleviate diarrhea in piglets. Additionally, multiple studies have highlighted the potential of fecal microbiota transplantation (FMT) in mitigating diarrhea in various models of intestinal diseases in young animals. However, the specific mechanisms by which FMT from targeted sources alleviates diarrhea in weaned piglets remain to be fully elucidated.

RESULTS: In this study, FMT from donor piglets fed an alfalfa fiber-supplemented diet effectively alleviated diarrhea, improved intestinal morphology, and enhanced gut barrier function in weaned piglets. FMT further promoted the colonization of beneficial bacterial genera (including UCG-005, unclassified Lachnospiraceae, Lachnospiraceae AC2044 group, UCG-002, Candidatus Saccharimonas, and Lachnospiraceae ND3007 group) while inhibiting the detrimental genus Tyzzerella, consequently enhancing the production of short-chain fatty acids (SCFAs). Additionally, FMT upregulated riboflavin metabolism, leading to elevated flavin adenine dinucleotide (FAD) levels and increased glutathione reductase activity, thereby collectively attenuating lipopolysaccharide (LPS)-induced oxidative stress and contributing to intestinal health.

CONCLUSIONS: We found that FMT modulates the structure of the gut microbiota, enhances microbial diversity and composition, increases the production of SCFAs, and upregulates riboflavin metabolism to elevate FAD levels. These changes collectively enhance immune and antioxidant capacities, thereby alleviating diarrhea.}, } @article {pmid41545303, year = {2026}, author = {Huang, JJ and YousefiAsl, M and Singh, N and Grivas, P and Bhatia, S}, title = {Steroid-sparing strategies for managing immune-related adverse events.}, journal = {Journal for immunotherapy of cancer}, volume = {14}, number = {1}, pages = {}, doi = {10.1136/jitc-2025-013776}, pmid = {41545303}, issn = {2051-1426}, mesh = {Humans ; *Neoplasms/drug therapy/immunology ; *Immune Checkpoint Inhibitors/adverse effects ; *Drug-Related Side Effects and Adverse Reactions/drug therapy/etiology ; *Steroids/therapeutic use ; *Immunotherapy/adverse effects/methods ; }, abstract = {Although immune checkpoint inhibitors (ICI) have greatly improved outcomes in several cancer types, their use is also associated with immune-related adverse events (irAEs) that can impact any organ system and lead to significant morbidity and even mortality. Current approaches to treatment of irAEs largely rely on the use of systemic corticosteroids, which can compromise antitumor immune responses and oncologic outcomes. Prolonged use of systemic corticosteroids is also associated with its own set of toxicities. Thus, there is a critical need for steroid-sparing treatment approaches for irAEs.In this article, we review the literature for alternative therapeutic approaches for irAEs, which include targeted delivery (alternate routes of administration) of steroids (eg, budesonide) as well as systemic non-steroidal strategies using other mechanisms of action, such as integrin/cytokine blockade, antibody depletion, disease-modifying antirheumatic drugs and fecal microbiota transplant, among others. Many of these approaches have shown significant promise in their ability to induce a clinical response and improve symptoms, even in the setting of steroid-refractory or steroid-dependent irAEs. These approaches are being increasingly used as primary and secondary prophylaxis in patients at high risk of irAEs. Importantly, these strategies may mitigate steroid-associated toxicities, preserve antitumor immune responses and allow continuation of ICI after development of irAEs, hence enabling the full potential of ICI against cancer.}, } @article {pmid41544875, year = {2026}, author = {Zuo, G and Chang, F and Yuan, X and Shen, Y and Guo, X and Tang, B and Huang, JA and Liu, Z and Lin, Y}, title = {Differential toll-like receptor 2 activation by Akkermansia muciniphila and Bacteroides thetaiotaomicron mediates the beneficial effects of Fu brick tea polysaccharide against colitis.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {108100}, doi = {10.1016/j.phrs.2026.108100}, pmid = {41544875}, issn = {1096-1186}, abstract = {Fu Brick Tea Polysaccharide (FBTP) ameliorates dextran sulfate sodium (DSS)-induced colitis in mice. However, the key intestinal bacterial strains and downstream molecular mechanisms mediating these protective effects remain unclear. In this study, FBTP ameliorated colitis and concurrent liver injury in a microbiota-dependent manner, primarily by enriching Akkermansia muciniphila (A. muciniphila) and depleting Bacteroides thetaiotaomicron (B. thetaiotaomicron). The essential role of the microbiota was confirmed through fecal microbiota transplantation. Mechanistically, A. muciniphila synergistically employed both its microbe-associated molecular patterns (MAMPs) and metabolic activity to activate the toll-like receptor 2 (TLR2)-Akt anti-inflammatory signaling pathway, favorably modulating Treg/Th17 immune homeostasis. However, challenging its established status as a beneficial commensal, B. thetaiotaomicron was found to activate the TLR2-NF-κB pro-inflammatory pathway driven primarily by its MAMPs, significantly exacerbating colitis, bacterial translocation, and liver injury. The pivotal role of TLR2 in mediating these divergent bacterial outcomes was confirmed through gene knockdown experiments. In conclusion, this study reveals that FBTP restores immune homeostasis by orchestrating a complex, TLR2-dependent interplay between beneficial (A. muciniphila) and pathobiontic (B. thetaiotaomicron) bacteria. This discovery not only clarifies the therapeutic mechanism of FBTP but also highlights the context-dependent risk of key commensals, offering critical insights for developing more precise microbiota-targeted interventions.}, } @article {pmid41543761, year = {2026}, author = {Munira, MS and Stevens, JE and Shahin, W and Wang, K and Franks, AE and Perez, ARJ and Scott, JW and Hill-Yardin, EL}, title = {Towards treatments targeting the gut to improve behavioural outcomes in autism spectrum disorder.}, journal = {Journal of neural transmission (Vienna, Austria : 1996)}, volume = {}, number = {}, pages = {}, pmid = {41543761}, issn = {1435-1463}, support = {APP2003848//National Health and Medical Research Council/ ; }, abstract = {Autism spectrum disorder (ASD; autism) is a prevalent and heterogeneous neurodevelopmental disorder characterised by social communication difficulties, repetitive behaviour, and restricted interests. For individuals with autism, in particular those who require substantial care-giver support, irritability, heightened sensitivity and aggressive behaviours in response to sensory, social, or environmental triggers can limit access to health, education and community services and impact quality of life. Although gastrointestinal (GI) symptom severity is associated with irritable behaviours in autism, there are few approved medications to address challenging behaviour or comorbid psychiatric disorders, or gut dysfunction in autism. Here, we review the mode of action of drugs undergoing clinical trials for treating irritable behaviour and improving social communication as well as potentially gastrointestinal symptoms in individuals with autism. Repurposed medications such as pimavanserin (an atypical antipsychotic) and the antiparasitic suramin are being trialled for treating irritable behaviours and impaired social interaction, respectively, in autism. NTI164 is a medicinal cannabis-derived biopharmaceutical undergoing clinical safety and efficacy trials for improving social communication and similarly, ML-004 is an investigational drug being assessed for treating social communication deficits. Two other repurposed medications previously utilised for schizophrenia; brexpiprazole and lumateperone, as well as AB-2004, a microbial metabolite sequestering agent (with proposed actions on gut function), are undergoing clinical trials to assess impacts on irritability associated with autism. We also outline emerging findings from clinical studies on the use of gut-targeted small molecules and bacteriophage therapy, prebiotics, probiotic supplementation and faecal microbiota transplantation (FMT), and their potential impact on behavioural symptoms in autism.}, } @article {pmid41543263, year = {2026}, author = {Baral, B and Parajuli, M and Pinilla, J and Muniz, J and Baral, B and Cançado, GGL}, title = {Safety and efficacy of oral microbiome therapy for the treatment of recurrent Clostridioides difficile infection: a systematic review and meta-analysis of randomized controlled trials.}, journal = {Scandinavian journal of gastroenterology}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/00365521.2026.2616310}, pmid = {41543263}, issn = {1502-7708}, abstract = {INTRODUCTION: This systematic review and meta-analysis aimed to assess the safety and efficacy of oral microbiome therapy (OMT) for the treatment of recurrent Clostridioides difficile infection (CDI).

METHODS: A comprehensive search was performed in PubMed, Cochrane library, Scopus and Embase. All randomized controlled trials (RCTs) meeting predefined inclusion criteria were included. Statistical analysis was performed using R software.

RESULTS: Three RCTs comprising 469 patients were analyzed, of whom 250 (53%) received OMT and 219 (47%) received placebo. OMT significantly reduced CDI recurrence at week 8 compared to placebo (risk ratio [RR] 0.57; 95% confidence interval [CI] 0.33-0.99; p = 0.04). In exploratory efficacy analyses, no significant differences in recurrence were observed between groups when stratified by prior fidaxomicin use (RR 0.36; 95% CI 0.03-4.01; p = 0.40) or vancomycin use (RR 0.68; 95% CI 0.30-1.55; p = 0.35). Similarly, Firmicutes engraftment at week 1 (mean difference [MD] 41.78; 95% CI -10.55 to 94.11; p = 0.12) and week 8 (MD 34.06; 95% CI -2.49 to 70.61; p = 0.07) did not show statistically significant between-group differences. Safety outcomes and adverse events were comparable between OMT and placebo.

CONCLUSION: OMT seems to reduce CDI recurrence at week 8 compared with placebo while demonstrating a comparable safety profile, supporting its role as an effective, well-tolerated therapy for recurrent CDI. New studies are necessary to confirm these findings.

REGISTRATION: The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420251022230.}, } @article {pmid41541603, year = {2026}, author = {Cheung, SLY and Kenway, LC}, title = {Pathophysiological Mechanisms and Nonpharmacological Interventions in Irritable Bowel Syndrome: Current Insights and Future Directions.}, journal = {Journal of nutrition and metabolism}, volume = {2026}, number = {}, pages = {4520019}, pmid = {41541603}, issn = {2090-0724}, abstract = {Irritable bowel syndrome, diagnosed using the ROME IV diagnostic criteria, is one of the most common dysfunctional disorders of the gastrointestinal system with a high global prevalence. Although symptom presentation is diverse, symptoms primarily manifest as abdominal pain, bloating, and alterations to bowel habits, negatively impacting quality of life but without an associated increase in mortality risk. Disruptions to the gut-brain axis, the bidirectional communication system between the central nervous system and the enteric nervous system, are hypothesised to be at the core of irritable bowel syndrome. Dysfunction may also be associated with stress and anxiety, as well as dietary factors, among other aspects related to physical and social environment, genetic predisposition and medical history. Patients with irritable bowel syndrome have also demonstrated increased vulnerability to neurotransmitter imbalances, with abnormalities associated with changes in gastrointestinal motility, low-grade inflammation and visceral pain. Moreover, chronic stress and anxiety may significantly exacerbate symptoms through the upregulation of cortisol secretion, disrupting the gut microbiome and elevating visceral sensitivity. While the gut microbiome maintains the integrity of the gut-brain axis and intestinal barrier, decreases in its diversity heighten susceptibility to intestinal inflammation. Although there is currently no known cure for irritable bowel syndrome, research supports stress management and behavioural therapies, a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet, and probiotic supplementation as key interventions to alleviate symptoms. Additionally, faecal microbiota transplantation emerges as a promising intervention that addresses some of the limitations in current interventions. This literature review explores the pathophysiological mechanisms relating to irritable bowel syndrome, with insight into current interventions and future directions to directly address the underlying factors driving symptomology.}, } @article {pmid41540689, year = {2026}, author = {Zhang, Y and Duan, Y and Zhang, C and Yu, L and Liu, Y and Xing, L and Wang, L and Yu, N and Peng, D and Chen, W and Wang, Y}, title = {[Poria cocos polysaccharide alleviates cyclophosphamide-induced intestinal barrier dysfunction and inflammation in mice by modulating gut flora].}, journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University}, volume = {46}, number = {1}, pages = {34-46}, doi = {10.12122/j.issn.1673-4254.2026.01.04}, pmid = {41540689}, issn = {1673-4254}, support = {82505171 and 82204748//Natural Science Foundation for the Youth (NSFY) of China/ ; }, mesh = {Animals ; Cyclophosphamide/adverse effects ; *Gastrointestinal Microbiome/drug effects ; Mice, Inbred BALB C ; Mice ; *Intestinal Mucosa/drug effects/microbiology ; *Polysaccharides/pharmacology ; Inflammation ; *Poria/chemistry ; Wolfiporia/chemistry ; Male ; }, abstract = {OBJECTIVES: To investigate the protective effects of Poria cocos polysaccharide (PCP) against cyclophosphamide (CTX)-induced intestinal mucosal injury and its impact on gut flora and their metabolites in mice.

METHODS: Adult BALB/C mice were randomized into normal control group, CTX model group, glutamine (positive control) group, and low-, medium- and high-dose PCP treatment groups. In all but the normal control group, the mice were subjected to modeling of CTX-induced intestinal mucosal injury by intraperitoneal CTX injections for 3 days, followed by treatment with gavage of normal saline, glutamine (300 mg/kg), or PCP at 75, 150, or 300 mg/kg for 7 consecutive days. The colonic expressions of tight junction proteins (occludin and ZO-1), serum endotoxin, D-lactate, and DAO levels, intestinal permeability, colon injury, and colonic cytokine levels (IL-4, IL-22, IL-17A, and IFN-γ mRNA) were assessed. Gut microbiota, short-chain fatty acids (SCFAs; mainly acetates and propionates) and colonic GPR41 expression were analyzed using 16S rRNA sequencing, GC-MS, and Western blotting, respectively. Fecal microbiota transplantation (FMT) experiment was conducted to validate the role of gut microbes in PCP-mediated repair of intestinal injuries.

RESULTS: Compared with those in the model group, the mice treated with PCP showed significantly increased colonic occludin and ZO-1 expressions, reduced serum endotoxin, D-lactate and DAO levels, and lowered intestinal permeability with increased colonic expressions of IL-4, IL-22, IL-17A, and IFN-γ mRNA. PCP treatment obviously increased the abundance of Muribaculaceae, decreased Lactobacillus and Bacteroides, increased the contents of acetate and propionate in the colon, and upregulated colonic GPR41 expression. The results of FMT experiment confirmed the crucial role of gut microbes in PCP-mediated repair of CTX-induced intestinal injuries in mice.

CONCLUSIONS: PCP can protect against CTX-induced intestinal mucosal injury in mice possibly by modulating gut flora and SCFAs metabolism to enhance intestinal defense capacity.}, } @article {pmid41539854, year = {2026}, author = {Choi, S and Kwon, H and Kim, WK and Ko, G}, title = {Attenuation of Clostridioides difficile Infection by Clostridium hylemonae.}, journal = {Journal of microbiology and biotechnology}, volume = {36}, number = {}, pages = {e2510017}, doi = {10.4014/jmb.2510.10017}, pmid = {41539854}, issn = {1738-8872}, mesh = {*Clostridium Infections/microbiology/therapy/prevention & control ; Animals ; *Clostridium/physiology/genetics ; Gastrointestinal Microbiome ; Mice ; *Clostridioides difficile ; Disease Models, Animal ; Feces/microbiology ; Metagenomics ; }, abstract = {Clostridioides difficile infection (CDI) is a bacterial infection of the colon that can cause diarrhea and colitis. The use of antimicrobials disrupts the intestinal microbiota, weakening colonization resistance and creating an environment in which C. difficile can establish infection. It is, therefore, necessary to identify specific bacteria that are helpful for the recovery of the intestinal microbiota in individuals with CDI. Previous studies have identified several strains that showed a negative correlation with C. difficile. Among these strains, C. hylemonae DSM 15053, which possesses the bai operon similar to Clostridium scindens, was selected. To test this hypothesis, we utilized a CDI mouse model and evaluated the inhibitory effect of C. hylemonae DSM 15053. Furthermore, to gain insights into the underlying mechanisms, we performed gut microbiota analysis. Contrary to our expectations, C. hylemonae DSM 15053 did not significantly produce SBAs. Interestingly, however, microbial diversity and richness were significantly higher in the C. hylemonae DSM 15053-treated group compared with the PBS control group. In addition, we observed a higher abundance of the genera Phocaeicola, Akkermansia, and Parabacteroides in the C. hylemonae DSM 15053 group. Moreover, metagenomic and metabolomic analyses revealed that C. hylemonae DSM 15053 mitigates CDI through a mechanism distinct from that of C. scindens KCTC 5591, which primarily functions as a regulator of bile acid metabolism.}, } @article {pmid41539785, year = {2026}, author = {Huang, F and Guo, A and Liu, S and Liu, H and Zhang, Z and Lin, T and Xiao, S and Luo, K and Kong, J and Wu, L and Yan, H}, title = {Gut microbiota-derived propionate alleviate traumatic painful neuroma through inhibiting the RIG-I-NF-κB-mediated neuroinflammation.}, journal = {Food research international (Ottawa, Ont.)}, volume = {226}, number = {}, pages = {118087}, doi = {10.1016/j.foodres.2025.118087}, pmid = {41539785}, issn = {1873-7145}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology/drug effects ; *NF-kappa B/metabolism ; Mice ; *Propionates/pharmacology/metabolism ; Fecal Microbiota Transplantation ; Male ; *DEAD Box Protein 58/metabolism ; *Neuroma/drug therapy ; Signal Transduction/drug effects ; Mice, Inbred C57BL ; Disease Models, Animal ; *Neuroinflammatory Diseases ; Sciatic Nerve/injuries ; }, abstract = {Traumatic painful neuroma (TPN) is a debilitating condition that frequently develops after peripheral nerve injury, yet its pathogenesis remains poorly elucidated. Growing evidence implicates the gut microbiota in the regulation of pain and inflammatory processes, but its specific role in TPN has not been investigated. This study examines the contribution of the gut microbiota and its metabolite propionate to TPN development via modulation of the RIG-I-NF-κB signaling pathway. In a murine model of sciatic nerve transection, we identified distinct gut microbial communities between TPN-susceptible and non-susceptible mice, characterized by a reduction in beneficial bacteria and decreased fecal propionate levels in TPN-prone mice. Depletion of gut microbiota through antibiotic treatment aggravated neuroma formation and pain-like behaviors, effects that were reversible by fecal microbiota transplantation (FMT). Administration of propionate dose-dependently ameliorated neuroinflammation, fibrotic progression, and pain responses. Mechanistic studies revealed that propionate suppressed the RIG-I-NF-κB pathway activation, downregulated pro-inflammatory cytokines, and enhanced intestinal barrier integrity. Notably, FMT from propionate-treated mice replicated these protective outcomes. Our results indicate that gut microbiota-derived propionate mitigates TPN by inhibiting RIG-I-NF-κB-driven neuroinflammation and preserving gut barrier function, underscoring the gut-brain-nerve axis as a promising target for TPN therapy.}, } @article {pmid41539758, year = {2026}, author = {Zhang, T and Liu, H and Yuan, J and Xie, B}, title = {Auricularia auricula polysaccharides intervention in vivo: inhibition of endogenous malodorous gas compounds through gut regulation and enhanced liver metabolism.}, journal = {Food research international (Ottawa, Ont.)}, volume = {226}, number = {}, pages = {118122}, doi = {10.1016/j.foodres.2025.118122}, pmid = {41539758}, issn = {1873-7145}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Polysaccharides/pharmacology ; *Liver/metabolism/drug effects ; Rats ; Male ; Prebiotics/administration & dosage ; *Auricularia/chemistry ; Rats, Sprague-Dawley ; Diet, High-Fat/adverse effects ; Feces/chemistry ; Fermentation ; Fecal Microbiota Transplantation ; *Gases/metabolism ; }, abstract = {High-fat and high-protein diets increase susceptibility to endogenous malodorous gas compounds (EMGCs), particularly in long-term enclosed environments with limited nutrients. Auricularia auricula polysaccharides (AAP) are proposed to mitigate protein residues fermentation by gut microbiota, thereby reducing EMGCs accumulation and benefiting both health and environmental quality. This study elucidated the prebiotic mechanisms of AAP via rat interventions, fecal microbiota transplantation in pseudo-sterile rats, and in vitro fermentation with AAP-derived functional components and specific bacterial strains. Results demonstrated that AAP intervention effectively reduced EMGCs levels in feces and adipose tissue induced by high-fat and high-protein diets. The degradation products of AAP, including mannitol, lactose, and lyxose, along with reshaped gut microbiota, especially the functional strain Bacteroides xylanisolvens, all exhibited independent EMGCs-inhibiting activities. Mechanistically, AAP or its degradation products enhanced hepatic CYP450 expression through bile acid-mediated enterohepatic circulation, forming a gut-liver axis for EMGCs suppression. Additionally, gut metabolites lactose and maltose promoted colonic carbohydrate absorption, hepatic Col5a3 and Col1a1 enhanced hepatic protein absorption. Upregulated gut metabolites (histidine, choline bitartrate, lactose, maltose) and hepatic genes (Abcg8, Abcb9) enriched the ABC transporter pathway, expediting hepatic EMGCs excretion. This study supports AAP as a dietary supplement to inhibit EMGCs, ensuring environmental livability and health.}, } @article {pmid41539609, year = {2026}, author = {Yang, D and Ren, D and Zhang, Y and Hao, Y and Yue, Y and Li, Q and Fan, Q and Sun, C and Cui, M and Zhang, M}, title = {The Gut Microbiota Dysbiosis in Geriatric Multimorbidity: Pharmacotherapeutic Implications, Pathophysiological Mechanisms, and Precision Modulation Strategies.}, journal = {Ageing research reviews}, volume = {}, number = {}, pages = {103023}, doi = {10.1016/j.arr.2026.103023}, pmid = {41539609}, issn = {1872-9649}, abstract = {Aging around the world is accelerating. With that comes the intersection of geriatric multimorbidity and polypharmacy, creating a large uncertainty about the pharmacological efficacy and therapeutic consequences of medications used when multiple concurrent health issues exist. The gut microbiota coordinates the way drugs work through multiple pathways: through the way drugs are metabolised, the way they maintain immune homeostasis, and the way they regulate the epithelial barrier. For these reasons, the gut microbiota is becoming an important therapeutic target for optimizing precision medicine strategies in treating patients with geriatric multimorbidities. In this narrative review, we systematically synthesize the evidence regarding how gut dysbiosis leads to decreased efficacy of multi-drug regimens through the interplay between metabolism, immune response, and barrier function in aging patients with multimorbidities, and we evaluate targeted interventions. Furthermore, we demonstrate that current interventions (e.g., probiotics, prebiotics, fecal microbiota transplants (FMT), phage therapy, and dietary modulation) have unique benefits but are limited by inter-individual variability, safety concerns, and a lack of proven long-term efficacy. Thus, many areas of microbiota-drug interactions in older adults with multimorbidity should be explored through future research. Key areas to address are: the establishment of large, multicenter longitudinal cohorts of older adults with multimorbidity that would allow for repeated collection of microbiota profiles, medication use, and health outcomes to identify the evolving interaction between multimorbidity, microbiota, and polypharmacy; the urgent need for standardized and integrated databases of microbiome-drug interactions that harmonize data formats, provide metabolic annotations and medication identifiers in order to support reproducible cross-study validation; and the further validation and application of artificial intelligence (AI) and machine learning (ML) in clinical trials. High-dimensional data collected from cohorts and databases will enable the development of predictive algorithms to identify individual drug responses and how effective microbiota-targeted interventions will be; these algorithms must then be prospectively validated. Ultimately, these initiatives are necessary to move toward the personalized management of microbiota-drug interactions in older adults with multimorbidity, providing greater safety of polypharmacy and promoting healthy aging.}, } @article {pmid41539110, year = {2026}, author = {Shrivastav, K and Pandey, M and Gor, H and Nema, V}, title = {Gut virome plays an extended role with bacteriome in neurological health and disease.}, journal = {Journal of the neurological sciences}, volume = {481}, number = {}, pages = {125754}, doi = {10.1016/j.jns.2026.125754}, pmid = {41539110}, issn = {1878-5883}, abstract = {The gut-brain axis (GBA) is a complex two-way communication system that links the gastrointestinal tract and the central nervous system (CNS) through neural, immune, hormonal, and microbial pathways. The microbiota-gut-brain axis (MGBA), a more specific concept, focuses on how gut microorganisms, including bacteria, viruses, and other microbes, modulate this communication and influence neurological health. This comprehensive review examines the intricate mechanisms through which gut microorganisms modulate neural function and contribute to neurological health and disease pathogenesis. The gut microbiota, comprising bacteria, viruses, fungi, and bacteriophages, produces essential neuroactive compounds including neurotransmitters- Gamma-Aminobutyric Acid (GABA), serotonin (5-HT), dopamine (DA), short-chain fatty acids (SCFAs), and metabolites that directly influence brain physiology through vagal, hormonal, and immunological pathways. Dysbiosis of the gut microbiota has been implicated in various neurological disorders, including Alzheimer's disease, Parkinson's disease, autism spectrum disorders, and schizophrenia. In healthy conditions, beneficial bacterial strains such as Lactobacillus species synthesize GABA and regulate mood, while SCFA-producing bacteria like Fecalibacterium prausnitzii maintain blood-brain barrier integrity and exert neuroprotective effects. Conversely, pathological states demonstrate altered microbial compositions, reduced bacterial diversity, and compromised production of beneficial metabolites. Emerging evidence highlights the previously underexplored role of the gut virome, particularly bacteriophages, in regulating bacterial populations and influencing neurodevelopment. Viral dysbiosis correlates with cognitive impairment and neurodegenerative processes through modulation of bacterial metabolism and inflammatory responses. Understanding these complex host-microbiome-virome interactions provides novel therapeutic opportunities for neurological disorders through targeted interventions including probiotics, fecal microbiota transplantation, and phage-based therapies, representing a paradigm shift toward microbiome-centered approaches in neurological medicine.}, } @article {pmid41539104, year = {2026}, author = {Gong, Z and Xia, Y and Jiang, Y and Zhang, Y and Xu, C and Zhao, L and Zhang, R and Cai, W and Wen, Y and Ma, J and Yang, S and Gao, S}, title = {Xin-Ji-Er-Kang alleviates heart failure induced by myocardial ischemia-reperfusion injury through reshaping gut microbiota and metabolites.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {151}, number = {}, pages = {157800}, doi = {10.1016/j.phymed.2026.157800}, pmid = {41539104}, issn = {1618-095X}, abstract = {BACKGROUND: The relationship between the gut-heart axis and heart failure has attracted growing interest, making the gut microbiota a potential target for new treatments. Previously, we have reported the beneficial effects of the traditional Chinese medicine Xin-Ji-Er-Kang (XJEK) on heart failure (HF), but the influence of the intestinal microbiota on XJEK's protection of the heart remains to be confirmed.

PURPOSE: This study investigates the role of gut microbiota in XJEK's therapeutic impact on HF and elucidates its potential mechanism.

STUDY DESIGN: MIR-induced HF model mice were established and different concentrations of XJEK were administered by gavage. The pharmacological effects of XJEK were evaluated by multiple pharmacodynamic methods. Subsequently, fecal microbiota transplantation (FMT) and antibiotic-induced microbiota inhibition were used to explore the effect of XJEK on HF. We next employed 16S rRNA sequencing combined with fecal metabolomics to investigate alterations in gut microbiota and metabolic profiles, and further investigated the effects of mono-colonization with D. piger in mice.

RESULTS: XJEK administration dose-dependently enhanced cardiac function and reduced myocardial damage in MIR-induced HF mice, as evidenced by reduced cardiomyocyte hypertrophy, diminished myocardial fibrosis, and a decline in serum levels of NT-proBNP and cTnI. FMT from XJEK-treated mice to recipient mice revealed that the therapeutic effects of XJEK on heart failure partially depend on the gut microbiota. XJEK reshaped the gut microbiota, leading to elevated abundance of probiotics Faecalibacterium, Limosilactobacillus and Bifidobacterium, while pathogenic bacteria Staphylococcus was depleted. Additionally, XJEK elevated the levels of beneficial metabolites, including deoxycholic acid and β-MCA. Notably, XJEK led to a rise in the relative abundance of D. fairfieldensis, and through the study of D. piger of the same genus, it was found that Desulfovibrio may produce beneficial effects in HF mice.

CONCLUSION: XJEK effectively improved cardiac function, mitigated myocardial injury, and suppressed the progression of heart failure. XJEK improved gut microbiota composition and related metabolism, alleviating heart failure.}, } @article {pmid41539094, year = {2026}, author = {Wang, L and Xiong, Z and Chen, J and Liu, J and Liu, M and Yan, X and Fang, Z}, title = {Synergistic gut microbiome-host lipid axis underlies the antihypertensive effect of Qianyang Yuyin formula.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {151}, number = {}, pages = {157804}, doi = {10.1016/j.phymed.2026.157804}, pmid = {41539094}, issn = {1618-095X}, abstract = {BACKGROUND: Prehypertension (Pre-HTN) is highly prevalent and substantially increases the risk of developing hypertension and cardiovascular disease. Gut microbiota (GM) dysbiosis and altered lipid metabolism are increasingly recognized as critical regulators of blood pressure (BP). Traditional Chinese Medicine (TCM) formulas, such as Qianyang Yuyin Granules (QYYY), offer multi-target interventions, yet their preventive mechanisms in Pre-HTN remain unclear.

PURPOSE: This study aimed to investigate the antihypertensive effects of QYYY and elucidate its underlying mechanisms in a prehypertensive rat model.

METHODS: Prehypertensive spontaneously hypertensive rats (SHRs) were treated with QYYY for four weeks. Multi-omics analyses, including metagenomics, plasma metabolomics, and transcriptomics, were conducted. Causal involvement of GM was tested using antibiotic-induced pseudo-germ-free SHRs with fecal microbiota transplantation (FMT) from QYYY-treated donors, administered alone or in combination with QYYY. Gut barrier integrity, systemic inflammation, and vascular function were evaluated by histology, immunofluorescence, transmission electron microscopy, and ELISA.

RESULTS: QYYY significantly lowered SBP and DBP, reversed GM dysbiosis, normalized the Firmicutes/Bacteroidetes ratio, and modulated differential bacteria including Frisingicoccus and Blautia. These microbial shifts correlated with restoration of lysophosphatidylethanolamines (LPEs), inversely associated with BP, revealing a GM-lipid-BP axis. FMT alone was insufficient, whereas the combination of FMT+QYYY produced the strongest antihypertensive effect, restoring intestinal barrier integrity, enhancing ZO-1 expression, and normalizing Ang-II and NO levels. Transcriptomic analyses suggested PPAR and ROS signaling pathways as potential mechanisms mediating the antihypertensive effect of QYYY.

CONCLUSION: QYYY prevents BP elevation in Pre-HTN via synergistic microbiota-dependent and independent mechanisms, offering a comprehensive strategy for early hypertension prevention.}, } @article {pmid41539089, year = {2026}, author = {Ou, G and Wu, J and Wang, S and Bi, W and Peng, R and Liu, P and Jiang, Y and Chen, Y and Xu, H and Deng, L and Zhao, H and Chen, X and Xu, L}, title = {Plantago asiatica L. extract alleviates hyperuricemia-associated renal injury by modulating gut microbiota to inhibit NLRP3 inflammasome activation.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {151}, number = {}, pages = {157771}, doi = {10.1016/j.phymed.2026.157771}, pmid = {41539089}, issn = {1618-095X}, abstract = {BACKGROUND: Plantago asiatica L. (PTGA) is a widely used herbal medicine for the treatment of gout and hyperuricemia (HUA). Emerging evidence highlights the pivotal role of the gut microbiota in the pathogenesis of gout and HUA. However, existing research has failed to identify and verify the key mediator strains of PTGA that exert its role in lowering uric acid.

METHODS: A hyperuricemia mouse model was established by intraperitoneal co-administration of hypoxanthine (100 mg/kg) combined with potassium oxonate (50 mg/kg) daily for 10 consecutive days. Serum uric acid (sUA) levels and renal function parameters were assessed using biochemical assay kits. 16S rRNA sequencing combined with non-targeted metabolomics was employed to characterize alterations in gut microbiota and intestinal metabolites. Western blotting was performed to examine the expression of intestinal and renal uric acid transporters, intestinal tight junction proteins, and NLRP3 inflammasome-related proteins. Finally, the mediate role of gut microbiota was verified through fecal microbiota transplantation (FMT) and oral supplementation with Lachnospiraceae bacterium.

RESULTS: In the HUA model, elevated sUA levels (p < 0.01), activation of the renal NLRP3 inflammasome (p < 0.05), renal edema, and impaired renal function were accompanied by gut microbiota dysbiosis. PTGA extract markedly reduced sUA levels by approximately 70 % compared to the model group (p < 0.01), regulated uric acid transporter expression in both the intestine and kidney (p < 0.05), and reshaped gut microbiota composition. Moreover, PTGA enhanced intestinal uric acid catabolism of uric acid in the intestine. FMT and Lachnospiraceae bacterium supplementation experiments further confirmed the regulation of the gut microbiota is a key mediator of PTGA's therapeutic efficacy.

CONCLUSION: This study demonstrates that PTGA exerts hypouricemic and renoprotective effects through modulation of the gut-kidney axis by enriching Lachnospiraceae, promoting intestinal uric acid catabolism, and suppressing renal NLRP3 inflammasome activation. These findings provide novel mechanistic insights into the gut microbiota-dependent therapeutic action of herbal medicine, distinguishing this work from previous studies focused solely on direct organ-level effects.}, } @article {pmid41538937, year = {2026}, author = {Yan, H and Wang, C and Wang, H and Liu, J and Zhou, H and Zhong, W and Wang, X and Chen, Y and Ju, Z and Tong, H and Zhang, Y}, title = {Perfluorooctane sulfonates drives colitis via a gut microbiota-bile acid-endoplasmic reticulum stress axis in mice: Mechanistic validation and targeted interventions.}, journal = {Journal of hazardous materials}, volume = {503}, number = {}, pages = {141122}, doi = {10.1016/j.jhazmat.2026.141122}, pmid = {41538937}, issn = {1873-3336}, abstract = {Perfluorooctane sulfonate (PFOS), a widespread environmental pollutant, is implicated in systemic toxicity, yet its role in colitis remains unclear. This study aimed to investigate whether PFOS exacerbates colitis via the gut microbiota-bile acid-endoplasmic reticulum stress (ERS) axis and to explore potential interventions. Following 15-week oral PFOS exposure (0.1 or 0.3 mg/kg/d), mice developed dose-dependent colitis, featuring weight loss, colon shortening, barrier dysfunction, and elevated inflammation. High-dose PFOS disturbed bile acid homeostasis, depleting conjugated species like tauroursodeoxycholic acid (TUDCA) while accumulating deconjugated bile acids such as deoxycholic acid (DCA), thereby activating ERS pathways (PERK/eIF2α, IRE1/XBP1, ATF6). Gut microbiota analysis revealed reduced diversity, a lower Firmicutes/Bacteroidetes ratio, increased bacteria with bile salt hydrolase (BSH) activity (e.g., Lachnospira), and decreased potential bacteria (e.g., Akkermansia). Interventions with TUDCA, a BSH inhibitor, or fecal microbiota transplantation from healthy donors alleviated colitis, restored conjugated bile acids, and suppressed ERS. These findings demonstrate that PFOS triggers colitis via BSH-mediated bile acid deconjugation and ERS activation, highlighting the therapeutic potential of targeting this axis.}, } @article {pmid41538653, year = {2026}, author = {Zhang, H and Sun, J and Zheng, X and Yang, H and Xie, A and Ding, Y and Mei, Y and Li, J and Hu, Y and Ren, M and Liu, Y and Liang, Y}, title = {Fermented Lacticaseibacillus Paracasei Cultures Ameliorate Colitis by Modulating Microbiota-Derived Tryptophan Metabolism and Macrophage Polarization.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e13920}, doi = {10.1002/advs.202513920}, pmid = {41538653}, issn = {2198-3844}, support = {HBNYHXGG2024-10//Hubei Provincial Agricultural Science and Technology Research Project/ ; 2024AFB698//Natural Science Foundation of Hubei Province, China/ ; 2022BCE006//Key Research and Development Program of Hubei Province/ ; 2662025SKPY011//Fundamental Research Funds for the Central Universities/ ; }, abstract = {High-density solid-state fermented probiotic products, combining live bacteria with microbial and substrate-derived bioactives, offer a potential solution to address dysregulation of gut microbiota-immune homeostasis associated with inflammatory bowel disease (IBD). However, their synergistic efficacy against IBD remains elusive. Here, we discuss our high-density solid-state fermented Lacticaseibacillus paracasei culture (PYW) and its effects on dextran sulfate sodium (DSS)-induced colitis. Comparison of the effects of PYW, enriched with viable cells and bioactive metabolites-obtained via fermentation with wheat bran-with those of its thermally inactivated postbiotic (SPYW) shows superior efficacy of PYW than SPYW, with a viable bacterial load of ≥ 5 × 10[10] CFU g[-1] being indispensable. PYW effectively restores microbiota structure, restructures the gut tryptophan metabolic network, enriching indole-3-lactic acid (ILA) and indole-3-acetic acid (IAA), which activate the aryl hydrocarbon receptor (AhR) signaling pathway, suppress pro-inflammatory mediators, and strengthen mucosal barriers. Antibiotic depletion abolishes the effects of PYW, while fecal microbiota transplantation from PYW-treated donors and exogenous ILA/IAA supplementation replicate its anti-colitic benefits. These findings suggest that PYW alleviates colitis via microbiota-dependent enrichment of ILA/IAA and subsequent AhR pathway activation, highlighting its potential as a probiotic therapeutic targeting the microbiota-metabolism-immunity regulatory axis in IBD.}, } @article {pmid41536244, year = {2026}, author = {Girdhar, K and Dedrick, S and Rhodes, L and Kim, D and Powis, A and Mahon, C and Chapdelaine, H and Obaid, L and McNamara, M and Altindis, E}, title = {Diet, gut microbiome, and type 1 diabetes: from risk to translational opportunity.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2614039}, doi = {10.1080/19490976.2026.2614039}, pmid = {41536244}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Diabetes Mellitus, Type 1/microbiology/therapy/etiology/immunology ; Animals ; *Diet ; Prebiotics/administration & dosage ; Probiotics/administration & dosage ; Fecal Microbiota Transplantation ; }, abstract = {The incidence of type 1 diabetes (T1D) has risen sharply in recent decades, implicating the role of environmental factors in disease pathogenesis. Diet, a primary driver of gut microbiome development and composition, along with other environmental exposures, has emerged as a potential modulator of T1D risk and progression. While nutrients, such as certain vitamins, may exert protective effects, the roles of other dietary factors (e.g., early exposure to dietary antigens) remain unclear. Importantly, diet shapes the gut microbiome, which produces immunomodulatory metabolites, including secondary bile acids, short-chain fatty acids (SCFAs), and others that directly influence immune responses. This review presents evidence on how specific dietary factors, including macronutrients (fats, carbohydrates, proteins, such as gluten and milk proteins), fibers, and breastfeeding, affect the gut microbiome and T1D. We also discuss the effects of microbiome-targeted interventions, including probiotics, prebiotics, and fecal microbiota transplantation, on T1D and their potential as future therapeutic strategies. Although animal studies provide compelling mechanistic insights, the results from human trials remain inconsistent, underscoring the urgent need for longitudinal and interventional studies to establish causality. Understanding the complex interplay between diet, the gut microbiome, and immune homeostasis is essential for developing personalized strategies to prevent and treat T1D and delay-related complications.}, } @article {pmid41535719, year = {2026}, author = {Almonte, AA and Thomas, S and Iebba, V and Kroemer, G and Derosa, L and Zitvogel, L}, title = {Gut dysbiosis in oncology: a risk factor for immunoresistance.}, journal = {Cell research}, volume = {}, number = {}, pages = {}, pmid = {41535719}, issn = {1748-7838}, support = {INCA_16698//CNIB (INCA)/ ; 955575//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; }, abstract = {The gut microbiome is recognized as a determinant of response to immune checkpoint inhibitor (ICI) therapies in cancer. However, the clinical translation of microbiome science has been hampered by inconsistent definitions of dysbiosis, inadequate biomarker frameworks, and limited mechanistic understanding. In this review, we synthesize the current state of knowledge on how gut microbial composition and function influence ICI efficacy, highlighting both correlative and causal evidence. We discuss computational approaches based on α-diversity or taxonomic abundance and argue for more functionally and clinically informative models, such as the topological score (TOPOSCORE) and other dysbiosis indices derived from machine learning. Using retrospective analyses of metagenomic datasets from thousands of patients and healthy controls, we examine microbial patterns that distinguish responders from non-responders. We also explore how dysbiosis perturbs immunoregulatory pathways, including bile acid metabolism, gut permeability, and mucosal immunomodulation. Finally, we assess emerging therapeutic strategies aimed at correcting microbiome dysfunction - including dietary modification, bacterial consortia, and fecal microbiota transplantation - and describe how they are being deployed in multiple clinical trials. We conclude with a brief discussion of the ONCOBIOME initiative, which works with international partners to incorporate microbiome science into oncology workflows. By refining our understanding of gut-immune interactions and translating it into action, microbiome-informed oncology may unlock new therapeutic potential for patients previously resistant to immunotherapy.}, } @article {pmid41535683, year = {2026}, author = {Chen, S and Yuan, Y and Wang, Y and Peng, Y and Tun, HM and Jiang, Z and Miao, Y and Lee, S and Yin, X and Shen, X and DeLeon, O and Chang, EB and Chan, FKL and Sun, Y and Ng, SC and Su, Q}, title = {Identification of antimicrobial peptides from ancient gut microbiomes.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-68495-0}, pmid = {41535683}, issn = {2041-1723}, support = {2025 Youth Science and Technology Talent Development Program//China Association for Science and Technology (China Association for Science & Technology)/ ; }, abstract = {Fecal coprolites preserve ancient microbiomes and are a potential source of extinct but highly efficacious antimicrobial peptides (AMPs). Here, we develop AMPLiT (AMP Lightweight Identification Tool), an efficient tool deployable to portable hardware for AMP screening in metagenomic datasets. AMPLiT demonstrates AUPRC performances of 0.9486 ± 0.0003 and reasonable overall training time of 3200 ± 53 s. By computationally utilizing AMPLiT, we analyze seven ancient human coprolite metagenomes, identifying 160 AMP candidates. Of 40 representative peptides synthesized, 36 (90%) peptides demonstrate measurable antimicrobial activity at 100 μM or less in vitro. Strikingly, approximately two-thirds of these peptides are sourced from Segatella copri, a dominant ancient gut commensal that is conspicuously underrepresented in modern populations, particularly those with Westernized lifestyles. Representative S. copri-derived AMPs exhibit disruptions against membranes of pathogenic bacteria, coupled with low cytotoxicity and hemolytic risk. In vivo, lead peptides demonstrate potent antibacterial and wound-healing efficacy comparable to traditional antibiotics, especially in combating gram-positive pathogens. Our findings highlight the ancient gut microbiomes as sources of novel AMPs, offering valuable insights into the historical role of S. copri in human health and its decline in contemporary populations.}, } @article {pmid41535300, year = {2026}, author = {Wong, OWH and Xu, Z and Chan, SSM and Mo, FYM and Shea, CKS and Su, Q and Wan, MYT and Cheung, CP and Ching, JYL and Tang, W and Tun, HM and Chan, FKL and Ng, SC}, title = {A novel synbiotic (SCM06) for anxiety and sensory hyperresponsiveness in children with autism spectrum disorder: an open-label pilot study.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-025-00902-8}, pmid = {41535300}, issn = {2055-5008}, support = {NCI202346//New Cornerstone Science Foundation/ ; }, abstract = {Anxiety and sensory hyperresponsiveness are common in children with autism spectrum disorder (ASD), but effective treatments are lacking. Targeting the microbiota-gut-brain axis is a promising strategy. This open-label pilot study evaluated SCM06, a novel synbiotic designed to target anxiety and sensory hyperresponsiveness, in 30 children with ASD (mean age 8.2 years, 22 males). We assessed symptom improvement, compliance, and safety, and collected stool samples for metagenomics and metabolomic analysis over 12 weeks. SCM06 was safe and well-tolerated, and significant improvements were observed in anxiety, sensory hyperresponsiveness, and abdominal pain. Following SCM06 treatment, increase in Bifidobacterium pseudocatenulatum was associated with improved functional abdominal pain (p = 0.0011, p_adj = 0.054), while the abundances of valeric acid and butyric acid increased (p_adj = 0.004 and p_adj = 0.072). Key microbial species, Coprococcus comes and Veillonella dispar, were candidate mediators of symptom improvements. Further randomised controlled trials are warranted to confirm its clinical efficacy.}, } @article {pmid41447757, year = {2026}, author = {Mandala, A and Undi, RB and Janssen, RC and Sugino, KY and Zhao, W and Nelson, BN and Teague, AM and Patil, NY and Zemsky Berry, K and Varshney, R and Bergman, BC and Rudolph, MC and Joshi, AD and Rajala, RVS and Jonscher, KR and Friedman, JE}, title = {Reprogramming offspring liver health: maternal indole supplementation as a preventive strategy against MASLD.}, journal = {EBioMedicine}, volume = {123}, number = {}, pages = {106098}, pmid = {41447757}, issn = {2352-3964}, mesh = {Animals ; Female ; *Indoles/administration & dosage/pharmacology ; Mice ; Humans ; Pregnancy ; Male ; Gastrointestinal Microbiome/drug effects ; *Liver/metabolism/pathology/drug effects ; *Dietary Supplements ; *Fatty Liver/prevention & control/etiology/metabolism/pathology ; Disease Models, Animal ; Prenatal Exposure Delayed Effects ; Receptors, Aryl Hydrocarbon/metabolism ; Diet, Western/adverse effects ; Maternal Exposure ; Ceramides/metabolism ; Fecal Microbiota Transplantation ; Hepatic Stellate Cells/metabolism/drug effects ; Indoleacetic Acids ; }, abstract = {BACKGROUND: Disruptions in early-life gut microbiota and metabolites associated with maternal Western-style diet (WD) during critical windows of development are linked to metabolic and inflammatory diseases in offspring, including metabolic dysfunction-associated steatotic liver disease (MASLD) in later life. These disturbances can alter microbial metabolite production, such as tryptophan derivatives, which are crucial for immune and metabolic regulation. However, the specific effects of maternal supplementation with tryptophan metabolites on offspring gut microbiome maturation and MASLD risk remain unexplored.

METHODS: WD-fed mouse dams were supplemented with microbial metabolites indole (Ind) or indole-3-acetic acid (I3A) during gestation and lactation; male offspring were weaned to chow diet for 9 weeks, followed by a 4-week WD challenge. Fecal microbiota transfer (FMT) was performed from offspring to naïve recipients, followed by a 4-week WD challenge. Human LX-2 stellate cells were used to study mechanisms for indole and very long-chain (VLC) ceramide effects on TGF-β-induced fibrosis.

FINDINGS: Maternal supplementation with Ind or I3A had long-term protective effects in adult WD-challenged offspring against excess weight gain, steatosis, stellate cell activation, and fibrosis. Perinatal exposure to Ind or I3A activated offspring aryl hydrocarbon receptor (AHR) signalling in gut and liver, which trans-repressed known and new target genes, including ceramidases Asah2 and Acer3, leading to increased VLC ceramides. FMT from offspring with perinatal exposure to Ind protected recipients from WD-induced fibrogenesis and increased beneficial VLC ceramides in recipient livers. In vitro, LX-2 stellate cells cultured with Ind or VLC ceramides demonstrated an anti-fibrotic effect, which was abolished by AHR inhibition.

INTERPRETATION: Maternal indole supplementation, through sustained activation of AHR in offspring gut and liver and an increase in hepatic VLC ceramides, prevents diet-induced MASLD and fibrosis in offspring, offering a novel therapeutic pathway for prevention of paediatric MASLD.

FUNDING: See Acknowledgements.}, } @article {pmid41392089, year = {2025}, author = {Wilson, BC and Tweedie-Cullen, RY and Albert, BB and Derraik, JGB and Ho, D and Depczynski, M and Creagh, C and Edwards, T and Gali, S and Thabrew, H and Cutfield, WS and O'Sullivan, JM}, title = {Encapsulated faecal microbiota transfer in young women with anorexia nervosa: an open-label feasibility pilot trial.}, journal = {Nature communications}, volume = {17}, number = {1}, pages = {571}, pmid = {41392089}, issn = {2041-1723}, mesh = {Humans ; *Anorexia Nervosa/therapy/microbiology ; Female ; Pilot Projects ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Gastrointestinal Microbiome/physiology ; Feasibility Studies ; Young Adult ; Adult ; Adolescent ; Treatment Outcome ; Feces/microbiology ; }, abstract = {Perturbations of the gut microbiome have been associated with anorexia nervosa (AN) suggesting microbiome-modulation treatments, like faecal microbiota transfer (FMT), may offer therapeutic benefits. This open-label feasibility pilot trial evaluated the tolerability and microbiological impact of encapsulated, multi-donor FMT in 18 young women with AN (Registration: ACTRN12621001504808). Participants completed clinical and microbiome assessments at enrolment (3 weeks pre-treatment), baseline, and 3, 6, and 12 weeks post-treatment. Fifteen participants completed FMT, and 11 completed the final follow-up. The primary outcome was the change in gut microbiome composition from baseline to 3 weeks compared with natural variation between enrolment and baseline. FMT produced a significantly greater shift post-treatment (mean ± SD Bray-Curtis dissimilarity 0.36 ± 0.11; p = 0.0007), with participants gaining 38 ± 16 new species. Donor-derived strains comprised 41 ± 12% of the microbiome at 3 weeks, with engraftment persisting at 6 and 12 weeks. FMT was generally well tolerated; adverse events were mostly mild to moderate and overlapped with typical AN symptomatology. Monitoring of clinical outcomes supported the safety profile and suggested potential improvements in anxiety and metabolic parameters; however, the small sample and absence of a control arm preclude safety and efficacy inference. Overall, these findings warrant further investigation through randomised controlled trials in AN.}, } @article {pmid41535289, year = {2026}, author = {Panah, FM and Støving, RK and Sjögren, M and Micali, N and Maschek, S and Reis, KD and Mirsepasi-Lauridsen, HC and Petersen, AM and Nielsen, DS and Helms, M and Rasmussen, MA and Barfod, KK}, title = {Impact of a single fecal microbiome transplantation in adult women with anorexia nervosa: an open-label feasibility pilot trial.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-68455-8}, pmid = {41535289}, issn = {2041-1723}, support = {R370-2021-863//Lundbeckfonden (Lundbeck Foundation)/ ; }, abstract = {Anorexia nervosa (AN) is a severe mental disorder characterized by restrictive eating and disturbance in the way one's body weight or shape is experienced, often accompanied by depression and anxiety. Current evidence-based treatments for AN have limited efficacy, with less than half of the patients achieving full recovery in long-term follow-up studies. Recent findings have identified gut microbiota (GM) dysbiosis as a potential contributor to AN pathology through the gut-brain axis. This open-label, non-randomized, feasibility trial (Clinicaltrials.gov Identifier: NCT05834010) evaluated the feasibility of utilizing fecal microbiota transplantation (FMT) to modify the GM and GM-associated signaling in females with AN and to examine biological effects following a single FMT procedure. Adult female participants diagnosed with AN were recruited. FMT was administered either orally via capsules or as rectal enema. Stool and blood samples were collected pre- and one week post-FMT to assess GM composition, hormonal changes, and biomarkers. Primary endpoints: Feasibility of FMT in individuals with AN and preferred route of FMT. Secondary endpoints: A single FMT treatment can alter GM composition in individuals with AN short term and relevant gut brain signaling in serum. 18/22 participants (81%) completed FMT and sampling and 19/22 participants chose oral capsules, with no serious adverse effects reported. GM analysis showed significant shifts toward donor composition 1-week post-FMT, with improved stool consistency. No significant changes were observed in psychopathology measures or appetite-related biomarkers. Oral FMT is a feasible intervention for adult women with AN, leading to changes in GM profile. Future studies should focus on placebo-controlled trials to assess the efficacy of repeated oral treatments and explore long-term effects on GM, appetite, body weight, sex hormones, disorder-specific symptoms, and overall well-being.}, } @article {pmid41532069, year = {2026}, author = {Mu, S and Chang, M and Shen, Y and Wu, X and Han, Y and Xiang, H and Luo, Y and Chen, Y and Zheng, H and Song, Z and Tong, C}, title = {Gut microbiota metabolite butyric acid alleviated Klebsiella Pneumoniae induced lung injury by regulating CX3CR1[+]NK via PI3K/AKT pathway.}, journal = {Burns & trauma}, volume = {14}, number = {}, pages = {tkaf069}, doi = {10.1093/burnst/tkaf069}, pmid = {41532069}, issn = {2321-3868}, abstract = {BACKGROUND: The expression of CX3CR1 is regulated by the gut microbiota and is correlated with the prognosis of sepsis in patients. However, the underlying mechanism has remained uncertain. This study aims to explore the role of gut microbiota components in regulating CX3CR1 expression and its impact on pneumonia-induced lung injury during sepsis.

METHODS: Mice were fed a mixture of antibiotics to establish a pseudogerm-free mouse model and then infected with Klebsiella pneumoniae. Fecal microbiota transplantation (FMT) was performed on microbiota-depleted mice, and 16S rRNA gene sequencing and targeted metabolomics were used to identify the key metabolites. Flow cytometry was employed to analyze the phenotypes of natural killer (NK) cells. Butyric acid was added as a supplement for rescue. Next, NK92 cells were pretreated with butyric acid to explore the potential signaling pathways involved.

RESULTS: In the animal study, we revealed that the expression of CX3CR1 on NK cells depended on the intestinal microbiota and its metabolites, which were related to the survival rates of gut microbiota-depleted mice after K. pneumoniae infection. FMT increased the percentage of CX3CR1[+] NK cells in the lungs of these mice, restored the disordered microbiota and metabolites, and alleviated the lung injury induced by infection. Among the metabolites, butyric acid was identified as the key metabolite and was shown to increase the proportion of CX3CR1[+] NK cells and interferon (IFN)-γ secretion, reduce bacterial loads, increase lung tissue damage, and increase survival rates. In vitro, butyric acid activated the PI3K/AKT pathway in NK92 cells, promoted CX3CR1 expression, and enhanced NK cell activity and migration ability.

CONCLUSIONS: We concluded that butyric acid alleviated K. pneumoniae-induced lung injury by regulating CX3CR1[+] NK cells via the PI3K/AKT pathway.}, } @article {pmid41530748, year = {2026}, author = {Zhang, Y and Sun, C and Wang, Y and Zhang, H and Fan, Y and Zhao, H and Li, P}, title = {Targeting gut-liver-kidney axis: microbiota-derived metabolites and therapeutic implications.}, journal = {Cell communication and signaling : CCS}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12964-025-02625-x}, pmid = {41530748}, issn = {1478-811X}, support = {82174296//National Natural Science Foundation of China/ ; }, abstract = {The gut-liver-kidney axis has emerged as a central regulatory network orchestrating metabolic, immune, and inflammatory homeostasis across organ systems. At its core lies the dynamic interplay between gut microbiota and host metabolism. Dysbiosis and impaired intestinal barrier integrity facilitate the systemic translocation of microbial metabolites-such as short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine-N-oxide (TMAO), and tryptophan derivatives-which profoundly influence hepatic lipid metabolism, renal immune responses, and overall metabolic balance. This review examines the molecular mechanisms through which gut-derived metabolites contribute to liver and kidney pathology, emphasizing inter-organ signaling and the pathological cascade of the "leaky gut-hepatic injury-renal dysfunction" loop. We critically evaluate emerging therapeutic strategies targeting this axis, including probiotic supplementation, fecal microbiota transplantation (FMT), dietary modulation (low-protein, high-fiber regimens), and pharmacological detoxification (e.g., AST‑120, molecular adsorbent recirculating systems [MARS]). Finally, we propose a conceptual "diet-microbiota-drug" triad to guide precision interventions, and discuss current challenges such as interindividual variability, the lack of standardized assessment tools, and the need for integrative multi‑omics and clinical validation. A deeper mechanistic understanding of gut-organ crosstalk may pave the way for innovative therapies to restore systemic metabolic homeostasis.}, } @article {pmid41530607, year = {2026}, author = {Miller, CB and Bader, GA and Kay, CL}, title = {Fecal Microbiota Transplantation in 2025: Two Steps Forward, One Step Back.}, journal = {Current gastroenterology reports}, volume = {28}, number = {1}, pages = {5}, pmid = {41530607}, issn = {1534-312X}, mesh = {*Fecal Microbiota Transplantation/trends/methods ; Humans ; *Irritable Bowel Syndrome/therapy ; *Clostridium Infections/therapy ; *Inflammatory Bowel Diseases/therapy ; }, abstract = {PURPOSE OF REVIEW: This review summarizes the history and current landscape of fecal microbiota transplantation (FMT), with an emphasis on use of the therapy for Clostridioides difficile infection (CDI), inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS). We clarify indications, evidence, and current recommendations for FMT-highlighting major advances and minor setbacks that have led to the state of FMT in 2025.

RECENT FINDINGS: After decades of steady progress, the U.S. Food and Drug Administration (FDA) approved the first FMT-based therapies: fecal microbiota, live-jslm and fecal microbiota spores, live-brpk-in 2022 and 2023, respectively. The 2024 American Gastroenterological Association (AGA) Practice Guideline on Fecal Microbiota-Based Therapies for Select Gastrointestinal Diseases made specific recommendations for conventional FMT and these FDA-approved therapies for multiple CDI presentations, as well as for IBD and IBS. Conventional FMT remains an option for CDI; however, OpenBiome's halt of shipped, frozen FMT preparations on December 31, 2024, has made access more challenging in 2025. Although first reported almost seventy years ago, extensive efforts over the last two decades have placed FMT in routine algorithms for many patients with CDI. While understanding of the intestinal microbiome's role in other gastrointestinal conditions is expanding, and FMT may modulate these pathways, additional evidence is needed before FMT becomes routine outside CDI.}, } @article {pmid41530574, year = {2026}, author = {Deng, YH and Liu, Q and Luo, XQ}, title = {The gut-kidney axis in pediatric acute kidney injury: a review of pathophysiological mechanisms and therapeutic frontiers.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {}, number = {}, pages = {}, pmid = {41530574}, issn = {1432-198X}, support = {2024JJ6595//Natural Science Foundation of Hunan Province/ ; }, abstract = {Acute kidney injury (AKI) is a frequent and severe condition in hospitalized children, leading to significant morbidity, mortality, and long-term risk of chronic kidney disease. This review explores the gut-kidney axis, a concept describing the bidirectional relationship between the gut microbiome and kidney function, as a critical driver of pediatric AKI. In critically ill children, interventions such as broad-spectrum antibiotics and necessary nutritional support strategies (e.g., parenteral nutrition or fasting) can cause profound gut microbial imbalance (dysbiosis). This dysbiosis initiates a deleterious feedback loop, exacerbating kidney injury. Key mechanisms include the disruption of the intestinal barrier (leaky gut), which allows bacterial endotoxins to enter the bloodstream, triggering renal inflammation via Toll-like receptor 4 signaling. Concurrently, the dysbiotic gut increases production of directly nephrotoxic gut-derived uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, while failing to produce protective anti-inflammatory metabolites like short-chain fatty acids. While therapies targeting the microbiome, such as probiotics, prebiotics, and fecal microbiota transplantation, are theoretically promising, their clinical use in pediatric AKI is unsupported by evidence and carries substantial risks, particularly iatrogenic infection. A significant knowledge gap exists due to a relative lack of pediatric-specific clinical research. The conclusion emphasizes an urgent need for longitudinal, multi-omics studies in children to understand this axis, identify functional biomarkers, and develop safe, targeted therapies to improve outcomes.}, } @article {pmid41529466, year = {2026}, author = {Wang, Z and Yu, Y and Shao, W and Zhao, Y and Li, Z and Han, J and Wen, J and Meng, Y and Lin, Y and Wang, S}, title = {Puerarin ameliorates alcoholic liver disease by regulating intestinal flora and MAPK/Nrf2 signalling pathways.}, journal = {Ecotoxicology and environmental safety}, volume = {309}, number = {}, pages = {119699}, doi = {10.1016/j.ecoenv.2026.119699}, pmid = {41529466}, issn = {1090-2414}, abstract = {Puerarin is a natural flavonoid glycoside extracted from the traditional Chinese medicine Puerariae Lobatae Radix or Pueraria lobata (Willd), known for its hepatoprotective properties. While prior studies indicate that PR can mitigate ALD, the underlying mechanisms by which PR exerts its anti-ALD effects via intestinal flora remain poorly understood. This study aimed to investigate the metabolic differences of PR in normal and ALD model rats were analyzed using UHPLC-HRMS. Further validation of PR metabolic products in vivo through in vitro fecal fermentation. Additionally, the relationship between the anti-ALD properties of PR and intestinal flora was explored using 16S rRNA sequencing technology, with confirmation obtained from fecal microbiota transplantation (FMT) experiments and functional strain experiments. Finally, through non-targeted metabolomics and liver transcriptomics combined with in vitro cell pharmacological studies, the mechanism of action of PR and its in vitro fermentation metabolites against ALD was explored. In the PR metabolic test, 20 metabolites were identified in the serum, urine, and feces of normal and ALD model rats, primarily associated with reactions including deglycosylation, hydrogenation, aldehyde esterification, hydroxylation, and methylation. 6 metabolites were verified in vitro transformation system. Subsequently, we used FMT experiments and 16S rRNA sequencing to find that intestinal flora imbalance can lead to liver disease and PR can improve liver disease by regulating intestinal flora. Based on multi-omics analysis and in vitro pharmacological activity analysis, PR and its in vitro fermented metabolites inhibit MAPK and Nrf2 pathways, further reducing inflammation and oxidative stress. The results of this study show that PR can improve ALD, with its mechanism of action potentially involving regulation of the intestinal flora, suppression of inflammatory responses, and inhibition of oxidative stress.}, } @article {pmid41527151, year = {2026}, author = {Li, JY and Huang, HB and Shi, CW and Pan, TX and Li, MH and Wang, N and Shan, JJ and Jiang, YL and Yang, WT and Cao, X and Wang, JZ and Guan, JY and Yu, SY and Wang, CF and Yang, GL}, title = {Increased caecal Intestinimonas abundance inhibits E. tenella gametogenesis via EtGFAT regulation and alleviates infection through immunity.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02302-8}, pmid = {41527151}, issn = {2049-2618}, support = {32072888, U21A20261, 32202819//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Chicken coccidiosis caused by Eimeria tenella (E. tenella) poses a major threat to global poultry production, with its tropism for the caecal microenvironment and dynamic interactions with the resident microbiota remaining incompletely understood. The caecal microbiota plays a critical role in host‒parasite interplay, yet the mechanisms through which microbial homeostasis influences E. tenella development and host resistance remain elusive. This study aimed to elucidate the causal relationship between caecal dysbiosis and E. tenella pathogenesis, with a focus on identifying microbiota-derived regulators of parasite development and host immunity.

RESULTS: Antibiotic-induced caecal dysbiosis (ABX) significantly impaired E. tenella macrogametogenesis, demonstrating microbiota-dependent regulation of parasitic development. Faecal microbiota transplantation (FMT) validated this causal link, revealing that microbial reconstitution restored parasite maturation. Notably, Intestinimonas spp. were identified as key inhibitors of E. tenella development through transcriptional regulation of the EtGFAT gene (Eimeria tenella glucosamine: fructose-6-phosphate aminotransferase), a critical mediator of macrogamete formation. Furthermore, the transplantation of Intestinimonas butyriciproducens (I. butyriciproducens) attenuated clinical manifestations of infection while increasing IFN-γ secretion from CD8[+] T lymphocytes, thereby enhancing host resistance to E. tenella.

CONCLUSIONS: This study revealed that caecal microbiota homeostasis is indispensable for E. tenella developmental progression and highlights Intestinimonas as a pivotal microbial regulator of parasite biology. The dual role of I. butyriciproducens in suppressing parasitic virulence and potentiating adaptive immune responses underscores the therapeutic potential of microbiota-targeted strategies. These findings provide a foundation for the development of novel anticoccidial interventions through targeted manipulation of caecal microbial communities. Video Abstract.}, } @article {pmid41461024, year = {2026}, author = {Ng, DZW and Koh, M and Low, A and Liu, L and Jumat, NHB and Zhang, Z and Koh, XQ and Zhu, M and Muthiah, M and Dan, YY and Lee, JWJ and Chan, ECY}, title = {Robust Workflow for Multiclass Host-Gut Microbial Cometabolite Quantitation in Human Stool via 3-Nitrophenylhydrazine Derivatization and LC-MS/MS: A Validated Analytical Platform for Translational Studies.}, journal = {Analytical chemistry}, volume = {98}, number = {1}, pages = {555-570}, doi = {10.1021/acs.analchem.5c05360}, pmid = {41461024}, issn = {1520-6882}, mesh = {Humans ; Tandem Mass Spectrometry/methods ; *Gastrointestinal Microbiome ; *Feces/chemistry/microbiology ; Chromatography, Liquid ; *Phenylhydrazines/chemistry ; *Fatty Acids, Volatile/analysis/metabolism ; *Bile Acids and Salts/analysis/metabolism ; Workflow ; Amino Acids, Branched-Chain/analysis/metabolism ; Tryptophan/analysis/metabolism ; Liquid Chromatography-Mass Spectrometry ; }, abstract = {Host-gut microbial co-metabolites, including short-chain fatty acids (SCFA), bile acids (BA), tryptophan metabolites, and branched-chain amino acids (BCAA), have key immune-metabolic functions affecting human health. Dysbiosis-induced alterations in their levels are implicated in the pathogenesis of diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD). However, simultaneous quantitation of these chemically diverse analytes in stool remains analytically challenging due to their diverse physicochemical properties and wide concentration ranges. Here, we developed and rigorously validated a derivatization and targeted liquid chromatography tandem mass spectrometry workflow for the simultaneous quantitation of host-gut microbial cometabolites in human stool. A 3-nitrophenylhydrazine derivatization protocol was optimized by systematically adjusting reagent concentrations and introducing postreaction quenching to suppress in-line acetic acid derivatization. Chromatographic separation was enhanced by using a novel dual-additive mobile-phase strategy (formic acid and ammonium acetate in aqueous and organic phase, respectively) coupled to a mixed-mode C18-anion-exchange stationary phase, enabling improved resolution and sensitivity across chemically diverse metabolite classes. Our optimized analytical method achieved accurate, sensitive, and efficient quantitation of 38 metabolites (15 SCFA, 16 BA, 4 tryptophan metabolites, 3 BCAA) within 23 min, demonstrating excellent linearity (r[2] > 0.99) and precision (CV < 15%), with short- (autosampler, 4 °C) and long-term (freezer, -20 °C) stability. Comparative analysis of healthy controls and MASLD stools revealed distinct metabolic signatures, including reduced SCFA and C6-oxidized BA, and elevated conjugated and secondary BA derivatives in MASLD. Our study establishes an analytically rigorous platform for multiclass host-gut cometabolite quantitation in stool, with demonstrated utility for translational research into gut-liver axis disorders.}, } @article {pmid41527019, year = {2026}, author = {Zhong, J and Zhu, B and Zou, Z and Li, Y and Feng, Y and Wu, K and Hou, X}, title = {Gut microbiota mediates the beneficial effects of exercise on autism-like behaviors.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-025-04632-x}, pmid = {41527019}, issn = {1471-2180}, support = {no. 2025A04J4356//the Guangzhou Municipal Science and Technology Bureau, Basic Research Program/ ; no. 2023B0303020001//the Key-Area Research and Development Program of Guangdong Province/ ; no. 2021ZDJS021//the Provincial Significant Scientific Research Projects for General Universities in Guangdong Province/ ; }, abstract = {BACKGROUND: The gut-brain axis plays a critical role in autism spectrum disorder (ASD), but the mechanisms through which exercise modulates gut microbiota, short-chain fatty acids (SCFAs), and central neurotransmitters to ameliorate ASD-like behaviors remain unclear. This study aimed to investigate the effects of exercise on ASD-like behaviors, gut microbiota, and metabolism in a valproic acid (VPA)-induced ASD rat model and to validate these findings via fecal microbiota transplantation (FMT).

METHODS: ASD rat models were established through prenatal exposure to VPA and divided into four groups: exercise (E_ASD), non-exercise (ASD), FMT, and sham FMT (sFMT). The E_ASD group underwent 6 weeks of voluntary wheel running, while the FMT group received fecal microbiota from the E_ASD group for 4 weeks. Behavioral assessments were conducted to evaluate cognitive and social functions. Fecal microbiota composition was analyzed via 16S rRNA sequencing, while SCFAs and neurotransmitters were measured using gas and liquid chromatography-mass spectrometry.

RESULTS: Six weeks of voluntary exercise significantly alleviated ASD-like behaviors, particularly improving social interactions. Exercise also altered gut microbiota composition, increasing Limosilactobacillus and Lactobacillus while decreasing Allobaculum. Additionally, SCFAs and neurotransmitter levels in the prefrontal cortex were modulated. Notably, FMT from the exercise group replicated these behavioral and metabolic improvements in ASD rats. Exercise improves ASD-like behaviors by modulating gut microbiota, SCFAs, and neurotransmitter levels, and FMT offers further validation of these effects.

CONCLUSION: These findings highlight exercise and FMT as promising strategies for alleviating ASD-related symptoms through gut-brain axis modulation.}, } @article {pmid41526816, year = {2026}, author = {Yang, Y and Wang, Y and Li, J and Gao, Y and Wu, Z and Tan, X and Feng, S and Cheng, W and Zhang, H and Gan, Q and Wei, H and Li, Q}, title = {Fecal microbiota transplantation from healthy piglets ameliorates intestinal inflammation in mice by modulating recipient metabolism.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-025-04590-4}, pmid = {41526816}, issn = {1471-2180}, support = {2025J01556//Fujian Provincial Natural Science Foundation of China/ ; }, } @article {pmid41525948, year = {2026}, author = {Valia, D and Karama, I and Ingelbeen, B and Garba, Z and Kleef, EV and Lompo, P and Tiendrebeogo, EW and Kaboré, B and Kiemdé, F and Yougbare, S and Tiendrebeogo, AL and Van Puyvelde, S and Prizzon, A and Vandenbroucke, AT and Argudín, MA and Kabamba, BM and Jacobs, J and Tinto, H and van der Sande, MAB and Robert, A and Rodriguez-Villalobos, H}, title = {Faecal colonisation with extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae in rural Burkina Faso.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2026.01.001}, pmid = {41525948}, issn = {1469-0691}, abstract = {OBJECTIVES: The burden of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) is rising globally and often linked to community-acquisition in low-resource settings. In sub-Saharan Africa (sSA), AMR occurrence in rural areas remains under-studied despite anticipated higher risks. We investigated the epidemiology and genetic characteristics of ESBL-E in rural Burkina Faso.

METHODS: In a community-based cross-sectional survey (May 2021-May 2022), participants were randomly selected in two health catchment areas and through face-to-face interviews, field workers collected data on hygiene, animal presence, household characteristics, and healthcare use. Stool samples were also collected for ESBL-E screening. Prevalence of ESBL-producing E. coli (ESBL-EC) and K. pneumoniae (ESBL-KP) was estimated, and associated factors assessed. Based on resistance profiles and PCR screening, selected isolates underwent whole-genome sequencing.

RESULTS: Among 1,482 participants, ESBL-E prevalence was 61.3% (58.8-63.7%): ESBL-EC 53.0% (50.5-55.5%) and ESBL-KP 22.3% (20.3-24.5%). Colonisation was more common in the rainy than dry season (70.2% vs 53.6%, p<0.001) and among individuals not washing hands with soap before meals (62.5% vs 49.0%, p<0.001). Ciprofloxacin-resistance exceeded 65% in both species. The predominant ESBL-gene was blaCTX-M-15 (47.3% in ESBL-EC, 19.9% in ESBL-KP), with one ESBL-EC isolate carrying blaNDM-5. IncF plasmids predominated, and plasmid-mediated quinolone-resistance genes (qnr, aac(6')-ib-cr, oqxAB) were frequently co-detected with ESBL genes.

CONCLUSION: ESBL-E prevalence was high and associated with poor hygiene and seasonal variation. Higher rainy season prevalence was not explained by reported antibiotic use and may reflect increased environmental exposure risks, which requires further exploration. Improving hygiene-standards and establishing community-level AMR surveillance can provide effective steps forward in mitigating AMR burden in rural sSA.}, } @article {pmid41525005, year = {2026}, author = {Mir, PA and Kumar, N and Bhutia, GT and Chaudhary, P and Kaur, G and Gupta, SK}, title = {The aging gut-glia-immune axis in alzheimer's disease: microbiome-derived mediators of neuroinflammation and therapeutic innovation.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {41525005}, issn = {2509-2723}, abstract = {Alzheimer's disease (AD), the most common cause of dementia in the aging population, is marked by amyloid-beta (Aβ) plaques, tau tangles, and progressive neuronal degeneration, placing heavy clinical and socioeconomic burdens on healthcare worldwide. Aging remains the strongest risk factor, with chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, and impaired proteostasis creating a vulnerable brain environment that accelerates AD onset and progression. Recent evidence highlights the gut-glia-immune axis as a critical pathway linking age-related microbiome changes to glial dysfunction. Microbial metabolites, such as short-chain fatty acids and tryptophan derivatives, regulate microglial maturation, astrocytic activity, and neuroimmune signaling. However, age-associated dysbiosis disrupts glial homeostasis, amplifies neuroinflammation, and impairs amyloid clearance, thereby worsening neurodegeneration. Preclinical models including germ-free mice and fecal microbiota transplantation along with clinical studies of elderly AD patients, provide compelling evidence of microbiome-driven modulation of disease. From a therapeutic perspective, microbiome-targeted interventions including probiotics, prebiotics, synbiotics, and microbiota-directed small molecules offer promising strategies to restore glial balance, reduce inflammation, and protect cognitive function. This review highlights the therapeutic potential of probiotics, synbiotics, and fecal microbiota transplantation for mitigating neuroinflammation and cognitive decline in Alzheimer's disease. However, given the multifactorial nature of neurodegenerative disorders, these strategies are unlikely to be universally effective and must be tailored to individual patient profiles.}, } @article {pmid41523758, year = {2025}, author = {Khan, AS and Kamthan, M and Ali, A}, title = {Understanding the intricate interactions between microbiota and host.}, journal = {World journal of experimental medicine}, volume = {15}, number = {3}, pages = {101277}, pmid = {41523758}, issn = {2220-315X}, abstract = {The review examines the intricate relationship between the microbiota and its host, highlighting how these microbial communities influence various physiological functions beyond simple coexistence. The microbiota plays a crucial role in regulating the immune system, metabolism, and overall health. We explore the diverse microbial populations inhabiting different body regions and their essential contributions to maintaining balance within the host. Recent research has uncovered molecular mechanisms that govern microbiota-host interactions, offering new insights into how these microbes support health and, conversely, how imbalances known as dysbiosis can increase susceptibility to diseases. While much attention has been given to the gut microbiota, this review also explores the influence of microbes in other parts of the body, including their effects on various organs and tissues. Additionally, we discuss emerging evidence on the gut-brain axis, illustrating how the microbiota can impact brain function and behavior. Understanding this connection could open new possibilities for treating neurological and psychological disorders. Finally, we evaluate microbiota-based therapies such as probiotics and fecal microbiota transplantation, emphasizing the importance of personalized approaches. By integrating findings from multiple disciplines, this review provides a comprehensive perspective on the microbiota's vital role in human health and its potential as a therapeutic target.}, } @article {pmid41523687, year = {2026}, author = {Zhang, S and Cheng, X and Chen, L and Wang, Y}, title = {2'-Fucosyllactose (2'-FL) alleviates choline-deficient fat diet-induced nonalcoholic steatohepatitis (NASH) by remodeling intestinal flora.}, journal = {Food science and biotechnology}, volume = {35}, number = {1}, pages = {203-213}, pmid = {41523687}, issn = {2092-6456}, abstract = {UNLABELLED: Non-alcoholic steatohepatitis (NASH) is a progressive liver disease lacking effective treatment. This study investigated 2'-Fucosyllactose (2'-FL) for its therapeutic potential. In vitro, 2'-FL reduced lipid accumulation, oxidative stress, and inflammation in Hepa1-6 cells. In a NASH mouse model, 2'-FL alleviated key disease features: hepatic steatosis, inflammation, and oxidative stress. Furthermore, 2'-FL intervention reversed NASH-associated gut microbiota dysbiosis, specifically by increasing Bacteroidota and decreasing Firmicutes at the phylum level. Fecal microbiota transplantation (FMT) validated the role of gut microbiota in these effects. The findings indicate that 2'-FL ameliorates NASH by remodeling the gut microbiota, thereby reducing endotoxemia and improving lipid metabolism. This suggests 2'-FL as a promising dietary intervention for metabolic liver diseases.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-025-02034-3.}, } @article {pmid41522487, year = {2026}, author = {Al Qassab, M and Chaarani, N and Hamou, A and Harb, R and Jradi, A and Zeineddine, M and Ghadieh, HE and Khattar, ZA and Azar, S and Kanaan, A and Harb, F}, title = {The Gut Microbiota-Insulin Resistance Axis: Mechanisms, Clinical Implications, and Therapeutic Potential.}, journal = {FASEB bioAdvances}, volume = {8}, number = {1}, pages = {e70080}, pmid = {41522487}, issn = {2573-9832}, abstract = {Emerging evidence highlights the pivotal role of the gut microbiota (GM) in regulating host metabolism and contributing to the development of insulin resistance (IR). Gut dysbiosis alters the production of critical metabolites, including short-chain fatty acids (SCFAs), bile acids, indole derivatives, and trimethylamine N-oxide (TMAO), which influence intestinal barrier integrity, inflammatory pathways, and glucose homeostasis. Recent clinical and translational studies indicate that SCFAs can improve fasting insulin and HOMA-IR, although the magnitude of benefit varies substantially across individuals, highlighting ongoing controversy surrounding their metabolic effects. Altered microbial regulation of bile-acid metabolism has also been implicated in impaired lipid and glucose signaling, reinforcing the relevance of FXR- and TGR5-mediated pathways in IR. Elevated TMAO levels have further been associated with adverse metabolic outcomes, though debate persists regarding its causal role versus its function as a diet-dependent biomarker. Microbiota-targeted strategies, including dietary fiber, probiotics, and fecal microbiota transplantation (FMT), show potential to modulate these metabolic pathways, yet clinical results remain inconsistent. This narrative review synthesizes recent mechanistic discoveries and clinical findings on microbiota-derived metabolites in IR, highlights key controversies, and outlines future priorities for translating microbiome science into effective and personalized interventions for metabolic disease prevention and management.}, } @article {pmid41522358, year = {2026}, author = {Jin, Y and Zhang, SJ and Zhuang, S and Li, P and Miao, H and Zhao, YY}, title = {Microbiota-gut-kidney axis in health and renal disease.}, journal = {International journal of biological sciences}, volume = {22}, number = {2}, pages = {750-770}, pmid = {41522358}, issn = {1449-2288}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Kidney/metabolism ; Animals ; *Renal Insufficiency, Chronic/microbiology/metabolism ; *Kidney Diseases/microbiology/metabolism ; Dysbiosis ; Acute Kidney Injury/microbiology/metabolism ; }, abstract = {Gut microbiota plays a central role in programming host metabolic function and immune modulation in both health and disease. Microbial dysbiosis leads to an increase in opportunistic pathogens and a reduction in beneficial bacteria, which collectively result in the excessive production of detrimental metabolites, particularly uremic toxins such as indoxyl sulfate and trimethylamine-N-oxide, while concurrently decreasing beneficial metabolites, such as short-chain fatty acids and tryptophan catabolites, including indole-3-aldehyde. The accumulation of harmful metabolites and depletion of protective metabolites contribute to fibrosis progression through various mediators, including the renin-angiotensin system, reactive oxygen species, Toll-like receptor 4, aryl hydrocarbon receptor, inhibitor of kappa B/nuclear factor kappa B, and Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 pathways. This review highlights the pathogenic link between gut microbiota and kidney damage via the gut-kidney axis, encompassing acute kidney injury (AKI) and chronic kidney disease (CKD). Innovative therapeutic strategies, including microbial therapeutics (such as probiotics, prebiotics, and synbiotics), natural products (such as neohesperidin, isoquercitrin, and polysaccharides), and fecal microbiota transplantation, have been proposed to restore microbial balance and improve kidney function. Targeted modulation of the gut microbiota offers a promising strategy for developing novel treatments in AKI, CKD, and the transition from AKI-to-CKD. This approach has the potential to prevent or mitigate these conditions and their complications.}, } @article {pmid41521300, year = {2026}, author = {Deng, W and Chen, D and Wei, Y and Chen, W and Chen, K and Zhong, H and He, X}, title = {Washed microbiota transplantation relieves atopic dermatitis via gut-skin microbiome rebalancing.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-026-04717-1}, pmid = {41521300}, issn = {1471-2180}, support = {2022B1111070006//Key-Area Research and Development Program of Guangdong Province/ ; 82300440//National Natural Science Foundation of China Youth Program/ ; }, abstract = {BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease in which dysbiosis of gut and skin microbiota contributes to pathogenesis and severity. Washed microbiota transplantation (WMT)-an improved form of fecal microbiota transplantation with enhanced safety and microbiota quality control-has shown efficacy in a single reported adolescent case. However, clinical data on WMT in AD and its effects on the skin and gut microbiota remain limited.

METHODS: Twenty-three patients with moderate-to-severe AD received at least two courses of WMT between January 2022 and December 2023. Disease activity was evaluated using the SCORing Atopic Dermatitis (SCORAD) index, the Eczema Area and Severity Index (EASI), the Numeric Rating Scale (NRS) for itch, and the Dermatology Life Quality Index (DLQI). Peripheral blood counts, cytokine profiles, lymphocyte subsets, and gut and skin microbiota were assessed before and after treatment.

RESULTS: WMT was well tolerated (58 sessions; 5.2% mild adverse events) and significantly improved SCORAD, EASI, DLQI, and NRS scores, with greater EASI reductions in adults than in children. Absolute basophil counts decreased significantly after treatment, whereas other hematologic and cytokine parameters remained stable. Gut microbiota showed an increased Gut Microbiome Health Index, a decreased Microbial Dysbiosis Index, and enrichment of short-chain fatty acid-producing taxa, including the Eubacterium coprostanoligenes group, Lachnospiraceae, and Coprococcus. Skin microbiota shifted from Staphylococcus dominance to higher abundances of Acinetobacter, Perlucidibaca, and other potentially protective genera, inversely correlating with disease severity and systemic inflammation.

CONCLUSIONS: WMT appears safe and effective in alleviating clinical manifestations of AD while reshaping both gut and skin microbiota. These parallel microbial shifts support the gut-skin axis as a therapeutic target and highlight WMT as a promising microbiota-centered intervention for immune-mediated skin diseases.}, } @article {pmid41520913, year = {2026}, author = {Yang, X and Liu, Y and Miao, K}, title = {Microbiome-Modulated Immunotherapy in Oncology: Current Applications and Future Prospects.}, journal = {Seminars in cancer biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2026.01.001}, pmid = {41520913}, issn = {1096-3650}, abstract = {Cancer immunotherapy has transformed oncology, yet therapeutic efficacy remains heterogeneous and frequently limited by primary or acquired resistance. Increasing evidence demonstrates that both intra- and extratumoral microbiota critically modulate antitumor immunity, influencing clinical responses of immunotherapy and immune-related adverse events (irAEs). Microbial communities regulate the tumor immune microenvironment through multiple mechanisms, including microbe-associated molecular patterns, microbial metabolites, and outer membrane vesicles, acting on tumor or immune cells. These insights have fostered the development of microbiome-based applications in oncology, ranging from predictive biomarkers to therapeutic interventions such as engineered bacteria, fecal microbiota transplantation, probiotics, prebiotics, outer membrane vesicles, bacteriophages, and dietary modulation. Early-phase clinical studies indicate that microbiota-targeted strategies can enhance immunotherapy efficacy or mitigate irAEs, although strain specificity, interindividual variability, and safety remain significant challenges. Future progress will require mechanistic elucidation, integration of multi-omics analyses, standardization of methodologies, and personalized intervention frameworks to translate microbiome modulation into clinically actionable, precision immunotherapy.}, } @article {pmid41520280, year = {2026}, author = {van de Guchte, M and Mondot, S and Cadiou, J and Raghuvanshi, R and Rous, C and Doré, J}, title = {Improving ulcerative colitis prospects through fecal microbiota transfer: atypical donor microbiota can boost success rate.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2609457}, doi = {10.1080/19490976.2025.2609457}, pmid = {41520280}, issn = {1949-0984}, mesh = {*Fecal Microbiota Transplantation/methods ; *Colitis, Ulcerative/therapy/microbiology ; Animals ; Rats ; *Gastrointestinal Microbiome ; Humans ; Disease Models, Animal ; *Feces/microbiology ; Dysbiosis/therapy ; Treatment Outcome ; }, abstract = {Fecal microbiota transfer (FMT) has been used with variable success in the experimental treatment of ulcerative colitis (UC), and efforts to improve its efficacy very much remain a matter of trial and error. We recently predicted that atypical donor microbiota could improve results. Here, we provide experimental support for this prediction in a rat model where we induced a transition of the intestinal ecosystem to an alternative state characterized by chronic low-grade inflammation and dysbiosis. While autologous FMT did barely or not enhance the restoration of a healthy microbiota compared to a control group without FMT, the atypical allogenic microbiota from one of two donor rat strains proved remarkably successful in the restoration of a healthy microbiota, in some cases accompanied by a healthy distal colon histology. These results allow the rationalization of research efforts towards improvement of FMT efficacy in humans, and indicate that (initial) success of FMT should be monitored at the microbiota level as much as at the level of clinical symptoms. More importantly, they provide further support for our earlier published, clinical-data-based, conceptual model of the intestinal ecosystem which suggests promising opportunities for therapeutic innovation in UC treatment. This model notably predicts that, and explains why, symbio-therapy, acting on both microbiota and inflammation, may be more efficient than conventional inflammation-directed therapies, and can be used to guide and monitor treatments.}, } @article {pmid41519323, year = {2026}, author = {Wang, L and Lu, C and Li, S and Wu, T and Ren, X and Song, S and Ai, C}, title = {Laminaria japonica fucoidan ameliorates D-galactose-induced cognitive impairment via the regulation of tryptophan metabolism along the gut-brain axis.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {150151}, doi = {10.1016/j.ijbiomac.2026.150151}, pmid = {41519323}, issn = {1879-0003}, abstract = {Aging is a multifactorial biological process in which chronic inflammation and oxidative stress are central to the development of age-related disorders, including neurodegenerative decline. Fucoidan, a sulfated polysaccharide extracted from brown algae, has well-documented anti-inflammatory and antioxidant effects, and therefore has the potential to be a neuroprotective agent against cognitive impairment associated with aging. In the present study, the major fucoidan fraction (LJF-2) isolated from Laminaria japonica was examined for its neuroprotective properties in a D-galactose induced aging mouse model. Oral administration of LJF-2 for 8 weeks significantly improved spatial learning and memory and suppressed neuroinflammatory responses and oxidative stress while significantly reducing the activation of astrocytes and microglia. These neuroprotective effects were linked to the regulation of key proteins involved in neuronal protection and synaptic function, such as neprilysin and synapsin, by cAMP response element-binding protein signaling. Furthermore, LJF-2 significantly remodeled the gut microbiota through a reduction in the abundance of the Bacteroidota, Proteobacteria, and several putative pathogenic genera, which enhanced the intestinal barrier integrity and modified the microbial metabolite profiles, especially those associated with tryptophan metabolism. Fecal microbiota transplantation experiments further confirmed the role of the gut microbiota modulated by LJF-2 in mediating its neuroprotective effects through reduction of oxidative stress and inflammation. Collectively, these findings suggest that LJF-2 may be a promising therapeutic approach to address the aging-related cognitive decline by modulating the gut-brain axis.}, } @article {pmid41519109, year = {2026}, author = {Hoedt, EC and Talley, NJ}, title = {Toward a personalized diet-microbiome strategy in inflammatory bowel disease: Matching donor, diet, and patient.}, journal = {Med (New York, N.Y.)}, volume = {7}, number = {1}, pages = {100918}, doi = {10.1016/j.medj.2025.100918}, pmid = {41519109}, issn = {2666-6340}, mesh = {Humans ; *Inflammatory Bowel Diseases/microbiology/therapy/diet therapy ; *Fecal Microbiota Transplantation/methods ; *Precision Medicine/methods ; *Gastrointestinal Microbiome ; *Diet ; }, abstract = {Fecal microbiota transplant plus dietary change to restore the imbalance of an individual's microbiome to relieve disorders such as inflammatory bowel disease has not been established but has promise. In this commentary, we suggest the need to embrace a more nuanced, personalized approach, one that considers microbial functionality, dietary context, and host compatibility.}, } @article {pmid41518808, year = {2026}, author = {Qu, J and Jiang, X and Ma, Y and Sheng, X and Pi, C and Wang, Y and Xu, Q and Li, R and Wang, P and Qian, D and Wang, J and Yi, Z and Yi, J and Wen, L and Liu, S}, title = {Unveiling the gut-brain axis: How chronic exposure to arsenic-induced microglial pyroptosis drives Alzheimer's disease-like pathology.}, journal = {Journal of hazardous materials}, volume = {503}, number = {}, pages = {141087}, doi = {10.1016/j.jhazmat.2026.141087}, pmid = {41518808}, issn = {1873-3336}, abstract = {Arsenic, a pervasive environmental contaminant in groundwater, poses a severe global threat to public health. Chronic arsenic exposure has been linked to neurological impairment, however, its specific pathogenic mechanism and whether the gut-brain axis plays a key role remain unclear. This study investigated the role of gut microbiota and its metabolite indoxyl sulfate (IS) in mediating chronic exposure to arsenic-induced cognitive impairment and Alzheimer's disease (AD)-like pathology, with a specific focus on microglial pyroptosis. We found that chronic arsenic exposure induced cognitive dysfunction and intestinal barrier injury, disrupted gut microbiota composition, promoted IS accumulation in serum and brain, and activated the AhR/NF-κB/NLRP3 signaling pathway, triggering microglial pyroptosis and elevating AD-like pathological markers in mice. Meanwhile, fecal microbiota transplantation (FMT) from arsenic-exposed mice recapitulated cognitive impairment, elevated IS levels, and neuroinflammation in recipient mice. Furthermore, arsenic upregulated hepatic IS-synthesis genes (CYP2E1, Sult1d1) and downregulated renal IS-excretion gene (ABCG2). In vitro, arsenic and IS co-exposure promoted M1 polarization and enhanced pyroptosis by activating the AhR/NF-κB/NLRP3 signaling pathway, while suppressing phagocytosis-related proteins (TREM2, SYK and CD36). Furthermore, SiAhR treatment could alleviated microglial inflammatory injury and enhancing the microglia's phagocytic capacity induced by arsenic and IS co-exposure in BV2 cells through inhibiting the AhR/NF-κB/NLRP3-mediated pyroptosis signaling pathway. In conclusion, chronic arsenic exposure induced cognitive impairment and AD-like pathological via the gut microbiota-AhR-pyroptosis cascade, where in IS accumulation served a key mediator. These findings provide new insights into preventing arsenic-related cognitive damage.}, } @article {pmid41517132, year = {2025}, author = {Lu, S and Gao, M and Kuttappan, D and Amalaradjou, MA}, title = {Low-Fat Cheddar Cheese Influences Gut Microbiota Composition and Diversity in Human Microbiota-Associated Mice.}, journal = {Foods (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, pmid = {41517132}, issn = {2304-8158}, support = {430855//Foundation for Food and Agriculture Research New Innovator Award/ ; }, abstract = {Cheese is a complex fermented dairy food containing bioactive nutrients and microorganisms that can influence host physiology. However, most existing evidence of its health effects derives from observational studies or investigations of isolated components rather than the whole food matrix. The present study examined the impact of low-fat Cheddar cheese as a whole food on the gut microbiota using a human microbiota-associated (HMA) mouse model. Germ-free C57BL/6 mice were colonized with human fecal microbiota and randomly assigned to either a control diet or a diet supplemented with low-fat Cheddar cheese (7.5% w/w) for six weeks. Fecal samples were collected longitudinally and analyzed by 16S rRNA gene (V3-V4 region) amplicon sequencing. Human microbiota transplantation successfully established a stable, human-like gut microbial community in the mice. Cheese supplementation significantly increased alpha diversity (Shannon and Chao1 indices) and altered microbial composition, characterized by a higher relative abundance of Firmicutes and a reduction in Bacteroidetes (p < 0.001). At the genus level, Lactococcus and Streptococcus were enriched in cheese-fed mice, reflecting potential viable transfer of cheese-derived lactic acid bacteria. These findings provide experimental evidence that low-fat Cheddar cheese can beneficially influence the human-derived gut microbiota in an animal model and highlight the need for further clinical research to validate these effects in humans.}, } @article {pmid41516340, year = {2026}, author = {Liu, M and Wang, Y and Huang, H}, title = {Gut Microbiota-Derived Propionic Acid Mediates ApoA-I-Induced Amelioration of MASLD via Activation of GPR43-Ca[2+]-CAMKII-ATGL Hepatic Lipolysis.}, journal = {International journal of molecular sciences}, volume = {27}, number = {1}, pages = {}, pmid = {41516340}, issn = {1422-0067}, support = {5232004//Beijing Natural Science Foundation/ ; 32071130//National Natural Science Foundation of China/ ; }, mesh = {*Gastrointestinal Microbiome ; *Propionates/metabolism/pharmacology ; Animals ; *Receptors, G-Protein-Coupled/metabolism ; *Apolipoprotein A-I/metabolism/genetics ; *Lipolysis/drug effects ; Liver/metabolism ; Male ; Mice ; Humans ; Fecal Microbiota Transplantation ; Calcium/metabolism ; Mice, Inbred C57BL ; *Fatty Liver/metabolism ; *Non-alcoholic Fatty Liver Disease/metabolism ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is a widespread hepatic condition characterised by hepatic lipid accumulation and inflammation. Emerging research highlights the contribution of the intestinal microbiota and its metabolic byproducts to the pathogenesis of MASLD through the gut-liver axis. Apolipoprotein A-I (apoA-I), the principal structural component of high-density lipoprotein (HDL), is linked to various metabolic disorders; however, its function in MASLD has not yet been clearly elucidated. This study sought to examine whether apoA-I protects against MASLD, with a focus on the possible role of the gut microbiota and propionic acid (PPA). The contribution of the gut microbiota was evaluated using faecal microbiota transplantation (FMT) and antibiotic cocktail (ABX)-mediated depletion. Microbial composition was assessed via 16S rRNA sequencing, and concentrations of short-chain fatty acids (SCFAs) were quantified. The effects of PPA on MASLD were examined using in vivo and in vitro models. The results showed that apoA-I overexpression alleviated MASLD in a gut microbiota-dependent manner, restored microbial homeostasis, and elevated PPA levels. PPA supplementation improved MASLD phenotypes. Mechanistically, PPA treatment was associated with the activation of the GPR43-Ca[2+]-CAMKII-ATGL pathway, suggesting that PPA plays a role in stimulating hepatic lipolysis and enhancing mitochondrial β-oxidation. These findings reveal a novel pathway through which apoA-I ameliorates MASLD by modulating the gut microbiota and increasing PPA levels, which activate a hepatic lipolysis cascade. The apoA-I-microbiota-PPA axis represents a promising therapeutic target for MASLD intervention.}, } @article {pmid41516146, year = {2025}, author = {Barbu, AC and Stoleru, S and Zugravu, A and Poenaru, E and Dragomir, A and Costescu, M and Aurelian, SM and Shhab, Y and Stoleru, CM and Coman, OA and Fulga, I}, title = {Dopamine and the Gut Microbiota: Interactions Within the Microbiota-Gut-Brain Axis and Therapeutic Perspectives.}, journal = {International journal of molecular sciences}, volume = {27}, number = {1}, pages = {}, doi = {10.3390/ijms27010271}, pmid = {41516146}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dopamine/metabolism ; *Brain/metabolism ; Animals ; Parkinson Disease/metabolism/microbiology/therapy ; *Brain-Gut Axis ; Gastrointestinal Tract/metabolism/microbiology ; Fecal Microbiota Transplantation ; }, abstract = {The microbiota-gut-brain axis (MGBA) comprises a complex bidirectional communication network integrating neural, immune, metabolic, and endocrine pathways. Dopamine, traditionally viewed as a central neurotransmitter, also plays essential roles in the gastrointestinal (GI) tract, where it regulates motility, secretion, barrier homeostasis, and mucosal immunity. Growing evidence indicates that the gut microbiota significantly contributes to intestinal dopamine metabolism through specialized enzymatic pathways, particularly tyrosine decarboxylase in Enterococcus species and catechol dehydroxylase in Eggerthella species. These microbial reactions compete with host processes, alter dopaminergic tone, and degrade orally administered levodopa (L-DOPA), providing a mechanistic explanation for the variability in treatment response in Parkinson's disease (PD). Beyond PD, microbially mediated alterations in dopaminergic signaling have been implicated in mood disorders, neurodevelopmental conditions, metabolic dysfunction, and immune-mediated diseases. This review synthesizes current mechanistic and translational evidence on the dopamine-microbiota interface, outlines microbial pathways shaping dopaminergic activity, and highlights therapeutic opportunities including microbiota modulation, dietary strategies, fecal microbiota transplantation, and targeted inhibitors of microbial dopamine metabolism. Understanding this interface offers a foundation for developing personalized approaches in neurogastroenterology and neuromodulatory therapies.}, } @article {pmid41515997, year = {2025}, author = {Ahmed, I and Nijs, J and Vanroose, M and Vandeputte, D and Kindt, S and Elma, Ö and Hendrix, J and Huysmans, E and Lahousse, A}, title = {Oral and Gut Health, (Neuro) Inflammation, and Central Sensitization in Chronic Pain: A Narrative Review of Mechanisms, Treatment Opportunities, and Research Agenda.}, journal = {International journal of molecular sciences}, volume = {27}, number = {1}, pages = {}, doi = {10.3390/ijms27010114}, pmid = {41515997}, issn = {1422-0067}, mesh = {Humans ; *Chronic Pain/therapy/microbiology/etiology/metabolism ; Animals ; *Gastrointestinal Microbiome ; *Central Nervous System Sensitization ; *Oral Health ; *Neuroinflammatory Diseases ; Dysbiosis ; }, abstract = {Given the limited efficacy of current interventions and the complexity of chronic pain, identifying perpetuating factors is crucial for uncovering new mechanistic pathways and treatment targets. The oral and gut microbiome has emerged as a potential modulator of pain through immune, metabolic, and neural mechanisms. Contemporary evidence indicates that chronic pain populations exhibit altered oral and gut microbiota, characterized by reduced short-chain fatty acid (SCFA)-producing taxa and an overrepresentation of pro-inflammatory species. These compositional changes affect metabolites such as SCFAs, bile acids, and microbial cell wall components, which interact with host receptors to promote peripheral and central sensitization. Microbiota-derived metabolites modulate peripheral sensitization by altering nociceptive neuron excitability and stimulating immune cells to release pro-inflammatory cytokines that increase blood-brain barrier permeability, activate microglia, and amplify neuroinflammation. Activated microglia further disrupt the balance between excitatory and inhibitory neurotransmission by enhancing glutamatergic activity and weakening GABAergic signaling, thereby contributing to the induction and maintenance of central sensitization. While observational studies establish associations between dysbiosis and chronic pain, animal models and early human fecal microbiota transplantation studies suggest a potential causal role of dysbiosis in pain, although human evidence remains preliminary and influenced by diet, lifestyle, and comorbidities. Overall, microbiota appears to regulate pain via peripheral and central mechanisms, and targeting it through specific interventions, such as dietary modulation to enhance SCFA production, alongside broader lifestyle measures like sleep, physical activity, stress management, and oral hygiene, may represent a new therapeutic strategy for the management of chronic pain.}, } @article {pmid41514614, year = {2025}, author = {Peddireddi, RSS and Kuchana, SK and Kode, R and Khammammettu, S and Koppanatham, A and Mattigiri, S and Gobburi, H and Alahari, SK}, title = {Role of Gut Microbiome in Oncogenesis and Oncotherapies.}, journal = {Cancers}, volume = {18}, number = {1}, pages = {}, doi = {10.3390/cancers18010099}, pmid = {41514614}, issn = {2072-6694}, abstract = {The gut microbiome has emerged as a key regulator of human health, influencing not only metabolism and immunity but also the development and treatment of cancer. Mounting evidence suggests that microbial dysbiosis contributes to oncogenesis by driving chronic inflammation, producing genotoxic metabolites, altering bile acid metabolism, and disrupting epithelial barrier integrity. At the same time, the gut microbiome significantly modulates the host response to oncotherapies including chemotherapy, radiotherapy, and especially immunotherapy, where microbial diversity and specific taxa determine treatment efficacy and toxicity. This review synthesizes current evidence on the role of the gut microbiome in both oncogenesis and oncotherapies, focusing on thirteen cancers with the strongest and most clinically relevant microbiome associations, colorectal cancer, gastric cancer, hepatocellular carcinoma, gallbladder cancer, esophageal cancer, pancreatic cancer, oral squamous cell carcinoma, cervical cancer, prostate cancer, breast cancer, lung cancer, brain cancer, and melanoma. These cancers were selected based on robust mechanistic data linking microbial alterations to tumor initiation, progression, and therapy modulation, as well as their global health burden and translational potential. In addition, we have provided mechanistic insights or clinical correlations between the microbiome and cancer outcomes. Across cancers, common microbial mechanisms included pro-inflammatory signaling (e.g., NF-κB and STAT3 pathways), DNA damage from bacterial toxins (e.g., colibactin, nitrosating species), and metabolite-driven tumor promotion (e.g., secondary bile acids, trimethylamine N-oxide). Conversely, beneficial commensals such as Faecalibacterium prausnitzii and Akkermansia muciniphila supported antitumor immunity and improved responses to immune checkpoint inhibitors. In conclusion, the gut microbiome functions as both a driver of malignancy and a modifiable determinant of therapeutic success. Integrating microbiome profiling and modulation strategies such as dietary interventions, probiotics, and fecal microbiota transplantation into oncology practice may pave the way for personalized and more effective cancer care.}, } @article {pmid41512666, year = {2026}, author = {Liu, JB and Li, S and Sun, GZ and Lin, ZX and Miao, ZM}, title = {Gut microbiota modulation by novel synbiotic improves production performance and ovarian function in aged laying hens via gut-ovary axis.}, journal = {Poultry science}, volume = {105}, number = {3}, pages = {106394}, doi = {10.1016/j.psj.2026.106394}, pmid = {41512666}, issn = {1525-3171}, abstract = {The management of oxidative stress and ovarian dysfunction associated with aged laying hens, which is highly involved in gut microbiota, has been suggested as a feasible approach to improve production performance. Here, we investigated the effects of a novel synbiotic (Bacillus amyloliquefaciens + inulin, BAI), a gut microbiota regulator, on the improvement of production performance in aged laying hens, and dissected the underlying mechanisms using multi-omics analysis. Our findings showed that, compared to the control, high-dosage BAI supplementation significantly improved production performance; enhanced intestinal health, evidenced by the increase of villus height (p < 0.01), the expression of gut barrier-related genes (Claudin-1 and Claudin-2) (all p < 0.001), and immune levels (SIgA and IFN-γ) (all p < 0.01); meliorated ovarian function, confirmed by reduced oxidative stress (p < 0.001) and pathological lesions, as well as increased follicle numbers (p < 0.01 or p < 0.001), serum contents of reproductive hormone (estrogen, luteinizing hormone, and follicle-stimulating hormone) (p < 0.05 or p < 0.001), and the mRNA levels of yolk precursor synthesis-associated genes (APOVLDL-Ⅱ, VTG-Ⅱ, and VLDLR) (all p < 0.001). The 16S rRNA sequencing showed that BAI augmented the relative amount of Lactobacillus, Akkermansia, and Bacteroides and other short-chain fatty acids (SCFAs)-producers. Blood metabolome analysis demonstrated that the predominant metabolites changed by BAI were principally involved in SCFA metabolism, steroid hormone biosynthesis, steroid biosynthesis, and intestinal immune network for IgA production. Ovarian transcriptome analysis indicated that BAI significantly inhibited pathways of ferroptosis and peroxisome, confirmed by RT-qPCR. Furthermore, fecal microbiota transplantation (FMT) from BAI-treated aged hens improved production performance, ovarian function, and oxidative stress status in antibiotic-administrated hens. In sum, our study uncovers that BAI improves production performance and ovarian dysfunction via gut microbiota in aged laying hens. Thus, modulating gut microbiome is an effective approach to laying rate reduction of aged hens.}, } @article {pmid41511706, year = {2026}, author = {Shekar, P and Pradeep, S and Shivamallu, C and Prashant, A and Vishwanath, P}, title = {Immune-microbiota crosstalk in colorectal cancer: mechanistic pathways, biomarkers, and translational therapeutics.}, journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {}, number = {}, pages = {}, pmid = {41511706}, issn = {1699-3055}, abstract = {Colorectal cancer (CRC) is caused by a complex interaction between genetic, environmental, and microbial risk factors, and intestinal microbiota has critical roles in inflammation, immunology, and epithelial integrity. Pathobionts from the intestines (Fusobacterium nucleatum, Bacteroides fragilis, and E. coli that produce colibactin) promote DNA damage, immunity protection from cancer therapy, and resistance to chemotherapy treatments. The beneficial commensals and metabolites of intestinal microbes (namely butyrate) increase the mucosal immune response and inhibit tumor-specific signaling mechanisms. Microbe controlled changes of populations of myeloid, lymphoid, and regulatory cells dictate the state of the tumor-immune system and provide actionable checkpoints and biomarkers for cancer therapy. An enormous variety of clinical interventions based on the gut microbiota (probiotics, prebiotics, and fecal microbiota transfer) and diagnostic approaches is currently being developed. Translational issues are difficult due to the interindividual variability and regulatory complexity of tumors. Research needs include standardizing multi-omics data from multidisciplinary teams and mechanistic validation in organoid and gnotobiotic models as well as prediction algorithms to optimize the microbiome-based medicine for individual patients. Targeting the immune-microbiota axis may provide new therapeutic strategies in the diagnosis, prognosis, and therapy of CRC.}, } @article {pmid41508489, year = {2026}, author = {Qu, Q and Zhou, Q and Peng, X and Li, Z and Jia, M and Zhang, Y and Yang, C and Dai, X and Sheng, M and Kang, J and Shi, X}, title = {Monascus fermentation enhances the lipid-lowering properties of ginseng in vivo and component assay.}, journal = {Food research international (Ottawa, Ont.)}, volume = {225}, number = {}, pages = {118067}, doi = {10.1016/j.foodres.2025.118067}, pmid = {41508489}, issn = {1873-7145}, mesh = {*Panax/chemistry ; Animals ; *Fermentation ; *Monascus/metabolism ; Mice ; Gastrointestinal Microbiome/drug effects ; Male ; *Hyperlipidemias/drug therapy ; Mice, Inbred C57BL ; *Hypolipidemic Agents/pharmacology ; Lovastatin/pharmacology ; Fecal Microbiota Transplantation ; Lipid Metabolism/drug effects ; Liver/metabolism ; Ginsenosides ; Lipids/blood ; }, abstract = {Hyperlipidemia is a global health concern characterized by elevated lipid levels and increased cardiovascular risk. Ginseng (Panax ginseng) has lipid-lowering properties, and Monascus fermentation can yield monacolin K, a natural statin. However, it remains unclear whether Monascus-fermented ginseng (MFG) offers synergistic benefits over ginseng or Monascus alone. This study aimed to compare the lipid-lowering efficacy of MFG versus unfermented ginseng, Monascus, and their non-fermented combination in hyperlipidemic mice. Multi-omics analyses (hepatic transcriptomics, serum/fecal metabolomics, and gut microbiota profiling) were integrated to elucidate underlying mechanisms, and fecal microbiota transplantation (FMT) assessed the causal role of MFG-altered microbiota. MFG supplementation markedly improved serum lipid profiles and attenuated hepatic steatosis, outperforming ginseng, Monascus, or their unfermented combination. Phytochemical analysis confirmed that fermentation introduced monacolin K into MFG and increased its rare ginsenoside content, distinguishing it from unfermented ginseng. Mechanistically, MFG increased hepatic p-AMPK and upregulated fatty acid oxidation while downregulating lipogenesis (SREBP-1c, FAS). Metabolomics revealed elevated short-chain fatty acid levels and enhanced bile acid biotransformation in MFG-treated mice. MFG reshaped gut microbiota composition and enriched beneficial taxa. Importantly, FMT from MFG-fed donors recapitulated the lipid-lowering effects in recipients, confirming a microbiota-mediated mechanism. In conclusion, MFG exerts superior lipid-lowering effects through complementary host metabolic and gut microbial modulation, highlighting fermented herbal products as promising interventions against hyperlipidemia.}, } @article {pmid41508463, year = {2026}, author = {Dong, Y and Xie, Y and Yao, R and Mai, Y and Zhang, L and Wang, H and Wang, H and Zhang, J}, title = {Lactobacillus fermentum ZNL16 attenuates ETEC-induced intestinal injury by regulating gut microbiota and short-chain fatty acid metabolism to suppress the IL-17/JAK2-STAT3 pathway.}, journal = {Food research international (Ottawa, Ont.)}, volume = {225}, number = {}, pages = {118038}, doi = {10.1016/j.foodres.2025.118038}, pmid = {41508463}, issn = {1873-7145}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Fatty Acids, Volatile/metabolism ; *Limosilactobacillus fermentum/physiology ; STAT3 Transcription Factor/metabolism ; Mice ; *Probiotics/pharmacology ; Interleukin-17/metabolism ; *Enterotoxigenic Escherichia coli ; Signal Transduction ; Fecal Microbiota Transplantation ; Janus Kinase 2/metabolism ; Mice, Inbred C57BL ; *Escherichia coli Infections/microbiology ; Male ; Intestinal Mucosa/microbiology/metabolism ; Intestines/microbiology ; Butyric Acid ; }, abstract = {Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea, threatening neonates, travelers, and livestock by disrupting the intestinal barrier and weakening immunity. Lactobacillus fermentum has been shown to enhance barrier integrity and modulate immune activity, while gut microbiota and their metabolites are critical regulators of intestinal health. Our findings demonstrate that Lactobacillus fermentum ZNL16 improved intestinal barrier function and reduced inflammation via the IL-17/JAK2-STAT3 signaling pathway, while also promoting microbial balance and short-chain fatty acid metabolism. Antibiotic-induced microbiota depletion confirmed that these protective effects are microbiota-dependent. Furthermore, fecal microbiota transplantation (FMT) from ZNL16-treated mice and sodium butyrate supplementation both alleviated ETEC-induced intestinal damage. Taken together, our findings demonstrate the capacity of L. fermentum ZNL16 to safeguard intestinal barrier integrity and modulate immune responses, supporting its promise as a candidate for probiotic development.}, } @article {pmid41507585, year = {2026}, author = {Hsu, CL and Shukla, S and Freund, L and Chou, AC and Yang, Y and Bruellman, R and Raya Tonetti, F and Cabré, N and Mayo, S and Lim, HG and Magallan, V and Cordell, BJ and Lang, S and Demir, M and Stärkel, P and Llorente, C and Palsson, BO and Mandyam, C and Boland, BS and Hohmann, E and Schnabl, B}, title = {Gut microbial ethanol metabolism contributes to auto-brewery syndrome in an observational cohort.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {41507585}, issn = {2058-5276}, support = {BX004594//Biomedical Laboratory Research and Development, VA Office of Research and Development (VA Biomedical Laboratory Research and Development)/ ; CTORA23-208366//American Association for the Study of Liver Diseases (AASLD)/ ; CTORA23-208366//American Association for the Study of Liver Diseases (AASLD)/ ; K99 AA031328/AA/NIAAA NIH HHS/United States ; R01 AA029106, R21 AA030654, P30 AR073761//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; DE-AC02-05CH11231//U.S. Department of Energy (DOE)/ ; }, abstract = {Auto-brewery syndrome (ABS) is a rarely diagnosed disorder of alcohol intoxication due to gut microbial ethanol production. Despite case reports and a small cohort study, the microbiological profiles of patients remain poorly understood. Here we conducted an observational study of 22 patients with ABS and 21 unaffected household partners. Faecal samples from individuals with ABS during a flare produced more ethanol in vitro, which could be reduced by antibiotic treatment. Gut microbiome analysis using metagenomics revealed an enrichment of Proteobacteria, including Escherichia coli and Klebsiella pneumoniae. Genes in metabolic pathways associated with ethanol production were enriched, including the mixed-acid fermentation pathway, heterolactic fermentation pathway and ethanolamine utilization pathway. Faecal metabolomics revealed increased acetate levels associated with ABS, which correlated with blood alcohol concentrations. Finally, one patient was treated with faecal microbiota transplantation, with positive correlations between gut microbiota composition and function, and symptoms. These findings can inform future clinical interventions for ABS.}, } @article {pmid41506765, year = {2026}, author = {Rognstad, ØB and Botteri, E and Hoff, G and Bretthauer, M and Nguyen, HD and Schult, AL and Holme, Ø and Randel, KR}, title = {Use of claims data to identify adverse events after colonoscopy in a randomised colorectal cancer screening trial in Norway: a cross-sectional study.}, journal = {BMJ open}, volume = {16}, number = {1}, pages = {e109883}, doi = {10.1136/bmjopen-2025-109883}, pmid = {41506765}, issn = {2044-6055}, mesh = {Humans ; Cross-Sectional Studies ; Norway/epidemiology ; Male ; Female ; Middle Aged ; *Colonoscopy/adverse effects ; *Colorectal Neoplasms/diagnosis ; Aged ; *Early Detection of Cancer/adverse effects/methods ; Retrospective Studies ; *Gastrointestinal Hemorrhage/etiology/epidemiology ; Intestinal Perforation/etiology/epidemiology ; *Insurance Claim Review ; Occult Blood ; }, abstract = {OBJECTIVES: Accurate identification of adverse events after colonoscopy is essential for quality assurance in colorectal cancer (CRC) screening. Review of medical records is labour intensive as adverse events are infrequent. The object of this study was to investigate the accuracy of claims data in identifying adverse events after colonoscopy in CRC screening.

DESIGN: Cross-sectional, retrospective.

SETTING AND PARTICIPANTS: Males and females aged 50-74 years were randomised to once-only sigmoidoscopy or biennial faecal immunochemical test in a CRC screening trial at two screening centres in Norway. Participants in the present study underwent follow-up colonoscopy from 2012 to April 2020 after initial positive screening test. We reviewed medical records for adverse events within 30 days following 11 205 colonoscopies.

The primary outcome of the study was to assess the sensitivity of claims data from the Norwegian Patient Registry to identify lower gastrointestinal bleeding using emergency contact International Statistical Classification of Diseases and Related Health Problems 10th Revision diagnostic code sets under two definitions: a stringent definition (codes explicitly identifying bleeding) and a broad definition (including suggestive codes). Secondary outcome measures included the sensitivity to identify perforation using a stringent and a broad definition. Additionally, we assessed whether incorporating procedure codes and non-emergency contacts improved accuracy.

RESULTS: 87 cases of lower gastrointestinal bleeding and eight perforations were confirmed. Sensitivity for bleeding differed between the centres (p<0.001). At centre 1, sensitivity was 48.6% (95% CI 31.9% to 65.6%) using the stringent and 89.2% (95% CI 74.6% to 97.0%) using the broad definition. At centre 2, sensitivity was 36.0% (95% CI 22.9% to 50.8%) and 50.0% (95% CI 35.5% to 64.5%), respectively. Combined sensitivity for perforation was 37.5% (95% CI 8.5% to 75.5%) using the stringent and 62.5% (95% CI 24.5% to 91.5%) using the broad definition. Adding procedure codes and non-emergency contacts slightly increased sensitivity but increased false positives.

CONCLUSIONS: Use of claims data underestimated adverse event rates following colonoscopy. Difference in coding practice across hospitals underscores the need for standardised reporting in screening programmes.

TRIAL REGISTRATION NUMBER: NCT01538550.}, } @article {pmid41506296, year = {2026}, author = {He, D and Chen, Y and Xue, M and Gao, X and Yan, A and Sun, Y and Li, X and Liu, J and Hu, G and Fu, S}, title = {Orally Administered Neohesperidin (Neo) Alleviates Lipopolysaccharide-Induced Mastitis by Suppressing TLR4/NF-κB and Activating AMPK/Nrf2/HO-1 Signaling, and Regulating Intestinal Flora Structure.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c12129}, pmid = {41506296}, issn = {1520-5118}, abstract = {The impairment of the blood-milk barrier (BMB) during mastitis severely compromises breastfeeding efficacy, highlighting an urgent need for effective nonantibiotic interventions. Natural anti-inflammatory and traditional Chinese medicine (TCM) compounds have thus garnered increasing attention as promising alternatives. Neohesperidin (Neo), a major bioactive flavonoid derived from the TCM herbs such as Citrus aurantium and its related species, has been historically associated with heat-clearing and detoxifying properties in TCM theory. However, its role in mastitis remains unclear. Herein, we investigated the protective effects of Neo on BMB integrity using an LPS-induced mastitis model. Our results demonstrate that Neo significantly alleviates mammary tissue damage and preserves BMB function. Further mechanistic studies indicate that Neo attenuates LPS-induced inflammatory responses and oxidative stress in mammary epithelial cells by inhibiting the TLR4/NF-κB pathway and concurrently activating the AMPK/Nrf2/HO-1 axis. Additionally, 16S rRNA sequencing and fecal microbiota transplantation (FMT) experiments demonstrated that Neo alleviates mastitis by modulating the gut microbiota (increasing beneficial bacteria and reducing harmful bacteria). In summary, this study confirms that Neo can mitigate mastitis and protect BMB function through its anti-inflammatory, antioxidant, and microbiota-regulating effects. The research not only elucidates the molecular mechanisms by which Neo exerts its mammary protective effects through inflammation-oxidative stress-gut microbiota but also provides new insights for the prevention and treatment of mastitis.}, } @article {pmid41505077, year = {2026}, author = {Ghaemi, M and Ghaemi, A and Tavakkoli, H and Mashhadinejad, M and Kheradmand, D}, title = {The MOF-Microbiome Axis: a New Paradigm for Precision Nanomedicine.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {41505077}, issn = {1867-1314}, abstract = {The gut microbiome is crucial for human health, and its imbalance, known as dysbiosis, is associated with diseases such as inflammatory bowel disease, metabolic disorders, and neurological disorders. Traditional treatments, such as probiotics and fecal microbiota transplants, often lack precision, making the emerging field of nanomedicine a promising alternative. This review introduces the "MOF-Microbiome Axis," which explores the interactions between metal-organic frameworks (MOFs), versatile, porous materials, and the gut microbiome. It focuses on designing gastrointestinal-targeted MOFs that are biocompatible and responsive to stimuli. We discuss how MOFs can serve as scaffolds, controlled-release vehicles, and metabolite scavengers, highlighting their therapeutic applications in targeted antimicrobial therapy, enhanced probiotic delivery, and immunomodulation. The review also addresses important challenges in biosafety, scalable production, and personalized treatment, suggesting future directions such as bio-hybrid systems and precision microbiome editing. Overall, the MOF-Microbiome Axis offers a new perspective on microbiome engineering and advanced therapeutic approaches.}, } @article {pmid41504254, year = {2026}, author = {Lin, P}, title = {The importance of the microbiome in uveitis.}, journal = {Current opinion in ophthalmology}, volume = {}, number = {}, pages = {}, doi = {10.1097/ICU.0000000000001197}, pmid = {41504254}, issn = {1531-7021}, abstract = {PURPOSE OF REVIEW: The purpose of this review was to summarize the literature on preclinical and clinical studies demonstrating the impact of the intestinal microbiome in noninfectious uveitis.

RECENT FINDINGS: Preclinical studies using the experimental autoimmune uveitis (EAU) model have shown commensals such as Desulfovibrio and Prevotella, as well as Ruminococcaceae, associated with uveitis, which overlap with some clinical studies in uveitis patients. Interventions that target the microbiome that can be developed for the treatment of uveitis include antibiotics, fecal metabolites or metabolite agonists that are protective in uveitis, probiotics, dietary interventions, or fecal microbial transplant.

SUMMARY: There is significant data supporting the importance of the intestinal microbiome in noninfectious uveitis through enrichment or depletion of certain gut bacteria as well as their metabolites. Targeting the intestinal microbiome or their metabolites might be a viable option for the treatment of noninfectious uveitis.}, } @article {pmid41503829, year = {2026}, author = {Zhang, H and Wang, Y and Ning, B and Wang, Y and Sun, T and Xu, J}, title = {The gut microbiota-obesity axis in the pathogenesis and prognosis of breast cancer.}, journal = {Annals of medicine}, volume = {58}, number = {1}, pages = {2611203}, doi = {10.1080/07853890.2025.2611203}, pmid = {41503829}, issn = {1365-2060}, mesh = {Humans ; *Obesity/complications/microbiology/immunology ; *Breast Neoplasms/microbiology/immunology/pathology/therapy ; *Gastrointestinal Microbiome/physiology/immunology ; Female ; *Dysbiosis/microbiology/complications/immunology ; Prognosis ; Probiotics/therapeutic use ; }, abstract = {BACKGROUND: Breast cancer (BC) remains a major global health concern, accounting for 11.7% of all cancer cases and ranking as the second leading cause of female cancer-related deaths worldwide. Increasing evidence highlights the interplay between gut microbiota (GM) dysbiosis and obesity-associated metabolic dysfunction in BC progression. This review aims to elucidate the role of GM in obese patients with BC.

METHODS: A systematic literature search was conducted in PubMed and Web of Science databases for publications from July 2015 to January 2025. Search terms combined BC, GM, obesity, dysbiosis, immunity, and microbiome. Article selection prioritized studies investigating microbial alterations in BC patients, mechanistic links between obesity and cancer progression, and GM-targeted interventions. Both original studies and authoritative reviews were included, supplemented by manual reference screening.

DISCUSSION: Obesity may trigger systemic inflammation, altered adipokine secretion, and disrupted steroid hormone metabolism via gut-derived β-glucuronidase activity, thereby exacerbating BC occurrence and recurrence. GM dysbiosis-driven metabolites such as branched-chain amino acids (BCAAs) and short-chain fatty acids (SCFAs) can activate oncogenic signaling pathways and immunosuppressive myeloid-derived suppressor cells (MDSCs), fostering tumor immune evasion. Conversely, dietary interventions, probiotics, and fecal microbiota transplantation (FMT) can alleviate dysbiosis, strengthen gut barriers, and restore anti-tumor immunity, improving chemotherapy response and reducing recurrence. However, challenges persist in deciphering BC subtype-related microbial signatures and optimizing microbiota-targeted therapies.

CONCLUSION: Future longitudinal studies are needed to clarify causal relationships, validate microbial biomarkers, and translate preclinical findings into clinical applications. Addressing the gut-breast axis may offer transformative potential for precision oncology in obesity-driven BC.}, } @article {pmid41503825, year = {2026}, author = {Kang, K and Kim, JY and Yim, JJ and Kim, D}, title = {Gut-lung axis and microbiome alterations in mycobacterial infections: from pathogenesis to therapeutic potential.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2612428}, doi = {10.1080/19490976.2025.2612428}, pmid = {41503825}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Dysbiosis/microbiology/therapy ; *Lung/microbiology/immunology ; Animals ; Probiotics ; Fecal Microbiota Transplantation ; *Mycobacterium Infections/microbiology/therapy ; }, abstract = {Mycobacterial lung diseases, including tuberculosis (TB) and nontuberculous mycobacterial pulmonary disease (NTM-PD), are increasingly recognized as disorders influenced not only by host immunity but also by microbiota. Emerging evidence identifies the gut-lung axis (GLA) as a key bidirectional communication network linking intestinal and pulmonary homeostasis. Mycobacterial infection itself induces airway and gut dysbiosis through immune and metabolic disturbances, which is further exacerbated by prolonged antibiotic therapy. Dysbiosis within either site reciprocally affects the other via GLA, leading to reduced microbial diversity, impaired epithelial integrity, and systemic inflammation. These alterations disrupt metabolite-mediated immunoregulation and attenuate IL-22-driven epithelial defense, thereby weakening bacterial clearance and promoting chronic inflammation. Distinct microbial features, such as the depletion of beneficial SCFA-producing taxa and enrichment of pro-inflammatory anaerobes, are observed in both TB and NTM-PD. Moreover, therapy-induced microbiome remodeling influences treatment response and disease relapse. Restoring microbial balance through probiotics, prebiotics, postbiotics, dietary modulation, or fecal microbiota transplantation offers a promising adjunctive strategy. This review integrates current evidence linking microbiome dysbiosis to mycobacterial pathogenesis and highlights microbiome-targeted interventions as an emerging therapeutic frontier in pulmonary mycobacterial diseases.}, } @article {pmid41503791, year = {2026}, author = {Jin, J and Yao, G and Zhang, X and Zhang, T and Ye, H and Zhou, X and Yu, Y and Zhao, Y and Qin, Z and Chen, H and Bi, Y and Wang, X and Ren, X and Zhang, Y and Wang, Z and Zhang, Q}, title = {Gut virome dysbiosis contributes to premature ovarian insufficiency by modulating gut bacteriome.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2611645}, doi = {10.1080/19490976.2025.2611645}, pmid = {41503791}, issn = {1949-0984}, mesh = {Female ; Animals ; *Dysbiosis/microbiology/virology ; *Primary Ovarian Insufficiency/microbiology/virology/therapy ; *Gastrointestinal Microbiome ; Rats ; Humans ; Adult ; *Virome ; Fecal Microbiota Transplantation ; *Bacteria/genetics/classification/isolation & purification/virology ; Young Adult ; Feces/virology ; Ovary ; Rats, Sprague-Dawley ; }, abstract = {BACKGROUND: Premature ovarian insufficiency (POI) significantly impairs female fertility and poses substantial health risks; however, its pathogenesis is incompletely understood, and effective therapeutic interventions are limited. Although gut bacteriome has been closely associated with ovarian dysfunction, the role and therapeutic potential of gut viruses, which far outnumber bacteria, remain largely unexplored.

RESULTS: Therefore, we recruited 60 healthy reproductive-aged women and recently diagnosed POI patients and investigated these concerns using various techniques, including whole-genome shotgun sequencing of virus-like particle (VLP) and fecal virome transplantation (FVT) in CTX-induced POI rats. We found considerable interindividual variability in the gut virome. The virome of POI patients exhibited significant dysbiosis, characterized by a marked reduction in virulent phage, significant changes in predominant phages, and a notable increase in horizontal gene transfer of resistance genes and virulence factors. Furthermore, gut VLPs from the healthy reproductive-aged women significantly improved the condition of POI rats. Conversely, gut VLPs from POI patients markedly impaired the ovarian function and reproductive capacity of healthy rats. The above regulatory effect is primarily due to modulations of gut bacteriome, specifically the estrobolome, and intestinal barrier integrity, which subsequently affect hypothalamic-pituitary-ovarian axis hormone levels and regulate ovarian oxidative stress and inflammation, thereby influencing ovarian function.

CONCLUSIONS: Our findings demonstrate the critical roles of the gut virome in regulating ovarian function and provide new insights into the pathogenesis of POI. This study also underscores the therapeutic potential of the gut virome in improving ovarian dysfunction and female infertility including POI.}, } @article {pmid41503704, year = {2026}, author = {De Palma, G and Costanzini, A and Mohan, V and Sidani, S and Saqib, Z and Pigrau, M and Lu, J and Causada Calo, N and Pinto-Sanchez, I and Verdu, EF and Marcon, M and Barbara, G and Stanghellini, V and De Giorgio, R and Collins, SM and Bercik, P}, title = {The role of gut microbiota in chronic intestinal pseudo-obstruction: exploring fecal microbiota transplantation as a treatment option.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2610597}, doi = {10.1080/19490976.2025.2610597}, pmid = {41503704}, issn = {1949-0984}, mesh = {*Fecal Microbiota Transplantation ; *Intestinal Pseudo-Obstruction/therapy/microbiology ; *Gastrointestinal Microbiome ; Animals ; Humans ; Mice ; Male ; Female ; Middle Aged ; Adult ; RNA, Ribosomal, 16S/genetics ; Bacteria/classification/genetics/isolation & purification ; Chronic Disease/therapy ; Aged ; Feces/microbiology ; Disease Models, Animal ; Italy ; }, abstract = {Chronic intestinal pseudo-obstruction (CIPO) is characterized by bowel dilation and obstructive symptoms without any structural blockage. Although the microbiota is known to affect gastrointestinal function, its role in CIPO is poorly understood. We aimed to characterize the CIPO microbiota, investigate its role in disease expression and explore the therapeutic role of fecal microbiota transplantation (FMT). CIPO patients (n = 14) and healthy controls (HC, n = 12) were recruited from Italy and Canada. Microbiota profiles and functions were assessed by 16S rRNA sequencing and PICRUSt. Germ-free NIH Swiss mice were colonized with HC and CIPO microbiota, their intestinal transit and bowel distension were assessed by videofluoroscopy and computed tomography (CT), and the expression of host genes by NanoString®. The CIPO microbiota exhibited reduced microbial diversity with dominance of Proteobacteria and altered metabolic function. Mice with CIPO microbiota developed marked bowel distension and slow intestinal transit associated with altered expression of multiple genes related to immunity, the intestinal barrier and neuromuscular function. FMT from a HC improved the microbiota profile, intestinal transit and bowel distension in both CIPO mice and a selected CIPO patient, in whom a marked clinical improvement was sustained for 8 y. Thus, our findings support the use of microbiota-directed therapies to induce clinical improvement in CIPO patients.}, } @article {pmid41503678, year = {2026}, author = {Zhou, S and Guo, L and Chen, N and Liu, H and Liu, X and Li, J and Dong, S and Liu, J and Wang, X and Ran, Y and Liu, M and Chu, H and Li, Y and Yang, H and Zhao, J and Zhou, L}, title = {Depression Aggravates Immune-Mediated Hepatitis Through NLRP3 Overactivation Induced by Intestinal Microbiota.}, journal = {CNS neuroscience & therapeutics}, volume = {32}, number = {1}, pages = {e70743}, pmid = {41503678}, issn = {1755-5949}, support = {81860109//National Natural Science Foundation of China/ ; 21JCZDJC00880//Natural Science Foundation of Tianjin Municipality/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Male ; Mice ; Humans ; Female ; *Hepatitis, Autoimmune/metabolism/immunology/complications ; Middle Aged ; Adult ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; *Depression/metabolism/complications ; Concanavalin A/toxicity ; *Depressive Disorder, Major/metabolism ; Inflammasomes/metabolism ; }, abstract = {BACKGROUND: Depression is associated with adverse effects in patients with autoimmune hepatitis (AIH). However, the underlying mechanism remains unclear. This study explores the impact of depression and related intestinal microbiota on immune-mediated hepatitis.

METHODS: We assessed depression in 260 AIH patients receiving 2-year standardized treatment and 173 healthy controls. In mice, depressive-like behaviors were induced by chronic unpredictable mild stress (CUMS), and immune-mediated hepatitis was induced by intravenous injection of concanavalin A (ConA). Fecal microbiota transplantation (FMT) was performed using samples from patients with major depressive disorder (MDD) and controls.

RESULTS: Depression was common in patients with AIH (106/260, 40.8%) and was associated with cirrhosis. Compared with nondepressed AIH patients, those with depression showed exacerbated intestinal barrier dysfunction and hepatic NLR family pyrin domain containing 3 (NLRP3) inflammasome overactivation. In the ConA-induced hepatitis model, CUMS exposure aggravated these abnormalities, which were then attenuated by mirtazapine. Furthermore, mice colonized with MDD microbiota exhibited greater intestinal barrier disruption and hepatic NLRP3 inflammasome overactivation than those colonized with control microbiota. Notably, gut-derived Lactococcus formosensis, isolated from the livers of MDD microbiota-colonized mice, could translocate to the liver and induce hepatic NLRP3 inflammasome overactivation. In addition, vaccination against L. formosensis prevented translocation and alleviated liver injury in monocolonized mice.

CONCLUSION: Depression aggravates immune-mediated hepatitis through disruption of intestinal barrier integrity and overactivation of hepatic NLRP3 inflammasome. Gut-derived L. formosensis could translocate to the liver and induce liver injury in mice. This study provides the necessity of screening for depression in patients with AIH.}, } @article {pmid41211649, year = {2026}, author = {Zhao, QK and Ning, YX and Xu, TC and Zhao, ZA and Pei, YF and Niu, JY and Li, XD and Chen, HS}, title = {Electroacupuncture Alleviates Brain Injury Through Vagus Nerve Activation and Gut Microbiota in a Rat Model of Ischemic Stroke.}, journal = {Journal of the American Heart Association}, volume = {15}, number = {1}, pages = {e045929}, doi = {10.1161/JAHA.125.045929}, pmid = {41211649}, issn = {2047-9980}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Electroacupuncture/methods ; *Vagus Nerve/physiopathology/metabolism ; Rats ; Male ; Disease Models, Animal ; Rats, Sprague-Dawley ; *Infarction, Middle Cerebral Artery/therapy/microbiology ; *Ischemic Stroke/therapy/microbiology/physiopathology/metabolism ; Brain/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Emerging evidence implicates gut microbiota dysbiosis in exacerbating stroke pathogenesis via the gut-brain axis, suggesting novel therapeutic targets. While electroacupuncture (EA) demonstrates anti-inflammatory effects through vagus nerve activation, its neuroprotective mechanisms via vagus nerve-microbiota crosstalk remain unexplored.

METHODS: Rats with middle cerebral artery occlusion received daily ST36 (Acupoint Zusanli) EA for 1 to 7 days postischemia. Subdiaphragmatic vagotomy and fecal microbiota transplant were implemented to validate pathway specificity. Multimodal assessments included longitudinal neurological scoring, infarct volume, systemic/neuroinflammatory profiling (enzyme-linked immunosorbent assay, immunohistochemistry), intestinal fucosylation dynamics (quantitative polymerase chain reaction, lectin staining), and 16S ribosomal RNA sequencing of gut microbiota.

RESULTS: EA significantly improved neurological outcomes and reduced infarct volumes at 3 to 7 days after middle cerebral artery occlusion (versus controls), which was abolished by vagotomy. Mechanistically, EA restored gut barrier integrity through vagus-dependent upregulation of fucosyltransferase 2 (Fut2)-driven epithelial α1,2-fucosylation, enhancing mucin 2+ goblet cell density and tight junction protein expression (ZO-1/occludin/claudin-1). Concurrent microbiota shifts included Lactobacillales/Bacteroidales enrichment (linear discriminant analysis >4.0) and pathobiont suppression, which was reversed by vagotomy. Crucially, fecal microbiota transplant from EA-treated donors replicated neuroprotection in germ-free recipients, achieving 33% infarct reduction and 30% survival improvement (P=0.012), whereas fecal microbiota transplant from vagotomized donors showed no therapeutic benefits.

CONCLUSIONS: EA at ST36 produced neuroprotection through activating vagal efferent pathways to orchestrate intestinal mucosal repair via Fut2-mediated fucosylation, which reshape microbial ecosystems and attenuate neuroinflammation. These findings establish a previously unrecognized vagus nerve-gut-brain axis mechanism for stroke recovery, positioning microbiota-directed neuromodulation by EA as a translatable therapeutic strategy.}, } @article {pmid41503571, year = {2026}, author = {Bajaj, JS and Fagan, A and Sterling, RK and Sikaroodi, M and Gallagher, ML and Lee, H and Matherly, SC and Bartels, A and Mousel, T and Davis, BC and Puri, P and Fuchs, M and Thacker, LR and McGinley, JP and Khoruts, A and Gillevet, PM}, title = {The multi-omic basis for hepatic encephalopathy recurrence: Analysis of the THEMATIC trial.}, journal = {JHEP reports : innovation in hepatology}, volume = {8}, number = {1}, pages = {101634}, doi = {10.1016/j.jhepr.2025.101634}, pmid = {41503571}, issn = {2589-5559}, abstract = {BACKGROUND & AIMS: The THEMATIC trial demonstrated that fecal microbiota transplantation (FMT) reduces recurrence of hepatic encephalopathy (HE) in patients already receiving lactulose and rifaximin. The aim of this analysis was to identify multi-omic predictors of HE recurrence among THEMATIC trial participants.

METHODS: The THEMATIC trial enrolled patients with cirrhosis and HE who received oral or enema FMT vs. placebo (1-3 administrations) and were followed for 6 months. Outcomes included safety and HE recurrence. Serum, urine, and stool samples were collected at baseline and post-FMT for all participants. Stool metagenomics, serum and urine metabolomics, inflammatory cytokines, and clinical data were analyzed. Differences between patients with and without HE recurrence were assessed using pathway, random forest, and latent factor analyses.

RESULTS: HE recurred in 10 of 60 patients (17%), with significantly higher recurrence in the placebo vs. the FMT groups (40% vs. 8%; p = 0.005). Due to the low recurrence rate in the FMT arms, all patients with recurrence were combined and compared with those without recurrence. Stool metagenomics showed that the abundance of short-chain fatty acid (SCFA) producers (Faecalibacterium, Eubacterium, Bacteroides, Blautia spp.) was lower, while that of GABA-producing taxa (Lactobacillus, Bifidobacterium spp.) was higher, in patients with recurrence. Urine and serum metabolomes separated HE recurrence groups on PLS-DA, with serum butyrate and isobutyrate being most significantly associated (p = 0.008). Pathway analyses revealed upregulation of GABA and neurotransmitter pathways in patients with HE recurrence. Random forest and latent factor analysis indicated that SCFA producers and secondary bile acids were protective, whereas IL-6, GABA producers, nicotine metabolites, and primary bile acids were associated with HE recurrence.

CONCLUSIONS: Secondary analysis of the THEMATIC randomized controlled trial indicates that HE recurrence in patients on lactulose and rifaximin is associated with distinct microbiome and metabolomic profiles, particularly involving SCFAs, GABA metabolism, bile acids, and IL-6.

IMPACT AND IMPLICATIONS: Fecal microbiota transplantation (FMT) reduced hepatic encephalopathy (HE) recurrence in patients receiving lactulose and rifaximin in the THEMATIC trial, but the multi-omic mechanisms underlying this effect were unclear. In this secondary analysis, we found that HE recurrence - regardless of FMT or placebo assignment - was associated with distinct multi-omic signatures, including reduced short-chain fatty acid-producing and increased pathobiont taxa, lower urinary and serum short-chain fatty acids, secondary bile acids, and acetaminophen derivatives, and higher GABA-related and nicotine metabolites, along with elevated IL-6 levels. Notably, patients with greater donor microbiota engraftment had lower rates of HE recurrence. These findings suggest that HE recurrence after FMT reflects a multifactorial process involving alterations in gut metagenomics, systemic metabolomics, inflammation, and donor engraftment.

TRIAL REGISTRATION: www.clinicaltrials.gov: NCT03796598.}, } @article {pmid41503356, year = {2025}, author = {Alobaidi, S}, title = {The gut-kidney axis in chronic kidney disease: mechanisms, microbial metabolites, and microbiome-targeted therapeutics.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1675458}, doi = {10.3389/fmed.2025.1675458}, pmid = {41503356}, issn = {2296-858X}, abstract = {Chronic kidney disease (CKD) remains a major global health issue, affecting millions and presenting persistent diagnostic and therapeutic challenges. Conventional biomarkers such as serum creatinine and estimated glomerular filtration rate have well-recognized limitations, underscoring the need for novel diagnostic tools and interventions. Emerging evidence highlights the gut-kidney axis as a central contributor to CKD pathogenesis, shaped by microbial dysbiosis and altered metabolite production. Harmful metabolites such as indoxyl sulfate, p-cresyl sulfate, and trimethylamine-N-oxide promote inflammation, endothelial dysfunction, and fibrosis, while loss of protective short-chain fatty acids impairs barrier integrity and immune regulation. This review integrates mechanistic, translational, clinical, and therapeutic perspectives, offering a comprehensive and distinctive synthesis of current knowledge. We emphasize both harmful and protective microbial metabolites, incorporate the often-overlooked oral-gut-kidney axis, and highlight advances in multi-omics and computational approaches for biomarker discovery. Microbiome-targeted interventions-including dietary strategies, prebiotics, probiotics, synbiotics, oral adsorbents, and fecal microbiota transplantation-are critically evaluated with respect to efficacy, safety, and translational readiness. By bridging basic science, clinical evidence, and therapeutic implications, this review provides a forward-looking framework for integrating microbiome insights into CKD diagnosis and management. Our synthesis complements existing literature while highlighting unmet needs, thereby informing future research priorities and guiding the development of clinically relevant microbiome-based strategies.}, } @article {pmid41502951, year = {2025}, author = {Oliveira, RA and McSpadden, E and Pandey, B and Lee, K and Yousef, M and Chen, RY and Triebold, C and Haro, F and Aksianiuk, V and Patel, R and Shriram, K and Ramanujam, R and Kuehn, S and Raman, AS}, title = {Statistical design of a synthetic microbiome that suppresses diverse gut pathogens.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.02.28.582635}, pmid = {41502951}, issn = {2692-8205}, abstract = {Engineering functional microbiomes is challenging due to complex interactions between bacteria and their environments [1-6] . Using a set of 848 gut commensal strains and clearance of multi-drug resistant Klebsiella pneumoniae (Kp -MH258) as a target function, we engineered a functional 15-member synthetic microbiome-SynCom15-through a statistical approach agnostic to strain phenotype, mechanism of action, bacterial interactions, or composition of natural microbiomes. Our approach involved designing, building, and testing 96 metagenomically diverse consortia, learning a generative model using community strain presence/absence as input, and distilling model constraints through statistical inference. SynCom15 cleared Kp -MH258 across in vitro , ex vivo , and in vivo environments, matching the efficacy of a fecal microbiome transplant in a clinically relevant murine model of infection. The mechanism of suppression by SynCom15 was related to fatty acid production coupled with environmental acidification. SynCom15 also suppressed other pathogens- Clostridioides difficile , Escherichia coli , and other K. pneumoniae strains-but through different mechanisms. Sensitivity analysis revealed models trained on strain presence/absence captured the statistical structure of pathogen suppression, illustrating that community representation was key to our approach succeeding. Our framework, 'Constraint Distillation', could be a general and efficient strategy for building emergent complex systems, offering a path towards synthetic ecology more broadly.}, } @article {pmid41500422, year = {2026}, author = {Jin, J and Li, F and Hu, Y and Zhang, Z and Zhang, R and Xing, F}, title = {Gut microbiota dysbiosis transmits deoxynivalenol toxicity and triggers liver inflammation.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2026.01.011}, pmid = {41500422}, issn = {2090-1224}, abstract = {INTRODUCTION: Deoxynivalenol (DON), a mycotoxin produced by Fusarium species, is known to compromise gut barrier integrity and induce systemic inflammation.

OBJECTIVES: This study demonstrates that intestinal microbiota play a central role in DON-induced liver inflammation.

METHODS: Through oral exposure and fecal microbiota transplantation (FMT) experiments in mice, we observed that DON disrupts intestinal structure, alters microbial composition, and activates liver inflammation via the TLR4/MyD88/NF-κB pathway.

RESULTS: Notably, liver inflammation was replicated in pseudo-germ-free mice colonized with microbiota from DON-exposed donors, even in the absence of direct DON exposure. Microbial analysis identified Alloprevotella, a mucin-degrading genus associated with increased intestinal permeability, and Pseudomonas, a pathogenic genus enriched in the liver, as key candidate microbial drivers of this effect.

CONCLUSION: These findings underscore that dysbiosis, especially involving specific bacterial genera, can independently trigger liver inflammation, highlighting a microbiota-mediated pathogenic mechanism in mycotoxin toxicity.}, } @article {pmid41498910, year = {2026}, author = {Li, Y and Shen, X and Wang, D and Sun, K}, title = {The gut microbiome in colorectal cancer: mechanisms of carcinogenesis and emerging microbiota-targeted therapies.}, journal = {Discover oncology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12672-025-04367-1}, pmid = {41498910}, issn = {2730-6011}, } @article {pmid41497693, year = {2025}, author = {Rusman, RD and Akil, F and Parewangi, ML and Daud, NA and Bachtiar, R and Kusuma, SH and Rifai, A}, title = {Gut microbiota and metabolic-associated steatosis liver disease: Unveiling mechanisms and opportunities for therapeutic intervention.}, journal = {World journal of experimental medicine}, volume = {15}, number = {4}, pages = {107316}, pmid = {41497693}, issn = {2220-315X}, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a leading cause of chronic liver disease, closely linked with metabolic syndrome. Recent evidence spotlights the gut-liver axis as a major player in MASLD pathogenesis. Dysbiosis of gut microbiota alters the intestinal barrier and enhances endotoxemia, hepatic inflammation, insulin resistance and fibrosis. Microbial metabolites including short-chain fatty acids, bile acids and ethanol impact host metabolism and immunity, and their dysregulation contributes to disease progression. This review summarises the mechanistic associations between dysbiosis and MASLD involving altered microbial composition, leaky gut, toll-like receptor signalling and immune dysregulation. It also reviews microbially targeted therapeutic strategies, such as probiotics, prebiotics, synbiotics, faecal microbiota transplantation, diet changes, and postbiotic metabolites. Although these interventions may have clinical potential, the heterogeneity of outcomes highlights the interindividual nature of the microbiome and warrant personalized interventions. Developments in multi-omics and precision medicine provide possibilities to discover microbial biomarkers and customize therapeutic approach. Resolving methodological heterogeneity and providing a clear definition of MASLD-related dysbiosis are key for translating microbiome science into the clinic. In conclusion, modulation of gut microbiota is an emerging strategy for the adjunctive treatment of MASLD alongside lifestyle and pharmacologic therapies.}, } @article {pmid41496455, year = {2026}, author = {Ramesh, A and Subbarayan, R and Shrestha, R and Adtani, PN}, title = {Exploring Fecal Microbiota Transplantation: Potential Benefits, Associated Risks, and Challenges in Cancer Treatment.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {9}, number = {1}, pages = {e70455}, doi = {10.1002/cnr2.70455}, pmid = {41496455}, issn = {2573-8348}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Neoplasms/therapy/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Tumor Microenvironment/immunology ; Immunotherapy/methods ; Animals ; Risk Assessment ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has emerged as a groundbreaking strategy for modulating the gut microbiome and improving cancer treatment outcomes. This review synthesizes the current evidence on the role of FMT in oncology, focusing on its potential to enhance the efficacy of immunotherapy, restore microbiome homeostasis, and mitigate cancer-associated complications.

RECENT FINDINGS: Preclinical and clinical studies have demonstrated that FMT can reprogram the tumor microenvironment, augment immune checkpoint inhibitor responses, and reduce chemotherapy-induced toxicity. However, risks such as pathogen transmission, immune dysregulation, and unintended microbial shifts necessitate rigorous donor screening and a personalized approach. Challenges in standardization, regulatory frameworks, and mechanistic understanding further complicate their clinical translation. Emerging innovations, including precision microbial consortia, synthetic biology, and biomarker-driven strategies, have the potential to address these limitations.

CONCLUSION: While FMT holds transformative potential in cancer care, its integration into oncological practice requires robust clinical validation, long-term safety assessments, and interdisciplinary collaboration to harness its full therapeutic potential.}, } @article {pmid41496048, year = {2026}, author = {He, C and Zhou, F and Fang, X}, title = {Meta-analysis of the effectiveness of fecal microbiota transplantation in the treatment of metabolic-associated fatty liver disease: A systematic review based on liver inflammation indicators and fat content.}, journal = {Medicine}, volume = {105}, number = {1}, pages = {e46886}, pmid = {41496048}, issn = {1536-5964}, support = {jkws202318//Health and Sanitation Scientific Research Project of the Metallurgical Safety and Health Branch of the Chinese Society for Metals/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Alanine Transaminase/blood ; Aspartate Aminotransferases/blood ; Randomized Controlled Trials as Topic ; Body Mass Index ; Treatment Outcome ; *Fatty Liver/therapy ; Gastrointestinal Microbiome ; *Non-alcoholic Fatty Liver Disease/therapy ; Male ; Middle Aged ; Liver/pathology ; }, abstract = {BACKGROUND: Metabolic-associated fatty liver disease (MASLD) affects over 25% of the global population, progressing from hepatic steatosis to fibrosis. Current therapies show limited efficacy, and gut microbiota dysbiosis via the gut-liver axis highlights fecal microbiota transplantation (FMT) as a novel intervention.

METHODS: Following preferred reporting items for systematic reviews and meta-analyses guidelines, 8 randomized controlled trials were systematically selected from PubMed, Cochrane, Embase, and Web of Science (inception to September 2025). MASLD patients receiving FMT (any protocol) versus standard care were evaluated for alanine aminotransferase (ALT), aspartate aminotransferase (AST), proton density fat fraction, and body mass index (BMI). Risk of bias was assessed using Cochrane ROB 1.0.

RESULTS: FMT significantly reduced ALT (mean difference [MD] = -6.81, 95% confidence interval [-10.29, -3.33], P = .0001) and AST (MD = -7.13, [-10.45, -3.80], P < .0001) versus standard care. Subgroup analysis revealed greater ALT improvement in patients aged <50 years (MD = -14.00, [-22.79, -5.20], P = .002). Proton density fat fraction decreased markedly (MD = -3.50, [-5.12, -1.87], P < .0001), while BMI showed no significant change (MD = -0.69, [-1.49, 0.11], P = .09).

CONCLUSION: FMT effectively improves hepatic inflammation and steatosis in MASLD, with age modulating ALT response. Lack of BMI improvement suggests localized liver effects rather than systemic metabolic impact, supporting FMT as a targeted adjunctive therapy.}, } @article {pmid41494302, year = {2025}, author = {Yi, J and Tang, Y and Chen, Y and Chen, L and Geng, D and Liu, L and Yu, J and Zou, L and Zeng, J and Lan, M and Gao, W and Gao, M}, title = {Kudzu root-derived carbon dots modulate gut microbiota and metabolites for pan-organ targeted macrophage polarization in synergistic diabetes therapy.}, journal = {Biomaterials}, volume = {329}, number = {}, pages = {123967}, doi = {10.1016/j.biomaterials.2025.123967}, pmid = {41494302}, issn = {1878-5905}, abstract = {Type 2 diabetes is a systemic disorder characterized by metabolic dysfunction and chronic inflammation, yet strategies that address both aspects remain limited. Here, we present kudzu root-derived carbon dots (KRCDs) as a natural nanomaterial that reprograms the gut microbiota-metabolite-immune axis to restore systemic homeostasis. KRCDs exhibit nanoscale crystallinity, abundant O/N functional groups, and strong antioxidant activity. In high-fat diet/streptozotocin-induced diabetic mice, KRCDs significantly lowered fasting glucose, improved glucose tolerance and insulin sensitivity, corrected lipid profiles, and reduced hepatic steatosis without detectable toxicity. Multi-omics analyses revealed increased microbial diversity, enrichment of beneficial genera such as Anaerostipes, and remodeling of fecal metabolites with a marked rise in indole-3-carboxaldehyde (I3A). This metabolite correlated with enhanced M2-like macrophage polarization across adipose tissue, intestine, kidney, liver, and pancreas, as confirmed by flow cytometry and immunofluorescence. Fecal microbiota transplantation from KRCDs-treated donors reproduced both the metabolic improvements and the organ-wide M2 polarization, confirming a microbiota-dependent mechanism. By establishing a gut microbiota-metabolite-macrophage polarization pathway, KRCDs act as safe, plant-based nanoplatforms that simultaneously correct metabolic and immune imbalance, offering a promising strategy for multi-target intervention in diabetes.}, } @article {pmid41494100, year = {2026}, author = {Wang, D and Dai, S and Li, D and Du, P and Zhao, Y and Chen, Y and Ye, Y and Zhou, M and Ren, W and Liu, X and Zhao, B}, title = {Bovine Milk-Derived Extracellular Vesicles Attenuate Liver Injury by Modulating the Gut-Liver Axis via Faecalibaculum-Mediated SCFA Production.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c12208}, pmid = {41494100}, issn = {1520-5118}, abstract = {Chronic liver injury represents a core pathological substrate in a spectrum of hepatic disorders, wherein gut-liver axis homeostasis critically drives progression. Although bovine milk extracellular vesicles (mEVs) positively regulate intestinal homeostasis, the mechanisms underlying their gut microbiota-linked hepatoprotection remain unclear. Herein, we demonstrated that mEVs (0.6 mg/kg/d) effectively alleviated carbon tetrachloride (CCl4, 1 mg/kg)-induced liver injury, as evidenced by reduced hepatic inflammation and fibrosis. Concurrently, mEVs also markedly attenuated colonic barrier disruption and inflammation concomitant with liver injury. Gut microbiota analysis revealed that mEVs notably enriched the relative abundances of Faecalibaculum and Lactobacillus, which correlated positively with mEV-enhanced colonic short-chain fatty acid (SCFA)/free fatty acid receptor (FFAR) signaling. Furthermore, a causal link between the mEV-reshaped gut microbiota and the resulting hepatoprotection was further established via fecal microbiota transplantation (FMT). In summary, these findings revealed that mEVs attenuated liver injury in a gut microbiota-dependent manner, offering valuable insights into microbiota-targeted and mEV-based therapeutic strategies for hepatic disorders.}, } @article {pmid41493848, year = {2026}, author = {Kawaguchi, Y and Terui, K and Fumita, T and Shibata, R and Yoshizawa, H and Ogasawara, S and Kondo, T and Ozawa, Y and Inaba, Y and Hishiki, T}, title = {Cholestasis-reducing effects of bezafibrate on survivors of biliary atresia with native livers: A prospective phase II trial.}, journal = {Hepatology communications}, volume = {10}, number = {1}, pages = {}, pmid = {41493848}, issn = {2471-254X}, mesh = {Humans ; Male ; Female ; *Bezafibrate/therapeutic use/administration & dosage ; *Biliary Atresia/complications/surgery ; *Cholestasis/drug therapy/etiology ; Prospective Studies ; Adult ; *Hypolipidemic Agents/therapeutic use/administration & dosage ; Young Adult ; Adolescent ; Alkaline Phosphatase/blood ; Liver ; Treatment Outcome ; Survivors ; gamma-Glutamyltransferase/blood ; }, abstract = {BACKGROUND: Long-term survivors of biliary atresia (BA) require liver transplantation owing to cholestasis-associated complications. Bezafibrate (BZF), an antihyperlipidemic agent, can improve cholestasis-induced liver damage. Herein, we evaluated the cholestasis-reducing effect of BZF on survivors of BA with native livers, a condition that has not been previously assessed in any study.

METHODS: In this single-center, single-arm, open-label, uncontrolled, prospective phase II trial, patients were enrolled from a central registry system at the Chiba University Data Center. Postoperative patients (n=10) aged older than 18 years (median age, 29 y) with BA and increased serum ALP levels were enrolled between July 2021 and March 2022. Patients with high total bilirubin or alanine aminotransferase levels, recent changes in BA medication, cholangitis within 3 months, renal dysfunction, or liver transplantation were excluded. Participants were administered 400 mg BZF orally in 2 daily doses for 12 weeks and subsequently underwent a 12-week observation. Other drugs were continued. The primary endpoint was the change in ALP levels after 12 weeks of oral BZF administration. The secondary and exploratory endpoints were changes in gamma-glutamyl transpeptidase and triglyceride levels, fecal microbiota, and bile acids.

RESULTS: The mean change in the ALP level was -67 U/L (±20 U/L; p=0.0042). Changes in ALP and gamma-glutamyl transpeptidase levels differed between week 0 and week 6. Adverse events occurred in 5 patients. BZF administration increased the number of Fusicatenibacter without affecting microbiome diversity or bacterial phylum abundance while decreasing lithocholic acid levels and increasing chenodeoxycholic acid levels.

CONCLUSIONS: BZF decreased cholestasis markers in survivors of BA with native livers, indicating its potential as an alternative to delayed liver transplantation for this population.}, } @article {pmid41492974, year = {2026}, author = {Qiu, Y and Lyu, X and Zhang, D and Xu, H and He, X and Chen, J and Liu, H and Liu, Y and Xie, L}, title = {Gut Microbiota in Pulmonary Arterial Hypertension: Murine Models and Human Microbial Signatures, Pathogenic Mechanisms, and Emerging Therapeutic Avenues.}, journal = {Comprehensive Physiology}, volume = {16}, number = {1}, pages = {e70094}, doi = {10.1002/cph4.70094}, pmid = {41492974}, issn = {2040-4603}, support = {U21A20333//National Natural Science Foundation of China/ ; 2023YFC2705701//National Key Research and Development Program of China/ ; XZ202501ZY0116//Science and Technology Projects of Xizang Autonomous Region/ ; XZ202401ZY0013//Science and Technology Projects of Xizang Autonomous Region/ ; 2023NSFSC0530//Sichuan Province Science and Technology Support Program/ ; }, mesh = {Humans ; Animals ; *Gastrointestinal Microbiome/physiology ; *Pulmonary Arterial Hypertension/microbiology/therapy/metabolism ; Mice ; Disease Models, Animal ; Fecal Microbiota Transplantation ; }, abstract = {Pulmonary arterial hypertension (PAH) is a chronic, severe cardiopulmonary disease characterized by the progressive increase in pulmonary vascular resistance (PVR) because of the proliferation and fibrosis of the pulmonary arterioles. Although the disease originates in the pulmonary vasculature, it ultimately leads to right heart failure and death. PAH is associated with high mortality rates and poor prognosis, with no therapies currently available to reverse pulmonary vascular remodeling, imposing substantial socioeconomic burdens. Growing interest in the gut-lung axis has highlighted the role of gut microbiota and their metabolites in the occurrence and development of PAH. Evidence showed that gut dysbiosis and metabolite imbalances, involving reduced short-chain fatty acids (SCFAs), increased trimethylamine-N-oxide (TMAO), and dysregulated tryptophan metabolism, contributed to pulmonary vascular remodeling. This review systematically compares gut microbiota and metabolites across PAH murine models (including chronic hypoxia, SU5416/hypoxia [SuHx], monocrotaline [MCT], and non-classical models) and patients (adults and children). The analysis aims to identify disease-specific microbial and metabolic signatures. It is also discussed how the microbiota and their metabolites may influence inflammation around the pulmonary vasculature. Furthermore, the potential of probiotic therapy, fecal microbiota transplantation (FMT), and mesenchymal stem cells (MSCs) therapies as novel treatment strategies for PAH is discussed.}, } @article {pmid41492376, year = {2026}, author = {Huang, L and Zheng, Y and Liu, Q and Feng, Y and Ma, Z and Zhao, X and Wei, X and Yu, X and Lv, X and Lv, J and Li, L and Liu, H and Ze, X and Zhang, M}, title = {Milk fat globule membrane ameliorates depressive-like behaviors in chronic unpredictable mild stress rats by modulating the microbiota-gut-brain axis.}, journal = {Bioscience of microbiota, food and health}, volume = {45}, number = {1}, pages = {66-78}, pmid = {41492376}, issn = {2186-6953}, abstract = {Depression is one of the common psychiatric disorders, and it has been reported that the imbalance in the microbiota-gut-brain (MGB) axis contributes to the pathogenesis of depression. Milk fat globule membrane (MFGM) can impact the gut-brain axis by regulating the intestinal flora and metabolite production. The aim of this study was to investigate whether MFGM could ameliorate depressive-like behaviors induced by chronic unpredictable mild stress (CUMS) and further elucidate the potential mechanism through a fecal microbiota transplantation (FMT) experiment. Male Sprague-Dawley rats were provided with an MFGM diet for 5 weeks after the induction with CUMS. Depressive-like behaviors were assessed, and the levels of neurotransmitters, neuroendocrine hormones, microbiota, short-chain fatty acids (SCFAs), and tight junction proteins, including occludin and zonula occludens-1 (ZO-1), were measured. It was revealed that MFGM could alleviate the depressive-like behaviors in CUMS rats. MFGM up-regulated the expression of occludin and ZO-1 and ameliorated intestine pathological changes in CUMS rats. Moreover, MFGM increased the levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine and decreased the levels of neuroendocrine hormones in CUMS rats. Furthermore, it was confirmed that the concentrations of SCFAs, DA, 5-HT, and tight junction proteins significantly increased in the recipient rats that were inoculated with the fecal microbiota from the rats after MFGM treatment. These findings demonstrated that MFGM could alleviate depressive-like behaviors in CUMS rats and was possibly associated with modulation of the gut microbiota and up-regulation of SCFAs and monoamine neurotransmitters.}, } @article {pmid41484843, year = {2026}, author = {Sadeghi, R and Abdol Homayuni, MR and Fateh, A and Ebrahimzadeh, N and Riazi-Esfahani, H and Yazdani Moghadam, M and Nikfar, R and Pakzamir, P and Siadat, SD}, title = {The gut-eye axis: microbiota and their role in diabetic retinopathy: a systematic review and meta-analysis.}, journal = {BMC ophthalmology}, volume = {26}, number = {1}, pages = {7}, pmid = {41484843}, issn = {1471-2415}, abstract = {PURPOSE: To systematically evaluate the relationship between gut microbiota dysbiosis and diabetic retinopathy (DR), exploring microbial diversity, composition, metabolic function, and causal associations via the gut–eye axis.

METHOD: A systematic review and meta-analysis were conducted following PRISMA guidelines. Searches across PubMed, Scopus, Embase, and Web of Science identified studies examining gut microbiota in diabetic patients with and without DR. Eighteen eligible studies—including observational, cohort, and Mendelian randomization (MR) designs—were critically appraised. Meta-analyses pooled standardized mean differences (SMDs) for alpha diversity indices (Chao1, ACE, OTUs, Shannon, Simpson) between DR, diabetes without retinopathy (DM), and healthy controls (HC), using random-effects models with heterogeneity assessments.

RESULTS: Gut microbiota in DR patients showed inconsistent alpha diversity changes but consistent beta diversity shifts, indicating distinct microbial community structures. Meta-analysis across eight studies (268 DR, 269 DM, 99 HC) revealed no significant differences in alpha diversity between DR and DM (e.g., Shannon SMD 0.01, 95% CI -0.44 to 0.45; I²=74%) or DR and HC (e.g., Shannon SMD 0.02, 95% CI -1.30 to 1.33; I²=71%), with moderate to high heterogeneity. DR cohorts exhibited altered Firmicutes/Bacteroidetes ratios, reduced short-chain fatty acid (SCFA)-producing genera (e.g., Faecalibacterium, Roseburia), and increased pro-inflammatory taxa (e.g., Escherichia-Shigella, Pseudomonas). Functional analyses revealed dysregulated amino acid and lipid metabolism, with specific taxa-metabolite correlations.

CONCLUSION: This review substantiates gut microbiota dysbiosis as a potential contributor to DR pathogenesis via the gut–eye axis. While no robust changes in alpha diversity were found, compositional and functional alterations highlight specific microbial taxa and pathways as potential therapeutic targets. Microbiota modulation through diet, probiotics, or fecal transplantation may offer novel strategies to complement conventional DR management. However, high heterogeneity, demographic limitations, and methodological variations warrant further longitudinal and ethnically diverse studies to validate these findings and guide clinical translation.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12886-025-04599-3.}, } @article {pmid41491927, year = {2026}, author = {Yao, T and Xiong, Y and Hu, Q and Chen, Y and Li, D and Yan, J and Yang, J and Wang, Y and Cao, H and Zhang, F and Zhuang, R and Sun, J}, title = {Maternal gestational diabetes mellitus leads to adverse growth patterns and disease risk in offspring in vivo: evidence from cross-generational effects on gut microbiota.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-025-04591-3}, pmid = {41491927}, issn = {1471-2180}, support = {2023YFF1104301//National Key R&D Program of China/ ; BK20241756//Basic Research Program of Jiangsu/ ; HB2023063//Medical Key Discipline Program of Wuxi Health Commission/ ; KX-25-A14; KX-25-C108//The Soft Science Project of Wuxi Science and Technology Association/ ; }, } @article {pmid41490838, year = {2026}, author = {Gao, W and Yan, S and Zhang, L and Chen, L and Che, J and Huang, W and Chen, Y and Liu, A and Zhu, Y and Yang, Y and Peng, Z and Tan, C and Schnabl, B and Hou, X and Yang, L and Chu, H}, title = {Escherichia coli expressing the kpsM gene exacerbates drug-induced liver injury through up-regulating α1,2-fucosyltransferase and disturbing the host taurine metabolism-from animal models and clinical studies.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.12.012}, pmid = {41490838}, issn = {2090-1224}, abstract = {BACKGROUND AND AIMS: Drug-induced liver injury (DILI) is a leading cause of acute liver failure. Patients with DILI have disorders of the gut microbiota, yet little is known about the influence of gut microbes on this disease. Herein, we investigated the alterations of gut microbiota in DILI patients, and elucidated the mechanism by which Escherichia coli expressing kpsM gene (kpsM[+]E. coli) exacerbates DILI, in order to provide targets for intervention of related signaling pathways to improve DILI.

METHODS: Full-length 16S sequencing was performed on fecal samples from a prospective cohort of patients with DILI (n = 42). Quantitative PCR was employed for analysis of E. coli and its kpsM gene in human feces. The DILI model was established by intraperitoneal injection of acetaminophen (300 mg/kg) into mice (n = 5-12). Two hours later, kpsM[+] or kpsM knockout E. coli strains were gavaged to determine their roles during DILI. Intestinal epithelial Fut2 gene knockout mice (Fut2[ΔIEC]) and hepatic metabolome were used to assess the pathogenic mechanisms of the kpsM[+]E. coli. Plasma metabolome of DILI patients was further validated the discoveries in mice.

RESULTS: The percentage of subjects carrying kpsM were 14.7 %, 40.0 %, 76.5 % in healthy controls, patients with mild DILI, and patients with moderate-to-severe DILI, respectively. Mice transplanted with kpsM[+]E. coli exhibited more severe DILI, primarily achieved through impaired gut barrier function and enhanced expression of intestinal Fut2. Fut2[ΔIEC] mice alleviated the aggravation of DILI caused by E. coli via up-regulating the hepatic levels of taurine and tauroursodeoxycholic acid. In addition, the level of plasma taurine was lower in patients with moderate-to-severe DILI than in those with mild DILI.

CONCLUSIONS: The kpsM[+] E. coli was associated with the severity of DILI in human. This strain can exacerbate DILI in mice through up-regulating intestinal Fut2 expression and disrupting taurine metabolism.}, } @article {pmid41490552, year = {2026}, author = {Ren, L and Chen, P and Xu, S and Liang, J and Wang, Y and Lin, C and Yu, Y and Li, Y}, title = {Gut microbiota-based bile acid metabolism mediates the intestinal barrier protection of Phellodendri chinensis Cortex polysaccharide against ulcerative colitis.}, journal = {Journal of ethnopharmacology}, volume = {360}, number = {}, pages = {121143}, doi = {10.1016/j.jep.2025.121143}, pmid = {41490552}, issn = {1872-7573}, abstract = {Ulcerative colitis (UC), a form of inflammatory bowel disease (IBD), is marked by the occurrence of colonic mucosal damage and immune system dysfunction. A notable challenge in the management of UC is the paucity of long-term effective and safe medications. Phellodendri Chinensis Cortex polysaccharide (PCP), one of the main bioactive compounds in Phellodendri Chinensis Cortex, exerts anti-inflammatory and immunomodulatory effects. However, the effects and mechanisms of PCP on mice with ulcerative colitis remain unclear.

AIM OF THE STUDY: This study explores that PCP attenuates colitis mice via regulation of gut microbiota and bile acid metabolism.

MATERIALS AND METHODS: Monosaccharide composition, molecular weight analysis, infrared spectroscopy, scanning electronic microscopy was used to analyze the chemical characterization of PCP. Mice were administrated by 3 % DSS for establishment of ulcerative colitis model and treated with PCP for 7 days. 16S rRNA gene sequencing and fecal microbiota transplantation (FMT) experiments was performed to evaluate the effect of gut microbiota in PCP-treated colitis mice. Targeted metabolomics analysis of bile acids (BAs) and in vivo inhibition of FXR were performed to analyze the key b BAs and key mechanism of PCP in colitis mice.

RESULTS: PCP alleviated colitis-associated symptoms, repaired, injured intestinal barrier and promoted FXR activation in DSS-induced colitis mice. 16S rRNA gene sequencing found that PCP increased beneficial microbiota such as Bifidobacterium and Lactobacillus, while reducing pathogenic microbiota such as Bacteroides and Romboutsia in colitis mice. FMT experiment confirmed that PCP improved colitis mice and enhanced intestinal barrier integrity through gut microbiota. Simultaneously, PCP altered BA profiles, notably reducing the ratios of primary to secondary BAs and conjugated to unconjugated BAs, with a particularly pronounced effect on the TαMCA/αMCA ratio. Finally, FXR antagonist Gly-β-MCA reversed the protect effect of PCP against colitis.

CONCLUSION: Taken together, our study demonstrates that PCP alleviates DSS-induced colitis symptoms and restores intestinal barrier by gut microbiota-BA metabolism-FXR axis.}, } @article {pmid41490547, year = {2026}, author = {Wang, Y and He, Y and Xie, J and Li, J and Guo, J}, title = {E. coli Nissle 1917 Modulates the RNF150/ELAVL1 Ubiquitination Pathway to Ameliorate Obesity-Driven Insulin Resistance in High-Fat Diet-Fed Mice.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {}, number = {}, pages = {101719}, doi = {10.1016/j.jcmgh.2025.101719}, pmid = {41490547}, issn = {2352-345X}, abstract = {BACKGROUND & AIMS: Obesity, a global epidemic, fuels metabolic dysfunction through complex gut microbiota‒immune system crosstalk. The probiotic Escherichia coli Nissle 1917 (EcN) holds promise for alleviating obesity-related complications, yet its mechanistic underpinnings remain unclear. This study explored the therapeutic potential of EcN, focusing on its ability to regulate the RNF150/ELAVL1 axis in macrophages to counter high-fat diet (HFD)-induced obesity and insulin resistance.

METHODS: We employed a 12-week dietary intervention in male C57BL/6J mice and administered EcN. Fecal microbiota transplantation (FMT) and myeloid-specific RNF150 and ELAVL1 knockout models were used to establish mechanistic causality. The gut microbiota composition was analyzed via 16S rRNA sequencing, while metabolic parameters, adipose tissue inflammation, and RNF150/ELAVL1 interactions were assessed via glucose/insulin tolerance tests, immunohistochemistry, Western blotting, coimmunoprecipitation, and ubiquitination assays. RNF150 expression was also evaluated in adipose tissue and peripheral blood mononuclear cells from overweight and normal-weight human subjects.

RESULTS: EcN treatment significantly reduced HFD-induced weight gain, adipose accumulation, and insulin resistance while restoring the gut microbiota balance (decreased the Firmicutes/Bacteroidetes ratio and increased Muribaculaceae). FMT from EcN-treated mice recapitulated these benefits. EcN attenuated inflammation across the liver, adipose, and colon, reducing proinflammatory cytokine levels and macrophage infiltration. RNF150 was upregulated in HFD-fed mice and human overweight samples but downregulated by EcN. Myeloid RNF150 deletion mirrored the effects of EcN, promoting anti-inflammatory M2 macrophages and insulin sensitivity. RNF150 mediated ELAVL1 ubiquitination and degradation, while ELAVL1 stabilization enhanced anti-inflammatory responses. Myeloid ELAVL1 deletion worsened metabolic outcomes.

CONCLUSION: EcN ameliorates obesity and insulin resistance by modulating the gut-adipose axis via RNF150/ELAVL1 in macrophages, suggesting novel therapeutic targets for metabolic disorders.}, } @article {pmid41490238, year = {2025}, author = {Ni, S and Chen, K and Wang, H and Chen, S and Qiu, Y and Wang, T and Mo, F and Wang, S and Li, B and Bai, Y and Zhao, J and Zhai, X and Li, Z}, title = {A new paradigm of bidirectional regulation of the gut-spinal cord axis.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-01016}, pmid = {41490238}, issn = {1673-5374}, abstract = {The bidirectional interactions of spinal cord injury, multiple sclerosis, and amyotrophic lateral sclerosis with the gut operate through a distinct gut-spinal cord axis, rather than being fully explained by the conventional gut-brain axis. The spinal cord, with its unique anatomical and physiological features, serves as a central hub of communication. The gut and spinal cord communicate through various pathways, including the immune system and the autonomic and enteric nervous systems. This review summarizes existing clinical and basic research on the relationship between gut homeostasis and spinal cord diseases. First, we present findings from epidemiological studies showing that patients with spinal cord disorders often exhibit altered gut function, which may be influenced by antibiotic exposure and environmental factors. Second, we review the key physiological and anatomical structures of the gut-spinal cord axis, including the intestinal barrier, gut microbiota, and enteric nervous system, all of which are involved in maintaining gut health, as well as sensory neurons, motor neurons, and interneurons in spinal nerve regulation. Third, we describe the roles of the three axes (microbial, immune, and neural) in bidirectional regulation and their pathological mechanisms. Moreover, vicious cycles involving these axes can exacerbate spinal cord disorders. Fourth, we outline potential biomarkers in the gut-spinal cord axis, such as uridine, hypoxanthine, and 5-methoxytryptophan. Fifth, we propose several treatment strategies with potential clinical applications, including fecal microbiota transplantation and the use of probiotics and prebiotics. Finally, this review emphasizes the gut-spinal cord axis as a promising therapeutic target, highlighting the need for multi-omics integration, longitudinal cohort studies, and individualized interventions to resolve existing debates. Overall, the recognition of the gut-spinal cord axis provides a conceptual shift that extends beyond the gut-brain framework.}, } @article {pmid41488894, year = {2025}, author = {Lin, B and Zhu, Z and Yang, X and Li, Z and Zhou, H and Luo, M and Guan, J and Zou, Y and Chen, H and Zhuang, Z and Meng, S and Li, W and Yang, Q and Dai, D}, title = {Protocol for the efficacy and safety of fecal microbiota transplantation in children with autism spectrum disorder: a prospective single-center, single-arm interventional study.}, journal = {Frontiers in pediatrics}, volume = {13}, number = {}, pages = {1660773}, pmid = {41488894}, issn = {2296-2360}, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition affecting 0.7% of children globally, with 90% experiencing comorbid gastrointestinal (GI) symptoms. Fecal microbiota transplantation (FMT) may modulate ASD symptoms via the microbiota-gut-brain axis (MGBA).

METHODS: This open-label single-arm trial enrolls 30 children (2-12 years) with moderate-to-severe ASD, defined as a Childhood Autism Rating Scale (CARS) score of ≥36. Participants receive 3 nasojejunal FMTs (5 mL/kg) over 5 days. The primary outcomes are GI symptom improvement, assessed using the Gastrointestinal Symptom Rating Scale (GSRS), and ASD severity, assessed using the CARS. Secondary outcomes include social responsiveness (Social Responsiveness Scale, SRS), aberrant behaviors (Aberrant Behavior Checklist, ABC), and gut microbiota changes assessed by metagenomic next-generation sequencing (mNGS).

ETHICS AND DISSEMINATION: Ethical approval obtained from Shenzhen Children's Hospital Ethics Committee. Results will be disseminated via peer-reviewed publications and conference presentations.Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=229136, identifier ChiCTR2400083998. Registered on 2024-05-08. Registered title: "Efficacy and safety of fecal microbiota transplantation in treatment of autism spectrum disorder: a prospective single-center intervention study".}, } @article {pmid41488304, year = {2025}, author = {Duan, Y and Li, X and Chai, Y and Chen, H and Hou, H}, title = {Adlercreutzia-modulated polyunsaturated fatty acid metabolism underlies nicotine's anti-obesity effects.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1682370}, pmid = {41488304}, issn = {1664-302X}, abstract = {BACKGROUND: The regulatory effects of nicotine on energy balance through central and peripheral mechanisms have been reported. However, its impact on obesity and gut microbiota at safe doses remains unclear.

RESULTS: In this study, it was found that chronic oral nicotine administration daily at relative low dose (0.5 mg/kg) significantly alleviated high-fat diet (HFD)-induced obesity phenotypes in mice, including body weight gain, fat deposits, hepatic steatosis, inflammation and metabolic dysfunction. Gut microbiota depletion and fecal microbiota transplantation (FMT) confirmed that these beneficial effects were microbiota-dependent. Metagenomic sequencing confirmed that nicotine administration reshaped gut microbiota composition, and specifically enriched the commensal genus Adlercreutzia, whose increased abundance correlated with improved biochemical indicators related to obesity. Furthermore, transplantation of Adlercreutzia reproduced anti-obesogenic effects, suggesting it was a key factor for nicotine reducing HFD-induced obesity. Untargeted metabolomics analysis combined association analysis further demonstrated that nicotine modulated host metabolic profiles via gut microbiota-metabolite axis, particularly enhancing Adlercreutzia-linked lipid metabolites involved in polyunsaturated fatty acid (PUFA) metabolism.

CONCLUSION: Collectively, our study elucidates the critical involvement of gut microbiota in nicotine-induced obesity amelioration, uncovers a novel Adlercreutzia-PUFA metabolic axis mediating nicotine's anti-obesity effects, and highlight Adlercreutzia potentiation as a promising microbiota-directed invention strategy for obesity and metabolic syndrome.}, } @article {pmid41488302, year = {2025}, author = {Liu, S}, title = {Mechanisms of gut microbiota in host fat deposition: metabolites, signaling pathways, and translational applications.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1675155}, pmid = {41488302}, issn = {1664-302X}, abstract = {Obesity and metabolic diseases are global health challenges, with gut microbiota playing a critical role in host fat deposition through symbiotic interactions. In recent years, the gut microbiota, as an important factor regulating fat deposition, has received widespread attention. Numerous studies have confirmed that gut microbes influence host fat accumulation by regulating energy metabolism, inflammatory response, and gut barrier function. In this review, we summarized the key roles of gut microbial metabolites, including short-chain fatty acids (SCFAs), bile acids, tryptophan metabolites, lipopolysaccharides (LPS), branched-chain amino acids (BCAAs), and trimethylamine N-oxide (TMAO) in host epigenetic regulation and lipid metabolism, and explored their regulatory mechanisms through mediated signaling pathways, including Wnt/β-catenin signaling pathway, transforming growth factor beta/SMAD3 pathway (TGF-β/SMAD3), peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). In terms of translational applications, we described the research progress and application potentials of intervention strategies, such as probiotics, prebiotics, synbiotics, postbiotics, and fecal transplantation in obesity control and animal production. Finally, we proposed the current bottlenecks and translational challenges in obesity control by precision nutrition and microecological intervention, and look forward to future directions. This review provides a theoretical basis for the in-depth understanding of the interactions between gut microbiota and host metabolism, and serves as a reference for the prevention and control of metabolic diseases by developing nutritional intervention strategies for animals.}, } @article {pmid41487047, year = {2026}, author = {Xie, W and Wang, X and Liu, Y and Cai, L and Song, B and Zhang, S and Shao, Y and Wang, W and Xue, X and Li, J and Cui, W and Jiang, Y and Wang, X and Tang, L}, title = {Gut Microbiota-Derived Ursodeoxycholic Acid Mediates the Resistance to Colonic Inflammation in Pigs.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c08687}, pmid = {41487047}, issn = {1520-5118}, abstract = {Microbes in the gut are crucial for host health, yet their role in disease resistance remains unclear. Using fecal microbiota transplantation from disease-resistant Min pigs to Duroc × Landrace × Yorkshire (DLY) pigs, combined with 16S rRNA sequencing and metabolomics, we investigated this relationship. The transferred microbiota alleviated lipopolysaccharide-induced intestinal inflammation and barrier damage in the DLY piglets. Key bacterial genera and bile acid metabolites have been identified, with in vitro evidence showing that the gut microbiome can convert bile acids to secondary forms, primarily ursodeoxycholic acid (UDCA). Subsequent mechanistic validation in a mouse model demonstrated that UDCA acts via the gut-liver axis on the farnesoid X receptor, inhibiting PI3K/AKT/NF-κB pathways and reducing inflammatory responses, thereby preserving tissue structure in the liver and colon. These findings establish a causal link between gut microbiota and disease resistance, indicating that targeting microbial bile acid metabolism may restore intestinal and hepatic health.}, } @article {pmid41486395, year = {2026}, author = {Hajjar, R and Mars, RAT and Kashyap, PC}, title = {Harnessing the microbiome for cancer therapy.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, pmid = {41486395}, issn = {1740-1534}, abstract = {The microbiome is increasingly recognized as a key player in cancer pathogenesis and treatment response, acting through both local and systemic mechanisms. Microbial communities and their metabolites can directly influence drug metabolism, shape the immune landscape, and alter transcriptional and epigenetic programmes in the gut, systemically and in the tumour microenvironment. Emerging data support the potential of microbiome-targeted interventions (such as faecal microbiota transplantation, diet, prebiotics and probiotics) as adjuncts to conventional cancer therapies, with the goal of enhancing efficacy and reducing toxicity. This Review highlights the promise of the microbiome as a prognostic and predictive biomarker, a modifiable factor in cancer care and prevention, and a therapeutic target. We also discuss major knowledge gaps, limitations in current study designs, and the need for mechanism-guided, personalized strategies to advance clinical translation.}, } @article {pmid40662627, year = {2026}, author = {Schmidt, AC and Seyferth, A and Hughes, M and Hughes, WB}, title = {Diverting Ostomy Practices in Burn Surgeons Treating Full-Thickness Perianal Injuries.}, journal = {Journal of burn care & research : official publication of the American Burn Association}, volume = {47}, number = {1}, pages = {231-235}, doi = {10.1093/jbcr/iraf141}, pmid = {40662627}, issn = {1559-0488}, mesh = {Humans ; *Burns/surgery ; *Anal Canal/injuries/surgery ; *Ostomy/methods ; Skin Transplantation ; Wound Healing ; Male ; *Practice Patterns, Physicians'/statistics & numerical data ; Surveys and Questionnaires ; Female ; }, abstract = {Burns to the perianal region pose specific challenges in management due to the complex structure of the surrounding tissue, bacterial contamination, and repetitive stress. Fecal diversion via diverting ostomy may be elected in these injuries because of its potential to enhance wound healing and skin graft adherence; however, its use introduces alternative risks such as prolonged ileus, fistula, leakage, and failure of reversal. This study aimed to determine the perspectives of burn surgeons regarding the use of diverting ostomy for perianal burn injuries. We conducted a survey of 12 physicians who are burn center directors in the Northeast Region of the American Burn Association regarding their practices for patients with full-thickness perianal burn injuries requiring a skin graft. Response rate was 11/12 (92%). Six individuals (54.5%) reported "Never (0%)" to performing a diverting ostomy in this context; the remaining 5 individuals responded "Rarely (<10%)." Reasons stated for performing a diverting ostomy in the "Rarely" group included cases where the patient suffered an intra-anal or anorectal injury. These results were summarized with a relevant review of the literature and experience in our clinical practice. Our findings indicate that diverting ostomy is a relatively uncommon practice for burn surgeons treating full-thickness buttocks injuries. With appropriate wound care and critical care management, good outcomes can be obtained without the need for diverting ostomy. Non-surgical alternatives to fecal diversion are commonly used by burn specialists and should be considered in perianal burn injuries.}, } @article {pmid41486262, year = {2026}, author = {Wu, J and Xiu, M and Wang, X and Zhang, P and Qin, Y and Li, J and Jiang, X and Duan, Y and Liu, Y and He, J}, title = {Dunhuang Gancao Fuling Xingren decoction and its components alleviate CPT-11 induced intestinal mucositis by regulating gut microbiota related innate immunity and inflammatory response in Drosophila and mice.}, journal = {Chinese medicine}, volume = {21}, number = {1}, pages = {4}, pmid = {41486262}, issn = {1749-8546}, support = {DHYX24-15//Foundation from Key Laboratory of Dunhuang Medicine/ ; 2024-QN-35//Lanzhou Youth Science and Technology Talent Innovation Project/ ; 25JRRA1177//Natural Science Foundation of Gansu Province/ ; 25JRRA303//Gansu Natural Science Foundation/ ; }, abstract = {BACKGROUND: Dunhuang Gancao Fuling Xingren decoction (GFXD) is a traditional formulation derived from the Dunhuang Ancient Medical Prescriptions, has been historically utilized for its immunomodulatory and anti-inflammatory properties. However, the protective effect against irinotecan (CPT-11)-induced intestinal mucositis (CIM) remains poorly elucidated.

PURPOSE: To investigate the therapeutic efficacy of GFXD in alleviating CIM and elucidate its underlying mechanism and components using Drosophila melanogaster and C57BL/6 J mouse models.

METHODS: The therapeutic efficacy of GFXD was assessed in both Drosophila and mouse models by phenotype assay, hematoxylin and eosin (H&E) staining, and Alcian blue-periodic acid schiff (AB-PAS) staining. Transcriptomic profiling combined with 16S rRNA sequencing were employed to identify potential mechanisms of GFXD regulating CPT-11-induced mucositis. Cytokine levels were measured using ELISA, while the expression levels of key signaling pathways, including Toll-Imd and JAK-STAT pathways were analyzed via qRT-PCR, immunofluorescence, fecal microbiota transplantation (FMT) experiment, and antibiotic treatment. Furthermore, functional components of GFXD were characterized via liquid chromatography-mass spectrometry (LC-MS), and their efficacy was validated in CPT-11-treated Drosophila.

RESULTS: GFXD significantly mitigated CPT-11-induced systemic and intestinal damage in Drosophila, evidenced by improved survival rate, restored digestive function, elongated intestinal length, reduced acid-base imbalance, and enhanced epithelial and stem cell proliferation. In mice, GFXD alleviated mucositis symptoms, attenuated histopathological damage, and normalized inflammatory cytokine levels. Mechanistically, GFXD suppressed gut microbiota dysbiosis by enriching probiotics (Lactobacillus, Prevotella) and reducing pathogens (Bacteroides, Enterobacter, Enterococcus and Helicobacter). Transcriptomic and molecular analyses revealed that GFXD inhibited hyperactivation of Toll-Imd pathways and JAK-STAT signaling. Finally, three compounds of GFXD, formononetin, kaempferol, and ergosterol were found to alleviate CPT-11 induced intestinal injury.

CONCLUSIONS: GFXD alleviates CPT-11-induced intestinal mucositis by modulating gut microbiota composition, suppressing JAK-STAT and Toll-Imd pathways. Thus, this study demonstrates GFXD and its bioactive constituents as novel therapeutic agents to mitigate CIM.}, } @article {pmid41485840, year = {2026}, author = {Jurgiel, J and Gromowski, T and Król, J and Bomba-Opoń, D and Kościółek, T and Wielgoś, M}, title = {The impact of maternal microbial transfer on the infant gut microbiome after cesarean delivery: a systematic review.}, journal = {American journal of obstetrics and gynecology}, volume = {233}, number = {6S}, pages = {S541.e1-S541.e16}, doi = {10.1016/j.ajog.2025.09.001}, pmid = {41485840}, issn = {1097-6868}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Cesarean Section ; Female ; Infant, Newborn ; Pregnancy ; *Fecal Microbiota Transplantation ; Vagina/microbiology ; Bacteroides ; Lactobacillus ; Bifidobacterium ; }, abstract = {OBJECTIVE: To systematically review the results of maternal microbial transfer in shaping microbial diversity, improving neonatal development, and evaluating the microbial transfer procedure's adverse events.

DATA SOURCES: A comprehensive search was conducted on April 25, 2024, using PubMed/MEDLINE, Academic Search Ultimate, and ClinicalTrials.gov for studies published in English from 2000 to 2023. The following keywords were used: "vaginal seeding," "microbiota," "maternal fecal microbiota transplantation," "maternal microbial transfer," and "bacterial baptism."

STUDY ELIGIBILITY CRITERIA: The review included English-language, peer-reviewed randomized controlled trials and nonrandomized interventional studies investigating maternal microbial transfer in neonates born via elective cesarean delivery.

Data were extracted and analyzed for key outcomes, including severe adverse effects, alpha diversity, beta diversity, and the abundance of key taxa such as Bacteroides spp., Bifidobacterium spp., and Lactobacillus spp.

RESULTS: A total of 10 studies, including 4 randomized controlled trials and 6 nonrandomized interventional studies with 1450 participants, were included in this qualitative review. The findings regarding changes in alpha diversity (a measure of microbial richness within individual samples) were inconclusive, while several studies indicated a potential increase in beta diversity (reflecting differences in microbial composition between samples) associated with the procedure. Bacteroides spp., Bifidobacterium spp., and Lactobacillus spp. were the most frequently assessed taxa, with some studies suggesting beneficial changes in their abundance. Developmental outcomes, such as anthropometric measures and allergy risks, showed limited evidence of benefit, with one study reporting preliminary findings of improved neurodevelopmental scores. No significant increase in severe adverse effects was observed in any of the included studies.

CONCLUSION: The efficacy of maternal microbial transfer in restoring neonatal microbiota and promoting health outcomes remains uncertain, with neonatal outcomes addressed in only 3 of the included studies-one on allergy and one on neurodevelopment. However, while no serious adverse effects have been consistently reported, data on safety remain limited.}, } @article {pmid41485542, year = {2026}, author = {Allani, M and Nath, G and Juyal, G and Chandra Joshi, M and Tiwari, V}, title = {Fecal Microbiota Transplantation Attenuates Neuropathic Pain in Rats via Gut Microbiota-Mediated Immunomodulation of Ion Channels and Nociceptors.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {108275}, doi = {10.1016/j.micpath.2026.108275}, pmid = {41485542}, issn = {1096-1208}, abstract = {INTRODUCTION: Neuropathic pain, resulting from somatosensory nervous system damage, presents significant treatment challenges due to limited effectiveness and adverse side effects of current therapies. Emerging evidence highlights the gut microbiome's potential role in pain regulation, yet the specific microbial species and mechanisms underlying chronic neuropathic pain remain largely unexplored.

OBJECTIVES: This study aimed to determine the relationship between gut microbiota and neuropathic pain using fecal microbiota transplantation (FMT) in rats with chronic constriction injury (CCI). Additionally, it sought to identify microbial species associated with pain modulation.

METHODS: CCI was performed in wildtype and antibiotic-treated pseudo-germ-free (PGF) rats. FMT was performed using fecal matter slurry from healthy (hFMT) and CCI-dysbiotic (dFMT) donors, transplanted into nerve-injured and healthy rats, respectively. Pain-related behaviors were assessed and microbial composition was analysed via 16sRNA sequencing. Western blot and RT-PCR assays were conducted on dorsal root ganglion (DRG) and spinal cord tissues.

RESULTS: CCI induced gut microbial dysbiosis, characterized by increased Proteobacteria and Fusobacteriota and decreased Actinobacteria. hFMT from healthy rats alleviated mechanical, thermal, and cold hyperalgesia but did not reverse mechanical allodynia in CCI rats. Conversely, dFMT from CCI rats induced pain-like hypersensitivity in healthy rats, mimicking nerve injury effects. Correlation analysis identified microbial species linked to pain modulation: Bifidobacterium animalis, Corynebacterium urealyticum, and Desulfovibrio piger were associated with reduced pain behaviors, while Pasteurellaceae bacterium, Bacillus sp., and Staphylococcus arlettae were linked to nerve injury-induced dysbiosis. hFMT restored claudin-5 and anti-inflammatory markers TGF-β and IL-10 while downregulating pain-related proteins TRPM8, Nav 1.8, Nav 1.7, and TRPA1 in CCI rats. In contrast, dFMT promoted neuroinflammation by increasing IBA1, TNF-α, and IL-1β, leading to microglial activation in healthy rats.

CONCLUSION: Our findings demonstrate that the composition of gut bacteria influences pain-like behaviors through nerve injury-induced microbial dysbiosis, operating in a bidirectional manner. Additionally, the study suggests that a cocktail of Bifidobacterium animalis, Corynebacterium urealyticum, and Desulfovibrio piger could serve as a promising alternative for managing neuropathic pain.}, } @article {pmid41485442, year = {2025}, author = {Ma, C and Liu, Y and Zeng, T and Li, X and Tan, X and Ma, X and Lu, X and Wang, Y and Wu, X}, title = {Zexie-Baizhu herb pair attenuates MASH via the gut-liver Axis by suppressing NLRP3 Inflammasome activation and M1-macrophage polarization.}, journal = {Bioorganic chemistry}, volume = {169}, number = {}, pages = {109451}, doi = {10.1016/j.bioorg.2025.109451}, pmid = {41485442}, issn = {1090-2120}, abstract = {Metabolic dysfunction-associated steatohepatitis (MASH), a severe form of MASLD lacking effective treatments, may be therapeutically targeted by the Traditional Chinese Medicine herb pair Zexie-Baizhu (ZB), known for its lipid-modulating and anti-inflammatory properties. This study investigated ZB's effects and mechanisms in diet-induced MASH mouse models. We began by identifying potential active ingredients in ZB using UPLC-MS/MS. When administered preventively over an 8-week period, ZB significantly improved serum lipids, reduced hepatic inflammation, and alleviated liver lipid accumulation. Mechanistic studies revealed that ZB restores beneficial gut microbiota, enhances intestinal barrier integrity, modulate the hepatic bile acid receptor FXR signaling pathway to regulate bile acid metabolism, and crucially suppresses NLRP3 inflammasome activation and M1 macrophage polarization. Fecal microbiota transplantation confirmed the role of gut microbiota modulation. Collectively, these results demonstrate that ZB alleviates MASH progression primarily via the gut-liver axis by inhibiting NLRP3 inflammasome and M1 macrophage polarization, highlighting this axis as a promising therapeutic target.}, } @article {pmid41485293, year = {2025}, author = {Meng, Y and Hou, Y and Zhang, R and Guo, Z and Zhang, Z and Li, J and Yan, Y and Chang, Y and Li, D and Chang, L and Li, M and Gao, H}, title = {Jinlida ameliorates diabetic kidney disease via gut microbiota-dependent production of pyridoxamine targeting renal AGEs/RAGE and TGF-β pathways.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {150}, number = {}, pages = {157744}, doi = {10.1016/j.phymed.2025.157744}, pmid = {41485293}, issn = {1618-095X}, abstract = {BACKGROUND: Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage renal disease (ESRD), necessitating novel therapies beyond conventional approaches. Emerging evidence indicates that gut microbiota dysbiosis promotes DKD progression through metabolite-mediated renal injury. Jinlida (JLD) is a clinically validated traditional Chinese medicine with antidiabetic activity, but its microbiota-mediated renoprotective mechanism remains unclear.

PURPOSE: This study investigates whether JLD alleviates DKD by modulating gut microbiota and vitamin B6 metabolism, and elucidates the renoprotective mechanism of its key metabolite, pyridoxamine (PM).

METHODS: To assess JLD's microbiota-dependent effects, we employed antibiotic-induced pseudo-germ-free mice and fecal microbiota transplantation (FMT). Metagenomics and untargeted metabolomics delineated gut microbiota and metabolite compositional changes. Renal PM levels were quantified by LC-MS/MS. The renoprotective effects and mechanisms of direct PM supplementation against DKD were further evaluated in vivo and in vitro.

RESULTS: JLD's therapeutic effects on proteinuria and glomerulosclerosis were shown to partially depend on microbiota homeostasis. Metabolomic analysis demonstrated that JLD significantly upregulated the vitamin B6 metabolic pathway and increased levels of related metabolites, including PM and pyridoxine (PN). Metagenomic analyses indicated that JLD remodeled the gut microbiota composition and enriched pathways related to cofactor biosynthesis, and markedly increased the relative abundance of key enzyme genes involved in the de novo (DXP-dependent) vitamin B6 biosynthesis pathway - namely pdxJ, pdxB, dxs and dxr. Genes related to vitamin B6 activation and conversion (pdxH, aldH) showed no significant changes, suggesting that JLD may promote PM accumulation by enhancing the microbiota's capacity for vitamin B6 biosynthesis rather than its subsequent activation/conversion. Source-tracking pinpointed Paramuribaculum intestinale as the core functional species. In vitro culture experiments showed that JLD markedly promoted the growth of this strain and elevated PM production, and that the strain's conditioned culture medium effectively inhibited formation of advanced glycation end-products (AGEs). Notably, direct supplementation with PM recapitulated the renoprotective effects of JLD in vivo. Mechanistically, PM inhibited the AGEs-RAGE-NF-κB-AP-1 axis and TGF-β receptor signaling, thereby suppressing NF-κB-driven inflammation and Smad2-mediated fibrosis.

CONCLUSION: JLD remodels the gut microbiota and enhances its de novo vitamin B6 biosynthetic capacity, leading to accumulation of PM. Gut-derived PM enters the circulation and functions as an effector molecule targeting the kidney; through PM's direct carbonyl-trapping activity it scavenges AGEs and suppresses the AGEs-RAGE axis as well as downstream inflammatory and profibrotic signaling, thereby exerting renoprotective effects. This study reveals PM as a microbially derived metabolite with therapeutic potential in DKD and offers a new metabolism-directed strategy for DKD treatment.}, } @article {pmid41484558, year = {2025}, author = {Zhang, B and Zheng, T and He, Z and Su, S and Yuan, S and Chen, D and Li, H and Guan, W and Zhang, S}, title = {Maternal purified fiber supplementation-enriched Akkermansia muciniphila regulates lactation and offspring growth via the gut-mammary axis.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, pmid = {41484558}, issn = {1869-1889}, abstract = {Maternal fiber intake alters the maternal gut microbiota and metabolites, which benefits offspring health through unclear mechanisms. Using a sow model, the study showed that supplementing with purified fiber (cellulose:guar gum=3:1) increased weaning weight and resistance to LPS-induced intestinal injury. Milk analysis revealed higher levels of immunoglobulins and milk fat. Fecal microbiota transplantation (FMT) from fiber-fed sows to mice replicated these benefits, increasing milk fat, immunoglobulins, and pup growth. Akkermansia muciniphila (AKK) abundance was positively associated with milk quality in both models. Supplementing with AKK mimicked the effects of fiber, boosting milk fat and immunoglobulins. In in vitro experiments with HC11 mammary epithelial cells showed that AKK metabolites enhanced milk fat synthesis and immunoglobulin transporter expression. Metabolite analysis indicated that AKK influences mammary gland function by increasing acetate and propionate levels, with acetate promoting milk fat synthesis via GPR43 and propionate regulating immunoglobulin transport through GPR41. Therefore, maternal fiber intake promotes intestinal AKK abundance, increases short-chain fatty acids (SCFAs) production, and influences lactation via GPR41/43 signaling.}, } @article {pmid41483616, year = {2026}, author = {Zhong, Y and Liu, J and Huang, J and Yu, J and Liu, Y and Zhuo, W and Xu, Y and Zhang, Y and Zhou, Z and Chen, L and Xiao, Q and Liu, D}, title = {Astragaloside IV alleviates ulcerative colitis via gut microbiota - butyrate metabolism axis to reshape Th17/Treg balance.}, journal = {International immunopharmacology}, volume = {171}, number = {}, pages = {116135}, doi = {10.1016/j.intimp.2025.116135}, pmid = {41483616}, issn = {1878-1705}, abstract = {Gut microbiota dysbiosis and Th17/Treg cell imbalance play critical roles in the pathogenesis of ulcerative colitis (UC). Astragaloside IV (AS-IV) exhibits extensive anti-inflammatory and immunomodulatory activities; however, the crosstalk between gut microbiota and Th17/Treg cells modulated by AS-IV remains unreported. Here, chronic colitis was induced in mice by free access to 2.5 % dextran sulfate sodium (DSS) solution over three 7-day cycles, with concurrent AS-IV administration. AS-IV effectively alleviated DSS-induced chronic colitis in mice, as evidenced by increased body weight and colon length, decreased disease activity index (DAI), colon weight, colon weight/colon length, and colon weight index, and enhanced the gene and protein expression of tight junction molecules Claudin-1, Occludin, ZO-1. Notably, AS-IV not only effectively regulated the differentiation balance of Th17/Treg cells, but also significantly improved the composition of gut microbiota and butyric acid metabolism in chronic colitis mice. Intriguingly, Th17/Treg cells and butyric acid were significantly correlated with α/β diversity, as well as the genera Enterorhabdus, Mucispirillum, and Helicobacter. However, AS-IV lost its therapeutic efficacy against colitis and its regulatory effects on Th17/Treg cell balance and butyric acid metabolism following gut microbiota depletion. Critically, FMT from AS-IV-treated mice restored the protective effects against colitis and the regulation of Th17/Treg cell balance and butyric acid metabolism. Collectively, AS-IV inhibits chronic colitis by regulating gut microbiota composition, butyric acid metabolism, and Th17/Treg cell differentiation balance, whose protective effects are dependent on the regulatory mechanism of Th17/Treg cell differentiation balance mediated by gut microbiota-derived butyrate metabolism.}, } @article {pmid41483363, year = {2026}, author = {Yang, J and Yan, H and Liu, J and Shen, X and Liu, H and Kang, X and Yang, X and Che, Y and Wang, X and Guo, L and Zhang, F and Fan, W}, title = {Lactobacillus Acidophilus Protects against alcohol-associated Liver Disease in Mice Via Gut Microbiota Modulation and Alleviation of Inflammation and Oxidative Stress.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {41483363}, issn = {1867-1314}, support = {202203021211239//Shanxi Provincial Natural Fund Project/ ; 202303021211126//Shanxi Provincial Natural Fund Project/ ; BYJL045//Shanxi Province Higher Education "Billion Project" Science and Technology Guidance Project/ ; }, abstract = {Alcohol-associated liver disease (ALD) is a severe liver disease caused by excessive alcohol consumption. ALD remains a clinical challenge with limited therapeutic options. Following 5-day pretreatment with Lactobacillus acidophilus (Lac), mice were administered ethanol by gavage to induce ALD. Tissues were collected and analyzed for serum markers, hepatic pathology/inflammation/oxidative stress, ileal morphology/tight junctions, and cecal microbiota via 16 S rRNA gene sequencing. The fecal microbiota transplantation (FMT) experiment was performed, and tissues were then collected and analyzed as above. Moreover, the anti-inflammatory and antioxidant properties of Lac-derived particulate matter (pLac) were evaluated on RAW264.7 macrophages in vitro. Lac administration improved gut microbiota composition, enhanced intestinal barrier integrity and reduced lipopolysaccharide (LPS) translocation to the liver, thereby inhibiting the toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB) pro-inflammatory pathway and activating the adenosine monophosphate activated protein kinase (AMPK)- peroxisome proliferator activated receptor α (PPARα) signaling axis. This led to significant attenuation of hepatic inflammation, oxidative stress and steatosis. The FMT experiments further validated that Lac-mediated protection is dependent on gut microbiota modulation. In vitro studies revealed that pLac exhibit direct anti-inflammatory and antioxidant properties. These findings elucidate the mechanistic basis for Lac in alleviating acute ALD, positioning it as a promising treatment or dietary intervention to enhance clinical management.}, } @article {pmid41483189, year = {2026}, author = {Rathee, S and Sen, D and Jain, A and Jain, SK}, title = {Advances in understanding, diagnosing, and treating hepatic encephalopathy: from epidemiology to emerging therapies.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {41483189}, issn = {1432-1912}, abstract = {This comprehensive review explores the multifaceted landscape of hepatic encephalopathy (HE), encompassing its epidemiology, pathophysiology, classification, and evolving therapeutic approaches. Delving into the prevalence and incidence of HE, it is found that the burden of this condition is on individuals and healthcare systems. The intricate mechanisms underlying HE, including abnormalities in synapse transmission, the ammonia hypothesis, the false neurotransmitter theory, the GABAergic theory, and the benzodiazepine theory, are scrutinized, providing a nuanced understanding of the disorder. The review examines altered gene expression, hyponatremia, neurosteroids, oxidative stress, electrolyte imbalance, and manganese accumulation as contributing factors to HE. Classifying HE and identifying precipitating risk factors form crucial aspects of the discussion, shedding light on the most widely used diagnostic tools. Conventional approaches for HE management are discussed, focusing on reducing elevated ammonia formation, improving ammonia-detoxifying liver capacity, and inhibiting false neurotransmitters. Antibiotics, metabolic ammonia scavengers, albumin, probiotics, dietary management, zinc, and secondary prophylaxis are analyzed as current therapeutic targets. Furthermore, the review examines emerging therapies at various stages, including clinical and pre-clinical development, such as glycerol/sodium phenylbutyrate, ornithine phenylacetate, fecal microbiota transplantation, engineered bacteria, liposome-supported peritoneal dialysis, GABAA receptor modulating steroid antagonists (GAMSA), activated carbon microspheres, and glutamine synthetase replacement. This review consolidates knowledge on HE, providing a comprehensive resource for clinicians, researchers, and healthcare professionals involved in managing this complex disorder. The synthesis of epidemiological data, pathophysiological insights, and therapeutic advancements offers a holistic view of HE, paving the way for improved diagnosis and targeted interventions.}, } @article {pmid41482667, year = {2026}, author = {Chen, Y and Du, H and Zhou, W and Qin, M and Li, M and Jin, Y and Xu, Y and Ma, C and Xia, J and Mo, Y and Chen, N and Huang, H and Li, H and Xie, Z and Wang, P and Hong, Y}, title = {Tamoxifen induced hepatotoxicity via gut microbiota-mediated hyodeoxycholic acid depletion and Farnesoid X receptor signaling disruption.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2610077}, doi = {10.1080/19490976.2025.2610077}, pmid = {41482667}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; *Tamoxifen/adverse effects/toxicity ; Mice ; *Chemical and Drug Induced Liver Injury/metabolism/microbiology ; Dysbiosis/microbiology/chemically induced ; Signal Transduction/drug effects ; Mice, Inbred C57BL ; Liver/metabolism/drug effects ; Bile Acids and Salts/metabolism ; Humans ; Fecal Microbiota Transplantation ; Male ; Feces/chemistry ; Bacteria/classification/genetics/isolation & purification/metabolism ; }, abstract = {Tamoxifen (TAM) is a widely used estrogen receptor modulator for breast cancer treatment. However, TAM exhibits significant hepatotoxicity in the clinic, affecting nearly 50% of patients and thereby limiting its clinical utility. The specific mechanisms underlying TAM-induced liver injury remain poorly understood. In this study, we elucidated the mechanistic role of the gut microbiota in the hepatotoxicity associated with TAM. TAM administration induced substantial liver injury and gut microbiota dysbiosis in mice, characterized by an increased abundance of Escherichia and a reduction in Lachnospiraceae NK4A136 group. These microbial shifts resulted in decreased levels of total fecal bile acids (BA), particularly hyodeoxycholic acid (HDCA), which was inversely correlated with TAM-induced liver injury. Additionally, TAM disrupted BA homeostasis by enhancing intestinal Farnesoid X receptor (FXR) activity and concurrently stimulating hepatic BA synthesis through an alternative nonintestinal FXR mechanism. Notably, gut microbiota depletion reversed these effects, demonstrating the critical role of the microbiota in modulating the gut‒liver FXR axis in TAM-induced liver injury. Fecal microbiota transplantation (FMT) further confirmed that TAM directly stimulated hepatic BA synthesis through a microbiota-dependent mechanism. The disruption of the gut‒liver BA‒FXR axis impaired enterohepatic BA circulation, contributing to the liver toxicity associated with TAM administration. Importantly, HDCA supplementation restored the gut‒liver BA‒FXR axis and alleviated TAM-induced liver injury. These findings highlight the intricate relationship between TAM, gut microbiota, and BA metabolism, suggesting that targeting the gut-liver FXR axis with HDCA may serve as a promising therapeutic strategy for alleviating TAM-associated liver injury.}, } @article {pmid41482085, year = {2025}, author = {Yang, B and Xia, Q and Ji, X and Su, K and Yu, T and Xiao, Z and Shi, C and Luo, Z and Wang, X and Xu, W and Gao, Y and Hua, H and Shan, J}, title = {Ganjie Decoction protects against respiratory syncytial virus infection by activating PI3K/AKT-apoptosis axis and regulating gut microbiota metabolism.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {121142}, doi = {10.1016/j.jep.2025.121142}, pmid = {41482085}, issn = {1872-7573}, abstract = {Ganjie Decoction (GJD), a traditional Chinese medicine (TCM) formula commonly used for respiratory diseases, has shown therapeutic potential against RSV pneumonia. However, its pharmacological mechanisms against respiratory syncytial virus (RSV) pneumonia are not fully understood.

AIM OF STUDY: This study aimd to characterize the active components of GJD and systematically investigate its therapeutic effects and underlying mechanisms in RSV-induced pneumonia.

MATERIALS AND METHODS: To evaluate the therapeutic efficacy of GJD in RSV-infected mice, we monitored body weight, performed qPCR, and conducted histopathological examination of lung tissues. The chemical constituents of GJD were characterized using UPLC-MS. Key bioactive compounds and their potential targets were predicted using network pharmacology and molecular docking. The underlying mechanisms were further elucidated using immunohistochemistry and western blotting. The interactions between GJD and the gut microbiota were explored using antibiotic depletion, fecal microbiota transplantation (FMT), metagenomic sequencing, and in vitro co-culture assays. Untargeted metabolomics was employed to assess GJD-induced metabolic alterations. Finally, the role of 4-hydroxyphenylacetic acid (4-HPA) was investigated through cell viability assays, immunofluorescence staining, and western blot analysis in vitro.

RESULTS: GJD significantly mitigated weight loss, attenuated pulmonary viral load, and suppressed inflammation in RSV-infected mice. Network pharmacology and molecular docking revealed that specific compounds in GJD target the PI3K/AKT signaling pathway. This finding was validated by western blotting and immunohistochemistry, which demonstrated that GJD suppresses PI3K/AKT pathway activation, thereby attenuating apoptosis and ameliorating RSV-induced pneumonia. Notably, these protective effects were markedly attenuated in mice with depleted gut microbiota. Furthermore, the therapeutic effects of GJD against RSV pneumonia were transferable via gut microbiota transplantation. GJD restored RSV-induced dysbiosis of the gut microbiota, with Lactobacillus reuteri emerging as one of the most enriched microbes following treatment. Metabolomics analysis identified 4-HPA as a microbiota-dependent metabolite significantly upregulated by GJD. Remarkably, administration of 4-HPA reproduced GJD's therapeutic effects in RSV-infected mice and activated the KEAP1/NRF2 antioxidant pathway, suggesting that 4-HPA functions as a key mediator of GJD's anti-RSV activity.

CONCLUSIONS: These findings suggest that GJD alleviates RSV pneumonia through a synergistic mechanism that modulates the PI3K/AKT-apoptosis pathway, restores gut microbial balance, and normalizes metabolic disturbances. This study systematically elucidates the mechanistic basis underlying the therapeutic effects of GJD against RSV pneumonia.}, } @article {pmid41481427, year = {2026}, author = {Wang, J and Zi, F and Liu, W and Liu, C and Zhang, Z and Kong, L and Xu, X and Wei, J and Chen, T and Li, J}, title = {Clostridium butyricum alleviates multiple myeloma by remodeling the bone marrow microenvironment and inhibiting PI3K/AKT pathway through the gut‒bone axis.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2609455}, doi = {10.1080/19490976.2025.2609455}, pmid = {41481427}, issn = {1949-0984}, mesh = {*Clostridium butyricum/physiology/metabolism ; Animals ; *Multiple Myeloma/microbiology/therapy/metabolism/pathology ; Humans ; *Gastrointestinal Microbiome/physiology ; Mice ; Phosphatidylinositol 3-Kinases/metabolism/genetics ; *Proto-Oncogene Proteins c-akt/metabolism/genetics ; Butyrates/metabolism ; Fecal Microbiota Transplantation ; Male ; *Bone Marrow/metabolism/pathology ; Signal Transduction ; Tumor Microenvironment ; Dysbiosis/microbiology ; Female ; Th17 Cells/immunology ; }, abstract = {Emerging evidence reveals a strong connection between the gut microbiota and cancer. However, the exact role of gut microbiota dysbiosis in multiple myeloma (MM) is poorly understood, and the therapeutic potential of microbiota-targeted interventions represents a promising strategy that demands urgent mechanistic and translational investigation. First, we conducted a comprehensive microbiome-metabolite analysis between MM patients and healthy individuals. The result revealed a marked compositional difference characterized by reduced abundances of butyrate-producing bacteria and diminished butyrate levels in the MM cohort. Subsequent fecal microbiota transplantation demonstrated that the gut microbiota critically modulates MM progression, with healthy donor-derived microbiota reducing the tumor burden and concomitantly elevating serum butyrate. Furthermore, through function-based culturomics screening, Clostridium butyricum (C. butyricum) was identified as a key butyrate-producing specialist. C. butyricum or its metabolite butyrate significantly reduced the systemic tumor burden in 5TGM1 mice. Notably, C. butyricum and butyrate alleviated bone marrow inflammation and osteolytic lesions by suppressing Th17 cells and IL-17 levels in the bone marrow. Moreover, cellular assays and transcriptome sequencing further revealed that butyrate could induce MM cells' apoptosis via HDAC inhibition-mediated upregulation of PPARγ, leading to sequential suppression of the PI3K/AKT pathway and antiapoptotic BCL-2 expression. This apoptotic signaling cascade was reversed by PPARγ antagonism. The direct antitumor effect was further confirmed in M-NSG mice. Our research systematically verifies the specific role of the gut microbiota in MM and provides the first evidence of the immune and molecular mechanisms by which C. butyricum alleviates MM progression, offering preclinical support for probiotic-based therapies against MM.}, } @article {pmid41480316, year = {2025}, author = {Majeed, AA and Butt, AS}, title = {Gut microbiota: An overlooked target in dyslipidemia management.}, journal = {World journal of gastroenterology}, volume = {31}, number = {48}, pages = {113178}, pmid = {41480316}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/physiology/immunology ; *Dyslipidemias/therapy/microbiology/metabolism ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; Lipid Metabolism ; Cardiovascular Diseases/prevention & control ; Bile Acids and Salts/metabolism ; Circadian Rhythm ; }, abstract = {With the global rise in sedentary lifestyles, obesity, and unhealthy dietary patterns, dyslipidemia has emerged as a leading modifiable risk factor for atherosclerotic cardiovascular disease. Beyond host genetics and diet, the gut microbiota has gained recognition as a critical regulator of lipid homeostasis through mechanisms involving bile acid metabolism, short-chain fatty acid signaling, and microbial modulation of inflammation. Lv et al provide a comprehensive synthesis of the diet microbe-lipid axis and therapeutic strategies, including probiotics, prebiotics, and fecal microbiota transplantation. In this correspondence, we expand on their framework by highlighting underexplored yet clinically relevant dimensions, including circadian rhythm alignment, pharmacotherapy microbe crosstalk, population-specific microbial signatures, and functional microbial phenotyping. Addressing these overlooked aspects could accelerate the translation of microbiome science into precision dyslipidemia management, with the potential to improve cardiovascular outcomes worldwide.}, } @article {pmid41480095, year = {2025}, author = {Wang, B and Ma, D and Li, N and Luo, T}, title = {The application of fecal microbiota transplantation in Parkinson's disease.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1713899}, pmid = {41480095}, issn = {1663-4365}, abstract = {BACKGROUND: Parkinson's disease (PD) is a multisystem neurodegenerative disorder characterized by the aggregation of α-synuclein (α-syn) in dopaminergic neurons of the substantia nigra. The pathogenesis of PD remains incompletely understood, and disease-modifying therapies are lacking. Emerging evidence suggests that gut microbiota and their metabolites influence both intestinal and central nervous system (CNS) functions via the microbiota-gut-brain axis (MGBA). Recent studies have identified dysbiosis in the gut microbiota of PD patients, which may contribute to disease progression through two primary mechanisms: First, increased intestinal permeability, allowing pro-inflammatory factors and microbial metabolites to affect the enteric nervous system (ENS) and subsequently spread to the CNS via the vagal neurons; Secondly, disruption of the Blood-Brain barrier (BBB), leading to neuroinflammation and aberrant α-syn aggregation, ultimately resulting in dopaminergic neuron degeneration. These findings underscore the critical role of the MGBA in PD pathogenesis, which makes gut microbiota modulation a promising therapeutic target.

HIGHLIGHTS: This review synthesizes current knowledge on gut microbiota alterations in PD and evaluates the potential of fecal microbiota transplantation (FMT) as an adjunctive therapy to alleviate motor and non-motor symptoms and slow disease progression.

CONCLUSION: FMT has demonstrated efficacy in ameliorating PD symptoms via the MGBA. However, further preclinical and clinical studies are needed to fully elucidate its mechanisms and optimize therapeutic protocols. Targeting the gut microbiota may offer novel biomarkers and intervention strategies for PD.}, } @article {pmid41479898, year = {2025}, author = {Abdel-Gaber, R and Albasyouni, S and Santourlidis, S and Al Quraishy, S and Al-Shaebi, E}, title = {Commiphora myrrha extract protects pigeons from Eimeria labbeana-like-triggered inflammatory dysregulation.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1714313}, pmid = {41479898}, issn = {1664-3224}, mesh = {Animals ; *Eimeria/drug effects/immunology ; *Coccidiosis/veterinary/immunology/parasitology/drug therapy ; *Commiphora/chemistry ; *Plant Extracts/pharmacology ; *Columbidae/parasitology/immunology ; Cytokines/metabolism ; *Bird Diseases/parasitology/immunology/prevention & control/drug therapy ; *Inflammation ; *Resins, Plant/pharmacology ; }, abstract = {BACKGROUND: Coccidiosis, caused by Eimeria species, is a major enteric disease in birds, with Eimeria labbeana-like isolates frequently inducing severe intestinal lesions, diarrhea, and reduced weight gain in pigeons. Conventional anticoccidial drugs face limitations due to resistance, residue concerns, and environmental impact, highlighting the need for alternative strategies. Commiphora myrrha (myrrh) is a resinous plant extract rich in bioactive compounds with antioxidant, antimicrobial, antiparasitic, and anti-inflammatory properties. This study evaluated the protective effects of C. myrrha resin in pigeons experimentally infected with E. labbeana-like isolates.

METHODS: Resin of C. myrrha was collected from Riyadh, Saudi Arabia, authenticated, and extracted with 70% methanol to prepare a crude extract (MyE). Its chemical composition was characterized using GC-MS. A laboratory strain of Eimeria labbeana-like oocysts was propagated in pigeons, sporulated, and used for experimental infection. Twenty-five pigeons were randomly assigned to five groups: uninfected control, uninfected + myrrh extract (MyE), infected control, infected + MyE, and infected + amprolium (standard drug). MyE and amprolium treatments were administered orally for 5 days post-infection. Parasitological, histological, immunohistochemical (NF-κB and IFN-γ), gene expression (MUC2, IL-1β, IL-10, IFN-γ, and TNF-α), and cytokine (IL-10 and TNF-α) analyses were conducted.

RESULTS: In this study, myrrh resin was methanol-extracted and characterized by GC-MS, revealing 29 phytochemical components. Experimental infection of pigeons with E. labbeana-like oocysts resulted in peak fecal oocyst shedding (~5.25 × 10[5] oocysts/g.feces), extensive development of intracellular parasite stages (meronts, gamonts, and developing oocysts), a marked reduction in goblet cell numbers, and elevated intestinal inflammatory responses, including increased NF-κB and IFN-γ immunoreactivity, as well as upregulated mRNA expression of IL-1β, IL-10, IFN-γ, and TNF-α. Oral administration of MyE significantly suppressed oocyst shedding by 60%, reduced the number of intracellular parasitic stages, restored goblet cell counts, and downregulated both gene and protein levels of pro-inflammatory markers while enhancing MUC2 expression, indicating effective modulation of Eimeria-induced intestinal damage and inflammatory dysregulation.

CONCLUSION: These findings demonstrate that C. myrrha extract effectively mitigates Eimeria-induced intestinal damage, inflammation, and immune dysregulation, highlighting its potential as a natural, plant-based intervention for managing pigeon coccidiosis.}, } @article {pmid41479812, year = {2025}, author = {Song, YJ and Yang, B and Feng, QS and Ma, FF and Xing, B and Bin, XL and Ha, XQ}, title = {Gut microbiota-derived trimethylamine N-oxide exacerbates diabetic nephropathy by promoting renal fibrosis.}, journal = {World journal of nephrology}, volume = {14}, number = {4}, pages = {112066}, pmid = {41479812}, issn = {2220-6124}, abstract = {BACKGROUND: Background diabetic nephropathy (DN), a major complication of diabetes, is linked to gut microbiota dysbiosis. Elevated trimethylamine N-oxide (TMAO), a microbiota-derived metabolite, plays a central role in inducing renal injury during DN pathogenesis.

AIM: To investigate the role of TMAO in renal dysfunction and intestinal microbiota alterations associated with DN, hypothesizing that TMAO exacerbates renal injury and fibrosis through gut microbiota-dependent mechanisms.

METHODS: A DN model was successfully established using Zucker diabetic fatty (ZDF) rats. Blood samples were analyzed for renal function parameters, and serum TMAO levels were quantified via high-performance liquid chromatography-tandem mass spectrometry. Renal tissue morphology and fibrosis were assessed using hematoxylin and eosin and Masson staining, respectively. Additionally, 16S rRNA sequencing was employed to profile fecal bacterial communities in rats with diabetes and DN. Fecal microbiota transplantation was conducted to verify alterations in TMAO production capacity in the gut microbiota of DN rats.

RESULTS: After 8 weeks of modeling, the ZDF rat model group exhibited blood glucose levels surpassing 16.7 mmol/L, and compared to the control group, renal function indicators, including β2-microglobulin, cystatin C, uric acid, and creatinine, were significantly elevated (P < 0.05). Renal fibrosis was more pronounced in the ZDF model group, accompanied by heightened P-smad3 expression, in contrast to the TMAO inhibition group. Although Masson staining results did not reach statistical significance (P > 0.05), notable alterations in intestinal flora structure were observed in DN rats, and fecal microbiota transplantation led to increased TMAO production within the intestinal flora of DN rats compared to controls (P > 0.05).

CONCLUSION: DN is associated with gut microbiota alterations that potentiate TMAO generation, contributing to renal injury and fibrotic progression. While TMAO's role in fibrosis warrants further validation, these findings implicate the gut-kidney axis in DN pathogenesis.}, } @article {pmid41479552, year = {2025}, author = {Qian, C and Hong, J and Shi, W and Liu, F and Li, W and Ma, L and Gao, X and Tang, YW and Wu, Q and Xia, L and Hong, M}, title = {Impact of Xpert[®] Carba-R-based screening for carbapenem-resistant organisms on infection-related mortality in hematopoietic stem cell transplant recipients.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1698525}, pmid = {41479552}, issn = {2235-2988}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Middle Aged ; Male ; Adult ; Female ; *Carbapenems/pharmacology ; Prospective Studies ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Transplant Recipients ; beta-Lactamases/genetics ; *Carbapenem-Resistant Enterobacteriaceae/isolation & purification ; Aged ; Bacterial Proteins/genetics ; Feces/microbiology ; Young Adult ; Mass Screening/methods ; }, abstract = {BACKGROUND: The emergence of carbapenem-resistant organisms (CROs) poses a major challenge to clinical infection control in hospitals. Patients undergoing hematopoietic stem cell transplants (HSCTs) infected with CROs are at high risk of mortality. Proactive screening of HSCT patients for CRO colonization may enable early and accurate preemptive anti-CRO therapy, reduce the probability of secondary infections, and contribute to infection prevention and control measures. However, screening CRO colonization with stool/rectal swab culture and sensitivity has a low positivity rate with a long turnaround time, which limits the effectiveness of the interventions. A more rapid and accurate method to detect CRO colonization is urgently needed. Xpert Carba-R assay provides a rapid and accurate detection of carbapenemase types, enabling targeted anti-infective therapy selection based on the identified resistance mechanism.

METHODS: We conducted a historically controlled prospective study at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between August 2021 and July 2022. The study population comprised adult HSCT patients (≥18 years old) who received preemptive anti-CRO therapy based on rectal culture and Xpert Carba-R screening during this period. A total of 381 patients who underwent HSCT from August 2020 to July 2022 were included in the study, and CRO colonization screening was performed on admission and weekly thereafter. In the historic control group from August 2020 to July 2021, HSCT patients were screened only by rectal swab traditional CRO culture, and CRO colonization was determined if the rectal culture was positive. In the study group from August 2021 to July 2022, two rectal swab specimens were collected from HSCT patients for both CRO traditional culture (RS-culture) and Xpert Carba-R testing (RS-Carba-R). CRO colonization was determined if either of the screening methods was positive. CRO-active antibiotics were immediately provided on the first febrile episode of neutropenia (FN) in CRO-colonized patients. Clinical outcome data for the CRO monthly colonization rate and anti-infection efficiency were collected and contrasted between the two groups.

RESULTS: In the historic group, 47 out of 197 patients (23.9%) were identified as colonized with CRO, detected only by RS-culture. In the study group, 41 out of 184 patients (22.3%) were identified as colonized with CRO, detected by either RS-culture or RS-Carba-R; among them, Escherichia coli was the most common CP-CRO strain, and the most prevalent carbapenemase type was NDM. This indicated a slightly lower annual detection rate of CRO gut colonization in the study group compared to the historic group, but no significant difference was observed (22.3% vs. 23.9%, p = 0.715). The incidence of CRO-related bloodstream infections (CRO-BSI) was significantly lower in the study group compared to the historic group (4.8% vs. 25.5%, p = 0.012), and the CRO-related mortality in colonized patients decreased from 19.4% in the historic group to 2.4% in the study group (p = 0.046). The monthly detection rate of CRO gut colonization by RS-culture in the historic group remained steady, with no significant fluctuation (19.7% in the first month and 18.8% in the last month). In contrast, the monthly detection rate of CRO gut colonization by either RS-culture or RS-Carba-R in the study group was higher in the first month compared to the historic group (21.2% in August 2021 vs. 18.8% in July 2021). However, a gradual decline in the monthly detection rates of CRO gut colonization by RS-culture and/or RS-Carba-R was observed in the study group, dropping from 21.2% in the first month to 2.9% in the last month. The univariate and multivariate analyses indicated that the study group had a shorter length of hospitalization (OR = 0.94, 95% CI 0.88-0.99, p = 0.038) and CRO-related mortality (OR = 0.12, 95% CI 0.01-0.75, p = 0.021) than the historic group.

CONCLUSIONS: Our study showed a positive effect of more rapid CRO colonization screening using rectal swabs with Xpert Carba-R and culture, which can guide potent CRO preemptive therapy for subsequent infections based on the detected carbapenemase mechanism, thereby reducing mortality and the spread of CRO infection in HSCT patients.

CLINICAL TRIAL REGISTRATION: chictr.org, identifier ChiCTR2100041976.}, } @article {pmid41479037, year = {2026}, author = {El-Daly, SM and Fayed, B and Talaat, RM and Gouhar, SA and Fahmy, CA and El-Jawad, AMA and Hamdy, NM and Abd Elmageed, ZY}, title = {The Intricate Interplay of Noncoding RNAs and the Gut Microbiome in Gastrointestinal and Endocrine-Related Cancers.}, journal = {Sub-cellular biochemistry}, volume = {114}, number = {}, pages = {61-121}, pmid = {41479037}, issn = {0306-0225}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Gastrointestinal Neoplasms/microbiology/genetics/pathology/metabolism ; *RNA, Untranslated/genetics/metabolism ; *Endocrine Gland Neoplasms/microbiology/genetics/metabolism/pathology ; Dysbiosis/microbiology/genetics ; Animals ; }, abstract = {The human gut microbiome and noncoding RNAs (ncRNAs) represent interconnected regulatory networks that profoundly influence cancer development, particularly in gastrointestinal and endocrine-related malignancies. This chapter delineates the intricate interplay of microbiome-ncRNA crosstalk in the context of gastrointestinal and endocrine-related cancers.The chapter begins with a comprehensive overview of the taxonomic and functional landscape of the healthy adult gut microbiome. The gut microbiome, comprising trillions of microorganisms, plays a crucial role in endocrine regulation through hormone metabolism, synthesis of bioactive compounds, and modulation of immune responses, thereby establishing a critical crosstalk with the host endocrine system. Dysbiosis, or microbial imbalance, has been linked to endocrine dysfunction and the pathogenesis of various diseases, including gastrointestinal and endocrine-related cancers.We then elucidate the classifications of noncoding RNAs and their function as key molecular regulators in cellular communication, gene expression, and disease progression. NcRNAs contribute significantly to the development and progression of endocrine-related malignancies. The intricate crosstalk between the gut microbiome and host ncRNAs demonstrates how gut dysbiosis can disrupt host ncRNA expression patterns, thereby affecting oncogenic pathways, immune surveillance, and metabolic reprogramming linked to tumor initiation, progression, and metastasis. Conversely, host-derived ncRNAs, secreted into the gut lumen, can directly shape microbial gene expression. In this section, we explore how dysregulation of this axis contributes to carcinogenesis through the promotion of chronic inflammation, epithelial barrier dysfunction, and oncogenic signaling. Therapeutic strategies targeting this interplay, including probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, are introduced in the context of restoring microbial balance.This comprehensive chapter provides crucial insights into the molecular mechanisms governing microbiome-ncRNA interactions and their implications for cancer biology, offering new perspectives for therapeutic interventions in gastrointestinal and endocrine-related malignancies.}, } @article {pmid41478424, year = {2025}, author = {Zhang, Y and Chen, L and Jin, J and Xin, Y and Wang, J and Zhang, A}, title = {Therapeutic application of fecal microbiota transplantation for neurological diseases: Exploring novel mechanisms and perspectives.}, journal = {Experimental neurology}, volume = {}, number = {}, pages = {115631}, doi = {10.1016/j.expneurol.2025.115631}, pmid = {41478424}, issn = {1090-2430}, abstract = {Recently, fecal microbiota transplantation (FMT) has garnered widespread attention as an emerging therapeutic approach in the field of neurological disorders. In this study, we review the research progress of FMT in treating neurological disorders. First, the development, safety, and efficacy of FMT are introduced. Subsequently, the application and potential mechanisms of FMT in neurodegenerative diseases (such as Parkinson's disease and Alzheimer's disease), neurodevelopmental disorders (such as autism spectrum disorder and attention deficit hyperactivity disorder), and other neurological conditions are elaborated in detail. Particularly, we explore the pivotal role of the microbiota-gut-brain axis in FMT for treating neurological disorders, as well as how FMT influences neurological function by regulating the gut microbiota and its metabolites, immune system and inflammatory responses, and neurotransmitters. However, FMT also faces numerous challenges in the treatment of neurological disorders, such as ethical issues, safety concerns, and standardization problems. Therefore, this review also prospects the future development directions of FMT in the treatment of neurological diseases, including personalized therapy and combination therapies. FMT may be a feasible and promising option for treating various neurological disorders, but a comprehensive understanding of its working principles and continuous improvement of its application in clinical practice are still ongoing.}, } @article {pmid41478268, year = {2025}, author = {Chen, J and Xu, J and Xu, J and Xu, F and Gong, F and Xiao, P and Ma, H and Zhang, Q and Feng, J and Min, Y}, title = {Gut microbiota-derived propionic acid mitigates age-related albumen quality deterioration by modulating magnum functions.}, journal = {Poultry science}, volume = {105}, number = {3}, pages = {106357}, doi = {10.1016/j.psj.2025.106357}, pmid = {41478268}, issn = {1525-3171}, abstract = {The declined albumen quality during the late laying phase is associated with age-related magnum dysfunction, in which to the roles of gut microbiota is unclear. This study aimed to elucidate the relationship between gut microbiota and magnum function, and its impact on albumen quality. Hy-Line Brown layers at peak (30 wk) and late (70 wk) laying phases were compared to assess age-related changes in albumen quality, magnum function, and gut microbiota. Fecal microbiota transplantation (FMT) from peak- to late-phase hens was conducted to assess functional effects. Microbiome and metabolome analyses were then integrated to identify key bacterial taxa and metabolites. The role of the leading candidate metabolite was further validated through dietary supplementation. Results showed that late-phase hens exhibited significant reductions in albumen height, magnum mucosal fold height, and tubular gland diameter (P < 0.05), alongside gut microbial dysbiosis. FMT from peak-phase donors effectively reversed age-related declines in magnum histomorphology and albumen height in late-phase hens. It also up-regulated the expression of barrier function genes (Claudin-1, ZO-2, MUC2, AGR2) and magnum secretory markers (OVOA), while down-regulating pro-inflammatory cytokines (IL-4, IFN-γ) (P < 0.05). Microbial analysis identified Anaerotruncus as the only genus consistently enriched following FMT and positively correlated with improved albumen height and magnum morphology. Metabolomic analysis revealed that propionic acid was the top metabolite associated with Anaerotruncus abundance. Crucially, dietary supplementation with sodium propionate recapitulated the key benefits of FMT. In summary, our findings revealed a gut microbiota-oviduct axis through which microbiota from peak-laying hens ameliorate age-related magnum decline and improve albumen quality in aging hens.}, } @article {pmid41477763, year = {2025}, author = {He, Z and Zhang, Y and Feng, C and Xie, T and Zhu, K and Yuan, W and Liu, Y and Xie, P and Zhang, N and Zhao, C and Bian, W and Hu, X and Fu, Y}, title = {Gut microbiota induces mammary gland sIgA production to alleviate S. aureus mastitis.}, journal = {Cell reports}, volume = {45}, number = {1}, pages = {116782}, doi = {10.1016/j.celrep.2025.116782}, pmid = {41477763}, issn = {2211-1247}, abstract = {Mastitis threatens dairy cow health and public safety. While gut dysbiosis increases mastitis susceptibility, the mechanism is unclear. We hypothesized that gut dysbiosis exacerbates Staphylococcus aureus (S. aureus)-induced mastitis by reducing milk secretory immunoglobulin A (sIgA). In mice, vancomycin-induced gut dysbiosis reduced sIgA and IgA[+] B cells in milk, gut, and Peyer's patches, impairing the blood-milk barrier and worsening mastitis, effects reversed by fecal microbiota transplantation. Dysbiosis specifically reduced intestinal M. intestinale abundance and GABA levels. Supplementing with M. intestinale or GABA restored sIgA, increased IgA[+] B cells, and alleviated mastitis. We identified an NADP-specific glutamate dehydrogenase (GDH) in M. intestinale; a GDH-expressing E. coli-produced glutamate, elevating gut GABA, enhancing sIgA, and mitigating mastitis. Mechanistically, GABA activated the mTOR pathway to drive macrophage M2 polarization and B cell differentiation. Thus, M. intestinale-derived GABA boosts sIgA to protect against mastitis, offering novel prevention strategies.}, } @article {pmid41476963, year = {2025}, author = {Ma, S and Zheng, L and Zhuang, X and Wang, M and Zou, Y}, title = {Pathogenic mechanisms and therapeutic potential of the microbiome in premature ovarian insufficiency.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1734367}, pmid = {41476963}, issn = {1664-3224}, mesh = {Humans ; *Primary Ovarian Insufficiency/therapy/microbiology/metabolism/etiology ; Female ; Animals ; *Microbiota ; Ovary/metabolism/microbiology ; Probiotics/therapeutic use ; }, abstract = {The postponement of childbearing age has become a global issue. Factors such as increased work pressures on women and environmental changes have led to a rising incidence and younger onset of premature ovarian insufficiency (POI). POI not only impacts patients' reproductive function but also heightens the risk of depression, anxiety, cognitive decline, premature mortality, osteoporosis, and cardiovascular disease. Exploring effective prevention and treatment strategies for POI can slow ovarian ageing and safeguard female reproductive health. Microbiome research confirms that most human tissues and organs form dynamic, interactive systems with symbiotic microbes that play a crucial role in female reproductive function. Previous studies on the microbiome and female reproductive health have rarely focused on POI. The proposed 'Microbiota-Ovary Axis' aims to establish an integrated regulatory framework. This theoretical model systematically elucidates how microbial signals influence ovarian function through four core pathways: the hypothalamic-pituitary-ovarian (HPO) axis, metabolism and endocrine regulation, immunoregulation, and oxidative stress. Evaluating the efficacy of dietary modifications, probiotics, and microbiota transplantation in animal models and preliminary clinical studies will establish a robust theoretical foundation for developing microbiota-targeted innovative diagnostic and therapeutic strategies for POI, thereby enhancing reproductive health throughout the female lifespan.}, } @article {pmid41476793, year = {2025}, author = {Jin, S and Cheng, X and Han, F and Li, Q and Shang, J and Xie, G and Qin, M}, title = {Total alkaloids of Corydalis saxicola Bunting ameliorate ulcerative colitis through regulation of metabolite networks and gut microbiota.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1721116}, pmid = {41476793}, issn = {1663-9812}, abstract = {BACKGROUND: Yanhuanglian (YHL), derived from the dried herb of Corydalis saxicola Bunting, can inhibit diarrhea and alleviate bleeding in traditional Chinese medicine. YHL is used to treat dysentery and hematochezia, which are recognized as ulcerative colitis (UC) in traditional Chinese medicine. However, the effectiveness and mechanisms of YHL treating UC remain largely unknown. This study aimed to reveal anti-colitis effect and mechanisms of YHL's total alkaloids (YTA) against UC.

METHODS: Three graded doses of YTA were introduced to DSS-induced colitis mice for 7 days to evaluate the anti-colitis effect. Colon, serum, and fecal untargeted metabolomics were applicated to analyze the differential metabolites. 16S rRNA sequencing was used to analyze changes in the gut bacteria, while gut microbiota depletion and fecal microbiota transplantation further verified the effects of gut microbiota. Lactobacillus spp. isolated from the mice feces were screened based on the enrichment abundance of YTA in vivo and in vitro, and the therapeutic effect of Lactobacillus johnsonii enriched with YTA was evaluated in colitis mice.

RESULTS: YTA alleviated weight loss, diarrhea, and hematochezia in colitis mice, reducing inflammation and oxidative stress while restoring intestinal barrier impairment. Untargeted metabolomics profiling of colon, serum, and feces demonstrated that YTA restored the disrupted metabolite profiles, with linoleic acid consistently identified as a key differential metabolite. Through the pathway enrichment, linoleic acid metabolism pathway was highlighted. YTA also ameliorated imbalance of the gut microbiota by significantly increasing the abundance of Lactobacillus. Gut microbiota depletion and fecal microbiota transplantation confirmed that the benefits of YTA depended on the presence of gut microbiota. Furthermore, Lactobacillus johnsonii enriched by YTA protected colitis mice against UC.

CONCLUSION: YTA exhibited potential anti-colitis activity by modulating metabolomic profiles and the gut microbiota, suggesting its potential as a complementary and alternative therapy in phytomedicine.}, } @article {pmid41476057, year = {2025}, author = {Wu, Y and Wong, O and Chen, S and Wang, Y and Lu, W and Cheung, CP and Ching, JYL and Cheong, PK and Chan, S and Leung, P and Chan, FKL and Su, Q and Ng, SC}, title = {Distinct diet-microbiome associations in autism spectrum disorder.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-025-67711-7}, pmid = {41476057}, issn = {2041-1723}, abstract = {Autism spectrum disorder (ASD) is linked to both altered gut microbiota and unhealthy diets; however, the mechanistic connections remain elusive. In this study, we conducted a systematic analysis of fecal microbiome metagenomic data, paired with granular dietary assessments and phenotypic profiles, across a cohort of 818 children (462 with ASD, 356 without ASD; mean age = 8.4 years; 27.3% female). By integrating dietary indices, nutrient intake, and food additive exposures, we uncovered ASD-specific linkages to the microbiome. Poor dietary quality correlated with aggregated core autistic symptoms, gastrointestinal complications, and atypical eating behaviors. Notably, children with ASD exhibited a more pronounced diet-microbiome interaction network compared to neurotypical peers, suggesting heightened microbial sensitivity to nutritional inputs. Furthermore, synthetic emulsifiers-specifically polysorbate-80 and carrageenan-were associated with disrupted microbial connectivity in ASD, a phenomenon attenuated in neurotypical children. Our findings elucidate the mechanistic links between dietary factors-particularly synthetic food additives-and microbiome dysregulation in ASD, urging a re-evaluation of dietary guidelines for ASD populations and laying the groundwork for personalized nutritional strategies.}, } @article {pmid41475762, year = {2026}, author = {Wu, X and Wei, J and Deng, R and Wang, J and Wu, B and Yan, T and Jia, Y}, title = {The Akkermansia muciniphila-tryptophan metabolism-aromatic hydrocarbon receptor axis mediates the protective effect of Schisandra chinensis pectin polysaccharide against colitis.}, journal = {Carbohydrate polymers}, volume = {375}, number = {}, pages = {124808}, doi = {10.1016/j.carbpol.2025.124808}, pmid = {41475762}, issn = {1879-1344}, mesh = {Animals ; *Tryptophan/metabolism ; *Schisandra/chemistry ; *Receptors, Aryl Hydrocarbon/metabolism ; Mice ; *Pectins/pharmacology/chemistry/therapeutic use ; Gastrointestinal Microbiome/drug effects ; *Colitis, Ulcerative/drug therapy/chemically induced/metabolism ; Mice, Inbred C57BL ; Male ; Dextran Sulfate/toxicity ; Akkermansia/drug effects/metabolism ; *Colitis/drug therapy/chemically induced/metabolism ; *Polysaccharides/pharmacology/chemistry ; Fecal Microbiota Transplantation ; Protective Agents/pharmacology ; }, abstract = {Current therapies for ulcerative colitis (UC) remain inadequate, necessitating novel treatment strategies. This study isolated SCPII-1, a homogeneous pectin polysaccharide (Mw: 278.153 kDa, DM: 57.21 %) from Schisandra chinensis, primarily composed of →4)-α-D-GalpA-(1 → units. In dextran sulfate sodium (DSS)-induced colitis mice, SCPII-1 alleviated symptoms, repaired mucosal ultrastructure (microvilli, mitochondria), and enhanced barrier integrity. Mechanistically, SCPII-1 ameliorated gut dysbiosis in UC mice, notably through the selective enrichment of the beneficial bacterium Akkermansia muciniphila (AKK). Interestingly, SCPII-1 not only promoted the proliferation of AKK but also modulated its tryptophan metabolism, particularly enhancing the production of the tryptophan-derived metabolite indole-3-ethanol (I3E). The beneficial role of SCPII-1-induced microbiota in UC was validated using pseudo-germ-free mice and fecal microbiota transplantation experiments. Moreover, I3E was identified as a key microbiota-derived active metabolite regulated by SCPII-1, and exogenous supplementation of I3E further confirmed its therapeutic efficacy in UC. Importantly, I3E activated the aryl hydrocarbon receptor (AhR), upregulated IL-22 expression, and promoted mucosal repair and immune homeostasis, thereby confirming the protective role of the SCPII-1-AKK-tryptophan metabolism axis in colitis. These findings highlight SCPII-1 as a promising prebiotic agent for UC treatment by modulating AKK-dependent tryptophan metabolism and activating the AhR/IL-22 signaling pathway, offering a novel microbiota-based therapeutic strategy.}, } @article {pmid41475736, year = {2026}, author = {Wu, J and Xu, Q and Yang, Y and Yang, Z and Li, Z and Chen, L and Song, Y and Che, H and Wang, G and Lv, Q and Han, J}, title = {A novel fructan from Atractylodes macrocephala ameliorates ulcerative colitis through gut microbiota-mediated PI3K/Akt signaling.}, journal = {Carbohydrate polymers}, volume = {375}, number = {}, pages = {124764}, doi = {10.1016/j.carbpol.2025.124764}, pmid = {41475736}, issn = {1879-1344}, mesh = {Animals ; *Atractylodes/chemistry ; *Colitis, Ulcerative/drug therapy/chemically induced/metabolism/pathology/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Proto-Oncogene Proteins c-akt/metabolism ; *Phosphatidylinositol 3-Kinases/metabolism ; Mice ; Signal Transduction/drug effects ; *Fructans/pharmacology/chemistry/isolation & purification/therapeutic use ; Male ; Mice, Inbred C57BL ; Dextran Sulfate ; Disease Models, Animal ; Fecal Microbiota Transplantation ; }, abstract = {Polysaccharides from edible and medicinal plants are promising natural agents for intestinal health. In this study, a homogeneous polysaccharide (AMP) was isolated from Atractylodes macrocephala Koidz. Structural characterization revealed that AMP (Mw = 3.56 kDa) primarily consisted of fructose (92.4 %) and glucose (7.6 %), with β-D-fructofuranose and α-d-glucopyranose residues linked through →1)-β-D-Fruf-(2→, →1,6)-β-D-Fruf-(2→, and α-D-Glcp-(1 → glycosidic bonds. In vivo studies confirmed the efficacy of AMP against ulcerative colitis (UC) in a DSS-induced mouse model, as evidenced by a significant improvement in disease symptoms, including increased body weight, longer colon length, and elevated goblet cell counts, coupled with a reduction in the disease activity index and histological damage. Mechanistically, AMP attenuated inflammation by restoring intestinal barrier integrity and regulating the gut microbiota to maintain its homeostasis. These regulatory effects were further validated through fecal microbiota transplantation (FMT) and antibiotic intervention (Abx). Olink proteomics and western blotting demonstrated that the ameliorative effect of AMP on UC, mediated via the PI3K/Akt pathway, was entirely dependent on the homeostasis of the gut microbiota. Collectively, these findings position AMP as a promising functional food ingredient or natural therapeutic for UC, providing a scientific basis for the high-value exploitation of A. macrocephala.}, } @article {pmid41475679, year = {2025}, author = {Morel, C and Li, R and Luces, CF and Brougham, MFH and Pascual-Gazquez, JF and Iniesta, RR and Torquati, L}, title = {Interventions targeting the gut microbiome to improve cancer treatment outcomes and their gastrointestinal side effects: a systematic review and meta-analysis.}, journal = {The Journal of nutrition}, volume = {}, number = {}, pages = {101300}, doi = {10.1016/j.tjnut.2025.101300}, pmid = {41475679}, issn = {1541-6100}, abstract = {BACKGROUND: Improvements in cancer treatment are essential to reduce premature mortality. Emerging evidence highlights the role of the gut microbiome (GM) in influencing treatment responses and modulating gastrointestinal adverse events (GIAEs). Because cancer therapy disrupts GM composition, restoring gut health may help mitigate side effects and support gut-associated immunity.

OBJECTIVE: This study aims to systematically evaluate and assess the effectiveness of GM interventions on the occurrence of GIAEs and clinical responses to cancer treatment.

METHODS: Three databases (PubMed, Web of Science, Cochrane Library) were systematically searched up to February 2025 for studies assessing gut microbiome interventions during cancer treatment. Risk of bias was evaluated using the EPHPP Quality Assessment Tool. Meta-analyses were conducted in Stata 18® using random-effects models to estimate the pooled relative risk of GM interventions on GIAEs (primary outcome) and objective disease response rates (secondary outcome).

RESULTS: Fifty-six studies were included in the systematic review and forty were meta-analysed (n=37 for GIAE outcomes, n=8 for treatment response). GM interventions reduced the overall risk of GIAEs (RR = 0.59, 95% CI = 0.53, 0.65, I[2] = 76.8%; 95% PI = 0.32, 1.08), including diarrhoea, constipation, nausea, and vomiting, but with considerable heterogeneity between studies. There was insufficient evidence to suggest improvements in objective disease response rates (RR = 1.06, 95% CI = 0.93, 1.20; I[2] = 0%; 95% PI = 0.93, 1.20).

CONCLUSION: GM interventions show promise in improving cancer care by reducing GIAEs, though evidence for direct effects on treatment response remains limited. Standardising intervention protocols and outcome reporting in future RCTs is essential to strengthen the evidence base and guide clinical recommendations.

PROSPERO REGISTRATION: Registration number: CRD42023443332 LINK TO PROTOCOL: Https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023443332.}, } @article {pmid41475542, year = {2025}, author = {Nayak, A and Bera, S and Purohit, S and Jain, CK}, title = {Gut Microbiota Mediated Neuroinflammation in Psychiatric Disorders: Current Perspectives and Challenges.}, journal = {Behavioural brain research}, volume = {}, number = {}, pages = {116019}, doi = {10.1016/j.bbr.2025.116019}, pmid = {41475542}, issn = {1872-7549}, abstract = {Psychiatric disorders remain a major global health concern, with complex diagnostic criteria and a lack of clear biological markers that continue to challenge therapeutic strategies. Current treatment methods, such as psychotherapy, brain stimulation therapy, and pharmacological interventions, often come with their own set of side effects, thus warranting the need to explore alternative approaches. Emerging research highlights the gut brain axis (GBA) and gut microbiota (GM) as key modulators of brain health and disease. Dysbiosis, a disruption in gut microbial composition, can influence blood brain barrier (BBB) integrity, immune signaling, and microbial metabolite production, collectively modulating neuroimmune homeostasis and contributing to the onset of neuroinflammation. While growing preclinical and clinical evidence links altered GM to depression, anxiety, schizophrenia, bipolar disorder (BD), and autism spectrum disorder (ASD), causal relationships remain incompletely defined. This review examines the established and emerging mechanisms connecting the GM to neuroinflammation underlying psychiatric disorders and evaluates current microbiome targeted interventions, such as diet based strategies, probiotics, next generation probiotics (NGPs), and fecal microbiota transplantation (FMT). We also discuss speculative microbiome engineering approaches and highlight translational limitations that must be addressed before clinical implementation. A holistic approach integrating these strategies with conventional psychiatric treatments could facilitate more effective and personalized interventions.}, } @article {pmid41475279, year = {2025}, author = {Singh, G and Ansari, S and Yadav, S and Aran, KR}, title = {Gut microbiota's role in NAFLD- and HBV/HCV-related hepatocellular carcinoma: Mechanisms and therapeutic implications.}, journal = {Microbial pathogenesis}, volume = {211}, number = {}, pages = {108273}, doi = {10.1016/j.micpath.2025.108273}, pmid = {41475279}, issn = {1096-1208}, abstract = {Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality globally and has been closely linked to chronic liver conditions, such as viral hepatitis and non-alcoholic fatty liver disease. Recent research has demonstrated that the gut microbiota significantly impacts the gut-liver axis, a crucial aspect of the pathophysiology of HCC. This review emphasizes the mechanisms by which gut dysbiosis contributes to liver inflammation, fibrosis, and tumor formation. In NAFLD-related HCC, modification in the microbiota composition facilitates intestinal barrier dysfunction, endotoxemia, and metabolic disturbances. In HCC associated with HBV/HCV, the microbiome modulates immune surveillance and viral persistence. Shared pathogenic pathways, such as LPS-TLR4 signaling, bile acid dysregulation, and immunosuppressive microenvironments, highlight the role of microbial imbalance across varied etiologies. We also discuss how antibiotics, diet, probiotics, and postbiotics influence gut-liver homeostasis, as well as their therapeutic potential in primary and secondary prevention and treatment of HCC. Short-chain fatty acids and valeric acid are examples of postbiotics with anti-inflammatory and pro-apoptotic anti-IBD effects, while fecal microbiota transplantation and dietary modulation have shown potential in improving outcomes. The review also identifies significant research gaps, particularly in establishing causality, understanding intrahepatic metastasis, and investigating the roles of the fungal and viral microbiome (mycobiome and virome). Finally, the incorporation of microbiome-based interventions into clinical practice could represent an effective future strategy for risk stratification, prevention, and adjuvant therapy of HCC. Future studies focusing on longitudinal analysis, mechanistic validation, and multi-kingdom profiling are essential for translating microbiome research into effective clinical applications.}, } @article {pmid41474687, year = {2025}, author = {Abulaiti, A and Yu, H and Ma, J and Wuji, A and Chi, H}, title = {Advancement on the Association between Gut Microbiota and Autism Spectrum Disorder in Children.}, journal = {Annals of nutrition & metabolism}, volume = {}, number = {}, pages = {1-24}, doi = {10.1159/000549716}, pmid = {41474687}, issn = {1421-9697}, abstract = {Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by deficits in social interaction, communication, and the presence of restricted, repetitive behaviors. The rising global prevalence of ASD suggests a multifactorial etiology involving genetic, environmental, and neurodevelopmental factors. This review explores the establishment of the early-life microbiome, highlighting rapid microbial colonization from maternal and environmental sources. Emerging evidence indicates that delivery mode and infant feeding practices may influence ASD susceptibility. Although the concept of a sterile intrauterine environment remains debated, its investigation is valuable. The bidirectional "microbiota-gut-brain axis" has emerged as a critical pathway linking gut microbiota and brain function, offering potential therapeutic targets for ASD. Dietary patterns in children with ASD are often characterized by selectivity and restriction, which may disrupt gut microbiota composition and exacerbate gastrointestinal symptoms, thereby increasing ASD risk. Nutritional interventions and early behavioral therapies are thus essential. The gluten-free, casein-free (GFCF) diet remains controversial, with inconsistent evidence regarding its efficacy. Probiotic supplementation shows strain-specific effects, necessitating rigorous evaluation before clinical application. Given the heterogeneity of ASD, pharmacological treatments have shown limited universal efficacy. This review provides a comprehensive analysis of the interplay between diet, gastrointestinal symptoms, and ASD, evaluates the gut-brain axis as a mechanistic framework, and assesses the therapeutic potential of microbial interventions, including probiotics, prebiotics, and fecal microbiota transplantation (FMT). While promising findings have emerged, further well-designed clinical studies are needed to elucidate the complex etiology of ASD and validate therapeutic strategies.}, } @article {pmid41473261, year = {2025}, author = {Zhou, Y and Yang, L and Nan, Y and , }, title = {Expert Consensus on Clinical Applications of Fecal Microbiota Transplantation for Chronic Liver Disease (2025 edition).}, journal = {Journal of clinical and translational hepatology}, volume = {13}, number = {12}, pages = {1107-1116}, pmid = {41473261}, issn = {2310-8819}, abstract = {The gut microbiota is crucial in maintaining host health and liver function. Fecal microbiota transplantation (FMT) has shown promising potential in treating chronic liver diseases. To help clinicians quickly master and standardize the clinical application of FMT for chronic liver disease, the Liver Related Digestive Diseases Group of the Chinese Society of Hepatology of the Chinese Medical Association has developed the "Expert Consensus on the Clinical Application of FMT for Chronic Liver Disease." This consensus addresses the key aspects of FMT, including the indications, contraindications, efficacy, safety, donor selection, transplantation routes, precautions, and the prevention and management of adverse reactions for chronic liver conditions, such as chronic hepatitis, cirrhosis, and liver cancer, thereby offering reference and guidance to clinicians implementing FMT in the treatment of chronic liver disease.}, } @article {pmid41473248, year = {2025}, author = {Zhang, Y and Cao, J and Wang, Y and Fan, X and Deng, R and Mi, J}, title = {Effects of fecal microbiota transplantation on glycemic and lipid profiles in overweight or obese patients with metabolic disorders: a systematic review and meta-analysis.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1737543}, pmid = {41473248}, issn = {1664-2392}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Obesity/therapy/blood/complications ; *Metabolic Diseases/therapy/blood ; *Overweight/therapy/blood ; *Lipids/blood ; *Blood Glucose/metabolism ; Gastrointestinal Microbiome ; Randomized Controlled Trials as Topic ; Lipid Metabolism ; }, abstract = {UNLABELLED: Obesity and its associated metabolic disorders (such as type 2 diabetes, metabolic syndrome, and NAFLD/MASLD) represent a global health challenge. Fecal microbiota transplantation (FMT), as a therapy regulating the gut microbiome, has demonstrated inconsistent clinical efficacy. This systematic review aims to evaluate the impact of FMT on key indicators of glucose and lipid metabolism in overweight/obese adults with metabolic diseases. We systematically searched PubMed, Embase, Cochrane, and Web of Science databases up to September 28, 2025, to identify randomized controlled trials evaluating FMT for obesity and metabolic disorders. Data were pooled using a random-effects model, with primary outcomes being changes in BMI, HOMA-IR, and HbA1c relative to baseline. A total of 11 RCTs (320 participants) were included. The primary analysis showed that FMT intervention demonstrated a trend toward improvement in the primary outcome measures, BMI (MD: -0.65, p = 0.070) and HOMA-IR (MD: -0.64, p = 0.062), but these trends did not reach statistical significance. There was no significant effect on HbA1c (MD: 0.06, p = 0.742). However, this negative conclusion based on the conventional assumption (Corr = 0.5) exhibited high instability: sensitivity analysis revealed that FMT's improvement effects on BMI became statistically significant (p = 0.010) when the correlation coefficient (Corr) used to estimate the standard deviation of change was adjusted to 0.75. Furthermore, meta-regression analysis revealed that treatment regimen, follow-up duration, and patient baseline characteristics were significantly associated with HbA1c efficacy. Based on the current "low" certainty evidence, the overall improvement of metabolic parameters in overweight or obese patients with metabolic diseases following FMT did not reach statistical significance in the primary analysis. However, the robustness of this negative finding is limited, exhibiting high sensitivity to statistical hypotheses and likely being significantly confounded by methodological factors (e.g., administration protocols) and donor variability. Consequently, the true efficacy of FMT for treating systemic metabolic disorders remains uncertain. Future trials should shift toward precision medicine, prioritizing the standardization of donor selection and optimization of administration protocols.

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251172011, identifier CRD420251172011.}, } @article {pmid41472848, year = {2025}, author = {Tang, B and Cao, Y and Li, J and Gao, N and Gao, P and Chen, X and Ming, Z and Li, Z and Hou, W}, title = {Whole microbiota transplantation restores gut homeostasis throughout the gastrointestinal tract.}, journal = {iMeta}, volume = {4}, number = {6}, pages = {e70091}, pmid = {41472848}, issn = {2770-596X}, abstract = {This study introduces whole microbiota transplantation (WMT), a synergistic therapeutic approach that concurrently transplants small intestinal and fecal microbiota. In germ-free mice, WMT outperforms conventional fecal microbiota transplantation (FMT) in restoring gut microbiota diversity and abundance. Moreover, in a chemotherapy-induced intestinal mucositis model, WMT alleviates intestinal inflammation and reverses microbiota dysbiosis. Encapsulation in layer-by-layer self-assembled nanocapsules further boosts microbial survival and colonization, amplifying WMT's anti-inflammatory effects and microbiota restoration in a mouse model of pan-intestinal infection. Overall, WMT represents a precise strategy for reshaping microbial homeostasis across the entire gastrointestinal tract, with therapeutic promise for inflammatory bowel diseases and small-intestinal disorders.}, } @article {pmid41472816, year = {2025}, author = {Lan, T and Hou, Q and Zhao, H and Luan, Y and Shi, Y and Hu, S and Wang, N and Yan, S and Gong, X and Song, Y}, title = {Gut microbiota dysbiosis impairs TGF-β/Smad4 signaling to drive postoperative metastasis in colorectal cancer.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1654227}, pmid = {41472816}, issn = {1664-302X}, abstract = {BACKGROUND: After surgical intervention, metastasis remains the primary contributor of mortality rates in colorectal cancer (CRC). While compelling evidence implicates gut microbiota dysbiosis as a key driver of CRC progression, its role in postoperative metastasis remains unclear.

METHODS: A total of 97 participants were recruited, comprising 21 postoperative CRC patients with metastasis (M group), 37 postoperative CRC patients without metastasis (C group), and 39 healthy individuals (H group). Fecal microbiota composition, short-chain fatty acid (SCFA) concentrations, and serum cytokines were quantified. Spearman correlation was used to assess the relationship between microbiota and SCFAs. Fecal microbiota transplantation (FMT) was performed by transferring patient specimens into antibiotic-pretreated orthotopic CRC mice models. Epithelial-mesenchymal transition (EMT) markers and TGF-β/Smad4 signaling were subsequently analyzed.

RESULTS: In humans, M group patients exhibited significant gut dysbiosis, characterized by enriched Fusobacterium and depleted Gemmiger, concomitant with markedly diminished fecal butyrate, propionate, and acetate (vs. H group, p < 0.05). In these patients, this dysbiosis was directly correlated with SCFA depletion (Padj  < 0.05). Serologically, patients in the M group exhibited elevated TGF-β while suppressed IL-10 compared to C group (p < 0.05). In the mouse model, the FMT from M group significantly increased Fusobacterium abundance and reduced fecal acetate/butyrate, concomitantly accelerating tumor progression with elevated hepatic and cecal tumor weights and upregulated EMT markers (N-cadherin and MMP9). This pro-metastatic phenotype was associated with downregulated hepatic mRNA expression of the key SCFA receptors, FFAR2 and FFAR3. Notably, in the animal model, the FMT-M group exhibited elevated hepatic TGF-β and a trend toward reduced Smad4 expression, suggesting a potential dysregulation of the TGF-β/Smad4 signaling pathway. Conversely, the fecal microbiota from C group markedly suppressed Fusobacterium colonization and restored acetic acid, butyric acid levels which ameliorates pathological changes by attenuating N-cadherin expression and normalizing TGF-β/Smad4 signaling.

CONCLUSION: Gut microbiota dysbiosis and SCFA depletion exert profound regulatory effects on postoperative CRC metastasis, potentially by promoting EMT through mechanisms involving the TGF-β/Smad4 signaling axis. Thus, targeting gut microbiota may offer promising therapeutic strategies to mitigate CRC metastasis.}, } @article {pmid41472805, year = {2025}, author = {Tian, Z and Li, C}, title = {The role of gut microbiota in the onset and development of sepsis and its therapeutic potential: mechanisms and research progress.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1718549}, pmid = {41472805}, issn = {1664-302X}, abstract = {Sepsis is a life-threatening disease triggered by infection-induced immune dysregulation, characterized by multi-organ dysfunction, and is one of the leading causes of death among critically ill patients worldwide. Recent studies have shown that gut microbiota (GM) imbalance plays a crucial role in the progression of sepsis. This review identifies the core mechanisms of GM imbalance: it disrupts the integrity of the intestinal mucosal barrier, induces bacterial and endotoxin translocation, activates systemic inflammatory responses, and forms a vicious cycle of "gut-organ" cross-damage, becoming a key driver of sepsis-associated multi-organ dysfunction. Existing research has confirmed that microbiota modulation strategies, such as probiotic supplementation and fecal microbiota transplantation (FMT), have potential therapeutic value. However, due to issues like strain specificity, lack of standardized protocols, and insufficient clinical evidence, the clinical translation of these strategies still faces significant barriers. Therefore, future research should focus on the identification of sepsis-specific GM core functional biomarkers, the development of personalized combined regulatory strategies, and the advancement of targeted delivery technologies. Multi-center large-scale clinical trials are needed to validate their efficacy and safety, providing innovative solutions for precision treatment of sepsis.}, } @article {pmid41472740, year = {2025}, author = {Chen, Q and Zhong, M and Lin, Y}, title = {Exploring gut microbiota and spinal cord injury: pathogenesis, treatment strategies and prospects.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1693883}, pmid = {41472740}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Spinal Cord Injuries/therapy/microbiology/etiology ; Animals ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; }, abstract = {Spinal cord injury (SCI) is a disabling central nerve system (CNS) injury, often caused by factors such as traffic accidents, falls from heights, violent trauma, and sports injuries, commonly resulting in permanent loss of motor and sensory function below the level of injury. Increasing evidence suggests that gut microbiota influences the occurrence and development of CNS diseases through the brain-gut axis. Recent studies indicate that patients with SCI frequently exhibit gut microbiota dysbiosis. Changes in gut microbiota can lead to gut barrier disruption, triggering neurogenic inflammatory responses, thereby hindering recovery after SCI, while reshaping gut microbiota may benefit the recovery of intestinal function and neurofunction after SCI. In this review, we summarize emerging literature on the role of microbiota after SCI. We elucidate the intrinsic connection between gut microbiota and SCI, explore the role of gut microbiota in the pathogenesis of SCI, and investigate potential intervention strategies targeting gut microbiota, including probiotic therapy, fecal microbiota transplantation (FMT), and regulation of metabolites, aiming to provide theoretical basis and translational prospects for developing innovative microecological targeted therapeutic approaches.}, } @article {pmid41472066, year = {2025}, author = {Vestad, B and Hanzely, P and Karaliūtė, I and Ramberg, O and Skiecevičienė, J and Lukoševičius, R and Bjørnholt, JV and Holm, K and Kupčinskas, J and Rasmussen, H and Hov, JR and Melum, E}, title = {Modulation of Dextran Sodium Sulfate-Induced Colitis in Germ-Free Mice by Enterococcus faecalis Monocolonization.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41472066}, issn = {2076-2607}, support = {LT08-2-LMT-K-01-060//EEA Grants 2014-2021/ ; 802544/ERC_/European Research Council/International ; }, abstract = {Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis (UC), are characterized by chronic gastrointestinal inflammation and involve complex interactions of genetic, environmental, and immune factors. Enterococcus faecalis, a gut commensal bacterium, has been implicated in IBD pathogenesis. This study investigated the effects of monocolonization with a UC-derived E. faecalis strain on acute dextran sulfate sodium (DSS)-induced colitis in germ-free (GF) mice, focusing on epithelial injury, inflammatory markers, hematologic indices, and bacterial translocation. In DSS-treated mice, monocolonization was associated with modest and mixed effects, including a higher colitis-related disease activity score, reduced anemia, increased fecal albumin and a trend towards reduced fecal calprotectin. Despite translocation of E. faecalis to mesenteric lymph nodes, no systemic dissemination was observed. Histological analysis revealed broadly similar inflammatory patterns between DSS-treated groups, with slightly more epithelial injury observed in colonized mice. These findings suggest that E. faecalis may influence discrete aspects of DSS injury in a strain-dependent and context-specific manner, rather than broadly altering overall disease severity. This study highlights the utility of GF models for examining strain-specific host-microbe interactions and underscores that individual bacterial isolates may exert heterogeneous and selective effects on acute colitis. Further research is needed to elucidate these complex mechanisms.}, } @article {pmid41471996, year = {2025}, author = {Zhang, X and Mao, G and Pei, Z and Sun, Y and Cen, J and Zhang, S and Li, S and Meng, W and Xiao, K and Xu, Q and Sun, M}, title = {Microbial Ecology of Sulfur Mustard Toxicity: From Dysbiosis to Restoration.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471996}, issn = {2076-2607}, support = {82103885//National Natural Science Foundation of China/ ; 82273672//National Natural Science Foundation of China/ ; 20ZR1470300//Natural Science Foundation of Shanghai Municipality/ ; 21ZR1477700//Natural Science Foundation of Shanghai Municipality/ ; GWV-10.2-YQ48//Shanghai Municipal Health Commission-Outstanding Youth Foundation of Public Health/ ; }, abstract = {Sulfur mustard (SM) causes multi-organ toxicity, yet its impact on intestinal tissue and the associated gut microbiota remains poorly characterized. This study demonstrates that in a mouse model of SM exposure, gut microbial ecological collapse occurs, characterized by depletion of protective taxa (Bifidobacteriales, Gordonibacter, and Lachnospiraceae UCG010) while promoting a 302-fold expansion of inflammation-associated Escherichia/Shigella. Mendelian randomization analysis established causal relationships between these SM-perturbed taxa and human inflammatory bowel disease. Fecal microbiota transplantation effectively restored microbial diversity (Simpson index: 0.85 to 0.95), suppressed Escherichia/Shigella by 97.4%, and ameliorated intestinal pathology. Longitudinal tracking revealed persistent vulnerability of Bifidobacteriales compared to other depleted taxa. Our findings establish the gut microbiota as a key mediator in SM intestinal toxicity and provide new insights for microbiota-targeted interventions against chemical injuries.}, } @article {pmid41471872, year = {2025}, author = {Yang, B and Zhong, S and Wang, J and Yu, W}, title = {Dietary Modulation of the Gut Microbiota in Dogs and Cats and Its Role in Disease Management.}, journal = {Microorganisms}, volume = {13}, number = {12}, pages = {}, pmid = {41471872}, issn = {2076-2607}, support = {No. 20242BAB20315//Natural Science Foundation for Youth of Jiangxi Province/ ; GJJ2200410//The Science and Technology Program of Jiangxi Provincial Department of Education/ ; }, abstract = {Food has a massive influence on the gut microbiota and is one of the most useful therapeutic levers in disease. Recent developments have highlighted how macronutrient balance, food format, and functional ingredients can regulate microbial diversity, metabolism, and host physiology in companion animals such as dogs and cats. This narrative review condenses evidence on the bidirectional gut microbiota-diet connection and on nutritional therapy for gastrointestinal, metabolic, renal, hepatic, and immune-mediated disorders. Protein-based diets including high or hydrolyzed protein, omega-3 acids, fermentative fiber, and probiotics can positively affect microbial composition, stimulate short-chain fatty acid synthesis, and enhance intestinal barrier functions. Conversely, excess fats or refined carbohydrates may cause dysbiosis, inflammation, and metabolic imbalances. Numerous studies have shown that therapeutic nutrition-e.g., low-protein renoprotective, hepatoprotective antioxidants, and allergen-elimination diets-holds enormous potential for treatment. In addition, fecal microbiota transplantation (FMT) can be used as an additive therapy for resistant gastrointestinal illnesses. Despite these developments, constraints remain in terms of standardization, study duration, and species-specific data, especially for cats. This review underscores dietary modification as a clinically actionable tool for microbiota-targeted therapy and calls for integrative, multi-omics research to translate microbiome modulation into precision nutrition for companion animals.}, } @article {pmid41471163, year = {2025}, author = {Ziaka, M}, title = {Targeting Gut-Lung Crosstalk in Acute Respiratory Distress Syndrome: Exploring the Therapeutic Potential of Fecal Microbiota Transplantation.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/pathogens14121206}, pmid = {41471163}, issn = {2076-0817}, mesh = {*Respiratory Distress Syndrome/therapy/microbiology ; Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Lung/microbiology/immunology ; Animals ; *Gastrointestinal Tract/microbiology ; }, abstract = {The gastrointestinal (GI) tract contributes significantly to the pathogenesis of acute respiratory distress syndrome (ARDS) by influencing systemic inflammation and sepsis, which are key factors in the development of multiple organ dysfunction syndrome (MODS), while the significant impact of gut microbiota in critically ill patients, including those with sepsis and ARDS, further underscores its importance. The intestinal microbiota is vital to immune system function, responsible for triggering around 80% of immune responses. Therefore, it may be hypothesized that modifying fecal microbiota, such as through fecal microbiota transplantation (FMT), could serve as a valuable therapeutic approach for managing inflammatory diseases like lung injury (LI)/ARDS. Indeed, emerging experimental research suggests that FMT may have beneficial effects in ARDS models by improving inflammation, oxidative stress, LI, and oxygenation. However, well-designed randomized clinical trials in patients with ARDS are still lacking. Our study seeks to examine how therapeutic interventions such as FMT might benefit LI/ARDS patients by exploring the interactions between the gut and lungs in this context.}, } @article {pmid41470815, year = {2025}, author = {Wei, X and Lang, F and Liu, H and Wang, S and Wang, T}, title = {Soluble Dietary Fiber from Highland Barley Bran Reduces Hepatic Lipid Accumulation in Mice via Gut Microbiota Modulation.}, journal = {Nutrients}, volume = {17}, number = {24}, pages = {}, doi = {10.3390/nu17243870}, pmid = {41470815}, issn = {2072-6643}, support = {2024-ZJ-963//Qinghai Provincial Natural Science Youth Foundation Project/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Dietary Fiber/pharmacology ; *Hordeum/chemistry ; *Liver/metabolism/drug effects ; Diet, High-Fat/adverse effects ; Mice ; *Lipid Metabolism/drug effects ; Male ; Mice, Inbred C57BL ; Fatty Acids, Volatile/metabolism ; Obesity/prevention & control/etiology/metabolism ; Lipidomics ; }, abstract = {BACKGROUND: Obesity has emerged as a significant public health challenge largely attributed to excessive dietary fat consumption. A growing body of evidence indicates that soluble dietary fiber (SDF) can prevent high-fat-diet (HFD)-induced obesity by modulating the gut microbiota. Our previous studies have shown that SDF derived from highland barley bran exhibits favorable lipid-lowering activity in vitro, but its lipid-lowering effect in vivo remains to be elucidated.

METHODS: This study aimed to investigate the lipid-lowering effects of SDF from highland barley bran in HFD-fed mice based on the gut microbiota. Mice were fed an HFD, and the intervention effects of SDF on hepatic lipid metabolism and its underlying molecular mechanisms were systematically evaluated using liver lipidomics, 16S rDNA sequencing, molecular biological techniques, and fecal microbiota transplantation (FMT).

RESULTS: Liver lipidomics analysis revealed that potential lipid biomarkers responsive to barley bran-derived SDF included phosphatidylethanolamines (PE, 18:2-20:3), phosphatidylserine (PS, 18:0-18:2), and PS (18:1-22:3). Furthermore, SDF modulated the composition and structure of the gut microbiota in HFD-fed mice. Notably, SDF increased the abundance of short-chain fatty acid (SCFA)-producing bacteria, particularly Dubosiella, as well as elevated SCFA levels.

CONCLUSIONS: The increase in SCFAs activated the hepatic AMP-activated protein kinase α (AMPK) signaling pathway, thereby ameliorating HFD-induced disturbances in lipid metabolism, reducing hepatic lipid accumulation, and lowering serum lipid concentrations.}, } @article {pmid41469665, year = {2025}, author = {Zheng, SH and Li, KZ and Feng, G and Wang, YT and Wang, JN and Li, SQ and Sun, YD}, title = {Gut microbiota reshaping the pancreatic cancer immune microenvironment: new avenues for immunotherapy.}, journal = {Molecular cancer}, volume = {24}, number = {1}, pages = {313}, pmid = {41469665}, issn = {1476-4598}, mesh = {Humans ; *Tumor Microenvironment/immunology ; *Gastrointestinal Microbiome/immunology ; *Pancreatic Neoplasms/therapy/immunology/etiology/pathology/microbiology/metabolism ; *Immunotherapy/methods ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {Pancreatic cancer remains one of the deadliest malignancies, primarily due to its highly immunosuppressive tumor microenvironment (TME) and poor response to conventional therapies. Increasing evidence highlights the gut microbiota as a pivotal regulator of antitumor immunity, modulating T cell activation, macrophage polarization, and dendritic cell function. Microbial communities and their metabolites can either inhibit or enhance immune surveillance, thereby influencing the efficacy of immunotherapies such as immune checkpoint inhibitors (ICIs) and CAR-T cell therapy. Approaches including dietary modulation, probiotics, fecal microbiota transplantation (FMT), and microbial metabolite supplementation show promise in restoring immune homeostasis and improving treatment outcomes. Additionally, gut microbiome profiling has emerged as a potential source of biomarkers for predicting therapeutic response and immune-related adverse events. This review summarizes current insights into microbiota-immune interactions in pancreatic cancer, emphasizes microbiome-targeted therapeutic strategies, and explores future opportunities for precision immunotherapy guided by microbial modulation.}, } @article {pmid41469027, year = {2025}, author = {Bu, T and Zhao, X and Kong, X and Huang, Z and Zhu, H and Sun, P and Yang, K and Chen, S and Cai, M}, title = {The Mechanism of Dendrobium officinale Polysaccharides in Alleviating Osteoporosis via Regulation of Wnt/β-Catenin Signaling Pathways and Modulation of Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c10301}, pmid = {41469027}, issn = {1520-5118}, abstract = {Osteoporosis (OP) poses a significant global health burden, with emerging therapies targeting the gut microbiota (GM). This study investigated the effects of Dendrobium officinale polysaccharides (DOP), characterized as an acetylated glucomannan with a linear β-(1 → 4)-mannose backbone, on ovariectomy (OVX)-induced OP through the gut-bone axis. DOP administration significantly attenuated bone loss in OVX mice by modulating bone turnover and inflammation markers, activating Wnt/β-catenin signaling, and preserving intestinal barrier function. Furthermore, DOP dose-dependently reshaped the GM composition, increasing the Firmicutes/Bacteroidetes ratio, especially enriching short chain fatty acids (SCFA)-producing genera Allobaculum and Clostridia_UCG-014, which consequently restored butyric and isovaleric acid levels. Crucially, fecal microbiota transplantation from DOP-treated donors reproduced the osteoprotective phenotype in recipient mice, establishing a causal role for DOP-modulated GM. These findings demonstrate that DOP alleviates OP via GM-driven SCFA production, barrier integrity, anti-inflammation, and Wnt/β-catenin signaling activation, underscoring its prebiotic potential for OP management.}, } @article {pmid41467904, year = {2026}, author = {Maruyama, D and Tian, X and Doan, TNM and Liao, WI and Chaki, T and Taenaka, H and Maishan, M and Matthay, MA and Prakash, A}, title = {Gut microbiome-derived propionate reprograms alveolar macrophages metabolically and regulates lung injury responses in mice.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2606486}, doi = {10.1080/19490976.2025.2606486}, pmid = {41467904}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Macrophages, Alveolar/metabolism/immunology ; Mice ; *Lung Injury/microbiology/metabolism/immunology ; Dietary Fiber/metabolism/administration & dosage ; Fatty Acids, Volatile/metabolism ; *Propionates/metabolism ; Mice, Inbred C57BL ; Male ; Bacteria/metabolism/classification/genetics/isolation & purification ; Lung/metabolism/immunology ; }, abstract = {Responses to lung injury can vary between individuals with the diet and gut microbiome representing two underappreciated sources for this variability. The gut microbiome can influence lung injury outcomes through the gut‒lung axis, but exactly how diet and its effects on the microbiota are involved remains unclear. We hypothesized that dietary fiber interventions would favor the presence of short-chain fatty acid (SCFA)-producing fermentative bacteria presence in the gut microbiome, thereby influencing the resting lung immunometabolic tone as well as influencing downstream responses to lung injury and infection. To test this hypothesis, we fed mice fiber-rich (FR) and fiber-free (FF) diets, and observed changes in the steady-state transcriptional programming of alveolar macrophages (AM). Next, we examined the effects of the FR and FF diets on murine responses to sterile and infectious lung injury in vivo while simultaneously profiling the gut microbiota and SCFA levels transmitted along the gut‒lung axis. Finally, we validated our in vivo observations with mechanistic studies of the metabolic, signaling, and chromatin-modifying effects of specific SCFAs on lung AM ex vivo and in vitro. Overall, our fiber-rich diet reprogrammed AMs and attenuated lung inflammation after sterile injury while exacerbating lung infection. This effect of FR diets could be transferred to germ-free (GF) mice by fecal microbiome transplantation (FMT) and depended on the ability of the microbiota to produce propionate. Mechanistically, SCFAs altered the metabolic programming of AMs and lung tissue ex vivo without a clear role for free fatty acid receptors (FFAR) or chromatin remodeling. These findings demonstrate that the gut‒lung axis can regulate resting lung metabolic tone through dietary fiber intake and the enrichment of SCFA-producing gut bacteria, as well as influence sterile and non-sterile lung injury responses. These results provide evidence to support the development of therapeutic dietary interventions to preserve or enhance specific aspects of host pulmonary immunity.}, } @article {pmid41466538, year = {2025}, author = {Zheng, B and Liu, L and Li, J and Chen, Y and Xie, J and Zhao, X and Feng, J and Zhou, Q and Hu, X and Yu, Q}, title = {Bound Polyphenols in Rice Bran Insoluble Dietary Fiber Ameliorate Intestinal Barrier Damage via Butyrate-Mediated Regulation of Apoptosis-Autophagy Signaling.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c12877}, pmid = {41466538}, issn = {1520-5118}, abstract = {Bound polyphenols (BPs) are critical to the anti-obesity effects of dietary fiber. However, their role in dietary-fiber-mediated intestinal barrier protection remains unclear. In this study, we demonstrated that rice bran insoluble dietary fiber (RIDF) alleviated intestinal barrier damage in high-fat-diet (high-fat diet)-fed mice, and this beneficial effect was dependent on BPs, as it was attenuated in mice treated with polyphenol-removed dietary fiber (RIDF_DF). Furthermore, fecal supernatant transplantation from RIDF-treated (not RIDF_DF-treated) mice alleviated obesity and reshaped the gut microbiota in recipient mice. Additionally, the fecal supernatant enhanced the intestinal barrier function and augmented the synthesis of short-chain fatty acids. Notably, butyrate administration upregulated intestinal tight junction proteins in Caco-2 cells and HFD-fed mice and increased Oscillospira abundance. Mechanistically, butyrate inhibited apoptosis and promoted autophagy, accompanied by alterations in the AMPK-Akt signaling pathway. These results indicate that BPs contribute to the ameliorative effect of RIDF on intestinal damage.}, } @article {pmid41466423, year = {2025}, author = {Chen, L and Tang, C and Hu, D and Yu, S and Liao, P}, title = {Brevilin a reverses colitis of inflammatory bowel disease via modulation of TNF-α signaling and microbiome dysregulation.}, journal = {Gut pathogens}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13099-025-00792-3}, pmid = {41466423}, issn = {1757-4749}, support = {2024000003-09//Middle-aged Backbone Talents in the Province/ ; }, abstract = {BACKGROUND: Brevilin A (Br) has shown potential in modulating inflammatory bowel disease (IBD). Our study aims to explore its mechanism of anti-inflammatory action.

METHODS: Colitis was induced in C57BL/6 mice with dextran sulfate sodium (DSS), followed by treatment with or without Br(20 mg/kg). Fecal microbiota and metabolites were profiled by metagenomic sequencing and liquid chromatography-mass spectrometry (LC-MS), respectively. Furthermore, to delineate the essential role of the gut microbiota, we employed antibiotic-treated (microbiota-depleted) mice in our investigation of Br's mechanism of action.

RESULTS: Br significantly alleviated DSS-induced colitis and modulated the gut microbiota profile. Specifically, Br enriched beneficial bacteria such as Lactobacillus, while suppressing pathogenic bacteria including Escherichia coli and Clostridium perfringens. Metabolomic analysis revealed that Br significantly altered bacterial metabolites, including 7-Oxolithocholic Acid, Kudinoside A, Veratrine, and Soyasaponin. These metabolites were linked to key pathways such as GPCR signaling, DNA damage response, aminoacyl-tRNA biosynthesis, riboflavin metabolism, and central carbon metabolism in cancer. Transcriptomic profiling indicated that Br inhibited the TNF-α signaling pathway, and this inhibition was confirmed as TNF-α overexpression reversed its anti-inflammatory effects. Furthermore, the therapeutic effects of Br were partially recapitulated in microbiota-depleted mice through fecal microbiota transplantation from Br-treated donors.

CONCLUSION: Br's ability to regulate gut microbiota and metabolites, improve gut barrier function, and eliminate inflammation by inhibiting TNF-α highlights its potential as a novel therapeutic medicine for IBD. Future research should focus on further exploring its mechanisms and clinical applications.}, } @article {pmid41466331, year = {2025}, author = {Li, J and Zhang, X and Zhao, X and Gong, G and Li, J and Dalai, B and Mo, Z and Xu, X and Jia, X and Li, Y and Lai, J and Wang, P and Sun, L and Liu, Y and Luo, X}, title = {Characterising gut microbiome dysbiosis in diarrhoea calves from multiple farms in Inner Mongolia using 16S and metagenomics.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {259}, pmid = {41466331}, issn = {2049-2618}, support = {2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; }, mesh = {Animals ; Cattle ; *Gastrointestinal Microbiome/genetics ; *Diarrhea/microbiology/veterinary/epidemiology ; RNA, Ribosomal, 16S/genetics ; *Metagenomics/methods ; China/epidemiology ; *Dysbiosis/microbiology/veterinary ; *Cattle Diseases/microbiology/epidemiology ; Feces/microbiology ; Escherichia coli/genetics/isolation & purification/pathogenicity ; *Bacteria/classification/genetics/isolation & purification ; Farms ; }, abstract = {BACKGROUND: The pathogenesis of neonatal calf diarrhoea (NCD), a critical disease that contributes to neonatal mortality in calves, remains nebulous.

RESULTS: Inner Mongolia, a key region for cattle farming in China, was selected as a study area to provide a comprehensive overview of the epidemiology and treatment of calf diarrhoea. No significant correlation was found between the incidence of diarrhoea and sampling points or medications. The severity of diarrhoea cases was stratified into five levels based on faecal characteristics. To elucidate the pathogenesis of NCD, 16S rRNA gene and metagenomic sequencing analyses were performed across severity levels. Microbial diversity analyses revealed distinct variations in microbial communities at different severity levels. Employing binning and LEfSe methodologies, two potential bacterial pathogens were identified: Escherichia coli (bin.216), leveraging non-canonical virulence mechanisms; and Streptococcus ruminantium (bin.338), an uncharacterised diarrhoeagenic bacterium. Furthermore, the viral agent Escherichia phage VpaE1_ev108 was significantly associated with disease progression. Gene function enrichment analysis revealed a broad spectrum of antibiotic resistance genes even in farms without direct antibiotic treatment, underscoring the pervasive prevalence of drug resistance.

CONCLUSIONS: The findings of this study revealed significant gut microbial dysbiosis in calves with severe diarrhoea, through which two putative NCD-associated pathogens were identified: E. coli (bin.216) and S. ruminantium (bin.338). Marked enrichment of Bacteroides spp. and Methanobrevibacter_A sp. 900313645 was observed in healthy cohorts, suggesting their potential protective roles. Therapeutic strategies employing phage-mediated pathogen targeting combined with probiotic transplantation have demonstrated dual benefits, potentially reducing antimicrobial dependency and preserving microbial homeostasis through ecological network reconstruction. Video Abstract.}, } @article {pmid41466105, year = {2025}, author = {Zhang, H and Shen, C and Lei, W and Wang, J and Liu, J and Qiu, Z}, title = {Pilot Clinical Trial of Fecal Microbiota Transplantation for Constipation in Parkinson's Disease.}, journal = {Journal of microbiology and biotechnology}, volume = {35}, number = {}, pages = {e2509029}, doi = {10.4014/jmb.2509.09029}, pmid = {41466105}, issn = {1738-8872}, mesh = {Humans ; *Constipation/therapy/etiology/microbiology ; *Fecal Microbiota Transplantation/methods ; *Parkinson Disease/complications/therapy/microbiology ; Aged ; Pilot Projects ; Middle Aged ; Male ; Gastrointestinal Microbiome ; Female ; Prospective Studies ; Feces/microbiology ; Treatment Outcome ; Dysbiosis/therapy ; Bacteria/classification/genetics/isolation & purification ; }, abstract = {The purpose of this study was to evaluate the safety and efficacy of fecal microbiota transplantation in patients with constipation due to parkinson's disease. Gut dysbiosis has long been associated with parkinson's and recent studies have shown that FMT can restore the normal flora of the gut. Therefore, this clinical trial aimed to test the therapeutic efficacy of FMT in 5 patients aged 55 to 71 diagnosed with PD who presented with constipation. The study was conducted as an open label, prospective trial and consisted of FMT performed every 3 days via nasojejunal tube placement followed by 8 weeks of patient follow-up to evaluate response to drug therapy and to assess neurological function using UPDRS-III OFF scores, and improvement in constipation assessed with Wexner scores. Samples taken before and after FMT were collected for shotgun metagenomic sequencing to analyze the composition of the microbial communities present in patients. Untargeted non-targeted metabolomic studies were performed to investigate the impact of FMT on metabolome changes due to FMT. The results indicate an improvement in constipation and neurological functioning following FMT, and significant alteration of the gut microbiota. Significant increases in Bifidobacteria bifidus, Alistipes shahi, Anaerotruncus coli, and uncharacterized Flavonifractor were found post-treatment compared to the baseline. Many of the other strains present prior to treatment, including Acinetobacter sp. and Proteobacteria sp., had significantly decreased after the FMT. The metabolomic studies found shifts in metabolic pathways involved with unsaturated fatty acid synthesis and amino acid metabolism due to FMT. FMT may be an effective treatment option for constipation and neurological symptoms associated with PD.}, } @article {pmid41465322, year = {2025}, author = {Rzeczycki, P and Pęciak, O and Plust, M and Droździk, M}, title = {Gut Microbiota in the Regulation of Intestinal Drug Transporters: Molecular Mechanisms and Pharmacokinetic Implications.}, journal = {International journal of molecular sciences}, volume = {26}, number = {24}, pages = {}, doi = {10.3390/ijms262411897}, pmid = {41465322}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; *Intestinal Mucosa/metabolism ; Multidrug Resistance-Associated Protein 2 ; *Membrane Transport Proteins/metabolism ; }, abstract = {Gut microbiota, through both its species composition and its metabolites, impacts expression and activity of intestinal drug transporters. This phenomenon directly affects absorption process of orally administered drugs and contributes to the observed inter-individual variability in pharmacotherapeutic responses. This review summarizes mechanistic evidence from in vitro and animal studies and integrates clinical observations in which alterations in gut microbiota are associated with changes in oral drug exposure, consistent with potential regulation of key intestinal drug transporters-such as P-glycoprotein (P-gp, ABCB1), Breast Cancer Resistance Protein (BCRP, ABCG2), MRP2/3 proteins (ABCC2/3), and selected Organic Anion-Transporting Polypeptides (OATPs, e.g., SLCO1A2, SLCO2B1)-by major bacterial metabolites including short-chain fatty acids (SCFAs), secondary bile acids, and tryptophan-derived indoles. The molecular mechanisms involved include activation of nuclear and membrane receptors (PXR, FXR, AhR, TGR5), modulation of transcriptional and stress-response pathways (Nrf2, AP-1) with simultaneous suppression of pro-inflammatory pathways (NF-κB), and post-translational modifications (e.g., direct inhibition of P-gp ATPase activity by Eggerthella lenta metabolites). The review also highlights the pharmacokinetic implications of, e.g., tacrolimus, digoxin, and metformin. In conclusion, the significance of "drug-transporter-microbiome" interactions for personalized medicine is discussed. Potential therapeutic interventions are also covered (diet, pre-/probiotics, fecal microbiota transplantation, modulation of PXR/FXR/AhR pathways). Considering the microbiota as a "second genome" enables more accurate prediction of drug exposure, reduction in toxicity, and optimization of dosing for orally administered preparations.}, } @article {pmid41464856, year = {2025}, author = {Sylwestrzak, T and Ciosek, M and Pastuszak, K and Jastrzębski, T}, title = {Fecal Short-Chain Fatty Acids in Colorectal Cancer Patients Versus Healthy Controls: A Systematic Review and Meta-Analysis.}, journal = {Journal of clinical medicine}, volume = {14}, number = {24}, pages = {}, doi = {10.3390/jcm14248949}, pmid = {41464856}, issn = {2077-0383}, abstract = {Background: Short-chain fatty acids (SCFAs), the main microbial fermentation products in the colon, have immunometabolic and anti-neoplastic properties. Alterations in fecal SCFA profiles have been proposed as potential non-invasive biomarkers for colorectal cancer (CRC), but previous findings remain inconsistent. This systematic review and meta-analysis aimed to determine whether fecal acetate, propionate, and butyrate concentrations differ between patients with CRC and healthy individuals. Methods: A comprehensive search of PubMed, Web of Science and Cochrane Library was conducted on 18 September 2025. Eligible studies were observational, included adults with histologically confirmed CRC and healthy controls, and reported fecal concentrations of at least one SCFA quantified using validated analytical methods. Two independent reviewers performed study screening, data extraction, and risk-of-bias assessment. Random-effects models were applied to calculate pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: Thirteen studies met inclusion criteria for qualitative synthesis, and four (141 CRC cases, 98 controls) were eligible for meta-analysis. Compared with healthy controls, patients with CRC had significantly lower fecal acetate (pooled SMD -0.37; 95% CI -0.63 to -0.10; p = 0.006; I[2] = 0%) and butyrate (pooled SMD -0.59; 95% CI -1.10 to -0.07; p = 0.026; I[2] = 64.4%), whereas propionate did not differ significantly (pooled SMD -0.02; 95% CI -0.85 to 0.82; p = 0.971; I[2] = 89%). Conclusions: CRC is associated with reduced fecal butyrate and, to a lesser extent, acetate, suggesting impaired microbial fermentation. Propionate shows no consistent difference. SCFA profiling currently lacks sufficient standardization and validation for clinical application. Future harmonized, longitudinal studies integrating diet, microbiome, and metabolomic data are warranted to confirm SCFAs as reproducible biomarkers of CRC.}, } @article {pmid41464526, year = {2025}, author = {Ichim, C and Boicean, A and Todor, SB and Boeras, I and Anderco, P and Birlutiu, V}, title = {Dynamics of Fecal microRNAs Following Fecal Microbiota Transplantation in Alcohol-Related Cirrhosis.}, journal = {Journal of clinical medicine}, volume = {14}, number = {24}, pages = {}, doi = {10.3390/jcm14248623}, pmid = {41464526}, issn = {2077-0383}, abstract = {Background: Micro-RNAs (miRNAs) are emerging as pivotal regulators of pathophysiological processes, reflecting systemic responses to stress, inflammation and metabolic imbalance. Their role in advanced liver disease and in modulating responses to therapeutic interventions, such as fecal microbiota transfer (FMT), remains insufficiently characterized. Methods: We conducted a prospective study including six male patients with toxic ethanolic liver cirrhosis undergoing FMT and six healthy controls. Stool and blood samples were collected pre- and post-FMT. Fecal micro-RNA expression (miR-21, miR-122, miR-125, miR-146 and miR-155) was quantified using RT-qPCR and normalized to miR-26c. Associations with noninvasive fibrosis markers (FIB-4, APRI, elastography, CAP) and biological parameters were analyzed through multivariable regression and Pearson correlation, with internal validation by bootstrapping. Results: One week after fecal microbiota transfer, miR-21 and miR-146 exhibited significant expression changes, while miR-122, miR-125, and miR-155 showed non-significant trends toward increased expression. Post-FMT increases in miR-21, miR-122, miR-146 and miR-155 were consistently associated with reductions in hepatic fibrosis markers (FIB-4, APRI and liver stiffness), whereas no significant associations were observed with CAP. Conclusions: Fecal micro-RNAs reflect interconnected molecular networks that capture systemic adaptations to FMT. Despite a limited cohort, these findings highlight their potential as integrative biomarkers and as therapeutic targets in advanced liver disease. Larger-scale studies are warranted to validate clinical utility.}, } @article {pmid41463403, year = {2025}, author = {Sun, X and Li, P and Chen, B and Chen, C and Zhao, J and Sun, S}, title = {Fucoidan Therapy for Extraintestinal Diseases: Targeting the Microbiota-Gut-Organ Axes.}, journal = {Biomolecules}, volume = {15}, number = {12}, pages = {}, doi = {10.3390/biom15121750}, pmid = {41463403}, issn = {2218-273X}, support = {82374218//National Natural Science Foundation of the People's Republic of China/ ; 82405310//National Natural Science Foundation of the People's Republic of China/ ; 2023DYPLHGG-09//The First Batch of Joint Research Projects of the China Association of Traditional Chinese Medicine/ ; MS2021002//Jiangsu Province Traditional Chinese Medicine Science and Technology Development Project/ ; 1020241792//Natural Science Foundation of the Jiangsu Higher Education Institutions of China/ ; }, mesh = {*Polysaccharides/therapeutic use/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Humans ; Animals ; Prebiotics ; Obesity/drug therapy/microbiology ; }, abstract = {The microbiota-gut-organ axis is widely recognized as a pivotal mediator of systemic health, primarily through gut-derived immune, metabolic, and inflammatory signaling. Fucoidans, a class of fucose-containing sulfated polysaccharides predominantly composed of L-fucose and exclusively found in brown seaweeds, have been demonstrated to modulate gut microbiota composition and function, resulting in the enrichment of beneficial bacteria and the suppression of harmful species. They enhance the production of beneficial metabolites, such as short-chain fatty acids and specific bile acids, while suppressing harmful metabolites, including lipopolysaccharide, thereby ameliorating organ damage via key mechanisms such as the mitigation of oxidative stress and inhibition of inflammatory responses. Furthermore, fucoidan supplementation was found to restore intestinal barrier integrity. Using disease models including Parkinson's disease, alcoholic liver disease, diabetic kidney disease, and obesity, the mechanisms through which fucoidans ameliorate extraintestinal diseases via the microbiota-gut-organ axis were elucidated. Microbiota-dependent mechanisms have been confirmed via experimental approaches such as fecal microbiota transplantation and specific bacterial strain supplementation. Fucoidans represent promising prebiotic agents for the restoration of microbial ecology and the treatment of extraintestinal diseases, highlighting the need for further clinical investigation.}, } @article {pmid41462485, year = {2025}, author = {Wang, D and Chen, Y and Yang, J and Zhang, Y and Deng, X and Liu, Y and Chen, Y and Yang, X and Wang, X and Liang, C and Xie, Q and Hao, Y and Yuan, H}, title = {Modulation of gut microbiota in Graves' orbitopathy: Prevotella dominance and atorvastatin's impact.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {258}, pmid = {41462485}, issn = {2049-2618}, support = {82270865//National Natural Science Foundation of China under Grant/ ; 231111313200//Henan Provincial Key Research and Development Projects/ ; SBGJ202301001//Henan Provincial Medical Science and Technology Research Program-the Provincial and Ministerial Major Projects/ ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; *Atorvastatin/pharmacology/therapeutic use/administration & dosage ; Humans ; Animals ; Mice ; Male ; Female ; Feces/microbiology ; Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S/genetics ; *Prevotella/drug effects/isolation & purification/genetics ; Middle Aged ; *Graves Ophthalmopathy/microbiology/drug therapy ; Adult ; Glucocorticoids/therapeutic use/administration & dosage ; Anti-Bacterial Agents/pharmacology ; }, abstract = {BACKGROUND: The gut microbiota in patients with Graves' orbitopathy (GO) may influence the disease's progression, but its specific role and function in the progression of GO treatment are not well understood.

METHODS: We performed fecal microbiota sequencing using the 16S rRNA-gene sequencing on patients with GO (n = 48), Graves' disease (GD, n = 40), and healthy controls (HC, n = 36). Subsequently, fecal samples from patients with GO, GD, and healthy donors were transplanted into antibiotic-treated pseudo-germ-free mice. Finally, the 48 patients with GO were randomly divided into two groups: one group received intravenous glucocorticoids (ivGC) and atorvastatin (n = 24), while the other group received ivGC only (n = 24), to observe the effects of atorvastatin on GO progression and its impact on gut microbiota.

RESULTS: Patients with GO exhibit a distinct gut microbiota composition, particularly marked by increased levels of Prevotella and Bacteroides, compared to patients with GD and HC. Correlation analysis revealed a direct positive association between Prevotella and thyrotropin receptor antibody levels. Antibiotic-treated pseudo-germ-free mice that received fecal transplants from patients with GO exhibited a slower rate of weight gain, significant impairment of intestinal barrier integrity, and markedly increased levels of serum LBP and inflammatory factors. A combined treatment regimen of ivGCs and atorvastatin significantly reduced ocular clinical symptoms in patients with GO, including clinical activity score, exophthalmos, and intraocular pressure, while also promoting a healthier gut microbiota composition and a reduction in Prevotella levels.

CONCLUSIONS: Gut microbiota imbalance, particularly involving Prevotella, contributes to GO's development and progression. Atorvastatin may slow GO progression by correcting dysregulated gut microbiota, especially reducing Prevotella. Video Abstract.}, } @article {pmid41461744, year = {2025}, author = {Cho, H and Nam, H and Kim, HE and Kim, JE and Park, JI and Park, J and Kim, YC and Lee, JP and Kim, DK and Joo, KW and Kim, YS and Kim, BS and Park, S and Lee, H}, title = {Gut microbiome and metabolite signatures for predicting acute kidney transplant rejection: a prospective study.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {44709}, pmid = {41461744}, issn = {2045-2322}, support = {2021R1I1A1A01060190//National Research Foundation grants funded by the Korean government/ ; 2018R1A3B1052328//National Research Foundation grants funded by the Korean government/ ; 2022R1A2C2011190//by National Research Foundation grants funded by the Korean government/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Kidney Transplantation/adverse effects ; Female ; Male ; Prospective Studies ; Middle Aged ; *Graft Rejection/metabolism/microbiology/diagnosis/etiology ; Adult ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Metabolomics/methods ; Dysbiosis/microbiology ; *Metabolome ; }, abstract = {Acute rejection (AR) remains a significant challenge in kidney transplantation (KT) despite advances in immunosuppressive treatment. Recognizing the critical influence of the gut microbiome on modulating host immunity, we investigated the association between gut dysbiosis and AR in KT recipients. A total of 97 patients with KT were prospectively enrolled from two centers, and their samples were collected at multiple time points, such as pre-transplant (n = 97), three months (n = 66), and twelve months (n = 37) post-transplant. Microbial profiling was performed using 16S rRNA sequencing and fecal metabolomics was done via nuclear magnetic resonance spectroscopy. Thirty-three patients developed AR after KT, exhibiting reduced bacterial richness and diversity compared with KT recipients without AR. In addition, these patients had increased Escherichia-Shigella and decreased Phascolarctobacterium abundance. Pathway analysis identified 47 enriched pathways in AR patients, notably those involved in lipopolysaccharide biosynthesis and short-chain fatty acid metabolism. Consistent results were obtained from stool metabolomics, showing reduced propionate and lactate concentrations compared with patients without AR. Finally, combining pre-KT bacterial and fecal metabolite features with clinical parameters significantly improved AR prediction accuracy. Our results suggest that integrating clinical, microbial, and metabolomic data may provide a more holistic patient care regimen across both pre- and post-transplant phases.}, } @article {pmid41461285, year = {2025}, author = {Bharathi, S and Soundara Rajan, YAPA and Prakash, S and Immanuel, G and Ramasubburayan, R}, title = {Pathobionts in the microbiome: Drivers of disease and targets for treatment.}, journal = {Microbial pathogenesis}, volume = {211}, number = {}, pages = {108268}, doi = {10.1016/j.micpath.2025.108268}, pmid = {41461285}, issn = {1096-1208}, abstract = {Pathobionts are commensal inhabitants of the human microbiome that can transition to a pathogenic state under specific genetic or environmental conditions. They have recently gained attention for their impact on various clinical conditions. This review discusses the key factors behind pathobiont emergence, including microbial dysbiosis, antibiotic use, dietary influences, immune dysfunction and host genetics. It provides a comprehensive overview of pathobionts associated with the gut, oral cavity, and vaginal microbiomes highlighting their roles in disease pathogenesis. A significant focus is also placed on the involvement of pathobiont in immune-related disorders. Furthermore, current and advanced therapeutic strategies aimed at mitigating the effects of pathobionts, such as faecal microbiota transplantation, phage therapy, probiotics and prebiotics, along with their advantages and limitations, were highlighted. Thus, the integrated perspective combining microbial ecology, host immunity, and therapeutic strategies outlines the need for targeted, microbiome-based interventions to address the complex behaviour of pathobionts.}, } @article {pmid41460363, year = {2025}, author = {Wang, C and Li, H and Wang, T and Li, X and Liu, J and Deng, A and Jiao, X}, title = {The gut-eye axis in blinding eye diseases: microbiota-driven immune dysregulation and immunomodulatory therapies.}, journal = {International ophthalmology}, volume = {46}, number = {1}, pages = {57}, pmid = {41460363}, issn = {1573-2630}, support = {2024BSQD05//the Doctoral Startup Fund of the Affiliated Hospital of Shandong Second Medical University/ ; ZR2025QC815//the Shandong Provincial Natural Science Foundation/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/immunology ; Animals ; Probiotics/therapeutic use ; Dysbiosis ; *Immunomodulation ; *Eye Diseases/therapy/microbiology/immunology ; }, abstract = {PURPOSE: To synthesize recent (2020-2025) advances on how gut, oral, and ocular-surface microbiota contribute to major blinding eye diseases, dry eye disease (DED), non-infectious uveitis, glaucoma, optic neuropathy, age-related macular degeneration (AMD), and diabetic retinopathy (DR), and to evaluate the therapeutic potential of microbiome-based interventions.

METHODS: PubMed and Web of Science were searched (January 2020-October 2025) using the terms "gut microbiota", "ocular diseases", and "immunomodulatory therapies". Eligible studies included original human and animal research demonstrating microbial dysbiosis or testing microbiome-directed therapies. Data were synthesized thematically across microbial composition, immune-metabolic mechanisms, and intervention outcomes.

RESULTS: Across all six diseases, dysbiosis was consistently characterized by depletion of anti-inflammatory taxa such as Akkermansia, Ruminococcaceae, and other short-chain fatty acid (SCFA) producers, with enrichment of pro-inflammatory bacteria including Proteobacteria, Staphylococcus, and Porphyromonas gingivalis. These changes were associated with increased intestinal permeability, systemic lipopolysaccharide (LPS) and trimethylamine N-oxide (TMAO), Th17 (T helper 17)/Treg (regulatory T cell) imbalance, and loss of SCFA-mediated neuroprotection. Probiotics containing Lactobacillus or Bifidobacterium improved tear stability and reduced inflammation in preclinical and pilot clinical studies, while high-fiber diets ameliorated lesions in age-related macular degeneration (AMD) and diabetic retinopathy (DR). Fecal microbiota transplantation confirmed microbial causality but revealed donor-dependent effects, and engineered Lactobacillus expressing angiotensin-converting enzyme 2 (ACE2) or Ang-(1-7) preserved retinal integrity in diabetic models.

CONCLUSIONS: Microbial dysbiosis acts as a common driver of immune-metabolic dysfunction in blinding eye diseases. Microbiome-targeted strategies show promising efficacy in experimental systems, but large, longitudinal human trials are needed for clinical translation.}, } @article {pmid41459531, year = {2025}, author = {Nikolaidis, CG and Gyriki, D and Stavropoulou, E and Karlafti, E and Didangelos, T and Tsigalou, C and Thanopoulou, A}, title = {Targeting the TLR4 axis with microbiota-oriented interventions and innovations in diabetes therapy: a narrative review.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1701504}, pmid = {41459531}, issn = {1664-3224}, mesh = {Humans ; *Toll-Like Receptor 4/metabolism/immunology ; *Gastrointestinal Microbiome/immunology/drug effects ; Fecal Microbiota Transplantation ; *Diabetes Mellitus, Type 2/therapy/immunology/microbiology/metabolism ; Animals ; Signal Transduction ; NF-kappa B/metabolism ; *Diabetes Mellitus, Type 1/therapy/immunology/microbiology/metabolism ; Insulin Resistance ; }, abstract = {The gut microbiota-Toll-like receptor 4(TLR4)-nuclear factor kappa B(NF-κB) signaling is a key controller of low-grade chronic inflammation and insulin resistance in type 1 (T1DM) and type 2 diabetes mellitus (T2DM). While TLR4-mediated inflammation contributes to both T1DM and T2DM, the bulk of microbiota-targeted interventions have been studied in T2DM. The focus of the current review is on T2DM, with relevant parallels in T1DM noted where appropriate. Modulation of this pathway by dietary natural bioactive molecules, fecal microbiota transplantation (FMT), and technological innovations hold therapeutic promise for the reconstitution of metabolic and immune homeostasis. Agents like celastrol, berberine, paeoniflorin, and licorice extract exhibit anti-inflammatory and antidiabetic effects by TLR4/Myeloid differentiation primary response 88(MyD88)/NF-κB signaling inhibition. FMT enhanced β-cell function and insulin sensitivity with evidence of immune-metabolic modulation. New technologies, like ingestible biosensors and gut-on-chip platforms, allow real-time monitoring and precision modulating of the microbiota. Gastric bypass-induced microbial remodeling is linked to long-term glycemic benefit. Pharmacological, surgical, and technological manipulation of gut microbiota-immune interactions is a potential complementary strategy to diabetes. The future encompasses personalized microbiota-matching, controlled FMT regimens, and incorporation of digital therapeutics into microbiome-based precision medicine.}, } @article {pmid41415394, year = {2025}, author = {Barcena-Varela, M and Shang, J and Mogno, I and Lozano, A and Liebling, I and Mead, KR and Li, Z and Grinspan, LT and Lindblad, KE and Ruiz de Galarreta, M and Donne, R and Gnjatic, S and Merad, M and Jun, T and Ang, C and Marron, TU and Faith, J and Lujambio, A}, title = {Bacteroidetes promote hepatocellular carcinoma progression and resistance to immunotherapy.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41415394}, issn = {2692-8205}, support = {S10 OD026880/OD/NIH HHS/United States ; S10 OD030463/OD/NIH HHS/United States ; T32 AI078892/AI/NIAID NIH HHS/United States ; P30 CA196521/CA/NCI NIH HHS/United States ; T32 CA078207/CA/NCI NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; R01 DK124133/DK/NIDDK NIH HHS/United States ; R37 CA230636/CA/NCI NIH HHS/United States ; UL1 TR004419/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND AND AIMS: Growing evidence highlight the critical role of the gut microbiome in tumorigenesis and response to immunotherapies. However, the impact of gut microbes on hepatocellular carcinoma (HCC) progression and response to immune-checkpoint blockade (ICB) remains unclear due to the lack of combined preclinical and clinical studies.

APPROACH & RESULTS: We performed 16S rRNA of cross-cohort stool samples from 10 HCC responders (R) and 40 non-responders (NR) to ICB at baseline and on-treatment time-points. We identified an enrichment of Bacteroidetes in NR. To study the role of the microbiome in the cancer immune response, we generated an immunogenic mouse model of HCC via hydrodynamic tail-vein injection (HDTVI) of DNA plasmids mimicking common HCC alterations and immunogenicity by expressing model antigens (MYC-lucOS;CTNNB1 tumors). We found that antibiotic (ABX)-induced dysbiosis promoted a pro-tumorigenic effect in the MYC-lucOS;CTNNB1 HCC model by the expansion of a specific Bacteroidetes, Parabacteroides distasonis. Colonization of mice carrying MYC-lucOS;CTNNB1 HCCs with Parabacteroides distasonis confirmed its pro-tumorigenic effect in vivo. Furthermore, we explored the effects of colonizing with microbiotas from patients and showed that microbiota from a NR donor enriched in Bacteroidetes promoted faster tumorigenesis than microbiota from a R donor with reduced Bacteroidetes. We isolated 6 Bacteroidetes species from the NR donor, cultured them, and used them as a cocktail to colonize mice; similarly, mice transplanted with this cocktail showed increased tumorigenesis and reduced survival.

CONCLUSIONS: This study identified Bacteroidetes enrichment as a potential biomarker of ICB resistance in HCC and, by using immunogenic mouse models, established that Bacteroidetes abundance influences tumor development.}, } @article {pmid41459433, year = {2025}, author = {Bhojiya, AA and Saurabh, A and Jain, D}, title = {Editorial: Microbial therapeutics: harnessing the human microbiome for disease treatment and prevention.}, journal = {Frontiers in medical technology}, volume = {7}, number = {}, pages = {1751147}, doi = {10.3389/fmedt.2025.1751147}, pmid = {41459433}, issn = {2673-3129}, } @article {pmid41459234, year = {2025}, author = {Xu, X and Zhang, Y and Zu, Y and Xu, Y and Liao, T and Li, X and Yan, J}, title = {The role of gut microbiota imbalance in preeclampsia pathogenesis: insights into FMO3-mediated inflammatory mechanisms.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1682007}, pmid = {41459234}, issn = {1664-302X}, abstract = {BACKGROUND: Preeclampsia (PE) is a severe pregnancy complication linked to systemic inflammation and metabolic dysregulation. Emerging evidence suggests gut microbiota imbalance may contribute to PE pathogenesis, but the underlying mechanisms remain unclear. This study investigated whether gut dysbiosis triggers PE through flavin-containing monooxygenase 3 (FMO3)-mediated inflammatory pathways.

METHODS: We transplanted fecal microbiota from PE rats, healthy pregnant (HP) rats, and non-pregnant (NP) rats into antibiotic-treated dysbiotic rats, with a control group receiving normal saline (CON). Additionally, FMO3 expression was inhibited using FMO3-RNAi in parallel groups. We measured blood pressure, urine protein, FMO3 protein and mRNA expression, inflammatory markers, liver and kidney function, embryo resorption rate, and fetal weight. Gut microbiota composition was analyzed by 16S rRNA gene sequencing. The impact of interleukin-8 (IL-8) on trophoblast cell function was assessed using cell counting kit-8 (CCK-8), transwell invasion, and tube formation assays.

RESULTS: Rats receiving PE fecal microbiota transplantation (FMT) exhibited a gradual rise in blood pressure post-pregnancy, varying degrees of liver and kidney damage, markedly elevated serum inflammatory cytokines, higher fetal resorption rates, and reduced placental weights. FMO3 protein and mRNA expressions were significantly higher in the PE-FMT group. FMO3 knockdown partially improved these perinatal outcomes. Antibiotic treatment significantly decreased gut microbiota alpha and beta diversity. At the genus level, the PE-FMO3-RNAi group showed increased Escherichia-Shigella and decreased Lactobacillus compared to the PE-CON-RNAi group. In cell experiments, elevated IL-8 levels decreased the viability and invasiveness of HTR-8/SVneo cells and diminished the angiogenic potential of human umbilical vein endothelial cells (HUVECs).

CONCLUSION: A disruption of gut microbiota could result in PE through the FMO3-driven inflammatory response, and targeting FMO3 may prove valuable in treating PE.}, } @article {pmid41459210, year = {2025}, author = {Yang, W and Wu, H and Li, X and Wan, Z and Kong, W and Huang, C}, title = {Gut-lung axis in allergic rhinitis: microbial dysbiosis and therapeutic strategies.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1654997}, pmid = {41459210}, issn = {1664-302X}, abstract = {BACKGROUND: Allergic rhinitis (AR) affects an estimated 10%-30% of people worldwide and places a significant burden on both health and healthcare systems. Recent research suggests that imbalances in the gut microbiota may contribute to the development of AR by disrupting immune regulation along the gut-lung axis. However, these insights have yet to be fully translated into clinical practice.

METHODS: We performed a systematic review of studies published between 2010 and 2025, including clinical research, animal experiments, and multi-omics analyses, retrieved from PubMed, Web of Science, Embase, Cochrane, CNKI, and Wanfang databases. The review aimed to evaluate immune mechanisms mediated by the gut microbiota and assess microbiota-targeted interventions in AR.

RESULTS: Patients with AR consistently show reduced fecal butyrate levels, with several studies reporting significant declines, alongside elevated serum IgE concentrations. These changes are closely linked to gut dysbiosis, characterized by reduced abundance of Faecalibacterium and imbalances in the Bacteroidetes/Firmicutes ratio. Dysbiosis appears to drive activation of the aryl hydrocarbon receptor (AhR) pathway, evidenced by a 1.5-fold increase in the kynurenine/tryptophan ratio (p < 0.05), and contributes to impaired regulatory T-cell function. Experimental evidence supports these associations: in murine models, fecal microbiota transplantation (FMT) reduced nasal IL-13 levels by as much as 60% in one study. In human trials, probiotic supplementation, particularly with Clostridium butyricum, was linked to reductions in serum IgE in some cohorts. Integration of multi-omics datasets further reveals conserved mechanisms, including butyrate-mediated histone deacetylase inhibition and vagus nerve-dependent suppression of mast cell activity. Moreover, combinatorial approaches, such as combining probiotics with FXR agonists, have yielded significant improvements in preclinical models, notably reducing nasal symptom scores.

CONCLUSION: Gut dysbiosis contributes to the development of AR by disrupting immune-metabolic pathways along the gut-lung axis. Microbiota-targeted interventions hold promise for both the prevention and management of AR, especially in pediatric populations. To achieve long-term impact, public health strategies that combine dietary modifications with measures to reduce air pollution are urgently needed.}, } @article {pmid41458114, year = {2025}, author = {Pan, D and Li, J and Chen, S and Gu, S and Jiang, M and Xu, Q}, title = {Microbiota-gut-brain axis pathogenesis and targeted therapeutics in sleep disorders.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1721606}, pmid = {41458114}, issn = {1664-2295}, abstract = {Sleep constitutes an essential physiological process that is vital for maintaining physical and mental wellbeing. However, the science of sleep focusing on basic questions such as "how" we sleep and "why" we sleep is still not clear. Over the past decade, substantial progress has also been made in elucidating the interactions between sleep and other biological processes, providing insights into the basic questions of sleep. Among these, emerging evidence highlights the microbiota-gut-brain axis (MGBA) as a pivotal bidirectional network that connects gut microorganisms with the central nervous system to regulate sleep architecture and homeostasis. This interaction is inherently bidirectional: sleep deprivation alters gut motility, mucosal integrity, and microbial composition, while microbial metabolites in turn influence neurotransmission (γ-aminobutyric acid, serotonin), immune-endocrine balance, and inflammatory signaling. In this article, we will review recent studies about MGBA-targeted therapeutic strategies for sleep disorders, such as probiotics, prebiotics, and fecal microbiota transplantation, which aim to restore microbial homeostasis and improve sleep quality. Furthermore, we discuss emerging interventions that modulate microbial metabolites and neuroimmune-endocrine signaling, as well as innovative pharmacological approaches targeting MGBA dysfunction. Collectively, we hope this review will contribute to a deeper understanding of MGBA-mediated mechanisms in sleep disorders promises to inform novel preventive and therapeutic strategies, ultimately improving clinical outcomes and quality of life for affected individuals.}, } @article {pmid41455148, year = {2025}, author = {Uoti, A and Neulasalmi, O and Hiippala, K and Oksanen, T and Arkkila, P and Puustinen, L and Satokari, R and Sjöstedt, N}, title = {Characterization of fecal deglucuronidation activity in healthy subjects and in patients treated with fecal microbiota transplantation.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {53}, number = {12}, pages = {100205}, doi = {10.1016/j.dmd.2025.100205}, pmid = {41455148}, issn = {1521-009X}, abstract = {Gut bacterial β-glucuronidase (GUS) enzymes contribute to the intestinal toxicity and/or enterohepatic recycling of glucuronidated compounds by cleaving glucuronide conjugates excreted into the intestinal lumen. The activities and substrate specificities of several GUS isoforms have been recently described. However, the extent of intraindividual and interindividual variability in gut microbial deglucuronidation activity has remained poorly characterized. In this study, we used pan-GUS reporter substrates as well as drug and steroid glucuronides to study the deglucuronidation activities of fecal lysates produced from individual fecal samples from healthy donors (n = 12), and sequential samples collected from fecal microbiota transplantation (FMT) donors (n = 3) and patients with recurrent Clostridioides difficile infection who underwent FMT (n = 7). To determine relationships between fecal deglucuronidation activity and gut microbiota composition, we used 16S rRNA gene sequencing to characterize the healthy donors' fecal microbiotas. Although we observed considerable interindividual variability specifically in the processing of steroid glucuronides, intraindividual variability in the fecal deglucuronidation activity of FMT donors was relatively modest. We observed the female sex and Alistipes, Faecalibacterium, and Gemmiger taxa to be associated with higher deglucuronidation activity, whereas the abundance of Roseburia correlated negatively with deglucuronidation activity. In addition, the baseline deglucuronidation activity of patients with recurrent C. difficile infection was low but increased by FMT treatment. The results of this study further highlight deglucuronidation as a function of a healthy gut microbiota. Moreover, these results improve our understanding of deglucuronidation activity as a source of individual variability in the pharmacokinetics and pharmacodynamics of glucuronidated drugs that undergo enterohepatic recycling. SIGNIFICANCE STATEMENT: Gut microbial deglucuronidation rates of specific compounds may vary considerably between individuals. Deglucuronidation activity is relatively stable within healthy individuals for ≥1 year, but fecal microbiota transplantation can significantly alter the deglucuronidation activity of an individual.}, } @article {pmid41454672, year = {2026}, author = {Aldriwesh, MG and Alotibi, RS and Alqurainy, N and Alrabiah, S and Arafah, AM and Alghoribi, MF and Ajina, R}, title = {The role of gut microbiome in aging-associated diseases: where do we stand now and how technology will transform the future.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2607076}, doi = {10.1080/19490976.2025.2607076}, pmid = {41454672}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Aging ; *Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Animals ; Precision Medicine ; }, abstract = {The gut microbiome has emerged as a critical regulator of human aging and healthspan, with age-related dysbiosis increasingly implicated in a broad spectrum of aging-associated diseases. This review synthesizes evidence linking gut microbial alterations to infectious diseases, antimicrobial resistance, autoimmune, neurodegenerative, psychiatric, cancer, metabolic, kidney, cardiovascular, bone, and muscular diseases, highlighting shared mechanisms such as chronic inflammation, immune dysregulation, and metabolite imbalance. We further explore how enabling technologies, including functional multi-omics, synthetic biology, artificial intelligence-driven analytics, biobanking, and autologous fecal microbiota transplantation, are revolutionizing microbiome research and the design of interventions. Ethical considerations surrounding microbiome-based therapies are also addressed. To translate these scientific insights into clinical innovations, we formulate the PRIME framework: a five-phase roadmap encompassing Profiling, Reviewing, Identifying, Mapping, and Evaluating microbiome-based interventions. By integrating microbiome science, aging biology, and emerging technologies, this review provides a comprehensive blueprint for advancing precision medicine and promoting healthy aging. Furthermore, it emphasizes the importance of building future-ready capabilities to navigate the evolving landscape of age-related diseases and microbiome-driven therapeutic innovations.}, } @article {pmid41453546, year = {2025}, author = {Huang, S and Huang, F and Yang, L and Li, J and Qin, B and Zhou, R and Zhou, D and Tang, Y}, title = {Shentao Ruangan Formula Ameliorates Cholestatic Liver Disease via Gut Microbiota Remodeling: Deciphering the "Gan Bing Zhi Pi" Mechanism of Traditional Chinese Medicine Through the Gut-Liver Axis.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {121069}, doi = {10.1016/j.jep.2025.121069}, pmid = {41453546}, issn = {1872-7573}, abstract = {The Shentao Ruangan (STR) formula, developed under Traditional Chinese Medicine (TCM)'s "Gan Bing Zhi Pi" (treating liver via spleen) theory, shows promise in cholestatic liver disease (CLD). TCM's "Pi Xu" (spleen deficiency) in CLD links to gut microbiota dysregulation, but STR's mechanisms remain unclear.

AIM OF THE STUDY: To decipher the anti-CLD mechanisms of STR, focusing on how it translates the "Gan Bing Zhi Pi" theory into biological effects via the gut-liver axis.

MATERIALS AND METHODS: This study employed an α-naphthyl isothiocyanate (ANIT)-induced C57BL/6 mouse model to verify the therapeutic efficacy of STR. Network pharmacology was utilized to predict underlying mechanisms; 16S sequencing characterized STR's effects on gut microbiota composition, and analysis via the gutMGene database helped elucidate STR's role in CLD. Finally, in vivo experiments assessed TLR4/NF-κB pathway expression and intestinal barrier function, with dual validation through gut microbiota depletion and transplantation assays, to unravel the molecular mechanisms underlying STR-mediated CLD amelioration.

RESULTS: STR ameliorated CLD by normalizing gallbladder index and serum ALP, TBA, TBIL, ALT, and AST, while attenuating hepatic inflammation. Network pharmacology identified 134 potential STR targets related to CLD, underscoring microbiota dysbiosis and inflammation and revealing LPS-related TLR4-mediated inflammatory pathways as regulatory hubs. 16S sequencing demonstrated STR-modulated gut microbiota, enriching Bacteroidetes and Akkermansia while depleting Enterococcus. These changes were associated with enhanced fecal bile acid excretion, intestinal barrier repair, and suppressed TLR4-mediated inflammatory cascades. Integrated network pharmacology/16S/gutMGene analyses established TLR4-mediated inflammation as the core microbiota-dependent mechanism. In vivo experiments confirmed STR reduced serum LPS, increased fecal bile acids, inhibited hepatic TLR4/NF-κB activation, and enhanced intestinal barrier integrity by upregulating tight junction proteins (ZO-1, occludin). These mechanisms were validated via gut microbiota depletion and transplantation assays.

CONCLUSION: STR ameliorates CLD via a microbiota-dependent "Gan Bing Zhi Pi" mechanism. By reshaping the gut microbiota, it coordinates bile acid excretion, repairs intestinal barrier, and suppresses LPS-driven hepatic inflammation to regulate the gut-liver axis. This bridges TCM theory with modern microbiology, validating the therapeutic potential of STR for CLD.}, } @article {pmid41452713, year = {2025}, author = {Gong, X and Wang, S and Xia, Q}, title = {The Emerging Triad in Cancer and Aging: Cellular Senescence, Microbiome, and Tumor Microenvironment.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2025.1495}, pmid = {41452713}, issn = {2152-5250}, abstract = {Aging is accompanied by a marked increase in cancer incidence and mortality, yet most studies still consider cellular senescence, the tumor microenvironment, and the microbiome as largely separate axes. Here, we propose an integrative triad framework in aging-related cancers in which cellular senescence, tumor microenvironment (conceptualized here as part of a broader tumor microecology), and the microbiome dynamically interact to shape tumor initiation, evolution, and treatment response. We summarize how senescent cells, via context-dependent senescence-associated secretory phenotypes (SASPs), remodel stromal, immune, and metabolic niches in aging hosts and how gut and intratumoral microbiota both induce and are reshaped by senescence. Focusing on colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC), together with pan-cancer transcriptomic and microbiome analyses. We highlight disease and subtype-specific patterns in which senescence signatures, immune contexture, and microbial features co-stratify prognosis and therapeutic outcomes, and integrate pan-cancer transcriptomic and microbiome analyses to illustrate shared and divergent triad configurations across tumor types. Finally, we discuss the therapeutic implications of this triad, including timing-dependent use of senolytics and senomorphics, diet and microbiome-targeted interventions, fecal microbiota transplantation (FMT), and the ecological risks of antibiotics, particularly in multimorbid older patients. We argue that triad-informed biomarkers and trial designs integrating senescence, microenvironment, and microbiome readouts will be important for mechanism-based, age-adapted cancer prevention and therapy in older adults, especially those with CRC, HCC, and PDAC.}, } @article {pmid41452451, year = {2025}, author = {Zhang, X and Li, C and Feng, X and Yuan, X}, title = {The interplay of microbiome, molecular mechanisms, and fertility -an integrated review.}, journal = {Folia microbiologica}, volume = {}, number = {}, pages = {}, pmid = {41452451}, issn = {1874-9356}, support = {LBH-Z21218//Postdoctoral funding of Heilongjiang Province/ ; }, abstract = {The human microbiome, particularly the gut and reproductive tract microbiota, plays a critical role in regulating fertility through complex molecular and immunological mechanisms. This review synthesizes emerging evidence on the bidirectional communication along the gut-reproductive axis, emphasizing how microbial-derived metabolites, such as short-chain fatty acids (butyrate), bile acids, and indoles, modulate systemic inflammation, immune tolerance, hormone metabolism, and energy homeostasis. Dysbiosis, or microbial imbalance, is strongly associated with a range of reproductive pathologies, including polycystic ovary syndrome, endometriosis, premature ovarian insufficiency, impaired spermatogenesis, and recurrent implantation failure. Furthermore, site-specific microbiomes, such as Lactobacillus-dominated vaginal and uterine communities, are vital for successful implantation and pregnancy maintenance. External factors including diet, environmental toxins, and antibiotic use can disrupt these microbial ecosystems, whereas interventions like probiotics like Lactobacillus and Clostridium butyricum, prebiotics, postbiotics, and fecal microbiota transplantation offer promising avenues for restoring microbial and reproductive health. However, translational challenges remain, including methodological heterogeneity in microbiome research and the need to establish causal mechanisms beyond correlation. Future efforts should prioritize multi-omics integration, randomized controlled trials, and personalized microbiome-based diagnostics and therapeutics to effectively address infertility.}, } @article {pmid41451964, year = {2025}, author = {Felippe, MFP and Fink, IA and Motta, LCN and de Macêdo Neto, MP and Lopes, JV and Petry, ACG and Sorato, GB and Gonçalves, DP and Maia, GG and Koehler, LB}, title = {Drug Development.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 5}, number = {}, pages = {e107684}, doi = {10.1002/alz70859_107684}, pmid = {41451964}, issn = {1552-5279}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Alzheimer Disease/therapy ; *Drug Development ; Gastrointestinal Microbiome ; *Cognitive Dysfunction/therapy ; Clostridium Infections/therapy ; }, abstract = {BACKGROUND: The gut-brain axis plays a crucial role in neurodegenerative diseases, such as Alzheimer's disease (AD). Fecal microbiota transplantation (FMT) has emerged as a potential therapy for AD by restoring microbial balance and reducing neuroinflammation. However, clinical evidence remains limited. This study reviews its potential effects on cognition in AD and other cognitive disorders.

METHOD: PubMed, Cochrane, Scopus, and Embase databases were searched for human studies on FMT and cognition in AD. Eligible studies included clinical trials, case series, and case reports. Reviews, editorials, animal, and non-English studies were excluded. Two reviewers screened studies; four extracted data and assessed quality. Meta-analysis was not performed due to heterogeneity.

RESULT: Five studies were included, totaling 26 dementia patients, all of whom had recurrent Clostridium difficile infection (CDI). The studies included one randomized controlled trial (RCT, n = 20) and four observational studies (three case reports and one case series, n = 6). FMT was associated with cognitive improvements, particularly in patients with mild cognitive impairment or AD. The RCT demonstrated significant gains in MMSE (MD 6.0, p=0.01) and CDR-SOB (MD -3.1, p=0.048) scores at three months follow-up. One case series (n=5) reported cognitive improvements post-FMT, with MMSE increasing from 11 to 17, MoCA from 12 to 21, and CDR-SOB decreasing from 10 to 5.5. The three case reports described cases of AD exhibiting increased MMSE after FMT (15 to 29, 8 to 13, 5 to 12, respectively). They also noted improvements in mood, social interaction, and performance of daily activities. Beyond cognitive changes, FMT led to gut microbiota modulation, with increased Bacteroidaceae and reduced Enterococcaceae. These microbiome shifts correlated with reduced neuroinflammation and metabolic improvements. Adverse effects were minimal, such as transient nausea and mild abdominal discomfort, with no serious events.

CONCLUSION: Preliminary evidence suggests FMT may have cognitive benefits in AD patients and recurrent CDI. However, the limited number of studies and the presence of CDI as a common comorbidity highlight the need for larger, controlled trials to better define its role in AD management.}, } @article {pmid41450949, year = {2025}, author = {Perzon, O and Ilan, Y}, title = {Understanding gut microbial diversity using systems based on the Constrained-Disorder Principle provides a novel approach to targeting gut microbiome therapies.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1713775}, pmid = {41450949}, issn = {1664-302X}, abstract = {BACKGROUND/AIMS: The diverse composition of the gut microbiome is vital for human health, influencing digestion, immune regulation, and disease resistance. While higher diversity is generally associated with resilience, reduced and excessive diversity can lead to health issues.

METHODS: This paper introduces the Constrained Disorder Principle (CDP) as a new framework for understanding microbial diversity.

RESULTS: The CDP emphasizes the significance of maintaining variability within certain boundaries to sustain ecosystem stability and promote health. It considers intra- and inter-individual variability, illustrating how microbial ecosystems adapt throughout different life stages, genetic backgrounds, and environmental exposures. Integrating CDP-based artificial intelligence systems may enable the establishment of personalized diversity thresholds, predict dysbiosis, and refine interventions such as probiotics, prebiotics, fecal microbiota transplantation, and customized dietary strategies. CDP-driven platforms enhance therapeutic precision by utilizing variability induction, feedback loops, and microbial signature analysis to optimize diversity goals and identify actionable biomarkers.

CONCLUSION: This platform can pave the way for adaptive, individualized disease prevention and treatment strategies, bridging the gap between microbial ecology and precision medicine. It provides a powerful tool for harnessing the therapeutic potential of gut microbial diversity to enhance human health.}, } @article {pmid41448004, year = {2025}, author = {Gao, J and Li, L and Zhang, S and Zhao, H and Feng, B and Liu, C and Wang, X and Li, S and Li, Y and Zhao, D}, title = {Taurodeoxycholic acid alleviates intestinal inflammation by modulating gut microbiota and TGR5-NF-kappaB axis in DSS-induced colitis.}, journal = {International immunopharmacology}, volume = {170}, number = {}, pages = {116056}, doi = {10.1016/j.intimp.2025.116056}, pmid = {41448004}, issn = {1878-1705}, abstract = {Taurodeoxycholic acid (TDCA), a metabolite of cholesterol, has been shown to be able to regulate various inflammatory responses and improve intestinal inflammation. However, its potential to alleviate colitis through modulating the gut microbiota-bile acid axis remains unclear. Mice were simultaneously administered dextran sulfate sodium (DSS) and TDCA via drinking water to estimate the effect of TDCA on colitis. TDCA-treated mice showed markedly relieved DSS-induced colitis. 16S rDNA sequencing revealed TDCA selectively remodeled the gut microbiota, notably decreasing the abundances of Desulfovibrionaceae_unclassified, Escherichia-Shigella and increasing Akkermansia. Furthermore, the reshaping of the microbial community was functionally characterized by a marked alteration in the gut bile acid profile, specifically a significant increase in secondary bile acids. Fecal microbiota transplantation (FMT) confirmed the protective role of the TDCA-shaped microbiota, which also transferred the reduction of Desulfovibrionaceae_unclassified and the characteristic bile acid profile to recipient mice. Similarly, transplanting feces after TDCA intervention into recipient mice still increased secondary bile acid levels in the gut to a certain extent. Spearman's correlation analysis further solidified the negative correlation between Desulfovibrionaceae_unclassified and secondary bile acids. Mechanistically, the altered bile acid profiles restored the activation of the bile acid receptor TGR5, but not FXR, thereby inhibiting the NF-κB signaling pathway. The essential role of TGR5 was substantiated as its inhibitor, SBI-115, largely abolished the protective effects of TDCA. In conclusion, our findings demonstrate that TDCA alleviates colitis by orchestrating a microbiota-bile acid-TGR5 signaling cascade, positioning it as a promising therapeutic candidate for inflammatory bowel disease.}, } @article {pmid41447836, year = {2025}, author = {Qiao, Z and Tong, H and Wang, Z and Liu, J and Chen, X and Song, Z and Wang, Y}, title = {Dehydrodiisoeugenol attenuates ulcerative colitis via regulating Anaerostipes caccae-mediated uric acid metabolism.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {150}, number = {}, pages = {157721}, doi = {10.1016/j.phymed.2025.157721}, pmid = {41447836}, issn = {1618-095X}, abstract = {BACKGROUND: The gut microbiota plays a crucial role in the pathogenesis of ulcerative colitis (UC). Dehydrodiisoeugenol (DEH) is a major benzofuran-type neolignane isolated from Myristica fragrans Houtt., a plant whose fruit has been incorporated into traditional Chinese medicine (TCM) formulations for clinical treatment of gastrointestinal disorders. However, the pharmacological mechanisms underlying the anti-colitic efficacy of DEH remain to be elucidated.

PURPOSE: The present study aimed to investigate the anti-colitic efficacy of DEH and its therapeutic mechanism, with a specific focus on the role of gut microbiota regulation.

METHODS: A dextran sulfate sodium (DSS)-induced murine model of UC was utilized to assess the effects of DEH on UC progression. Co-housing experiments and fecal microbiota transplantation (FMT) were conducted to verify whether DEH's anti-colitic effects depend on the gut microbiota. 16S rRNA gene sequencing and quantitative PCR (qPCR) were performed to identify gut bacterial taxa altered by DEH. Bacterial colonization was carried out to evaluate the effects of differential species on symptoms of UC. Metabolomic analyses and in vitro incubations were conducted to identify key metabolites.

RESULTS: First, DEH exerted potent anti-colitic efficacy in DSS-induced UC mice by alleviating colonic inflammation and enhancing intestinal epithelial integrity. Administration of DEH at 50 mg/kg significantly prolonged the colon length to 6.27 ± 0.19 cm, which was longer than that of the vehicle group (4.85 ± 0.18 cm) and the positive control drug SASP group (200 mg/kg, 5.83 ± 0.18 cm). Co-housing and FMT validated that DEH's efficacy is dependent on the gut microbiota. Subsequently, we found that DEH significantly upregulated the abundance of Anaerostipes caccae, the colonization with which could alleviate symptoms of UC. Furthermore, we identified A. caccae as a uric acid (UA)-metabolizing microbe, and its colonization in UC mice obviously reduced UA levels. Blocking UA synthesis with allopurinol (Allo) completely abolished A. caccae's anti-colitic effects, verifying its therapeutic effects rely on the UA-lowering capacity. Finally, we found the pathologically elevated UA exacerbated UC via activating the p38 mitogen-activated protein kinase (MAPK) signaling pathway.

CONCLUSION: Our study highlights that the A. caccae-mediated maintenance of UA metabolic homeostasis restrains UC pathogenesis, a process that is the core mechanism through which DEH exerts its anti-colitic efficacy.}, } @article {pmid41445729, year = {2025}, author = {Yu, S and Zhang, M and Dou, Z and Tian, B and Lu, J}, title = {Gut microbiota metabolites in the immunoregulation of enteritis: research progress.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1706472}, pmid = {41445729}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Enteritis/immunology/metabolism/microbiology/therapy ; Animals ; Immunomodulation ; Bile Acids and Salts/metabolism ; Fatty Acids, Volatile/metabolism ; Probiotics ; }, abstract = {The interaction between gut microbiota metabolites and the host immune system plays a crucial role in maintaining intestinal homeostasis and in the development of inflammatory bowel disease and other enteric conditions. This article presents a systematic review of the sources and functions of short-chain fatty acids, tryptophan metabolites, bile acids, and other microbial metabolites, focusing on how these metabolites regulate the function of immune cells, such as T cells, B cells, neutrophils, macrophages, and dendritic cells, as well as key inflammatory signaling pathways, including the NF-κB, NLRP3 inflammasome, and JAK-STAT pathways, thereby influencing intestinal barrier integrity. Also explored are potential therapeutic strategies based on microbial metabolites, including the application status and prospects of probiotic and prebiotic interventions, the direct administration of metabolites, and fecal microbiota transplantation. Although current research faces challenges such as unclear mechanisms, significant differences among individuals, and barriers to clinical translation, the development of multiomics technologies and precision medicine holds promise for providing more effective and personalized treatment strategies targeting gut microbiota metabolites for patients with enteritis.}, } @article {pmid41445292, year = {2025}, author = {Govindarajan, M and Aware, C and Ivanich, K and Pathak, I and Zhu, Y and Balchandani, P and Davis, D and Ericsson, A and Ma, L and Lin, AL}, title = {Basic Science and Pathogenesis.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 1}, number = {}, pages = {e105884}, doi = {10.1002/alz70855_105884}, pmid = {41445292}, issn = {1552-5279}, mesh = {Animals ; Mice ; *Alzheimer Disease/microbiology ; *Nitric Oxide Synthase Type II/genetics ; Humans ; *Gastrointestinal Microbiome ; Disease Models, Animal ; *Cognitive Dysfunction/microbiology ; Mice, Knockout ; *Dysbiosis ; Male ; Aged ; Fecal Microbiota Transplantation ; Female ; Cerebrovascular Circulation ; Mice, Transgenic ; Middle Aged ; Aged, 80 and over ; }, abstract = {BACKGROUND: Inducible Nitric Oxide Synthase (iNOS) is implicated in exacerbating Alzheimer's Disease (AD) mechanisms. The relationship between imbalanced gut microbiota composition (dysbiosis) and AD pathology is well characterized. Many gut bacteria, including E. Coli induce iNOS production, potentially contributing to AD development. To investigate the antagonistic role of iNOS, we created a novel iNOS knockout (iNOS-KO) mouse model using the 3xTg-AD mouse model background and performed fecal microbiome transplantation (FMT) to iNOS-KO/3xTg-AD mice from mild cognitive impairment (MCI) patients and age-matched healthy controls (HC). We aim to determine, whether iNOS-KO can protect cerebral blood flow (CBF), an early marker of AD progression, despite dysbiosis induced by FMT from MCI donors.

METHOD: Stool samples from MCI patients (n =  3) and HC (n =  3) (aged 55-80) were used for FMT in 4-month-old iNOS-KO/3xTg-AD mice (FMT-MCI, n = 4 and FMT-HC, n = 6) for three consecutive days after a 7-day antibiotic treatment. Mice without FMT (CTL, n = 8) served as naive controls. Four weeks post-FMT, mouse fecal samples and corresponding donor samples were analyzed using 16S rRNA metagenomic sequencing. Global CBF was measured in a subset of mice (n = 4/group) using 7T MRI with Continuous Arterial Spin Labelling (CASL) - Echo Planar Imaging (EPI) sequence.

RESULT: Beta diversity analysis revealed that the significant microbial diversity observed in MCI and HC donors was imprinted in their respective FMT-MCI and FMT-HC recipient mice, indicating a strong donor-derived microbial signature (Figure 1). FMT-MCI mice showed increased levels of pathobiont Gram-positive bacteria (Clostridium bolteae, Sellimonas intestinalis) when compared to FMT-HC mice indicating higher dysbiosis. Despite FMT induced dysbiosis, CBF levels (Figure 2) across the three groups were comparable to each other, attributable to the effect of the iNOS knockout.

CONCLUSION: We observe that MCI patients had higher gut dysbiosis than HC. However, despite increased dysbiosis, iNOS-KO may preserve CBF and mitigate AD-like symptoms, highlighting its potential neuroprotective role in the 3xTg-AD model. Future studies should investigate the impact of iNOS-KO on mitigating AD pathology, such as amyloid-β and tau accumulation, or preserving cognitive functions. Our preliminary data shows that iNOS could be a potential target to ameliorate AD risk.}, } @article {pmid41444705, year = {2025}, author = {Oladele, P and Dong, W and Richert, BT and Johnson, TA}, title = {Route of fecal microbiota transplantation delivery determined the dynamics and predictability of donor microbe colonization.}, journal = {Animal microbiome}, volume = {7}, number = {1}, pages = {130}, pmid = {41444705}, issn = {2524-4671}, support = {ICASASHTWG0000000082//Foundation for Food and Agriculture Research,United States/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) and the colonization of delivered donor microbes has been reported to improve the negative effects (decrease in body weight, diarrhea, and gut barrier disruption) associated with weaning in pigs. However, delivery of FMT in pigs is still invasive and predicting the colonization or rejection of donor microbes remains challenging. Therefore, this study developed a non-invasive in-feed delivery of FMT and evaluated the effect of FMT mode of delivery on growth performance, gut physiology, microbiota dynamics, and predictability of colonization or rejection of donor microbes in recipient pigs. Forty weaned piglets (10 per group) were administered FMT through one of three routes; oral, rectal, or amended in-feed. The control group was orally administered sterile saline to simulate handling stress.

RESULTS: Pigs in the FMT groups had higher average daily weight gain (ADG) from day 0–2 post-weaning. An increase in community diversity and a shift in the recipient community towards the donor in all FMT groups was observed on day 5. The oral group had the highest colonization (15.12%) and the lowest rejection (19.34%) rates, while colonization was 13.82% and 11.78% in rectal and in-feed group respectively. On day 4, colon crypt depth was increased in all FMT groups but an increase in villus length was only observed in the in-feed group. Colonization and rejection of donor microbes in the recipient animals could be predicted in all routes of administration, but the efficacy of prediction was influenced by the route of delivery. In-feed FMT had the lowest colonization prediction which may have been influenced by the need for voluntary consumption of fecal materials in the in-feed group. The ten most abundant genera (Prevotella, Alloprevotella, Phascolarctobacterium, Lactobacillus, Cloacibacillus, Bacteroides, Lachnoclostridium, Escherichia-Shigella, unclassified Lachnospiraceae sequences, and archaea Methanobrevibacter) in the recipient prior to FMT (background community) was the most important feature in predicting colonization for all routes of fecal microbiota transplant.

CONCLUSION: FMT administered as a lyophilized feed additive shows promise in altering microbiome community structure. While colonization and rejection of donor microbes within the recipient community are predictable, the efficacy of these predictions varies with the route of transplant. This suggests that different prediction models are necessary for each delivery mode of FMT in pigs.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42523-025-00495-9.}, } @article {pmid41443865, year = {2025}, author = {Takeda, T and Hojo, M and Asaoka, D and Nagahara, A}, title = {Targeting Gut Microbiota in the Management of Functional Constipation: A Narrative Review.}, journal = {Internal medicine (Tokyo, Japan)}, volume = {}, number = {}, pages = {}, doi = {10.2169/internalmedicine.6457-25}, pmid = {41443865}, issn = {1349-7235}, abstract = {Functional constipation (FC) is a prevalent gastrointestinal disorder that negatively affects the quality of life. Recent studies have suggested that the gut microbiota plays a key role in the pathophysiology of FC, with dysbiosis, reduced diversity, and altered production of short-chain fatty acids that influence intestinal motility. Probiotics have shown potential for improving bowel movements and related symptoms in adults with FC. However, clinical outcomes vary depending on strain, dosage, and study design. Fecal microbiota transplantation has also emerged as a promising treatment, demonstrating improved stool frequency and colonic transit in selected patients. This narrative review summarizes the current understanding of the relationship between gut microbiota and FC and highlights the therapeutic potential of probiotics and fecal microbiota transplantation. Further research is warranted to clarify the underlying mechanisms and optimize microbiota-targeted interventions for effective management of FC.}, } @article {pmid41440851, year = {2025}, author = {Tao, Y and Zhang, N and Wang, Z and Pan, Y and Zhong, S and Liu, H}, title = {SGLT2 Inhibitors Confer Cardiovascular Protection via the Gut-Kidney-Heart Axis: Mechanisms and Translational Perspectives.}, journal = {Journal of cardiovascular development and disease}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/jcdd12120471}, pmid = {41440851}, issn = {2308-3425}, abstract = {Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated significant cardiovascular and renal benefits beyond glycemic control, yet their integrated mechanisms remain incompletely understood. Emerging evidence highlights the gut-kidney-heart axis as a pivotal pathological network, wherein gut dysbiosis, toxic metabolite accumulation, intestinal barrier disruption, and systemic inflammation synergistically drive cardiorenal injury. This review systematically elucidates how SGLT2i modulate this axis through multi-level interventions: reshaping gut microbiota composition, enriching short-chain fatty acid-producing bacteria, suppressing trimethylamine and other toxin-generating microbes, restoring tight junction integrity, and regulating bile acid metabolism. These upstream effects reduce systemic inflammatory and metabolic stress, interrupt kidney-derived toxin amplification, and mitigate myocardial remodeling. Unlike previous reviews focusing on single-organ pathways, this work integrates microecological regulation, metabolite reprogramming, and cross-organ protection into a unified "three-axis convergence to the heart" framework. We also highlight potential species-specific microbiota regulatory profiles among different SGLT2i and propose future directions, including fecal microbiota transplantation and microbiota-targeted co-therapies, to clarify causal relationships and optimize therapeutic strategies. By positioning the gut as a modifiable upstream driver, this framework provides novel mechanistic insight and translational potential for expanding SGLT2i applications in metabolic cardiovascular disease, including in non-diabetic populations.}, } @article {pmid41440729, year = {2025}, author = {Hirji, I and John, D and Jith, J and Khoshnaw, H and Ganeshananthan, M}, title = {Challenges and Strategies in Managing Recurrent Clostridioides difficile Infection in Older Adults.}, journal = {Geriatrics (Basel, Switzerland)}, volume = {10}, number = {6}, pages = {}, doi = {10.3390/geriatrics10060158}, pmid = {41440729}, issn = {2308-3417}, abstract = {BACKGROUND: Clostridioides difficile infections (CDIs) are caused by a Gram-positive, spore-forming bacillus and are defined by more than three episodes of watery diarrhoea per day. CDI is a major cause of morbidity and mortality in older adults, particularly over 65 years. Recurrent CDI leads to higher mortality and prolonged, debilitating illness.

CASE PRESENTATIONS: This article presents two patients, aged over 80 years old, who developed recurrent CDI causing complicated and prolonged treatment courses. Patient 1 required an extended course of antibiotics for treatment of discitis and a congruent psoas abscess. Patient 2 developed CDI after multiple short courses of antibiotics for urinary tract infections (UTIs) in the context of multiple comorbidities. Both patients experienced three distinct episodes of CDI and were treated in collaboration with microbiology specialists. Following the third episode, both were successfully treated with oral capsule faecal microbiome transplants (FMTs). Their cases highlight the challenge of balancing systemic antibiotic use against CDI risk.

DISCUSSIONS: These cases underscore known risk factors for recurrent CDI, including advanced age and prolonged antibiotic exposure. Recurrence rates in patients over 65 can reach 58%. The British Society of Gastroenterology and Healthcare Infection Society support the use of FMTs in recurrent cases. Environmental decontamination, including terminal cleaning with sporicidal agents, is critical in reducing reinfection in hospital settings.

CONCLUSIONS: Recurrent CDI in elderly patients reflects a complex interplay between infection control and managing comorbidities. New guidelines suggest that FMTs can significantly reduce morbidity and mortality. These cases emphasise the need for individualised, multidisciplinary care, adherence to guidelines, and further research to improve safe, effective CDI management in older adults.}, } @article {pmid41440201, year = {2025}, author = {Ye, G and Zhang, H and Feng, Q and Xiao, J and Wang, J and Liu, J}, title = {Important Role of Bacterial Metabolites in Development and Adjuvant Therapy for Hepatocellular Carcinoma.}, journal = {Current oncology (Toronto, Ont.)}, volume = {32}, number = {12}, pages = {}, doi = {10.3390/curroncol32120673}, pmid = {41440201}, issn = {1718-7729}, support = {2021ZQNZD009//Major Scientiffc Research Program for Young and Middle-aged Health Professionals of Fujian Province, China/ ; 2023Y9416//Fujian Science and Technology Innovation Joint Fund Project/ ; }, mesh = {Humans ; *Carcinoma, Hepatocellular/therapy/microbiology/immunology/metabolism ; *Liver Neoplasms/therapy/microbiology/immunology/metabolism ; *Bacteria/metabolism ; Tumor Microenvironment/immunology ; Animals ; }, abstract = {Bacterial metabolites play a dual role in hepatocellular carcinoma (HCC), exhibiting both tumor-promoting and tumor-suppressing activities dictated by their structural diversity. This review synthesizes recent advances in understanding how key microbial metabolites-such as bile acids, short-chain fatty acids, and polyamines-remodel the tumor immune microenvironment through mechanisms including immunometabolic reprogramming, epigenetic modification, and regulation of signaling pathways (e.g., FXR, TLR, and mTOR). We highlight their roles in modulating the function of T cells, NK cells, and tumor-associated macrophages and discuss emerging strategies that target these metabolites-including probiotic interventions, fecal microbiota transplantation, and metabolite-based adjuvants-to enhance immunotherapy efficacy and overcome resistance. By integrating mechanistic insight into translational potential, this work outlines a metabolite-immunometabolism-hepatocarcinogenesis framework and proposes novel combinatorial approaches for HCC treatment.}, } @article {pmid41439979, year = {2025}, author = {Mostafavi Abdolmaleky, H and Pirani, A and Pettinato, G}, title = {Psychosomatic Disorders, Epigenome, and Gut Microbiota.}, journal = {Cells}, volume = {14}, number = {24}, pages = {}, doi = {10.3390/cells14241959}, pmid = {41439979}, issn = {2073-4409}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Epigenome/genetics ; *Psychophysiologic Disorders/genetics/microbiology ; Animals ; *Epigenesis, Genetic ; }, abstract = {Psychosomatic disorders are conditions in which physical (somatic) symptoms are triggered or aggravated by psychological distress. These disorders result from complex interactions among the endocrine, central nervous, and immune systems. Emerging evidence indicates that gut microbiota (GM) dysbiosis, epigenetic alterations, and immune system dysregulation play pivotal roles in the pathogenesis of psychosomatic disorders and may serve as potential biomarkers for disease states and therapeutic outcomes. This review first outlines how epigenetic dysregulation contributes to psychosomatic disorders through altered expression of genes such as GRM2, TRPA1, SLC6A4, NR3C1, leptin, BDNF, NAT15, HDAC4, PRKCA, RTN1, PRKG1, and HDAC7. We then examine current evidence linking psychosomatic disorders with changes in GM composition and GM-derived epigenetic metabolites, which influence immune function and neurobiological pathways. The core focus of this review is on therapeutic interventions-including probiotics, prebiotics, postbiotics, fecal microbiota transplantation, and targeted dietary approaches-that modulate the gut-brain axis through epigenetic mechanisms for the management of psychosomatic disorders. Finally, we highlight the current challenges and future directions in elucidating the interplay between epigenetics, the GM, and psychosomatic disease mechanisms. In this context, human iPSC-derived multicellular organoids may serve as powerful platforms to unravel mechanistic pathways underlying inter-organ interactions.}, } @article {pmid41439929, year = {2025}, author = {Geladari, EV and Kalergi, AC and Evangelopoulos, AA and Sevastianos, VA}, title = {Sepsis and the Liver.}, journal = {Diseases (Basel, Switzerland)}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/diseases13120388}, pmid = {41439929}, issn = {2079-9721}, abstract = {BACKGROUND/OBJECTIVES: Sepsis-associated liver injury (SALI) is a critical and often early complication of sepsis, defined by distinct hyper-inflammatory and immunosuppressive phases that shape patient phenotypes.

METHODS: Characterizing these phases establishes a foundation for immunomodulation strategies tailored to individual immune responses, as discussed subsequently.

RESULTS: The initial inflammatory response activates pathways such as NF-κB and the NLRP3 inflammasome, leading to a cytokine storm that damages hepatocytes and is frequently associated with higher SOFA scores and a higher risk of 28-day mortality. Kupffer cells and infiltrating neutrophils exacerbate hepatic injury by releasing proinflammatory cytokines and reactive oxygen species, thereby causing cellular damage and prolonging ICU stays. During the subsequent immunosuppressive phase, impaired infection control and tissue repair can result in recurrent hospital-acquired infections and a poorer prognosis. Concurrently, hepatocytes undergo significant metabolic disturbances, notably impaired fatty acid oxidation due to downregulation of transcription factors such as PPARα and HNF4α. This metabolic alteration corresponds with worsening liver function tests, which may reflect the severity of liver failure in clinical practice. Mitochondrial dysfunction, driven by oxidative stress and defective autophagic quality control, impairs cellular energy production and induces hepatocyte death, which is closely linked to declining liver function and increased mortality. The gut-liver axis plays a central role in SALI pathogenesis, as sepsis-induced gut dysbiosis and increased intestinal permeability allow bacterial products, including lipopolysaccharides, to enter the portal circulation and further inflame the liver. This process is associated with sepsis-related liver failure and greater reliance on vasopressor support. Protective microbial metabolites, such as indole-3-propionic acid (IPA), decrease significantly during sepsis, removing key anti-inflammatory signals and potentially prolonging recovery. Clinically, SALI most commonly presents as septic cholestasis with elevated bilirubin and mild transaminase changes, although conventional liver function tests are insufficiently sensitive for early detection. Novel biomarkers, including protein panels and non-coding RNAs, as well as dynamic liver function tests such as LiMAx (currently in phase II diagnostics) and ICG-PDR, offer promise for improved diagnosis and prognostication. Specifying the developmental stage of these biomarkers, such as identifying LiMAx as phase II, informs investment priorities and translational readiness. Current management is primarily supportive, emphasizing infection control and organ support. Investigational therapies include immunomodulation tailored to immune phenotypes, metabolic and mitochondrial-targeted agents such as pemafibrate and dichloroacetate, and interventions to restore gut microbiota balance, including probiotics and fecal microbiota transplantation. However, translational challenges remain due to limitations of animal models and patient heterogeneity.

CONCLUSION: Future research should focus on developing representative models, validating biomarkers, and conducting clinical trials to enable personalized therapies that modulate inflammation, restore metabolism, and repair the gut-liver axis, with the goal of improving outcomes in SALI.}, } @article {pmid41439481, year = {2026}, author = {Zou, Y and Li, N and Li, X and Kuang, M and Xu, X and Guan, L and Li, X and Zheng, P and Li, L and Wan, J and Lu, N and Liu, J and He, C and Zhu, Y}, title = {Gut microbiota dysbiosis exacerbates acute pancreatitis via Escherichia coli-driven neutrophil heterogeneity and NETosis.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2606480}, doi = {10.1080/19490976.2025.2606480}, pmid = {41439481}, issn = {1949-0984}, mesh = {Animals ; *Dysbiosis/microbiology/immunology/complications ; *Gastrointestinal Microbiome ; Mice ; Humans ; *Neutrophils/immunology ; *Extracellular Traps/immunology/metabolism ; *Escherichia coli/physiology ; *Pancreatitis/microbiology/immunology/pathology ; Male ; Mice, Inbred C57BL ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; Specific Pathogen-Free Organisms ; }, abstract = {Gut microbiota dysbiosis contributes to acute pancreatitis (AP) severity, but the specific microbes and mechanisms remain unclear. In this study, we employed both germ-free (GF) and specific-pathogen-free (SPF) murine models of AP to investigate the role of the intestinal microbiota. Our findings demonstrate that GF mice exhibited markedly attenuated pancreatic injury, inflammatory cell infiltration, and neutrophil extracellular traps (NETs) formation. Through fecal microbiota transplantation (FMT) from AP patients, differential antibiotic modulation, and single-bacterial colonization experiments, we identified Gram-negative bacteria, particularly Escherichia coli (E. coli), as critical microbial drivers of disease exacerbation. Single-cell RNA sequencing revealed that microbiota dysbiosis profoundly reprogrammed both local pancreatic and systemic immune landscapes. Specifically, dysbiosis promoted emergency granulopoiesis in the bone marrow, enhanced neutrophil mobilization and activation, and facilitated the expansion of pro-inflammatory neutrophil subpopulations (Neutrophils_2 and Neutrophils_3). These subsets exhibited upregulated signaling through NETosis-associated pathways, including TLR, NF-κB, and IL-17 axes. Conversely, in GF conditions, we observed a predominance of an anti-inflammatory neutrophil subset (Neutrophils_4), characterized by the expression of tissue repair-associated genes such as Reg1 and Reg2. Shotgun metagenomic profiling of fecal samples from patients with AP revealed an enrichment of E. coli during the acute phase, positively correlating with circulating cell-free DNA, a marker of NETosis. Together, these insights suggest that gut microbiota dysbiosis, notably increased E. coli abundance, may aggravate AP by reshaping immunity and promoting aberrant NETs formation, supporting microbiota or NETs targeted therapies.}, } @article {pmid41439235, year = {2026}, author = {Zou, B and Huo, Q and Zhou, X and Lv, Y and Li, G and Fu, G and Shen, H and Shu, S}, title = {Characteristics and longitudinal stability of Gut Microbiota in healthy individuals across different age groups.}, journal = {Current research in microbial sciences}, volume = {10}, number = {}, pages = {100512}, pmid = {41439235}, issn = {2666-5174}, abstract = {Fecal microbiota transplantation (FMT) efficacy relies on donor microbiome composition and temporal stability, yet the influence of donor age remains inadequately investigated. This longitudinal analysis addressed this gap by examining 81 healthy individuals (3-30 years), stratified into four age groups, who provided monthly fecal samples over 12 months (n = 972 samples). Gut microbiota composition (16S rDNA sequencing) and temporal stability were assessed using Bray-Curtis dissimilarity, intraclass correlation coefficient (ICC), and genus-level co-occurrence network analysis. Results demonstrated a strong age-dependency in microbiota stability. The teenage cohort (13-17 years) exhibited the highest stability, characterized by minimal fluctuations in α- and β-diversity and significantly stronger network centrality. Furthermore, specific genera, notably Faecalibacterium and Bifidobacterium, displayed exceptionally high ICC values (>0.90), identifying them as core taxa associated with temporal consistency. These findings underscore the critical role of donor age in microbial stability and highlight teenagers as possessing optimal microbiota characteristics for FMT. They strongly support the development of an ICC-based screening framework to enhance donor selection protocols.}, } @article {pmid41439197, year = {2025}, author = {Liang, J and Qiu, Y and Fu, T and Li, J and Yang, J and Tong, Y}, title = {The Gut-Kidney Axis in Uric Acid Nephropathy: Microbiota, Metabolic Crosstalk, and Translational Prospects.}, journal = {Journal of multidisciplinary healthcare}, volume = {18}, number = {}, pages = {8111-8132}, pmid = {41439197}, issn = {1178-2390}, abstract = {Uric acid nephropathy (UAN) represents a critical and multifactorial renal disorder closely linked to hyperuricemia, inflammation, and gut microbiota dysregulation. Recent advances have revealed the pivotal role of the gut-kidney axis in modulating urate metabolism, immune activation, and oxidative stress. This review synthesizes emerging preclinical and clinical evidence to construct an integrative framework for understanding UAN, highlighting both crystal-dependent and crystal-independent mechanisms that drive tubular injury and fibrosis. Accumulating data underscore the reciprocal crosstalk between renal dysfunction and gut dysbiosis, mediated by microbial metabolites such as short-chain fatty acids (SCFAs), indoxyl sulfate, and p-cresol sulfate. We further evaluate therapeutic interventions targeting the gut-kidney axis-including probiotics, synbiotics, postbiotics, fecal microbiota transplantation (FMT), and engineered microbial therapies-which have shown promise in restoring microbial balance and improving urate handling. By integrating multi-omics profiling with systems biology, this review proposes a precision-medicine roadmap that leverages microbiome signatures and metabolic phenotyping for risk stratification and personalized intervention. Moreover, we emphasize the need for supportive regulatory frameworks and interdisciplinary collaboration to enable the clinical translation of microbiota-based strategies. Collectively, this work provides a strengthened conceptual foundation for microbiome-informed prevention and treatment of uric acid-related kidney disease.}, } @article {pmid41438742, year = {2025}, author = {Chen, PJ and Devkota, S and Shiao, S and Hendifar, A and Yang, JD}, title = {Gut microbiome, a novel precision medicine biomarker for hepatocellular carcinoma.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1568962}, pmid = {41438742}, issn = {1664-3224}, mesh = {Humans ; *Carcinoma, Hepatocellular/therapy/immunology/microbiology/metabolism ; *Liver Neoplasms/therapy/immunology/microbiology/metabolism ; *Gastrointestinal Microbiome/immunology ; Precision Medicine/methods ; Biomarkers, Tumor ; Animals ; Immune Checkpoint Inhibitors/therapeutic use ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Immunotherapy/methods ; }, abstract = {Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors (ICIs) have transformed systemic therapy, durable responses are achieved in only a subset of patients, highlighting the need for reliable predictive biomarkers. The gut-liver axis, a bidirectional network linking intestinal microbiota, microbial metabolites, and hepatic immune pathways, has emerged as a key regulator of liver immunity and tumor progression. Growing evidence indicates that the gut microbiome modulates ICI efficacy by shaping immune activation, cytokine signaling, and drug metabolism. This review summarizes current insights into how gut microbial composition and metabolites influence immunotherapy outcomes in HCC and discusses microbiome-targeted strategies, including fecal microbiota transplantation (FMT), prebiotics, probiotics, and dietary interventions. Further research and clinical validation are needed before these insights can be effectively integrated into HCC management.}, } @article {pmid41438381, year = {2025}, author = {Chen, X and Zhang, Y and Zhang, G and Wang, D and Dou, L and Wang, Y and Huang, Z and Liu, X}, title = {Spatial microbiome-metabolic crosstalk drives CD8[+] T-cell exhaustion through the butyrate-HDAC axis in colorectal cancer.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1704491}, pmid = {41438381}, issn = {1664-302X}, abstract = {BACKGROUND: The spatial organization of intratumoral microbiota and its metabolic impact on immunotherapy response in colorectal cancer (CRC) is unclear, limiting targeted interventions.

METHODS: We integrated single-cell RNA-seq, spatial transcriptomics, and microbial multi-omics from a discovery cohort of 23 treatment-naïve CRC patients. Findings were validated in an independent validation cohort from The Cancer Genome Atlas (TCGA-CRC, n = 159).

RESULTS: Spatial depletion of Streptococcus and Acetivibrio in tumor niches disrupts butyrate-histone deacetylase (HDAC) signaling, leading to programmed cell death 1 (PDCD1) hyperacetylation and CD8[+] T-cell exhaustion. The Colorectal Cancer Microbiome Score (CMS) may serve as a predictive biomarker for immunotherapy response and HDAC inhibitor-based combination therapy. We developed the CMS, a spatial biomarker that stratifies patients by microbial-metabolic dysfunction, predicting immunotherapy resistance (e.g., higher tumor immune dysfunction and exclusion (TIDE) scores; p < 0.01) and guiding combinatorial HDAC inhibition for CMS-defined subgroups. In silico fecal microbiota transplantation (FMT) validated CMS as an actionable target for microbiota modulation. Butyrate supplementation in vitro restored HDAC activity and reduced PD-1 expression on CD8[+] T cells, validating the proposed mechanism.

CONCLUSION: Our study unveils a spatially defined, microbiome-driven metabolic niche that epigenetically programs CD8[+] T-cell exhaustion via the butyrate-HDAC axis, revealing a targetable mechanism to overcome immunotherapy resistance in CRC.}, } @article {pmid41438339, year = {2026}, author = {Van Espen, L and Brol, MJ and Close, L and Schierwagen, R and Gu, W and Keller, MI and Balogh, B and Fullam, A and De Coninck, L and Nakamura, T and Kuhn, M and Bork, P and Laleman, W and Bajaj, JS and Papp, M and Schnabl, B and Trebicka, J and Matthijnssens, J and , }, title = {L actococcus A phages predict ACLF while Enterococcus B phages predict bacterial infection in decompensated cirrhosis.}, journal = {JHEP reports : innovation in hepatology}, volume = {8}, number = {1}, pages = {101622}, pmid = {41438339}, issn = {2589-5559}, abstract = {BACKGROUND & AIMS: As portal hypertension progresses in cirrhosis, bacterial translocation across a compromised gut barrier leads to endotoxemia, systemic inflammation and immune dysfunction. Gut phages play a key role in these processes by influencing bacteria-host interactions. This study explores the role of the human gut virome in acute decompensation of cirrhosis and acute-on-chronic liver failure (ACLF).

METHODS: The fecal virome was longitudinally assessed by metagenomic sequencing in two independent cohorts: 93 patients (292 samples) with acute decompensation or ACLF from the PREDICT study, and 94 patients (94 samples) with decompensated cirrhosis undergoing TIPS (transjugular intrahepatic portosystemic shunt) surgery collected in a tertiary care setting. Besides descriptive analysis, phages were grouped according to their predicted bacterial host and lifestyle, and associated with clinical parameters.

RESULTS: Phage alpha-diversity was higher in patients with ACLF and correlated with ACLF severity. In the absence of ACLF, the phageome was dominated by virulent phages, but in ACLF, temperate phages became more prevalent. Genus-level analysis showed that phageomes were highly patient-specific. Lactococcus A phages were the only phage-host group predicting ACLF development (odds ratio [OR] = 14; Fisher test p = 0.0129). Enterococcus B phages (OR = 14.7; p = 0.0015; adj. p = 0.037) and their bacterial hosts (OR = 2.8; p = 0.020) were significantly more prevalent in cases of proven systemic bacterial infection. The presence of both phage families was linked to increased 90-day mortality rates.

CONCLUSION: ACLF is characterized by increased fecal virome diversity and a shift from virulent toward temperate phages at disease onset. Our study links Lactococcus A phages to ACLF development, and Enterococcus B phages to bacterial infection, while both are associated with increased 90-day mortality.

CLINICAL TRIAL NUMBER: NCT03056612.

IMPACT AND IMPLICATIONS: The human gut virome is a poorly investigated part of the human gut microbiome, especially in the context of decompensated cirrhosis and acute-on-chronic liver failure. This study identified two phage groups (Lactococcus A phages and Enterococcus B phages) with particular prognostic value. In the future, virome analysis of fecal samples could be useful for patient stratification in clinical practice.}, } @article {pmid41437855, year = {2025}, author = {Aware, C and Govindarajan, M and Ivanich, K and Ericsson, A and Gu, Z and Cui, J and Zuckerman, A and Ma, L and Lin, AL}, title = {Basic Science and Pathogenesis.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 1}, number = {}, pages = {e106078}, doi = {10.1002/alz70855_106078}, pmid = {41437855}, issn = {1552-5279}, mesh = {Animals ; Mice ; Male ; Female ; Humans ; Aged ; *Alzheimer Disease/pathology/metabolism ; Mice, Transgenic ; Middle Aged ; Fecal Microbiota Transplantation ; *Dysbiosis ; Aged, 80 and over ; *Brain/metabolism/pathology ; Disease Models, Animal ; Gastrointestinal Microbiome ; *Stroke/complications ; }, abstract = {BACKGROUND: Stroke increases the risk of Alzheimer's disease (AD), but underlying mechanisms remain unclear. This study investigates whether gut dysbiosis (imbalance in gut microbes) from acute ischemic stroke worsens AD pathology. Using fecal microbiota transplantation (FMT) from stroke patients into 3xTg-AD mice, we examine its impact on neuroinflammation and AD markers (Total Tau, GFAP, and IBA1). By integrating immunohistochemistry (IHC) and single-cell spatial transcriptomics, we assess dysbiosis-driven changes in neuroinflammation, AD pathology, cell typing, and targeted gene expression in the brain to elucidate the gut-brain axis and explore therapeutic strategies.

METHOD: Stool samples from stroke patients (n = 8) and age-matched healthy controls (n = 8, aged 55-80 years) were used for FMT in three-month-old 3xTg-AD mice. Mice were randomized into naïve control (male: n = 5, female: n = 8), Healthy-FMT (male: n = 12, female: n = 15), and Stroke-FMT (male: n = 14, female: n = 17) groups. FMT followed a one-week antibiotic treatment. IHC assessed Total Tau (hippocampus and cortex), GFAP, and IBA1 (hippocampus) and CosMx Spatial Molecular Imaging (SMI) analyzed cell type-specific changes and targeted gene expression in the whole brain of mice.

RESULT: IHC analysis revealed a significant increase in neuroinflammation and AD pathology in Stroke-FMT mice, with Total Tau levels significantly elevated in the hippocampus and cortex (p <0.001) (Figure 1a, c), and more pronounced increase in males (p <0.01) (Figure 1b, d), also shown the representative IHC images for all groups (Figure 1e-g). GFAP expression in astrocytes (Figure 2a, b) and IBA1 expression in microglia (Figure 2c, d) were significantly higher in Stroke-FMT than Healthy-FMT (p <0.05) in hippocampus, indicating glial activation and neuroinflammation. CosMx-SMI cell typing showed increased astrocyte and microglia density in Stroke-FMT, consistent with gut dysbiosis-induced neuroinflammation compared to Healthy-FMT in UMAP clustering (Figure 3a, c). Stroke-FMT mice exhibited dysregulated expressions of ApoE, GFAP, APP, PSEN1, BIN1, and SORL1 across astrocytes, microglia, CA3, and DG, suggesting intensified neuroinflammation and synaptic impairment compared to Healthy-FMT, potentially exacerbating AD pathology (Figure 3b, d).

CONCLUSION: Stroke donor FMT-induced gut dysbiosis exacerbates AD pathology, emphasizing the critical role of the gut-brain axis in linking stroke and AD. Targeting gut dysbiosis may offer a novel therapeutic strategy for stroke-related AD progression.}, } @article {pmid41437305, year = {2025}, author = {Gong, Z and Zou, J and Fang, Y and Li, J and Luo, Y and Xue, Q and Yu, B and Hua, B and Liu, Z}, title = {The role of gut microbiota in neuropathic pain: insights into immune mechanisms.}, journal = {The journal of headache and pain}, volume = {}, number = {}, pages = {}, doi = {10.1186/s10194-025-02260-4}, pmid = {41437305}, issn = {1129-2377}, abstract = {Neuropathic pain (NP), characterized by its complex pathophysiological mechanisms, has long posed a formidable therapeutic challenge. The burden of NP is further exacerbated by the increasing prevalence of chronic diseases. Emerging evidence highlights the pivotal role of gut microbiota in modulating immune responses, offering novel insights into NP pathogenesis. This review explores recent advancements in understanding how gut microbiota-derived metabolites - including short-chain fatty acids (SCFAs), bile acids, and tryptophan derivatives - regulate immune processes that influence neuroinflammation and nociceptive signaling. We focus on key immune mediators, including macrophages, microglia, T cells, and astrocytes, elucidating their involvement in microbiota-driven immune regulation via pathways such as TLR4/NF-κB signaling, histone deacetylase (HDAC) inhibition, and aryl hydrocarbon receptor (AhR) activation. Additionally, we examine emerging evidence of sex-specific immune mechanisms in NP. Despite promising preclinical findings on microbiota-targeted therapies, such as probiotics and fecal microbiota transplantation, translational challenges, such as microbiota heterogeneity and sex-specific responses, necessitate further investigation. This review aims to bridge microbiology, neuroimmunology, and pain research, offering a multidimensional perspective and actionable insights for the future management of NP.}, } @article {pmid41436018, year = {2025}, author = {Yue, CB and Luan, WW and Qiu, D and Ding, X and Gu, HW and Liu, PM and Hashimoto, K and Yang, JJ and Wang, XM}, title = {A vagus-dependent gut microbiota-metabolite axis drives chronic inflammatory pain and working-memory deficits in mice.}, journal = {Brain research bulletin}, volume = {}, number = {}, pages = {111702}, doi = {10.1016/j.brainresbull.2025.111702}, pmid = {41436018}, issn = {1873-2747}, abstract = {Chronic inflammatory pain (CIP) has been increasingly linked to gut microbiota (GM)-brain interactions, yet whether these effects rely on vagal signaling remains unclear. Here, we investigated whether GM from CIP mice is sufficient to transfer pain-like behaviors to healthy recipients and whether this process depends on the vagus nerve. Fecal microbiota transplantation (FMT) from mice treated with complete Freund's adjuvant induced mechanical and thermal hypersensitivity and impaired working memory in recipients, accompanied by hippocampal neuroinflammation and GM dysbiosis. Subdiaphragmatic vagotomy (SDV) performed prior to FMT attenuated these behavioral and neuroinflammatory alterations and partially normalized microbial community structure. Plasma metabolomics further showed that SDV restored phosphatidylcholines while reducing pro-inflammatory lipid classes, with several metabolites and bacterial taxa correlating significantly with pain sensitivity and hippocampal cytokine levels. Collectively, these findings demonstrate that a vagus-dependent GM-metabolite-brain axis contributes to CIP-like behaviors and neuroinflammation. Targeting vagal pathways and GM-regulated lipid metabolism may offer therapeutic strategies and pharmacodynamic biomarkers for inflammatory pain.}, } @article {pmid41431379, year = {2026}, author = {Al-Btoosh, S and Donnelly, RF and Kelly, SA}, title = {Microbes and medicines: interrelationships between pharmaceuticals and the gut microbiome.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2604867}, doi = {10.1080/19490976.2025.2604867}, pmid = {41431379}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/drug effects ; Humans ; Animals ; Probiotics ; *Bacteria/drug effects/metabolism/classification/genetics ; Fecal Microbiota Transplantation ; Pharmaceutical Preparations/metabolism ; Prebiotics ; Biotransformation ; }, abstract = {The human gut microbiome plays a critical role in modulating pharmacological and toxicological responses to medications. With a gene pool vastly exceeding that of the human host, the gut microbiome acts as a metabolically active organ capable of transforming, inactivating, or accumulating drugs. This review explores the bidirectional interplay between prescription medicines and the gut microbiome, encompassing three key mechanisms: direct biotransformation by microbial enzymes, indirect modulation of host metabolism and signaling pathways, and drug bioaccumulation within microbial cells. Particular attention is given to six major drug classes: immunotherapeutics, chemotherapeutics, antidepressants, statins, hypoglycemics, and antihypertensives. The ways in which individual microbial profiles can influence therapeutic outcomes are also reviewed. We examined how common non-antibiotic pharmaceuticals can significantly alter microbial diversity and promote antimicrobial resistance. Strategies to enhance drug efficacy through microbiome modulation, including probiotics, prebiotics, and fecal microbiota transplantation (FMT), are critically assessed. Experimental models ranging from in vitro batch and chemostat systems to animal and clinical studies are compared in terms of their utility for studying drug‒microbiome interactions. Finally, emerging evidence suggesting the gut microbiota composition may serve as a predictive biomarker for personalized medicine and therapeutic success is highlighted. Understanding and harnessing the complex interrelationships between medicines and microorganisms could offer novel avenues to optimize treatment outcomes and mitigate adverse drug effects.}, } @article {pmid41430282, year = {2025}, author = {He, Y and Zhang, Y and Zhao, L and Zhou, Z and Su, N and Zhang, C and Wang, K and Jin, L and Yang, B and Hu, X and Fu, Y}, title = {Vagus nerve stimulation alleviates S. aureus-induced mastitis by regulating gut microbiota S24-7-PPARγ and NF-ΚB/NLRP3 signaling in mice.}, journal = {Journal of neuroinflammation}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12974-025-03654-6}, pmid = {41430282}, issn = {1742-2094}, support = {212558JC010286222//Jilin Province Department of Science and Technology/ ; 32422086//the National Natural Science Foundation of China/ ; 32301247//the National Natural Science Foundation of China/ ; }, abstract = {Gut microbiota dysbiosis has been implicated in the pathogenesis of mastitis. While the vagus nerve exerts well-documented anti-inflammatory effects and modulates gut microbiota, its potential influence on mastitis progression via gut microbiota modulation remains unclear. To investigate this, we employed vagus nerve stimulation (VNS) in Staphylococcus aureus (S. aureus)-induced mastitis in mice. We demonstrate that VNS significantly attenuated mammary gland inflammation and restored epithelial barrier integrity following S. aureus challenge. Crucially, antibiotic depletion of the gut microbiota abrogated the protective effects of VNS, and fecal microbiota transplantation (FMT) from VNS-treated mice conferred protection against mastitis, establishing a causal role for the gut microbiota in mediating the VNS effect. Specifically, VNS markedly increased the abundance of Muribaculaceae. in the gut. Replenishment with S24-7, a representative strain of this genus, alleviated S. aureus-induced mammary gland inflammation in mice. Transcriptomic analysis revealed that S24-7 exerted its effects by activating peroxisome proliferator-activated receptor gamma (PPARγ), which subsequently suppressed the NF-κB/NLRP3 signaling pathway. Overall, our findings suggest that targeting the vagus nerve - mediated Muribaculaceae/PPARγ axis may represent a promising strategy for mastitis treatment.}, } @article {pmid41429881, year = {2025}, author = {Hanzely, P and Holm, K and Bjørnholt, JV and Melum, E and Hov, JR and Rasmussen, H}, title = {Efficacy of oral and rectal administration of human faecal microbiota transplant (FMT) in human microbiota-associated mouse models.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-025-32072-0}, pmid = {41429881}, issn = {2045-2322}, support = {802544/ERC_/European Research Council/International ; }, abstract = {The gut microbiome has gained significant interest due to its association with immune dysregulation, allergies, autoimmune conditions, metabolic disorders, and inflammation-associated malignancies. Understanding underlying mechanisms requires appropriate in vivo models, such as human microbiota-associated mouse models to study the microbiota-host interactions. This study compared the efficacy of oral and rectal administration of human faecal microbiota transplant (FMT) from a single donor in C57BL/6J germ-free mice as these methods are often used interchangeably. Using 16S rRNA sequencing, we quantified colonisation efficacy in luminal and tissue samples from orally- (n = 6) and rectally- (n = 6) colonised mice. We detected 84 genera in the FMT sample, 17 of which were not transferred at all, while additional 7 genera were found exclusively in rectally-colonised mice. A significantly higher proportion of amplicon sequence variants (ASVs) (33% vs. 26%; P < 0.05) and genera (32% vs. 25%; P < 0.05) were absent in orally- compared to rectally-colonised group. Some taxa showed different relative abundances in human vs. mouse samples (e.g. Alistipes and Bacteroides relatively more abundant in mice while Faecalibacterium considerably decreased). Beta diversity analysis revealed greater similarity between FMT and tissue samples irrespective of the administration route, with distinct separation of the tissue and luminal samples. Overall, rectal administration yielded more overlapping genera and ASVs with FMT, highlighting that it could have advantages compared with oral administration for microbiota establishment studies.}, } @article {pmid41429215, year = {2025}, author = {Korenblik, V and Schilder, NKM and de Lange, IGS and Daams, JG and Bockting, CLH and Brul, S and Nieuwdorp, M and Lok, A and Korosi, A}, title = {From gut to glee: Is butyrate a promising antidepressant? A systematic review and mechanistic insights.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {106237}, doi = {10.1016/j.bbi.2025.106237}, pmid = {41429215}, issn = {1090-2139}, abstract = {INTRODUCTION: Despite available therapies for depression, many patients do not achieve adequate improvement, illustrating the need for innovative treatment strategies. Nutritional psychiatry is an emerging area, with increasing evidence that microbially derived butyrate contributes to the beneficial effects of dietary, pre-, pro- and synbiotics interventions - raising the exciting possibility that direct butyrate administration might alleviate depressive symptoms. The main objective was to systematically review the effects of butyrate on depressive symptoms in humans and depressive-like behavior in animals (PROSPERO; CRD42023g0739).

METHODS: A search was conducted in MEDLINE, Embase, PsycINFO, and Web of Science, ICTPR and ClinicalTrials.gov up to October 2025. Studies were included if they examined depressive symptoms in humans or relevant behaviors in animal models of depression/anxiety, involved treatment with butyrate formulations, included a control or pre-post comparison, and reported behavioral or clinical outcomes. Eligible designs included case-control, cohort, (randomized) controlled trials, experimental, or in vivo studies published in English or Dutch. Studies were excluded if depression was not the primary focus or if butyrate was combined solely with another treatment. Risk of bias was assessed with SYRCLE for animal studies and RoB 2 for the human studies.

RESULTS: Of the two randomized controlled trials, one found no measurable effect of 1-week oral butyrate in healthy males, whereas the other found reductions in depressive and anxiety symptoms in patients with ulcerative colitis after 12-weeks oral butyrate. Thirty-two animal studies showed that butyrate generally modulated depressive- and anxiety-like phenotypes in rodents, potentially via anti-inflammatory, neuroplastic, epigenetic and gut-mediated mechanisms.

DISCUSSION: Preclinical findings support the therapeutic promise of butyrate as a novel intervention for depression, warranting further clinical investigation.

ABBREVIATIONS: BDNF, Brain-derived neurotrophic factor; CRS, Chronic restraint stress; CSD, Chronic social defeat; CUMS, Chronic unpredictable mild stress; DASS, Depression, anxiety, Stress Scales; EPM, Elevated plus maze; FMT, Fecal microbiota transplant; FST, Forces swim test; HDAC, Histone deacetylase; HFD, High-fat diet; HPA, Hypothalamic-pituitary-adrenal; ICTRP International Clinical Trials Registry Platform; IL, Interleukin; LDB, Light-dark box; LEIDS-R Leiden Index of Depression Severity-Revised; LPS, Lipopolysaccharide; MD, Maternal deprivation; MDD, Major depressive disorder; MGBA, Microbiota-gut-brain axis; NORT, Novel object recognition test; OFT, Open field test; PFC, Prefrontal cortex; PRISMA Preferred reporting items for systematic reviews and meta-analyses; SCFA, Short-chain fatty acid; SPT, Sucrose preference test; SYRCLE, Systematic Review Centre for Laboratory Animal Experimentation; TCA, Tricarboxylic acid; TNF, Tumor necrosis factor; TST, Tail suspension test; ZO-1, Zonulin-1.}, } @article {pmid41425939, year = {2025}, author = {Chen, J and Sun, K and Zhang, X and Chen, X and Chu, Y and Geng, L and Bian, Z and Su, Y and Cong, X and Wang, G}, title = {Psoriasis and gut microbes: research advances from mechanism to therapy.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1711288}, pmid = {41425939}, issn = {1664-302X}, abstract = {BACKGROUND: Psoriasis is a chronic, immune-mediated, relapsing inflammatory skin condition, with its pathogenesis remaining incompletely understood and clinical eradication presenting significant challenges. Recent studies have highlighted the role of gut microbiota in psoriasis pathogenesis, emerging as a focal point of research.

OBJECTIVE: This review aims to systematically elucidate the core mechanisms by which gut microbiota contribute to psoriasis pathogenesis, summarize advances in gut microbiota-based therapeutic strategies, and provide theoretical support and innovative insights for both basic research and clinical treatment of psoriasis.

METHODS: Comprehensively retrieve and analyze recent research literature on the gut microbiota characteristics of psoriasis patients, the regulatory mechanisms of the gut-skin axis, and related therapeutic interventions, focusing on the microbiota's effects on immune modulation, intestinal barrier integrity, and metabolic products.

RESULTS: Accumulating evidence supports a complex, bidirectional regulatory relationship between gut dysbiosis and skin inflammation, with notable alterations in the diversity and relative abundance of gut microbial communities in patients with psoriasis compared to healthy individuals. This review comprehensively examines the mechanisms through which gut microbes contribute to psoriasis development via the gut-skin axis, influencing immune regulation, intestinal barrier integrity, and related metabolites. Additionally, the potential of gut microbiota-based therapies-such as oral probiotics, prebiotics, synbiotics, and fecal microbiota transplantation-in alleviating psoriasis symptoms and reducing disease recurrence is emphasized.

CONCLUSION: Dysbiosis of the gut microbiota is a key factor in the pathogenesis of psoriasis. The regulatory mechanisms of the gut-skin axis offer new insights into the multisystemic associations of psoriasis. Gut microbiota-based therapeutic strategies hold promise as important adjuncts to conventional treatments, laying the foundation for developing novel targeted therapies. This approach carries significant clinical implications for improving the prognosis of psoriasis patients.}, } @article {pmid41425837, year = {2025}, author = {Oladele, P and Johnson, TA}, title = {Trehalose and maltodextrin preserve microbial community structure in freeze-dried fecal samples for fecal microbiota transplantation.}, journal = {ISME communications}, volume = {5}, number = {1}, pages = {ycaf204}, pmid = {41425837}, issn = {2730-6151}, abstract = {Fecal microbiota transplantation (FMT) is a promising approach for restoring gut microbial balance in both humans and animals. However, the logistical limitations of transplanting fresh fecal samples have increased interest in freeze-dried (lyophilized) fecal material as a transplant inoculum. While lyophilization facilitates storage, it can compromise bacterial viability, which is essential for FMT effectiveness. Lyoprotectants are often used to protect bacterial cultures during freeze-drying, but their effect on complex microbial communities remains unclear, as they may preferentially preserve some taxa over others. This study investigated the impact of four lyoprotectants-mannitol, maltodextrin, trehalose, and a maltodextrin-trehalose mixture-on bacterial viability and community structure in pig fecal samples post-lyophilization. Propidium monoazide (PMA) treatment combined with 16S rRNA sequencing (PMAseq) was used to differentiate viable from non-viable bacteria. In the total community (without PMA), microbial profiles appeared similar across treatment groups. However, when focusing on the viable community (PMA-treated), lyoprotectant choice significantly influenced the post-lyophilization community composition. Gram-negative bacterial viability was especially sensitive to lyophilization. Trehalose and maltodextrin preserved bacterial viability and community structure more effectively than mannitol. Mannitol-treated samples had reduced viable bacterial cells and altered community composition, while trehalose and maltodextrin better maintained diversity and structure of the viable (PMA-treated) communities. Taken together, lyoprotectants have differential effects on microbial composition during lyophilization. Among those tested, trehalose and maltodextrin best preserved both viability and community structure, making them promising candidates for FMT applications. Future research should explore optimizing lyoprotectant formulations to enhance microbiome stability and functional outcomes.}, } @article {pmid41424968, year = {2025}, author = {Shayya, M and Wehbi, Z and Matar, M and Elzein, M and Safieddine, Z and El Khoury, K and Ibrahim, JN and Hassan, HF and Jamal, O and Chatila, R and Kobeissy, PH}, title = {Awareness and perception of fecal microbiota transplantation in Lebanon: a cross-sectional survey among the general population, healthcare workers, physicians, and patients.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848251399034}, pmid = {41424968}, issn = {1756-283X}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection (CDI) and shows promise for other dysbiosis-related conditions such as inflammatory bowel disease (IBD). Awareness and acceptance remain underexplored in the Middle East, where cultural and social factors may influence adoption.

OBJECTIVES: To evaluate awareness, perceptions, willingness, and acceptance of FMT among the Lebanese population.

DESIGN: A nationwide cross-sectional survey with nonprobability sampling was conducted between April and November 2024.

METHODS: A total of 725 participants were recruited through mixed sampling across Lebanon's governorates: 379 from the general population, 109 healthcare workers, 155 physicians, and 82 IBD or CDI patients. A structured bilingual questionnaire assessed awareness, perceptions, treatment preferences, and willingness to disclose or undergo FMT. Analyses included Chi-square tests, logistic regression, and false discovery rate-adjusted comparisons.

RESULTS: Overall, 31% of participants had prior awareness of FMT, while 60.1% reported positive perception. Awareness and perception were significantly associated (p = 0.0017) and were highest among physicians (59.4% and 70.2%) and lowest among patients (17.1% and 52.4%). Sources varied by group: universities for the general population, media for patients, and professional networks for healthcare workers and physicians. Logistic regression identified physician status, younger age, and prior awareness as predictors of favorable perception. Capsules were the preferred delivery route across groups. Willingness to disclose (81.4%) and to donate stool (68.4%) were high, while 17.2% expressed stigma-related concerns. Major concerns included hygiene, infection risk, and psychological discomfort.

CONCLUSION: FMT awareness in Lebanon remains limited, particularly among patients and the public. Although perceptions are generally positive, misconceptions, stigma, and unrealistic expectations persist. These findings stem from a nonprobability sample that overrepresents younger, female, and highly educated participants and is not nationally representative. Targeted education, stronger physician-patient communication, and culturally sensitive approaches are needed to promote FMT acceptance and integration into practice.}, } @article {pmid41424618, year = {2025}, author = {Pandey, SN and Goyal, K and Rana, M and Menon, SV and Ray, S and Ali, H and Kumbhar, PS and Disouza, J and Singh, SK and Gupta, G and Wong, LS and Kumarasamy, V and Subramaniyan, V}, title = {Microbiome-derived bile acids as endogenous regenerative mediators in liver repair.}, journal = {Regenerative therapy}, volume = {30}, number = {}, pages = {681-690}, pmid = {41424618}, issn = {2352-3204}, abstract = {The liver's extraordinary capacity for self-repair is often compromised by chronic injury, fibrosis, or extensive resection, creating an urgent need for innovative regenerative therapies to restore liver function. Emerging evidence suggests that microbiome-derived bile acid metabolites are potent endogenous mediators of hepatic regeneration. Beyond their canonical role in lipid emulsification, these chemically diverse molecules engage nuclear and membrane receptors, most notably the farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5), to stimulate hepatocyte proliferation, modulate inflammatory responses, and reactivate quiescent progenitor cells. In this review, we integrate mechanistic insights from partial hepatectomy, germ-free, and antibiotic-treated animal models with early clinical observations to illuminate how primary and secondary bile acids orchestrate cell cycle progression, cytokine balance, and extracellular matrix remodeling. We then examined the therapeutic landscape, from synthetic FXR/TGR5 agonists to live-biotherapeutic approaches, genetically modified probiotic strains, and fecal microbiota transplantation. We highlight the preliminary indicators of efficacy and challenges in manufacturing consistency, safety profiling, and regulatory classification. We address the interindividual variability in microbiome composition, potential biomarkers such as serum FGF19, imaging-based measures of functional liver mass, and considerations for optimal trial design. This is the first comprehensive review to frame microbiome-driven bile acids as direct modulators of liver regeneration and chart a coherent translational development pathway. By integrating stem cell biology, hepatology, microbiology, and bioengineering perspectives, we demonstrate the underexplored therapeutic potential of these approaches to transform the future of hepatic repair.}, } @article {pmid41424605, year = {2025}, author = {Kay, E and Kazi, M and Burton, J and Parvathy, SN}, title = {Therapeutic properties of plant-derived prebiotics in melanoma.}, journal = {Exploration of targeted anti-tumor therapy}, volume = {6}, number = {}, pages = {1002354}, pmid = {41424605}, issn = {2692-3114}, abstract = {Immune checkpoint inhibitor (ICI) therapy has revolutionized metastatic melanoma treatment, yet only a subset of patients respond effectively, and the treatment can induce a variety of immune-related adverse events (irAEs), including colitis. The gut microbiome plays a critical role in determining patient responses to immunotherapy, prompting exploration of gut-modifying strategies such as prebiotics, probiotics, and fecal microbiota transplantation (FMT) to overcome both primary and acquired resistance and improve treatment outcomes. Prebiotics, defined as dietary substrates that selectively support the growth and/or activity of beneficial gut microorganisms, represent a feasible and safe strategy for microbiome reshaping. Plant-derived prebiotics like castalagin, inulin, fructooligosaccharides, galactooligosaccharides, mushroom extract, kale extract, and konjac glucomannan offer unique advantages over synthetic or animal-derived alternatives due to their natural fiber content alongside their ability to enhance gut microbial diversity. Prebiotics are known to achieve health benefits by selectively stimulating beneficial gut bacteria, producing short-chain fatty acids (SCFAs) that modulate the host immune system, suppressing pathogenic microbes, enhancing mucin production, and modulating systemic and gut-associated immune responses. SCFAs generated through prebiotic fermentation influence host innate and adaptive immunity and regulate metabolic activity via inhibition of histone deacetylases (HDACs), influencing mTOR/MAPK signaling and cytokine production. They also act as ligands for G-protein-coupled receptors (GPCRs), altering intracellular calcium and cAMP to modulate immune cell gene expression. However, the specific mechanisms by which individual prebiotics interact with host genetics, beneficial gut bacteria, and their metabolites are not very well understood. This is crucial to optimize their therapeutic potential in cancer immunotherapy. This review synthesizes current evidence on plant-derived prebiotics, highlighting the impact of beneficial gut bacteria and their metabolites. Given their established safety for human consumption, prebiotics represent a promising, low-risk option to improve gut microbiome composition and potentially enhance immunotherapy and clinical outcomes in cancer.}, } @article {pmid41424069, year = {2025}, author = {Prokopidis, K}, title = {Probiotics, prebiotics, and synbiotics to counteract sarcopenia: Where are we now and what challenges need to be faced?.}, journal = {The Proceedings of the Nutrition Society}, volume = {}, number = {}, pages = {1-17}, doi = {10.1017/S0029665125102036}, pmid = {41424069}, issn = {1475-2719}, abstract = {Sarcopenia, the age-related decline in muscle mass and strength, is a contributor to frailty and reduced quality of life. Emerging evidence suggests an emerging role of the gut microbiome in modulating skeletal muscle through microbial species and metabolites, such as short-chain fatty acids (SCFAs), potentially influencing glucose profile, inflammation, nutrient absorption, and protein metabolism. This review considers the potential of probiotics, prebiotics, and synbiotics as interventions to mitigate sarcopenia based on animal and human studies, while providing a critique of present barriers that need to be addressed. Preclinical models, including germ-free mice and faecal microbiota transplantation, demonstrate that gut microbiota from healthy or young donors may enhance overall muscle health via reductions in inflammatory and muscle atrophy markers. Limited human studies show that probiotics such as Lactobacillus and Bifidobacterium could improve branched chain amino acid (BCAA) bioavailability and potentially sarcopenia indices, although findings have been inconsistent. Particularly, challenges including inconsistent microbial assessments, lack of dietary control, and interindividual variability due to diet, age, genetics, comorbidities, and medications may hinder progress in this field. Delivery methods (e.g., capsules, fermented foods, or fortified products) could further complicate efficacy through probiotic stability and dietary restrictions in older adults. Standardized protocols (e.g., Strengthening The Organization and Reporting of Microbiome Studies (STORMS) checklist), and multi-omics approaches may be critical to address these limitations and identify microbial signatures linked to sarcopenia outcomes. While preclinical evidence highlights mechanistic pathways pertinent to amino acid metabolism, translating findings to humans requires rigorous experimental trials.}, } @article {pmid41421285, year = {2025}, author = {Sun, C and Tian, Y and Zheng, Y and Yang, K and Liu, S and Zhao, D and Li, L and Yin, X and Li, H and Duan, J and Mu, H and Liu, Q and Luo, J}, title = {KuiAnNingFang alleviates ulcerative colitis by modulating gut microbiota and NF-κB/NLRP3 pathway.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {150}, number = {}, pages = {157677}, doi = {10.1016/j.phymed.2025.157677}, pmid = {41421285}, issn = {1618-095X}, abstract = {BACKGROUND: Ulcerative colitis (UC), a major form of inflammatory bowel disease, is a chronic and relapsing inflammatory condition of the colonic mucosa. Despite the efficacy of the Traditional Chinese Medicine formula KuiAnNingFang (KANF) in alleviating UC, its therapeutic mechanisms remain incompletely understood.

PURPOSE: This study aimed to elucidate the ameliorative effect of Chinese medicine KANF and its potential mechanism against UC.

METHODS: The therapeutic efficacy of KANF against UC was initially assessed in clinical cohorts. A murine model of UC was subsequently established by administering DSS in drinking water and oral treatment with KANF extracts. The prototype components of KANF absorbed into the bloodstream were identified using UPLC-MS/MS. RNA-seq was conducted to identify differentially expressed genes and altered signaling pathways in colonic tissue. Furthermore, 16S rDNA sequencing and fecal microbiota transplantation were employed to determine whether KANF ameliorates UC by modulating the gut microbiota.

RESULTS: KANF demonstrated significant therapeutic efficacy in alleviating UC in both clinical patients and animal models. Integrated analysis combining network pharmacology and RNA-seq validated that KANF attenuates intestinal inflammation by inhibiting NF-κB/NLRP3 activation. Furthermore, 16S rDNA sequencing revealed that KANF restores gut microbial homeostasis, and fecal microbiota transplantation experiments confirmed that the suppressive effect of KANF on NF-κB/NLRP3 signaling is primarily mediated through gut microbiota remodeling.

CONCLUSION: KANF can significantly ameliorate symptoms in both clinical UC patients and DSS-induced colitis mice. KANF exerts its multi-target anti-colitic effects through regulation of the gut microbiota and subsequent suppression of the NF-κB/NLRP3 signaling cascade.}, } @article {pmid41419954, year = {2025}, author = {Huang, SJ and Ye, HL and Xu, S and Liu, T and Zhang, WC and Wang, YL and Duan, SZ}, title = {T cell KAT6A deficiency relieves inflammatory bowel disease in mice.}, journal = {Cell & bioscience}, volume = {15}, number = {1}, pages = {167}, pmid = {41419954}, issn = {2045-3701}, support = {82330015//the National Natural Science Foundation of China/ ; 81991503//the National Natural Science Foundation of China/ ; 2023YFA1801100//the National Key Research and Development Program of China/ ; 2023YFA1801104//the National Key Research and Development Program of China/ ; 2024R01003//Zhejiang Provincial Leading Innovation and Entrepreneurship/ ; }, abstract = {The incidence of inflammatory bowel disease (IBD) has been increasing, and while the interaction between T cells and intestinal microorganisms is crucial in its pathogenesis, the related epigenetic mechanisms remain unclear. This study found that the expression of lysine acetyltransferase 6A (KAT6A) was increased in T cells of patients with acute colitis. Knocking out KAT6A in CD4[+] T cells alleviated dextran sulfate sodium (DSS)-induced colitis in mice, as manifested in body weight, disease activity index, colon length, inflammation, and the expression of proinflammatory factors. Mechanistically, KAT6A deficiency upregulated the senescence of CD4[+] T cells and affected the expression of related genes. Moreover, the regulation of colitis by CD4[+] T cell KAT6A was dependent on the gut microbiota. Antibiotic treatment could reverse the protective effect in T cell KAT6A knockout (TK6AKO) mice, and fecal transplantation experiments confirmed that it was related to the change of the microbiota. 16S rRNA sequencing showed that the composition of the gut microbiota was changed, and specific bacteria such as Akkermansia muciniphila were enriched in TK6AKO mice. This study reveals that KAT6A affects colitis through the interaction between regulating T cell senescence and the gut microbiota, providing a new strategy for treatment.}, } @article {pmid41417461, year = {2025}, author = {Drew, G and Kraft, CS and Mehta, N}, title = {Fecal Microbiota Therapy: Clinical Laboratory Testing and Metabolomic Approaches for Donor Screening, Product Assessment, and Patient Monitoring.}, journal = {Clinical chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1093/clinchem/hvaf156}, pmid = {41417461}, issn = {1530-8561}, abstract = {BACKGROUND: The safety and efficacy of fecal microbiota transplantation for prevention of recurrent Clostridioides difficile infection relies on complex interactions between the donor and recipient microbiome.

CONTENT: Screening of donor stool has largely aimed to ensure safety; however, metagenomic and metabolic features of the stool, which may affect efficacy of the fecal microbiota transplantation (FMT), have been largely overlooked.

SUMMARY: In this review, we discuss the nascent field of metagenomic and metabolic donor and recipient characteristics that may affect efficacy of FMT and future directions for this field to allow for more precise and personalized therapies.}, } @article {pmid41416604, year = {2025}, author = {Rychlik, A}, title = {Fecal microbiome transplantation in the treatment of chronic enteropathies.}, journal = {Polish journal of veterinary sciences}, volume = {28}, number = {4}, pages = {691-700}, doi = {10.24425/pjvs.2025.157285}, pmid = {41416604}, issn = {2300-2557}, mesh = {*Fecal Microbiota Transplantation/veterinary ; Animals ; *Intestinal Diseases/therapy/veterinary ; *Gastrointestinal Microbiome ; Chronic Disease ; }, abstract = {The intestinal microbiome is essential for the proper functioning of the immune system and the course of metabolic processes in the living organism. Intestinal bacteria produce a variety of metabolites that affect the health of many organs, especially the intestines. Disturbances in the composition of the intestinal microflora are referred to as dysbiosis. Dysbiosis occurring in chronic enteropathies may exacerbate intestinal inflammation. Therefore, effective methods of treating enteropathy are still being sought, which involve restoring the proper composition of the intestinal microbiome. In recent years, many scientific centers have drawn attention to the possibility of treating enteropathy by transplanting intestinal contents from a healthy donor. This review presents the advantages and disadvantages of this therapeutic method, described in the latest available literature and the newest guidelines regarding the donor and transplant administration methods.}, } @article {pmid41416026, year = {2025}, author = {Wan, L and Park, A and Lio, P}, title = {Fecal Microbiota Transplantation as a Potential Treatment for Pediatric Atopic Dermatitis.}, journal = {The Journal of clinical and aesthetic dermatology}, volume = {18}, number = {10}, pages = {16}, pmid = {41416026}, issn = {1941-2789}, } @article {pmid41415268, year = {2025}, author = {Wei, YF and Wang, YS and Song, JY and Wang, H and He, XX and Zhong, HJ}, title = {Restoration of peripheral ILC3s by washed microbiota transplantation improves lipid profiles in hyperlipidemia patients.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1688070}, pmid = {41415268}, issn = {1664-3224}, mesh = {Humans ; *Hyperlipidemias/therapy/immunology/blood/metabolism ; Animals ; Mice ; Male ; Gastrointestinal Microbiome/immunology ; Female ; Middle Aged ; *Lymphocytes/immunology/metabolism ; *Fecal Microbiota Transplantation/methods ; Immunity, Innate ; *Lipid Metabolism ; *Lipids/blood ; Interleukin-22 ; Interleukins/blood ; Adult ; Liver/metabolism/immunology ; Disease Models, Animal ; Mice, Inbred C57BL ; Prospective Studies ; }, abstract = {BACKGROUND: The contribution of circulating group 3 innate lymphoid cells (ILC3s) to lipid dysregulation has remained poorly defined, and the mechanisms through which washed microbiota transplantation (WMT) improves lipid metabolism require further clarification.

METHODS: Peripheral ILC subsets and plasma IL-22 were assessed in hyperlipidemia patients and healthy controls. The lipid-lowering effects of WMT were evaluated in a prospective cohort without lipid-lowering medications. Gut microbial and plasma metabolite profiles before and after WMT were analyzed. A hyperlipidemic mouse model was used to determine whether healthy microbiota promote hepatic ILC3 homing via integrin α4.

RESULTS: Hyperlipidemia was characterized by reduced circulating ILC3s, integrin α4[+] ILC3s, and plasma IL-22, all of which showed inverse correlations with TC, TG, LDL-C, non-HDL-C, and ApoB. Significant lipid improvements were achieved after WMT, accompanied by increased circulating ILC3s and integrin α4[+] ILC3s, paralleling reductions in TC and LDL-C. WMT induced marked remodeling of gut microbiota and plasma metabolites, including taxa and metabolites positively associated with ILC3 restoration and lipid improvement. In hyperlipidemic mice, healthy microbiota transplantation increased hepatic ILC3 and integrin α4[+] ILC3 accumulation and improved lipid levels, whereas integrin α4 blockade impaired ILC3 liver homing and attenuated the metabolic benefit.

CONCLUSION: Hyperlipidemia is associated with depletion of circulating ILC3s and reduced IL-22. Restoration of ILC3 subsets and enhancement of integrin α4-dependent hepatic homing are achieved after WMT, accompanying improvements in lipid metabolism.}, } @article {pmid41413564, year = {2025}, author = {Han, M and Xie, B and Yu, Y and Xu, D and Shi, Y and Xu, M and Wu, Y and Zhang, Y and Wen, X and Wang, X and Zhen, Z and Zhang, X and Sun, X and Yuan, Y and Shang, Y and Yuan, S and Hashimoto, K and Zhang, J}, title = {Intestinal γδ T17-IL-17A signaling disrupts hippocampal mitophagy in stress-induced depression and is restored by arketamine.}, journal = {Journal of neuroinflammation}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12974-025-03656-4}, pmid = {41413564}, issn = {1742-2094}, support = {82402568//National Natural Science Foundation of China/ ; 82302471//National Natural Science Foundation of China/ ; 82272231//National Natural Science Foundation of China/ ; 82472223//National Natural Science Foundation of China/ ; 2021YFC2500800//National Key Research and Development program from Ministry of Science and Technology of the People's Republic of China/ ; 2024ZD0529004//Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; }, abstract = {Chronic stress precipitates depression, yet how gut-immune-brain interactions translate stress into mood pathology remains unclear. We tested the hypothesis that stress-primed small intestinal γδ T cells drive hippocampal mitochondrial dysfunction and depression-like behavior via interleukin-17A (IL-1A). In mice exposed to chronic restraint stress (CRS), we combined behavioral assays (open-field, sucrose-preference, tail-suspension, forced-swim), 16S rRNA profiling, fecal microbiota transplantation, Kaede photoconversion, conditional CD8α deletion in γδ T cells, hippocampal IL-17A overexpression, rapamycin treatment, and administration of the antidepressant arketamine. CRS increased gut and brain permeability, induced gut-microbiota dysbiosis, and promoted migration of small intestinal CD8α[+] γδ T17 cells to the meninges and brain; γδ T cells were the predominant IL-17A source in the brain. Kaede tracing confirmed an intestinal origin, and CRS-associated microbiota alone transferred γδ T cell trafficking and depression-like behavior to recipients. In the hippocampus, CRS elevated IL-17A and impaired PINK1/Parkin-mediated mitophagy (decreased PINK1, Parkin, Beclin-1, and LC3B-II/I; increased p62), reduced ATP, and produced mitochondrial and synaptic ultrastructural deficits. IL-17A overexpression further worsened mitophagy and behavior, whereas rapamycin restored both. Conditional deletion of CD8α in γδ T cells reduced brain γδ T17 infiltration, lowered hippocampal IL-17A, rescued mitophagy and synapses, and improved behavior. Arketamine normalized dysbiosis and barrier markers, curtailed γδ T cell trafficking, decreased hippocampal IL-17A, restored mitophagy, and alleviated depression-like behavior in both sexes. These findings delineate a stress-responsive microbiota-γδ T cell-IL-17A pathway that compromises hippocampal mitophagy and identify arketamine as a candidate modulator of this axis, nominating mitophagy and γδ T cell trafficking as translational targets.}, } @article {pmid41373016, year = {2025}, author = {Qian, J and Tao, Q and Shen, Y and Wang, L and Wang, M and Wang, N and Liang, Q and Lu, J and Huang, Y and Liao, W and Chen, R and Ge, R and Yuan, Z and Li, Y and Shen, H and Gao, Q and Yan, F}, title = {Periodontitis salivary microbiota exacerbates colitis by CXCL3 derived from gut microbiota-induced macrophages.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {255}, pmid = {41373016}, issn = {2049-2618}, support = {No. 0224C030//High-Level Hospital Construction Project of Nanjing Stomatological Hospital/ ; No. 82270979, 81970939//The National Natural Science Foundation of China/ ; JSDW202246//Jiangsu Provincial Medical Key Discipline (Laboratory) Cultivation Unit/ ; No. 2019060009//Nanjing Clinical Research Center for Oral Diseases/ ; }, mesh = {*Gastrointestinal Microbiome ; *Periodontitis/complications/microbiology ; *Saliva/microbiology ; *Colitis/microbiology/therapy ; Probiotics/therapeutic use ; Case-Control Studies ; Humans ; Male ; Animals ; Mice ; Mice, Inbred C57BL ; RAW 264.7 Cells ; Lacticaseibacillus rhamnosus ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Increasing research has focused on the role of the oral-gut axis in the development of colitis. Saliva contains a large number of oral bacteria that influence gut microbiota and colitis, but the underlying mechanisms remain unclear. In this study, we investigated the role and mechanisms of gut microbiota in salivary microbiota-affected colitis.

RESULTS: We confirmed that periodontitis salivary microbiota (PSM) exacerbated colitis compared to healthy salivary microbiota (HSM). Antibiotics could reverse the effect of PSM in exacerbating colitis, suggesting that the altered gut microbiota was pathogenic. PSM resulted in the enrichment of pathogens, such as Escherichia coli, and lipopolysaccharide in the gut microbiota, and this gut microbiota was shown to be detrimental to colitis by C-X-C motif chemokine ligand 3(CXCL3) in our study. Mechanistically, PSM-derived gut microbiota significantly upregulated CXCL3 in the macrophages, and these Cxcl3 + macrophages contributed to colitis pathology by secreting CXCL3. The macrophages-derived CXCL3 exacerbated colitis via neutrophil chemotaxis and macrophage polarization. CXCL3 induced M2b-like polarization in macrophages, with functions related to immunomodulation and lipid catabolism. These macrophages exacerbated colitis in a gut microbiota-dependent manner. In terms of treatment, administration of Lactobacillus rhamnosus GG, a well-known probiotic, improved gut microbiota and CXCL3, and ameliorated the PSM-exacerbated colitis.

CONCLUSIONS: Gut microbiota was a key factor in PSM-exacerbated colitis, which was by activating macrophage to secrete CXCL3. Our study provides new insights into the role of gut microbiota with macrophages and chemokines in colitis, and the mechanism of oral disease affecting the distal organs systemically.}, } @article {pmid41315900, year = {2025}, author = {Ardis, CK and Bui, TPN and Nieuwdorp, M}, title = {Gut microbiota in cancer cachexia: a new frontier for research and therapy.}, journal = {Genes & nutrition}, volume = {20}, number = {1}, pages = {28}, pmid = {41315900}, issn = {1555-8932}, support = {09150182010020//European Union's Horizon Training Mobility Actions- Consortium Grant agreement MiCCrobioTAckle/ ; 09150182010020//NWO VICI grant 2020/ ; 101141346//ERC Advanced grant/ ; }, abstract = {Cancer cachexia is a multifactorial syndrome characterized by systemic inflammation, progressive weight loss, muscle wasting, and metabolic alterations, which negatively affect quality of life, treatment response, and survival in cancer patients. Despite its prevalence and impact, effective treatments remain limited, in part due to the complex and poorly understood pathophysiology of the syndrome. Recent studies have revealed that gut microbiota alterations may contribute to the development and progression of cachexia through mechanisms involving immune activation, impaired gut barrier function, and disrupted metabolic signaling. This review explores the interplay between the altered gut microbiome and cancer cachexia, focusing on microbial metabolites such as short-chain fatty acids, gut barrier dysfunction and the impact of cancer therapies on microbial homeostasis. We evaluate emerging microbiota-targeted strategies, including traditional and next-generation probiotics and fecal microbiota transplantation, as novel therapeutic avenues. A deeper understanding of host–microbiome interactions may lead to the development of more effective, personalized interventions to improve cancer cachexia patient care.}, } @article {pmid41409175, year = {2025}, author = {Ng, DZW and Low, A and Khairul Sani, KRB and Liu, L and Zhang, Z and Koh, XQ and Zhu, M and Mitra, K and Muthiah, M and Dan, YY and Lee, JWJ and Chan, ECY}, title = {Dysbiosis-Driven Reprogramming of Secondary Bile Acid Metabolism in Metabolic Dysfunction-Associated Steatotic Liver Disease: Insights from an Ex Vivo Human Fecal Microbiota Model.}, journal = {ACS pharmacology & translational science}, volume = {8}, number = {12}, pages = {4335-4344}, pmid = {41409175}, issn = {2575-9108}, abstract = {Gut microbial dysbiosis-induced perturbations in bile acid (BA) metabolism are implicated in metabolic dysfunction-associated steatotic liver disease (MASLD), yet evidence remains largely associative. Using an optimized ex vivo fecal microbiota model, we modeled the metabolism kinetics of conjugated- and primary-BA between MASLD and healthy donors. Enzymes for known BA metabolic reactions were inferred using functional metagenomics. MASLD cultures exhibited impaired deconjugation capacity but preserved downstream primary-BA clearance and demonstrated a substrate-independent shift that favored oxidative metabolism over 7α-dehydroxylation. This was marked by increased formation clearance of 7-keto-deoxycholic acid (175%) and 3-oxo-cholic acid (51.7%) from cholic acid (CA) and 7-keto-lithocholic acid (77.9%) from chenodeoxycholic acid (CDCA). C7-oxidized BA constituted the major proportion of total BA clearance (CA = 56.0%, CDCA = 72.3%) in MASLD cultures. Enrichment of C3- and C7-hydroxysteroid dehydrogenases in MASLD compared to control corroborated the differential secondary BA profiles. Together, microbes catalyzing C7-oxidation warrants further investigation as potential pharmacological targets of MASLD.}, } @article {pmid41408061, year = {2025}, author = {Wang, Z and Cui, Y and Li, D and Yan, L and Zhu, S and Ma, X and Lu, Z and Li, C and Feng, J and Yuan, W and He, X}, title = {Alternate-day fasting ameliorates α-synuclein pathology and suppresses inflammation via the gut-brain axis in an MPTP-induced subacute mouse model of Parkinson's disease.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {228}, pmid = {41408061}, issn = {2055-5008}, support = {2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; }, mesh = {Animals ; Mice ; *Fasting ; *alpha-Synuclein/metabolism/genetics ; *Gastrointestinal Microbiome ; Disease Models, Animal ; *Parkinson Disease/pathology/metabolism/therapy ; *Brain/metabolism/pathology ; *Inflammation ; Male ; Fecal Microbiota Transplantation ; *Brain-Gut Axis ; Mice, Inbred C57BL ; Dopaminergic Neurons/metabolism ; }, abstract = {Dietary restrictions like alternate-day fasting (ADF) can counteract several age-related disorders, but its role in Parkinson's disease (PD) is still controversial. Recent findings highlight the imbalances in the gut-brain axis in PD, herein, we aim to study whether ADF can confer protection in PD mice through the gut-brain axis. Firstly, we assessed the neuroprotective effect of ADF in a time-dependent manner and found that 16 -week ADF could confer the optimal neuroprotection by preserving dopaminergic neurons and reducing the level of α‑synuclein (α‑syn) in the substantia nigra (SN), and it could decrease inflammatory cytokine levels in both the brain and the gut. Furthermore, ADF reshaped gut microbial composition and altered metabolites associated with PD. Relative abundances of several intestinal flora, including Alistipes, Helicobacter and Lactobacillus, were identified as potential mediators. In addition, we conducted fecal microbiota transplantation (FMT) to further investigate the role of the gut-brain axis in the neuroprotective effects of ADF. Notably, we found that FMT from ADF mice conferred equal protection to ADF in ameliorating the pathology and inflammation in both the brain and the gut. Collectively, our findings suggest that the microbiota-gut-brain axis is crucial to the neuroprotective effect of ADF in PD.}, } @article {pmid41408007, year = {2025}, author = {Abrishami, M and Sabouri, M and Joneidi, F and Haghshenas, Z and Khalili-Tanha, G and Nazari, E}, title = {The role of gut microbiota in breast cancer: biomarker identification and therapeutic applications.}, journal = {Antonie van Leeuwenhoek}, volume = {119}, number = {1}, pages = {14}, pmid = {41408007}, issn = {1572-9699}, support = {1403-1121//Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran/ ; }, mesh = {Humans ; *Breast Neoplasms/therapy/microbiology/diagnosis ; *Gastrointestinal Microbiome/physiology ; Female ; *Biomarkers, Tumor ; Dysbiosis/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Recent studies have established the gut microbiome as a crucial player in breast cancer diagnosis, progression, and treatment. Distinct microbial patterns have shown promise as non-invasive diagnostic and prognostic biomarkers, supporting patient stratification and risk assessment based on microbiota composition. The gut microbiome also modulates estrogen metabolism, influencing the risk of hormone receptor-positive breast cancer, while dysbiosis can promote chronic inflammation and tumor expansion. Moreover, accumulating evidence demonstrates that gut bacteria can alter responses to chemotherapy and immunotherapy, suggesting that microbiota modulation may enhance treatment efficacy. With the advent of omics technologies and machine learning, intricate host-microbe interactions are being decoded, revealing new molecular targets and therapeutic opportunities. Importantly, early clinical and interventional studies using probiotics, prebiotics, and fecal microbiota transplantation (FMT) are being explored to restore microbial balance, mitigate therapy-related side effects, and improve antitumor immunity in breast cancer patients. Together, these advances underscore the translational potential of microbiome research, paving the way for microbiota-guided diagnostic, prognostic, and therapeutic strategies in personalized breast cancer management.}, } @article {pmid41406837, year = {2025}, author = {Wu, C and Hu, S and Li, D and Jiang, X and Bi, G and Wang, P and OuYang, H and Fang, J and Yang, X and Bi, H}, title = {Gut microbiota affects the role of mPXR agonist PCN in alleviating sepsis-induced liver injury by regulating YAP activation.}, journal = {International immunopharmacology}, volume = {169}, number = {}, pages = {116013}, doi = {10.1016/j.intimp.2025.116013}, pmid = {41406837}, issn = {1878-1705}, abstract = {BACKGROUND: Sepsis severity is primarily driven by exaggerated inflammatory responses that contribute to hepatic injury. The pregnane X receptor (PXR), a nuclear receptor that regulates xenobiotic and endobiotic metabolism, plays a crucial protective role against sepsis-induced liver injury and modulates hepatic regeneration. Concurrently, the gut microbiota contributes to sepsis pathogenesis via intestinal signaling and the gut-liver axis. This study aimed to evaluate how the gut microbiota mediates the protective effects exerted by the mouse PXR (mPXR) agonist pregnenolone-16α‑carbonitrile (PCN) against sepsis-induced liver injury and to elucidate the underlying mechanisms.

METHODS: Sepsis was induced by cecal ligation and puncture (CLP) or lipopolysaccharide (LPS) treatment. Mice were pretreated with PCN for three consecutive days prior to model construction. Gut microbiota depletion was achieved using a cocktail of broad-spectrum antibiotics (ABX), and fecal microbiota transplantation (FMT) was performed to restore microbial communities.

RESULTS: We found that depletion of gut microbiota abrogated PCN-mediated hepatoprotection in septic mice. Conversely, FMT from PCN-treated donors attenuated sepsis-induced liver injury. Furthermore, PCN-activated PXR significantly altered the gut microbiota composition in septic mice. Mechanistically, PCN treatment enhanced activation of the Yes-associated protein (YAP) signaling pathway, an effect that was diminished upon depletion of gut microbiota. Correspondingly, FMT from PCN-treated donors enhanced YAP activation and upregulated its downstream target proteins in septic mice.

CONCLUSIONS: In summary, this study demonstrated that the gut microbiota mediated the protective effects of PCN against sepsis-induced liver injury by activating the YAP pathway. These findings provide novel insights into the role of gut microbiota in PXR-mediated protection during sepsis.}, } @article {pmid41405935, year = {2025}, author = {D'Amico, F and Nardone, OM and Bruno, A and Allocca, M and Zilli, A and Furfaro, F and Parigi, TL and Solitano, V and Ungaro, F and Faggiani, I and La Mantia, A and Calabrese, G and Fiorino, G and Jairath, V and Peyrin-Biroulet, L and Massimino, L and Castiglione, F and Danese, S}, title = {Bowel Urgency Improvement Correlates With Clinical, Biochemical, and Intestinal Ultrasound Improvements in Inflammatory Bowel Disease: A Cross Sectional Multicenter Study.}, journal = {United European gastroenterology journal}, volume = {}, number = {}, pages = {}, doi = {10.1002/ueg2.70129}, pmid = {41405935}, issn = {2050-6414}, abstract = {BACKGROUND: Bowel urgency (BU) is reported by over 80% of patients with ulcerative colitis (UC) and 60% of those with Crohn's disease (CD). However, the impact of advanced therapies on BU has not been consistently evaluated.

OBJECTIVES: To assess the effect of advanced therapies on BU improvement in patients with UC and CD.

METHODS: This retrospective cohort study included all consecutive patients with confirmed UC or CD who started an advanced therapy with available data regarding BU before and after induction therapy between 2023 and 2024 at two tertiary centers. BU was assessed using the numeric-rating-scale urgency score (NRS-us), with BU defined as NRS-us ≥ 3. The primary endpoint was BU improvement (NRS-us ≤ 3 or reduction of at least two points) after the induction phase. Multivariate logistic regression analysis identified factors associated with BU improvement.

RESULTS: A total of 159 patients were included (56% male; 65% UC; median age: 36 years (Interquartile range [IQR] 27-25)). TNFα inhibitors were the most frequently used agents (49.6%). At baseline, the median NRS-us was 7. After induction, 50.9% of patients achieved BU improvement, with a mean reduction of 2.3 ± 2.9 points. BU improvement was significantly associated with clinical remission (false-discovery-rate [FDR] = 0.009 in CD and FDR = 0.010 in UC), normalization of fecal calprotectin (FDR = 0.001), CRP (FDR = 0.008), and bowel wall thickness on intestinal ultrasound (FDR = 0.001). No significant differences were observed between therapeutic classes.

CONCLUSION: BU improved in approximately half of IBD patients following induction with advanced therapies. Its improvement correlated with clinical, biochemical, and ultrasound remission, supporting the incorporation of BU assessment into routine clinical monitoring.}, } @article {pmid41403899, year = {2025}, author = {Shi, W and Wu, L and Qin, Q and Li, Y and Chen, W}, title = {Research progress on the role of microbiome-immune-neurotransmitter network in post-stroke sleep disorders.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1694709}, pmid = {41403899}, issn = {1663-4365}, abstract = {Post-stroke sleep disorders, as a significant complication affecting patient rehabilitation, are closely associated with dysregulation of the microbiome-immune-neurotransmitter network. Following stroke, activation of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system triggers intestinal barrier disruption (reduced tight junction proteins and intestinal permeability) along with microbial imbalance (decreased Bifidobacterium and increased Enterobacteriaceae). Reduced short-chain fatty acids and lipopolysaccharide (LPS) translocation exacerbate systemic inflammatory responses and neurotransmitter imbalances (inhibited serotonin synthesis and excitotoxic glutamate production). These changes further disrupt circadian regulation by the hypothalamic suprachiasmatic nucleus, leading to reduced REM sleep and disrupted slow-wave sleep architecture. Future research should prioritize interventional strategies targeting the gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation, integrated with multi-omics technologies and neural circuit modulation approaches, to elucidate the spatiotemporal dynamics of the microbiome-immune-neurotransmitter network and provide a theoretical basis for clinical translation. Restoring brain-gut axis homeostasis is expected to improve post-stroke sleep disorders and neurological functional outcomes in patients.}, } @article {pmid41403286, year = {2025}, author = {Yoshinami, Y and Yamaguchi, S and Shoji, H and Okita, N and Takamaru, H and Hirose, T and Hirano, H and Takashima, A and Imazeki, H and Yamamoto, S and Koyama, S and Ishikawa, D and Terauchi, J and Tanaka, K and Ogawa, K and Watanabe, H and Kato, K}, title = {Feasibility of antibiotic-assisted fecal microbiota transplantation with immunotherapy for esophageal and gastric cancer.}, journal = {Future oncology (London, England)}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/14796694.2025.2599371}, pmid = {41403286}, issn = {1744-8301}, abstract = {AIMS: Immune checkpoint inhibitors (ICIs) have improved outcomes in several malignancies, but survival remains poor for patients with unresectable advanced or recurrent esophageal or gastric cancer. Recent evidence suggests that modulation of the intestinal microbiota may influence the therapeutic response to ICIs. This study aims to evaluate the safety and preliminary efficacy of fecal microbiota transplantation following antibiotic pretreatment (A-FMT) in patients scheduled to receive ICI-containing regimens.

METHODS: This phase I - II, single-institution clinical trial enrolls patients with unresectable advanced or recurrent esophageal or gastric cancer. Participants receive a 1-week course of oral antibiotics (amoxicillin, fosfomycin, and metronidazole) prior to transplantation. A single dose of donor-derived intestinal microbiota solution is administered via colonoscopy, followed by initiation of ICI-based therapy on the next day. The primary endpoint is the incidence of dose-limiting toxicity. Secondary endpoints include response rate, disease control rate, progression-free survival, overall survival, and adverse events. Comprehensive translational research is conducted using stool, blood, and tissue samples to characterize immune responses and identify biomarkers associated with A-FMT and ICI efficacy.Trial registration: jRCTs031240170.The study is ongoing, and patients are currently being enrolled. Enrollment started in June 2024. A total of 7 patients have been enrolled as of August 2025. This protocol is version 3.2.}, } @article {pmid41402129, year = {2025}, author = {Wang, J and Li, J and Li, Y and Huang, W and Huang, C and Xu, Q and Sun, J and Gong, J and Ma, X and Wang, G and Meng, Y and Li, X}, title = {Angiotensin-(1-7) alleviates intestinal barrier dysfunction and dysbiosis in mice with polymicrobial sepsis.}, journal = {British journal of pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bph.70248}, pmid = {41402129}, issn = {1476-5381}, support = {82170641//National Natural Science Foundation of China/ ; 82470663//National Natural Science Foundation of China/ ; 82270089//National Natural Science Foundation of China/ ; 81873583//National Natural Science Foundation of China/ ; 2021A1515012595//Guangdong Provincial Science and Technology Projects under Grant/ ; 2024A1515220136//Guangdong Provincial Science and Technology Projects under Grant/ ; 202312121006//National College Students' Innovation and Entrepreneurship Training Program/ ; S202012121056//Guangdong Provincial Innovation Training Projects under Grant/ ; 2017B020209003//Guangdong Science and Technology Project under Grant/ ; JCYJ20210324112807021//Technical Research and Development Project of Shenzhen/ ; }, abstract = {BACKGROUND AND PURPOSE: The intestine plays a key role in the initiation of sepsis. The gut barrier impedes the translocation of commensal bacteria to the liver in sepsis. Previous studies have reported that angiotensin-(1-7) [Ang-(1-7)] attenuated sepsis-induced organ injury and mortality. However, its role in sepsis-induced intestinal barrier dysfunction remains unclear. Here we have investigated therapeutic effects of Ang-(1-7) on the intestinal barrier dysfunction and dysbiosis in a murine model of sepsis.

EXPERIMENTAL APPROACH: We used a model of sepsis in C57BL/6 mice with caecal ligation and puncture (CLP), to assess mortality and histological and biochemical changes in the gut and liver tissues. Faecal microbiota transplantation (FMT) was used to assess the role of the gut microbiome. 16-s rDNA and metabolomics analyses were performed to characterize differences in the gut microbiome signatures and metabolic profiles.

KEY RESULTS: Plasma Ang-(1-7) was decreased in patients with sepsis. In CLP mice, exogenous Ang-(1-7) attenuated intestinal barrier dysfunction and liver damage. FMT experiments showed that the protective effects of Ang-(1-7) on the gut depended on the gut microbiota. Furthermore, 16-s ribosomal DNA analysis revealed that Ang-(1-7) treatment increased the abundance of Lactobacillus gasseri (L. gasseri) among commensal bacteria. Mechanistically, L. gasseri regulated the production of antimicrobial peptides in intestinal epithelia by activating NLRP6 inflammation.

CONCLUSION AND IMPLICATIONS: Ang-(1-7) protected against sepsis-induced intestine barrier dysfunction and liver injury in mice by modulating gut homeostasis and NLRP6 inflammasome. Ang-(1-7) is a promising candidate drug for protecting intestinal homeostasis in sepsis, offering new insights for clinical treatment.}, } @article {pmid41400824, year = {2025}, author = {Liu, M and Liu, W and Zhao, K and Zhang, W and Lei, B and Zhang, Y and Li, L and Yuan, W}, title = {Adult duck fecal microbiota transplantation alleviates short beak and dwarfism syndrome in ducklings by inhibiting Th17 cell differentiation.}, journal = {Virulence}, volume = {}, number = {}, pages = {2605745}, doi = {10.1080/21505594.2025.2605745}, pmid = {41400824}, issn = {2150-5608}, abstract = {Novel goose parvovirus (NGPV) infection in ducklings induces short beak and dwarfism syndrome (SBDS), leading to significant economic losses. Since NGPV predominantly infects ducklings, whether reshaping the intestinal flora of ducklings through fecal microbiota transplantation from adult ducks (FMT-A) can alleviate SBDS is an interesting question. This study aimed to investigate the impact of FMT-A on the susceptibility of ducklings to NGPV infection, to elucidate the potential relationship between gut microbiota and viral pathogenicity. The results showed that ducklings were more susceptible to NGPV than adults, and that adult ducks exhibited higher fecal microbiota richness and diversity. FMT-A treatment attenuated NGPV-induced reductions in body weight, beak and tibia length, and muscle mass. Furthermore, FMT-A alleviated gut dysbiosis and intestinal tissue damage, increased glycogen in the intestinal mucosa, upregulated ZO-1 expression, expanded the epiphyseal region, and reduced osteoclast numbers in the tibia of ducklings. Moreover, FMT-A suppressed the expression of the Th17 cell-specific transcription factor retinoic acid receptor-related orphan receptor γt in the ileum and bone, and decreased the expression levels of pro-inflammatory cytokines in the ileum, bone, and serum. These findings indicate that ducklings are more susceptible to NGPV than adult ducks, with significantly lower diversity and abundance of fecal microbiota. FMT-A can stabilize intestinal flora, mitigate intestinal barrier damage, inhibit Th17 cell differentiation, thereby reducing abnormal bone development, and ultimately alleviate SBDS in ducklings. These findings provide a theoretical basis for developing novel strategies targeting gut microbiota modulation to prevent and control SBDS in ducklings.}, } @article {pmid41400783, year = {2025}, author = {Wei, Q and Wang, Y and Rui, M and You, JHS}, title = {Health economic evaluations of fecal microbiota transplantation for non-clostridioides difficile related diseases: a systematic review.}, journal = {Health economics review}, volume = {15}, number = {1}, pages = {103}, doi = {10.1186/s13561-025-00698-5}, pmid = {41400783}, issn = {2191-1991}, } @article {pmid41399570, year = {2025}, author = {Bheemaneni, RS and Sakarkar, P and Nigam, A and Nwachukwu, EC and Sekar Lakshmisai, S and Mohammed, L}, title = {Unraveling the Association Between Fibromyalgia and Irritable Bowel Syndrome: A Systematic Review.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {e96801}, pmid = {41399570}, issn = {2168-8184}, abstract = {Fibromyalgia (FM) and irritable bowel syndrome (IBS) often occur together. Patients with FM and IBS present similar symptoms, such as pain and fatigue; this leads to a delay in diagnosis and management. This systematic review explored the shared pathophysiology of these conditions in adults, focusing on the roles of immune dysfunction, gut dysbiosis, neurotransmitter imbalances, and disturbances in the gut-brain axis. We searched five databases, PubMed, PubMed Central, Google Scholar, Cochrane, and ScienceDirect, for relevant free full-text English articles from 2015 to 2025. Ten studies were selected after screening, identification, and quality assessment, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Our review found that immune system dysregulation involves mast cells and pro-inflammatory cytokines that damage the gut barrier. The gut microbiome and neurotransmitter levels seem to have a reciprocal influence on each other, and their alteration contributes to pathogenesis, with an increase of certain species showing an association with symptom severity. Serotonin and tryptophan metabolism appear to have a crucial role in pain perception, particularly visceral hypersensitivity. Therapeutic strategies targeting the gut microbiome, such as probiotics and fecal microbiota transplantation, have potential but require further research. Overall, this review identified overlapping mechanisms of FM-IBS comorbidity, which can pave the way to effective and combined treatment approaches. Future research should explore gender distinctions in the mechanisms, medications that act on neurotransmitter receptors (especially serotonergic pathways), and the utility of fecal microbiota transplantation and probiotics.}, } @article {pmid41399411, year = {2025}, author = {Li, X and Ji, J and Li, J and Li, S and Luo, Q and Gu, M and Yin, X and Zhang, M and Fan, H and Yao, R}, title = {Gut microbiota-bile acid metabolic disorder involved in the cognitive impairments in epilepsy through HO-1 dependent ferroptosis.}, journal = {Journal of pharmaceutical analysis}, volume = {15}, number = {11}, pages = {101291}, pmid = {41399411}, issn = {2214-0883}, abstract = {Abnormal bile acid (BA) metabolism has been implicated in the pathogenesis of central nervous system (CNS) diseases, but its role in epilepsy remains unclear. In this study, we investigated the relationship between gut microbiota-driven dysregulation of BA metabolism and seizure-induced ferroptotic neuronal death in epilepsy. Our targeted metabolomic analysis revealed elevated levels of deoxycholic acid (DCA) in the serum and cerebrospinal fluid (CSF) of epileptic patients, which correlated with cognitive impairment. In a pentylenetetrazol (PTZ)-induced mouse model of epilepsy, 16S ribosomal RNA (16S rRNA) sequencing showed significant alterations in gut microbiota composition. Importantly, fecal microbiota transplantation (FMT) from healthy mice into epileptic mice significantly reduced seizure activity and improved cognitive function, primarily by normalizing serum and brain levels of secondary bile acids (SBAs), including DCA. Both in vitro and in vivo experiments demonstrated that DCA promotes ferroptosis in hippocampal neurons by activating the farnesoid X receptor (FXR). This activation triggered the nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase-1 (HO-1) signaling pathway, known to be involved in oxidative stress and cell death regulation. Our findings suggest that the upregulation of DCA, through its effects on FXR and HO-1, plays a critical role in the progression of epilepsy by inducing ferroptosis in hippocampal neurons. Targeting the DCA-FXR-HO-1 axis may provide a novel therapeutic strategy for treating seizures and associated cognitive deficits in epilepsy.}, } @article {pmid41399387, year = {2026}, author = {Yu, Y and Zhao, W and Yang, M and Wu, B and Yuan, X}, title = {Tumor-Promoting Gut Microbes in Colorectal Cancer: Mechanisms and Translational Perspectives.}, journal = {International journal of medical sciences}, volume = {23}, number = {1}, pages = {63-75}, pmid = {41399387}, issn = {1449-1907}, mesh = {Humans ; *Colorectal Neoplasms/microbiology/therapy/diagnosis/pathology/immunology ; *Gastrointestinal Microbiome/immunology/physiology ; *Dysbiosis/microbiology/complications/therapy/immunology ; Fecal Microbiota Transplantation/methods ; Probiotics/therapeutic use ; Carcinogenesis/immunology ; Translational Research, Biomedical ; }, abstract = {Colorectal cancer (CRC) represents a predominant global malignancy, characterized by increasing incidence and mortality rates. Recent investigations have underscored the gut microbiota as a pivotal element in the pathogenesis and progression of CRC. This review synthesizes current evidence regarding the association between gut microbial dysbiosis and CRC, with a particular emphasis on pathogenic bacteria such as Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, pks[+] Escherichia coli, and Enterococcus faecalis, among others. The mechanisms through which these microbes contribute to tumorigenesis include the induction of DNA damage, the promotion of chronic inflammation, and the induction of immunosuppression, and the production of oncogenic metabolites. Additionally, the review examines the clinical implications of gut microbiota, highlighting their potential as non-invasive biomarkers for early CRC detection and their impact on the efficacy and toxicity of chemotherapy, radiotherapy, and immunotherapy. Furthermore, emerging microbiota-targeted interventions, such as fecal microbiota transplantation, dietary modification, and probiotics, are evaluated for their therapeutic potential. Despite substantial progress, challenges remain in standardizing microbial markers and optimizing individualized microbiota modulation strategies. Future studies integrating multi-omics and machine learning approaches may pave the way for microbiome-based precision medicine in CRC.}, } @article {pmid41399025, year = {2025}, author = {Zhao, D and Wang, X and Wang, K and Yang, B and Zhu, H and Xu, Y and Ye, C and Li, L and Lv, X and Zhou, S and Ma, C and Chen, X and Yin, F and Zhu, Y and Cao, Z and Li, N and Zuo, T and Qin, H and Chen, Q}, title = {Recipients' native bacteria determine the outcome of FMT treatment in inflammatory bowel disease.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2600055}, doi = {10.1080/19490976.2025.2600055}, pmid = {41399025}, issn = {1949-0984}, mesh = {Humans ; Male ; Female ; Adult ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/adverse effects ; Middle Aged ; *Bacteria/classification/isolation & purification/genetics ; Treatment Outcome ; Retrospective Studies ; Feces/microbiology ; *Colitis, Ulcerative/therapy/microbiology ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Crohn Disease/therapy/microbiology ; Young Adult ; Prospective Studies ; Aged ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a promising treatment for inflammatory bowel disease (IBD), achieving clinical response rate of ~50% for ulcerative colitis (UC), and Crohn's disease (CD). While prior research has emphasized donor selection and treatment protocols, the role of the patient's native intestinal microbiota in FMT outcomes remains underexplored.

METHODS: This study analyzed a retrospective cohort of 96 IBD patients (45 CD, 51 UC) undergoing FMT, with 192 paired stool samples collected pre- and post-treatment, alongside 332 healthy donor samples from 18 donors. A prospective cohort of 45 IBD patients provided 45 baseline stool samples, and a validation cohort of 112 non-IBD patients contributed 224 paired samples. Retrospective cohort patients were monitored for 4 weeks to assess FMT responsiveness and 52 weeks for treatment effectiveness. Microbiome analysis identified enterotype-specific bacteria and native bacterial genera influence FMT outcomes. Random forest, permissivity, and mathematical models predicted treatment response, characterized microbiome remodeling, and defined microecological remission thresholds.

RESULTS: The FMT regimen was safe, with no serious adverse events reported. At week 4, the clinical response rates were 58.8% (26/45) for CD patients and 66.7% (34/51) for UC patients; by week 52, the remission rates were 82.4% (37/45) for CD patients and 84.4% (43/51) for UC patients. Microbiome analysis identified 54 bacterial genera linked to enterotype classification, 57 to UC response, and 93 to CD response. Notably, 38 high-frequency retentions of recipient native bacteria after FMT were predictive of FMT responsiveness. The permissivity model revealed a shift toward Bacteroidetes-dominated enterotypes in IBD patients post-FMT, which was validated in 112 non-IBD patients. The abundance ranges of recipients' native bacteria predictive of treatment responsewere determined by mathematical interpretation model.

CONCLUSION: The patient's native microbiota significantly influences FMT efficacy in IBD, influencing microbiome remodeling and clinical outcomes, highlighting the importance of baseline microbial profiles in predicting FMT responsiveness and optimizing therapy.}, } @article {pmid41398400, year = {2025}, author = {Myagmankhuu, S and Tsuji, S and Akagawa, S and Kino, J and Akagawa, Y and Yamanouchi, S and Kaneko, K}, title = {Depletion of gut microbiota alleviates proteinuria in puromycin aminonucleoside-induced nephrosis in rats.}, journal = {Pediatric research}, volume = {}, number = {}, pages = {}, pmid = {41398400}, issn = {1530-0447}, abstract = {BACKGROUND: The gut-kidney axis has been implicated in chronic kidney disease, however its role in minimal change nephrotic syndrome (MCNS) is poorly understood. We investigated the impact of gut microbiota on proteinuria in MCNS.

METHODS: A puromycin aminonucleoside (PAN)-induced rat model of MCNS was used. Rats received a cocktail of antibiotics, PBS (control), or antibiotics plus indoxyl sulfate (IS). To assess causality, fecal microbiota transplantation (FMT) was performed in additional PAN rats. Urinary protein, kidney histology, urinary IS, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and gut microbiota composition were evaluated.

RESULTS: On day 8 after PAN injection, antibiotic-treated rats exhibited markedly reduced proteinuria (1.4 g/gCre) compared with controls (16.8 g/gCre, p = 0.014), whereas IS-treated rats developed severe proteinuria (117.3 g/gCre). Electron microscopy revealed podocyte foot process effacement in control and IS-treated rats but not in antibiotic-treated rats. Antibiotic-treatment decreased indole-producing bacteria, lowered urinary IS, and reduced 8-OHdG levels, indicating attenuation of oxidative stress. Importantly, FMT abolished the protective effect of antibiotics, re-emerging proteinuria.

CONCLUSION: Depletion of the gut microbiota by antibiotic treatment in a rat MCNS model alleviated proteinuria, which was reversed by FMT. This causally implicates gut microbiota, particularly indole-producing bacteria that generate toxins including IS, as a key therapeutic target for MCNS.

IMPACT: This study demonstrated that depleting the gut microbiota with antibiotics reduced proteinuria in a rat model of minimal change nephrotic syndrome, suggesting that harmful gut bacteria play a critical role in this disease. This research also identified indoxyl sulfate as a key uremic toxin produced by gut bacteria that worsens proteinuria and kidney damage, highlighting its role in disease progression. These findings could lead to novel treatments that target gut microbiota, including antibiotics or activated charcoal adsorbents that reduce proteinuria in minimal change nephrotic syndrome, and potentially minimize steroid use.}, } @article {pmid41397827, year = {2025}, author = {Mei, ZB and Cao, YL and Lv, BB and Wang, SY and Tian, K and Liu, QL and Ma, LZ and Wang, YS and Wei, D}, title = {[Efficacy observation of pelvic floor autologous fascia integrated repair based on membrane anatomy for complete rectal prolapse].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {12}, pages = {1441-1447}, doi = {10.3760/cma.j.cn441530-20250810-00300}, pmid = {41397827}, issn = {1671-0274}, support = {LHGJ20250781//Medical Science and Technology Project of Henan Province/ ; }, mesh = {Humans ; Retrospective Studies ; *Pelvic Floor/surgery ; *Fascia/transplantation ; *Rectal Prolapse/surgery ; Female ; Treatment Outcome ; Male ; Laparoscopy ; Middle Aged ; Aged ; Adult ; Quality of Life ; }, abstract = {Objective: To compare the clinical efficacy of laparoscopic pelvic floor autologous fascia integral repair based on membrane anatomy versus transperineal proctosigmoidectomy (Altemeier procedure) in the treatment of patients with complete rectal prolapse (CRP). Methods: This study employed a retrospective observational cohort design. Clinical data were collected from a total of 55 CRP patients who underwent surgical treatment between January 2018 and July 2023, including 25 patients from Luoyang Central Hospital, affiliated with Zhengzhou University, and 30 patients from the 989th Hospital of the Joint Logistics Support Force & Military Anorectal Surgery Research Institute. All patients undergoing surgery met the following criteria: aged ≥ 18 years, rectal prolapse protruding outside the anus, prolapse length > 5 cm with inability to self-reduce, conforming to the diagnostic criteria for CRP, and being first-time treated patients. Twenty-seven patients who underwent the Altemeier procedure between January 2018 and March 2021 were assigned to the Altemeier group; 28 patients who underwent laparoscopic pelvic floor autologous fascia integral repair based on membrane anatomy between April 2021 and July 2023 were assigned to the integral repair group. The therapeutic efficacy differences between the two groups were analyzed and compared, including the CRP length (DCRP), Wexner Constipation Score, Wexner Fecal Incontinence Score, and Gastrointestinal Quality of Life Index (GIQLI) before surgery and at 6, 12, and 24 months after surgery, as well as postoperative complications and recurrence at 24 months after surgery. Results: There were no statistically significant differences between the two groups in terms of gender distribution, age, preoperative body mass index (BMI), defecation frequency, DCRP, Wexner Constipation Score, Wexner Fecal Incontinence Score, and GIQLI (all P>0.05). All patients completed the surgery. The length of hospital stay and intraoperative blood loss in the integral repair group were significantly less than those in the Altemeier group (both P<0.01). At 6, 12, and 24 months after surgery, the DCRP, Wexner Constipation Score, Wexner Fecal Incontinence Score, and GIQLI in both groups significantly improved compared with the preoperative values (all P<0.001). At 6, 12, and 24 months after surgery, the CRP treatment effect, Wexner Constipation Score, Wexner Fecal Incontinence Score, and GIQLI in the integral repair group were significantly better than those in the Altemeier group (χ[2]=15.821, P<0.001; χ[2]=18.238, P<0.001; χ[2] = 12.558, P=0.001; and χ[2] =22.413, P<0.001, respectively). In the integral repair group, 4 patients (14.3%) developed grade I-III postoperative complications, including 2 cases of urinary retention, 1 case of anastomotic bleeding, and 1 case of anastomotic stenosis. In the Altemeier group, 11 patients (40.7%) developed grade I-III postoperative complications, including 4 cases of urinary retention, 3 cases of anastomotic bleeding, 1 case of anastomotic stenosis, 2 cases of intestinal fistula, and 1 case of fecal incontinence. The difference between the two groups was statistically significant (χ[2]=4.850, P=0.028). There was no recurrence of CRP in the integral repair group at 24 months after surgery, while 7 cases of CRP recurrence were observed in the Altemeier group at 24 months after surgery. The difference between the two groups was statistically significant (χ[2]=6.148, P=0.013). Conclusion: The autologous fascia repair technique based on membrane anatomy and the pelvic floor integral theory is superior to the transperineal Altemeier procedure in the treatment of CRP. Furthermore, it is an effective surgical method for CRP.}, } @article {pmid41397823, year = {2025}, author = {Huang, YS and Tong, WD and Xiao, GD and Li, Q and Guo, M}, title = {[Transformation and evidence-based progress of chronic constipation treatment mode].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {12}, pages = {1411-1416}, doi = {10.3760/cma.j.cn441530-20251013-00379}, pmid = {41397823}, issn = {1671-0274}, support = {82370547//National Natural Science Foundation of China/ ; CSTB2023NSCQZDJ0012//Key Project of Chongqing Natural Science Foundation/ ; 2022XLC05//Clinical Innovation Research Project of Army Medical University/ ; }, mesh = {Humans ; *Constipation/therapy ; Chronic Disease ; Fecal Microbiota Transplantation ; }, abstract = {In recent years, significant progress has been made in the treatment of chronic constipation, with high-quality studies emerging in areas such as fecal microbiota transplantation (FMT), sacral neuromodulation (SNM), acupuncture, and surgical techniques. The therapeutic approach is shifting from a traditional "medication and surgery" model toward an integrated strategy that includes dietary and defecation habit adjustment, FMT, SNM, acupuncture, pharmacotherapy, and surgery. Although FMT can partially improve stool frequency and consistency, its standardization and long-term efficacy require further validation. SNM demonstrates limited effectiveness in treating chronic constipation and is relatively cost-inefficient. Electroacupuncture remains controversial, though some studies support its value. Biofeedback therapy is recommended by multiple guidelines as the first-line treatment for dyssynergic defecation (DD), with portable home-based biofeedback systems showing considerable potential. For internal rectal prolapse (IRP) and rectocele (RC), various surgical options exist without a clear superiority, though laparoscopic ventral rectopexy (VMR) is increasingly favored due to its low recurrence rate and high patient satisfaction. In the surgical management of slow transit constipation (STC), total colectomy with ileorectal anastomosis remains the mainstream approach, while subtotal colectomy is gaining attention as an alternative.}, } @article {pmid41397742, year = {2025}, author = {Kragsnaes, MS and Gilbert, BTP and Sofíudóttir, BK and Rooney, CM and Hansen, SM and Mauro, D and Mullish, BH and Bergot, AS and Mankia, KS and Goel, N and Bakland, G and Johnsen, PH and Miguens Blanco, J and Li, S and Dumas, E and Lage-Hansen, PR and Wagenaar, C and Bakdash, G and Robinson, M and Kristiansen, K and Marchesi, JR and Schett, G and Zaiss, MM and Orlu, M and van Schaadenburg, D and Scher, JU and McGonagle, D and Elewaut, D and Breban, M and Tugwell, P and Finckh, A and Ciccia, F and Kriegel, MA and Daien, C and Ellingsen, T and Christensen, R and , }, title = {Efficacy and safety of microbiota-targeted therapeutics in autoimmune and inflammatory rheumatic diseases: protocol for a systematic review and meta-analysis of randomised controlled trials.}, journal = {BMJ open}, volume = {15}, number = {12}, pages = {e101593}, doi = {10.1136/bmjopen-2025-101593}, pmid = {41397742}, issn = {2044-6055}, mesh = {Humans ; Systematic Reviews as Topic ; Meta-Analysis as Topic ; Randomized Controlled Trials as Topic ; *Gastrointestinal Microbiome ; *Rheumatic Diseases/therapy/microbiology ; *Autoimmune Diseases/therapy/microbiology ; Probiotics/therapeutic use ; Research Design ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {INTRODUCTION: An abnormal composition of gut bacteria along with alterations in microbial metabolites and reduced gut barrier integrity has been associated with the pathogenesis of chronic autoimmune and inflammatory rheumatic diseases (AIRDs). The aim of the systematic review, for which this protocol is presented, is to evaluate the clinical benefits and potential harms of therapies targeting the intestinal microbiota and/or gut barrier function in AIRDs to inform clinical practice and future research.

METHODS AND ANALYSIS: This protocol used the reporting guidelines from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. We will search Embase (Ovid), Medline (Ovid) and the Cochrane Library (Central) for reports of randomised controlled trials of patients diagnosed with an AIRD. Eligible interventions are therapies targeting the intestinal microbiota and/or gut barrier function including probiotics, synbiotics, faecal microbiota transplantation, live biotherapeutic products and antibiotics with the intent to modify disease activity in AIRDs. The primary outcome of the evidence synthesis will be based on the primary endpoint of each trial. Secondary efficacy outcomes will be evaluated and selected from the existing core domain sets of the individual diseases and include the following domains: disease control, patient global assessment, physician global assessment, health-related quality of life, fatigue, pain and inflammation. Harms will include the total number of withdrawals, withdrawals due to adverse events, number of patients with serious adverse events, disease flares and deaths. A meta-analysis will be performed for each outcome domain separately. Depending on the type of outcome, the quantitative synthesis will encompass both ORs and standardised mean differences with corresponding 95% CIs.

ETHICS AND DISSEMINATION: No ethics approval will be needed for this systematic review. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to disseminate the study results through a peer-reviewed publication.

PROSPERO REGISTRATION NUMBER: CRD42025644244.}, } @article {pmid41395840, year = {2025}, author = {Wang, J and Wei, Y and Chen, D and Li, X and Zhang, H and Feng, S and Lu, S and Yang, J and Zeng, Q and He, X and Wu, L}, title = {Targeted Therapy for Gut Microbiota: Candidates for a Novel Strategy to Ameliorate Type 2 Diabetes Mellitus.}, journal = {Microbial biotechnology}, volume = {18}, number = {12}, pages = {e70283}, doi = {10.1111/1751-7915.70283}, pmid = {41395840}, issn = {1751-7915}, support = {2022B1111070006//the Key-Area Research and Development Program of Guangdong Province/ ; 2025A1515011113//the Basic and Applied Basic Research Fund of Guangdong Province/ ; 2023A1515012578//the Basic and Applied Basic Research Fund of Guangdong Province/ ; 2025KTSCX058//the Characteristic Innovation Project of Regular Colleges and Universities in Guangdong Province/ ; 32202380//the National Natural Science Foundation of China/ ; B2022209//the Medical Scientific Research Foundation of Guangdong Province/ ; 20221232//the Scientific Research Projects of Guangdong Bureau of Traditional Chinese Medicine/ ; }, mesh = {*Diabetes Mellitus, Type 2/therapy/microbiology ; *Gastrointestinal Microbiome/drug effects ; Humans ; *Fecal Microbiota Transplantation/methods ; Probiotics/administration & dosage/therapeutic use ; Prebiotics/administration & dosage ; Synbiotics/administration & dosage ; Animals ; }, abstract = {Type 2 diabetes mellitus (T2DM) poses a significant threat to public health and is associated with the gut microbiota. Gut microbiota modulators, including probiotics, prebiotics, and synbiotics, together with faecal microbiota transplantation (FMT), can restore the gut microbiota in patients and are recognised as powerful modulators of this ecosystem. Consequently, gut microbiota modulators are promising in the prevention and treatment of T2DM. The roles and mechanisms by which these therapeutic approaches target the gut microbiota in patients with T2DM warrant further investigation and elucidation. Key potential mechanisms associated with gut microbiota regulation include the modulation of gut microbiota composition alteration of gut microbiota metabolites, enhancement of intestinal barrier function, and suppression of inflammation. This study provides a comprehensive review of the relationship between the gut microbiota and T2DM, presents promising research findings and controversial issues, emphasises the potential roles and mechanisms of the gut microbiota in T2DM, and investigates the factors influencing the therapeutic efficacy of FMT. This review serves as a valuable reference for future studies on FMT.}, } @article {pmid41395487, year = {2025}, author = {Bai, Z and Wang, Y and Li, Y and Xu, J and Lai, Z}, title = {The gut microbiota in liver transplantation recipients during the perioperative and postoperative recovery period.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1684303}, pmid = {41395487}, issn = {1664-302X}, abstract = {BACKGROUND: Chronic Liver Disease (CLD) is one of the frequent causes of death, especially in the developing world. Liver transplantation (LT) is an effective modality to treat end-stage liver disease. Perioperative management of liver transplantation patients and prevention of postoperative complications are the key to improving patient prognosis and quality of life, and the intestinal flora of these patients can affect postoperative complications and overall prognosis.

METHOD: We collected a total of 151 fecal samples from 59 liver transplantation patients at different stages from the First Hospital of Shanxi Medical University. Using 16S rRNA sequencing technology, we compared the characteristics and changes of their microbiota. We selected 42 samples for metagenomic sequencing using the microPITA method to further analyze the composition and functional differences of the microbiota during the perioperative period of liver transplantation across various time points.

RESULTS: After liver transplantation (LT), the diversity of gut microbiota initially decreased and then increased. Firmicutes, Proteobacteria, and Bacteroidota were the main bacterial groups during the perioperative period. Firmicutes and Proteobacteria initially decreased and then increased, while Bacteroidota exhibited the opposite process. Alpha diversity and beta diversity analyses indicated that 1 month post-transplantation was a turning point for microbiota recovery (P < 0.01). Metagenomic sequencing, analyzed using the LEfSe method, identified a total of 50 genera that played significant roles in this process. The changes in microbiota exhibited the same trend as the 16S rRNA results. KEGG pathway analysis also indicated that 1 month was a critical time point, with Ko02010 potentially being a key pathway for recovery in LT patients, and it showed a negative correlation with Bacteroidota (P < 0.05).

CONCLUSION: The diversity of intestinal flora in the perioperative period of LT patients decreased first and then increased, and the turning point of intestinal flora recovery was 1 month after LT surgery.}, } @article {pmid41395479, year = {2025}, author = {Yang, J and Wang, J and Li, J and Yang, S}, title = {Lung-gut axis, intestinal microbiota, and pulmonary fibrosis: mechanisms and therapeutic potential.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1711299}, pmid = {41395479}, issn = {1664-302X}, abstract = {Pulmonary fibrosis (PF) is a progressive and life-threatening interstitial lung disease with irreversible lung function loss. The bidirectional interaction between respiratory and gut microbiota mediated by the "lung-gut axis" has emerged as a core regulatory link in PF pathogenesis. This review integrates clinical and preclinical data to systematically clarify the association between microbiota dysbiosis and PF. Clinical evidence shows that PF patients (including idiopathic pulmonary fibrosis, silicosis, and coal workers' pneumoconiosis) exhibit reduced pulmonary microbiota diversity, increased pro-inflammatory microbial abundance, and altered gut microbiota composition. Preclinical studies using bleomycin or silica-induced PF models confirm consistent microbiota changes and abnormal metabolites. Further, five core pathophysiological mechanisms (immune dysregulation, gut-lung barrier dysfunction, sustained activation of Type 2 epithelial-mesenchymal transition, autophagy modulation, and alveolar epithelial cell apoptosis mediated by microbial peptides) explain how microbiota alterations drive PF progression. Key microbial mediators (e.g., tryptophan metabolites, short-chain fatty acids, lipopolysaccharide, bile acid metabolites) exert bidirectional regulatory effects on PF through synergistic or antagonistic interactions. Additionally, microbiota-targeted strategies such as probiotic/prebiotic intervention, fecal microbiota transplantation, dietary adjustment, and antibiotics have shown experimental anti-fibrotic efficacy. This review highlights the gut microbiota as a potential therapeutic target for PF, while discussing current challenges (e.g., unclear causal relationship, lack of standardized intervention protocols) and future research directions, providing a new framework for PF mechanism research and clinical intervention.}, } @article {pmid41395459, year = {2025}, author = {Li, Q and Liu, Y}, title = {Analyzing the gut liver axis: a dual role of the microbiome in the genesis, progression, and treatment of liver cell carcinoma.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1701101}, pmid = {41395459}, issn = {1664-302X}, abstract = {Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, and the poor prognosis highlights the pressing need for innovative therapeutic strategies. The gut-liver axis, a critical bidirectional pathway linking the gut microbiota to the liver, plays a pivotal role in HCC pathogenesis. This review systematically delineates current evidence on how gut dysbiosis, compromised intestinal barrier function, and resultant microbial metabolites (e.g., bacterially metabolized bile acids) drive hepatocarcinogenesis via specific signaling pathways, while also addressing the loss of protective effects due to the depletion of beneficial microbes. Moving beyond descriptive summaries, this article focuses on elucidating the core molecular mechanisms of microbiome-regulated HCC-a key knowledge gap that remains unaddressed-and reconciles conflicting findings into a unified framework. We further explore the translational potential of microbiome signatures as non-invasive biomarkers and evaluate microbiota-targeting interventions (e.g., probiotics, dietary modulation, fecal microbiota transplantation) for enhancing treatment efficacy. Ultimately, this review aims to provide a clear roadmap for developing microbiome-based precision medicine in HCC, with the goal of improving clinical management and patient outcomes.}, } @article {pmid41395292, year = {2025}, author = {Ren, H and Wen, J and Liu, J and Wang, L}, title = {Gut microbiota in immunomodulation and infection prevention among multiple myeloma patients after chemotherapy: current evidence and clinical prospects.}, journal = {American journal of cancer research}, volume = {15}, number = {11}, pages = {4621-4638}, pmid = {41395292}, issn = {2156-6976}, abstract = {Multiple Myeloma (MM) is the second most common hematological malignancy, with its pathogenesis involving complex cytogenetic variations, tumor clonal evolution, and dynamic interactions between tumor cells and bone marrow stromal microenvironment. Recent studies highlight the role of the intestinal microbiota, a key component of the tumor-associated microenvironment, in regulates MM occurrence, progression, and treatment response via the "gut-bone marrow axis". Under physiological conditions, it protects the local microenvironment by regulating host metabolism and maintaining immune homeostasis. However, intestinal dysbiosis causes metabolic disorders and immune surveillance defects, promoting tumor growth, drug resistance, and poor prognosis. Though traditional treatments such as chemotherapy and hematopoietic stem cell transplantation have been optimized, chemotherapy disrupts intestinal mucosal integrity and impairs immunity, significantly increasing post-chemotherapy infections. These infections can interrupt treatment, worsen conditions, and reduce quality of life, leaving MM still intractable. Notably, microbiota-targeted interventions (e.g., probiotics, fecal microbiota transplantation [FMT]) have shown potential to reduce infection risk by restoring microbiota balance and repairing intestinal barriers. These interventions may also exert potential anti-tumor effects through immune microenvironment regulation and alleviate chemo/radiotherapy-related adverse reactions (e.g., nausea, diarrhea), offering a new direction for relapsed/refractory MM. This article summarizes the molecular regulatory network of the intestinal microbiota in the pathogenesis of MM and the research progress of microbiota-based interventions, aiming to provide a foundation for developing novel microbiome-oriented precision treatment regimens and improving chemotherapy tolerance and patient prognosis.}, } @article {pmid41393538, year = {2025}, author = {Manoria, PC}, title = {The Obesity Drug Revolution: New Frontiers in Pharmacotherapy.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {e96713}, pmid = {41393538}, issn = {2168-8184}, abstract = {Obesity is the most prevalent condition in high-income nations, primarily associated with increased risk of diabetes, cardiovascular disease (CVD), hypertension, and hyperlipidemia. Lifestyle modifications are a key determinant in non-pharmacological management that includes a combination of nutritional therapy, a low-calorie diet, and exercise. Earlier, anti-obesity drugs had been withdrawn from the market due to their safety profiles with cardiovascular and neuropsychiatric toxicity. The current FDA-approved pharmacotherapy consists of orlistat, setmelanotide, phentermine-topiramate, naltrexone-bupropion, liraglutide, semaglutide, and tirzepatide. Among these, semaglutide has a better clinical and regulatory profile with the feasibility of dosing and frequency. Orforglipron, a non-peptide oral glucagon-like peptide-1 receptor agonist, offers parenteral efficacy with convenient dosing. Probiotics, prebiotics, and fecal microbiota transplantation promote moderate weight loss by regulating metabolism and inflammation. Mitochondrial uncouplers help energy utilization rather than appetite regulation, which focuses on metabolic efficiency. A few challenges in obesity management are financial barriers, weight-promoting medications, inadequate obesity training, discomfort with prescribing, and lack of reimbursement. Innovative therapeutic approaches, multidisciplinary care, and a patient-centered plan are required for better clinical outcomes. This review highlights the current and emerging therapies designed to enhance long-term outcomes in obesity care.}, } @article {pmid41393108, year = {2025}, author = {Sun, Y and Yang, H and Zhang, J and Cong, S and Wang, L and Yu, T}, title = {Development and emerging trends in gastrointestinal dysfunction of Parkinson's disease: a decade-long bibliometric analysis.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1712302}, pmid = {41393108}, issn = {1663-4365}, abstract = {Gastrointestinal (GI) dysfunction represents a prevalent non-motor symptom of Parkinson's disease (PD) that not only contributes significantly to disease progression but also substantially compromises patients' quality of life. Over the past decade, research in this domain has expanded considerably. To systematically delineate the knowledge framework and evolving trends, we performed a bibliometric analysis of publications on GI and PD from 2015 to 2025. A total of 924 articles were retrieved from the Web of Science Core Collection (WoSCC). Co-occurrence, clustering, and collaboration network analyses were performed using VOSviewer, CiteSpace, and the R package Bibliometrix. For findings validation, the PubMed database was incorporated as an independent external validation dataset, providing complementary verification of keyword analyses derived from WoSCC. Our analysis revealed a steady annual increase in publication output. China and the United States emerged as the most prolific contributors globally, with the latter attaining the highest total citation count. At the institutional level, Capital Medical University led in publication output, whereas the University of Helsinki ranked highest in both total and average citations. Among journals, Parkinsonism & Related Disorders published the most papers on this topic, while Movement Disorders received the most citations. Keyword cluster analyses identified three primary research frontiers: (1) pathogenesis, focusing on α-synuclein (α-syn), the brain-gut-microbiome axis, and the enteric nervous system; (2) clinical manifestations, especially dysphagia and constipation; and (3) therapeutic interventions, particularly fecal microbiota transplantation and probiotics. By integrating established knowledge and highlighting emerging trends, this review aims to inform and guide future research and clinical practice in the field of gastrointestinal dysfunction in PD.}, } @article {pmid41392314, year = {2025}, author = {Abahussin, HM and Alotaibi, MS and Alhazzaa, OA and Alotaibi, AG and Alsaab, SM and Aljawini, NA and Alawad, AO}, title = {Exploring the intricate link between gut microbiota dysbiosis and the aging process: implications for age-related diseases.}, journal = {Gut pathogens}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13099-025-00788-z}, pmid = {41392314}, issn = {1757-4749}, abstract = {Aging is a complex process marked by the gradual accumulation of impairments in molecules and tissues, leading to frailty and dysfunction. This decline is a significant risk factor for many debilitating conditions. Recently, gut microbiota dysbiosis has been identified as one of the hallmarks of aging. This review sheds light on the role of gut microbiota dysbiosis in accelerating aging and its relation to age-associated diseases, including neurodegenerative disorders, cardiovascular diseases, cancer and diabetes. Emerging research demonstrates a strong link between the gut microbiome and the aging process, although the underlying mechanisms remain under investigation. Animal studies suggest that targeting the gut microbiome may offer a promising approach to mitigate aging and related diseases. However, further human studies are needed to confirm these findings.}, } @article {pmid41109531, year = {2025}, author = {Kapoor, HK and Appolon, CB and Bardsley, CA and Kharel, K and Schneider, KR and Sharma, M and Mishra, AK and Dev Kumar, G and Pires, AFA and Dunn, LL and Mishra, A}, title = {Temporal and Environmental Drivers for Survival of Escherichia coli in Florida Soils Amended with Heat-Treated Poultry Pellets and Composted Poultry Litter.}, journal = {Journal of food protection}, volume = {88}, number = {12}, pages = {100639}, doi = {10.1016/j.jfp.2025.100639}, pmid = {41109531}, issn = {1944-9097}, mesh = {*Escherichia coli/growth & development/isolation & purification ; *Soil Microbiology ; Random Allocation ; Onions/growth & development/microbiology ; Colony Count, Microbial ; Florida ; *Fertilizers/microbiology ; Composting ; Poultry/microbiology ; Feces/microbiology ; Hot Temperature ; Soil/chemistry ; Linear Models ; Models, Biological ; Time Factors ; Humidity ; }, abstract = {Previous studies have shown that field environmental conditions influence pathogen survival in the soils amended with biological soil amendments of animal origin (BSAAOs). To address this, a two-year completely randomized design field study in Florida was conducted with plots amended with heat-treated poultry pellets (HTPPs), composted poultry litter (PL), and unamended (UN), all inoculated with E. coli. Onion bulbs were transplanted into selected HTPP plots (O-HTPP) and field cured after harvesting. Soil samples were enumerated for E. coli on days 0, 1, 3, 7, 14, 28, 56, 84, 112, 140, 147 (harvest day), and 161 (after curing). The E. coli data were used to fit a linear mixed effect model (LME) with five weather variables: cumulative rainfall (cmrain4), average air temperature (at601234), relative humidity (RH1234), wind speed (W1), soil temperature (ast1). Overall, E. coli levels were 1.8 and 1.6 log10CFU or MPN/g higher in HTPP than UN plots in Year 1 and Year 2. The LME for soil amendment plots identified weather parameters that significantly influenced E. coli survival; cmrain4 and W1 increased and decreased survival by 0.698 and 0.712 log10CFU or MPN/g (p < 0.01), in Year 1. In the LME that compared plots with and without onions, W1 significantly increased survival in soils by 0.504 log10CFU or MPN/g (p < 0.05) in Year 1 (p < 0.05). These robust LME models (R[2]: 0.88-0.92) can predict the E. coli population in soils amended with poultry-litter-based amendments with or without onions. However, future studies will benefit from frequent samplings at later time points.}, } @article {pmid41391369, year = {2025}, author = {Wang, S and Wu, J and Xu, L and Wu, S and Pei, X and Wang, H and Deng, L and Xu, H and Chen, X}, title = {WenDan Decoction activates neuronal autophagy in the hippocampus via the gut-brain axis to improve depressive-like behavior in HFD mice.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {150}, number = {}, pages = {157686}, doi = {10.1016/j.phymed.2025.157686}, pmid = {41391369}, issn = {1618-095X}, abstract = {BACKGROUND: High-fat diet (HFD) is implicated in depression pathogenesis. WenDan Decoction (WDD), a classical traditional Chinese medicine formula, shows promise for metabolic and psychiatric disorders, but its precise mechanisms require elucidation.

METHODS: The chemical constituents of WDD were characterized by UPLC-MS/MS. The antidepressant effects of WDD in HFD mice were evaluated through behavioral tests, ELISA, and histopathology. Gut-brain axis mechanisms were investigated via 16S rRNA sequencing, untargeted metabolomics, network pharmacology, Nissl staining, transmission electron microscopy, Western blot, and RT-qPCR. Validation was performed through antibiotic depletion, fecal microbiota transplantation (FMT), and exogenous prostaglandin F2α (PGF2α) supplementation experiments.

RESULTS: WDD administration significantly ameliorated depressive-like behaviors of HFD mice with relatively low hepatorenal toxicity. It restored intestinal mucosal integrity, mitigated inflammation, re-established gut microbial homeostasis and subsequently regulated arachidonic acid metabolism. Correlation analysis revealed that the strongest negative association between the differential microbiota Lactobacillus murinus and the arachidonic acid metabolite PGF2α. WDD attenuated blood-brain barrier disruption by diminishing pro-inflammatory metabolites, suppressed PI3K/AKT/mTOR pathway, and restored autophagic flux, thereby rescuing neuronal ultrastructural and functional impairments. The application of PI3K agonists reversed the effective regulation of WDD. Crucially, FMT experiments further confirmed that the gut microbiota and metabolite PGF2α are essential for WDD's antidepressant effects.

CONCLUSION: WDD ameliorates depressive-like behaviors in HFD mice by modulating the gut microbiota and metabolism to suppress PI3K/AKT/mTOR pathway activation and restore autophagic flux. This study provides crucial mechanistic insights into WDD's effects against depression.}, } @article {pmid41391320, year = {2025}, author = {Tang, N and Deng, G and Jin, Z and Chen, J and Wang, D and Luo, Y and Luo, Y and Zhang, G}, title = {Bacillus sp. S361 isolated from bioaerosols in pharmaceutical wastewater treatment plants aggravates Klebsiella pneumoniae-induced lung injury in rats by modulating the gut microbiota.}, journal = {Journal of hazardous materials}, volume = {501}, number = {}, pages = {140669}, doi = {10.1016/j.jhazmat.2025.140669}, pmid = {41391320}, issn = {1873-3336}, abstract = {Current research on bioaerosol diversity in pharmaceutical wastewater treatment plants (PWWTPs) remains limited, especially concerning pulmonary injury mechanisms. Bacterial diversity in two PWWTPs was investigated via high-throughput sequencing and culture-based isolation, revealing functional interactions with pathogenic Klebsiella pneumoniae (Kpn). Emissions showed bimodal size distributions: Plant A dominated by ≥ 7μm particles, Plant B by 0.65-1.1μm submicron fractions enriched with Pseudomonadota (formerly Proteobacteria). Strain S361 (Bacillus sp., Bacillota) isolated from AeT1 exhibited significant synergistic pathogenicity with Kpn. Whole-genome sequencing identified 51 antibiotic resistance genes (ARGs) across 12 resistance mechanisms and 86 virulence factors in Bacillus sp. S361. Mechanistically, Bacillus sp. S361 synergistically enhances pulmonary colonization and pathogenicity of Kpn via distinctive metabolic crosstalk. Co-exposure to S361 and Kpn disrupts gut microbiota homeostasis, inducing dysregulated short-chain fatty acid (SCFA) metabolism and intestinal barrier impairment. This gut-derived dysfunction mediates systemic inflammation through the gut-lung axis, ultimately amplifying Kpn-induced lung injury. Fecal microbiota transplantation (FMT) experiments confirmed gut microbiota's mediating role, as recipient rats developed pathological changes (alveolar septal thickening, inflammatory infiltration) mirroring co-infected groups. Notably, microbiota-depleted rats suffered more severe lung injury than protected counterparts, establishing gut dysbiosis as a critical determinant of pulmonary damage. These findings implicate PWWTP bioaerosols in driving Kpn pathogenicity via Bacillus sp. S361-mediated synergy and gut-lung dysregulation, necessitating targeted interventions for occupational risk mitigation.}, } @article {pmid41390868, year = {2025}, author = {Iskander, O and Michot, N and Courtot, L and Bourbao-Tournois, C and Artus, A and Thiery, J and Deffain, A and Proutheau, G and Bouayed, A and Salame, E and Demtröder, CR and Giger-Pabst, U and Ouaïssi, M}, title = {Evaluating the influence of metabolic bariatric surgery on urinary and fecal incontinence outcomes: a one-year postoperative analysis.}, journal = {Langenbeck's archives of surgery}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00423-025-03947-7}, pmid = {41390868}, issn = {1435-2451}, } @article {pmid41390455, year = {2025}, author = {Isnard, S and Berini, CA and Parvathy, SN and Feng, H and Aiyana, O and Royston, L and Mabanga, T and Lakatos, PL and Bessissow, T and Klein, MB and Lebouché, B and Costiniuk, CT and Routy, B and Silverman, MS and Routy, JP}, title = {Fecal microbiota transplantation to reduce immune activation in ART-treated people with HIV with low CD4/CD8 ratio: protocol for the single-blind, randomized, placebo-controlled Gutsy study (CIHR/CTN PT038).}, journal = {Trials}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13063-025-09345-0}, pmid = {41390455}, issn = {1745-6215}, support = {CTN PT038//Canadian HIV Trials Network, Canadian Institutes of Health Research/ ; Cell Therapy network//Fonds de Recherche du Québec - Santé/ ; }, abstract = {BACKGROUND: Despite antiretroviral therapy (ART) controlling HIV viral replication, people with HIV (PWH) remain at risk for inflammatory non-AIDS comorbidities. Factors contributing to comorbidities in PWH on ART include spontaneous release of HIV products, CMV co-infection, microbial translocation, and gut dysbiosis, each driving systemic T-cell activation. In addition to ART, novel gut microbiota-modulating therapies could reduce epithelial gut permeability, microbial translocation, and immune activation. Fecal microbiota transplantation (FMT) from healthy volunteer is a promising therapy to counteract dysbiosis, protect from gut barrier damage, and lower systemic immune activation.

METHODS: The Gutsy study is a single-blind, randomized, placebo-controlled clinical trial evaluating the effects of FMT in PWH on ART for more than 3 years, with a viral load below 50 copies/mL, a CD4 count above 200 cells/mL, and a CD4/CD8 ratio below 1.0. All participants undergo a bowel cleanse before receiving FMT or placebo capsules. In the treatment group, 10 participants receive a bowel cleanse then two high doses of FMT delivered via 30 to 40 capsules twice, 3 weeks apart. The placebo group of 10 participants receive a bowel cleanse and capsules filled with microcrystalline cellulose for equivalence in weight and color, administered under the same time course. Peripheral blood mononuclear cells (PBMCs) and stool samples are collected at each visit: before bowel cleanse (baseline 1), before the first (baseline 2) and the 2nd (visit 4) FMT/placebo, 6 weeks (visit 5) and 12 weeks (visit 6) after the first FMT/placebo; colon biopsies are obtained at visits 3 and 6 in an optional sub-study. The primary objective is to assess the effect of FMT on plasma markers of gut epithelial permeability. Secondary objectives include microbial translocation, immune activation, and HIV latent reservoir biomarkers.

DISCUSSION: We hypothesize that large-dose FMT in capsules, but not placebo capsules, will increase the abundance of beneficial microbes in the gut of PWH on ART, leading to decreased gut damage markers and reduced immune activation. The results of the Gutsy pilot study will inform for the calculation of sample size of larger definitive randomized clinical trials assessing the influence of FMT on immune activation in PWH.

TRIAL REGISTRATION: ClinicalTrials.gov NCT06022406. Registered on 2024-08-01. https://clinicaltrials.gov/study/NCT06022406?cond=HIV&term=Gutsy&rank=1.}, } @article {pmid41390118, year = {2025}, author = {Dai, Z and Bao, X and Jiang, H and Zhang, Y and Shen, Q and Xue, Y}, title = {Grain proteins ameliorate glucose metabolism disorders by activating intestinal AhR and the hepatic NLK/FOXO1 pathway via gut microbiota-derived indole metabolites.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.12.010}, pmid = {41390118}, issn = {2090-1224}, abstract = {INTRODUCTION: Consumption of gran proteins has been associated with lower risk of type 2 diabetes (T2D), but the underlying mechanisms remain unclear. Gut microbiota plays a key role in glucose metabolism, and dietary proteins can modulate microbial composition and function.

OBJECTIVE: This study aims to evaluate the effects of grain proteins on glucose metabolism, identify key gut microbiota-derived metabolites, and elucidate the molecular mechanisms underlying grain protein-mediated glucose metabolism regulation.

METHODS: Glucose homeostasis and gut microbiota composition were assessed in mice fed a high-fat diet (HFD) supplemented with proteins isolated from rice, soybean, highland barley (HB), oats, and quinoa. The alterations in gut microbiota and their causal roles in glucose regulation were determined by in vitro fermentation and fecal microbiota transplantation (FMT). Key tryptophan (Trp) metabolites in fecal and serum samples were identified, and their glucose-regulating effects were validated in mice and HepG2 cells. Liver transcriptomics and molecular analyses were subsequently performed to elucidate the underlying regulatory pathways.

RESULTS: HB, oat, and quinoa proteins significantly improved glucose metabolism, increased Lactobacillus and Bifidobacterium abundance, and enriched Trp-derived metabolites. FMT reproduced the metabolic improvements in recipient mice, supporting a microbiota-mediated mechanism. Among Trp metabolites, indole-3-ethanol (IEt), indole-3-acrylic acid (IArA), and indole-3-aldehyde (IAld) promoted glucose homeostasis via aryl hydrocarbon receptor (AhR) activation and intestinal homeostasis maintenance. Cell-based and liver transcriptomic analyses demonstrated that these metabolites suppressed hepatic gluconeogenesis by modulating the Nemo-like kinase (NLK)/forkhead box protein O1 (FOXO1)/phosphoenolpyruvate carboxykinase 1 (PCK1)/glucose-6-phosphatase (G6PC) pathway.

CONCLUSIONS: Grain proteins diet-induced alleviate glucose metabolic disorders by enriching gut microbiota-derived indole metabolites, which improve intestinal homeostasis and inhibit hepatic gluconeogenesis through AhR and NLK/FOXO1 signaling. These findings highlight the therapeutic potential of grain proteins for T2D prevention and management.}, } @article {pmid41389504, year = {2025}, author = {Meenakshi, S and Amrutha, TV and Abubakar, M and Prakash, V and Kumar, N and Murti, K}, title = {Fluoride-induced gut dysbiosis in metabolic disorders: Mechanisms and public health implications.}, journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)}, volume = {93}, number = {}, pages = {127806}, doi = {10.1016/j.jtemb.2025.127806}, pmid = {41389504}, issn = {1878-3252}, abstract = {AIM: This review explores the effects of fluoride exposure and metabolic alterations linked to obesity and diabetes, and highlights preventive and therapeutic approaches to mitigate fluoride-driven metabolic risks.

SUMMARY: While fluoride is beneficial to dental health, but excessive exposure disrupts gut microbiota composition, reducing short-chain fatty acids (SCFA) production and impairing intestinal barrier integrity. These disruptions alter the oxidative stress, inflammation and insulin resistance. Evidence from animal and human studies suggest a dose-dependent pattern, with depletion of beneficial bacteria such as Lactobacillus and Faecalibacterium and enrichment of pro-inflammatory microbes. Such microbial imbalances influence bile acid metabolism. lipopolysaccharide (LPS) translocation and glucose regulation. This review discusses potential microbiome modulating strategies include probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT) and glucose lowering agents such as metformin and GLP-1 receptor agonists as possible therapeutic interventions to restore microbial balance and improve metabolic outcome However, the long-term and epigenetic effects of fluoride on intestinal and metabolic health remain unclear.

CONCLUSION: Since fluoride contaminates drinking water in areas with an endemic tendency, defluoridation, exposure monitoring, and public awareness are essential preventive strategies. Future mechanistic and clinical studies are necessary to elucidate the pathways linking fluoride metabolic disease progression.}, } @article {pmid41389450, year = {2025}, author = {Mittal, A and Sharma, S}, title = {Gut microbiota and nutritional interventions in alcohol-associated liver disease: Mechanisms and therapeutic advances.}, journal = {Nutrition research (New York, N.Y.)}, volume = {145}, number = {}, pages = {8-24}, doi = {10.1016/j.nutres.2025.11.004}, pmid = {41389450}, issn = {1879-0739}, abstract = {Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality worldwide. Despite growing awareness of its burden, treatment options remain limited, with abstinence as the only widely accepted intervention. Recent research underscores the critical role of the gut-liver axis and nutritional status, particularly dietary protein, in modulating ALD pathogenesis and progression. This review aims to integrate current knowledge on the interplay between gut microbiota, dietary protein, and alcohol-induced liver injury, and to evaluate microbiota-targeted therapeutic strategies, including fecal microbiota transplantation (FMT), within this context. We examine how chronic alcohol intake reshapes the gut microbiome, impairs barrier function, and alters microbial metabolism. We discuss how dietary protein, based on source, quantity, and amino acid composition, influences microbial ecology and metabolite profiles, with plant and dairy proteins emerging as beneficial. The review also highlights advances in FMT, which shows promise in improving outcomes in severe alcoholic hepatitis. However, its efficacy is modulated by donor microbial composition and recipient compatibility, both of which may be influenced by diet. Furthermore, we address emerging evidence on the role of fungal and viral communities, which remain understudied contributors to ALD. Despite substantial progress, significant knowledge gaps persist. These include the need for clinical validation of preclinical findings, deeper exploration of nonbacterial microbiota, and a lack of personalized, nutrition-based interventions. Addressing these gaps through integrative, multiomic approaches will be essential to advancing precision therapeutics in ALD.}, } @article {pmid41388767, year = {2025}, author = {Hou, B and Shao, H and Yuan, D and Tham, EH}, title = {Skin and gut microbiome in atopic dermatitis: Mechanisms and therapeutic opportunities.}, journal = {Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology}, volume = {36}, number = {12}, pages = {e70265}, doi = {10.1111/pai.70265}, pmid = {41388767}, issn = {1399-3038}, support = {//National Medical Research Council/ ; }, mesh = {Humans ; *Dermatitis, Atopic/therapy/microbiology/immunology ; *Gastrointestinal Microbiome/immunology ; *Skin/microbiology/immunology ; *Dysbiosis/immunology/therapy ; Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {The pathogenesis of atopic dermatitis (AD) comprises a combination of genetic, immune, and microbial factors. An imbalance in skin and gut microbiota composition, termed dysbiosis, may contribute to AD pathogenesis and severity through overgrowth of pathogenic microbes and suppression of healthy commensal colonization. These, in turn, promote barrier disruption and pro-inflammatory responses. The skin and gut microbiota composition plays crucial roles in AD, namely as early predictive biomarkers of AD onset; indicators of treatment response; and as future novel therapeutics such as probiotics, fecal, and skin microbiota transplantation. Such interventions aim to directly "reset" and restore a healthy microbial equilibrium, thereby fundamentally repairing barrier function, regulating immune homeostasis, and establishing new adjunctive pathways for the long-term management of AD.}, } @article {pmid41387927, year = {2025}, author = {Shi, F and Yang, Z and Zhang, L and Zou, D and Yu, J and Guo, N and Ren, S and Tang, X and Gu, C and Xu, R and Ru, Y and Zhang, Y and Wang, D}, title = {Deoxycholic acid derived from the gut microbiota involved in the regulation of adaptive thermogenesis in response to dietary protein restriction in plateau pika.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02233-4}, pmid = {41387927}, issn = {2049-2618}, support = {32301301//National Natural Science Foundation of China/ ; 32330012//National Natural Science Foundation of China/ ; 23-2-1-26-zyyd-jch//Natural Science Foundation of Qingdao/ ; ZR2024QC355//Natural Science Foundation of Shandong/ ; }, abstract = {BACKGROUND: Most winter-active mammals experience protein restriction. Gut microbiota is a key regulator of host energy homeostasis during nutrient deficiency, yet cross talk between microbiota and factors (e.g., hormones, signaling molecules) that regulate host energy metabolism in a low-protein (LP) context has not been studied sufficiently.

RESULT: The LP diet triggered the hepatic FGF21 adaptive metabolic pathway, which increased thermogenesis and reduced body weight, and this adaptive response was dependent on the composition and function of gut microbiota. Specifically, the LP diet induced a reshaping of the gut microbiota, altering its metabolic profile to increase deoxycholic acid levels and thereby increasing UCP1-induced thermogenesis of brown adipose tissue in an FGF21-dependent manner. Fecal transplantation with LP-associated microbiota increased thermogenesis through activation of GCN2-eIF2α-FGF21 signaling. Supplementation of the LP diet with yak fecal bacteria in plateau pika reduced UCP1-associated thermogenesis by altering the gut microbiome, decreasing deoxycholic acid production, suppressing activation of GCN2-eIF2α-FGF21 signaling, and alleviating LP-induced weight loss.

CONCLUSIONS: Our study reveals an association between the gut microbiota and LP diet-associated regulation of FGF21 signaling and thermogenesis and further demonstrates that this relationship is influenced by interspecies microbial transfer, indicating a critical mechanism whereby horizontal microbial exchange between sympatric species enhances host energy homeostasis. These findings provide novel insights into our understanding of the adaptations of mammals to high-elevation environments. Video Abstract.}, } @article {pmid41115624, year = {2025}, author = {Mishra, R and Harvey, A and Guo, A and Tillotson, G and Feuerstadt, P and Khanna, S and Shannon, WD and Blount, KF}, title = {Microbiome and metabolome changes after fecal microbiota, live-jslm, administration are associated with health-related quality of life improvements.}, journal = {Anaerobe}, volume = {96}, number = {}, pages = {103006}, doi = {10.1016/j.anaerobe.2025.103006}, pmid = {41115624}, issn = {1095-8274}, mesh = {Humans ; *Quality of Life ; *Metabolome ; *Gastrointestinal Microbiome ; Male ; Female ; *Feces/microbiology ; Middle Aged ; *Fecal Microbiota Transplantation/methods ; *Clostridium Infections/prevention & control/therapy/microbiology ; Adult ; Aged ; Clostridioides difficile ; }, abstract = {OBJECTIVES: Increasing evidence indicates a gut microbiome-brain axis, but more robust statistical methods are needed to solidify this connection. In a large phase 3, randomized, placebo-controlled clinical trial (PUNCH CD3; NCT03244644), fecal microbiota, live-jslm (REBYOTA; RBL, previously RBX2660), was effective in preventing recurrent Clostridium difficile infections, and trial participants had significant gut microbiome and metabolome shifts concurrent with significant changes in health-related quality of life (HRQOL). Advanced statistical methods were applied to data from this trial to further explore and demonstrate associations between changing HRQOL and microbiome or metabolome changes.

METHODS: A categorical statistical analysis queried whether patient-reported Cdiff32 HRQOL scores were more likely to improve after RBL than after placebo among PUNCH CD3 participants, and a Dirichlet-multinominal recursive partitioning model assessed whether mental domain Cdiff32 HRQOL scores were linked to participants' fecal microbiome or bile acid compositions.

RESULTS: Cdiff32 mental domain HRQOL scores were more likely to be improved after RBL administration compared with placebo among treatment responders. Cdiff32 mental domain scores were associated with changing gut microbiome and metabolome compositions, with a gradient of increased Clostridia and Bacteroidia and increased secondary bile acid predominance associated with better Cdiff32 scores.

CONCLUSIONS: The microbiota-gut-brain axis is posited to modulate health-related quality of life, microbiome, and metabolome changes through immune, gastrointestinal, and central nervous system functions in patients with recurrent C. difficile infection following RBL administration. These analyses provide a novel approach for investigating multi-omics data and categorical health-related quality of life questionnaires and generate new insights for further clinical studies.

CLINICAL TRIAL REGISTRATION: NCT03244644.}, } @article {pmid41385953, year = {2025}, author = {Pan, Z and Guo, J and Wang, H and Cai, Y and Wu, L and Zhang, J and Wu, L and Jia, X and Wang, Q and Yu, K and Shen, C and Zhao, L}, title = {Shenling Baizhu Powder attenuates cognitive impairment via the gut-brain axis in diet-induced obese mice.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {150}, number = {}, pages = {157654}, doi = {10.1016/j.phymed.2025.157654}, pmid = {41385953}, issn = {1618-095X}, abstract = {BACKGROUND: Obesity is closely associated with cognitive dysfunction, and markedly increases the risk of developing neurodegenerative diseases. Currently, obesity-related cognitive impairment lacks effective therapeutic interventions. Shenling Baizhu Powder (SLBZ) is a classical formula used to strengthen the spleen and promote the ascent of clear qi in traditional Chinese medicine (TCM). According to the TCM, this formula has great potential for the treatment of obesity-related cognitive impairment. However, research on SLBZ has focused primarily on its gastrointestinal effects, leaving its neurocognitive mechanisms largely unexplored.

PURPOSE: This study aimed to elucidate the therapeutic mechanisms of SLBZ in obesity-related cognitive impairment.

MATERIALS AND METHODS: Obese mice were obtained by subjecting male mice to a 16-week high-fat diet (HFD, 60 kcal % fat). During the final four weeks of the study, a SLBZ decoction (10 and 20 g/kg/day) was administered orally. The mice were then subjected to two behavioral tests and a glucose tolerance test. To evaluate the therapeutic effects of HFD on metabolic dysregulation, neuroinflammation, and intestinal barrier impairment, a range of analytical techniques, including biochemical analysis, immunofluorescence, RT-qPCR, and Western blotting, were used. Subsequently, 16S rRNA gene sequencing and metabolomic profiling were used to detect changes in the gut microbes and metabolite levels. Finally, fecal microbiota transplantation was performed to assess the functional link between SLBZ remodeling of the gut microbiota, metabolic alterations, and hippocampal cognitive function.

RESULTS: Our study demonstrated that HFD-fed mice developed significant cognitive impairment, supporting the notion that obesity adversely affects cognitive function. In the Morris water maze and open-field tests, SLBZ administration effectively ameliorated HFD-induced cognitive dysfunction. This improvement was accompanied by the restoration of the hippocampal synaptic ultrastructure and the recovery of the key synaptic proteins BDNF and PSD95. In agreement with this, SLBZ suppressed microglial activation and associated neuroinflammatory responses in HFD-fed mice. In the colon, SLBZ administration markedly alleviated HFD-induced gut barrier impairment, as evidenced by increased colonic mucus thickness and elevated expression of tight junction proteins, ZO-1, Occludin, and Claudin-1. Furthermore, SLBZ reduced endotoxin translocation and downregulated the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. Notably, HFD-induced gut microbiota dysbiosis was remodeled by the SLBZ treatment, which was characterized by an increased capacity for microbial vitamin B6 synthesis. SLBZ increased the serum levels of vitamin B6 in HFD-fed mice. Intriguingly, fecal microbiota transplantation from SLBZ-treated HFD-fed mice facilitated the amelioration of cognitive deficits, including superior performance in behavioral tests and synaptic repair in the hippocampus compared to recipients of HFD-microbiota.

CONCLUSION: Our findings highlight that SLBZ is a promising therapeutic agent mitigating obesity-related cognitive impairment via the "gut microbiota-vitamin B6-neuroprotection" axis.}, } @article {pmid41385961, year = {2025}, author = {Zhao, H and Akram, MZ and Comer, L and Corion, M and Fako, E and Everaert, N}, title = {Early life fecal microbiota transplantation enhances fermentation potential by changing the microbial profiles in broiler chickens.}, journal = {Poultry science}, volume = {105}, number = {1}, pages = {106189}, doi = {10.1016/j.psj.2025.106189}, pmid = {41385961}, issn = {1525-3171}, abstract = {The early gut microbiota of broiler chickens plays a critical role in shaping physiological functions later in life. Broilers have a limited capacity to utilize dietary fiber at an early stage of life. Fecal microbiota transplantation (FMT) can modify the gut microbial composition of broilers, potentially enhancing their fiber utilization capability. In this study, fecal samples from different chicken donors (broilers, laying hens, and broiler breeders) were collected and used for in vitro fermentation with two structurally distinct fibers, inulin and citrus pectin. FMT was then performed on newly hatched broilers, followed by additional in vitro fermentation to evaluate changes in the recipients' fiber fermentation capacity. Laying hen fecal microbiota exhibited the fastest fermentation rates for both fibers, while broilers showed the slowest. Notably, laying hens produced the highest levels of propionic acid during fermentation. These donor-specific fermentation differences were likely driven by Bacteroides, Subdoligranulum, Collinsella, Clostridium, and Bifidobacterium. The in vivo experiment demonstrated that FMT significantly altered the microbial composition and volatile fatty acid production in recipient broilers up to 14 days of age. Subsequent in vitro fermentation of the recipients' cecal content revealed that fermentation capacity was influenced by both the donor microbiota and the fiber substrate, with recipients of laying hen microbiota showing significantly enhanced propionic acid production, mirroring donor patterns. In conclusion, differences in donor fecal microbiota composition reflect their distinct capacities to utilize different fibers. Through FMT, recipient's cecal microbiota composition can be changed, and the donor's fermentative capacity is reflected in the recipients. These findings highlight the potential of early microbial interventions to improve fiber utilization in broilers, offering a promising strategy to optimize gut health.}, } @article {pmid41384118, year = {2025}, author = {Bautista, J and Cardona-Maya, WD and Gancino-Guevara, K and López-Cortés, A}, title = {Reprogramming prostate cancer through the microbiome.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1690498}, pmid = {41384118}, issn = {2296-858X}, abstract = {Prostate cancer (PCa) is a major global public health challenge, driven by a multifactorial interplay of genetic, epigenetic, hormonal and environmental determinants. In recent years, the human microbiome has emerged as a critical and previously underappreciated contributor to PCa initiation, progression, and therapeutic response. Emerging high-resolution multi-omics studies have demonstrated that microbial communities across the gut, urinary tract and prostate form a functional axis that shapes immune surveillance, hormonal metabolism, inflammatory tone and epigenetic regulation. Dysbiosis in these compartments promotes chronic inflammation, modulates androgen receptor signaling, and produces bioactive metabolites, including short-chain fatty acids, that activate oncogenic IGF-1/MAPK/PI3K and NF-κB/JAK/STAT pathways. Cross-compartmental trafficking of bacterial taxa and metabolites reinforces tumor-promoting circuits, while specific commensals such as Akkermansia muciniphila enhance antitumor immunity and improve responses to androgen deprivation therapy. Importantly, microbiota-derived factors also modulate microRNA (miRNAs) expression and epigenetic signatures, thereby affecting tumor plasticity and resistance to therapy. These mechanistic insights have catalyzed interest in microbiome-based therapeutic approaches, including probiotics, prebiotics, fecal microbiota transplantation, dietary modulation and bacteriophage therapy, which hold promise for restoring eubiosis and enhancing treatment efficacy. Nevertheless, clinical translation remains limited by inter-individual variability and the need for well-designed, longitudinal studies integrating shotgun metagenomics, metabolomics and host-microbe interactomics. Overall, the prostate, urinary and gut microbiomes represent interconnected targets that may inform precision diagnostics and novel therapeutic strategies in PCa.}, } @article {pmid41383731, year = {2025}, author = {Zhang, M and Liu, L and Lian, J and Zhang, M and Yang, X and Wang, H}, title = {Changes in gut microbiota in Gynura segetum-induced liver injury.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1684570}, pmid = {41383731}, issn = {1664-302X}, abstract = {INTRODUCTION: Gynura segetum (GS) has been shown to induce hepatotoxicity. Growing evidence suggests that the response to herbal medicines may be linked to shifts in the gut microbiota. This study aims to investigate the association between gut microbiota and liver injury induced by GS.

METHODS: The mice model of liver injury was established by oral gavage of GS decoction for 4 weeks, with or without the broad-spectrum antibiotics (Abx) or fecal microbiota transplantation (FMT). Liver function was assessed through the hematoxylin and eosin (H&E) staining and biochemical indices. The microbiota in the intestinal tract and peritoneal cavity were determined by 16S rRNA gene sequencing. Senecionine, seneciphylline, ferulic acid, beta-sitosterol, vanillic acid, vanillin, isorhamnetin, quercetin, kaempferol, and luteolin were isolated from GS plants, and the effects of these chemical compounds on the intestinal flora were analyzed.

RESULTS AND DISCUSSION: Compared to controls, mice treated with the GS decoction exhibited decreased body weight and increased serum levels of total bilirubin, direct bilirubin, alanine aminotransferase, and aspartate aminotransferase, regardless of whether they were given Abx or FMT. The abundance of Akkermansia (phylum Verrucomicrobia) persistently increased in the GS group. In contrast, other bacterial groups showed different trends under Abx or FMT conditions. Additionally, compared with the GS group, the linear discriminant analysis (LDA) score revealed the increase in abundance of Bifidobacterium, Bacteroides, Ruminococcaceae_UCG-007, and Coriobacteriaceae_UCG-002 in the Abx group, and Blautia and Bifidobacterium in the FMT group. 16S sequencing of ascitic fluid detected multiple bacterial phyla. Moreover, the administration of chemical compounds isolated from the GS plant by gavage did not increase the abundance of Akkermansia in the intestine.

CONCLUSION: GS increased the relative abundance of the Akkermansia genus in the intestinal tract. None of the above chemical compounds had this effect. This suggests that some components of GS may promote the growth of beneficial bacteria such as Akkermansia, offering new perspectives for drug development.}, } @article {pmid41383587, year = {2025}, author = {Bibbò, S and De Maio, F and Capone, F and Quaranta, G and Rondinella, D and Rosato, R and Minelli, M and De Lorenzis, D and Sanguinetti, M and Cammarota, G and Di Lazzaro, V and Masucci, L}, title = {Case Report: Fecal microbiota transplantation via capsules ameliorated clinical outcomes in a patient with multiple sclerosis.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1678759}, pmid = {41383587}, issn = {1664-3224}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Female ; Adult ; *Gastrointestinal Microbiome ; *Multiple Sclerosis/therapy/microbiology ; Treatment Outcome ; Capsules ; Dysbiosis/therapy ; }, abstract = {Multiple Sclerosis (MS) has long been recognized as a multifactorial disease, associated with both genetic and enviromental factors. Its link to inflammatory processes has led to significant advances in understanding the immunological and neurobiological mechanisms underlying the disease. The presumed autoimmune etiology is currently guiding the development of therapeutic protocols in this direction. The intestinal bacteria population, known as Gut Microbiota (GM), plays a well-documented role in autoimmune and inflammatory diseases. Gut microbiota dysbiosis is associated in patients affected by MS. Fecal Microbiota Transplantation (FMT) is emerging as a potential strategy to restore eubiosis and modulate systemic inflammation. We treated a 42-year-old woman with severe MS disability by FMT via colonoscopic infusion followed by a 3-month treatment of daily oral capsules, containing frozen microbiota, in order to resolve gastrointestinal symptoms. Clinical follow-up was conducted at 30, 60, and 90 days. Microbiota profiling (16S rRNA sequencing) and intestinal permeability testing were performed at several time points before and post infusion. Post-FMT, gastrointestinal symptoms improved significantly, as well as in limb spasticity, trunk stability, and fine motor skills. Microbiota analysis revealed a marked reduction in the abundance of Akkermansia muciniphila (22.5% vs 6.6%). At phylum level, Actinomycetota remained elevated (22%), while Bacteroidota consistently showed low abundance (14%). The most favorable microbiota profile was observed at 90 days, which coincided with the peak of clinical improvement. Intestinal permeability also improved over time, despite the patient's microbiota profile remaining distinct from the donor. This is the first report about combined FMT in MS. The procedure was safe, well tolerated, and associated with both gastrointestinal and neurological improvements. These findings support further exploration of FMT as a therapeutic adjunct in MS through controlled clinical trials.}, } @article {pmid41381864, year = {2025}, author = {Tang, A and Chen, Y and Si, K and Lai, J and Gong, W and Hu, S}, title = {Gut microbiota modulates synaptic plasticity, connectivity, and dopamine transmission in the VTA-mPFC pathway in bipolar depression.}, journal = {Molecular psychiatry}, volume = {}, number = {}, pages = {}, pmid = {41381864}, issn = {1476-5578}, support = {LR20F050002//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; LR22F050007//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; 82201676//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82471542//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Adequate evidence has shown that gut microbial dysbiosis is an emerging disease phenotype of bipolar disorder (BD), and is closely related to clinical symptoms of this intractable disease. However, how gut microbiota affects the nervous system in BD remains largely unclear. In this study, we constructed a BD depression-like mouse model via fecal microbiota transplantation, and explored the changes of synaptic plasticity and connectivity in the medial prefrontal cortex (mPFC) of BD mice. We found that bipolar depression-like mice presented with a decrease in the density of dendritic spines in medial prefrontal neurons, and "Translation at postsynapse" as a key contributor to the changes in synaptic plasticity. In addition, analysis of synaptic connectivity in the mPFC revealed that compared to control mice, less connections were observed between ventral tegmental area and mPFC glutamate neurons and dopamine response was decreased in BD mice. These findings suggest that gut microbiota from BD depression patients induces the development of bipolar depression possibly by modulating aberrant synaptic connectivity and dopamine transmission in the VTA-mPFC pathway, which sheds light on the microbiota-gut-brain mechanisms underlying BD.}, } @article {pmid41378445, year = {2025}, author = {Behling, AH and Portlock, T and Ho, D and Wilson, BC and Paramsothy, S and Kamm, MA and Cutfield, WS and Kaakoush, NO and O'Sullivan, JM and Vatanen, T}, title = {Cohort-specific determinants of donor strain engraftment following multi-donor faecal microbiota transplantation in two randomised clinical trials.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2597628}, doi = {10.1080/19490976.2025.2597628}, pmid = {41378445}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Colitis, Ulcerative/therapy/microbiology ; Tissue Donors ; Feces/microbiology ; *Obesity/therapy/microbiology ; Bacteria/classification/isolation & purification/genetics ; Randomized Controlled Trials as Topic ; Male ; Female ; Adult ; Middle Aged ; Cohort Studies ; }, abstract = {Disrupted human gut microbiota have been associated with the development of certain disease states, including obesity and ulcerative colitis (UC). Faecal microbiota transplantation (FMT) from healthy donors is a promising avenue to shift the microbiome profile of the recipient towards that of the donor, potentially ameliorating related symptoms. Several recent meta-analyses have investigated the clinical and microbial determinants that influence the retention of transplanted donor microbial strains within the recipient gut microbiome following FMT (i.e. engraftment). However, the specific factors that affect donor strain engraftment in different disease states require further exploration. Here, we perform a strain engraftment analysis on data from two multi-donor FMT clinical trials: the Gut Bugs Trial for obesity and the FOCUS Trial for UC. Using donor strain matching, the donor-recipient pairings of the FOCUS Trial were first predicted in a blinded manner. The subsequent, unblinded, strain engraftment analysis of both datasets highlighted a differential effect of donor-recipient microbiome complementarity on engraftment across the two disease cohorts; greater engraftment efficiency was associated with increased donor-recipient microbial similarity in the FOCUS Trial, and decreased similarity in the Gut Bugs Trial, suggesting that the factors influencing engraftment may differ across disease cohorts.}, } @article {pmid41378248, year = {2025}, author = {Abdulaal, R and Afara, I and Harajli, A and Al Mashtoub, E and Tarchichi, A and Hassan, K and Afara, A and Abou Fakher, J and Salhab, S and Fassih, I and Tlais, M}, title = {Gut microbiome and chemotherapy-induced cardiotoxicity: A systematic review of evidence and emerging therapies.}, journal = {World journal of biological chemistry}, volume = {16}, number = {4}, pages = {112221}, pmid = {41378248}, issn = {1949-8454}, abstract = {BACKGROUND: Chemotherapy-induced cardiotoxicity is a significant complication in cancer therapy, limiting treatment efficacy and worsening patient outcomes. Recent studies have implicated the gut microbiome and its key metabolites, such as short-chain fatty acids (SCFAs) and trimethylamine-N-oxide (TMAO), in mediating inflammation, oxidative stress, and cardiac damage. The gut-heart axis is increasingly recognized as a pivotal pathway linking microbiota dysregulation to chemotherapy-related cardiac dysfunction.

AIM: To systematically review existing evidence on the role of gut microbiome alterations in chemotherapy-induced cardiotoxicity and evaluate emerging microbiome-based therapeutic strategies aimed at mitigating cardiovascular risk in cancer patients.

METHODS: A systematic literature search was conducted in PubMed, Scopus, and Web of Science for studies published between January 2013 and December 2024. Studies were included if they examined chemotherapy-induced cardiotoxicity in relation to gut microbiota composition, microbial metabolites (e.g., SCFAs, TMAO), or microbiome-targeted interventions. Selection followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data extraction focused on microbiota alterations, mechanistic pathways, cardiac outcomes, and quality assessments using standardized risk-of-bias tools.

RESULTS: Eighteen studies met the inclusion criteria. Chemotherapy was consistently associated with gut dysbiosis characterized by reduced SCFA-producing bacteria and increased TMAO-producing strains. This imbalance contributed to gut barrier disruption, systemic inflammation, and oxidative stress, all of which promote myocardial damage. SCFA depletion weakened anti-inflammatory responses, while elevated TMAO levels exacerbated cardiac fibrosis and dysfunction. Preclinical studies showed promising cardioprotective effects from probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation, though human data remain limited.

CONCLUSION: Gut microbiome dysregulation plays a crucial role in the development of chemotherapy-induced cardiotoxicity. Altered microbial composition and metabolite production trigger systemic inflammation and cardiac injury. Microbiome-targeted therapies represent a promising preventive and therapeutic approach in cardio-oncology, warranting further clinical validation through well-designed trials.}, } @article {pmid41378072, year = {2025}, author = {Wang, SY and Zhang, MZ and Chen, ZM and Li, ZM and Xie, CY and Yang, GH and Xu, B and Xu, TC}, title = {Intestinal-related substances in obesity regulation: A comprehensive review.}, journal = {World journal of gastrointestinal pharmacology and therapeutics}, volume = {16}, number = {4}, pages = {111082}, pmid = {41378072}, issn = {2150-5349}, abstract = {With the rising global obesity rates, particularly in industrialized nations, obesity has become an increasingly significant public health concern. This review analyzes 132 relevant studies published between 2020 and 2025, with a focus on the role of gut-derived substances in regulating obesity. These include gut hormones [such as glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), peptide YY, cholecystokinin, and ghrelin], microbial metabolites [such as short-chain fatty acids (SCFA) and indole-3-propionic acid (IPA)], and neurotransmitters (such as serotonin and dopamine).The findings suggest that gut hormones play a crucial role in regulating appetite, glucose metabolism, and energy expenditure, and their dysregulation is closely linked to the development of obesity. Moreover, microbial metabolites like SCFA and IPA are strongly associated with metabolic health and significantly influence obesity-related mechanisms. This review also explores emerging therapeutic strategies, including GLP-1 receptor agonists, dual GLP-1/GIP receptor agonists, modulation of the gut microbiota, and fecal microbiota transplantation, all of which demonstrate promising potential in obesity management. However, challenges remain in optimizing these interventions, mitigating adverse effects, and establishing regulatory standards for microbiota-based therapies. Future research should aim to develop personalized, multi-targeted approaches to more effectively combat obesity and its associated metabolic disorders.}, } @article {pmid41378067, year = {2025}, author = {Vargas-Beltran, AM and Mialma-Omana, SJ and Vivanco-Tellez, DO}, title = {Targeting gut microbiota in liver disease: A pharmacological approach for hepatic encephalopathy and beyond.}, journal = {World journal of gastrointestinal pharmacology and therapeutics}, volume = {16}, number = {4}, pages = {110271}, pmid = {41378067}, issn = {2150-5349}, abstract = {The gut microbiota plays a pivotal role in the pathogenesis of liver diseases, particularly hepatic encephalopathy (HE), in which dysbiosis contributes to ammonia production, systemic inflammation, and neurocognitive dysfunction. Emerging evidence suggests that targeting the gut-liver axis through pharmacological and microbiota-based interventions can mitigate liver disease progression and HE severity. This review explored the latest therapeutic strategies aimed at modulating gut microbiota in liver disease, focusing on traditional approaches such as non-absorbable disaccharides (lactulose, lactitol), antibiotics (rifaximin), and probiotics as well as novel interventions, including postbiotics, synbiotics, and fecal microbiota transplantation. Additionally, bile acid modulators, short-chain fatty acid derivatives, and microbiome-targeted small molecules are being investigated for their potential to restore gut-liver homeostasis. We also discussed the implications of gut microbiota modulation in conditions beyond HE, such as metabolic dysfunction-associated steatotic liver disease and cirrhosis. By integrating gut microbiota-targeted therapies into liver disease management, we may develop more effective, personalized approaches to improve patient outcomes and reduce complications.}, } @article {pmid41377642, year = {2025}, author = {Edpuganti, S and Subhash, S and Subrahmaniyan, SL and Latheef, S and Albarari, SS}, title = {Gut Microbiome and Cardiovascular Health: Mechanisms, Therapeutic Potential and Future Directions.}, journal = {Heart international}, volume = {19}, number = {2}, pages = {12-20}, pmid = {41377642}, issn = {2036-2579}, abstract = {BACKGROUND: The gut microbiome has a crucial role in host metabolism and immune regulation, and there is growing evidence that dysbiosis may be associated with the pathogenesis of cardiovascular disease (CVD). This narrative review provides an overview of the recent literature on mechanistic connections between the gut and heart, as well as on the therapeutic strategies and research gaps in the gut-heart axis.

METHODS: We conducted a systematic literature search on PubMed and Embase databases with MeSH and keyword terms: 'gut microbiome', 'cardiovascular disease', 'TMAO', 'short-chain fatty acids', 'probiotics' and 'faecal microbiota transplantation'. We considered human and relevant animal studies focusing on mechanistic pathways or microbiome treatments and excluded editorials, small (less than 10 subjects) case series and articles not published in the English language.

RESULTS: Key microbiota-derived metabolites, trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), contribute to atherogenesis, blood pressure and myocardial inflammation. Dysbiosis-induced barrier dysfunction and disturbed bile acid signalling also serve as the mediators of cardiac remodelling. Dietary fibre, probiotics/prebiotics, postbiotics and faecal microbiota transplantation are emerging interventions for the modulation of CVD risk. Nevertheless, most result from observational studies, whilst such are heterogeneous in sequencing platforms and too small to draw any definitive conclusions.

CONCLUSION: The modulation of gut microbiome might be a new target for CVD prevention and treatment. Large-scale, standardized randomized trials with hard cardiovascular endpoints, as well as integrated multi-omics profiling, will be required to validate microbial biomarkers and to optimize microbiome-based interventions.}, } @article {pmid41377546, year = {2025}, author = {Wang, JDJ and Suan, E and Li, SS and Shelat, VG}, title = {Sepsis and the diverse organ-gastrointestinal tract axis.}, journal = {World journal of critical care medicine}, volume = {14}, number = {4}, pages = {105547}, pmid = {41377546}, issn = {2220-3141}, abstract = {Sepsis remains a leading cause of morbidity and mortality worldwide, driven by a dysregulated host immune response to infection that culminates in multi-organ dysfunction. Recent advances highlight the gut microbiota's pivotal role in modulating immune responses and influencing the pathophysiology of sepsis through the organ-gastrointestinal tract axis. This review synthesizes current evidence on the bidirectional interplay between gut dysbiosis and the dysfunction of major organ systems-liver, lungs, kidneys, brain, and heart-during sepsis. We explore how gut-derived factors such as microbial translocation, endotoxins, and altered metabolite production exacerbate systemic inflammation and organ injury. In particular, we emphasize the roles of short-chain fatty acids, uremic toxins, bile acids, and trimethylamine-N-oxide in mediating immune dysfunction across the gut-organ axes. Therapeutic strategies targeting the gut microbiota- including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation- show promise in preclinical and early clinical settings. However, challenges related to patient heterogeneity, safety, and the lack of precise biomarkers persist. This review consolidates disparate findings to underscore the gut as a central modulator in sepsis and advocates for microbiota-based interventions as adjunctive therapies in sepsis management.}, } @article {pmid41377246, year = {2025}, author = {Singh, PK and Rathi, D and Shweliya, MA and Farooq, A and Anfaal, Z and Saleem, NUA and Hamza, M and Qadri, M and Rath, S and Hemida, MF and Rani, H and Mahgoub, AMA and Wazir, HU}, title = {The interplay of the microbiome and breast cancer: beyond the gut: a narrative review.}, journal = {Annals of medicine and surgery (2012)}, volume = {87}, number = {12}, pages = {8496-8507}, pmid = {41377246}, issn = {2049-0801}, abstract = {Breast cancer remains a leading cause of morbidity and mortality among women worldwide, with emerging evidence underscoring the microbiota's pivotal role in its etiology, progression, and therapeutic response. This narrative review synthesizes the intricate interplay between the breast tissue, skin, and lung microbiomes in breast cancer pathogenesis, with particular emphasis on inflammatory breast cancer (IBC) and metastatic dissemination. The healthy breast microbiome, dominated by Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes, maintains tissue homeostasis through pH regulation, metabolite production, and immune modulation. Dysbiosis disrupts this equilibrium, fostering carcinogenesis via chronic inflammation, estrogen deconjugation, and DNA damage-induced genomic instability, with subtype-specific microbial signatures influencing tumor growth and therapy resistance. In IBC, skin microbiome alterations characterized by overgrowth of pathogens like Pseudomonas aeruginosa and Staphylococcus aureus exacerbate inflammation, epithelial-mesenchymal transition (EMT), and lymphatic invasion, while promoting a pro-tumorigenic microenvironment enriched in regulatory T cells and M2 macrophages. Concurrently, lung microbiota dysbiosis impairs immune surveillance, remodels the extracellular matrix, and facilitates metastatic seeding through neutrophil extracellular traps and cytokine storms. Cross-talk among these microbiomes amplifies systemic effects, highlighting their synergistic contributions to disease aggressiveness. Advanced analytical techniques, including 16S rRNA sequencing, metagenomics, and metabolomics, offer promising microbial biomarkers for early detection and risk stratification. By elucidating these host-microbe dynamics, this review advocates for microbiome-centric interventionssuch as probiotics, fecal microbiota transplantation, and targeted antimicrobials to enhance precision diagnostics and therapies, ultimately improving outcomes in breast cancer management.}, } @article {pmid41375654, year = {2025}, author = {Soares Ferreira Junior, A and Amanda Niz Alvarez, D and da Silva Souza, L and Linares Silva, N and Dias Machado, L and Yoshio Hirai, W and Mesquita Ciconelli, R and Piccolo Feliciano, JV and Colturato, I and Maurício Navarro Barros, G and Scheinberg, P and Chao, NJA and Lelis Vilela de Oliveira, G}, title = {A Distinct Intestinal Domination Fingerprint in Patients Undergoing Allo-HSCT: Dynamics, Predictors and Implications on Clinical Outcomes.}, journal = {Journal of clinical medicine}, volume = {14}, number = {23}, pages = {}, doi = {10.3390/jcm14238351}, pmid = {41375654}, issn = {2077-0383}, support = {#2022/12989-6//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; #2023/08142-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; #2024/02936-8//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; #2023/12271-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; #313190/2021-6//National Council for Scientific and Technological Development/ ; Finance Code 001//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; }, abstract = {Background: Although Enterococcus domination has been extensively evaluated in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT), the prevalence and clinical implications of other dominant genera remain poorly understood. Objective: In this study, we sought to determine the dynamics, predictors and clinical implications of intestinal domination in Brazilian patients undergoing allo-HSCT. Methods: In a prospective study of four Brazilian centers, fecal specimens were collected longitudinally prior to allo-HSCT until six months post-transplantation. To identify intestinal domination, we performed 16S rRNA gene sequencing using the Illumina platform. We then evaluated the impact of intestinal domination on overall survival and acute Graft-versus-Host-Disease (aGvHD) incidence. Finally, to identify predictors of intestinal domination, we performed a logistic regression model. Results: A total of 192 fecal specimens were collected from 69 patients. No significant changes in alpha or beta diversity were observed over the course of allo-HSCT. Among the 192 specimens, 131 (68%) presented intestinal domination. The top four dominant genera were Bacteroides, Akkermansia, Phascolarctobacterium, and Escherichia-Shigella. No significant associations were found between domination by these genera and either overall survival or aGvHD incidence. Furthermore, no patient-level characteristics, including age, sex, underlying disease, conditioning regimen, or stem cell source, reliably predicted intestinal domination. Conclusions: Our findings reveal a unique intestinal domination fingerprint in Brazilian patients and highlight the importance of geographic context in interpreting microbiota-outcome associations in allo-HSCT settings.}, } @article {pmid41375540, year = {2025}, author = {Schank, N and Cottone, A and Wulf, M and Seiter, K and Thomas, B and Miller, LMJ and Anderson, SL and Sahyoun, A and Abidi, AH and Kassan, M and Verma, A}, title = {The Role of Short-Chain Fatty Acids (SCFAs) in Colic and Anti-Inflammatory Pathways in Horses.}, journal = {Animals : an open access journal from MDPI}, volume = {15}, number = {23}, pages = {}, doi = {10.3390/ani15233482}, pmid = {41375540}, issn = {2076-2615}, abstract = {Equine colic remains a prevalent and potentially life-threatening condition with multifactorial origins, including dietary imbalances, stress, and microbial dysbiosis. Central to equine gut health is the production of short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, generated through microbial fermentation of dietary fibers in the hindgut. These metabolites not only serve as vital energy sources but also play crucial roles in maintaining intestinal barrier integrity, modulating motility, and suppressing inflammation. This review explores the role of SCFAs in equine gastrointestinal health, with particular emphasis on their anti-inflammatory effects and potential to prevent or mitigate colic. We examine how SCFAs interact with immune pathways, via G-protein-coupled receptors and regulatory T-cell promotion, to reduce pro-inflammatory cytokines such as TNF-α and IL-6. Evidence suggests that dietary shifts toward high-starch or low-fiber intake can reduce SCFA production, contributing to microbial imbalance, increased gut permeability, and systemic inflammation, all hallmarks of colic pathophysiology. Strategies to enhance SCFA levels, including high-forage diets, targeted prebiotic and probiotic supplementation, and emerging approaches like fecal microbiota transplantation, are discussed. Despite promising findings, significant gaps remain in equine-specific research, highlighting the need for longitudinal and mechanistic studies. Understanding and harnessing the therapeutic potential of SCFAs could pave the way for novel, microbiome-based interventions in colic prevention and treatment.}, } @article {pmid41374078, year = {2025}, author = {Biscaglia, G and Gentile, A and Parente, P and Calvo, A and Fontana, R and Continisio, A and Di Brina, ALP and Ciardiello, D and McIlwain, G and Latiano, A and Perri, F and Palmieri, O}, title = {Inflammatory Bowel Disease, Gastrointestinal Graft-Versus-Host Disease and Immune Checkpoint Inhibitors Induced Colitis: Similar Diseases to Treat with Fecal Microbiota Transplantation.}, journal = {Nutrients}, volume = {17}, number = {23}, pages = {}, doi = {10.3390/nu17233788}, pmid = {41374078}, issn = {2072-6643}, support = {n/a//This research was funded by the Italian Ministry of Health (Ricerca Corrente) and 5 per mille/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Immune Checkpoint Inhibitors/adverse effects ; *Graft vs Host Disease/therapy/microbiology ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Colitis/therapy/chemically induced ; Gastrointestinal Microbiome ; }, abstract = {Fecal microbiota transplantation (FMT) is a therapeutic strategy designed to modify and enrich the recipient's gut microbiota by administering processed donor stool, with the goal of treating dysbiosis and related conditions. In 2013, the United States Food and Drug Administration (FDA) approved FMT for recurrent Clostridioides difficile infection (rCDI). Since then, its use has been proposed and investigated in several other disorders characterized by gut microbiota imbalance and altered host-microbiota interactions, including inflammatory bowel disease (IBD), immune checkpoint inhibitor-induced colitis (ICI-iC), and gastrointestinal graft-versus-host disease (GI-GVHD). This review aims to highlight the commonalities among these conditions, the pathophysiological mechanisms that support the rationale for FMT, and emerging evidence from clinical studies. Although available studies are heterogeneous, FMT is a rapidly evolving field of research with promising potential to treat IBD and improve outcomes following oncological immunotherapy and allogenic stem cell transplantation. With further validation, FMT could become an important approach in managing immune-mediated gastrointestinal diseases.}, } @article {pmid41373570, year = {2025}, author = {Mashal, R and Al-Muhanna, A and Khader, S and Khudair, A and Khudair, A and Butler, AE}, title = {The Role of the Gut Microbiome in Type 2 Diabetes Mellitus.}, journal = {International journal of molecular sciences}, volume = {26}, number = {23}, pages = {}, doi = {10.3390/ijms262311412}, pmid = {41373570}, issn = {1422-0067}, mesh = {Humans ; *Diabetes Mellitus, Type 2/microbiology/metabolism/therapy ; *Gastrointestinal Microbiome ; Probiotics/therapeutic use ; Dysbiosis/microbiology ; Animals ; Fecal Microbiota Transplantation ; Prebiotics ; }, abstract = {The gastrointestinal tract in humans hosts trillions of microorganisms, collectively termed the gut microbiota, which perform essential physiological processes and roles, including nutrient metabolism and immunomodulation. Influenced by genetics, age, diet, medication, and the environment, the disruption of this system leads to dysbiosis, which has been linked to a range of diseases, notably type 2 diabetes mellitus (T2DM). As the global prevalence of T2DM continues to trend upwards, research investigating and highlighting the influence the gut microbiome exerts on this disease is warranted. The literature was examined regarding microbial metabolites and metabolic signaling pathways, as well as interventions relating to diet, prebiotics, probiotics, pharmacological agents, and fecal microbiota transplantation (FMT). The gut microbiome, through its effects on insulin resistance, inflammation, bile acid signaling, and glucose-lipid metabolism, impacts the development and progression of T2DM. Furthermore, patients with T2DM have demonstrated reduced microbial diversity, depletion of butyrate-producing bacteria, and an increase in pathogenic species. Interventions including high-fiber diets, metformin, probiotics, and FMT were shown to enrich beneficial microbes and improve metabolic outcomes. Targeted modulation of the microbiome, such as through next-generation probiotics and CRISPR-based therapies, may enhance metabolic control in the context of the future of personalized medicine. This review investigates the intricate relationship between the gut microbiome and T2DM, emphasizing its role in disease pathogenesis, the factors that may impact the microbiome in these patients, as well as therapeutic approaches toward its management.}, } @article {pmid41372103, year = {2025}, author = {Lee, YT and Akan, A and Önel, DB and Medawar, E and Jensen, DEA and Villringer, A and Witte, AV}, title = {Impacts of Lifestyle and Microbiota-Targeted Interventions for Overweight and Obesity on the Human Gut Microbiome: A Systematic Review.}, journal = {Obesity reviews : an official journal of the International Association for the Study of Obesity}, volume = {}, number = {}, pages = {e70037}, doi = {10.1111/obr.70037}, pmid = {41372103}, issn = {1467-789X}, support = {209933838//German Research Foundation (DFG)/ ; WI 3342/3-1//German Research Foundation (DFG)/ ; //Max Planck Society/ ; }, abstract = {Obesity is intricately associated with the gut microbiome, and emerging research suggests that lifestyle interventions, such as dietary changes and active lifestyle, can significantly affect the composition and function of the gut microbiome. However, evidence demonstrating a causal link between these changes and long-term weight loss or metabolic improvements remains limited. This systematic review investigates how overweight- and obesity-targeted interventions, such as dietary modifications, physical activity, supplementation with prebiotics and probiotics, and fecal microbiota transplantation (FMT), manipulate gut microbiome diversity and composition, major metabolites, and weight status. We conducted a systematic literature search and included 87 out of 255 randomized clinical trials with 6086 adults aged 18-84 with a BMI ≥ 25 kg/m[2]. The quality of the included RCTs ranged from very low to moderate risk of bias. Most interventions did not cause any significant changes in microbial alpha or beta diversity, however, positive associations between prebiotic consumption and abundance of Actinobacteria and Bifidobacterium were observed, and intake of probiotics was related to increased levels of Lactobacillus and reduced body weight and body fat. We did not observe strong evidence for associations between SCFA levels, gut microbiome, and obesity. Overall, diversity and heterogeneity in reported outcomes, both in methods and results, were large. Taken together, our findings suggest that overweight- and obesity-targeted dietary interventions of at least 4 weeks, particularly those involving prebiotics and probiotics, have the potential to beneficially alter the gut microbiome, although standardized protocols and harmonized reporting are needed to confirm this through meta-analysis.}, } @article {pmid41371856, year = {2026}, author = {Na, C and Shi, X and Fu, J and Li, J and Jiang, H and Guo, Z and Lai, H and Zhang, Z and Zhao, L and Yuan, Q and Zhang, B}, title = {Pectic polysaccharides from Mongolian medicinal Hypecoum leptocarpum: Structure and ulcerative colitis amelioration via gut microbiota and intestinal inflammation regulation.}, journal = {Carbohydrate polymers}, volume = {374}, number = {}, pages = {124717}, doi = {10.1016/j.carbpol.2025.124717}, pmid = {41371856}, issn = {1879-1344}, abstract = {Ulcerative colitis (UC) poses a global health burden due to its refractoriness. Our previous study demonstrated that Hypecoum leptocarpum (H. leptocarpum) crude polysaccharides mitigate UC-related intestinal inflammation. In this study, we extracted, purified, and characterized a pectic polysaccharide (HLP-4-2, 19.7 kDa) from H. leptocarpum, which contained homogalacturonan (HG) and rhamnogalacturonan-I (RG-I). Specifically, RG-I comprises a repeating disaccharide unit of 1,4-α-GalpA and 1,2-α-Rhap (with arabinogalactan branches), whereas HG has partially methyl-esterified GalA residues. In DSS-induced UC mice, HLP-4-2 alleviated disease symptoms in a dose-dependent manner, as evidenced by a reduced disease activity index (DAI), restored colon length, and decreased spleen index. Mechanistically, HLP-4-2 modulated gut microbiota by promoting growth of short-chain fatty acid (SCFA)-producing bacteria (e.g., Prevotella) and reducing abundance of pathogenic bacteria (e.g., Klebsiella). This microbial shift elevated SCFA levels (particularly propionic and isobutyric acids) and reduced isocaproic acid levels. These changes may, in turn, strengthen the intestinal barrier by enhancing mucin secretion, preserving goblet cells, and reducing inflammation via downregulating proinflammatory cytokines. Fecal microbiota transplantation (FMT) experiments confirmed that these microbial changes contributed to HLP-4-2's therapeutic effects. These findings endorse the traditional use of H. leptocarpum for inflammation and indicate HLP-4-2 as a potential treatment for ulcerative colitis.}, } @article {pmid41370178, year = {2025}, author = {Peto, L and Fawcett, N and Kamfose, MM and Scarborough, C and Peniket, A and Danby, R and Peto, TEA and Crook, DW and Llewelyn, MJ and Walker, AS}, title = {The impact of different antimicrobial exposures on the gut microbiome in the ARMORD observational study.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, doi = {10.7554/eLife.97751}, pmid = {41370178}, issn = {2050-084X}, support = {NIHR200915//National Institute for Health and Care Research/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Male ; Female ; Adult ; Cross-Sectional Studies ; Middle Aged ; Aged ; *Anti-Bacterial Agents/pharmacology ; *Anti-Infective Agents/pharmacology ; Feces/microbiology ; Metagenomics ; United Kingdom ; *Bacteria/drug effects/classification/genetics ; Young Adult ; }, abstract = {Better metrics to compare the impact of different antimicrobials on the gut microbiome would aid efforts to control antimicrobial resistance (AMR). The Antibiotic Resistance in the Microbiome - Oxford (ARMORD) study recruited inpatients, outpatients, and healthy volunteers in Oxfordshire, UK, who provided stool samples for metagenomic sequencing. Data on previous antimicrobial use and potential confounders were recorded. Exposures to each antimicrobial were considered as factors in a multivariable linear regression, also adjusted for demographics, with separate analyses for those contributing samples cross-sectionally or longitudinally. Outcomes were Shannon diversity and relative abundance of specific bacterial taxa (Enterobacteriaceae, Enterococcus, and major anaerobic groups) and antimicrobial resistance genes (targeting beta-lactams, tetracyclines, aminoglycosides, macrolides, and glycopeptides). 225 adults were included in the cross-sectional analysis, and a subset of 79 patients undergoing haematopoietic cell transplant provided serial samples for longitudinal analysis. Results were largely consistent between the two sampling frames. Recent use of piperacillin-tazobactam, meropenem, intravenous co-amoxiclav, and clindamycin was associated with large reductions in microbiome diversity and reduced abundance of anaerobes. Exposure to piperacillin-tazobactam and meropenem was associated with a decreased abundance of Enterobacteriaceae and an increased abundance of Enterococcus and major AMR genes, but there was no evidence that these antibiotics had a greater impact on microbiome diversity than iv co-amoxiclav or oral clindamycin. In contrast, co-trimoxazole, doxycycline, antifungals, and antivirals had less impact on microbiome diversity and selection of AMR genes. Simultaneous estimation of the impact of over 20 antimicrobials on the gut microbiome and AMR gene abundance highlighted important differences between individual drugs. Some drugs in the WHO Access group (co-amoxiclav, clindamycin) had similar magnitude impact on microbiome diversity to those in the Watch group (meropenem, piperacillin-tazobactam) with potential implications for acquisition of resistant organisms. Metagenomic sequencing can be used to compare the impact of different antimicrobial agents and treatment strategies on the commensal flora.}, } @article {pmid41370004, year = {2025}, author = {Syed, S and Moayyedi, P and Kao, D and Patel, J and Marshall, JK and Surette, M and Narula, N}, title = {Combination Therapy With Fecal Microbiota Transplantation and Vedolizumab for Induction of Remission in Ulcerative Colitis: An Open-Label Pilot Study.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izaf284}, pmid = {41370004}, issn = {1536-4844}, support = {//Takeda Canada/ ; }, } @article {pmid41369516, year = {2025}, author = {Yang, J and Yu, J and Chen, Y and Xu, A and Yang, C and Li, J and Wu, F and Li, X and Bi, J and Xiang, B and Jiang, K}, title = {Hyperoside, a dietary flavonoid, protects against endometritis via gut microbiota-dependent production of hydroxyphenyllactic acid and the gut-uterus axis.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d5fo04275e}, pmid = {41369516}, issn = {2042-650X}, abstract = {Endometritis, primarily caused by Escherichia coli (E. coli) infection, poses significant therapeutic challenges due to rising antibiotic resistance. The associated pro-inflammatory cytokines cause persistent endometrial damage, thereby leading to infertility, pregnancy loss, and other gynecological complications, which impose substantial long-term medical and socioeconomic burdens. Hyperoside, a flavonol glycoside abundant in various common fruits (e.g., hawthorn) and vegetables, exhibits significant anti-inflammatory activity, highlighting its potential as a functional food or nutraceutical. Our present study firstly demonstrated that hyperoside could alleviate E. coli-induced endometritis in mice through a gut-uterus axis mechanism. Specifically, hyperoside remodeled the gut microbiota by enriching beneficial genera, such as Lactobacillus and Prevotella, which subsequently elevated the production of the metabolite hydroxyphenyllactic acid (HPLA). Crucially, antibiotic treatment and fecal microbiota transplantation (FMT) experiments further confirmed that gut microbiota restructuring was essential for the anti-endometritic effect of hyperoside. Mechanistically, HPLA enters systemic circulation and targets uterine tissue, where it is directly bound to TLR4 to suppress the activation of the TLR4/NF-κB pathway and then the release of inflammatory cytokines. The present study provides the first systematic evidence of the gut-uterus axis, establishing microbiota-derived HPLA as a key effector against E. coli-induced endometritis, offering a novel nutritional intervention strategy for inflammatory reproductive disorders.}, } @article {pmid41368686, year = {2025}, author = {Wu, J and Zheng, W and Ding, X and Jin, Q and Ding, M}, title = {Obesity-induced gut microbiota transplantation promotes the occurrence and development of hepatocellular carcinoma.}, journal = {Future science OA}, volume = {11}, number = {1}, pages = {2599729}, doi = {10.1080/20565623.2025.2599729}, pmid = {41368686}, issn = {2056-5623}, abstract = {OBJECTIVE: Obesity is a recognized risk factor for hepatocellular carcinoma (HCC), yet the causal role of obesity-remodeled gut microbiota remains poorly defined. This study aims to investigate the direct impact of obesity-related gut microbiota on the development of hepatocellular carcinoma.

METHODS: C57BL/6J mice were fed a high-fat diet (HFD) to establish obesity. Fecal microbiota from HFD or normal-chow diet (NCD) mice was transplanted into DEN-initiated recipients. Tumor burden was assessed by incidence, multiplicity, and size. Histomorphology and biochemical methods were employed to assess liver injury, inflammation, fibrosis, lipid metabolism, and the potential signaling pathways involved in these events.

RESULTS: The gut microbiota of obese mice significantly promoted the incidence of HCC, and increased tumor number, and size spectrum. Specifically, obesity-related gut microbiota significantly aggravated hepatocarcinogenesis (increasing GPC3, GP73, AFP, and N-cadherin, and decreasing E-cadherin), pro-inflammatory cytokine surge (increasing IL-6, IL-1β, IL-17, and TNF-α), and fibrotic activation (increasing α-SMA, TGF-β, and Col1a1) were observed. Mechanistically, obesity-FMT dysregulated lipid metabolism (increasing free fatty acids, total cholesterol, and triglycerides) and activated TLR4-NF-κB and mTOR pathways.

CONCLUSION: Our findings suggest that gut microbiota from obese donors directly promotes HCC progression via TLR4-NF-κB/mTOR-driven inflammation, fibrosis, and metabolic dysregulation, offering novel targets for microbiota-based interventions in obesity-associated liver cancer.}, } @article {pmid41368634, year = {2025}, author = {Shen, X and Li, Y and Wang, D and Sun, K}, title = {The gut microbiota and its metabolites: novel therapeutic targets for inflammatory bowel disease.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1690279}, pmid = {41368634}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Inflammatory Bowel Diseases/therapy/microbiology/metabolism/immunology ; Fecal Microbiota Transplantation ; Animals ; Probiotics/therapeutic use ; Bile Acids and Salts/metabolism ; Dysbiosis/therapy ; Fatty Acids, Volatile/metabolism ; Tryptophan/metabolism ; }, abstract = {Inflammatory bowel disease (IBD) pathogenesis is critically influenced by gut microbiota dysbiosis and perturbations in associated metabolites. This review outlines current IBD diagnostic and therapeutic paradigms, highlighting the persistent focus on the management of inflammatory symptoms and the absence of curative interventions. We elucidate the mechanistic links between gut microbiota dysregulation and IBD progression, with an emphasis on the immunomodulatory functions of microbial metabolites-specifically short-chain fatty acids (SCFAs), bile acids (BAs), and tryptophan (Trp) metabolism-in maintaining intestinal barrier integrity and attenuating inflammation. Furthermore, we evaluate microbiota-targeted therapeutic strategies, including probiotics, fecal microbiota transplantation (FMT), and metabolite-based interventions, as novel approaches for IBD management. This synthesis aims to inform future therapeutic development and accelerate the clinical translation of microbiota-modulating regimens.}, } @article {pmid41368309, year = {2025}, author = {Liu, L and Yang, L and Zhang, H and Li, H and Shang, T and Liu, L}, title = {Lung cancer and the Gut-microbiota-lung Axis: emerging evidence and potential clinical implications.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1655780}, pmid = {41368309}, issn = {2296-858X}, abstract = {Lung cancer remains the leading cause of cancer-related deaths globally, with a 5-years survival rate of only around 20%. Merging cohort and Mendelian-randomization studies indicate that gut dysbiosis is associated with-though not yet proven to cause-an elevated risk and worse prognosis of non-small-cell lung cancer. Lower fecal abundance of butyrate producers such as Faecalibacterium prausnitzii and expansion of Enterobacteriaceae correlate with reduced systemic CD8 + T-cell infiltration and shorter progression-free survival during immune-checkpoint blockade. Antibiotic exposure within 30 days before anti-PD-1 initiation is consistently linked to diminished objective response and overall survival in retrospective cohorts, whereas supplementation with butyrogenic probiotics or fecal microbiota transplantation from responders restores therapeutic efficacy in pre-clinical models. This review integrates epidemiological, mechanistic and clinical data to clarify the current evidence, identify gaps and outline the steps needed to translate gut-lung-axis research into safe, effective adjunctive therapies for patients with lung cancer.}, } @article {pmid41367416, year = {2025}, author = {Liu, SH and Yang, XF and Liang, L and Song, BB and Song, XM and Yang, YJ and Alhoot, MA}, title = {Regulatory mechanisms of the gut microbiota-short chain fatty acids signaling axis in slow transit constipation and progress in multi-target interventions.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1689597}, pmid = {41367416}, issn = {1664-302X}, abstract = {Slow-transit constipation (STC) is an increasingly prevalent disorder that imposes a substantial health and economic burden. Mounting evidence highlights the "gut microbiota-short-chain fatty acid (SCFA)-motility" axis as a central pathophysiological link between dysbiosis and impaired colonic transit. This review synthesizes current knowledge of how SCFAs, especially acetate, propionate and butyrate, shape motility through serotonergic signaling, enteric nervous system modulation, epithelial barrier integrity and immune regulation. Particular attention is devoted to the biased-signaling properties of the SCFA receptors FFAR2 and FFAR3 (free fatty acid receptors 2 and 3, respectively), including emerging data on their heterodimerization. The article then appraises recent randomized controlled trials and meta-analyses of multi-target interventions (dietary fibers, synbiotics, postbiotics, fecal microbiota transplantation, phytochemicals, and small-molecule FFAR agonists) highlighting their efficacy, safety, and translational hurdles. Finally, the authors propose a precision-medicine framework that integrates multi-omics microbiome profiling, metabolomics, and host genetics to enable phenotype-stratified therapy. Key research gaps include limited long-term safety data, heterogeneous human cohorts and the need for large multicenter trials and machine-learning-guided responder prediction. Collectively, the review provides a roadmap for shifting STC management from symptom control to mechanism-based, personalized care.}, } @article {pmid41361827, year = {2025}, author = {Tao, M and Wu, T and Li, S and Tan, Y and Zhou, X and Chen, Y and Huang, L and Wang, W and Li, S and Wang, L and Luo, Z and Wang, Y and Ling, K and Liang, Z}, title = {Intratumoral Collinsella aerofaciens exhibits antitumor activity in endometrial carcinoma through activation of the p53 signaling pathway.}, journal = {Journal of translational medicine}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12967-025-07543-7}, pmid = {41361827}, issn = {1479-5876}, support = {2019YFC1005202//National Key Research and Development Program of China/ ; }, abstract = {BACKGROUND: The intratumoral microbiota plays dual roles in cancer progression and suppression, but its composition and functional mechanisms in endometrial carcinoma (EC) remain incompletely defined. This study aimed to characterize the EC intratumoral microbiome, elucidate microbial spatial localization, and identify bacteria with tumor-suppressive properties.

METHODS: Tumor and adjacent normal tissues from patients with EC were analyzed using 5R 16S rRNA sequencing to profile microbial communities, with fluorescence in situ hybridization (FISH) validating bacterial localization. Spatial transcriptomics (ST), single-cell RNA sequencing (scRNA-seq), and FISH were integrated to map microbiota-niche cell interactions. RNA sequencing was performed on EC cells treated with bacterial supernatant. Fecal microbiota transplantation (FMT) from EC patients to mice was used to assess gut-tumor microbial crosstalk.

RESULTS: Collinsella aerofaciens (C. aerofaciens), Haloamaerobium gallinarum, and Massilia oculi were enriched in adjacent normal tissues, while Bacteroides vulgatus (B. vulgatus) and Delfia tsuruhatensis dominated tumor tissues. Tumors exhibited reduced microbial richness versus normal tissues. C. aerofaciens localized predominantly to smooth muscle cells and modulated the tumor microenvironment, as revealed by FISH and ST-scRNA-seq integration. RNA sequencing suggested that C. aerofaciens suppressed EC progression by activating the p53 signaling pathway. FMT experiments demonstrated gut microbiota-driven remodeling of the tumor microbiome.

CONCLUSIONS: This study identifies C. aerofaciens as a novel tumor-suppressive bacterium in EC, with mechanistic evidence linking its activity to p53 pathway activation. Gut microbiota modulates intratumoral microbial composition, suggesting potential dual-target therapeutic strategies for EC.}, } @article {pmid41361755, year = {2025}, author = {Dong, R and Meng, X and Hu, H and Pan, J and Wang, W}, title = {Integrating gut microbiota and metabolomics in pediatric inflammatory bowel disease: insights into pathogenesis and potential role of precision medicine.}, journal = {European journal of medical research}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40001-025-03658-1}, pmid = {41361755}, issn = {2047-783X}, abstract = {Pediatric inflammatory bowel disease (IBD) is a chronic and relapsing disorder with rising global incidence. Gut microbiota dysbiosis and metabolic alterations have been implicated in disease pathogenesis, yet their precise roles in pediatric IBD remain incompletely understood. This review synthesizes current evidence on the interplay between the gut microbiota and metabolomics in pediatric IBD, highlighting their contributions to disease onset, progression, and therapeutic response. We examine changes in microbial composition, alterations in short-chain fatty acid, bile acid, and amino acid metabolism, and their effects on intestinal immunity and barrier function. In addition, we discuss microbiota-based therapies, such as probiotics, prebiotics, and fecal microbiota transplantation, along with the potential of metabolomic profiles for diagnostic and prognostic use. Finally, we emphasize integrating multi-omics approaches to uncover novel therapeutic targets and advance precision medicine strategies in pediatric IBD. A deeper understanding of microbiota-metabolite interactions may pave the way for personalized interventions to improve clinical outcomes in pediatric patients with IBD.}, } @article {pmid41361135, year = {2025}, author = {Konturek, PC and Ghopreal, T and Dieterich, W and Zopf, Y}, title = {[Gut-lung axis from a gastroenterological perspective].}, journal = {MMW Fortschritte der Medizin}, volume = {167}, number = {Suppl 6}, pages = {22-26}, doi = {10.1007/s15006-025-5477-3}, pmid = {41361135}, issn = {1613-3560}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/immunology ; Dysbiosis/immunology/therapy ; *Lung/microbiology/immunology ; Fecal Microbiota Transplantation ; *Lung Diseases/microbiology/immunology ; Lung Neoplasms/immunology ; Probiotics/therapeutic use ; }, abstract = {BACKGROUND: The microbiome is unique to each individual. It plays a key role in numerous physiological processes in the body. Intestinal dysbiosis is associated with various diseases.

METHOD: This work provides an overview of the current state of knowledge regarding the role of microbiota in the lungs and the gut-lung axis.

RESULTS AND CONCLUSIONS: Numerous studies have demonstrated a link between respiratory diseases and an altered lung microbiome. Dysbiosis of the gut microbiota influences the lung's immune response via gut-lung axis. Changes in the lung microbiome due to various environmental factors, such as smoking, particulate matter, or air pollution, contribute to lung cancer development. The composition of the gut microbiome influences the response to therapy with immune checkpoint inhibitors. Modulation of the gut microbiota through fecal microbiota transplantation (FMT), diet, prebiotics, probiotics, and synbiotics can positively influence the response to immunotherapy.}, } @article {pmid41358173, year = {2025}, author = {Othman, AAA}, title = {From rescue to recovery: Reframing severe alcoholic hepatitis management through 90-day survival.}, journal = {World journal of gastroenterology}, volume = {31}, number = {43}, pages = {113141}, pmid = {41358173}, issn = {2219-2840}, mesh = {Humans ; *Hepatitis, Alcoholic/mortality/therapy/diagnosis ; Treatment Outcome ; Severity of Illness Index ; Fecal Microbiota Transplantation ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Adrenal Cortex Hormones/therapeutic use ; Time Factors ; Randomized Controlled Trials as Topic ; }, abstract = {Severe alcoholic hepatitis remains one of hepatology's most urgent challenges, with rapid clinical deterioration and high early mortality. This manuscript comments on and contextualizes the recent systematic review by Quiñones-Calvo et al, which redirects attention from short-term endpoints toward 90-day survival, integrating evidence from associated clinical studies. For decades, corticosteroids have been the mainstay of treatment, reducing 28-day mortality but offering limited benefit for three months. The review emphasizes that the most critical threats to recovery, late infections, renal decline, and relapse, often emerge after the first month. By synthesizing recent studies, it highlights promising interventions such as fecal microbiota transplantation (FMT), which improved 90-day survival in a small randomized trial, and granulocyte colony-stimulating factor (G-CSF), which showed a robust survival benefit in a large retrospective cohort, alongside emerging strategies like plasma exchange and targeted biologics. These findings support a shift toward a two-phase care model: Early stabilization followed by recovery consolidation. For clinicians, such a model may help guide treatment decisions, with therapies like FMT or G-CSF warranting consideration in corticosteroid non-responders, pending further validation in larger randomized controlled trials. Adoption of 90-day survival as a central metric could bridge the gap between initial rescue and sustained remission, providing a more realistic measure of therapeutic success in one of hepatology's most unforgiving conditions.}, } @article {pmid41357887, year = {2025}, author = {Peng, Q and Hao, L and Li, S and Yu, F and Li, N and Hu, X}, title = {A critical review of natural products driven correction of bile acid dysregulation: a therapeutic strategy for nonalcoholic fatty liver disease.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1640873}, pmid = {41357887}, issn = {1663-9812}, abstract = {Nonalcoholic fatty liver disease (NAFLD) represents a significant global health challenge. While two drugs (semaglutide, resmetirom) have recently been approved for nonalcoholic steatohepatitis (NASH), their clinical utility is constrained by gastrointestinal side effects, insufficient efficacy against fibrosis, and dose-related adverse events. Similarly, obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist with antifibrotic potential, is associated with significant side effects, including severe pruritus. Dysregulation of bile acid (BA) metabolism is a central driver of NAFLD progression, characterized by imbalances in synthesis, impaired enterohepatic circulation, and aberrant nuclear receptor signaling. Certain hydrophobic BAs contribute to hepatocyte apoptosis, oxidative stress, and inflammation, thereby exacerbating liver injury. Targeting BA homeostasis is thus a promising therapeutic strategy, with natural products emerging as attractive candidates due to their multi-target actions and favorable safety profiles. This review summarizes 10 major classes of natural products, including traditional Chinese medicine (TCM) formulas, flavonoids, saccharides, saponins, alkaloids, curcuminoids, lignans, iridoid glycosides, sterols/terpenoids, and phenolic acids/other phenolics, that alleviate NAFLD by regulating BA metabolism. These agents modulate BA-sensing receptors, reshape the gut microbiota to optimize BA conversion, and regulate key BA transporters and enzymes. Compared with synthetic drugs, natural products offer broader efficacy, lower toxicity, and greater adaptability to the heterogeneity of NAFLD. However, significant limitations persist. Preclinical studies rely heavily on single-sex rodent models, while clinical evidence remains inconsistent. Crucially, mechanistic causality, such as the interplay between the gut microbiota and BAs, lacks rigorous validation through methods like fecal microbiota transplantation (FMT) or gene knockout studies. Furthermore, challenges in metabolite standardization and dose rationality hinder clinical translation. Future research must prioritize human-relevant models, large-scale randomized controlled trials (RCTs) with histological endpoints, and robust causal validation. By addressing these gaps, natural products targeting BA metabolism hold great promise to complement or replace existing therapies, offering safer and more effective personalized treatments for NAFLD.}, } @article {pmid41357831, year = {2025}, author = {Xiao, J and Xia, J and Chen, Z and Zha, W and Xu, T and Chen, X and Yin, X}, title = {Gut microbiota dysbiosis drives stroke-associated pneumonia: mechanisms and targeted therapeutic strategies.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1677744}, pmid = {41357831}, issn = {1662-4548}, abstract = {The gut microbiota has been increasingly recognized as a central regulator of immune function, with growing research highlighting its association with the development of stroke-associated pneumonia (SAP). This review provides an overview of current research on the correlation between SAP and alterations in gut microbial composition and metabolism, with a focus on microbial imbalance, changes in key metabolites, and relevant biological mechanisms. Clinical and preclinical studies consistently report a decline in short-chain fatty acids (SCFAs)-producing bacteria, an increase in potentially harmful microbial species, reduced SCFAs levels, and elevated lipopolysaccharide (LPS) concentrations. These disturbances appear to be associated with SAP progression through the microbiota-gut-brain and microbiota-gut-lung axes by affecting immune regulation and inflammatory responses. The review also examines microbiota-targeted treatment approaches, including dietary modification, antibiotic therapy, probiotics, microbiota-regulating compounds, fecal microbiota transplantation (FMT), and respiratory microbiota transfer. A deeper understanding of how microbial disturbances are correlated with SAP may help explain the increased vulnerability to pulmonary infections following stroke and support the design of more effective, microbiota-based therapeutic strategies.}, } @article {pmid41356558, year = {2025}, author = {Wang, H and Yang, F and Gao, Z and Cheng, Z and Liang, X}, title = {The gut-brain axis in Alzheimer's disease: how gut microbiota modulate microglial function.}, journal = {Frontiers in aging}, volume = {6}, number = {}, pages = {1704047}, pmid = {41356558}, issn = {2673-6217}, abstract = {Alzheimer's disease (AD) is a complex neurodegenerative disorder that can be caused by multiple factors, such as abnormal amyloid-beta (Aβ) deposition, pathological changes in Tau protein, lipid metabolism disorders, and oxidative stress. Recent studies have revealed the potential link between gut microbiota and AD, particularly the impact of gut microbiota and its derivatives on microglia. As immune cells in the central nervous system (CNS), microglia are involved in neuroinflammation and the regulation of cognitive function. Research indicates that the dysregulation of gut microbiota may affect the phenotype and function of microglia through various mechanisms, including direct metabolite action and indirect immune and neurotransmitter regulation. This article reviews the direct and indirect effects of gut microbiota and its derivatives on microglia, explores their role in the pathogenesis of AD, and discusses therapeutic strategies based on gut microbiota, such as dietary regulation, probiotics, fecal microbiota transplantation, and traditional Chinese medicine. Although existing studies have shown the potential of these interventions, further research is needed to completely understand their application in the treatment of AD.}, } @article {pmid41356485, year = {2025}, author = {Bai, B and Ma, J and Xu, W and Chen, X and Chen, X and Lv, C and Su, W and Li, Y and Sun, H and Zhang, B and Xiang, D and Li, Z and Wu, Y and Sun, J and Yin, M}, title = {Gut microbiota and colorectal cancer: mechanistic insights, diagnostic advances, and microbiome-based therapeutic strategies.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1699893}, pmid = {41356485}, issn = {1664-302X}, abstract = {Colorectal cancer (CRC) is closely linked to gut microbiota dysbiosis. We synthesize evidence that carcinogenic microbes promote CRC through chronic inflammation, bacterial genotoxins, and metabolic imbalance, highlighting key pathways involving Fusobacterium nucleatum, pks [+] Escherichia coli, and enterotoxigenic Bacteroides fragilis (ETBF). Building on these mechanisms, we propose a minimal diagnostic signature that integrates multi-omics with targeted qPCR, and a pathway-therapy-microbiome matching framework to guide individualized treatment. Probiotics, fecal microbiota transplantation (FMT), and bacteriophage therapy show promise as adjunctive strategies; however, standardization, safety monitoring, and regulatory readiness remain central hurdles. We advocate a three-step path to clinical implementation-stratified diagnosis, therapy matching, and longitudinal monitoring-supported by spatial multi-omics and AI-driven analytics. This approach aims to operationalize microbiome biology into deployable tools for risk stratification, treatment selection, and surveillance, advancing toward microbiome-informed precision oncology in CRC.}, } @article {pmid41355913, year = {2025}, author = {Roganovic, J and Radosevic, M and Dordevic, A}, title = {Role of the gut microbiome in the development and prognosis of pediatric leukemia.}, journal = {World journal of clinical oncology}, volume = {16}, number = {11}, pages = {111419}, pmid = {41355913}, issn = {2218-4333}, abstract = {The gut microbiome plays a pivotal role in immune homeostasis and systemic inflammatory regulation, both of which are critically involved in the pathogenesis and progression of pediatric leukemias. Recent evidence reveals that children with leukemia often exhibit distinct gut microbiome profiles at diagnosis, marked by reduced microbial diversity and the enrichment of pro-inflammatory taxa such as Enterococcus and Streptococcus. This microbial dysbiosis may promote leukemogenesis by disrupting immune regulation and driving chronic inflammation. Chemotherapy significantly alters the gut microbiome, inducing dysbiosis characterized by a loss of beneficial commensals and the dominance of pathobionts. Specific microbial signatures, such as the enrichment of Bacteroides, correlate with reduced inflammation and improved prognosis, underscoring the gut microbiome's prognostic value. Emerging therapies, including dietary adjustments, probiotics, and fecal gut microbiome transplantation, aim to restore microbial balance and reduce treatment-related complications. Moreover, gut microbiome profiling shows potential for identifying biomarkers linked to leukemia predisposition, paving the way for early diagnosis and tailored preventive strategies. This mini-review explores recent advancements in understanding the influence of the gut microbiome on pediatric leukemias, emphasizing its role as both a therapeutic target and a prognostic biomarker. Integrating gut microbiome research into clinical practice may help optimize treatment outcomes and improve quality of life for children with leukemia.}, } @article {pmid41352744, year = {2025}, author = {Wei, D and Sun, Y and Han, J and Liu, J}, title = {Microbiota and Cancer Immunotherapy: Mechanisms, Clinical Implications, and Precision Therapeutics.}, journal = {Seminars in cancer biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2025.12.002}, pmid = {41352744}, issn = {1096-3650}, abstract = {The microbiome has emerged as a pivotal modulator of cancer immunotherapy, offering novel insights into the efficacy and toxicity of immune checkpoint inhibitors (ICIs). Recent evidence highlights that microbial communities and their metabolites dynamically regulate host immunity by priming dendritic cells, enhancing T-cell infiltration, and reprogramming the tumor microenvironment. Microbiome dysbiosis is implicated in immune-related adverse events (irAEs), underscoring its dual role in therapeutic outcomes. Leveraging these findings, precision microbiome interventions, including fecal microbiota transplantation, engineered probiotics, and dietary modulation, which demonstrate potential to enhance ICIs responsiveness and mitigate irAEs in preclinical and early-phase clinical studies. However, translating these strategies into clinical practice requires rigorous validation through multicenter trials to establish safety, efficacy, and standardized protocols. This review synthesizes current knowledge on the microbiome-immune-oncology axis, with a focus on mechanistic underpinnings, translational challenges, and innovative therapeutic strategies. By integrating microbiome profiling with patient-specific factors, proposing a roadmap for personalized immunotherapy, aligning with the emerging paradigm of precision oncology.}, } @article {pmid41352125, year = {2025}, author = {Taki, AG and Shareef, A and Arora, V and Oweis, R and Jyothi, SR and Singh, U and Sahoo, S and Chauhan, AS and Alimova, F and Sameer, HN and Yaseen, A and Athab, ZH and Adil, M}, title = {Unraveling the microbiome's role in breast cancer progression and treatment response.}, journal = {Current problems in cancer}, volume = {60}, number = {}, pages = {101264}, doi = {10.1016/j.currproblcancer.2025.101264}, pmid = {41352125}, issn = {1535-6345}, abstract = {The human microbiome, encompassing microbial communities in the gut and breast tissue, has emerged as a critical modulator of breast cancer (BC) initiation, progression, and treatment response. This review synthesizes current evidence on the microbiome's role in BC, highlighting its influence on tumorigenesis, tumor microenvironment (TME), and therapeutic outcomes. Breast cancer, the most prevalent malignancy among women globally, exhibits significant heterogeneity across its molecular subtype's hormone receptor-positive, HER2-enriched, and triple-negative-each with distinct clinical challenges. Recent studies reveal that microbial dysbiosis in the gut and breast tissue can drive oncogenesis through mechanisms such as immune modulation, estrogen metabolism, and inflammation. Gut microbes, via the "estrobolome," regulate circulating estrogen levels, impacting hormone-driven BC, while breast tissue microbiota contributes to local inflammation and DNA damage, promoting tumor progression. Specific microbial taxa, including Bacillus, Staphylococcus, and Escherichia coli, are enriched in BC patients, whereas beneficial species like Lactobacillus and Bifidobacterium are diminished. The microbiome also influences treatment efficacy, with gut microbial diversity linked to enhanced chemotherapy and immunotherapy responses, while antibiotic-induced dysbiosis may impair outcomes. Emerging research suggests microbiome signatures as potential biomarkers for predicting therapeutic success, with Akkermansia muciniphila and short-chain fatty acids showing promise in enhancing anti-tumor immunity. Probiotics, prebiotics, and fecal microbiota transplantation offerel therapeutic avenues, though challenges such as standardization, interindividual variability, and safety concerns remain. Integrating multi-omics and machine learning could elucidate microbiome-host interactions, paving the way for precision oncology. This review underscores the transformative potential of microbiome-based diagnostics and interventions in improving BC management, emphasizing the need for large-scale, longitudinal studies to validate these findings and address existing research gaps.}, } @article {pmid41351979, year = {2025}, author = {Yang, Q and Huo, J and Peng, R and Qiu, S and Li, P and Wei, W and Zhou, J and Tang, Q and Wang, W}, title = {Glycitein in Zhi-Zi-Chi decoction alleviates anxiety via inosine enrichment mediated by Akkermansia muciniphila to regulate MT3-Sema7a interaction.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {150}, number = {}, pages = {157622}, doi = {10.1016/j.phymed.2025.157622}, pmid = {41351979}, issn = {1618-095X}, abstract = {BACKGROUND: Zhi-Zi-Chi Decoction (ZZCD) is used for treating emotional disturbances and insomnia. Its potential anti-anxiety efficacy has been proposed, yet the bioactive constituents and underlying mechanisms remain poorly defined.

OBJECTIVE: This study aimed to investigate the anxiolytic effects of ZZCD, identify its active components, and elucidate the mechanisms involved, with particular emphasis on the gut-microbiota-brain axis.

METHODS: The anxiety model was established using the chronic restraint stress (CRS) method. 16S rRNA gene sequencing and fecal microbiota transplantation (FMT) were employed to investigate the role of gut microbiota in the development and treatment of anxiety. N500-targeted metabolomics and RT-qPCR identified key microbial taxa and their functionally relevant metabolites. Key bioactive components of ZZCD were screened through in vitro bacterial co-culture and confirmed by in vivo pharmacological experiments. Molecular mechanisms were further explored via transcriptomics, western blotting, and co-immunoprecipitation.

RESULTS: ZZCD alleviated CRS-induced anxiety behaviors, restored brain neurotransmitter homeostasis, and reduced pro-inflammatory cytokine expression. Mechanistically, its anxiolytic effect was associated with Akkermansia muciniphila (A. muciniphila). A. muciniphila supplementation improved anxiety symptoms and promoted neurotransmitter balance. Targeted metabolomics identified inosine as a key microbial metabolite. Inosine enhanced neuronal activity, restored intestinal barrier integrity, and suppressed hippocampal NLRP3/Caspase-1/IL-18 signaling. Further, -a major isoflavone in ZZCD-was confirmed as a key anxiolytic compound, acting by promoting inosine production from A. muciniphila and regulating Metallothionein3-Sema7a protein interaction in the hippocampus.

CONCLUSION: Glycitein in ZZCD exerts anxiolytic effects by facilitating A. muciniphila -derived inosine production and modulating hippocampal MT3-Sema7a signaling, highlighting a novel microbiota-mediated therapeutic strategy for anxiety.}, } @article {pmid41351660, year = {2025}, author = {A, AP and Daksh, R and Dinil, A and B, AC and Nampoothiri, M and Nampoothiri, KM}, title = {Investigations on the Prospects of Using Lactiplantibacillus plantarum to Combat Depression through Gut Microbiota-Brain Axis.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {259}, pmid = {41351660}, issn = {1559-1182}, support = {DBT/2021-22/NIIST/1743//DBT/ ; IF230068//INSPIRE, New Delhi/ ; }, mesh = {*Gastrointestinal Microbiome/physiology/drug effects ; Humans ; *Depression/therapy/microbiology ; *Brain/metabolism ; *Probiotics/therapeutic use/pharmacology ; Animals ; *Lactobacillus plantarum ; }, abstract = {Depression is a common neurological disorder that causes a substantial burden of disease due to higher mortality and prevalence rates. The gut microbiota plays a major role in mood regulation and offers novel insights into the etiology and management of depression. However, gut dysbiosis has a negative impact on mood, cognition, behavior, and brain development. Therefore, approaches to restore the normal gut composition, such as probiotics, prebiotics, and fecal microbiota transplant, may offer novel tactics to improve therapy for depression, among which probiotics have drawn significant attention as a therapeutic intervention. Although there is no consensus on the most effective probiotic strain for treating depression, Lactiplantibacillus plantarum (L. plantarum) has gained considerable prominence due to its therapeutic potential in managing depression. The mechanisms by which L. plantarum regulates depression involve modulating the gut-brain axis through the production of various compounds, including gamma-aminobutyric acid (GABA), tryptophan, lactate, short-chain fatty acids (SCFAs), acetylcholine, and vitamins. This review highlights the antidepressant potential of L. plantarum through modulation of the gut microbiota and explores the possible mechanism of action of L. plantarum and its metabolites, as well as the genetic and epigenetic regulation of host responses and potential microRNA interactions that modulate the gut microbiota. Furthermore, metabolic engineering techniques for the L. plantarum strain, as well as promising strategies for delivering L. plantarum to the brain, have been discussed. A deeper insight into the mechanisms and gut microbiota interventions may provide effective treatment approaches for depression.}, } @article {pmid41351413, year = {2025}, author = {Xu, Y and Tao, Y and Pan, H and Wang, Z and Wang, H and Luo, Q}, title = {Microbiome Modulation in Lung Cancer Immunotherapy: Unveiling the Role of Respiratory and Gut Microbiota in the PD-1/PD-L1 Response.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {30}, number = {11}, pages = {41531}, doi = {10.31083/FBL41531}, pmid = {41351413}, issn = {2768-6698}, support = {24ZR1464400//Shanghai Municipal Natural Science Foundation/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Lung Neoplasms/therapy/immunology/microbiology ; *Immunotherapy/methods ; Tumor Microenvironment/immunology ; *B7-H1 Antigen/antagonists & inhibitors/immunology ; Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology ; Immune Checkpoint Inhibitors/therapeutic use ; Dysbiosis/immunology ; Animals ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Lung cancer, the leading cause of cancer-related mortality worldwide, poses considerable therapeutic challenges due to the varied responses to programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors. Emerging highlight the pivotal role of host-microbiome interactions in modulating antitumor immunity and influencing clinical outcomes. This review examines how the respiratory and gut microbiota contribute to the immunosuppressive tumor microenvironment through dysbiosis-induced T-cell exhaustion and regulatory cell activation, while certain commensals facilitate dendritic cell-mediated recruitment of cytotoxic T lymphocytes. Additionally, this review explores the molecular mechanisms by which microbial metabolites, such as short-chain fatty acids, influence myeloid-derived suppressor cells. Therapeutically, microbiota-modulation strategies-such as tailored probiotic formulations and precision fecal microbiota transplantation-offer potential to enhance immunotherapy efficacy. This review provides a foundation for microbiome-guided immunotherapy, advocating for biomarker-driven patient stratification and the use of engineered microbial consortia to counteract therapeutic resistance. These findings pave the way for the integration of microbiome science into next-generation precision oncology.}, } @article {pmid41350095, year = {2025}, author = {Deleu, S and Sabino, J}, title = {Cutting edge developments and novel targets in IBD: Microbiome in IBD.}, journal = {Best practice & research. Clinical gastroenterology}, volume = {78}, number = {}, pages = {102060}, doi = {10.1016/j.bpg.2025.102060}, pmid = {41350095}, issn = {1532-1916}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; *Inflammatory Bowel Diseases/therapy/microbiology ; Anti-Bacterial Agents/therapeutic use ; *Crohn Disease/microbiology/therapy ; *Colitis, Ulcerative/microbiology/therapy ; Synbiotics/administration & dosage ; }, abstract = {Inflammatory bowel disease (IBD), a non-communicable disease encompassing Crohn's disease and ulcerative colitis, is a chronic disorder with increasing prevalence and complex etiology. Emerging evidence highlights the gut microbiome's pivotal role in IBD pathogenesis, driving interest in microbiome-targeted therapeutic strategies. This narrative review explores the latest advancements in microbiome modulation for IBD management, encompassing antibiotics, prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation. Additionally, dietary interventions, physical activity, as well as non-bacterial microbiota components such as fungi, archaea, and bacteriophages are examined for their potential roles in restoring microbial equilibrium and mitigating intestinal inflammation. As research progresses, a multimodal approach integrating microbiota-targeted therapies with lifestyle modifications and conventional pharmacologic treatments may offer a personalized and effective strategy for IBD management.}, } @article {pmid41297113, year = {2025}, author = {Lyu, L and Ma, Y and Sun, X and Luo, M and Wang, Z and Fang, L and Li, W and Chen, Y and Liu, S and Jia, X}, title = {Human cord blood mononuclear cells alleviate intestinal inflammation and barrier dysfunction by regulating gut metabolites and Th17/Treg balance.}, journal = {Molecular immunology}, volume = {188}, number = {}, pages = {179-191}, doi = {10.1016/j.molimm.2025.11.004}, pmid = {41297113}, issn = {1872-9142}, mesh = {Animals ; *Th17 Cells/immunology ; *T-Lymphocytes, Regulatory/immunology ; Humans ; Mice, Inbred C57BL ; Male ; Mice ; *Colitis/immunology/therapy/chemically induced/metabolism ; *Fetal Blood/cytology ; *Leukocytes, Mononuclear/immunology/transplantation ; Dextran Sulfate ; *Inflammation/immunology ; *Intestinal Mucosa/metabolism/immunology ; Inflammatory Bowel Diseases/immunology/therapy ; }, abstract = {BACKGROUND: Cord blood mononuclear cells (CB-MNCs) are a potential alternative therapy for inflammatory bowel disease (IBD). Gut metabolites, T helper 17 (Th17) and regulatory T (Treg) cells are crucial for intestinal hemeostasis and recovery. However, the role of CB-MNCs in modulating IBD, gut metabolites and the Th17/Treg balance remains unclear.

METHODS: In this study, dextran sodium sulfate (DSS) was used to induce acute colitis in male C57BL/6 J mice, followed by treatment with CB-MNCs, umbilical cord-derived mesenchymal stem cells (UC-MSCs), or mesalazine. The severity of colitis was assessed daily using the disease activity index (DAI), and feces were collected for metabolomic analysis. Upon sacrifice, the colons, mesenteric lymph nodes (MLNs) and spleens of the mice were preserved for further study.

RESULTS: Our findings demonstrated that compared with UC-MSCs and mesalazine, CB-MNCs treatment had superior efficacy in improving clinical symptoms, tissue repair, promoting intestinal regeneration and integrity. While CB-MNCs were equivalent to UC-MSCs and mesalazine in terms of preserving colon length and anti-inflammatory activity. At the molecular level, CB-MNCs exhibited unique and powerful effects. CB-MNCs were found to significantly increase the abundance of cortisol, corticosterone, and several metabolites with anti-inflammatory and antioxidant activities in the feces of colitis mice. CB-MNCs were also more effective than UC-MSCs and mesalazine at maintaining Th17/Treg balance than UC-MSC and mesalazine in colitis mice.

CONCLUSIONS: The intravenous injection of CB-MNCs can alleviate intestinal inflammation and barrier dysfunction by modulating gut metabolites and the Th17/Treg balance. Therefore, CB-MNCs be a promising treatment for IBD.}, } @article {pmid41349548, year = {2025}, author = {Zarour, HM and Trinchieri, G}, title = {Harnessing the Microbiome in Cancer Immunotherapy: Regulation, Prediction, and Therapeutic Targeting.}, journal = {Annual review of immunology}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-immunol-082323-114522}, pmid = {41349548}, issn = {1545-3278}, abstract = {Humans are metaorganisms, composed of both host (human) cells and a roughly equal number of commensal microorganisms-collectively known as the microbiome-residing primarily at epithelial barrier surfaces. This review considers human cancer as a disease of the metaorganism, to which the microbiome contributes by influencing genome stability, tissue organization, inflammation, immunity, tumor initiation and promotion, metastasis formation, and therapeutic response. We summarize evidence demonstrating that machine learning models trained on patients' microbiome features moderately predict clinical response to immunotherapy and the development of immune-related adverse events. We review results from single-arm and randomized clinical trials wherein fecal microbiome transplantation from therapy-responsive patients or healthy donors, when combined with therapy targeting programmed cell death 1 (PD-1), improved outcomes in PD-1-refractory patients or served as an effective first-line intervention. We conclude by highlighting the emerging opportunities and ongoing challenges in leveraging the microbiome to enhance the efficacy and safety of cancer immunotherapy.}, } @article {pmid41348832, year = {2025}, author = {Cervantes-Echeverría, M and Jimenez-Rico, MA and Manzo, R and Hernández-Reyna, A and Cornejo-Granados, F and Bikel, S and González, V and Hurtado Ramírez, JM and Sánchez-López, F and Salazar-León, J and Pedraza-Alva, G and Perez-Martinez, L and Ochoa-Leyva, A}, title = {Human-derived fecal virome transplantation (FVT) reshapes the murine gut microbiota and virome, enhancing glucose regulation.}, journal = {PloS one}, volume = {20}, number = {12}, pages = {e0337760}, doi = {10.1371/journal.pone.0337760}, pmid = {41348832}, issn = {1932-6203}, mesh = {Animals ; *Gastrointestinal Microbiome ; Humans ; Mice ; *Fecal Microbiota Transplantation/methods ; *Virome ; Male ; Diet, High-Fat/adverse effects ; Obesity/therapy/microbiology ; *Feces/virology ; Mice, Inbred C57BL ; *Glucose/metabolism ; Metabolic Syndrome/therapy/microbiology ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics ; }, abstract = {The gut microbiome, comprising bacteria, viruses, archaea, fungi, and protists, plays a crucial role in regulating host metabolism and health. This study explored the effects of fecal virome transplantation (FVT) from healthy human donors on metabolic syndrome (MetS) in a diet-induced obesity (DIO) mouse model, without diet change. Mice received a single oral dose of human-derived virus-like particles (VLPs) and continued on a high-fat diet (HFD) for 17 weeks. Despite persistent dietary stress, FVT significantly improved glucose tolerance. Longitudinal profiling by virome shotgun metagenomics and bacterial 16S rRNA sequencing revealed marked, durable shifts in both viral and bacterial community composition. Notable bacterial changes included a decrease in Akkermansia muciniphila and Peptococcaceae and increases in Allobaculum and Coprococcus; A. muciniphila positively correlated with glucose levels and negatively correlated with body weight. Together, these results suggests that human-derived virome can durably reshape gut microbial ecology and improve glucose metabolism in mice with obesity, even without dietary modification, offering a novel avenue for developing phage-based therapies. This proof-of-concept study provides foundational observations for using human-derived VLPs for FVT in standard laboratory mouse models, and provides a foundation for elucidating bacteria-phage interactions and their role in host metabolic health.}, } @article {pmid41346377, year = {2025}, author = {Ishikawa, D and Zhang, X and Nomura, K and Nagahara, A}, title = {Fecal Microbiota Transplantation for Inflammatory Bowel Disease: Where We Stand and What Is Next.}, journal = {Inflammatory intestinal diseases}, volume = {10}, number = {1}, pages = {371-386}, pmid = {41346377}, issn = {2296-9365}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an emerging therapeutic strategy for inflammatory bowel disease (IBD). Every step of the FMT process, from donor recruitment and patient selection to pretreatment protocols, administration techniques, and post-FMT interventions, can significantly influence treatment outcomes. These components are interrelated, and even subtle differences in methodology may affect the overall efficacy of FMT for IBD. This review aimed to outline the current clinical experience and findings regarding FMT for IBD during the application process.

SUMMARY: Donor screening has traditionally focused on safety. In recent years, although safety remains essential, increasing attention has been paid to the donor selection efficacy. Particularly, identifying patients who are most likely to benefit from FMT is crucial because timely and appropriate patient selection can prevent delays in effective treatment. Pretreatment strategies and FMT procedures remain hot topics of current research. Approaches, such as antibiotic pretreatment, may enhance microbial engraftment; however, the optimal antibiotic combination remains unclear. Bowel lavage is commonly used to reduce the microbial burden and facilitate donor microbiota colonization, whereas corticosteroid pretreatment has shown conflicting results. There are various routes of administration, and oral capsules are gaining popularity owing to their safety and patient acceptability. Stool preparation factors, including the use of single versus pooled donors, anaerobic processing, and storage form (fresh, frozen, or freeze-dried), can significantly influence microbial viability and clinical outcomes. Repeated FMTs tend to be more effective than single infusions; nonetheless, the optimal frequency remains unclear. Post-FMT interventions, such as dietary modifications and supplementation with prebiotics, such as pectin and alginic acid, are also promising strategies.

KEY MESSAGES: Despite encouraging results, variations in treatment protocols, donor characteristics, and host factors continue to obscure the definitive predictors of FMT success. Further randomized controlled trials and mechanistic studies are required to standardize these procedures and optimize their long-term efficacy.}, } @article {pmid41346294, year = {2025}, author = {Salinas-Velarde, ID and Donaciano-Domínguez, JM and Oros-Pantoja, R and Aguirre-Garrido, JF and González-Cervantes, RM and Munguía-Cervantes, JE and López, MG and Bustos-Martínez, J and Soto-Piña, AE}, title = {Narrative Review: Gut Microbiota and Its Impact on α-syn Function in Parkinson's Disease.}, journal = {MicrobiologyOpen}, volume = {14}, number = {6}, pages = {e70173}, doi = {10.1002/mbo3.70173}, pmid = {41346294}, issn = {2045-8827}, support = {//This review was funded by the "Consorcios Proyectos de Colaboración Interinstitucional UAM-IPN -UAEMEX" (grant number 7152/2024ECON) and publication grant 34503067 (UAM-Xochimilco). Additionally, I.D.S.V. received a grant from the Consejo Mexiquense de Ciencia y Tecnología (COMECYT, grant number CAT2024-0080)./ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; *Parkinson Disease/microbiology/therapy/metabolism ; Humans ; *alpha-Synuclein/metabolism ; Fecal Microbiota Transplantation ; Animals ; Bacteria/metabolism/classification ; }, abstract = {Gut microbiota (GM) plays a pivotal role in human health and disease, and its alterations have been implicated in various neurological disorders, including Parkinson's disease (PD). Growing evidence reveals correlations between the abundance of specific bacterial taxa and the severity of motor symptoms and intestinal dysfunction in PD. Moreover, bacterial metabolites have been shown to influence α-synuclein (α-syn) aggregation and neurodegeneration. This narrative review aims to explore the current understanding of the gut-brain axis in PD, specifically the connection between GM and α-syn function in PD experimental models and patients. Several therapeutic strategies aimed at modulating gut microbiota, such as dietary interventions, fecal microbiota transplantation, and targeted bacterial therapies with the goal of alleviating or preventing PD symptoms, are examined. Understanding the mechanisms through which GM influence neurodegeneration, including inflammation, immune modulation, and microbial metabolite production, offers promising avenues for the development of novel therapeutic strategies targeting the microbiome.}, } @article {pmid41345102, year = {2025}, author = {Pope, R and Visconti, A and Zhang, X and Louca, P and Baleanu, AF and Lin, Y and Asnicar, F and Bermingham, K and Wong, KE and Michelotti, GA and Wolf, J and Segata, N and Berry, SE and Spector, TD and Leeming, ER and Gibson, R and Menni, C and Falchi, M}, title = {Faecal metabolites as a readout of habitual diet capture dietary interactions with the gut microbiome.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {10051}, pmid = {41345102}, issn = {2041-1723}, support = {27/2023//Chronic Disease Research Foundation (CDRF)/ ; }, mesh = {Humans ; *Feces/chemistry/microbiology ; *Gastrointestinal Microbiome/physiology ; *Diet ; Male ; Female ; Metabolome ; Middle Aged ; Metabolomics/methods ; Aged ; Metagenomics ; Adult ; Machine Learning ; }, abstract = {The interplay between diet and gut microbiome composition is complex. Faecal metabolites, the end products of human and microbial metabolism, provide insights into these interactions. Here, we integrate faecal metabolomics, metagenomics, and habitual dietary data from 1810 individuals from the TwinsUK and 837 from the ZOE PREDICT1 cohorts. Using machine learning models, we find that faecal metabolites accurately predict reported intakes of 20 food groups (area under the curve (AUC) > 0.80 for meat, nuts and seeds, wholegrains, tea and coffee, and alcohol) and adherence to seven dietary patterns (AUC from 0.71 for the Plant-based Diet Index to 0.83 for the Dietary Approaches to Stop Hypertension score). Notably, the faecal metabolome is a stronger predictor of atherosclerotic cardiovascular disease risk (AUC = 0.86) than the Dietary Approaches to Stop Hypertension score (AUC = 0.66). We identify 414 associations between 19 food groups and 211 metabolites, that significantly correlate with microbial α-diversity and 217 species. Our findings reveal that faecal metabolites capture mediations between diet and the gut microbiome, advancing our understanding of diet-related disease risk and informing metabolite-based interventions.}, } @article {pmid40967279, year = {2025}, author = {Liao, XN and Huang, LL and Yang, J and Hou, YY and Quan, YX and Bai, YH}, title = {Analysis of the potential mechanism of stem cells in the treatment of diabetic nephropathy based on 16S, metabolome and transcriptome.}, journal = {Genomics}, volume = {117}, number = {6}, pages = {111113}, doi = {10.1016/j.ygeno.2025.111113}, pmid = {40967279}, issn = {1089-8646}, mesh = {*Diabetic Nephropathies/therapy/metabolism/genetics ; Animals ; *Metabolome ; Mice ; *Transcriptome ; RNA, Ribosomal, 16S/genetics ; Male ; *Mesenchymal Stem Cell Transplantation ; *Mesenchymal Stem Cells/metabolism ; Gene Regulatory Networks ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Diabetic nephropathy (DN) has become a major cause of end-stage renal failure. The therapeutic mechanism of mesenchymal stem cells (MSCs) in DN is not fully understood. In this study, we used transcriptome sequencing, 16S rRNA sequencing, and metabolomics sequencing to perform a combined multi-omics analysis to investigate the potential mechanisms of MSCs for DN.

METHODS: First, DN mouse model was established. Kidneys, feces, and blood were collected from 6 control, 6 model, and 6 intervention (MSCs) groups for transcriptome sequencing, 16S RNA sequencing, and metabolome sequencing, respectively. Then, candidate genes between the 3 groups were identified and enriched using transcriptomic analysis. Next, with the help of metabolomics analysis, differential metabolites were screened by OPLS-DA analysis for control and model groups, as well as model and MSCs groups, respectively. Similarly, differential microorganisms and candidate microorganisms were selected by 16S rRNA gene sequencing data. Subsequently, the correlations between candidate genes and candidate metabolites, candidate genes and candidate microorganisms, as well as candidate metabolites and candidate microorganisms were explored by Spearman correlation analysis, respectively. Finally, a microbe-metabolite-gene network was constructed to identify key genes, key metabolites and key microbes, and their expression levels were analyzed.

RESULTS: There were differences in genes, microorganisms, and metabolites among the samples in the control, model, and MSCs groups. Candidate genes enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways included adhesion molecules and 2-oxocarboxylic acid metabolism. GDP-mannose biosynthesis and purine ribonucleoside degradation were significantly enriched by different microorganisms. The KEGG pathways mainly enriched for differential metabolites were PPAR signaling pathway, arachidonic acid metabolism, and Rap1 signaling pathway. A microorganisms-metabolite-gene network containing 25 nodes and 53 edges was constructed with interactions including Sorangium-neg-M501T271 and Tmem238l-pos-M373T270, among others. In addition, 10 key genes, 5 key microorganisms and 10 key metabolites were significantly expressed in both the MSCs group and the control group.

CONCLUSION: This study identified 10 key genes, 10 key metabolites and 5 key microorganisms and a correlation network diagram was constructed. It provided a theoretical reference for exploring the molecular mechanisms of MSCs for DN treatment.}, } @article {pmid41344956, year = {2025}, author = {Jia, D and Wang, L}, title = {Opportunities and challenges in applying microbiota to clinical cancer immunotherapy.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2025.11.011}, pmid = {41344956}, issn = {1878-4380}, abstract = {Fundamental research has elucidated the indispensable role of gut microbiota in modulating cancer immunotherapy efficacy. Despite promising preclinical findings, few related approaches have reached clinical trials. In this opinion, we provide insights based on current clinical trials using fecal microbiota transplant or specific bacterial strains as adjuvants to enhance immune checkpoint blockade therapy. We also systematically analyze the challenges in trial design, with a focus on donor selection, patient enrollment, implantation procedures, antibiotic use, safety assessment, and endpoint evaluation. Moving forward, we offer a comprehensive '4D' framework (diversity, diffusion, depth, and delicacy) for accelerating the bench-to-bedside translation. It is hoped that this opinion will help researchers and clinicians aiming to harness microbiome-based strategies to improve cancer immunotherapy outcomes.}, } @article {pmid41344523, year = {2025}, author = {Yang, Y and Gan, D and Liang, B and Qian, S and Yang, H and Han, C and Wang, Z}, title = {Quyushengxin formula restores the integrity of intestinal barrier by regulating the gut microbiota to ameliorate DSS-induced ulcerative colitis in mice.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {120992}, doi = {10.1016/j.jep.2025.120992}, pmid = {41344523}, issn = {1872-7573}, abstract = {The Quyushengxin formula (QYSXF), a clinically validated traditional Chinese medicine (TCM) formula, has been demonstrated to be safe and effective for the treatment of ulcerative colitis (UC), but its mechanism of action in UC treatment is still unclear.

AIMS OF THE STUDY: The aim of this study was to investigate the effects of QYSXF on gut microbiota modulation in DSS-induced colitis mice and to explore its role in regulating intestinal barrier function and inflammation.

MATERIALS AND METHODS: First, the chemical constituents of QYSXF and mouse plasma were identified using high-performance liquid chromatography coupled with mass spectrometry. An active UC mouse model was established by treating the mice with 3% DSS. The efficacy of QYSXF was evaluated by colonoscopy, body weight, disease activity index (DAI), colon length and histological examinations. Faecal microbiota transplantation (FMT) was performed by transferring the faecal from QYSXF-treated donor mice to DSS-induced UC recipient mice. Intestinal barrier integrity and inflammation were assessed through immunofluorescence, ELISA, and western blotting. Additionally, 16S rDNA sequencing was used to elucidate the composition of the QYSXF-regulated microbiota.

RESULTS: QYSXF effectively ameliorated local ulcer surface, reduced weight loss, decreased the DAI, restored colon length, and improved histopathological scores in UC model mice. QYSXF restored the integrity of the mechanical barrier by increasing the expression of tight junction proteins and restored the integrity of the chemical barrier through increased secretion of Mucin 2 (MUC2). FMT with faecal from QYSXF-treated mice ameliorated inflammation and restored both the mechanical barrier and the chemical barrier. Moreover, both QYSXF and FMT reduced the release of proinflammatory cytokines by inhibiting the NF-κB signalling pathway and increasing the release of anti-inflammatory cytokines. 16S rDNA sequencing demonstrated that QYSXF modulated the composition of the gut microbiota by increasing the abundance of beneficial bacterial, specifically Dubosiella and Ligilactobacillus, while concurrently reducing the prevalence of the pathogenic Escherichia-Shigella.

CONCLUSIONS: The mechanism underlying the efficacy of QYSXF involves restoring the composition of the gut microbiota to improve intestinal barrier, reducing the release of proinflammatory cytokines, and ultimately alleviating UC. This research not only confirms the therapeutic potential of QYSXF in UC treatment but also, more importantly, highlights the critical role of gut microbiota regulation in restoring barrier dysfunction and mitigating inflammatory responses involved in the pathogenesis of UC.}, } @article {pmid41343181, year = {2025}, author = {Roth, TD and Russo-Savage, L and Bahojb Habibyan, Y and Keenan, CM and Wallace, LE and Nasser, Y and Mawe, GM and Lavoie, B and Sharkey, KA}, title = {Microbial dysbiosis alters serotonin signaling in a post-inflammatory murine model of visceral pain.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpgi.00240.2025}, pmid = {41343181}, issn = {1522-1547}, support = {FDN148380//Canadian Institutes of Health Research (CIHR)/ ; DK113800//HHS | National Institutes of Health (NIH)/ ; AT011203//HHS | National Institutes of Health (NIH)/ ; }, abstract = {Serotonin (5-HT) is a multifunctional signaling molecule in the gastrointestinal (GI) tract. 5-HT synthesis is regulated by the gut microbiota. Microbial dysbiosis has been implicated in visceral pain and persistent alterations in gut function that occur following inflammation. Here we tested the hypothesis that alterations in gut microbiota in a post-inflammatory model of visceral pain contribute to dysregulated 5-HT signaling. We used mice treated with dextran sodium sulfate (DSS) 42 days earlier (post-colitis) or untreated mice as donors for fecal microbiota transplants (FMTs) into germ-free mice to explore changes in enterochromaffin (EC) cell populations, expression of 5-HT synthesis, transport, and degradation genes, levels of 5-HT and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and 5-HT release. Significant differences were observed in EC cells, Tph1, Slc6a4, and Maoa gene expression, 5-HT and 5-HIAA levels and 5-HT release between germ-free mice and mice receiving an FMT from either control or post-colitis donor mice. We observed no differences in the total number of EC cells, Tph1, or Slc6a4 gene expression of mice after FMT from post-colitis or control mice. However, there was a significant increase in Maoa gene expression in the terminal ileum, an increased 5-HIAA/5-HT ratio in the proximal colon and reduced 5-HT release to mechanical and chemical stimulation in the proximal and distal colon after FMT from post-colitis mice. Collectively, these findings provide additional evidence that the gut microbiota regulates 5-HT signaling. Moreover, they reveal functional changes in EC cell sensitivity in the presence of an altered microbiota after recovery from inflammation.}, } @article {pmid41342899, year = {2025}, author = {Wang, LJ and Mo, YK and Cheng, Y}, title = {The role of intratumoral microbiota in the occurrence and progression of tumors and its implications for guiding tumor treatment.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {}, number = {}, pages = {}, doi = {10.1556/030.2025.02747}, pmid = {41342899}, issn = {1588-2640}, abstract = {In recent years, the presence of microbiota in tumors has been discovered through extensive research, overturning the longstanding belief that "tumors are sterile." Advanced techniques such as 16S rRNA gene sequencing, fecal microbiota transplantation, and the construction of mouse models specific to different tumor types have been utilized to validate the existence of microbiota within various tumors. The intratumoral microbiota significantly influences tumor development by modulating immune responses, mediating inflammatory reactions, and interfering with or enhancing immunotherapy or chemotherapy. For instance, Aspergillus sydowii in lung adenocarcinoma promotes immunosuppression via the Dectin-1/CARD9 pathway, while colibactin-producing Escherichia coli in colorectal cancer facilitates tumor progression through lipid metabolism dysregulation. Moreover, intratumoral microbiota can predict patient prognosis and guide personalized cancer treatment strategies, highlighting their potential as therapeutic targets. This review synthesizes current evidence on the roles of intratumoral microbiota across multiple cancer types and discusses their clinical implications.}, } @article {pmid41341415, year = {2025}, author = {Memariani, M and Memariani, H}, title = {Dysbiosis and Therapeutic Modulation of the Gut Microbiota in Multiple Sclerosis: A Narrative Review.}, journal = {Health science reports}, volume = {8}, number = {12}, pages = {e71564}, pmid = {41341415}, issn = {2398-8835}, abstract = {BACKGROUND AND AIMS: Multiple sclerosis (MS) is a persistent autoimmune disease that affects the central nervous system. The etiology of MS is complex, involving a variety of genetic and environmental factors. Mounting evidence suggests that dysbiosis significantly impacts the progression of MS mainly through its direct effects upon the immune system. Given the vital connection between the gut microbiota and immune health, particularly in the context of autoimmune diseases, this review aims to summarize the existing knowledge regarding alterations in the gut microbiota among MS patients, with a focus on microbiota-based therapeutic approaches.

METHODS: A detailed literature review was carried out to gather contemporary evidence on dysbiosis of the gut microbiota in MS patients. Furthermore, studies dealing with the modification of gut microbiota for therapeutic applications in MS have been included.

RESULTS: A distinct variation in specific bacterial phyla, orders, families, and genera, as well as metabolites, was found in MS patients. Exploring therapeutic options such as antibiotics, probiotics, dietary interventions, fecal microbiota transplantation, phage therapy, and helminth therapy may present valuable opportunities for gut microbiota modification in MS treatment.

CONCLUSION: Altering the gut microbiota in patients with MS may serve as a potentially effective treatment strategy. Nevertheless, future research should prioritize the standardization of these therapies. Finally, it is imperative that researchers concentrate on large-scale studies or trials to scrutinize the practical relevance of these therapeutic options.}, } @article {pmid41340133, year = {2025}, author = {Abavisani, M and Sajjadi, SM and Ebadpour, N and Karav, S and Sahebkar, A}, title = {Gut microbiota-cholesterol crosstalk in cardiovascular diseases: mechanisms, metabolites, and therapeutic modulation.}, journal = {Nutrition & metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12986-025-01051-7}, pmid = {41340133}, issn = {1743-7075}, abstract = {Cardiovascular diseases (CVD) are one of the leading causes of death worldwide. Genetic factors, and various environmental factors, including nutrition and the composition of the gut microbiota, have been identified as important factors in the initiation of CVD. Among them, the pivotal role of the gut microbiota in modulating cholesterol metabolism and influencing cardiovascular outcomes has recently been highlighted. Extensive research has confirmed that the gut microbiota has direct and indirect regulatory effects on host cholesterol homeostasis. Recent studies have shown that the microbiota can influence blood cholesterol levels and thus the risk of CVD through various pathways, such as the production of certain metabolites such as bile acids (BAs), SCFAs, and TMAO, the activation of nuclear and membrane-bound receptors such as farnesoid X receptor (FXR), the regulation of gene expression involved in lipid metabolism and inflammatory responses, as well as microbial enzymatic pathways. These complex regulatory mechanisms make the gut microbiota a potential therapeutic target in cholesterol-related diseases and CVD. Microbiota-modulating strategies, including the use of probiotics, prebiotics, fecal microbiota transplantation (FMT), and selective antibiotics, have shown beneficial effects in previous studies. In this regard, in this study, we conducted an in-depth investigation of the regulatory effect of intestinal microbiota on cholesterol metabolism and their impact on the development and progression of atherosclerosis and CVD, and described potential therapeutic pathways based on the regulation of intestinal microbiota in CVD.}, } @article {pmid41339929, year = {2025}, author = {Yang, Y and Chen, H and Lu, J and Yang, N and Liu, L and Zhang, Q and Tang, M and Li, X and Meng, B and Li, Y and Yu, L and Gao, L and Zhang, H and Wu, T and Zheng, Y and Liu, Y and Shen, Y and Li, J}, title = {Modulating the gut-bladder axis: fecal transplantation protects antibiotic-treated mice from E. coli cystitis via the Ahr/Prg4 pathway.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02267-8}, pmid = {41339929}, issn = {2049-2618}, support = {U24A20643, 82270015, 82400132, 82100017，82302577，82304209, 82370016//National Natural Science Foundation of China/ ; 2023B700,2024C875//Anhui Province Postdoctoral Research Funding Project/ ; 2208085QH236, 2208085MH264, 2308085QH284, 2308085MH243//Anhui Provincial Natural Science Foundation/ ; 202304295107020032, 202304295107020043//Anhui Province Clinical Medical Research Transformation Special Project/ ; 2023AH01008, 2023AH053282//Anhui Province Scientific Research Planning Project/ ; 2023AH010083, 2024AH010114, 2024AH050826//Anhui University Natural Science Research Project/ ; gxbjZD08//Top Talents Academic Funding Key Programs in Universities/ ; 2021xkjT021//Basic and Clinical Cooperative Research Program of Anhui Medical University/ ; MTP2022A015//China Primary Health Care Foundation/ ; }, abstract = {BACKGROUND: Bacterial cystitis, caused by Escherichia coli (E. coli), is a common urinary tract infection that frequently recurs and seriously affects patient health. Although it is known that gut dysbiosis increases susceptibility to recurrent urinary tract infections, its impact on non-complicated bacterial cystitis-the most common and primary form of urinary tract infection-remains uncertain.

RESULTS: This study found that bacterial infection can cause long-term alterations in gut microbiota structure and affect the production of metabolites. Depletion of the gut microbiota worsens the inflammatory response to bacterial infection, disrupts the epithelial barrier of the bladder, and increases E. coli retention in the bladder and bloodstream. Fecal microbiota transplantation was found to significantly alleviate these excessive inflammatory responses. The study also identified that several tryptophan derivatives derived from the gut microbiota were significantly altered during bacterial microbiota depletion and bacterial infection, with indole-3-propionic acid (IPA) exhibiting the most significant alleviating effect on the excessive inflammatory response during infection. Additionally, the study demonstrated that transcriptional activation of the immune-inhibitory protein Prg4 is regulated by the IPA receptor AhR, which is expressed in bladder urothelial cells. Knockout of AhR in bladder urothelial reduced Prg4 expression and overactivated NF-κB signaling, resulting in the loss of the IPA-alleviating effect. This study suggests that the normal gut microbiota can activate AhR in bladder urothelial cells through its metabolite IPA, regulating the transcription of Prg4 and subsequently modulating the inflammatory response to bacterial cystitis caused by E. coli infection.

CONCLUSIONS: These findings provide a theoretical foundation for the clinical diagnosis and treatment of bacterial cystitis by leveraging the gut microbiota and their metabolites as promising therapeutic targets. Video Abstract.}, } @article {pmid41082373, year = {2025}, author = {Chen, K and Geng, H and Zheng, Y and Xie, H and Qin, R and Chen, J and Ye, C}, title = {Disruption of Gut Microbiota-Mediated De Novo NAD[+] Synthesis Contributes to the Development of Polycystic Ovary Syndrome.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {45}, pages = {e06497}, doi = {10.1002/advs.202506497}, pmid = {41082373}, issn = {2198-3844}, support = {20240402019GH//Jilin Province Science and Technology Development Plan project/ ; 2024SCZ07//Health Research Talents of Jilin Province/ ; 2024CL04//Spring-Bud Plan Construction Project of China-Japan Union Hospital of Jilin University/ ; }, mesh = {*Polycystic Ovary Syndrome/metabolism/microbiology ; Female ; *Gastrointestinal Microbiome/physiology ; Animals ; Mice ; Humans ; *NAD/biosynthesis/metabolism ; *Dysbiosis/metabolism ; Disease Models, Animal ; Fecal Microbiota Transplantation ; }, abstract = {Polycystic ovary syndrome (PCOS) is a severe disorder that compromises female ovarian health and elevates the risk of various diseases, including endometrial cancer. The pathogenesis of PCOS remains poorly understood, which has hindered the development of effective interventions. In this study, it is demonstrated that patients with PCOS exhibit significant gut dysbiosis. FMT from PCOS patients (P-FMT) into mice induced PCOS-associated symptoms and histological alterations. Notably, both PCOS patients and P-FMT mice exhibit distinct metabolic profiles in the gut, suggesting a gut microbiota-mediated metabolic reprogramming. Furthermore, impaired tryptophan metabolism, particularly reduced levels of 3-hydroxyanthranilic acid (3-HAA), is observed in both PCOS patients and P-FMT mice. Administration of 3-HAA to mice alleviated DHEA-induced PCOS. Mechanistically, 3-HAA promoted NAD[+] synthesis via the de novo biosynthesis pathway, thereby inhibiting DHEA-induced ferroptosis by modulating the mitochondrial DNA-cGAS-STING axis. Collectively, these findings reveal the critical role of gut microbiota-mediated NAD[+] synthesis in the pathogenesis of PCOS, underscoring the potential of targeting gut microbiota and NAD[+] homeostasis as a therapeutic strategy for PCOS prevention and management.}, } @article {pmid41338385, year = {2025}, author = {Zhang, X and Qi, J and Dong, C and Zhang, L and Chen, J and Liu, J and Jiang, T and Song, J}, title = {Intratumoral microbiota in colorectal cancer: roles, therapeutic potential, and challenges.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.11.067}, pmid = {41338385}, issn = {2090-1224}, abstract = {BACKGROUND: Colorectal cancer (CRC) is a multifactorial disease characterized by disruptions in cellular and immune functions, influenced by genetic mutations, environmental factors, and infections. Recent studies have highlighted the intratumoral microbiota as a critical component of the tumor microenvironment (TME), with a significant role in CRC initiation, progression, and therapeutic response. While the gut microbiota's influence on CRC is well-established, the specific contribution of intratumoral microbiota remains inadequately explored. Emerging evidence suggests that intratumoral microbiota may promote cancer progression through inflammatory pathways, metabolic alterations, and resistance to chemotherapy. Conversely, certain microbial communities exhibit tumor-suppressive properties by modulating immune responses and inducing apoptosis in tumor cells.

AIM OF REVIEW: This review aims to highlight the dual role of the intratumoral microbiota in CRC and explore the potential of microbial interventions such as probiotics, phage therapy, and fecal microbiota transplantation (FMT) in enhancing therapeutic outcomes. Furthermore, the review examines the potential of microbiota-targeted therapies to optimize cancer treatment strategies and stresses the need for personalized approaches based on microbial biomarkers.

Intratumoral microbiota, as emerging tumor components, has been identified in various solid tumors. The review emphasizes the mechanisms by which intratumoral microbiota mediate inflammation, metabolic alterations, and immune modulation in CRC. It highlights how certain intratumoral microbiota are associated with resistance or sensitivity to treatments, and how manipulating the microbiota could enhance immunotherapy efficacy. By integrating advancements in multi-omics and clinical research, targeting the intratumoral microbiota represents a promising avenue for improving CRC therapies and overcoming treatment resistance. The clinical application of the intratumoral microbiota has the potential to revolutionize the treatment of CRC, paving the way for novel therapeutic strategies in oncology.}, } @article {pmid41339918, year = {2025}, author = {Liu, H and Xiong, X and Zhu, W and Wang, S and Huang, W and Zhu, G and Xu, H and Yang, L}, title = {Gut microbial metabolites in cancer immunomodulation.}, journal = {Molecular cancer}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12943-025-02521-5}, pmid = {41339918}, issn = {1476-4598}, support = {2022YFC3602900//National Key Research and Development Program of China/ ; 82372831//National Natural Science Foundation of China/ ; }, abstract = {Gut microbiota-derived metabolites are emerging as systemic "remote immunoregulators" that shape tumor immunity across tissues. Integrating evidence across short-chain fatty acids, tryptophan derivatives, secondary bile acids, polyamines and other metabolites, we advance a metabolite-immune pathway-cancer framework that links receptor-mediated signaling, epigenetic remodeling and metabolic reprogramming to context-dependent, bidirectional immune effects. Importantly, in addition to the g protein-coupled receptor / aryl hydrocarbon receptor pathway, the selected microbial small molecule metabolites are the true T-cell receptor ligands of unconventional T cells, directly shaping the tissue resident immune and tumor microenvironment, supplementing the receptor signaling and epigenetic programs in our framework. We synthesize how these metabolites recalibrate the tumor immune microenvironment-modulating antigen presentation, T-cell effector fitness and exhaustion, regulatory T-cell activity, and myeloid polarization-and why the same metabolite can either potentiate immune surveillance or entrench immunosuppression depending on ligand-receptor pairing, dose and tissue niche. We compare tumor-type specific patterns (e.g., colorectal, liver, lung, breast and prostate cancers) to highlight common circuits and organ-restricted idiosyncrasies. Methodologically, we outline how single-cell and spatial multi-omics, imaging mass spectrometry and functional biosensors now enable co-registration of metabolite exposure with immune-cell states in human tumors, providing an actionable basis for biomarker discovery. Given ongoing debate about signals attributed to intratumoral microbiota in low-biomass tumor tissues, we foreground quantifiable, spatially mappable and pharmacologically tractable metabolite-receptor pathways, using microbe-associated molecular patterns / translocation as comparators to judge when chemical signals should be prioritized as intervention targets. Finally, we evaluate precision intervention avenues-including fecal microbiota transplantation, rational bacterial consortia, engineered microbes and nanoparticle-enabled metabolite delivery-and propose stratification rules that pair metabolite/receptor signatures with fit-for-purpose delivery. Together, mapping tissue-specific metabolite-immune circuits and embedding them in robust biomarker frameworks may convert microbial metabolites from correlative markers into therapeutic targets and tools, improving the efficacy and durability of cancer immunotherapy.}, } @article {pmid41338419, year = {2025}, author = {Wei, MX and Wu, XY and Lin, JW and Huang, JY and Cheng, J and Huang, WF and Xu, GH and Yi, LT}, title = {Astaxanthin alleviates DSS-induced ulcerative colitis in mice associated with Nrf2-mediated ferroptosis independently of gut microbiota modulation.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {110212}, doi = {10.1016/j.jnutbio.2025.110212}, pmid = {41338419}, issn = {1873-4847}, abstract = {Astaxanthin, a natural carotenoid predominantly synthesized by marine microorganisms, has shown promise in attenuating inflammatory diseases, yet its role in colitis remains unclear. Here, we evaluated the therapeutic effects of astaxanthin in dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. Our findings revealed that astaxanthin significantly ameliorated colitis symptoms, notably at the dose of 100 mg/kg, demonstrated by reduced Disease Activity Index (DAI), increased colon length, diminished colon histopathological damage, and enhanced goblet cell population. Mechanistically, astaxanthin decreased proinflammatory cytokines and malondialdehyde (MDA) levels, suppressed Keap1 expression, activated phosphorylated Nuclear factor erythroid 2-related factor 2 (Nrf2), and increased downstream protein expression of HO-1 and GPX4, ultimately inhibiting ferroptosis. Although astaxanthin altered gut microbiota composition, antibiotic treatment and fecal microbiota transplantation confirmed that its anti-colitis effects were independent of microbiota changes. These findings suggest that astaxanthin alleviates colitis associated with Nrf2 pathway mediated ferroptosis, rather than through gut microbiota modulation.}, } @article {pmid41338112, year = {2025}, author = {Hu, L and Zhang, Z and Xu, T and Ma, P and Wang, Z and Zhang, L and Chen, J and He, P and Yang, X and Du, G and Lian, F and Li, X and Qiang, G}, title = {Jiangtang Tiaozhi Formula alleviates obesity by enhancing adipose thermogenesis via TGR5-mediated gut-liver-adipose axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {150}, number = {}, pages = {157608}, doi = {10.1016/j.phymed.2025.157608}, pmid = {41338112}, issn = {1618-095X}, abstract = {BACKGROUND: Development of safe and effective anti-obesity drugs has emerged as an urgently needed issue. Jiangtang Tiaozhi Formula (JTTZF), a traditional Chinese medicine formulation, has demonstrated potential antidiabetic and hypolipidemic properties. However, the anti-obesity efficacy of JTTZF and its mechanisms remain insufficiently understood.

METHODS: We assessed the pharmacodynamic effects of JTTZF in diet-induced obese (DIO) mice, as well as in HepG2 cells and adipocytes, focusing on body weight and glucose/lipid metabolism in vivo and in vitro, respectively. 16S rDNA sequencing profiling and fecal microbiota transplantation (FMT) were applied to validate the contribution of gut microbiota in anti-obesogenic effects of JTTZF. Untargeted fecal metabolomics was utilized to explore the potential metabolic pathways mediating gut-liver-adipose axis leading to anti-obesity effect of JTTZF via thermogenesis, which were subsequently confirmed by qPCR detection.

RESULTS: JTTZF exhibited a significant effect of anti-obesity and metabolic benefit, including inhibiting weight gain and adiposity, reducing blood glycolipid, ameliorating glucose intolerance and insulin resistance, together with protecting against hepatic steatosis, compared with orlistat. Mechanistically, JTTZF boosted white fat browning and brown fat thermogenesis. More importantly, JTTZF remodeled gut microbiota by enhancing the colonization of beneficial bacteria. Further JTTZF-FMT induced weight loss and metabolic benefits in DIO mice, verifying that gut microbiota played a crucial role in the anti-obesity effect of JTTZF. Additionally, enrichment analysis of differential metabolites revealed that JTTZF obviously upregulated bile acid metabolism pathway, which promoted TGR5-mediated thermogenesis and energy expenditure in adipose tissue.

CONCLUSION: JTTZF exerted significant anti-obesity effect and metabolic benefits via gut-liver-adipose axis, indicating that JTTZF hold a promising potential at the preclinical stage for obesity treatment.}, } @article {pmid41337940, year = {2025}, author = {Han, M and Dong, X and Zhao, R and Hu, X and Li, D and Yan, X and Liu, Y and Du, Q and Li, M}, title = {Fecal metabolomics in Crohn's disease reveal N-Acetylglutamine as a Th17/Treg modulator.}, journal = {Molecular immunology}, volume = {189}, number = {}, pages = {82-97}, doi = {10.1016/j.molimm.2025.11.012}, pmid = {41337940}, issn = {1872-9142}, abstract = {The gut microbiota is widely recognized as a key component in the pathogenesis of inflammatory bowel disease (IBD), and one of its primary modes of interaction with the host occurs via metabolites. Studies have confirmed that gut microbiota dysbiosis affects immune maturation, immune homeostasis, host energy metabolism, and the maintenance of mucosal integrity. However, the specific metabolites that influence the differentiation of mucosal CD4[+] T cells remain insufficiently elucidated. This study aimed to identify and validate unknown metabolites capable of affecting the differentiation of CD4[+] T cell subsets by characterizing changes in fecal metabolites between IBD patients and non-IBD controls. Using untargeted metabolomics, we quantitatively detected a total of 1480 metabolites in positive ion mode and 1178 metabolites in negative ion mode. Regression analysis results showed that N-Acetylglutamine was significantly downregulated in IBD patients and was identified as a key differential metabolite. Further in vitro functional experiments confirmed that this metabolite could directly regulate the differentiation balance of CD4[+] T cells, specifically inhibiting the differentiation of pathogenic Th17 (pTh17) cells while promoting the generation of Treg. This study verifies the critical role of the metabolite N-Acetylglutamine in regulating the Treg/pTh17 cell balance, providing a theoretical basis for its potential as a therapeutic target for IBD.}, } @article {pmid41337660, year = {2025}, author = {Silva, IB and Puig-Domingo, M}, title = {The impact of thyroid disorders on the gut microbiome: emerging mechanisms and clinical relevance.}, journal = {Archives of endocrinology and metabolism}, volume = {70}, number = {Spe1}, pages = {e250075}, doi = {10.20945/2359-4292-2025-0075}, pmid = {41337660}, issn = {2359-4292}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/immunology ; *Thyroid Diseases/microbiology/immunology/metabolism ; Dysbiosis/microbiology/immunology ; Thyroid Gland/metabolism/immunology ; Animals ; Clinical Relevance ; }, abstract = {The thyroid-gut axis represents a dynamic interaction between the intestinal microbiota and thyroid function, with growing evidence linking gut dysbiosis to thyroid diseases. The gut microbiome, comprising over 100 trillion microorganisms, influences immune modulation, iodine metabolism, and thyroid hormone regulation. Short-chain fatty acids, produced by beneficial gut bacteria, support immune homeostasis and thyroid function, while pathogenic bacteria and lipopolysaccharides trigger inflammatory pathways that impair thyroid activity. Alterations in gut microbiota composition have been associated with autoimmune thyroid diseases, including Hashimoto's thyroiditis and Graves' disease. Dysbiosis increases intestinal permeability, antigen exposure, and immune activation, exacerbating thyroid autoimmunity. A reduction in short-chain fatty acids-producing bacteria weakens immune tolerance, promoting inflammatory cytokine release and autoantibody production. Recent studies highlight microbial metabolites such as tryptophan derivatives and their role in immune regulation. Gut dysbiosis is also implicated in thyroid nodules and cancer. Decreased butyrate-producing bacteria and increased inflammatory bacterial taxa have been observed in thyroid malignancies. Microbiota influence iodine and selenium bioavailability, essential for thyroid hormone synthesis, and modulate sodium-iodide symporter expression, affecting thyroid cancer response to radioactive iodine therapy. Microbiome-targeted interventions, including probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation, may restore microbial balance, enhance immune regulation, and improve thyroid treatments. This review synthesizes our current understanding of the thyroid-gut axis, indicating that the intestinal microbiota and its metabolites may act directly or indirectly on the thyroid gland, highlighting potential clinical implications and paving the way for therapeutic strategies targeting the intestinal microbiota.}, } @article {pmid41335362, year = {2025}, author = {Jia, Y and Shi, Y and Wang, J and Liu, H and Wang, H and Huang, Y and Liu, Y and Chen, P and Peng, J}, title = {Astragalin attenuates caerulein-induced acute pancreatitis by targeting the NLRP3 signaling pathway and gut microbiota.}, journal = {Bioresources and bioprocessing}, volume = {12}, number = {1}, pages = {139}, pmid = {41335362}, issn = {2197-4365}, support = {82170661//National Natural Science Foundation of China/ ; 2023DK2002//Key Project of Research and Development Plan of Hunan Province/ ; 2025JJ60669//Hunan Provincial Natural Science Foundation of China/ ; 2024M763719//China Postdoctoral Science Foundation/ ; GZC20242045//Postdoctoral Fellowship Program of CPSF/ ; }, abstract = {BACKGROUND: Acute pancreatitis (AP) has caused great concern worldwide due to its serious threat to human health. Astragalin is a bioactive natural flavonoid compound with several pharmacological activities, but it remains unclear about its effect on AP. The objective of this experiment was to explore the mitigating efficacy of astragalin on caerulein-induced AP model and examine the underlying mechanisms.

METHODS: Following the assessment of astragalin's direct effects on pancreatic acinar cells using an in vitro AP model, an in vivo mouse model was established to further validate its efficacy and elucidate the underlying mechanisms. Pancreatic histopathology, amylase, and lipase levels of mice were observed to determine the optimal therapeutic dose of astragalin. The network pharmacology and RNA sequencing technology were used to reveal the possible targets and pathways. Subsequent molecular docking and western blot were conducted to validate the association between astragalin and key target molecules, as well as the NLRP3 signaling pathway. Combined with metagenomics and metabolomics analysis, the astragalin effective gut microbiota-metabolite-gene network was constructed. Moreover, fecal microbiota transplantation experiments were performed to clarify the importance of gut microbiota in astragalin-mediated alleviation of AP.

RESULTS: The results showed that astragalin attenuated caerulein-induced injury in AR42J cells in vitro. Consistent with these findings, in vivo experiments revealed that astragalin treatment significantly improved pancreatic pathological injury, cell apoptosis, and systemic inflammatory response in AP mice, particularly at high doses. The integrated analysis of network pharmacology and transcriptomics revealed that the NLRP3 signaling pathway was a key molecular pathway, which was further validated using western blot. Docking analysis showed that 12 target genes had good docking activity with astragalin. More intriguingly, it was found that astragalin could reverse gut microbiota dysbiosis by restoring microbial diversity, altering bacterial community composition, and modulating key metabolic pathways. Specifically, astragalin-effective correlation networks were constructed with Lachnoclostridium sp. YL32, Roseburia intestinalis, Ruminococcus gnavus, Lachnospiraceae bacterium Choco86, Anaerobutyricum hallii, etc. as the core strains, 22 metabolites, including 5-Methoxytryptophan, D-Serine, L-Tryptophan, L-Methionine, etc. as core metabolites, and NLRP3 pathway-related genes as the main regulatory targets. Furthermore, fecal microbiota transplantation experiments confirmed the involvement of gut microbiota in AP remission.

CONCLUSION: Collectively, these findings identify astragalin as a promising therapeutic agent for AP, targeting both the NLRP3 signaling cascade and gut microbial homeostasis.}, } @article {pmid41334562, year = {2025}, author = {Yurtseven, B and Aydemir, E and Ayaz, F}, title = {The Role of Intestinal Microbiota and Immune System Interactions in Autoimmune Diseases.}, journal = {ImmunoTargets and therapy}, volume = {14}, number = {}, pages = {1347-1372}, pmid = {41334562}, issn = {2253-1556}, abstract = {BACKGROUND: The intricate interplay between the intestinal microbiota and the immune system has emerged as a central theme in understanding autoimmune disease pathogenesis. This review comprehensively explores the role of gut microbiota in shaping immune development, establishing immune tolerance, and contributing to both local and systemic immune regulation.

METHODS: This review synthesizes the modulatory effects of microbial metabolites (eg, short-chain fatty acids and indole derivatives) on regulatory T cells (Tregs) and inflammatory pathways. The concept of "dysbiosis" is examined from functional and compositional perspectives, linking microbial imbalances to autoimmune disorders (IBD, MS, RA, and T1D). Microbiota-targeted therapeutic interventions (probiotics, prebiotics, FMT) are also evaluated.

KEY FINDINGS: The synthesis of the literature confirms that microbial metabolites have a direct impact on Treg differentiation and inflammatory pathways. Dysbiosis, through functional and compositional disruptions, is strongly associated with the pathogenesis of various autoimmune disorders, including Inflammatory Bowel Disease, Multiple Sclerosis, Rheumatoid Arthritis, and Type 1 Diabetes. Therapeutic interventions such as probiotics, prebiotics, and Fecal Microbiota Transplantation show promising potential in restoring microbial and immune homeostasis.

CONCLUSION: This review highlights the role of the gut-immune axis in autoimmune diseases. Despite current challenges, such as individual variability and determining causality, future directions toward precision microbiota and immune modulation are promising. This study provides a robust foundation for researchers and clinicians seeking to understand and therapeutically target the gut-immune axis.}, } @article {pmid41334445, year = {2025}, author = {Jing, M and Jiang, Y}, title = {Microbiome-mediated crosstalk between T2DM and MASLD: a translational review focused on function.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1677175}, pmid = {41334445}, issn = {1664-2392}, mesh = {Humans ; *Diabetes Mellitus, Type 2/microbiology/metabolism/complications ; *Gastrointestinal Microbiome/physiology ; Animals ; *Non-alcoholic Fatty Liver Disease/microbiology/metabolism ; *Fatty Liver/microbiology/metabolism ; }, abstract = {Type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) frequently co-occur and aggravate one another through shared pathways of insulin resistance, low-grade inflammation and disordered lipid handling. Framing their interaction through the gut-liver-pancreas axis, this review synthesizes recent progress with a function-first emphasis, moving beyond taxonomic lists to the microbial outputs most consistently linked to dual metabolic-hepatic endpoints. We summarize how short-chain fatty acids (SCFAs), bile acids (BAs), lipopolysaccharide (LPS) and other microbe-associated molecular patterns, branched-chain amino-acid (BCAA) catabolites, trimethylamine N-oxide (TMAO) and endogenous ethanol reach the liver via portal inflow or the enterohepatic BA cycle and act on epithelial, immune and endocrine interfaces, including the farnesoid X receptor (FXR), G-protein-coupled BA receptor 1 (TGR5) and fibroblast growth factor 19/15 signaling. Mechanistic routes-barrier dysfunction and endotoxaemia; SCFA signaling with effects on enteroendocrine tone and substrate flux; BA remodeling that resets hepatic and pancreatic set-points; and nitrogen/choline and ethanol pathways that promote lipotoxic injury-offer biologically coherent explanations for parallel trajectories of hyperglycemia and steatosis/inflammation. We appraise therapeutic modulation spanning diet and fermentable substrates, live biotherapeutics/postbiotics, BA-targeting drugs, fecal microbiota transplantation and metabolic/bariatric surgery, and we outline clinically actionable biomarker opportunities using function-based panels (fermentative capacity, BA transformation, inflammatory ligands, nitrogen/methyl flux) integrated with host metabolites and genetics for diagnosis, risk stratification and response prediction. By advocating standardized reporting, careful control of diet/medications and composite metabolic-hepatic endpoints in prospective trials, this review provides a practical framework to accelerate translation from association to targeted prevention and therapy that improves glycemic control and MASLD activity in parallel.}, } @article {pmid41332712, year = {2025}, author = {Romo, R and Ricks, E and Ogden, R and Bonnette, PE and Olson, SC and Pearman, K and Call, GB and Chaston, JM}, title = {Whole-body homogenates restore disrupted microbiota composition in a model insect better than feces or no restoration treatment.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.11.17.688872}, pmid = {41332712}, issn = {2692-8205}, abstract = {UNLABELLED: Antibiotic treatment can disrupt gut microbiota and pose challenges and opportunities for the establishment or restoration of healthy microbial communities. Using the fruit fly, Drosophila melanogaster , as an experimental model, we evaluated the impact of two types of microbial transplants-fly feces and whole-body fly homogenates-on host microbiota composition, following, or independent of, tetracycline-induced community disruption. Using 16S rRNA sequencing, we compared community beta diversity between treatments. We show that antibiotic treatment significantly altered microbiota composition and community structure relative to untreated controls. Flies inoculated with whole body homogenates of age-matched, antibiotic-free flies had a more similar microbial community composition to the untreated communities than flies exposed to fly feces or to flies that received no restoration treatment. We also found that the presence of Wolbachia was associated with variation in microbiota composition and specific locomotor functions. These findings show that whole-body homogenates are a superior method for microbiota restoration in Drosophila melanogaster and contribute to a growing body of research on microbial community restoration following disturbance.

IMPORTANCE: Gut microbes play a critical role in animal biology, influencing digestion, immunity, development, and behavior. Disruptions to the gut microbiota-whether from antibiotics, disease, or other interventions-can have lasting effects, and restoring these communities remains an important challenge across biological and biomedical research. Model organisms like fruit flies (Drosophila melanogaster) provide a powerful system for testing microbial restoration methods because their gut communities are relatively simple and easy to manipulate. In this study, we compared various strategies for repopulating the microbiota of flies following antibiotic treatment. We found that flies fed whole-body homogenates of untreated flies more closely resembled the microbiota of untreated flies than flies exposed to fly feces or to flies that received no restoration treatment. These findings contribute to broader efforts to understand and develop methods for microbiota recovery following disturbance and suggest applications across animal systems.}, } @article {pmid41332430, year = {2025}, author = {Li, L and Zhou, N and Wang, Z and Wang, T and Wang, Y and Qiao, F and Du, ZY and Zhang, ML}, title = {Intestinal microbiota contributes to the heterogeneity of fat deposition by promoting mitochondrial fatty acid β-oxidation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2593076}, doi = {10.1080/19490976.2025.2593076}, pmid = {41332430}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; *Fatty Acids/metabolism ; Carnitine/biosynthesis/metabolism ; Oxidation-Reduction ; *Mitochondria/metabolism ; Zebrafish ; Lipid Metabolism ; *Bacteria/classification/genetics/metabolism/isolation & purification ; Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S/genetics ; Male ; Humans ; Feces/microbiology ; }, abstract = {The gut microbiota plays a crucial role in lipid metabolism in both humans and animals. However, the specific contributions of gut microbiota and their associated metabolites to fat deposition, as well as the underlying mechanisms, remain largely unexplored. In this study, we demonstrated that the intestinal microbiota mediated the heterogeneity of mesenteric fat index (MFI), as evidenced by fecal microbiota transplantation (FMT) experiments. Notably, analysis of the 16S rRNA gene amplicon sequencing of 44 samples revealed a significantly higher abundance of Cetobacterium somerae in the Low MFI group, with a positive correlation to reduced MFI. Serum metabolomics analysis confirmed that L-Carnitine emerged as the most differentially abundant metabolite in the Low MFI group and exhibited a strong positive correlation with C. somerae abundance. Metagenomic analysis showed that microbial genes related to L-Carnitine biosynthesis were significantly enriched in the Low MFI group. Further, C. somerae was isolated and cultured, and its subsequent monocolonization in germ-free zebrafish and tilapia demonstrated its lipid-lowering effects by enhancing mitochondrial fatty acid β-oxidation. Whole genome sequencing demonstrated C. somerae could encode the [EC:1.2.1.3] gene, which promotes the production of 4-trimethylammoniobutanoate, a precursor of L-Carnitine, thereby enhancing L-Carnitine biosynthesis by the host and gut microbiota, leading to the reduced fat deposition in Nile tilapia. In conclusion, C. somerae, a core gut microbe with high abundance in aquatic teleost intestines, plays an important role in host lipid metabolism. This study advances our understanding of how core gut microbes shape host phenotypes and provides novel insights into manipulating core gut colonizers to reduce fat deposition.}, } @article {pmid41331614, year = {2025}, author = {Yu, H and Zhang, Y and Yang, D and Luo, H and Zhou, Y}, title = {Advances in capsule-based fecal microbiota transplantation: clinical applications and innovations.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {1370}, pmid = {41331614}, issn = {1479-5876}, support = {LTGD23C040008//Zhejiang Provincial Natural Science Foundation of China/ ; LBY23H200006//Natural Science Foundation of Hebei Province/ ; 2023020612//Ningbo Top Medical and Health Research Program/ ; 2023-S013//Ningbo Public Welfare Project/ ; 06-445-1211//Talent Initiation Program of the High-Level University Development Project at Guangzhou Medical University/ ; }, } @article {pmid40389632, year = {2025}, author = {Doyle, B and Reynolds, GZM and Dvorak, M and Maghini, DG and Natarajan, A and Bhatt, AS}, title = {Absolute quantification of prokaryotes in the microbiome by 16S rRNA qPCR or ddPCR.}, journal = {Nature protocols}, volume = {20}, number = {12}, pages = {3441-3476}, pmid = {40389632}, issn = {1750-2799}, support = {R01 AI148623/AI/NIAID NIH HHS/United States ; R01 AI143757/AI/NIAID NIH HHS/United States ; T32GM007276//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; D43TW010540//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01 AI148623/AI/NIAID NIH HHS/United States ; R01 AI143757/AI/NIAID NIH HHS/United States ; }, mesh = {*RNA, Ribosomal, 16S/genetics ; Humans ; Feces/microbiology ; *Gastrointestinal Microbiome/genetics ; *Polymerase Chain Reaction/methods ; *Real-Time Polymerase Chain Reaction/methods ; *Microbiota/genetics ; *Bacteria/genetics ; *Prokaryotic Cells ; }, abstract = {Measurements of prokaryotic absolute abundance can provide important insights into human gut microbiome biology and correct misinterpretations of relative abundance data. Despite the existence of several relatively well-established methods for making these measurements, most microbiome studies do not report absolute abundance. To enable researchers equipped with standard molecular biology capabilities to incorporate absolute quantification into their microbiome studies, we present a detailed, step-by-step protocol for rigorous and reproducible quantification of prokaryotic concentration in stool samples. We include methods for measuring stool sample moisture content, quantifying the concentration of the 16S rRNA prokaryotic marker gene by qPCR or digital droplet PCR (ddPCR) and analyzing the resulting data. We also highlight and provide strategies to overcome common pitfalls of the quantification method, such as 16S rRNA gene contamination. The final output of this approach is 16S rRNA copies per wet or dry gram of stool. In cases where samples have matched metagenomic sequencing information, data can be converted into absolute concentration of prokaryotes and taxon-specific absolute concentrations. To enable researchers to choose the appropriate method for their specific applications, we also compare and contrast our qPCR and ddPCR methods. In 4 days, ~80 samples can be taken from frozen stool to absolute concentration by using qPCR or ddPCR without the need for resequencing. Overall, this protocol provides a sensitive and straightforward way to measure the absolute concentration of prokaryotes in human gut microbiome samples stored with or without preservative.}, } @article {pmid41329233, year = {2025}, author = {Guarino, M and Di Ciaula, A and Portincasa, P and De Giorgio, R}, title = {Narrative review on microbiota and sepsis: the host's betrayal?.}, journal = {Internal and emergency medicine}, volume = {}, number = {}, pages = {}, pmid = {41329233}, issn = {1970-9366}, abstract = {Sepsis remains a leading cause of morbidity and mortality worldwide. Increasing evidence suggests that the gut microbiota, long considered a "less relevant" to human body health, it plays a crucial role in the pathophysiology of sepsis. Disruption of the host-microbe balance contributes to impaired barrier integrity, microbial translocation, and dysregulated immune responses. This perspective raises the possibility that dysbiosis is not merely a consequence of critical illness, rather an active driver of septic progression. This narrative review explores the relationship between sepsis and gut microbiome. PubMed, Scopus, and EMBASE were searched from inception to September 2025. Recent studies have highlighted the triangular interplay between the intestinal barrier, gut microbiota, and immune system. Altered microbial composition and increased permeability foster systemic inflammation and immune dysfunction. Biomarkers such as diamine oxidase and intestinal fatty acid-binding protein are emerging as promising indicators of gut injury. Experimental therapies (i.e., faecal microbiota transplantation, targeted probiotics, prebiotics, postbiotics, and personalized antibiotic regimens guided by microbial profiling) provide potential to modulate host-microbe interactions. Integration of microbiome analysis with multi-omics and advanced bioinformatics may enable stratification of septic patients by microbial signatures, paving the way for precision medicine approaches. Modulation of gut microbiota represents a novel therapeutic frontier in sepsis. Conceptualizing sepsis as a disease of disrupted host-microbe symbiosis may unravel new diagnostic and therapeutic strategies. Future research should aim at prioritizing high-quality trials, innovative designs, and equitable implementation to target microbiota to improve survival and recovery in patients with sepsis.}, } @article {pmid41329062, year = {2025}, author = {Yun, Y and Xu, GQ and Jiang, XJ and Ren, XY and Lu, MF and Chen, JW and Zhang, SX}, title = {Gut Microbiota in Rheumatoid Arthritis: Unraveling Pathogenic Mechanisms and Therapeutic Opportunities.}, journal = {Comprehensive Physiology}, volume = {15}, number = {6}, pages = {e70078}, doi = {10.1002/cph4.70078}, pmid = {41329062}, issn = {2040-4603}, support = {202203021221269//Natural Science Foundation of Shanxi Province/ ; 82001740//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Arthritis, Rheumatoid/microbiology/immunology/therapy ; *Gastrointestinal Microbiome/physiology/immunology ; Animals ; Dysbiosis/immunology ; Antirheumatic Agents/therapeutic use ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Rheumatoid arthritis (RA), a chronic autoimmune disorder driven by genetic-environmental interplay, manifests as progressive synovitis and irreversible joint damage. Despite mechanistic advances in disease-modifying antirheumatic drugs (DMARDs) and biologics, upstream mucosal triggers of autoimmunity remain elusive. Mounting evidence implicates gut microbiota dysbiosis as a pivotal environmental factor in RA pathogenesis through multifaceted mechanisms: (1) compromising intestinal barrier integrity, (2) facilitating molecular mimicry via cross-reactive microbial antigens, (3) skewing mucosal immunity toward pro-inflammatory T helper 17 (Th17)/T follicular helper (Tfh) cell responses, and (4) generating bioactive metabolites with dual roles in regulating osteoclastogenesis and synovial inflammation. This review synthesizes recent advances in gut microbiome profiling, mechanistic studies, and preclinical models, elucidating microbial-host crosstalk in autoimmune cascades. Furthermore, we critically evaluate microbiota-directed strategies, including dietary and probiotic modulation, microbiome-informed optimization of conventional DMARDs and biologics, and investigational approaches like fecal microbiota transplantation and Chinese herbal medicine, that may offer promising adjunctive approaches to complement conventional RA management.}, } @article {pmid41327482, year = {2025}, author = {Wu, J and Guo, P and Wang, M and Men, Z and Lin, Z and Wang, J and Zhang, S and Zhou, M and Zhao, J and Liu, H and Ma, X}, title = {Butyrate-producing commensal bacteria confers colon immune defense function via enhancing H4K31 Crotonylation of macrophages.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02234-3}, pmid = {41327482}, issn = {2049-2618}, support = {32302758//National Natural Science Foundation of China/ ; 32402706//National Natural Science Foundation of China/ ; 31829004//National Natural Science Foundation of China/ ; 2022M723422//China Postdoctoral Science Foundation/ ; GZB20230848//Postdoctoral Fellowship Program of CPSF/ ; 2022YFD1300404//National Key Research and Development Program of China/ ; 1041-00109019//2115 Talent Development Program of China Agricultural University/ ; }, abstract = {BACKGROUND: The mechanisms by which microbiota from disease-resistant populations or animals improve intestinal immune defense remain incompletely elucidated. Tibetan pig, a renowned disease-resistant breed, serve as a valuable research subject for the health of humans and economic animals.

RESULTS: In this study, fecal microbiota transplantation from Tibetan piglets into mice conferred enhanced resistance to C. rodentium DBS100. Further microbiota profiling and metabolomics analysis showed this protection may be partly ascribed to C. butyricum SLZX19-05 in recipients' colon. Administration of C. butyricum SLZX19-05 to germ-free mice resulted in the significantly increased lysozyme expression within colonic macrophages, subsequently bolstering the resistance to C. rodentium infection. In mice and piglets, this C. butyricum similarly elevated the lysozyme level in colon and decreased diarrhea incidence. Conversely, lyz1-knockout heightened mice's susceptibility to C. rodentium, highlighting lysozyme's critical role in immune defense. Mechanistically, this study systematically revealed that C. butyricum enhanced lysozyme expression by inhibiting mTORC1-HDAC3/8 pathway, leading to the increased H4K31 Crotonylation (H4K31Cr) and openness of an upstream region of lyz1 promoter via butyrate in macrophages. Additionally, H4K31-mutant mice showed the leukopenia, further validating the significance of H4K31Cr in immune regulation.

CONCLUSIONS: Collectively, mTORC1-HDAC3/8-H4K31Cr pathway is a key mechanism by which butyrate-producing commensal bacteria enhance immune defense in gut. This discovery provides a novel foundation for the screening and application of the next generation of butyrate-producing probiotics. Video Abstract.}, } @article {pmid41323559, year = {2025}, author = {Tian, S and Liu, Y and Yang, H and Chen, K and Li, J and Chen, L and Wu, T and Zhang, L}, title = {Multi-Omics Reveal That Gut Microbial Dysbiosis Drives Lipid Metabolic Disturbances and Inflammation in Gestational Hypertension.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {16411-16425}, pmid = {41323559}, issn = {1178-7031}, abstract = {BACKGROUND: Gestational hypertension (GH) is a common complication during pregnancy that poses serious health risks to both mother and fetus. Recent studies have underscored the potential roles of gut microbiota, lipid metabolism, and inflammatory response in GH's development and progression. However, the exact mechanisms behind these interactions are still unclear. Understanding how gut microbial composition impacts lipid metabolism and inflammation could offer valuable insights into GH's pathogenesis and may lead to new prevention and treatment methods.

METHODS: In this study, we conducted ELISA experiments to detect inflammatory cytokines in the serum of GH patients. Additionally, we performed 16S-rDNA sequencing analysis on the feces of GH patients to investigate the characteristics of their intestinal microbial communities; GH mouse model was constructed to assess the impact of intestinal flora on offspring. Furthermore, we utilized non-targeted lipid metabolomics to analyze lipid metabolic characteristics in the feces and blood of GH patients and established connections between the microbiome and lipidome through correlation analysis.

RESULTS: ELISA tests suggested the levels of inflammatory factors in the serum of GH patients increased significantly, including IL-6, IL-8, IL-17, IL-18, and IFN-γ. In comparison to the normal group, the GH group exhibited a marked reduction in microbial richness. LEfSe analysis found 16 distinct bacterial communities between the two groups. Animal models suggested that fecal microbiota transplantation from the GH group's intestinal flora resulted in a significant decrease in the birth weight of the offspring. Furthermore, comparative analysis of fecal and blood metabolic profiles suggested that TG (54:5/FA22:5) may serve as a key metabolite. Correlation analysis demonstrated that f-Oxalobacteraceae exhibited a significant negative correlation with the inflammatory factor IL-17 and TG (54:5/FA22:5) in the blood, while showing a significant positive correlation with g-Oxalobacter and s-formigenes.

CONCLUSION: Our results establish a connection between gut microbiota, lipid metabolism, and the inflammatory response in patients with GH. This understanding may enhance our comprehension of the underlying mechanisms associated with GH.}, } @article {pmid41322104, year = {2025}, author = {Khawaja, TW and Zhao, L and Siddiq, R and Ahmad, MU and Burns, CP and Parker, JM and Wakefield, MR and Fang, Y}, title = {Unmasking the microbiome: the hidden role of gut bacteria in the pathogenesis of colorectal cancer and its prevention strategies.}, journal = {Exploration of targeted anti-tumor therapy}, volume = {6}, number = {}, pages = {1002351}, pmid = {41322104}, issn = {2692-3114}, abstract = {Colorectal cancer (CRC) is a significant global health problem, ranking as the third most common cancer and the second leading cause of cancer deaths in the world. The highest incidence of CRC is found in developed regions, thus underlining its characterization as a Western disease. Major risk factors for CRC include an unhealthy diet, lack of physical exercise, and cigarette smoking. The gut microbiota refers to the complex community of microorganisms inhabiting the digestive tract and plays a crucial role in the maintenance of host health and modulation of immune responses. Gut dysbiosis can be caused by poor diet and alcohol consumption, increasing CRC risk. Specific bacteria, such as Fusobacterium nucleatum and Escherichia coli, may have a close relationship with CRC development, while the beneficial bacteria are frequently depleted in CRC patients. This paper will discuss the mechanisms of colorectal carcinogenesis, focusing on the effects of bacterial genotoxins, immune evasion, inflammation, and diet. Additionally, it reviews preventative strategies including short-chain fatty acids (SCFAs), prebiotics, probiotics, synbiotic supplements, and the method of fecal microbiota transplantation (FMT), showing their potential to improve overall gut health and reduce the risk for CRC. Understanding these mechanisms and implementing specific preventative strategies could significantly enhance clinical interventions and reduce the global burden of CRC.}, } @article {pmid41321823, year = {2025}, author = {Zheng, Z and Xie, D and Han, Y and Li, G and Wang, S and Zhang, X and Huang, T and Xu, W and Wu, G}, title = {Deciphering the urinary microbiome and urological cancers: from correlation to mechanisms and treatment.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1699308}, pmid = {41321823}, issn = {1664-302X}, abstract = {Given that the sterility of urine and the urinary tract has been questioned by research, urinary microbiome dysbiosis has been recognized as one of the potential cancer-promoting factors. The composition of the urinary microbial community in healthy individuals has a relatively high similarity at the phylum level, with factors like age and gender influencing the expression and distribution. In contrast, the urinary microbiome of patients with urologic cancers shows significant variability and diversity depending on the type of cancer. Most of the early studies focused on the distribution, aggregation, and expression of microbiota in urologic cancers, warranting advanced studies on the causal relationship between microbes and urologic cancers. Bladder and prostate cancer tumorigenesis and progression can be influenced by microbes through chronic inflammatory or immunomodulatory pathways making them cancer models strongly associated with the urinary microbiome. Here, we summarize the expression characteristics of the microbiomes associated with these cancers and analyze the pathophysiological mechanisms and signaling pathways of the microbiome in the tumor promotion or suppression. By examining the role played by the urinary microbiome in the pathogenesis of urologic cancers, we assess the potential of specific microbial groups as biomarkers for diagnosis and surveillance. Additionally, involving the microbiome or using adjunctive participation in tumor therapy is becoming an emerging cancer treatment option. Improving urinary microbial homeostasis in urinary cancers by direct treatment with microbial products, microbial co-immunotherapy, probiotic-assisted therapy, and fecal microbial transplantation may broaden the scope of therapy and enhance the efficacy of conventional medicines.}, } @article {pmid41321593, year = {2025}, author = {Zhao, N and Wang, K and Jiang, Y and Huang, R}, title = {Clinical Treatment and Clinical Application Research Progress of Psoriasis and Intestinal Microbiota Dysbiosis.}, journal = {Clinical, cosmetic and investigational dermatology}, volume = {18}, number = {}, pages = {3155-3164}, pmid = {41321593}, issn = {1178-7015}, abstract = {Psoriasis is a prevalent chronic inflammatory dermatosis. Recent evidence indicates a significant association between gut microbiota dysbiosis and its pathogenesis, potentially mediated through immunoinflammatory modulation and skin barrier integrity. This article systematically reviews the mechanisms linking gut microbiota to psoriasis, with emphasis on clinical treatment strategies targeting microbiota modulation-including probiotics, fecal microbiota transplantation (FMT), dietary interventions, and antibiotic therapies. However, current research exhibits notable limitations: most evidence derives from small-scale studies or animal models, lacking validation via large-scale clinical trials; microbiota-targeted interventions are poorly standardized, and the impact of individual variability on therapeutic outcomes remains unclear; the long-term safety of antibiotics and FMT requires further assessment. While summarizing existing advances, this review presents an evaluative overview to highlight research gaps and proposes future directions, such as integrated multi-omics studies, development of standardized therapeutic protocols, and exploration of personalized microbiota-based strategies, to innovate clinical management of psoriasis.}, } @article {pmid41321404, year = {2025}, author = {Shalbaf, N and Sadeghi, S and Homaee, S and Saberian, F}, title = {Probiotics, prebiotics, synbiotics, and FMT for glycemic control: A systematic review of clinical efficacy and mechanistic readouts in type 2 diabetes and related dysglycemia.}, journal = {Metabolism open}, volume = {28}, number = {}, pages = {100419}, pmid = {41321404}, issn = {2589-9368}, abstract = {OBJECTIVE: To systematically evaluate the clinical efficacy of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) on glycemic control in adults with type 2 diabetes (T2D) and related dysglycemia, and to synthesize associated mechanistic changes in microbial metabolites and composition.

METHODS: A systematic review was conducted following PRISMA 2020 guidelines. PubMed/MEDLINE, Scopus, and Web of Science were searched from inception through August 2025 for randomized controlled trials (RCTs) in adults with T2D, prediabetes, or metabolic syndrome. Interventions included probiotics, prebiotics, synbiotics, or FMT compared to control. Outcomes were glycemic indices (e.g., HbA1c, HOMA-IR) and mechanistic biomarkers (e.g., SCFAs, bile acids). Risk of bias was assessed using the Cochrane RoB 2 tool. A narrative synthesis was performed.

RESULTS: Thirty studies were included. Multi-strain probiotics, prebiotics, and synbiotics yielded modest but significant improvements in HbA1c (≈-0.2 to -0.4 %), fasting glucose, and HOMA-IR, particularly with durations ≥12 weeks. These benefits were linked to mechanistic shifts, including increased circulating butyrate and ursodeoxycholate, enrichment of SCFA-producing taxa, and reduced endotoxemia. Efficacy was moderated by concomitant medications: metformin use was synergistic, while sulfonylureas attenuated effects. FMT consistently improved clamp-measured insulin sensitivity in insulin-resistant phenotypes, but its effects on HbA1c were less consistent and donor-dependent.

CONCLUSION: Microbiome-targeted interventions, especially multi-strain probiotics and substrate-matched synbiotics, are effective adjuncts for improving glycemic control, with effects mediated through microbial metabolite production. FMT primarily modulates insulin sensitivity. Clinical outcomes are context-dependent, influenced by intervention design, duration, and pharmacomicrobiomic interactions.}, } @article {pmid41320323, year = {2025}, author = {Wu, X and Wu, M and Li, H and Yang, Y and Shen, H and Huang, S and Pan, Y and Tao, L and Guo, S and Chen, J and Wu, Y and Zhong, X and Li, S and Liu, B and Zhang, W and Zhu, R and Fan, L and Wang, W}, title = {Intraperitoneal translocation of gut microbiota induces NETosis and promotes endometriosis.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-336185}, pmid = {41320323}, issn = {1468-3288}, abstract = {BACKGROUND: Endometriosis is a debilitating gynaecological disorder with an elusive pathogenesis. While gut microbiota dysbiosis has been implicated, the causal role of gut-peritoneum microbial translocation and the specific mechanisms driving disease progression remain elusive. Notably, the role of peritoneal neutrophils and neutrophil extracellular traps (NETs) in the development of endometriosis remains unknown.

OBJECTIVE: This study aims to delineate the pathogenic pathway linking gut microbiota to peritoneal neutrophil activation and the development of endometriosis.

DESIGN: We combined single-cell RNA sequencing of clinical peritoneal fluid immune cells with functional validation in heterologous and homologous mice models. We further adopted microbial source-tracking analysis of patient cohorts and interventional strategies, including faecal microbiota transplantation (FMT) and administration of green fluorescent protein (GFP)-tagged Pseudomonas aeruginosa.

RESULTS: We identified a unique membrane metalloendopeptidase (MME) positive neutrophil subset (Neu_MME) that is expanded in endometriosis and primed for NETs formation (NETosis). These Neu_MME released NETs in response to bacterial lipopolysaccharides (LPS), which directly captured endometrial cells and enhanced their proliferation and migration, driving lesion development. Accordingly, inhibiting NETosis or degrading NETs significantly suppressed endometriosis in mice. Furthermore, FMT from patients with endometriosis to mice disrupted the intestinal barrier, promoting the translocation of gut microbiota, particularly Pseudomonas, into the peritoneal cavity and the lesions. This translocated Pseudomonas was identified as a key driver of LPS-induced NETosis and disease progression.

CONCLUSION: Our findings define a gut-peritoneum axis in endometriosis, where gut-derived Pseudomonas triggers NETosis in peritoneal Neu_MME to promote disease, suggesting that targeting this bacterium or NETosis represents a viable therapeutic strategy.}, } @article {pmid41318842, year = {2025}, author = {Malard, F and Holler, E and Peric, Z and Mehra, V and Duarte, R and Sanz, J and Spyridonidis, A and Poiré, X and Morsink, L and Clausen, J and Bazarbachi, A and Nagler, A and Ciceri, F and Ruggeri, A and Mohty, M}, title = {Microbiotherapy and fecal microbiota transplantation in hematology-oncology: a European clinical perspective to navigate the evolving regulatory framework and the emergence of a new therapeutic class.}, journal = {Bone marrow transplantation}, volume = {}, number = {}, pages = {}, pmid = {41318842}, issn = {1476-5365}, } @article {pmid41317880, year = {2025}, author = {Colica, C and Vecchio, I}, title = {Gut microbiota: origin or panacea for all ills? Part 1: Immune and Metabolic Diseases, Nutrition, and Microbiota-Based Interventions.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {108213}, doi = {10.1016/j.micpath.2025.108213}, pmid = {41317880}, issn = {1096-1208}, abstract = {Chronic non-communicable diseases (CNCDs), including obesity, type 2 diabetes, allergies, and autoimmune conditions, represent a significant global health burden, exacerbated by the interplay between genetic and environmental factors, such as diet, and gut microbiota. The gut microbiota is a complex and dynamic microbial community that influences host immune and metabolic systems from birth through adulthood. Dysbiosis - an imbalance in gut microbial composition - has been implicated in the development of low-grade inflammation, insulin resistance, and metabolic and immune disorders. This paper reviews the critical role of gut microbiota in CNCDs, emphasizing its interactions with the immune system, including regulatory T cell induction and the Th1/Th2 balance. Furthermore, it explores the influence of birth mode, diet, and xenobiotics on microbiota composition and function. Finally, the study highlights the potential of microbiota-targeted interventions - such as prebiotics, probiotics, synbiotics, and fecal microbiota transplantation - to modulate gut ecology and mitigate disease risk. From literature revision emerges the need for integrative approaches in disease prevention and management, considering microbiota as a key player in health and disease.}, } @article {pmid41317866, year = {2025}, author = {Davido, B and Corcione, S}, title = {Re: 'Faecal microbiota transplantation for urinary tract infections' by Gardlik et al.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2025.11.028}, pmid = {41317866}, issn = {1469-0691}, } @article {pmid41317323, year = {2025}, author = {Phelps, CM and Rodriguez J, DM and Meisel, M}, title = {Protocol for preparing murine fecal microbiota transplant and fecal microbiota metabolites for in vivo and in vitro use.}, journal = {STAR protocols}, volume = {6}, number = {4}, pages = {104240}, doi = {10.1016/j.xpro.2025.104240}, pmid = {41317323}, issn = {2666-1667}, abstract = {Accumulating evidence demonstrates that microbiota-derived metabolites can modulate host immune responses and influence complex pathologies. Despite their therapeutic potential, the isolation of fecal microbial metabolites and their scalable ex vivo production remain challenging. Here, we present a protocol for preparing murine fecal microbiota transplant (FMT) and fecal microbiota metabolites for in vivo and in vitro use. We describe steps for collecting and preparing donor feces, isolating fecal microbial metabolites, and producing fecal microbial metabolites ex vivo with a broth expansion culture. For complete details on the use and execution of this protocol, please refer to Phelps et al.[1].}, } @article {pmid41317234, year = {2025}, author = {Hetta, HF and Alanazi, FE and Alqifari, SF and Ali, MAS and Albalwi, MA and Albalawi, AA and Ramadan, YN}, title = {The Gut-Brain Axis in Autism: Inflammatory Mechanisms, Molecular Insights, and Emerging Microbiome-Based Therapies.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {211}, pmid = {41317234}, issn = {1559-1182}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Brain/metabolism/pathology ; Animals ; *Inflammation/microbiology ; Fecal Microbiota Transplantation ; *Autism Spectrum Disorder/therapy/microbiology ; Dysbiosis ; Probiotics/therapeutic use ; *Brain-Gut Axis ; *Autistic Disorder/therapy/microbiology ; }, abstract = {Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with multifactorial etiology, including genetic, environmental, and microbial influences. Recent studies have highlighted the gut-brain axis as a crucial mediator in ASD pathophysiology, linking alterations in gut microbiota to neurodevelopmental and behavioral abnormalities. Individuals with ASD frequently exhibit dysbiosis, characterized by an imbalance in gut microbial composition, reduced microbial diversity, and increased intestinal permeability. These changes contribute to systemic inflammation, altered neurotransmitter synthesis, and metabolic dysfunctions, ultimately impacting brain function. Emerging therapeutic approaches targeting gut microbiome, such as probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation (FMT), have shown potential in alleviating both gastrointestinal (GI) and ASD-related symptoms. This review explores the latest evidence on microbiome alterations in ASD, the mechanisms by which gut dysbiosis influences neurodevelopment, and the therapeutic potential of microbiome-based interventions. Understanding these connections may open new avenues for targeted treatments in ASD management.}, } @article {pmid41316345, year = {2025}, author = {Li, M and Zhang, X and Lu, J and Xiang, J and Wu, J and Zheng, M and Yang, S and He, L and Shao, X}, title = {Isoliquiritigenin ameliorates Parkinson's disease via gut microbiota remodeling: potential mediating role of Parabacteroides distasonis.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {1363}, pmid = {41316345}, issn = {1479-5876}, support = {2024ZF031//Zhejiang Traditional Chinese Medicine Administration/ ; 2024ZF165//Zhejiang Traditional Chinese Medicine Administration/ ; 2023RC287//Medical Science and Technology Project of Zhejiang Province/ ; 2023KY345//Medical Science and Technology Project of Zhejiang Province/ ; 2022KY001//Shaoxing Bureau of Science and Technology/ ; 2023SKY015//Shaoxing Bureau of Science and Technology/ ; 2023A14011//Shaoxing Bureau of Science and Technology/ ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Chalcones/pharmacology/therapeutic use ; *Parkinson Disease/drug therapy/microbiology ; Fecal Microbiota Transplantation ; *Bacteroidetes/drug effects/physiology ; Male ; Mice, Inbred C57BL ; Dopaminergic Neurons/drug effects/pathology/metabolism ; Mice ; Neuroprotective Agents/pharmacology/therapeutic use ; Behavior, Animal/drug effects ; }, abstract = {BACKGROUND: Increasing evidence implicates the gut microbiota in the pathogenesis of Parkinson's disease (PD). Microbiota-targeted interventions may be a promising therapeutic approach. Isoliquiritigenin (ISL), a natural flavonoid and primary pharmacological constituent of licorice (Glycyrrhiza), has neuroprotective effects. Whether this neuroprotection involves modulation of the gut microbiota is unclear.

PURPOSE: The study assessed whether ISL mediates neuroprotective in PD by modulating the gut microbiota, and investigated the functional involvement of Parabacteroides distasonis (P. distasonis) in this process.

METHODS: Mice with chemically-induced PD were first treated with ISL via oral gavage to assess its therapeutic effects. To investigate the microbiota-mediated mechanisms, fecal microbiota transplantation (FMT) from ISL-treated donors and direct gavage of live or heat-killed P. distasonis were performed in separate cohorts. Behavioral performance, dopaminergic neuron integrity, intestinal barrier function, neuroinflammation, gut microbiota composition, and serum metabolomic profiles were systematically evaluated.

RESULTS: ISL and FMT significantly improved motor deficits and protected dopaminergic neurons in the substantia nigra. ISL treatment compositionally reshaped the gut microbiota by suppressing pro-inflammatory genera and enriching beneficial bacteria, such as Parabacteroides. Oral administration of live P. distasonis fully reproduced the neuroprotective effects of ISL, including improved motor function, reduced neuroinflammation, restoration of blood-brain barrier integrity, and attenuation of intestinal mucosal damage. Heat-killed P. distasonis had no significant effects. Metabolomic analysis revealed that ISL and live P. distasonis jointly regulate neuroprotective pathways and metabolites related to the gut-brain axis.

CONCLUSION: ISL alleviates PD-related pathology partly through gut microbiota remodeling, with P. distasonis as a potential mediator.}, } @article {pmid41316344, year = {2025}, author = {Ren, Y and Liang, J and Xie, J and Hu, W and Lai, M and Li, X and Zhang, J and Zheng, Y and Wu, Q and Zhou, H and Yin, J}, title = {Sodium oligomannate modulates the gut-brain axis to alleviate post-stroke cognitive impairment by restoring butyrate metabolism.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02257-w}, pmid = {41316344}, issn = {2049-2618}, support = {82171317//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Post-stroke cognitive impairment (PSCI) affects up to half of stroke survivors, severely impacting their quality of life. Despite its prevalence, the pathogenesis of PSCI remains poorly understood, and no specific pharmacological treatments are currently available.

RESULTS: In PSCI patients, fecal butyrate levels were significantly reduced and correlated with cognitive scores. A machine learning model incorporating butyrate levels, butyrate-producing bacteria, and clinical factors (education, smoking, body mass index [BMI], hemoglobin) demonstrates strong predictive performance (area under the curve [AUC]: 0.793 internal, 0.795 external validation). In a transient middle cerebral artery occlusion (tMCAO) mouse model, both sexes displayed sustained gut microbiota dysbiosis featuring decreased butyrate-producing bacteria and fecal butyrate concentrations, concomitant with hippocampal neuronal loss and microglial activation. Sodium oligomannate (GV-971) treatment ameliorated cognitive impairment in a sex-independent manner and restored butyrate-producing gut bacteria. Metagenomic analysis revealed that GV-971 enhanced butyrate production by promoting D-glucuronate degradation and upregulating butyrate synthesis pathway abundance. The elevated butyrate promoted acetylation of histone H3 at lysines 9 and 14 (Ac-H3K9/K14) in colonic and hippocampal neurons, stimulating neurogenesis, while concurrently reducing gut-derived lipopolysaccharide (LPS) and microglial inflammation. Antibiotic treatment and fecal microbiota transplantation established the essential role of butyrate-producing microbiota in mediating GV-971's effects. In vitro, butyrate supplementation significantly inhibited HDAC3 enzymatic activity in HT22 cells and alleviated LPS-induced inflammatory responses in BV2 microglia.

CONCLUSIONS: Intestinal butyrate levels are significantly associated with PSCI. GV-971 mitigates post-stroke cognitive decline by modulating the gut microbiota to increase butyrate production, highlighting its potential as a therapeutic agent for PSCI.}, } @article {pmid41313610, year = {2025}, author = {Butcher, J and Gosse, JT and Gobin, J and Ravel-Chapuis, A and Jasmin, BJ and Stintzi, A}, title = {Dystrophic Skeletal Muscle Phenotypes Can Be Horizontally Transferred via Fecal Microbiome Transplantations.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {39}, number = {23}, pages = {e71281}, pmid = {41313610}, issn = {1530-6860}, support = {OGI-149//Genome Canada (GC)/ ; Project 13440//MDECEC | Ontario Ministry of Research and Innovation (MRI)/ ; //Defeat Duchenne Canada (Vaincre Duchenne Canada)/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Mice ; Mice, Inbred mdx ; *Muscle, Skeletal/pathology/microbiology/metabolism ; *Muscular Dystrophy, Duchenne/therapy/microbiology/pathology ; Mice, Inbred C57BL ; Phenotype ; *Muscular Dystrophy, Animal/microbiology/therapy ; *Gastrointestinal Microbiome ; Male ; }, abstract = {Duchenne muscular dystrophy (DMD) has no cure and accounts for > 80% of muscular dystrophy cases around the world. DMD patients experience severe muscle degeneration that continues until death and also suffer from gastrointestinal complications that undoubtedly impact their microbiotas. It is unclear whether dystrophic microbiotas simply reflect the disease or whether microbes are directly involved in muscle phenotypes. Here, we sought to determine the microbiota's causal role in promoting dystrophic muscles by performing intra/inter-genotype fecal microbiota transplantations (FMT) between wildtype and mdx mice; assessing FMT's impact on muscles and microbiotas over 9 weeks. Transplanting mdx microbiotas into wildtype mice induced an mdx-like muscle phenotype while the inverse improved muscle features. We identified several taxa differentially abundant between wildtype mice receiving either wildtype or mdx FMT, highlighting their potential role in muscle health. Our results highlight the active role microbes have in impacting muscle health through both beneficial and detrimental mechanisms. Accordingly, microbes represent unexploited therapeutic targets for improving health outcomes in muscular dystrophies.}, } @article {pmid41313537, year = {2025}, author = {Vishwakarma, RK and Gautam, P and Sahu, M and Nath, G and Yadav, BS}, title = {Gut Microbiome in Obesity: A Narrative Review of Mechanisms, Interventions, and Future Directions.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {41313537}, issn = {1867-1314}, abstract = {Obesity has reached pandemic levels worldwide and is increasingly recognized as a multifactorial condition beyond excess caloric intake and sedentary lifestyle. Accumulating evidence emphasizes that the gut microbiota (GM), primarily composed of Firmicutes and Bacteroidetes, plays a crucial role in regulating energy balance, immune response, and host metabolism. Gut dysbiosis, characterized by reduced microbial diversity and altered phylum-level composition and shifts toward commonly observed higher Firmicutes-to-Bacteroidetes ratios (although this finding is inconsistent across studies), contributes to enhanced energy harvest, systemic inflammation, and metabolic dysfunction. Key mechanisms involve GM production of short-chain fatty acids (SCFAs) and modulation of hormonal signals, including leptin, ghrelin, insulin, GLP-1, and PYY, alongside interactions via the gut-brain axis. These pathways link microbial composition to appetite regulation, fat storage, and energy balance. Emerging microbiome-targeted therapies, such as probiotics, prebiotics, dietary modulation (e.g., fiber-rich diets), fecal microbiota transplantation, and bacteriophage therapy, show promise in restoring GM balance, promoting weight loss, and improving metabolic health, though results vary and require further validation. Despite advances in metagenomics and metabolomics, gaps persist in establishing causality and long-term efficacy. The integration of GM data with host genetics, diet, and environmental factors through systems biology has the potential to facilitate personalized management of obesity. This review synthesizes the GM's role in obesity pathogenesis and hormonal regulation, highlighting therapeutic potential and research directions for microbiota-based prevention and treatment.}, } @article {pmid41312988, year = {2025}, author = {Schluter, J and Jogia, W and Matheis, F and Ebina, W and Sullivan, AP and Gordon, K and Cruz, EFdl and Victory-Hays, ME and Heinly, MJ and Diefenbach, CS and Kang, UJ and Peled, JU and Foster, KR and Levitt, A and McLaughlin, E}, title = {A retrospectively registered pilot randomized controlled trial of postbiotic administration during antibiotic treatment increases microbiome diversity and enriches health-associated taxa.}, journal = {Infection and immunity}, volume = {}, number = {}, pages = {e0039025}, doi = {10.1128/iai.00390-25}, pmid = {41312988}, issn = {1098-5522}, abstract = {Antibiotic-induced microbiome injury, defined as a reduction of ecological diversity and obligate anaerobe taxa, is associated with negative health outcomes in hospitalized patients, and healthy individuals who received antibiotics in the past are at higher risk for autoimmune diseases. Postbiotics contain mixtures of bacterial fermentation metabolites and bacterial cell wall components that have the potential to modulate microbial communities. Yet, it is unknown if a fermentation-derived postbiotic can reduce antibiotic-induced microbiome injury. Here, we present the results from a single-center, randomized placebo-controlled trial involving 32 patients who received an oral, fermentation-derived postbiotic alongside oral antibiotic and probiotic therapy for non-gastrointestinal (GI) infections. At the end of the antibiotic course, patients receiving the postbiotic (n = 16) had significantly higher fecal bacterial alpha diversity (+40%, inverse Simpson index) compared to the placebo group (n = 16), and the treatment was well-tolerated. Analysis of 157 longitudinal fecal samples revealed that this increased diversity was driven by enrichment of health-associated taxa, notably obligate anaerobic Firmicutes, particularly Lachnospiraceae. In contrast, Escherichia/Shigella species, often linked to pathogenicity and antibiotic resistance, were reduced in postbiotic-treated patients at the end of antibiotic treatment and remained lower up to 10 days later. Our findings suggest that postbiotic co-administration during antibiotic therapy may augment health-associated gut microbiome composition and mitigate antibiotic-induced microbiome injury.Trial registration ISRCTN30327931 retrospectively registered.}, } @article {pmid41312383, year = {2025}, author = {Miao, Z and Long, J and Huang, B and Yan, D and Wang, A}, title = {Roseburia hominis enriched by baicalin reverses the non-response to metformin via upregulating linolenic acid metabolism.}, journal = {iScience}, volume = {28}, number = {11}, pages = {113892}, pmid = {41312383}, issn = {2589-0042}, abstract = {Metformin is the most commonly used hypoglycemic drug for patients with type 2 diabetes (T2D), but about 30% of patients show non-response potentially linked to gut microbiota imbalance. Although baicalin exhibits potent gut microbiota-modulating activity, its role in reversing metformin non-response remains unclear. Here, we recruited patients with T2D who were non-responders to metformin treatment and collected their fecal samples to construct a humanized mouse model via fecal microbial transplantation. We found that baicalin combined with metformin improved the abnormal glucose tolerance in non-response mice, in which Roseburia hominis was considerably enriched. Mechanically, baicalin combined with metformin activated the AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC)/carnitine palmitoyl transferase 1 (CPT1) pathway, and its enriched R. hominis promoted linolenic acid metabolism, thus reversing the non-response to metformin. Besides, the efficacy of R. hominis in reversing the non-response of metformin was dependent on phospholipase A2 (linolenic acid metabolism key enzyme). Our findings provide feasibility strategies for the metformin treatment of non-responsive patients.}, } @article {pmid41310268, year = {2025}, author = {Fazeli, SA and Soleimani Samarkhazan, H}, title = {Metabolic Memory Following Metabolic Bariatric Surgery: Mechanisms, Clinical Implications, and Strategies for Long-Term Success.}, journal = {Obesity surgery}, volume = {}, number = {}, pages = {}, pmid = {41310268}, issn = {1708-0428}, abstract = {Metabolic bariatric surgery (MBS) treats severe obesity, but long-term benefits are often lost to weight regain and metabolic relapse driven by persistent molecular imprints. This narrative review synthesizes recent evidence and examines epigenetic, inflammatory, mitochondrial, and microbiota mechanisms underlying metabolic memory after MBS. Key imprints include altered adipose transcriptomes (e.g., lower IGF1 and GPX3), persistent NLRP3 inflammasome activation, and gut dysbiosis with variable, individual patterns. We highlight how these mechanisms drive clinical outcomes such as type 2 diabetes recurrence and residual cardiovascular risk, with tissue-specific epigenetic retention slowing renal and cardiac recovery. We evaluate evidence-based strategies to counteract or modulate metabolic memory. These include the strategic selection of bariatric procedure, preoperative metabolic optimization, Mediterranean diets rich in polyphenols, GLP-1/GIP co-agonists, senolytics (e.g., dasatinib + quercetin), and autologous fecal microbiome transplantation. Emerging preclinical approaches like CRISPR-dCas9 epigenetic editing and exploratory strategies like vagal neuromodulation show theoretical promise in targeting obesogenic memory pathways but remain far from clinical application. The review underscores the need for longitudinal multi-omics cohorts and metabolic memory biomarkers (e.g., PPARGC1A methylation, CCL25) to enable personalized interventions. By targeting metabolic memory proactively, MBS can evolve from weight-loss procedure to a durable reset of metabolic set points. However, it is crucial to acknowledge that many proposed strategies are derived from preliminary studies with limited sample sizes and follow-up, necessitating further validation in large-scale trials.}, } @article {pmid41077329, year = {2025}, author = {González-Rico, C and Hernández, M and Rodríguez-Grande, J and Fernández-Luis, S and Bermúdez Rodríguez, A and González-Huerta, AJ and Llaneza Velasco, E and Vázquez López, L and García García, I and Arnaiz de Las Revillas, F and Fariñas-Álvarez, C and Calvo Montes, J and Ocampo-Sosa, A and Fernández-Martínez, M and Fariñas, MC and , }, title = {Changes in the bacterial profile and diversity of the gut microbiota in allogeneic hematopoietic stem cell transplant recipients.}, journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases}, volume = {161}, number = {}, pages = {108117}, doi = {10.1016/j.ijid.2025.108117}, pmid = {41077329}, issn = {1878-3511}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome/genetics ; Male ; Female ; Middle Aged ; Prospective Studies ; Adult ; RNA, Ribosomal, 16S/genetics ; *Bacteria/classification/genetics/isolation & purification ; Transplantation, Homologous ; Graft vs Host Disease/microbiology ; Feces/microbiology ; Young Adult ; Aged ; Spain ; }, abstract = {OBJECTIVES: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with significant alterations in gut microbiota (GM) composition, affecting transplant success. This study aimed to correlate these GM changes with post-transplant (post-HSCT) outcomes.

METHODS: A prospective multicentre cohort study was conducted between June 2017 and December 2021 in three Spanish hospitals. Stool samples from allo-HSCT recipients were collected before HSCT, and at 14-, 30-, 60-, and 100-days post-HSCT. Bacterial 16S rRNA gene sequences were characterized and microbial diversity assessed.

RESULTS: Analysis of 409 samples from 95 patients revealed significant longitudinal GM shifts. Alpha diversity significantly decreased at days 14 (P < 0.001), 30 (P < 0.001), and 60 (P = 0.002) compared to baseline. A distinct shift in dominant taxonomic profiles was observed, notably a significant decrease in Blautia abundance (P < 0.001). Patients with acute gastrointestinal graft-versus-host disease (GI-GVHD) (P = 0.009), bacteraemia (P = 0.014), or death (P < 0.001) exhibited significantly lower Blautia levels. LEfSe analysis identified 22 differential taxa between deceased and surviving patients; the former showed higher abundance of potential pathogens such as Enterococcus_H (P = 0.026), Enterococcus_A (P = 0.019), and Staphylococcus (P = 0.009).

CONCLUSIONS: Significant variations in the GM's taxonomic profiles and relative abundances post-HSCT, particularly the decrease in Blautia and the increase in certain pathogens, are associated with poorer clinical outcomes.}, } @article {pmid41309372, year = {2025}, author = {Xu, S and Su, W and Qin, Z and Xuan, Z and Wang, J and Wang, J and Tang, R and Yin, J and Liang, J and Jia, X}, title = {Er Miao San Attenuates Collagen-Induced Arthritis Mice by Regulating Gut Microbiota and Its Metabolites.}, journal = {Journal of microbiology and biotechnology}, volume = {35}, number = {}, pages = {e2507054}, doi = {10.4014/jmb.2507.07054}, pmid = {41309372}, issn = {1738-8872}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Arthritis, Experimental/drug therapy/microbiology ; Fecal Microbiota Transplantation ; Male ; RNA, Ribosomal, 16S/genetics ; Dysbiosis/drug therapy ; Fatty Acids, Volatile/metabolism ; *Arthritis, Rheumatoid/drug therapy/microbiology ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Mice, Inbred DBA ; Butyrates/metabolism ; Bacteria/classification/genetics/metabolism/drug effects ; Disease Models, Animal ; Bacteroidetes/drug effects ; }, abstract = {Dysbiosis of the gut microbiota plays a key role in the pathogenesis of rheumatoid arthritis (RA). However, it is still unclear whether the classic prescription Er Miao San (EMS) can exert therapeutic effects on RA by regulating the gut microbiota. In this study, we investigated whether EMS alleviates collagen-induced arthritis (CIA) by modulating the gut microbiota and its metabolites. We demonstrated that EMS significantly reduced arthritis severity, paw swelling, and systemic inflammation in CIA mice. In addition, 16S rRNA sequencing analysis revealed that EMS restored gut microbiota homeostasis, as evidenced by an increased abundance of Bacteroidetes, and a decreased Bacteroidetes/Firmicutes ratio. Crucially, antibiotic depletion of the gut microbiota abolished the protective effects of EMS, whereas fecal microbiota transplantation (FMT) from EMS-treated donors replicated its anti-arthritic efficacy, confirming the indispensable role of the microbiota. Measurement of short-chain fatty acids (SCFAs) further revealed a significant increase in the microbial metabolite butyrate following EMS treatment. Subsequent supplementation with sodium butyrate mimicked the therapeutic effects of EMS, ameliorating joint inflammation and cartilage damage. Mechanistically, butyrate enhanced the expression of intestinal tight junction proteins (ZO-1 and occludin), thereby restoring intestinal barrier integrity. Collectively, our results demonstrate that EMS exerts its anti-arthritic effects by modulating the gut microbiota-butyrate-intestinal barrier axis, highlighting the critical value of microbial metabolites in RA treatment. This study provides novel insights into the mechanism of EMS and suggests the therapeutic potential of butyrate for RA.}, } @article {pmid41308739, year = {2025}, author = {Zhang, Y and Liu, J and Zhang, X and Cheng, S and Liu, S and Huang, A and Yu, Y and Liu, J and Chen, H and Shang, D and Yin, P and Ma, S}, title = {Rhein alleviates acute pancreatitis by inhibiting TMAO-mediated inflammatory signaling pathways and reducing acinar cell injury.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.11.056}, pmid = {41308739}, issn = {2090-1224}, abstract = {INTRODUCTION: Acute pancreatitis (AP) represents a significant global health challenge. Despite recent advances in medical treatment, the development of novel therapeutic strategies remains crucial.

OBJECTIVES: Rhein, a natural compound of the Chinese herb Rheum, shows promise in the treatment of AP. However, the exact mechanism underlying its therapeutic effect is still not fully understood.

METHODS: To investigate the association between the rhein-related gut microbiota and AP, we conducted antibiotic-mediated microbiota depletion experiments, fecal microbiota transplantation (FMT), and in vitro bacterial culture experiments. Concurrently, we performed 16S rRNA gene sequencing, metagenomic sequencing, and liquid chromatography‒mass spectrometry (LC‒MS) analyses on mouse fecal samples to characterize alterations in the microbiota and metabolome. Transcriptomic studies were also performed to elucidate the mechanisms underlying acinar cell inflammation.

RESULTS: Rhein alleviated AP by modulating the gut microbiota, as demonstrated by changes in the gut microbiota composition and improvements in AP after FMT in rhein-treated mice compared with those in cerulein-induced AP mice. Specifically, rhein is concentrated mainly in the stomach and intestines, where it exerts anti-inflammatory effects on acinar cells by antagonizing the TLR4/NF-κB/NLRP3 signaling pathway activated by trimethylamine-N-oxide (TMAO). This mechanism is associated with lipid peroxidation and necrosis mediated by oxidative stress. Clinically, disease severity in patients with AP is positively correlated with serum TMAO concentration.

CONCLUSION: Rhein alleviates AP by modulating the intestinal microbiota to reduce TMAO production, thereby suppressing TMAO-induced activation of the TLR4/NF-κB/NLRP3 signaling pathway and inhibiting acinar cell inflammation.}, } @article {pmid41308392, year = {2025}, author = {Lv, Y and Yang, L and Li, W and Hu, Y and Zhu, B and Zhou, M and Ye, Y and Ding, Z and Zhou, F}, title = {Tetrastigma hemsleyanum polysaccharides alleviate inflammatory bowel disease via the gut microbiota-SCFA-GPR43 signaling axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {149}, number = {}, pages = {157523}, doi = {10.1016/j.phymed.2025.157523}, pmid = {41308392}, issn = {1618-095X}, abstract = {INTRODUCTION: This study investigates the protective mechanism of Tetrastigma hemsleyanum polysaccharides (THP) against inflammatory bowel disease (IBD) by focusing on its interactions with gut microbiota and metabolites.

OBJECTIVES: The study aims to elucidate how THP exerts anti-inflammatory effects on IBD through modulating gut microbiota and activating relevant signaling pathways.

METHODS: A dextran sulfate sodium (DSS)-induced IBD mouse model was used. Antibiotic-treated mice showed that THP's protective effect is microbiota-dependent. Fecal microbiota transplantation (FMT) from THP-treated donors replicated the therapeutic benefits in recipient mice. In vivo studies with GPR43 agonists/inhibitors and in vitro experiments in GPR43-knockdown HT-29 cells explored the signaling pathways. A Caco-2/HT-29 co-culture model assessed the direct protection of intestinal epithelial cells by THP-derived metabolites. 16S rRNA sequencing and metabolomics analyzed microbiota and metabolic changes.

RESULTS: THP's protective effect was abolished in microbiota-depleted mice. FMT confirmed the microbiota-mediated effect. THP suppressed intestinal inflammation via the GPR43/β-arrestin2-JNK pathway. THP-derived metabolites directly protected intestinal epithelial cells. THP modulated gut microbiota, increased short-chain fatty acid (SCFA) production, and stimulated Resolvin E1 biosynthesis, which were associated with inflammation resolution and epithelial repair.

CONCLUSION: THP exerts anti-colitic effects by modulating gut microbiota, activating GPR43-mediated signaling, and enhancing pro-resolving lipid mediators, showing potential for IBD treatment.}, } @article {pmid41308390, year = {2025}, author = {Fan, Q and Tao, X and Huang, H and Jiang, S and Ren, H and Liu, Y and Yang, C and Wang, Y and Yan, K and Li, J and Zhao, C and Li, X}, title = {Evodiamine relieves ulcerative colitis through reinventing the communication of "host-gut microbiota-macrophages".}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {149}, number = {}, pages = {157541}, doi = {10.1016/j.phymed.2025.157541}, pmid = {41308390}, issn = {1618-095X}, abstract = {BACKGROUND AND PURPOSE: Accumulating evidence suggests that Evodiamine (EVO) exerts anti-inflammatory properties in ulcerative colitis (UC). Macrophages serve as driving factors of inflammation and the crosstalk within the "host-gut microbiota-macrophages" is considered essential in the pathogenesis of UC, however the underlying connections and mechanisms involved remained unclear. This study aimed to investigate how EVO modulates macrophages polarization balance in UC model through remodeling of host-microbiota interactions.

METHODS: UC models were induced in zebrafish and C57BL/6J mice through trinitro-benzene-sulfonic acid (TNBS) and dextran sulfate sodium salt (DSS), respectively. The key indicators of intestinal inflammation, macrophage polarization ratio in colon, colon transcriptomics and fecal microbiota were detected. Additionally, fecal microbiota transplantation (FMT) experiment was conducted to determine whether EVO ameliorates UC symptoms by regulating the intestinal microbiota and subsequently influencing M1/M2 macrophage polarization balance.

RESULTS: We found that EVO administration significantly alleviated intestinal tissue damage in both zebrafish and murine models of UC. Additionally, EVO treatment restored the M1/M2 macrophage polarization balance in the intestinal tissue of UC mice, and 16S rRNA analysis indicated that EVO alleviated the intestinal inflammation by modulating the composition of the intestinal microbiota. Furthermore, antibiotics and FMT experiments confirmed that modulation of M1/M2 macrophages polarization balance by EVO was mediated by the intestinal microbiota, potentially through NF-κB/STAT3 and interferon regulatory factor 5 (IRF5) pathway.

CONCLUSIONS: EVO remodeled the communication of "host-gut microbiota-macrophages" by regulating the NF-κB/STAT3 and IRF5 pathway, thereby providing novel perspectives into underling mechanism of EVO in the therapeutic effects against UC.}, } @article {pmid41308055, year = {2025}, author = {Oprea, A and Steinman, J and Huang, G and Soyinka, O and Brookbank, M and Abesteh, J and Hartman, M and McEvoy, A and Dionne, JC and Milev, R and Samaan, Z}, title = {Oral Methods of Microbiota Manipulation for Depression Symptoms: A Systematic Review: Méthodes orales de manipulation du microbiote pour traiter les symptômes de dépression : Une revue systématique.}, journal = {Canadian journal of psychiatry. Revue canadienne de psychiatrie}, volume = {}, number = {}, pages = {7067437251394369}, doi = {10.1177/07067437251394369}, pmid = {41308055}, issn = {1497-0015}, abstract = {ObjectiveThe effectiveness of current treatment options for depressive symptoms has been widely investigated with acknowledgment that some patients were either not adequately responding to treatment, finding the existing treatment intolerable, or otherwise prefer alternative options. There is increasing interest in microbiota modulation as an alternate form of depression treatment, with a growing number of trials and reviews on the subject published in the last five years. This systematic review aimed to analyze all completed randomized control trials (RCTs) that assessed depression symptoms in adults not using antidepressants, before and after oral methods of microbiota manipulation.MethodAll completed parallel-arm RCTs that assessed depression symptoms in adult participants before and after oral methods of microbiota manipulation were retrieved from four databases, MEDLINE, Embase, PsycINFO, and Cochrane Central Register of Controlled Trials. Data on study and intervention characteristics as well as RCT conclusions were collected independently and in duplicate, and each study's findings were summarized individually. Risk of bias was completed.ResultsWe included 66 RCTs in our review, 34 of which concluded significant differences between the intervention and control group in depressive symptom using different interventions and measures. Of the 66 trials, 54 used probiotic interventions, seven used prebiotic, eight used synbiotic and two used oral fecal microbiota transplantation. Wide variation was observed in studies' design, intervention composition and consumption methods across all 66 RCTs. No statistical synthesis or meta-analyses were possible due to the wide variety of interventions, measures and outcomes.ConclusionsThe heterogeneity of the existing RCTs did not allow for concrete conclusions on whether oral microbiota manipulation interventions are viable alternative treatment options for adults experiencing depression symptoms. We encourage the development of standardized guidelines for the design and reporting of microbiota studies in depression for the possibility of future intervention efficacy testing.}, } @article {pmid41306971, year = {2025}, author = {Han, T and Zhang, Y and Zheng, G and Guo, Y}, title = {From pathogenic mechanisms to therapeutic perspectives: a review of gut microbiota and intestinal mucosal immunity in inflammatory bowel disease.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1704651}, pmid = {41306971}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Immunity, Mucosal ; *Intestinal Mucosa/immunology/microbiology ; *Inflammatory Bowel Diseases/therapy/immunology/microbiology/etiology ; Animals ; Dysbiosis/immunology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; }, abstract = {Inflammatory bowel diseases (IBDs), which comprises Crohn's disease (CD) and ulcerative colitis (UC), is a multifactorial disorder with an as-yet undetermined etiology, with its global incidence rising rapidly, particularly in developing and Western countries. Although the exact etiology remains unclear, recent research implicates genetic predisposition, environmental factors, gut microbiota, and immune responses in the pathogenesis of IBD. Notably, dysbiosis of the gut microbiota-characterized by a reduction in the abundance and diversity of specific bacterial genera-has been suggested as a potential trigger for the onset of IBD, accompanying with dysregulated intestinal mucosal immunity involving in immune cells and nonimmune cells. Understanding and restoring the imbalanced gut microbiota, as well as identifying key bacterial species involved in IBD, are critical for elucidating disease mechanisms and developing therapeutic strategies. In this review, we explore the role of gut microbiota and intestinal mucosal immunity in the pathogenesis of IBD and offers insights into microbiota-centered therapeutic interventions, including probiotics, fecal microbiota transplantation, and microbial metabolites, that aim to modulate the gut microbiota for the treatment of IBD.}, } @article {pmid41306279, year = {2025}, author = {Feng, S and Wang, J and Si, X and Lu, S and Lu, C and Gao, Z and Yang, J and Wu, J and He, X and Wu, L}, title = {Washed microbiota transplantation: candidates for a novel strategy for ameliorating autism spectrum disorder.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1688325}, pmid = {41306279}, issn = {1664-302X}, abstract = {Autism Spectrum Disorder (ASD) is a severe neurodevelopmental disorder with an increasing global incidence, imposing substantial burdens on both society and affected families. The pathogenesis of ASD is complex, involving genetic, environmental, and other factors. Notably, children with ASD often exhibit gut microbiota dysbiosis, and the relationship between gut microbiota and ASD has garnered growing attention. Current treatments for ASD remain limited and unsatisfactory. As an emerging therapeutic approach, Washed Microbiota Transplantation (WMT) reduces undigested food residues, fungi, parasite eggs, and pro-inflammatory metabolites, thereby lowering the incidence of adverse clinical events. WMT also addresses ethical and aesthetic concerns associated with Fecal Microbiota Transplantation (FMT), enhances treatment safety, and offers new hope for ASD management. This review integrates global literature to analyze the latest findings on ASD epidemiology, societal impacts, existing therapies, and clinical research on WMT, aiming to provide scientific evidence for the clinical application of WMT in ASD treatment.}, } @article {pmid41305918, year = {2025}, author = {Shao-Yu, Y and Niu, D and Chen, J and Li, WY and Wang, X and Meng, QW and Song, WJ and Yang, YG and Wang, H and Li, RR and Li, BY and Zhang, LG and Hu, CJ and Xu, LF and Wang, HH and Zhang, L and Liang, CZ and Du, HX}, title = {Antibiotic cocktail-induced changes in gut microbiota drive alteration of bile acid metabolism to restrain Th17 differentiation through the FXR-NLRP3 axis.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2582944}, doi = {10.1080/19490976.2025.2582944}, pmid = {41305918}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Th17 Cells/drug effects/immunology/cytology ; Male ; *Bile Acids and Salts/metabolism ; *Anti-Bacterial Agents/pharmacology/administration & dosage ; Mice ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; Humans ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; Mice, Inbred C57BL ; Cell Differentiation/drug effects ; Fecal Microbiota Transplantation ; *Prostatitis/immunology/microbiology/drug therapy ; Disease Models, Animal ; Interleukin-17 ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Antibiotics influence both gut microbial composition and immune regulation, but the detailed mechanisms are still undefined. Shifts in the microbiome caused by antibiotic exposure can modulate immune activity through various pathways. Therefore, we aimed to explore how antibiotics affect immune-inflammation by regulating Th17 cells through the gut microbiota of mice with experimental autoimmune prostatitis (EAP). Antibiotic-driven shifts in gut microbial communities and metabolite profiling in EAP mice were performed by integrating 16S rRNA sequencing with mass spectrometry-driven metabolomic analysis. Antibiotic cocktail (ABX) therapy mitigated EAP, modified the gut microbiome composition, and influenced bile acid metabolism. Fecal microbiota transplantation (FMT) using microbiota from ABX-treated feces into EAP mice effectively altered gut microbiome composition and alleviated disease symptoms, indicating that microbiome intervention reduces autoimmune inflammation and decreases deoxycholic acid (DCA) in mice. Subsequent experiments demonstrated that DCA suppresses farnesol X receptor (FXR) expression which can inhibit the NLRP3‒ IL17A axis, thus promoting Th17 cell development and exacerbating inflammatory cell infiltration of the prostate. Our initial clinical examination of patients with prostatitis and antibiotic treatment indicated that bile acid metabolism and Th17 cell development are affected by antibiotic therapy. This work revealed that antibiotic-induced gut microbiota dysbiosis decreases the bile acid metabolite DCA, further restraining Th17 cell differentiation via the FXR‒NLRP3 axis to alleviate autoimmune prostatitis. Our results reveal new perspectives regarding the interconnected dynamics of antibiotics, gut microbiota, bile acid metabolism, and immune regulation, with potential relevance for therapies targeting immune-mediated diseases.}, } @article {pmid41305382, year = {2025}, author = {Zhang, Z and Kang, W and Mi, Y and Zhong, X and He, Y}, title = {The Microbiota-Gut-Brain Axis in Autism: Associations, Causal Inference, and Interventions-A Narrative Review.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, doi = {10.3390/pathogens14111145}, pmid = {41305382}, issn = {2076-0817}, support = {Grant No. LCYSSQ20220823091203008//the Shenzhen Clinical Research Center for Gastroenterology/ ; Grant No. A2402008//the Shenzhen Medical Research Fund/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Brain ; Probiotics/therapeutic use ; *Autism Spectrum Disorder/microbiology/therapy ; *Autistic Disorder/microbiology/therapy ; *Brain-Gut Axis ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; }, abstract = {Autism spectrum disorder is markedly heterogeneous and frequently accompanied by gastrointestinal symptoms that often correlate with behavioral phenotypes. Emerging evidence suggests that the microbiota-gut-brain axis may contribute to these associations through multiple bidirectional communication routes-including neural, immune, and endocrine pathways, as well as microbial metabolites such as short-chain fatty acids and tryptophan-kynurenine intermediates. This narrative review synthesizes clinical, mechanistic, and interventional evidence published between January 2010 and July 2025, clarifies the extent to which current data support association versus causation, evaluates key confounding factors, summarizes evidence for interventions such as probiotics, prebiotics, and fecal microbiota transplantation, and outlines future directions for precision research and targeted interventions based on functional pathways and stratified subgroups.}, } @article {pmid41304963, year = {2025}, author = {Golčić, M and Radoš, L and Skočilić, I and Badovinac, I and Hauser, G and Krznarić Zrnić, I and Šantić, M and Fučkar Čupić, D and Francetić, S and Lisica, K and Juras, L and Škrtić, M and Bešvir Džubur, A and Šeparović, R and Tomašić, V and Tečić Vuger, A and Mikolašević, I}, title = {Fecal Microbiota Transplantation in Refractory Immune-Mediated Colitis: Case Series and Review of the Literature.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {11}, pages = {}, doi = {10.3390/ph18111719}, pmid = {41304963}, issn = {1424-8247}, abstract = {Background/Objectives: Immune checkpoint inhibitors (ICI) represent a significant breakthrough in cancer management, but they can cause adverse effects such as immune-mediated colitis (IMC). The standard first-line treatment is corticosteroids, and second-line treatment is infliximab or vedolizumab. However, a proportion of immune-mediated colitis (IMC) cases are refractory to immunosuppressive treatment, which has led to the exploration of novel approaches such as fecal microbiota transplantation. Methods: We present two patients who both developed grade III IMC following application of durvalumab and pembrolizumab, respectively. Both patients were refractory to corticosteroid therapy, while the first one also showed no improvement to infliximab. We performed two separate applications of FMT on both patients, from different donors, as a rescue treatment. Results: After unsuccessful immunosuppressive treatment and following rescue FMT, both patients demonstrated a rapid and sustained improvement in inflammatory markers, clinical symptoms, quality-of-life scores, and colonoscopy findings, without additional immunosuppressive treatment. Conclusions: FMT appears to be safe and a potentially effective treatment option for patients with refractory IMC both as second- and third-line therapy options. Continued efforts toward rigorous donor screening, use of standardized biobanks, and standardizing FMT protocols will further enhance safety and reproducibility.}, } @article {pmid41304215, year = {2025}, author = {Arruda, ISA and Cavalcante, CDS and Rubens, RS and Castro, LNPF and Nóbrega, YKM and Dalmolin, TV}, title = {Changes in the Gut Microbiota of Patients After SARS-CoV-2 Infection: What Do We Know?.}, journal = {Microorganisms}, volume = {13}, number = {11}, pages = {}, doi = {10.3390/microorganisms13112529}, pmid = {41304215}, issn = {2076-2607}, support = {DPI/BCE nº 01/2025//University of Brasilia/ ; FAPDF nº 09/2023//Fundação de Apoio à Pesquisa do Distrito Federal/ ; }, abstract = {COVID-19 can cause long-term symptoms, such as a post-infection syndrome, known as Long-COVID. Among the symptoms present during this period, the most reported are gastrointestinal symptoms. This study discusses the effects of changes in the gut microbiota of post-COVID-19 patients. SARS-CoV-2 infection is associated with significant alterations in gut microbial composition, disturbing its homeostasis and promoting a reduction in the abundance of beneficial symbiotic bacteria and an increase in the abundance of opportunistic pathogens. Furthermore, the composition of the gut microbiota may play a role in the prognosis of patients with post-COVID-19 infection. The microbiota of the intestinal tract and the respiratory tract influence each other; therefore, the gut-lung axis has attracted increasing interest in understanding COVID-19. Moreover, the brain-gut axis has been studied, since there have been reports of anxiety and depression along with post-COVID-19 gastrointestinal symptoms. Treatments options for intestinal dysbiosis in Long-COVID patients include probiotics, prebiotics, and fecal microbiota transplantation. These treatments may serve as an approach to improve gastrointestinal symptoms during Long-COVID, increasing microbiome diversity, strengthening the integrity of intestinal barrier functions, and consequently influencing the treatment of COVID-19.}, } @article {pmid41304202, year = {2025}, author = {Feng, JJ and Maddirala, NR and Saint Fleur, A and Zhou, F and Yu, D and Wei, F and Zhang, Y}, title = {Gut Microbiome and Immune System Crosstalk in Chronic Inflammatory Diseases: A Narrative Review of Mechanisms and Therapeutic Opportunities.}, journal = {Microorganisms}, volume = {13}, number = {11}, pages = {}, doi = {10.3390/microorganisms13112516}, pmid = {41304202}, issn = {2076-2607}, abstract = {The gut microbiota, a complex community of trillions of microorganisms residing in the gastrointestinal tract, plays a vital role in maintaining host health and regulating a wide range of physiological functions. Advances in molecular biology have greatly expanded our understanding of the dynamic interactions between the gut microbiome and the immune system. Disruption of this microbial community, known as dysbiosis, can compromise epithelial barrier integrity, trigger aberrant immune activation, and lead to the production of proinflammatory metabolites. These changes are increasingly recognized as contributing factors in the pathogenesis of chronic inflammatory diseases. Emerging research highlights the gut microbiota as a key modulator of immune homeostasis, influencing both local and systemic inflammatory processes during the initiation and progression of these diseases. Understanding the mechanisms underlying gut microbiota-immune interactions will offer new avenues for therapeutic interventions. This review focuses on six representative chronic inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, systemic lupus erythematosus, asthma, and vasculitis, all of which are characterized by dysregulated immune responses and persistent inflammation. Our goal is to synthesize the recent research on the role of gut microbiome in the pathogenesis of the diseases listed above and provide insights into the development of microbiota-based therapies, particularly fecal microbiota transplant, dietary modifications, prebiotic and probiotic interventions, for their treatment.}, } @article {pmid41304151, year = {2025}, author = {Reveles, KR and Meehan, J and Tillotson, G}, title = {Fecal Microbiota Transplantation in Animals: Therapeutics, Conservation, and Farming.}, journal = {Microorganisms}, volume = {13}, number = {11}, pages = {}, doi = {10.3390/microorganisms13112465}, pmid = {41304151}, issn = {2076-2607}, abstract = {Fecal microbiota transplantation (FMT) is increasingly used in both human and veterinary settings to restore gut microbiota and promote health. Advances in sequencing technologies and microbiome analysis have expanded our understanding of microbial communities and enabled broader FMT applications. As insights grow into what constitutes a healthy microbiome, interest in using FMT across a range of animal contexts has also increased. This narrative review highlights recent progress in the use of FMT to improve the welfare of farm animals, manage infectious and chronic conditions in companion animals, and support the health of wildlife in conservation and reintroduction programs. Representative examples from each domain are discussed.}, } @article {pmid41304131, year = {2025}, author = {Lv, D and Han, N and Liu, H and Tang, H}, title = {Hepatitis B Virus-Related Liver Disease and Gut Microbiota: An Updated Review.}, journal = {Microorganisms}, volume = {13}, number = {11}, pages = {}, doi = {10.3390/microorganisms13112445}, pmid = {41304131}, issn = {2076-2607}, abstract = {Although gut microbiota plays a pivotal role in numerous biological functions (e.g., energy, nutrients, metabolism, and immunological processes), growing evidence demonstrates that the gut microbiota is involved in the progression of liver diseases. The liver can be greatly influenced by alterations in intestinal microbiota due to increased gut permeability, allowing for the entry of bacterial products into the liver through the gut-liver axis. Recently, clinical and experimental research findings have demonstrated that microbiota dysbiosis plays an important role in the pathogenesis and progression of HBV-related liver diseases. In this review, we provide an overview of the gut microbiota and the microbiota-gut-liver axis in health; review HBV infection interactions with microbiota; discuss the role of microbiota dysbiosis in the pathogenesis of HBV-related liver disease, such as chronic HBV infection, liver cirrhosis, and hepatocellular carcinoma; and, finally, assess the potential for microbiota-targeted therapies, such as probiotics and fecal microbiota transplantation. This review will provide novel insights into individualized therapy for CHB patients based on gut microbiota alteration.}, } @article {pmid41303703, year = {2025}, author = {Qassadi, FI and Johnson, C and Robinson, K and Griffin, R and Polytarchou, C and Kao, D and Kim, DH and Griffiths, RL and Zhu, Z and Monaghan, TM}, title = {Untargeted Metabolomics Identifies Faecal Filtrate-Derived Metabolites That Disrupt Clostridioides difficile Metabolism and Confer Gut Barrier Cytoprotection.}, journal = {International journal of molecular sciences}, volume = {26}, number = {22}, pages = {}, doi = {10.3390/ijms262211221}, pmid = {41303703}, issn = {1422-0067}, support = {1074742634//Saudi Ministry of Higher Education/ ; }, mesh = {*Clostridioides difficile/metabolism ; *Metabolomics/methods ; Humans ; *Feces/microbiology/chemistry ; *Clostridium Infections/metabolism/therapy/microbiology ; Fecal Microbiota Transplantation ; *Cytoprotection ; Metabolome ; Gastrointestinal Microbiome ; *Intestinal Mucosa/metabolism/microbiology ; Female ; Male ; }, abstract = {Recurrent Clostridioides difficile infection (rCDI) remains a major therapeutic challenge. Although faecal microbiota transplantation (FMT) is highly effective and thought to restore microbial composition and metabolic function, the mechanisms underlying its success are not fully understood. In particular, the contribution of non-bacterial components such as soluble metabolites remains unclear. Therefore, further investigation is needed to identify the mechanistic drivers of FMT efficacy and clarify how non-bacterial factors contribute to therapeutic outcomes. Here, we applied untargeted three-dimensional Orbitrap secondary ion mass spectrometry (3D OrbiSIMS) to profile faecal metabolic reprogramming in rCDI patients pre- and post-FMT, alongside C. difficile cultures exposed to sterile faecal filtrates. FMT induced extensive metabolic shifts, restoring glyoxylate/dicarboxylate and glycerophosphoinositol pathways and normalising disrupted bile acid and amino acid profiles. Faecal filtrate exposure caused strain-specific metabolic disruption in C. difficile, depleting proline, fumarate and succinate while enriching tryptophan. While multiple metabolite classes were profiled, the most significant functional changes were observed in lipids. Lipidomics identified >3.8-fold enrichment of phosphatidylinositol (PI) species, which localised to bacterial membranes and conferred cytoprotection against C. difficile toxins and other epithelial insults. Spatial metabolomics imaging revealed, for the first time, metabolite compartmentalisation within C. difficile, with proline and succinate broadly distributed across the cell surface and fumarate confined to distinct microdomains, highlighting functional heterogeneity in pathogen metabolism. Collectively, these findings demonstrate that soluble metabolites within faecal filtrates mediate pathogen suppression and epithelial barrier protection, establishing metabolite-driven mechanisms underlying FMT efficacy and identifying PI lipids as candidate post-biotic therapeutics for rCDI.}, } @article {pmid41301795, year = {2025}, author = {Seguiti, C and Tettoni, E and Pezzuto, E and Gerardi, V and Quadarella, A and Cesaro, P and Colombini, P}, title = {Clostridioides difficile Infection in Special Populations: Focus on Inflammatory Bowel Disease-A Narrative Review from Pathogenesis to Management.}, journal = {Biomedicines}, volume = {13}, number = {11}, pages = {}, doi = {10.3390/biomedicines13112702}, pmid = {41301795}, issn = {2227-9059}, abstract = {Clostridioides difficile infection (CDI) is a major complication in inflammatory bowel disease (IBD), due to coexistence of altered microbiota, chronic inflammation, and immune dysregulation. This narrative review summarizes recent evidence on the epidemiology, pathogenesis, risk factors, diagnosis, and management of CDI in IBD. Overall, IBD patients have a four- to five-fold higher risk of CDI than the general population and face more severe courses, higher rates of hospitalization, colectomy, recurrence, and mortality. Pathogenesis involves profound dysbiosis with loss of butyrate-producing Firmicutes and Bacteroidetes, bile acid imbalance that promotes spore germination, and enhanced toxin effects on an already inflamed mucosa. Major risk factors include active colonic disease, broad-spectrum antibiotic exposure, prolonged hospitalization, and corticosteroid or combined immunosuppressive therapy. Diagnosis requires careful integration of stool assays with clinical evaluation, supported by endoscopy or imaging when needed, to distinguish infection from IBD flares. Recommended first-line treatments are fidaxomicin or oral vancomycin, reserving fecal microbiota transplantation for recurrent or high-risk cases. Optimal IBD control is essential to reduce both primary and recurrent infection. CDI and IBD share a mutual pathogenic interplay in which microbial, immune, and therapeutic factors from each condition drive and magnify the other. Early recognition, guideline-based antibiotic therapy, judicious use of immunosuppression, and microbiota-based preventive strategies are crucial to improve patient outcomes and limit recurrence, thus reducing healthcare costs.}, } @article {pmid41301443, year = {2025}, author = {Papavassiliou, KA and Sofianidi, AA and Spiliopoulos, FG and Margoni, A and Papavassiliou, AG}, title = {Emerging Issues Regarding the Effects of the Microbiome on Lung Cancer Immunotherapy.}, journal = {Biomolecules}, volume = {15}, number = {11}, pages = {}, doi = {10.3390/biom15111525}, pmid = {41301443}, issn = {2218-273X}, mesh = {Humans ; *Lung Neoplasms/therapy/microbiology/immunology ; *Immunotherapy/methods ; *Microbiota/immunology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Animals ; }, abstract = {Lung cancer remains the deadliest malignancy, with limited effective and long-term therapeutic options. Immunotherapy has revolutionized the therapeutic landscape of lung cancer. However, not everyone with lung cancer responds to immunotherapy, while, inpatients who temporarily derive clinical benefit, resistance eventually develops. The host microbiome has emerged as a pivotal player in cancer growth and progression. It has been implicated in the intricate connections between immune cells and tumor cells, ultimately augmenting immunotherapy efficacy in solid tumors, while simultaneously mitigating the immune-related adverse events associated with this type of treatment. Notably, lung cancer patients who obtain benefit from immunotherapy have been found to be colonized with specific bacterial populations, and it is this observation that the scientific community is trying to exploit, aspiring to improve lung cancer immunotherapy response rates. Delving deeper into the molecular mechanisms underpinning the effects of the microbiome on immunotherapy is an area that we should pay attention to if we want to utilize microbiome modulation in everyday clinical practice. Fecal microbiota transplantation, probiotics, targeted antibiotic interventions, and dietary modifications are among the strategies that are under investigation in clinical trials, with the ultimate endpoint of lengthening the life expectancy of lung cancer patients.}, } @article {pmid41300985, year = {2025}, author = {De Lucia, SS and Nista, EC and Candelli, M and Archilei, S and Deutschbein, F and Capuano, E and Gasbarrini, A and Franceschi, F and Pignataro, G}, title = {Microbiota and Pancreatic Cancer: New Therapeutic Frontiers Between Engineered Microbes, Metabolites and Non-Bacterial Components.}, journal = {Cancers}, volume = {17}, number = {22}, pages = {}, doi = {10.3390/cancers17223618}, pmid = {41300985}, issn = {2072-6694}, abstract = {Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive and lethal human malignancies, with five-year survival rates showing only marginal improvement despite decades of intensive research. Its dismal prognosis reflects a combination of intrinsic biological aggressiveness, late clinical presentation, and marked resistance to standard therapies, underscoring the urgent need for innovative diagnostic and therapeutic approaches. Growing evidence indicates that the microbiome is a modifiable factor influencing the onset, progression, and treatment response of PDAC. Microbial communities originating from the gut, oral cavity, and even the tumor microenvironment can shape carcinogenic pathways, modulate immune activity, and alter the efficacy of chemotherapy and immunotherapy. In addition to bacteria, fungal and viral populations are emerging as relevant contributors within this complex ecosystem. This review provides a comprehensive overview of the current mechanistic and translational evidence linking the microbiome to PDAC biology and therapy. It further explores microbiota-targeted interventions-such as probiotics, postbiotics, engineered bacterial strains, bacteriophages, oncolytic viruses, and fecal microbiota transplantation-as promising adjuncts to conventional treatments. A deeper understanding of host-microbiome interactions could yield novel biomarkers and open innovative avenues for precision medicine in PDAC, ultimately improving patient outcomes and reshaping therapeutic paradigms. Integrating microbiome-based strategies into PDAC management may thus represent a crucial step toward more effective and personalized oncologic care.}, } @article {pmid41300676, year = {2025}, author = {Marano, G and Sfratta, G and Marzo, EM and Cozzo, G and Abate, F and Traversi, G and Mazza, O and Capristo, E and Gaetani, E and Mazza, M}, title = {The Pediatric Microbiota-Gut-Brain Axis: Implications for Neuropsychiatric Development and Intervention.}, journal = {Children (Basel, Switzerland)}, volume = {12}, number = {11}, pages = {}, doi = {10.3390/children12111561}, pmid = {41300676}, issn = {2227-9067}, abstract = {BACKGROUND: The gut microbiota plays a crucial role in brain development and function, especially in early life. Disruptions in the pediatric microbiota-gut-brain axis have been linked to neurodevelopmental and psychiatric disorders. We hypothesize that early-life dysbiosis can perturb neurodevelopment via the pediatric microbiota-gut-brain axis, increasing risk and/or severity of neuropsychiatric outcomes, and that microbiota-targeted strategies may mitigate this risk.

METHODS: We conducted a narrative review by searching PubMed, Scopus, and Web of Science up to January 2025 for studies addressing pediatric microbiota, neuropsychiatric development, and interventions. Human and animal studies were included if they provided mechanistic or clinical insights.

RESULTS: Key determinants of microbiota development in childhood include mode of delivery, feeding practices, antibiotic exposure, diet, and environment. Altered microbial composition has been associated with autism spectrum disorder, attention-deficit/hyperactivity disorder, mood disorders, anxiety, and anorexia nervosa. Mechanistic pathways involve immune modulation, neural signaling (including the vagus nerve and enteric nervous system), and microbial metabolites such as short-chain fatty acids. Interventions targeting the microbiota-ranging from dietary strategies and probiotics to psychobiotics and fecal microbiota transplantation-show promise but require further pediatric-focused trials.

CONCLUSIONS: The pediatric microbiota-gut-brain axis represents a critical window for neuropsychiatric vulnerability and intervention. Early-life strategies to support a healthy microbiota may help reduce the risk or severity of psychiatric disorders. Future research should prioritize longitudinal pediatric cohorts and clinical trials to translate mechanistic insights into precision interventions.}, } @article {pmid41299731, year = {2025}, author = {Zhao, Y and Li, H and Xu, J and Li, H and Bao, L and Wu, K and Qiu, M and Yu, H and Shang, S and He, Y and Yuan, C and Zhang, N and Hu, X and Fu, Y and Li, W and Zhao, C and Wang, J}, title = {Phytosphingosine contributes gut microbiota metabolism to alleviate low-grade endotoxemia-induced mastitis.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02266-9}, pmid = {41299731}, issn = {2049-2618}, support = {32330105//National Natural Science Foundation of China/ ; 2023M741348//China Postdoctoral Science Foundation/ ; }, abstract = {BACKGROUND: Recently, evidence has indicated that mastitis is closely associated with the ruminal dysbiosis caused by subacute ruminal acidosis (SARA) and subsequent low-grade endotoxemia (LGE). However, whether and how ruminal metabolic dysbiosis influences SARA-associated mastitis is still unclear.

RESULTS: Using untargeted metabolomics, we found that cows with SARA-associated mastitis exhibited altered ruminal metabolic profiles, particularly a reduced level of phytosphingosine (PS), compared to healthy cows. Oral administration of PS to mice alleviated LGE-induced mastitis, as evidenced by attenuated mammary injury and improved function of mammary tight junctions (TJs). Furthermore, we demonstrated that LGE induced significant gut dysbiosis, characterized by increased abundances of opportunistic pathogens such as Enterococcus, which was mitigated by PS treatment. Interestingly, transplantation of both fecal microbiota (FMT) and matched sterile supernatant (FST) from PS-treated mice alleviated LGE-induced mastitis, restored the blood-milk barrier, and modulated the gut microbiota in recipient mice following LGE exposure. Additionally, PS and PS-FMT treatments increased the abundances of fecal short-chain fatty acid (SCFA) producers, accompanied by elevated fecal SCFA levels, particularly butyric acid, in PS- and PS-FMT-treated mice. Butyric acid was negatively correlated with mammary inflammatory markers, and butyrate administration attenuated LGE-induced mastitis in mice. Mechanistically, butyrate promotes M2 macrophage polarization and inhibits NF-κB and NLRP3 inflammasome activation via G-protein-coupled receptor 41 (GPR41).

CONCLUSIONS: Collectively, our results demonstrate that gut microbiota from PS-dosed mice alleviate LGE-induced mastitis in mice by promoting SCFA production and regulating macrophage polarization. Our findings provide deeper insights into gut dysbiosis-associated mastitis and highlight the potential of modulating gut microbiota and its metabolism as a strategy for managing mastitis and other related diseases. Video Abstract.}, } @article {pmid41299728, year = {2025}, author = {Vaziri, Y and Olia, JBH and Avci, CB and Nourazarian, A}, title = {Molecular mechanisms of gut microbiota dysbiosis and metabolites in Alzheimer's disease pathogenesis: implications for precision therapeutics.}, journal = {Molecular brain}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13041-025-01263-1}, pmid = {41299728}, issn = {1756-6606}, abstract = {Alzheimer's disease (AD) originates from both central and peripheral pathways. The gut microbiota is a clear risk factor. In AD, microbiota imbalances drive immune system activation, disrupt protective barriers, and alter neuromodulatory signaling. Additionally, gut microbiota dysbiosis has been identified as a risk factor for AD. Recent research indicates that dysbiosis of the microbiota in AD is linked to immune activation, barrier dysfunction, and neuromodulatory signaling. Studies of AD pathology reveal that short-chain fatty acids, indole derivatives, and bile acids can have both protective and harmful effects. New strategies, such as probiotics, dietary changes, and fecal microbiota transplantation, may influence disease progression in AD. However, conflicting methods, unaccountable motives, and ethical concerns surrounding microbiome interventions pose significant hurdles. To translate findings related to the gut-brain axis into effective solutions, we need standardized multi-omics approaches, personalized therapies, and oversight from regulatory authorities. Ultimately, leveraging insights from the gut microbiome holds great promise for transforming how we diagnose, prevent, and treat AD.}, } @article {pmid41298101, year = {2025}, author = {Liu, CS and Merrick, B and Taboun, ZS and Mullish, BH and Goldenberg, SD and Terveer, EM and Porcari, S and Bradbury, RS and Ianiro, G and Ng, SC and , and Kao, D and Kuijper, E}, title = {Towards optimising and standardising donor screening for faecal microbiota transplantion.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-336532}, pmid = {41298101}, issn = {1468-3288}, abstract = {Rigorous donor screening is fundamental for the safe and effective delivery of faecal microbiota transplantion (FMT) services, whether in the treatment of Clostridioides difficile infection or within microbiome intervention clinical trials. Donor screening is of paramount importance given the potential risk of pathogen transmission-a feared complication. While rare in practice, documented cases of FMT-associated infections have resulted in significant morbidity and even mortality. Despite the importance of screening, evidence-based approaches to developing donor-screening protocols are lacking. Inadequate screening for transmissible pathogens may lead to infections in recipients, while overly cautious screening for pathogens with negligible transmission potential could strain healthcare resources and unnecessarily exclude donors, who are already in limited supply. This review aimed to evaluate the evidence underpinning current FMT donor screening protocols. We began by comparing protocols from major FMT guidelines and manufacturers, highlighting their differences in lists of screened pathogens, laboratory assays and clinical characteristics used for donor selection. We critically appraised the existing literature on transmission dynamics for pathogens. These findings were incorporated into a Delphi process with an expert panel group to develop a rational and streamlined screening approach. We further emphasised the importance of maintaining transparency with regard to donor recruitment, screening, monitoring and traceback record keeping. Finally, we explored future directions in donor screening, including approaches to monitoring emerging pathogens and the potential for integration of new technologies, such as metagenomic assays, to enhance and refine donor selection.}, } @article {pmid41134466, year = {2025}, author = {Strzępa, A and Szczepanik, M}, title = {The role of microbiota modulation in preventing Alzheimer's disease- a review.}, journal = {Pharmacological reports : PR}, volume = {77}, number = {6}, pages = {1468-1490}, pmid = {41134466}, issn = {2299-5684}, support = {N43/DBS/000345//Polish Ministry of Science and Higher Education/ ; }, abstract = {Alzheimer’s disease (AD) is the most common form of dementia, and its incidence is projected to triple worldwide over the next 25 years. The most prevalent form, late-onset Alzheimer’s disease (LOAD), develops in genetically predisposed individuals exposed to environmental risk factors. Hallmarks of AD include accumulation of amyloid-β (Aβ), neurofibrillary tangles (NFTs), neuroinflammation, and mitochondrial dysfunction, resulting in oxidative stress, impaired glucose metabolism, and cognitive decline. Such metabolic disruptions result in early cerebral glucose hypometabolism and other metabolic disruptions, including altered lipid and branched-chain amino acid profiles. Recent evidence suggests that gut microbiota alterations, although individually variable, are a consistent and influential factor in AD progression via inflammatory and metabolic pathways. This narrative review explores therapeutic interventions targeting the gut-brain axis, including fecal microbiota transplantation (FMT), probiotic and antibiotic treatments, and dietary strategies such as the ketogenic and Mediterranean diets, as well as nutritional compounds such as omega-3 fatty acids. The aim is to evaluate the latest findings in both preclinical and clinical studies to identify multi-targeted, microbiota-based approaches for the prevention and management of AD.}, } @article {pmid41297775, year = {2025}, author = {Ferrini, A and He, M and Mont, MA and Goodman, SB and Parvizi, J}, title = {Osteonecrosis of the femoral head: A Dysbiotic Condition?.}, journal = {The Journal of arthroplasty}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.arth.2025.11.044}, pmid = {41297775}, issn = {1532-8406}, abstract = {Osteonecrosis of the femoral head (ONFH) is a progressive and disabling condition of the hip joint that primarily affects young and active individuals, leading to progressive collapse of subchondral bone and often secondary arthritis. Despite extensive investigation, the precise etiology often remains unclear. While high-dose corticosteroids, chronic alcohol ingestion, and smoking are known associated risk factors, approximately 20 to 30% of ONFH cases are classified as idiopathic. Recently, the concept of gut dysbiosis, i.e., disruption of the normal intestinal microbial balance, has gained increasing attention due to its systemic immunologic and metabolic implications. Dysbiosis is associated with an increase in gut permeability, leading to the translocation of bacteria and their metabolic products, including lipopolysaccharides and short-chain fatty acids (SCFAs), into the systemic circulation. This may stimulate proinflammatory cascades throughout the body, including the joints, initiating a bone remodeling process. Emerging evidence from preclinical and human research suggests that specific gut microbiota taxa may influence key mechanisms involved in the pathogenesis of ONFH. Additionally, early findings support the therapeutic potential of microbiota-targeted therapies such as probiotics, SCFAs-enriched diets, and fecal microbiota transplantation (FMT). Although a growing number of descriptive studies support this link, the current evidence remains associative rather than causal, as no longitudinal cohort studies have confirmed this relationship. Future investigations are needed to establish causality between gut dysbiosis and ONFH. To our knowledge, this review offers the first comprehensive synthesis of the literature aiming to explore current evidence and the potential link between gut dysbiosis and ONFH, highlighting future directions for microbiome-based therapeutic interventions.}, } @article {pmid41296090, year = {2025}, author = {Wang, M and Zeng, Y and Jin, Y and Wu, J and Li, J}, title = {Progress and Perspectives on the Estrogen-Microbiota-Brain Axis in Alzheimer's Disease.}, journal = {Neurochemical research}, volume = {51}, number = {1}, pages = {3}, pmid = {41296090}, issn = {1573-6903}, support = {No. QKHJC-ZK[2022]-260//Guizhou Provincial Science and Technology Projects/ ; NO.gzwjrs2023-005//Guizhou Provincial High level Innovative Talent Fund/ ; }, mesh = {Humans ; *Alzheimer Disease/metabolism/microbiology ; *Estrogens/metabolism ; *Gastrointestinal Microbiome/physiology ; *Brain/metabolism/drug effects ; Animals ; Dysbiosis/metabolism ; }, abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder shaped by genetic, metabolic, environmental, and sex-specific factors. Emerging evidence highlights the estrogen-gut microbiota-brain (EGMB) axis as a critical framework linking endocrine regulation, microbial activity, and cognitive outcomes. Estrogen exerts neuroprotective effects by modulating synaptic plasticity, oxidative stress, amyloid and tau pathology, and neuroinflammation, while its decline during menopause increases AD vulnerability. Parallel to this, gut dysbiosis and altered microbial metabolites, particularly short-chain fatty acids (SCFAs) and secondary bile acids (sBAs), contribute to barrier dysfunction, chronic inflammation, and synaptic impairment. Importantly, estrogen remodels microbial composition and metabolite profiles, whereas microbial β-glucuronidase (β-GUS) activity sustains estrogen bioavailability, establishing a reciprocal regulatory loop. Preclinical studies demonstrate that depletion of gut microbiota diminishes estrogen's protective effects, underscoring the central role of microbial metabolites as signaling bridges.Therapeutically, these insights support the integration of hormone replacement therapy with microbiota-targeted interventions such as probiotics, prebiotics, and fecal microbiota transplantation. Such combined strategies may synergistically enhance neuroprotection, though their efficacy depends on timing, dosage, and individual variability. Future precision approaches integrating multi-omics profiling and sex-specific stratification hold promise for identifying predictive biomarkers and optimizing treatment windows. In summary, the EGMB axis offers a mechanistic foundation for understanding sex differences in AD and a translational framework for developing individualized, multidimensional strategies for early diagnosis, prevention, and therapy.}, } @article {pmid41294832, year = {2025}, author = {Susiriwatananont, T and Eiamprapaporn, P and Vazquez Roque, M and Farraye, FA and Perlman, A and Chumsri, S}, title = {The Gut Microbiome as a Biomarker and Therapeutic Target of Immune Checkpoint Inhibitors: A Review for Oncologists.}, journal = {Cells}, volume = {14}, number = {22}, pages = {}, doi = {10.3390/cells14221779}, pmid = {41294832}, issn = {2073-4409}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/immunology ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Oncologists ; *Neoplasms/drug therapy/immunology/microbiology ; Biomarkers/metabolism ; Immunotherapy/methods ; Biomarkers, Tumor/metabolism ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, yet their benefits remain limited to a subset of patients, underscoring the need for more reliable biomarkers and novel therapeutic strategies. The gut microbiome has emerged as a critical modulator of systemic immunity and a promising determinant of ICI response. Evidence links specific microbial features, taxa, and bioactive metabolites to enhanced antitumor immunity, whereas disruptions, such as antibiotic exposure, are associated with poorer outcomes. Advances in sequencing and multi-omics technologies have provided more profound insights into microbiome-immune crosstalk, though methodological heterogeneity continues to challenge reproducibility. Translational studies demonstrate that microbiome-based intervention, including fecal microbiota transplantation (FMT), biotics supplementation, and engineered microbial strains, can enhance ICI efficacy or mitigate immune-related toxicities. Despite encouraging early clinical signals, broader implementation requires methodological rigor, standardized protocols, and innovative trial designs that account for host and environmental factors. For clinicians, the most immediate strategies involve prudent antibiotic stewardship and patient enrollment in microbiome-focused clinical trials. Overall, the gut microbiome is a promising biomarker and a therapeutic target, representing a new frontier for personalizing immunotherapy and improving patient outcomes in oncology.}, } @article {pmid41293177, year = {2025}, author = {Li, P and Wang, Y and Dong, Y and Zhang, X}, title = {Unveiling the gut-liver axis: the behind-the-scenes "manipulator" of human immune function.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1638197}, pmid = {41293177}, issn = {1664-3224}, mesh = {Humans ; *Liver/immunology/metabolism ; *Gastrointestinal Microbiome/immunology ; Animals ; Bile Acids and Salts/metabolism ; }, abstract = {The "gut-liver axis" enables bidirectional immunoregulation between the intestine and the liver through the portal venous circulation, bile acid metabolism, and the neuro-lymphatic network. This paper reviews its physiological pathways (vascular, biliary, neural, and lymphatic), immunomodulatory mechanisms (interaction of innate/adaptive immune cells, balance between inflammation and tolerance), and associations with diseases such as PSC, MAFLD, and IBD. Metabolites of gut microbiota activate immune cell receptors to regulate the differentiation of Tregs, while cytokines (such as IL-6) and chemokines (such as CCR9) drive the synergy of gut-liver immunity. In pathological conditions, dysbiosis, endotoxin translocation, and bile acid metabolic disorders trigger immunological dysregulation through this axis. Strategies such as targeted fecal microbiota transplantation and bile acid receptor (FXR) agonists show clinical potential. This paper systematically elaborates on the physiological and immunoregulatory mechanisms of the "gut-liver axis", explores the associations between its abnormalities and immune diseases, as well as the prospects of translational medicine. It is proposed that future research should deepen the analysis of single-cell interactions, conduct personalized interventions, and establish a new paradigm of "gut-liver axis medicine" to provide cross-organ solutions for the precise prevention and control of immune-related diseases.}, } @article {pmid41292506, year = {2025}, author = {Arawker, MH and Habibullah, F and Baral, S and Fu, L and Sun, N and Li, H and Ji, F and Qiu, X}, title = {Microbiome Mediated Immune Crosstalk on the Gut-Thyroid Axis in Autoimmune Thyroid Disease.}, journal = {Immunological investigations}, volume = {}, number = {}, pages = {1-21}, doi = {10.1080/08820139.2025.2593335}, pmid = {41292506}, issn = {1532-4311}, abstract = {BACKGROUND: The gut microbiota plays an important role in systemic immune homeostasis and is increasingly implicated in autoimmune thyroid disease (AITD). Evidence suggests that gut dysbiosis, impaired intestinal barrier function, and altered microbial metabolites particularly short-chain fatty acids contribute to immune imbalance along the gut-thyroid axis. Although molecular mimicry between microbial and thyroid antigens has been proposed, current human evidence remains associative rather than causal.

METHODS: This review synthesized current observational, translational, and preclinical studies evaluating microbial composition, barrier integrity, microbial metabolites, and immune pathways relevant to AITD. Mechanistic insights into T-lymphocyte regulation and microbial-host interactions were integrated with emerging interventional data.

RESULTS: Gut dysbiosis in AITD is linked to reduced regulatory T-lymphocytes, expansion of Th17 cells, increased intestinal permeability, and the loss of short-chain-fatty-acid-producing taxa. Observational studies consistently report disease-associated taxonomic alterations, while preclinical models support causal pathways through barrier disruption and microbiota-driven immune activation. Early interventional approaches such as high-fiber dietary patterns, probiotics, prebiotics, and experimental fecal microbiota transplantation show modest reductions in thyroid autoantibodies in small trials, though effects are strain-specific, short-term, and not disease-modifying.

CONCLUSION: Despite largely associative human evidence, converging mechanistic findings highlight the gut microbiota as a modifiable contributor to thyroid autoimmunity. Future priorities include clarifying causality, identifying keystone microbial taxa and metabolites, and establishing standardized interventional frameworks to facilitate translation into endocrine practice.}, } @article {pmid41292332, year = {2025}, author = {Bø, S and Wiig, H and Juul, FE and Garborg, KK and Johnsen, PH and Bretthauer, M}, title = {Faecal microbiota transplantation for primary Clostridioides difficile infection.}, journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke}, volume = {145}, number = {14}, pages = {}, doi = {10.4045/tidsskr.25.0276}, pmid = {41292332}, issn = {0807-7096}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Clostridium Infections/therapy ; Female ; Clostridioides difficile ; Anti-Bacterial Agents/therapeutic use/adverse effects ; Middle Aged ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is recommended for recurrent Clostridioides difficile (C. difficile) infection. The recommended treatment for primary C. difficile infection is antibiotics. We present a patient who requested FMT for primary C. difficile infection.

CASE PRESENTATION: A patient in her sixties developed primary C. difficile infection following antibiotic therapy atter surgery for small bowel volvulus. The patient refused antibiotic treatment and contacted a research group that had just concluded a randomised phase III trial assessing FMT for primary C. difficile infection. The trial had not yet been published, and FMT was not included in guideline recommendations for this indication. After joint decision-making involving the patient, her general practitioner, gastroenterologists and the research group, the patient received FMT and experienced complete remission of C. difficile symptoms within two days of treatment.

INTERPRETATION: This case illustrates how to evaluate experimental versus established treatments in light of new evidence and patient preferences that do not align with guideline recommendations.}, } @article {pmid41291207, year = {2025}, author = {Li, C and Wang, H and Lin, X and Zeng, G and Li, X and Chen, W and Lu, H and Pan, J and Zhang, X and Rong, X and He, L and Peng, Y}, title = {Chronic alcohol consumption disrupts the integrity of the blood-brain barrier through the gut-brain axis.}, journal = {Communications biology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s42003-025-09235-w}, pmid = {41291207}, issn = {2399-3642}, abstract = {Chronic alcohol consumption can lead to disruption of the blood-brain barrier. The gut-brain axis may be involved in this pathological process. We investigated the gut microbiota of 30 healthy individuals and 30 alcohol use disorder (AUD) patients and found that at the genus level, AUD patients had decreased Faecalibacterium and increased Streptococcus. Liquid chromatography mass spectrometer (LC-MS/MS) revealed that 604 metabolites were upregulated and 606 were downregulated in AUD patients with cognitive impairment, compared to healthy controls. Chronic alcohol consumption led to cognitive decline in mice, with increased 20 kDa FITC-dextran leakage in the prefrontal cortex (PFC) and hippocampus, and decreased expression of ZO-1, occludin, and claudin-5. Transplantation of feces from AUD patients into germ-free mice resulted in increased 20 kDa FITC-dextran leakage in PFC and hippocampus, and decreased expression of ZO-1, occludin, and claudin-5, compared to mice receiving feces from healthy individuals. Administration of Faecalibacterium prausnitzii to chronically alcohol-fed mice improved cognitive function, reduced 20 kDa FITC-dextran leakage in PFC and hippocampus, and increased the expression of ZO-1, occludin, and claudin-5. Chronic alcohol consumption can disrupt the blood-brain barrier through the gut-brain axis. Faecalibacterium prausnitzii can improve alcohol-induced blood-brain barrier disruption and cognitive impairment.}, } @article {pmid41290520, year = {2025}, author = {Kumari, A and Priya, S and Barman, I and Dhasmana, A and Rustagi, S and Thapliyal, S and Deshwal, RK and Malik, S and Bora, J}, title = {Gut Microbiota Dynamics and Their Role in Pathogenesis and Management of Diabetes.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {133}, number = {11}, pages = {e70090}, doi = {10.1111/apm.70090}, pmid = {41290520}, issn = {1600-0463}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Diabetes Mellitus, Type 2/microbiology/therapy ; Dysbiosis/microbiology ; *Diabetes Mellitus, Type 1/microbiology/therapy ; Fecal Microbiota Transplantation ; Animals ; Probiotics/therapeutic use ; Prebiotics ; }, abstract = {The gut microbiota (GM) has emerged as an important element in the management of host metabolism, immune functions, and overall metabolic well-being. This review consolidates contemporary research regarding the intricate relationship between GM and diabetes mellitus, focusing on the mechanisms by which microbial composition and activity affect the development of both Type 1 (T1D) and Type 2 diabetes (T2D). Dysbiosis-characterized by diminished microbial diversity, a modified Firmicutes/Bacteroidetes ratio, and a reduction in advantageous SCFA-producing bacteria-has been significantly associated with disrupted glucose metabolism, insulin resistance, and persistent inflammation. Additionally, the review discusses the potential for microbial signatures and metabolites, such as SCFAs, lipopolysaccharides (LPS), and trimethylamine N-oxide (TMAO), to serve as novel biomarkers for early detection and risk evaluation. Moreover, it investigates therapeutic approaches designed to reestablish microbial balance through the use of probiotics, prebiotics, dietary changes, fecal microbiota transplantation (FMT), and microbiome engineering. By integrating findings from recent research, this paper emphasizes the groundbreaking possibilities of microbiome-centric diagnostics and treatments in individualized diabetes care.}, } @article {pmid41288714, year = {2025}, author = {Quiroga-Centeno, AC and Atanasova, K and Ebert, MP and Thomann, AK and Reindl, W}, title = {Emerging microbiome-directed therapies in inflammatory bowel disease: beyond diet modification and FMT.}, journal = {Seminars in immunopathology}, volume = {47}, number = {1}, pages = {42}, pmid = {41288714}, issn = {1863-2300}, mesh = {Humans ; *Inflammatory Bowel Diseases/therapy/microbiology/etiology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/immunology ; Probiotics/therapeutic use ; Animals ; Dysbiosis/therapy ; }, abstract = {Inflammatory bowel disease (IBD) is a multifactorial and heterogeneous disorder that remains challenging to manage. Growing evidence implicates the gut microbiome as a key player in IBD pathogenesis, with many patients displaying intestinal dysbiosis that can drive aberrant immune responses. Traditional microbiome-targeted interventions, such as dietary modifications, probiotics, and fecal microbiota transplantation (FMT), have yielded mixed and often temporary benefits in IBD. This shortcoming of broad-spectrum approaches underscores the need for more precise, personalized strategies that account for each patient's unique microbiota and disease phenotype. Recent advances in omics and bioengineering have catalyzed the development of emerging microbiome-directed therapies that move beyond these broad approaches. This narrative review highlights emerging microbiome-directed therapies that aim to restore gut homeostasis and mitigate inflammation in IBD. We critically evaluate the rationale and therapeutic potential of rationally designed bacterial consortia and genetically engineered bacteria, which represent next-generation probiotics tailored to complement deficient microbial functions or deliver anti-inflammatory agents in situ. We also expand the discussion to underexplored microbiome constituents - archaea, protists, bacteriophages, and fungi - highlighting their roles in IBD and potential as therapeutic targets. Finally, we discuss the key advances and ongoing challenges of these innovative approaches, from ecological stability and engraftment to safety and regulatory considerations.}, } @article {pmid41287858, year = {2025}, author = {Liu, N and Wang, DX and Hao, JX and Yan, XF and Lv, CL and Yan, JG and Liu, GF}, title = {Fecal Microbiota Transplantation Combined with Lifestyle Modification in the Management of Metabolic Dysfunction-Associated Fatty Liver Disease: Two Case Reports and Literature Review.}, journal = {Diabetes, metabolic syndrome and obesity : targets and therapy}, volume = {18}, number = {}, pages = {4299-4307}, pmid = {41287858}, issn = {1178-7007}, abstract = {Metabolic dysfunction-associated fatty liver disease (MAFLD) is highly prevalent condition, with gut microbiota dysbiosis playing a contributory role in its pathogenesis and progression. Fecal microbiota transplantation (FMT) has emerged as a potential therapeutic approach for MAFLD. This report describes two patients diagnosed with MAFLD who underwent FMT in combination with lifestyle intervention. Post treatment findings demonstrated notable improvements in body mass index (decreased by 20.7% and 3%, respectively), serum transaminases levels (decreased by 51% and 27.2%, respectively), lipid profiles, uric acid concentrations, and liver stiffness measurements (decreased by 22.2% and 24.2%, respectively). Additionally, microbiome analysis showed increased diversity, improved anti-inflammatory and colonization resistance capacity, reduced pathogens, and enriched probiotics. A review of seven Chinese and international randomized controlled trials (RCTs) investigating the application of FMT in MAFLD was conducted. Among these, four trials reported improvement in liver function post-treatment. Two trials reported reductions in small intestinal or gastric permeability, one trial demonstrated a decrease in homeostasis model assessment of insulin resistance (HOMA-IR), one trial noted a reduction in blood lipid levels, and one trial documented a decrease in fat attenuation index (FAI). Only one trial included histological evaluation of liver tissue before and after FMT, which did not demonstrate significant pathological improvement. The combination of FMT and lifestyle intervention has achieved quite satisfactory therapeutic effects in the treatment of MAFLD, providing new ideas and potential therapeutic targets for the management of MAFLD. This approach holds broad application prospects. However, further confirmation through large-scale RCTs is still needed.}, } @article {pmid41287633, year = {2025}, author = {Marques, I and Marcos, P}, title = {Acute hepatic porphyrias.}, journal = {Porto biomedical journal}, volume = {10}, number = {6}, pages = {e308}, pmid = {41287633}, issn = {2444-8672}, abstract = {INTRODUCTION: Porphyrias are rare genetic disorders caused by heme biosynthesis pathway enzyme mutations, leading to porphyrin precursors build up in various tissues and diverse symptoms. This review centers on acute hepatic porphyrias (AHP).

METHODS: A MEDLINE through PubMed database literature review was conducted. Systematic reviews, clinical trials, cohort studies, case-control studies, expert reviews, and guidelines were preferred for analysis.

RESULTS: There are 4 types of AHP: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and δ-aminolevulinic acid dehydratase deficiency porphyria. These conditions primarily present as neurovisceral attacks, characterized by severe abdominal pain, neuropsychiatric symptoms, or skin lesions, predominantly affecting women aged 15 to 50 years. The diagnostic methods include biochemical tests that assess urinary levels of aminolevulinic acid and porphobilinogen. In addition, measuring porphyrin levels in urine or feces can provide more insights into the type of AHP; however, a definitive diagnosis of the specific type is made through genetic testing. Treatment involves high-glucose diets, intravenous hemin for acute attacks, and givosiran for the prophylaxis of frequent attacks. Liver transplantation remains the only curative option. It is crucial to monitor chronic complications associated with hepatic porphyrias, particularly hepatocellular carcinoma, kidney disease, and arterial hypertension.

CONCLUSION: AHP continues to be an underrecognized condition, warranting consideration in individuals experiencing unexplained abdominal pain, neuropathy, psychiatric symptoms, or skin lesions. There is a need for improved diagnostic techniques and treatment options.}, } @article {pmid41285255, year = {2025}, author = {Wang, S and Ma, G and Qi, C and Cheng, S and Lai, H and Zhou, L and Wu, G and Chen, Z and Mao, X and Jing, T and He, Y and Zhou, H}, title = {Trimethylamine-N-oxide disrupts spermatogenesis by inducing mitochondrial oxidative stress injury through Hippo signaling.}, journal = {Free radical biology & medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.freeradbiomed.2025.11.052}, pmid = {41285255}, issn = {1873-4596}, abstract = {BACKGROUND: The gut-testis axis is increasingly recognized as a regulator of male reproductive health; however, the key microbial contributors, metabolites, and underlying mechanisms remain unclear.

METHODS: We performed fecal metagenomic sequencing in 107 participants to identify microbial taxa associated with abnormal semen parameters. Serum trimethylamine-N-oxide (TMAO) levels were measured and correlated with semen quality. In mouse models, including fecal microbiota transplantation, dietary choline supplementation, mono-colonization, and direct TMAO administration, we assessed sperm morphology, testicular androgen synthesis, and testicular histology. Testicular transcriptomics, in vitro Leydig cell assays, and mitochondrial function analyses were conducted to investigate the effects of TMAO on Hippo signaling, oxidative phosphorylation, mitochondrial membrane damage, and steroidogenesis.

RESULTS: Choline-to-trimethylamine converting bacteria, including Phocaeicola massiliensis, Veillonella spp., and Klebsiella pneumoniae, were enriched in men with abnormal semen parameters. Circulating TMAO levels were inversely associated with semen volume, total sperm count, and motile sperm count. In mouse models, elevated TMAO induced testicular dysfunction characterized by impaired sperm morphology, reduced testicular androgen synthesis, and histological abnormalities. Consistently, gene set enrichment analysis (GSEA) of testicular transcriptomes revealed significant suppression of mitochondrial translation, membrane integrity, oxidative phosphorylation, and adenosine triphosphate (ATP) metabolism. TMAO also suppressed steroidogenesis by reducing the expression of steroidogenic acute regulatory protein (StAR). Mechanistic studies in TM3 Leydig cells further demonstrated that TMAO, by promoting Yap phosphorylation, disrupted mitochondrial structure and morphology, decreased mitochondrial membrane potential, increased mitochondrial reactive oxygen species (ROS) levels, impaired ATP synthesis, and promoted mitochondrial fragmentation with upregulation of the mitochondrial fission molecule (Fis1).

CONCLUSIONS: In conclusion, our findings demonstrate that TMAO activates Hippo signaling to induce mitochondrial dysfunction and suppress testosterone synthesis, thereby impairing spermatogenesis. These results highlight TMAO biosynthesis and its downstream signaling as potential therapeutic targets for improving male fertility.}, } @article {pmid41284175, year = {2025}, author = {Olesen, RH and Larsen, EB and Rubak, T and Baunwall, SMD and Paaske, SE and Gregersen, M and Erikstrup, C and Olsen, K and Dahlerup, JF and Kjaer, TK and Krogh, CB and Ehlers, LH and Hvas, CL}, title = {Increasing patient access to faecal microbiota transplantation with remote delivery: a cost analysis of outpatient versus home-based treatment.}, journal = {Health economics review}, volume = {}, number = {}, pages = {}, doi = {10.1186/s13561-025-00706-8}, pmid = {41284175}, issn = {2191-1991}, support = {NNF22OC0074080//Novo Nordisk Foundation/ ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) is used in less than 10% of the patients in Europe who meet the indication. Encapsulated FMT allows increased use for CDI because capsules can be safely shipped to local healthcare facilities and administered orally to patients without use of e.g. colonoscopy. The aim of this study was to calculate and compare the costs of alternative ways of delivering encapsulated FMT to patients with CDI in Denmark, including outpatient treatment at a specialised FMT centre, outpatient treatment at local hospitals including remote delivery to the Faroe Islands, and home-based care.

METHODS: Applying a healthcare perspective, we used an activity-based costing approach, combining data from a pragmatic clinical randomised trial with the best available literature and expert input. Only relevant costs were included. The main outcome was the average cost of delivering outpatient, encapsulated FMT treatment at an FMT centre, at a local hospital, or in the patient's home, only including additional costs related to delivery. An 8-week time horizon was applied for the analysis. Probabilistic and deterministic sensitivity analyses were applied to evaluate decision uncertainty and the robustness of the results.

RESULTS: In a pragmatic randomised trial including 217 patients with CDI, 135 patients received FMT. Analysing relevant costs in a base case analysis, local outpatient treatment (€145) was cost-saving compared with both treatment at the FMT centre (€209) and home-based treatment (€353). These differences remained robust across sensitivity analyses, including those accounting for patients' time costs. In the Faroe Islands case, shipment to remote locations added an average cost of €54 per FMT to the cost for the local outpatient treatment.

CONCLUSION: Capsule-based FMT treatment has made it clinically and economically feasible to administer FMT in contextual settings outside of specialised hospitals. Our findings highlight the importance of local hospital-based treatment for increasing patient access to FMT, the ability to ship FMT to remote locations lacking a FMT centre, and the option of home-based treatment for a selected group of patients who may not tolerate transport to hospital.}, } @article {pmid41282240, year = {2025}, author = {Gancz, A and Zhang, G and McMillan, A and Dougherty, M and McGill, S and Gulati, A and Baker, E and Theriot, C}, title = {Successful Fecal Microbiota Transplants in Post-antibiotic Treated Recurrent Clostridioides difficile Patients Induce Acylcarnitine and Sphingolipid Lipidomic Shifts.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-7888346/v1}, pmid = {41282240}, issn = {2693-5015}, abstract = {Clostridioides difficile infection (CDI) is an urgent public health threat in the United States, resulting on an annual basis in over half a million cases, more than 29,000 deaths, and $4.8 billion in healthcare costs. While fecal microbiota transplants (FMTs) have proven more effective than standard-of-care antibiotics in resolving recurrent CDI (rCDI), their inherent risks underscore the need for advancements in regulated alternative therapies such as live biotherapeutic products (LBPs). The development of effective LBPs, however, is contingent upon better understanding the biological mechanisms underlying FMT efficacy. Building on our previously published untargeted metabolomic study which identified lipids as major explanatory factors associated with successful FMTs, we assessed additional lipid species using an instrumental platform coupling liquid chromatography, ion mobility spectrometry, collision induced dissociation, and mass spectrometry (LC-IMS-CID-MS) techniques. This platform and data analysis workflow enable the evaluation of >850 unique lipid species across 26 classes. Here, we confidently identified 397 lipids in the stools of 15 rCDI patients at pre- and post-FMT (2 week, 2 month, and 6 month) time points. Statistical evaluations of the lipidomic data illustrated that FMT-administration drastically reshapes the lipidome (adonis test, R [2] =0.11999, Pr(>F) <0.001), including 96 specific lipid species across 18 lipid classes (mixed effects modeling, BH correction, p < 0.05). In particular, we noted that medium and long-chain acylcarnitines decreased following FMT administration, while very long-chain acylcarnitines were elevated in post-FMT samples. Additionally, we observed assayed sphingolipids to be elevated pre-FMT with the exception of trihydroxy ceramides, which were highly upregulated post-FMT. These lipidomic alterations suggest that FMT administration may influence intestinal barrier integrity, inflammatory signaling, or apoptosis pathways. Interestingly, there was a strong co-occurrence of medium and long-chain acylcarnitines with Enterobacteriaceae, a bacterial family that has been demonstrated to utilize carnitine for growth. These findings highlight the critical role of the lipidome in patient susceptibility to rCDI and suggest the interactions between microbiota and lipids pre- and post-FMT as targets for developing next-generation LBPs.}, } @article {pmid41282164, year = {2025}, author = {Gavini, C and Raux, L and Labouèbe, G and Gornick, E and Hugh, SM and Elshareif, N and Calcutt, N and Summa, PD and Gorostidi, F and Vonaesch, P and Mansuy-Aubert, V}, title = {Dietary Fiber Improves Somatosensory Function in Western Diet-Fed Mice by Remodeling Adipose Immune Cells via FFAR2 Signaling.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-7868021/v1}, pmid = {41282164}, issn = {2693-5015}, abstract = {Westernized diets (WDs)-high in fat and sugar and low in fiber-produce somatosensory deficits, chronic pain, and neuropathy, yet the mechanisms linking diet to peripheral nervous system (PNS) pathology remain incompletely defined. Emerging evidence implicates gut-derived metabolites in sensory homeostasis; for example, fecal microbiota transplantation (FMT) from lean donors to WD fed mice reduces hypersensitivity and attenuates PNS inflammation, although FMT outcomes are variable. We therefore tested whether targeted modulation of the gut microbiota with fermentable complex carbohydrates could reproducibly improve somatosensory function in WD-fed mice. Using an integrated pipeline-behavioral and physiological assays, peripheral nerve electrophysiology, and molecular and immune profiling-we show that short-chain fatty acids (SCFAs) generated by fermentation remodel adipose tissue depots and act via the SCFA receptor FFAR2 (GPR43) to ameliorate sensory deficits. These findings identify a microbiota-SCFA-FFAR2 axis that couples dietary fiber to PNS function and provide a tractable alternative to FMT for mitigating WD-associated sensory neuropathy.}, } @article {pmid41282140, year = {2025}, author = {Gascoigne, N and Wojciech, L and Prasad, M and Brzostek, J and Rybakin, V and Hoerter, J and Hou, B and Tung, D and Chua, YL and Ampudia, J and Rai, A and Chodaczek, G and Fu, G and Pettersson, S}, title = {The role of Themis in development of type 2 diabetes.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-7943370/v1}, pmid = {41282140}, issn = {2693-5015}, abstract = {Type 2 diabetes (T2D) is a complex metabolic disorder driven by chronic inflammation and immune dysregulation, particularly within adipose tissue. This study investigates the role of the T cell-specific protein Themis in modulating immune-metabolic interactions that contribute to T2D pathogenesis. Using high-fat diet (HFD)-induced obesity models, we demonstrate that Themis -deficient (KO) mice exhibit accelerated weight gain, glucose intolerance, and insulin resistance compared to wild-type (WT) controls. These metabolic abnormalities are linked to functional alterations in the CD8[+] T cell compartment, including site-specific clonal expansion and reshaping of the T cell receptor (TCR) repertoire within adipose tissue, suggesting antigen-driven activation. Additionally, Themis deficiency leads to significant shifts in gut microbiome composition, characterized by reduced diversity and increased abundance of Firmicutes , particularly Clostridium species. However, fecal microbiota transplantation from Themis KO mice into germ-free WT hosts failed to recapitulate the full T2D phenotype, underscoring the dominant role of intrinsic immune dysfunction over microbial dysbiosis. These findings highlight a synergistic interplay between adaptive immunity and the microbiome in shaping metabolic outcomes and suggest that T cells play a central role in responses that influence T2D progression. Our data advocate for a more integrated approach to T2D research, incorporating genetic, immunological, and microbial factors.}, } @article {pmid41281485, year = {2025}, author = {Demirli Atici, S}, title = {Innovative insights into gut microbiota modulation in colorectal cancer: From microbial dysbiosis to therapeutic strategies.}, journal = {World journal of gastrointestinal oncology}, volume = {17}, number = {11}, pages = {108747}, pmid = {41281485}, issn = {1948-5204}, abstract = {Colorectal cancer (CRC) is increasingly recognized as a multifactorial disease influenced by hereditary, environmental, and microbial factors. This article explores recent insights into the role of gut microbiota dysbiosis in CRC pathogenesis and progression. Key differences in microbial composition, characterized by enrichment of pro-carcinogenic species such as Fusobacterium nucleatum and Bacteroides fragilis and depletion of beneficial commensals like Faecalibacterium prausnitzii, have been identified alongside changes in microbial metabolites such as short-chain fatty acids and secondary bile acids. We discuss immune system modulation by the microbiota, formation of bacterial biofilms, and the activation of host pathways such as the urea cycle during tumorigenesis. Special attention is given to therapeutic innovations, including microbiota-informed precision modelling, synthetic biology-based engineered probiotics, and evolving alternatives to fecal microbiota transplantation. These integrative strategies represent promising tools in the era of personalized oncology for CRC.}, } @article {pmid41281468, year = {2025}, author = {Rijkers, GT and Langcauon, Y and van Leersum, P and Popović, L and van Overveld, FJ}, title = {Role of microbiota in the outcome of immune checkpoint inhibition therapy of cancer.}, journal = {Exploration of targeted anti-tumor therapy}, volume = {6}, number = {}, pages = {1002348}, pmid = {41281468}, issn = {2692-3114}, abstract = {The realization that the composition and functionality of gut microbiota have an impact on the outcome of immune checkpoint inhibition (ICI) therapy of cancer has initiated research into the potential of microbiota management as adjunctive therapy. Fecal microbiota transplantation can improve the outcome of ICI, but for optimal donor selection, safety, and large-scale implementation, there remain bottlenecks. Alternative strategies, such as the use of selected bacterial species, require fundamental knowledge of the underlying mechanisms governing the interaction between (intestinal) microbiota and the immune system. Gut microbiota also appears to be able to colonize the tumor microenvironment. Some bacterial species directly or indirectly promote tumor growth. Other defined species have tumoricidal properties. These findings and insights are now being used to further optimize the functionality of the immune system and shape the tumor microenvironment in order to improve the outcome of ICI.}, } @article {pmid41280983, year = {2025}, author = {Nadeem, O and Imran, MS and Siddique, N}, title = {Recurrent Clostridium difficile Infections in a Patient With Ulcerative Colitis: A Case Report.}, journal = {Cureus}, volume = {17}, number = {10}, pages = {e95130}, pmid = {41280983}, issn = {2168-8184}, abstract = {Clostridium difficile infection (CDI) poses a substantial clinical challenge, especially in patients with inflammatory bowel disease (IBD), particularly ulcerative colitis (UC). Patients with UC are at greater risk of CDI and tend to experience a more severe disease course and higher rates of recurrence than the general population. We report a case of an elderly man in his early 90s with a long-standing history of UC treated with mesalazine, who had a prior hospitalization for hyponatremia and a history of CDI. During his most recent four-month hospitalization, he developed three separate episodes of CDI, confirmed by stool PCR and toxin assays. Despite treatment with vancomycin, metronidazole, and fidaxomicin in succession, he experienced recurrent episodes of CDI that ultimately progressed to septic shock and death. This case highlights the nature of recurrent CDI in this patient population and the complexity and increased morbidity associated with its management in elderly patients with UC. It underscores the importance of careful evaluation of underlying risk factors, judicious antibiotic use, and consideration of alternative treatment modalities, such as faecal microbiota transplantation (FMT), for the prevention of recurrent CDI.}, } @article {pmid41280921, year = {2025}, author = {Li, X and Yuan, Q and Huang, H and Wang, L}, title = {Gut microbiota in irritable bowel syndrome: a narrative review of mechanisms and microbiome-based therapies.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1695321}, pmid = {41280921}, issn = {1664-3224}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/microbiology/immunology ; *Gastrointestinal Microbiome/immunology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Dysbiosis/therapy ; Animals ; Prebiotics/administration & dosage ; }, abstract = {Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction, and its pathogenesis remains unclear. Dysbiosis of the gut microbiota is associated with IBS. The gut microbiota may modulate IBS symptoms via the epithelial barrier, mucosal immunity, microbial metabolites (e.g., short-chain fatty acids and bile acids), and gut-brain signaling. Currently, dietary approaches, probiotics, prebiotics, rifaximin, and fecal microbiota transplantation show variable benefit; effects are strain-/context-dependent and evidence certainty varies, with adverse-event reporting inconsistent. This narrative review takes a subtype-aware, mechanism-first perspective to summarize microbiota functions, symptom links, and intervention evidence with safety considerations. This review offers new perspectives and insights for precision treatment and microbiome research in IBS.}, } @article {pmid41280320, year = {2025}, author = {Shackelford, BB and Kedir, K and Babiker, A and Sintayehu, B and Negash, AA and Abdissa, A and Taye, WA and Beyene, E and Woodworth, MH and Hennink, MM}, title = {Knowledge and Acceptability of Fecal Microbiota Transplantation Among Patients, Caregivers, and Health Care Providers in Ethiopia.}, journal = {Open forum infectious diseases}, volume = {12}, number = {11}, pages = {ofaf676}, pmid = {41280320}, issn = {2328-8957}, abstract = {BACKGROUND: Malnutrition and antimicrobial-resistant infections are major causes of morbidity and mortality in low-income countries. These conditions have been associated with the gut microbiome, although little is known about the acceptability of microbiota therapies such as fecal microbiota transplantation (FMT). We explored the acceptability of FMT among health care providers (HCPs) and patients in Addis Ababa, Ethiopia.

METHODS: In this qualitative study, we purposively sampled patients with bacterial infections and acute malnutrition, caregivers, and HCPs at two hospitals. Eight focus group discussions were held. Amharic and English discussion guides covered knowledge of FMT and perceived barriers or facilitators for uptake. Data were transcribed and translated into English when necessary. MAXQDA software was used for a thematic analysis, with trained researchers closely reading transcripts to identify issues, develop a codebook, iteratively code data, and assess intercoder agreement. Description, comparison, and categorization were conducted to discern core themes, and validity checks ensured that findings were grounded in the data.

RESULTS: HCPs indicated a general willingness to prescribe FMT, provided that there was sufficient evidence supporting its efficacy and safety and they were confident on patient adherence. Patient acceptability of FMT was categorized along a continuum from those who were unconvinced, persuadable, amenable, and accepting of salvage treatment.

CONCLUSIONS: FMT may be acceptable for HCPs and patients in Addis Ababa, although interventions are needed to enhance acceptance among some groups, such as marketing it as standard medication, obtaining endorsement by religious leaders, providing multiple formulations, and/or providing thoughtful health communication.}, } @article {pmid41280275, year = {2026}, author = {Qi, X and Zhang, Y and Sun, Z and Wang, G and Ling, F}, title = {A simplified synthetic microbial community enhances resistance of crucian carp (Carassius auratus) to Aeromonas hydrophila infection through host immune activation.}, journal = {Synthetic and systems biotechnology}, volume = {11}, number = {}, pages = {407-418}, pmid = {41280275}, issn = {2405-805X}, abstract = {Bacterial diseases represent a major bottleneck in the sustainable development of aquaculture. The gut microbiota plays a vital role in host growth and health, including the enhancement of disease resistance. Although substantial progress has been made in elucidating the mechanisms of disease resistance in fish, the precise role of the gut microbiota in enhancing pathogen resistance in aquatic animals remains poorly understood. In this study, crucian carp (Carassius auratus) were used as a model to investigate the role of intestinal microbiota in modulating resistance to Aeromonas hydrophila. Individual crucian carp exhibited distinct clinical phenotypes following A. hydrophila infection. Specifically, significant differences were observed in the composition of the intestinal microbiota between fish displaying mild symptoms and those exhibiting severe phenotypic manifestations (α diversity: p < 0.01; β diversity: p = 0.001). Fecal microbiota transplantation (FMT) experiments demonstrated that fish with mild symptoms conferred enhanced resistance to A. hydrophila when their intestinal contents were transplanted into other individuals (p = 0.006). Further microbial analysis identified Cetobacterium (p = 0.013), Paraclostridium (p < 0.01), and Pseudomonas (p < 0.01) as key differential taxa. A simplified microbial community comprising these three strains was subsequently constructed. Feeding experiments confirmed that administration of this community significantly improved host resistance to A. hydrophila (p < 0.05) by activating intestinal immune responses and reinforcing the gut barrier. Overall, our findings underscore the potential of the microbial community as a novel strategy for disease prevention and control in aquaculture, providing a theoretical foundation for the development of microbiome-based therapies in fish health management.}, } @article {pmid41278627, year = {2025}, author = {Pandey, S and Abu, YF and Singh, P and Roy, S}, title = {Cross-Fostering with control dams rescues Gut Dysbiosis and Chromatin-associated Transcriptional Changes in Offspring of Opioid-Exposed Dams.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.11.07.687278}, pmid = {41278627}, issn = {2692-8205}, abstract = {Prenatal opioid exposure disrupts gut homeostasis and causes gastrointestinal complications in offspring, but the mechanisms remain unclear. Here using a murine model of prenatal hydromorphone exposure, we examined gut microbiota, intestinal injury, transcriptomic signatures, and chromatin accessibility. Exposed pups displayed marked dysbiosis, epithelial damage, and upregulation of inflammatory gene programs accompanied by relaxed ileal chromatin. Cross-fostering to opioid-naïve dams restored microbial diversity, reestablished metabolite-producing taxa, and reversed injury-associated transcriptional and chromatin changes. Fecal microbiota transplantation from exposed dams recapitulated intestinal injury, indicating a microbiome-driven mechanism. These findings reveal a novel gut-microbiome-epigenome axis underlying opioid-induced injury and highlight early microbial intervention as a potential strategy to mitigate developmental harm.}, } @article {pmid41278477, year = {2025}, author = {Chang, L and Liu, Y and Li, H and Yan, J and Wu, W and Chen, N and Ma, C and Zhao, X and Chen, J and Zhang, J}, title = {Gut microbiome and its metabolites in liver cirrhosis: mechanisms and clinical implications.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1717696}, pmid = {41278477}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Liver Cirrhosis/microbiology/metabolism/pathology ; Dysbiosis/microbiology ; Bile Acids and Salts/metabolism ; Fatty Acids, Volatile/metabolism ; Animals ; }, abstract = {Cirrhosis remains a significant global health burden, causing approximately 1.4-1.5 million deaths each year and contributing to nearly 46 million disability-adjusted life years (DALYs) worldwide. Increasing evidence identifies the gut-liver axis as a central driver of disease progression, wherein intestinal dysbiosis, barrier disruption, and microbe-derived metabolites collectively exacerbate inflammation, fibrogenesis, and related complications. Across more than 40 recent studies, gut microbial α-diversity declined by 30-60%, and over 80% reported a marked depletion of short-chain fatty acid (SCFA)-producing taxa, particularly Lachnospiraceae and Ruminococcaceae. Meta-analyses indicate that fecal butyrate levels decrease by 40-70%, accompanied by a two- to fourfold increase in endotoxin concentrations. Bile acid profiling demonstrates an approximately 50% reduction in secondary bile acids and significant suppression of FXR/TGR5 signaling, whereas tryptophan metabolism shifts toward the kynurenine pathway, weakening epithelial defense and exacerbating portal hypertension. Clinically, dysbiosis and microbial translocation are associated with higher MELD scores, and patients in the lowest quartile of microbial diversity have a threefold increased risk of hepatic encephalopathy or spontaneous bacterial peritonitis. Microbiome-targeted interventions-including lactulose, rifaximin, probiotics or synbiotics, fecal microbiota transplantation, and bile acid modulators-restore community balance in 70-85% of clinical trials, although efficacy and safety vary by etiology and baseline microbiota composition. Integrated microbiome-metabolome models achieve areas under the curve (AUCs) of 0.82-0.90 for noninvasive classification and early detection of cirrhosis. Collectively, these findings underscore reproducible, quantitative microbiome-metabolite alterations and outline a roadmap for microbiome-informed precision care that connects mechanistic insight with clinical application, emphasizing the need for longitudinal and multi-ethnic validation.}, } @article {pmid41278154, year = {2025}, author = {Zheng, L and Duan, SL and Wang, K}, title = {Research progress concerning the involvement of the intestinal microbiota in the occurrence and development of inflammatory bowel disease.}, journal = {World journal of gastroenterology}, volume = {31}, number = {42}, pages = {113170}, pmid = {41278154}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/genetics ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Intestinal Mucosa/microbiology/immunology/pathology ; *Crohn Disease/microbiology/therapy/immunology ; *Colitis, Ulcerative/microbiology/therapy/immunology ; Genetic Predisposition to Disease ; Dysbiosis/microbiology/immunology/therapy ; *Inflammatory Bowel Diseases/microbiology/therapy ; Metagenomics ; Animals ; Metabolomics ; Immunity, Mucosal ; }, abstract = {Inflammatory bowel disease (IBD), a chronic disorder characterized by intestinal inflammation and mucosal damage, includes mainly Crohn's disease and ulcerative colitis. However, the cause of its onset remains unclear. The pathogenesis of IBD is closely related to host genetic susceptibility, disorders of the intestinal flora, damage to the intestinal mucosal barrier, and abnormal intestinal mucosal immunity. On the basis of the progress in research on the structure of the intestinal microbiota involved in IBD, the influence of genetics on the intestinal barrier and intestinal microbiota; the metagenomics, metatranscriptomics, and metabolomics of the intestinal microbiota involved in IBD; and treatments such as probiotics and fecal microbiota transplantation are important for the future treatment of IBD and the development of drugs for effective treatment.}, } @article {pmid41278045, year = {2025}, author = {Hamza Saeed, M and Qamar, S and Ishtiaq, A and Umaira Khan, Q and Atta, A and Atta, M and Ishtiaq, H and Khan, M and Saeed, MR and Iqbal, A}, title = {Retraction: Fecal Microbiota Transplantation (FMT) in Clostridium difficile Infection: A Paradigm Shift in Gastrointestinal Microbiome Modulation.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {r206}, doi = {10.7759/cureus.r206}, pmid = {41278045}, issn = {2168-8184}, abstract = {[This retracts the article DOI: 10.7759/cureus.85054.].}, } @article {pmid41277972, year = {2025}, author = {Ye, N and Song, X and Yu, J and Bao, X and Ye, M and Jiang, L}, title = {Effects of gut microbiota interventions on patients with schizophrenia: a systematic review and meta-analysis.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1681559}, pmid = {41277972}, issn = {1664-302X}, abstract = {INTRODUCTION: Schizophrenia (SCH) is a chronic psychiatric disorder characterized by disturbances in thought, emotion, perception, and behavior. Although gut microbiota interventions (e.g., probiotics, prebiotics, synbiotics, dietary modifications and fecal microbiota transplantation) have been widely applied in the treatment of SCH, the most effective intervention strategy remains uncertain.

METHODS: By searching four databases, only randomized controlled trials (RCTs) were included to examine the impacts of gut microbiota interventions on SCH. The Cochrane risk-of-bias tool for randomized trials (RoB 2.0) was employed to assess the methodological quality of the included studies, RevMan5.4 was used for the meta-analysis, Stata 18 was used for sensitivity analysis, Engauge Digitizer was used to convert pictures to numbers and GRADEPro3.6 was used to grade the evidence quality.

RESULTS: This study incorporated RCTs published from the earliest records up to December 2024. A total of 10 RCTs, encompassing 585 participants, were analyzed. The meta-analysis demonstrated that interventions primarily utilizing probiotics to modulate gut microbiota significantly lowered the total Positive and Negative Syndrome Scale (PANSS) scores among patients (p = 0.001). Furthermore, substantial improvements were observed across multiple metabolic parameters: fasting blood sugar, triglycerides, total cholesterol, homeostasis model assessment of insulin resistance, and quantitative insulin sensitivity check index (all p < 0.05). While no significant effects were observed on high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, body weight, body mass index, and insulin.

CONCLUSION: This meta-analysis suggests that auxiliary probiotic interventions hold promise as an adjunctive therapy for schizophrenia, potentially yielding benefits in psychopathological, metabolic, and physiological domains. However, the current evidence remains inconclusive due to the limited number of studies, small sample sizes, and methodological variations. Firm therapeutic recommendations cannot be made at this time. The findings underscore the need for more robust, large-scale, and rigorously designed randomized controlled trials to definitively establish the efficacy and optimal protocols of auxiliary probiotic supplementation for SCH.

https://www.crd.york.ac.uk/PROSPERO, CRD 420250652507.}, } @article {pmid41277959, year = {2025}, author = {Zhang, S and Li, J and Li, L and Yuan, X}, title = {Gut microbiota on cardiovascular diseases-a mini review on current evidence.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1690411}, pmid = {41277959}, issn = {1664-302X}, abstract = {The gut microbiome has emerged as a critical modulator of cardiovascular disease (CVD) risk, offering a novel frontier for therapeutic intervention. This mini-review synthesizes current evidence on how probiotic-like bacteria and their metabolites mediate protective physiological mechanisms against CVD. Drawing from both animal models and human clinical trials, we elucidate the biological pathways, including trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs), and bile acid metabolism, through which the gut microbiota influences hypertension, atherosclerosis, and heart failure. Furthermore, we examine microbiota-based strategies such as dietary modification, fecal microbiota transplantation (FMT), and pharmacological agents aimed at restoring microbial homeostasis. Despite promising mechanistic insights, human trials have yet to consistently demonstrate significant clinical benefits in reversing CVD outcomes via gut microbiota modulation. This review underscores the necessity of moving from correlation to causation, highlighting current limitations and future prospects for leveraging gut microbiome research in the development of personalized, effective therapeutic strategies for cardiovascular diseases.}, } @article {pmid41277418, year = {2025}, author = {Guggeis, MA and Andreani, NA and López-Agudelo, VA and Tran, F and Kadibalban, AS and Moors, KA and Marinos, G and Saboukh, A and Harris, D and Falk-Paulsen, M and Weber-Stiehl, S and Järke, L and Sommer, F and Welz, L and Bang, C and Franke, A and Chung, CJ and Bronowski, C and Schuchardt, S and Künzel, S and Aden, K and Schreiber, S and Kaleta, C and Baines, JF and Rosenstiel, P}, title = {Cross-species engraftment biases and metabolic divergence in gnotobiotic mice humanized with ulcerative colitis microbiota.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2581445}, doi = {10.1080/19490976.2025.2581445}, pmid = {41277418}, issn = {1949-0984}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; *Colitis, Ulcerative/microbiology/therapy/metabolism ; *Fecal Microbiota Transplantation ; Germ-Free Life ; Mice, Inbred C57BL ; Mice ; Bacteria/classification/genetics/isolation & purification/metabolism ; Disease Models, Animal ; Male ; Female ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Dysbiosis/microbiology ; Fungi/classification/genetics/isolation & purification ; Middle Aged ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory disease of the human colon. Dysbiotic gut microbiota play a central role in its pathogenesis, and alterations in microbial composition and function are closely linked to disease activity. Humanized gnotobiotic mice are increasingly used to study how dysbiotic, human-derived microbial communities shape intestinal inflammation. However, the fidelity of microbiota engraftment and its impact on host physiology and metabolism remain incompletely understood. In this study, we performed a multiomics analysis following fecal microbiota transfer (FMT) from eight patients with active UC into germ-free C57BL/6N mice (five mice per donor). The mice were monitored over three weeks. Longitudinal analysis of microbial communities was performed using 16S rRNA (bacteria) and ITS2 (fungi) amplicon sequencing. Microbial metabolic flux was inferred via genome-scale metabolic modeling, and plasma metabolites were assessed by targeted metabolomics. We observed donor-specific physiological changes in recipient mice, including variations in body weight and adipose tissue. Spontaneous colonic inflammation occurred in one group and was subsequently linked to unintended transfer of Clostridioides difficile, which was previously clinically unrecognised in the donor. While bacterial engraftment overall was generally donor-specific and stable across mice, fungal taxa were transferred inconsistently and at low abundance. Despite similar overall plasma metabolomic profiles, select metabolites, including 3-indoleacetic acid, were differentially associated with specific microbial taxa. Moreover, metabolic modeling revealed disrupted metabolic exchange networks in the mouse microbiota compared to the original human donor communities. In conclusion, while human FMT into germ-free mice reliably transmits bacterial features, it introduces metabolic alterations and fails to fully reproduce the fungal microbiome. These findings underscore the need for cautious interpretation of microbiota-driven effects in gnotobiotic models and highlight the limitations of current approaches in replicating the full complexity of human gut ecosystems.}, } @article {pmid41277357, year = {2025}, author = {Zheng, X and Jiang, Y and Wang, W and Sun, K and Zhou, L and Zhang, Y and Cui, J and Yu, H and Dong, W and Yan, B}, title = {Asiatic Acid Alleviates Ulcerative Colitis Through a Gut Microbiota-Driven cAMP/PKA/NF-κB Pathway: γ-Glutamyltyrosine Is a Crucial Player.}, journal = {Phytotherapy research : PTR}, volume = {}, number = {}, pages = {}, doi = {10.1002/ptr.70132}, pmid = {41277357}, issn = {1099-1573}, support = {82304807//National Natural Science Foundation of China/ ; BK20220299//Natural Science Foundation of Jiangsu Province/ ; Syhky202307//Clinical Pharmaceutical Research Foundation of Jiangsu Hengrui Medicine/ ; JLY2021052//Clinical Medical Science and Technology Development Foundation of Jiangsu University/ ; KS2203//Science and Technology Project of Kunshan/ ; KSF202139//Science and Technology Project of Kunshan/ ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, characterized by recurrent flare-ups and limited effectiveness of available drug therapies. Asiatic acid (AA), a triterpenoid compound extracted from Centella asiatica, has shown promising pharmacological activities and therapeutic potential in several inflammation-related diseases. However, AA's efficacy in treating UC and its precise mechanisms of action remain to be fully explored. This study aimed to provide a comprehensive assessment of AA's therapeutic effects on UC and to investigate its underlying mechanisms, with a focus on gut microbiota interactions. In our study, a dextran sulfate sodium-induced UC mouse model was used to evaluate AA's therapeutic potential and explore its impact on gut microbiota composition and function. We further used an antibiotic cocktail and fecal microbiota transplantation assays to substantiate the role of gut microbiota in AA's mechanisms of action. A metabolomic analysis was also conducted to identify key metabolic pathways and gut microbiota-derived metabolites involved in AA's effects. Our findings demonstrated that AA significantly alleviates symptoms of UC, including reducing weight loss, slowing disease progression, mitigating colonic inflammation, and restoring immune balance. Mechanistically, the beneficial effects of AA were strongly linked to alterations in the gut microbiota and its metabolites, particularly γ-glutamyltyrosine. This metabolite was found to regulate the cyclic adenosine monophosphate/protein kinase A/nuclear factor kappa-B signaling pathway, which plays a crucial role in inflammatory responses. Overall, these findings strongly suggest that AA holds promise as a therapeutic agent for UC by modulating the gut microbiota and influencing critical inflammatory pathways.}, } @article {pmid41276714, year = {2025}, author = {Mustafa, MA and Vadia, N and Varma, P and Al-Shaker, H and Mohanty, B and Dhyani, A and Kaur, I and Chauhan, AS and Garg, G}, title = {The Gut-Brain Axis in Alzheimer's Disease: Exploring Microbial Influences and Therapeutic Strategies.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {151}, pmid = {41276714}, issn = {1559-1182}, mesh = {*Alzheimer Disease/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; *Brain/metabolism/pathology ; Dysbiosis ; Probiotics/therapeutic use ; *Brain-Gut Axis ; }, abstract = {Microbiota residing in the human gastrointestinal tract play a critical role in maintaining homeostasis through immune regulation, metabolic activity, and signaling to the central nervous system. Recent studies have highlighted the influence of gut microbiota on neurodegenerative diseases, particularly Alzheimer's disease (AD), through the microbiota-gut-brain axis. This bidirectional communication system involves neural, hormonal, and immunological pathways, linking gut health directly with brain function. Disruption of the gut microbial balance-known as dysbiosis-has been associated with increased amyloid-beta (Aβ) deposition, tau hyperphosphorylation, oxidative stress, neuroinflammation, and impaired neurotransmission, all of which are key pathological features of AD. Microbial metabolites such as short-chain fatty acids, trimethylamine N-oxide, and gasotransmitters influence the permeability of the blood-brain barrier and modulate neuroimmune responses. Emerging evidence also indicates that gut microbiota may contribute to the early onset and progression of AD through systemic inflammation and metabolic dysfunction. Modulating the gut microbiome, therefore, presents a novel avenue for therapeutic intervention. This review aims to synthesize current findings on how gut microbiota alterations contribute to AD pathology. Furthermore, it explores therapeutic strategies-including diet, probiotics, prebiotics, polyphenols, and fecal microbiota transplantation-that hold potential in restoring microbial balance and mitigating cognitive decline in AD.}, } @article {pmid40516101, year = {2025}, author = {Saqr, A and Cheng, S and Al-Kofahi, M and Staley, C and Jacobson, PA}, title = {Microbiome-Informed Dosing: Exploring Gut Microbial Communities Impact on Mycophenolate Enterohepatic Circulation and Therapeutic Target Achievement.}, journal = {Clinical pharmacology and therapeutics}, volume = {118}, number = {6}, pages = {1477-1488}, doi = {10.1002/cpt.3740}, pmid = {40516101}, issn = {1532-6535}, mesh = {Humans ; *Mycophenolic Acid/pharmacokinetics/administration & dosage/analogs & derivatives ; *Gastrointestinal Microbiome/drug effects/physiology ; *Enterohepatic Circulation ; *Immunosuppressive Agents/pharmacokinetics/administration & dosage ; Male ; Female ; Middle Aged ; Hematopoietic Stem Cell Transplantation ; Adult ; Models, Biological ; Feces/microbiology ; }, abstract = {Pharmacomicrobiomics is an emerging field due to important microbiome effects on pharmacokinetics and clinical outcomes. However, the application of this knowledge remains limited. Mycophenolic acid (MPA) is the primary active metabolite of the immunosuppressant, mycophenolate mofetil (MMF). MPA undergoes glucuronidation to form MPA glucuronide (MPAG) which is deglucuronidated by bacterial β-glucuronidases and reformed as MPA through enterohepatic circulation (EHC). We studied the stool microbiome effect on the pharmacokinetics of MPA, its metabolites, and EHC in hematopoietic cell transplant (HCT) recipients using a semi-mechanistic population pharmacokinetic model. Microbiome communities were identified using correlation network analysis, and their impact on pharmacokinetics was assessed using full fixed-effects modeling. Simulations were then conducted to evaluate MMF dosing regimens and to assess the impact of community abundance on EHC and MPA therapeutic target achievement. High abundance of Bacteroides uniformis-dominant and Bacteroides vulgatus-dominant communities was associated with higher EHC and an increase in MPA exposure. Low abundance of these communities was associated with a 52-80% and 4-83% lower EHC and MPA exposure, respectively. Simulations showed 70% of individuals with low abundance of these communities achieved the therapeutic target at the typical HCT MMF dose of 1,000 mg Q8 hours IV; however, ≥ 95% were within the therapeutic target at 1,250 mg Q8 hours or 1,750 mg Q12 hours. EHC accounted for 34% of the MPA area under the curve. Elimination of EHC reduced troughs by 100%. This work quantifies the microbiome's effect on pharmacokinetics, paving the way for future microbiome-informed dosing to optimize therapeutic target attainment.}, } @article {pmid41276052, year = {2025}, author = {Huan, P and Wang, W and Qi, Y and Sun, J and Zhou, R and Liu, L and Pan, S and Xu, Y and Wang, Z and Zhu, Z and Han, C}, title = {Cynomorium songaricum polysaccharide attenuates high-fat diet-induced testicular dysfunction by modulating the gut microbiota.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {149114}, doi = {10.1016/j.ijbiomac.2025.149114}, pmid = {41276052}, issn = {1879-0003}, abstract = {Obesity disrupts gut microbiota homeostasis and impairs spermatogenesis; however, microbiota-targeted therapies remain insufficiently explored. In this study, a water-soluble polysaccharide(CSP1) was purified from the medicinal plant Cynomorium songaricum. Structural characterization identified CSP1 as a homogeneous α-glucan (Mw 5776 Da) with a backbone of →4)-α-D-Glcp-(1 → residues and C-6 branching. In high-fat diet (HFD)-induced obese mice, CSP1 administration alleviated testicular dysfunction by enhancing sperm count and motility, restoring serum testosterone levels, and ameliorating histopathological damage and germ cell apoptosis. Mechanistically, CSP1 remodeled the gut microbiota composition by suppressing LPS-producing taxa while enriching beneficial populations including SCFA-producing Lachnospiraceae and Bacteroidota. This reshaping reinforced intestinal barrier integrity, as evidenced by the upregulation of ZO-1, occludin, and MUC2. Consequently, CSP1 treatment led to a favorable shift in gut microbiota-derived metabolites, significantly reducing systemic LPS translocation while increasing beneficial short-chain fatty acids (SCFAs) such as acetate and propionate. These changes collectively inhibited testicular TLR4/MyD88/NF-κB activation and downstream pro-inflammatory cytokines (TNF-α, IL-1β). Fecal microbiota transplantation confirmed the causal role of the gut microbiota in mediating CSP1's protective effects. Our findings establish CSP1 as a gut-microbiota-targeting polysaccharide that alleviates obesity-associated male infertility by orchestrating a beneficial remodeling of the gut microbial ecosystem and its metabolic output, offering a novel therapeutic strategy for metabolic reproductive disorders.}, } @article {pmid41275982, year = {2025}, author = {Huang, Y and Hu, J and Xu, H and Zhu, R and Liu, L and Chen, X and Sun, Y and Zhao, Y and Zhong, Y and Cheng, B and Huang, X and Lu, H and Xu, ZZ}, title = {Propylparaben Induces Immunotoxicity in Zebrafish via Oxidative Stress and Gut Microbiota-Immune Axis Dysregulation.}, journal = {Fish & shellfish immunology}, volume = {}, number = {}, pages = {111024}, doi = {10.1016/j.fsi.2025.111024}, pmid = {41275982}, issn = {1095-9947}, abstract = {Propylparaben (PP), a widely used preservative, has an unclear immunotoxicity profile. In this study, zebrafish embryos were exposed to 2.5, 5, and 10 μM PP to investigate its developmental and immunological effects. PP induced dose-dependent developmental abnormalities and immunotoxicity. Specifically, it significantly reduced the populations of neutrophils, macrophages, and hematopoietic stem cells (HSCs) in zebrafish embryos. Mechanistically, PP suppressed the TLR4/MyD88/NF-κB pathway and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in embryos, whereas adult zebrafish exhibited marked upregulation of this pathway and these cytokines in intestinal and splenic tissues. PP exposure also elevated reactive oxygen species (ROS) and lipid peroxidation. Co-treatment with the antioxidant astaxanthin (AST) attenuated PP-induced immunotoxicity by reducing ROS level and restoring HSCs, neutrophil, and macrophage populations, confirming oxidative stress as a key mechanism. Furthermore, PP induced gut microbiota dysbiosis and intestinal developmental defects. Exposing germ-free (GF) zebrafish embryos to PP resulted in no significant changes in neutrophils and HSCs, indicating that its immunotoxicity is microbiota-dependent. This was confirmed by fecal microbiota transplantation (FMT), where embryos receiving microbiota from PP-treated donors showed concentration-dependent decreases in neutrophils and HSCs. Our study elucidates the ecological and health risks of PP, advocating for reevaluation of preservative safety and microbiota-targeted mitigation strategies.}, } @article {pmid41274019, year = {2025}, author = {Chen, R and Qian, J and Wang, Q and Li, Y and Xu, Z and Zhang, M and Wang, M and Nie, H and Yang, W and Tong, X and Yan, F}, title = {Periodontitis exacerbates metabolic dysfunction-associated steatotic liver disease via the gut microbiota-derived tryptophan metabolism-AHR axis in obesity.}, journal = {EBioMedicine}, volume = {122}, number = {}, pages = {106037}, doi = {10.1016/j.ebiom.2025.106037}, pmid = {41274019}, issn = {2352-3964}, abstract = {BACKGROUND: Periodontitis is linked to metabolic dysfunction-associated steatotic liver disease (MASLD); however, the underlying mechanisms remain unclear.

METHODS: Periodontitis was investigated in male mice with high-fat diet (HFD)-induced MASLD. Gut microbiome and metabolomic profiling were conducted using16S rRNA gene sequencing, along with both untargeted and targeted metabolomic profiling via liquid chromatography-tandem mass spectrometry. Intestinal barrier integrity was evaluated by histopathological analysis. Faecal microbiota transplantation was conducted and the vital role of the aryl hydrocarbon receptor (AHR) was confirmed using Ahr gene knockout (Ahr[-/-]) mice. The protective roles of tryptophan derivative indole-3-propionic acid (IPA) and the tryptophan-metabolising probiotic Limosilactobacillus reuteri were assessed following their administration via oral gavage. The impact of endotoxin-mediated hyperinflammation on hepatic mitochondrial dynamics was examined in vitro.

FINDINGS: Periodontitis promoted MASLD, gut microbiota dysbiosis, and tryptophan metabolism depletion, leading to intestinal barrier dysfunction, systemic inflammation, and endotoxin overexpression in HFD-fed mice. Periodontitis-accelerated MASLD was attenuated in HFD-fed Ahr[-/-] mice. In an AHR-dependent manner, IPA or L. reuteri alleviated the detrimental effects of periodontitis on MASLD progression, intestinal barrier impairment, systemic inflammation, and endotoxin translocation to the liver. Conditioned medium from endotoxin-stimulated THP-1 cells promoted mitochondrial fission in HepG2 cells by upregulating Drp1 expression.

INTERPRETATION: Periodontitis exacerbates MASLD by disrupting the gut microbiota-tryptophan metabolism-AHR axis, leading to intestinal barrier dysfunction, systemic inflammation, and endotoxin translocation. Endotoxin plays a pivotal role in promoting hepatic mitochondrial fission during the exacerbation of MASLD by periodontitis. AHR agonists offer a novel intervention strategy for patients with comorbid MASLD and periodontitis.

FUNDING: This work was supported by the Jiangsu Province Key Research and Development Program [No. BE2022670]; National Natural Science Foundation of China [No. 82270979]; Jiangsu Provincial Medical Key Discipline Cultivation Unit [No. JSDW202246]; and High-Level Hospital Construction Project of Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University [No. 0224C001].}, } @article {pmid41273871, year = {2025}, author = {Jie, L and Liu, J and Liu, Y and Zhang, K and Shen, X and Xu, B and Ji, W and Shi, X}, title = {Sclareol alleviates synovial inflammation in knee osteoarthritis by regulating sphingolipid metabolism along the gut-bone axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {149}, number = {}, pages = {157563}, doi = {10.1016/j.phymed.2025.157563}, pmid = {41273871}, issn = {1618-095X}, abstract = {OBJECTIVE: Sclareol(SCL) is a diterpene alcohol compound with anti-inflammatory, antibacterial, and antioxidant properties, and it has high oral bioavailability. However, its pharmacological effects in the field of knee osteoarthritis(KOA) remain unclear.

METHODS: The pharmacological effects of SCL intervention on synovial inflammation in KOA rats were observed using methods such as histopathology and molecular biology. Subsequently, further in vivo and in vitro experiments were conducted to explore the effects of SCL. By combining metabolomics and 16S rRNA sequencing, the impact of SCL on the gut microbiota and metabolic levels was investigated. Based on the results of the omics analyses, the mechanism by which SCL alleviates synovial inflammation in KOA was verified.

RESULTS: Histopathology and molecular biology showed that SCL can significantly improve synovial inflammation and pathological progression in KOA. However, SCL did not exhibit anti-inflammatory effects in vitro experiments or in rats treated with antibiotics. Combined analysis of untargeted metabolomics and 16S RNA-seq indicated that SCL may exert its effects by altering the abundance of bacterial groups like Prevotellaceae ga6a1 group and Corynebacterium and regulating the levels of lipid metabolites such as ceramides. Finally, our combined in vivo and in vitro experiments confirmed that fecal microbiota transplantation (FMT) from SCL-treated rats could modulate gut microbiota composition, reduce sphingolipid metabolism, lower necroptosis levels of synovial macrophages, and decrease inflammation in KOA rats.

CONCLUSION: SCL reduces the abundance of Prevotellaceae ga6a1 group and Corynebacterium decreased levels of ceramides, sphingomyelin, and sphingosine, which in turn lower synovial macrophage necroptosis and synovial inflammation.}, } @article {pmid41271774, year = {2025}, author = {Qin, W and Mei, Q and Wang, G and Wang, R and Huang, Z and Fu, Y and Xu, B and Huang, C and Ai, L and Zeng, Y}, title = {Faecalibacterium prausnitzii alleviates experimental recurrent acute pancreatitis by producing oleic acid to regulate MAPK/NF-κB signaling and Th17/Treg balance.}, journal = {NPJ biofilms and microbiomes}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41522-025-00845-0}, pmid = {41271774}, issn = {2055-5008}, support = {No.82200714//National Natural Science Foundation--Youth Foundation/ ; No. 82300731//National Natural Science Foundation--Youth Foundation/ ; No.10-21-308-420//USST Medical-engineering Cross-project/ ; No. 32025029//National Science Foundation for Distinguished Young Scholars of China/ ; No. 82270671//Natural Science Foundation of China/ ; CCTR-2022B02//Shanghai General Hospital Characteristic Research Program/ ; }, abstract = {Acute pancreatitis (AP) is a complex gastrointestinal disorder associated with disruptions in the gut microbiome. However, the gut microbial and metabolomic profiles in recurrent acute pancreatitis (RAP), which is a clinically distinct subtype of AP, remain unclear. This study integrated microbiome-metabolome analysis to identify the key gut microbial species and metabolic pathways associated with RAP. The findings reveal that the abundance of Faecalibacterium prausnitzii (Fp) is significantly diminished in RAP patients, exhibiting a strong negative correlation with disease severity. Consistent with this observation, fecal microbiota transplantation enriched with Fp significantly ameliorated pancreatic injury in RAP mice. We further isolated Fp Ai 3-16 strain from the stool of healthy volunteers. Functional validation using experimental AP models demonstrates that Fp Ai 3-16 and its metabolite oleic acid (OA) can effectively attenuate pancreatitis by modulating MAPK/NF-κB signaling pathways and restoring the intestinal Th17/Treg balance. Importantly, these results extend beyond the context of RAP, as they highlight the broader significance of the gut-pancreas axis in the pathogenesis of AP. Thus, the elucidation of the underlying molecular mechanisms offers novel therapeutic avenues for RAP management and provides a foundation for further investigations into the intricate interplay between the gut microbiome and the pancreas.}, } @article {pmid41270737, year = {2025}, author = {Long, X and Wang, H and Lu, Y and Gao, X and Xiao, Y and Zhang, M and Guo, J and Yang, J and Zhang, R and Li, Q and Zhou, G and Yang, R and Chen, F and Wu, Q and Sun, L and Chu, C and Zhu, X and Wu, Z and Ren, Q and You, C and Liu, Z and Li, Q and Liu, D and Cheng, D and Kang, P and Chen, A and Wu, Q and Fang, Q and Wei, L and Zhang, L and Li, J and Panagiotou, G and Jia, W and Zeng, R and Ni, Y and Chen, L and Li, H}, title = {Interindividual variability in gut microbiome mediates the efficacy of resistant starch on MASLD.}, journal = {Cell metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmet.2025.10.017}, pmid = {41270737}, issn = {1932-7420}, abstract = {Our randomized, placebo-controlled trial showed resistant starch (RS), a type of prebiotic, has therapeutic effects in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we observed its heterogeneous efficacy, where 30% of participants exhibited limited benefits, which was replicated in a multi-center trial (ChiCTR2300074588). Multi-omics analysis and fecal microbiota transplantation identified baseline microbiota as a dominant contributor of response. Further population stratification and network analysis combined with in vitro and in vivo experiments revealed Prevotella as the key cause of low response by inhibiting RS-degrading bacteria, thereby impairing RS utilization. Conversely, Bifidobacterium pseudocatenulatum RRP01, a strain isolated from our cohort, restored RS degradation and improved Prevotella-attenuated RS response. Furthermore, we developed a predictive model integrating baseline microbial and clinical features (area under the curve [AUC] = 0.74-0.87), enabling stratification for personalized interventions. Our study indicates that gut microbiota determines the heterogeneity in RS efficacy and offers possibilities for novel microbiota-oriented precision therapeutics for MASLD.}, } @article {pmid41270390, year = {2025}, author = {Chen, L and He, W and Gao, L and Lu, Y and Zhu, L}, title = {Shouhui Tongbian Capsules ameliorate heart failure and atrial fibrillation via gut microbiota regulation.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {149}, number = {}, pages = {157549}, doi = {10.1016/j.phymed.2025.157549}, pmid = {41270390}, issn = {1618-095X}, abstract = {BACKGROUND: Heart failure (HF) with atrial fibrillation (AF) poses a significant therapeutic challenge due to its complex pathophysiology. Shouhui Tongbian Capsules (SHTB) contain multiple active components that have been proven to affect HF or AF through the intestinal flora. However, the specific therapeutic effects of this drug on HF combined with AF, as well as whether these effects are achieved by regulating the intestinal flora, still require systematic research.

PURPOSE: This study aimed to elucidate the cardioprotective effects of SHTB in a doxorubicin (DOX)-induced HF/AF rat model, focusing on gut microbiota modulation and myocardial transcriptome regulation.

METHODS: Rats were randomized into control, model (DOX-induced HF/AF), SHTB treatment (low/medium/high doses), and metoprolol groups. Pharmacodynamically, cardiac function was assessed via echocardiography and electrocardiography. And myocardial fibrosis was quantitatively evaluated using pathomorphology analysis. Mechanistically, microvascular integrity was examined via immunofluorescence, while the neural activity ligand-receptor interaction pathway-related protein expression was analyzed by immunohistochemistry. Additionally, gut microbiota composition was determined via 16S rRNA sequencing, and myocardial transcriptome profiling was performed using RNA sequencing. Furthermore, fecal microbiota transplantation (FMT) experiments were performed to validate the role of gut microbiota in the observed effects.

RESULTS: The SHTB intervention significantly improved the cardiac function and electrophysiological stability of HF/AF rats, along with enhancing microvascular maturation and reducing myocardial fibrosis. The analysis of the intestinal microbiota showed that SHTB effectively restored the microbial ecological balance, especially regulating the abundance of key genera (such as Turicibacter) closely related to disease progression and treatment efficacy. Transcriptional analysis identified the neural activity ligand-receptor pathway as the key mechanism, and FMT experiments demonstrated that SHTB modulates the Edn1-Agtr1a-Bdkrb2 axis through gut microbiota, ultimately leading to improved cardiac function. The synergistic effect of the composition of the intestinal microbiota and myocardial molecular targets jointly contributed to the improvement of cardiac remodeling in HF/AF.

CONCLUSION: SHTB ameliorates HF with AF by synergistically modulating the gut-heart axis, involving gut microbiota restoration, myocardial fibrosis suppression, and vascular tension regulation via the Edn1-Agtr1a-Bdkrb2 axis. This multi-target mechanism substantiates SHTB's potential as a promising adjunct therapy for HF/AF.}, } @article {pmid41270389, year = {2025}, author = {Zheng, M and Meng, Y and Feng, J and Liang, H and Mu, X and Feng, C}, title = {Shenling Baizhu Powder potentiates immunotherapy response: putative roles of gut microbial remodeling and fatty acid metabolism modulation.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {149}, number = {}, pages = {157559}, doi = {10.1016/j.phymed.2025.157559}, pmid = {41270389}, issn = {1618-095X}, abstract = {BACKGROUND: Low response rates and immune-related adverse events (irAEs) are major factors affecting the efficacy of PD-1 monoclonal antibody (mAb) immunotherapy in NSCLC. Modulating the gut microbiota-immune-tumor axis is considered a key strategy to overcome these challenges.

PURPOSE: This study aimed to investigate whether Shenling Baizhu powder (SLBZS), a traditional Chinese medicine formula, could enhance the efficacy of PD-1 mAb immunotherapy and mitigate irAEs by regulating gut microbiota and host metabolism.

STUDY DESIGN: Two experimental models were employed: (1) a standard Lewis subcutaneous tumor mouse model to evaluate therapeutic effects and irAEs, and (2) a lung metastasis model using bioluminescence imaging to assess tumor progression. Additionally, an antibiotic-cleared mouse model combined with fecal microbiota transplantation (FMT) was used to validate gut microbiota-mediated mechanisms.

METHODS: Subcutaneous tumor growth, organ toxicity, and metastasis were monitored in vivo. Multi-omics approaches included fecal 16S rDNA sequencing, untargeted/targeted plasma metabolomics, and immune profiling of splenic and tumor microenvironment (TME) lymphocytes. SLBZS/FMT interventions were applied to antibiotic-treated mice to assess microbiota-dependent effects.

RESULTS: SLBZS synergized with PD-1 mAb to significantly inhibit tumor growth and reduce multi-organ irAEs. In the metastasis model, SLBZS suppressed early tumor implantation and late-stage dissemination. Multi-omics analyses revealed that SLBZS enriched beneficial gut bacteria (e.g., Akkermansia, Lactobacillus, Muribaculum) and microbial metabolites, including short-chain fatty acids (SCFAs), while enhancing anti-tumor T-cell subsets in the spleen and TME. Critically, SLBZS/FMT restored gut microbiota homeostasis and reversed antibiotic-induced immunotherapy resistance.

CONCLUSION: SLBZS, as a traditional Chinese medicinal formulation, enhances the efficacy of PD-1 mAb through a unique dual-regulatory mechanism. It concurrently remodels the gut microbiota structure and optimizes the metabolic microenvironment, with these synergistic actions collectively amplifying anti-tumor immunity while reducing irAEs. This dual-mode efficacy distinguishes SLBZS from conventional microbial modulators that solely target microbiota without metabolic coordination. Our study provides the first experimental validation of SLBZS as a clinically valuable adjuvant of Chinese medicinal origin for NSCLC immunotherapy. Furthermore, we pioneer a novel research paradigm integrating traditional Chinese medical theory with the "microbiota-metabolism-immune network" axis, thereby offering innovative therapeutic strategies for refining cancer immunotherapies.}, } @article {pmid41270175, year = {2025}, author = {Liu, W and Yang, J and Wei, Z and Kong, W and Dong, Z and Wei, Y and Zhuang, J and Qi, J}, title = {miRNA-loaded biomimetic nanoparticles orchestrate gut microbe to ameliorate inflammatory bowel disease.}, journal = {Science advances}, volume = {11}, number = {47}, pages = {eadw5984}, doi = {10.1126/sciadv.adw5984}, pmid = {41270175}, issn = {2375-2548}, mesh = {*MicroRNAs/genetics/chemistry/administration & dosage ; *Nanoparticles/chemistry ; Animals ; *Inflammatory Bowel Diseases/microbiology/therapy/pathology/drug therapy ; *Gastrointestinal Microbiome/drug effects ; Mice ; Lacticaseibacillus rhamnosus/metabolism/genetics ; Extracellular Vesicles/metabolism ; *Biomimetic Materials/chemistry ; Disease Models, Animal ; Humans ; Colitis/pathology ; Biomimetics ; Probiotics ; }, abstract = {Modulation of gut microbiota has emerged as a promising therapeutic strategy for inflammatory bowel disease (IBD). However, current interventions such as probiotics and fecal microbiota transplantation remain limited by insufficient safety and efficacy. To address this, we engineered commensal Lactobacillus rhamnosus (LGG) using miRNA-loaded biomimetic nanoparticles to enhance its proliferation and indole-3-carboxaldehyde production. By functionalizing bacterial extracellular vesicles (BEVs) derived from LGG with lipid nanoparticles (LNPs), we developed BEV-LNPs that exhibited enhanced targeting efficiency toward LGG compared to Escherichia coli. In vitro and in vivo studies demonstrated that BEV-LNPs showed superior stability in simulated physiological fluids and gastrointestinal environments compared to conventional LNPs. When combined with 5-aminosalicylic acid, the BEV-LNP formulation notably improved outcomes in acute and chronic colitis models, reducing inflammation, restoring epithelial barrier integrity, and promoting microbial balance. This study presents an effective strategy for colitis treatment by leveraging miRNA-loaded nanoparticles.}, } @article {pmid41269489, year = {2025}, author = {Lapauw, L and Amini, N and Switsers, E and Dupont, J and Vercauteren, L and Derrien, M and Raes, J and Gielen, E}, title = {Effect of host and gut microbiota-altering interventions on sarcopenia or its defining parameters: a systematic review and meta-analysis of nutrition-based intervention studies.}, journal = {Aging clinical and experimental research}, volume = {}, number = {}, pages = {}, doi = {10.1007/s40520-025-03216-z}, pmid = {41269489}, issn = {1720-8319}, abstract = {AIM: To investigate effects of host- and gut microbiota (GM)-altering interventions on sarcopenia (parameters).

METHODS: Upon PROSPERO registration (CRD42022347363), six databases and one registry were searched until January 5th 2024 and updated on June 10th 2025 for diet, pre-, pro-, or synbiotics mono-interventions in populations with mean age ≥ 50 years. (Standardized) mean differences (SMD) and 95% confidence intervals (CI) were computed using random-effects models if heterogeneity was > 50%. Risk of bias (Rob) & GRADE assessments were carried out to assess the evidence' quality and certainty.

RESULTS: The qualitative analysis included 38 diet, 13 prebiotics, 11 probiotics and 1 synbiotics studies, totaling 4842 participants (59%♀), mostly of high RoB. The quantitative analysis included 49 studies. Probiotics improved muscle strength by 1.90 kg and gait speed by 0.08 m/s. Fiber (whole-food)-enriched diets improved muscle strength with 1.25 kg and energy-restricted diets, aimed at weight loss, improved muscle mass if mean age was < 60 years and if the intervention lasted no longer than 12 weeks. High-protein diets improved muscle mass in women and if the intervention lasted at least 12 weeks. Studies involving participants with sarcopenia were only included in the qualitative analysis, since none provided sufficient data to allow a quantitative synthesis.

DISCUSSION: Fiber (whole food)-enriched diets and probiotics improve muscle strength. The latter intervention also improves gait speed. High-protein diets improve muscle mass in women and with intervention durations ≥ 12 weeks. Future studies should include fecal sampling to assess whether GM modulate the observed effects.

CONCLUSION: Specific diets and probiotics offer potential to improve sarcopenia parameters.}, } @article {pmid41269457, year = {2025}, author = {Younis, NK and Alfarttoosi, KH and Sanghvi, G and Roopashree, R and Kashyap, A and Krithiga, T and Taher, WM and Alwan, M and Jawad, MJ and Ali Al-Nuaimi, AM}, title = {Attenuating Neurotoxicity Through Fecal Microbiota Transplant: Mechanisms and Therapeutic Potential.}, journal = {Molecular neurobiology}, volume = {63}, number = {1}, pages = {128}, pmid = {41269457}, issn = {1559-1182}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; Animals ; *Gastrointestinal Microbiome/physiology ; *Neurotoxicity Syndromes/therapy/microbiology ; }, abstract = {Neurotoxicity, triggered by drugs, environmental pollutants, metabolic disorders, or infections, can cause lasting neurological dysfunction and cognitive impairment. Recent research highlights the gut microbiota's crucial role in regulating brain health and vulnerability to neurotoxic damage, sparking interest in fecal microbiota transplantation (FMT) as a potential treatment. This review examines how FMT may counteract neurotoxicity and assesses its therapeutic potential for neurodegenerative diseases, neuroinflammation, and cognitive decline. The gut-brain axis-a bidirectional communication system between the gut and the central nervous system (CNS)-acts as the primary route through which gut microbes influence brain function. Growing evidence suggests that microbiota imbalances can exacerbate neuroinflammation, oxidative stress, blood-brain barrier disruption, and altered neurotransmitter production, all of which contribute to neurotoxicity. FMT, the transfer of donor fecal microbes to a recipient's gut, has demonstrated promise in restoring microbial equilibrium and reducing neurotoxic effects in both animal studies and human trials. The review also explores microbial profiles tied to neuroprotection versus those linked to neurotoxic conditions, along with the prospects of tailored microbiome therapies. Despite its potential, FMT faces challenges, including protocol standardization, donor selection criteria, and long-term efficacy. More research is needed to unravel the intricacies of gut-brain interactions and optimize FMT for clinical use. If these hurdles are addressed, FMT could become a transformative therapy for neurotoxicity-related disorders.}, } @article {pmid41268538, year = {2025}, author = {Jiao, JM and Liu, CG and Zang, D and Chen, J}, title = {Gut microbiota and metabolites: emerging prospects in the treatment of non-small cell lung cancer.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1638942}, pmid = {41268538}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Carcinoma, Non-Small-Cell Lung/therapy/metabolism/microbiology ; *Lung Neoplasms/therapy/metabolism/microbiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; }, abstract = {Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer, accounting for approximately 85% of all cases, and is associated with a poor prognosis. Despite significant advancements in treatment modalities, therapeutic efficacy remains suboptimal, underscoring the urgent need for novel strategies. In recent years, increasing attention has been directed toward the pivotal role of gut microbiota-host interactions in the treatment of NSCLC. This review systematically examines the influence of current NSCLC therapies on gut microbiota and metabolism, explores the relationship between the microbiome and therapeutic response, and highlights the critical functions of probiotics, microbial metabolites, fecal microbiota transplantation (FMT), and dietary interventions in NSCLC management. By elucidating the mechanisms through which gut microbiota and their metabolites modulate treatment efficacy, we investigate the potential of exogenous interventions targeting the gut ecosystem to enhance therapeutic outcomes and mitigate adverse effects. Modulating the intestinal microbiota represents a promising clinical avenue and offers a new frontier for the development of future NSCLC treatment strategies.}, } @article {pmid41268164, year = {2025}, author = {Zhao, M and Chen, D and Hu, X and Xie, C and Xu, L and Zhou, F}, title = {Gut-ovary axis in polycystic ovary syndrome: mechanistic insights and gut microbiota-targeted therapeutic strategies.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1684492}, pmid = {41268164}, issn = {1664-2392}, mesh = {Humans ; *Polycystic Ovary Syndrome/microbiology/therapy/metabolism ; *Gastrointestinal Microbiome/physiology ; Female ; Probiotics/therapeutic use ; *Ovary/metabolism ; Fecal Microbiota Transplantation/methods ; }, abstract = {Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that significantly affects women's reproductive health and quality of life. Its pathogenesis involves multiple factors, including genetics, environment, and metabolism. In recent years, with the growing body of research on PCOS, the "gut-ovary axis" hypothesis has become a prominent research focus. This hypothesis suggests that an imbalance in gut bacteria may significantly influence the onset and progression of PCOS through various pathways, such as immune regulation, metabolic disturbances, and hormonal imbalances. This article aims to review the role of the "gut-ovary axis" in PCOS and to explore novel treatment strategies based on gut microbiota modulation, including probiotics, fecal microbiota transplantation, and dietary interventions. These strategies represent promising research avenues for future PCOS treatments, with preliminary studies demonstrating their potential to improve clinical symptoms. However, it is crucial to note that these are not yet established therapies and require substantial further validation. Novelty and Significance of this Review: This review moves beyond a descriptive catalog of associations to provide a critical appraisal of the gut-ovary axis in PCOS. We systematically differentiate well-established mechanisms from speculative hypotheses, explicitly identify persistent knowledge gaps, and evaluate the translational potential of microbiota-targeted therapies, thereby offering a refined framework for future basic and clinical research.}, } @article {pmid41267780, year = {2025}, author = {Sharma, I and Sudarsanan, D and Moonah, S}, title = {The gut microbiome as a major source of drug-resistant infections: emerging strategies to decolonize and target the gut reservoir.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1692582}, pmid = {41267780}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; *Bacterial Infections/microbiology/therapy/prevention & control ; *Drug Resistance, Bacterial ; Phage Therapy ; *Bacteria/drug effects ; Antimicrobial Peptides/therapeutic use ; }, abstract = {Infections caused by antimicrobial-resistant bacteria represent a significant global health crisis that continues to worsen, creating an urgent need for alternative treatment and prevention strategies. A major source of drug-resistant bacteria is the human gut. The gut microbiota consists of bacteria that are frequently exposed to antibiotics, leading to selective pressure that promotes the development of resistant strains such as carbapenem-resistant Enterobacterales (CRE) and vancomycin-resistant enterococci (VRE). These drug-resistant bacteria can spread from the gut to other body sites, leading to hard-to-treat and potentially life-threatening infections such as bacteremia, surgical site infections, and urinary tract infections. Targeting the gut reservoir is essential in the fight against antimicrobial resistance. In this review, we focus on emerging non-antibiotic strategies aimed at eliminating drug resistant bacteria from the gut before they cause invasive infections, with particular emphasis on clinical evidence. Approaches discussed include fecal microbiota transplantation, bacteriophage therapy, antimicrobial peptides, probiotics, and dietary interventions. Optimizing these strategies, while continuing to explore newer approaches, will be essential to combat the growing threat of drug-resistant infections.}, } @article {pmid41265661, year = {2025}, author = {Cao, P and Li, Y and Zhang, S and Li, C and Sun, Y and An, B}, title = {Study on the efficacy and mechanism of fecal microbiota transplantation for depression based on circadian rhythm.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {106186}, doi = {10.1016/j.bbi.2025.106186}, pmid = {41265661}, issn = {1090-2139}, abstract = {BACKGROUND: Depression is closely associated with disruptions in circadian rhythms, and emerging evidence highlights critical roles of gut dysbiosis in its pathogenesis. However, the mechanisms by which FMT chronotherapy influences circadian gene in depression-via gut microbiota-remain poorly understood.

METHODS: In this study, we established a chronic unpredictable mild stress (CUMS) mouse model and performed fecal microbiota transplantation (FMT) using donor microbiota from healthy mice at two distinct circadian time points-zeitgeber time (ZT) 4 or ZT16 to identify the optimal timing for FMT based on behavioral assessments. Integrating omics dependent mechanisms of antidepressant effects mediated by these key functional bacteria.

RESULTS: Health-FMT significantly alleviated depressive-like behaviors, with superior efficacy at ZT4. It restored circadian gene expressions and attenuated neuroinflammation expression in the hippocampus and prefrontal cortex. 16S rRNA sequencing revealed that Health-FMT reduced uncultured_bacterium_g_Alistipes abundance, a genus linked to tryptophan availability. Tryptophan supplementation regulated circadian gene expressions, inflammatory factors, brain-derived neurotrophic factors (BDNF), microglial and astrocytic activation, and exerted antidepressant effects via the ERK signaling pathway.

CONCLUSIONS: These findings suggest that Health-FMT exerts antidepressant effects by restoring gut homeostasis, particularly by reducing Alistipes, thereby rebalancing tryptophan metabolic and circadian gene expressions. These findings offer a new possible mechanism and novel insights into the microbiota-gut-brain axis in depression, and underscore the importance of chronotherapy in FMT-based therapeutic strategies.}, } @article {pmid41265501, year = {2025}, author = {Yan, S and Xie, Y and Xv, J and Wang, K and Wang, J and Cao, Y and Han, X and Chen, F and Zhou, L and Jiang, Y and Liu, Y}, title = {Shengjiang San attenuates sepsis-induced acute intestinal injury via Lactobacillus murinus derived IAAld-mediated macrophage polarization through NF-κB and TGF-β signaling.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {120910}, doi = {10.1016/j.jep.2025.120910}, pmid = {41265501}, issn = {1872-7573}, abstract = {ETHNOPHARMACOLOGY ASSOCIATED: Sepsis is a life-threatening condition triggered by a dysregulated host response to infection, characterized by uncontrolled systemic inflammation and often culminating in multiple organ damage. Shengjiang San (SJS), a classic traditional Chinese medicinal (TCM) formula, has been historically utilized for its efficacy in removing heat, resolving toxicity, and reducing inflammation. Nevertheless, the precise role and mechanisms through which SJS modulates inflammatory responses and protects against sepsis-induced multi-organ injury are not yet fully understood.

OBJECTIVE: To investigate the protective mechanisms of SJS that improve sepsis-induced acute intestinal injury (SAII) by modulating the abundance and metabolism of the gut microbiota.

METHODS: A sepsis animal model was established using cecal ligation and puncture. The protective effects of SJS in SAII were evaluated through behavioral assessments, enzyme-linked immunosorbent assay, histological examination, and immunofluorescence analysis. Fecal samples were subjected to 16S rRNA sequencing and non-targeted metabolomics to identify probiotic taxa and metabolites associated with SJS administration. Proteomic analysis integrated with network pharmacology was performed to explore the underlying mechanisms. Fecal microbiota transplantation (FMT) and microbial metabolite analysis were utilized to elucidate the potential mechanism.

RESULTS: SJS was observed to significantly improve clinical scores, reduce pro-inflammatory cytokines, including IL-6, TNF-α and IL-1β. SJS also restored integrity of the intestinal barrier by upregulating the expression of ZO-1 and Claudin-1. 16S rRNA sequencing analysis demonstrated that SJS induced significant restructuring of the gut microbiota, including a marked increase in Lactobacillus murinus (L.M.) abundance. Proteomic and network pharmacological analyses revealed that SJS was protected against SAII by inhibiting NF-κB-mediated M1 polarisation while promoting TGF-β-mediated M2 polarisation. In particular, this protective effect was found to depend on the abundance of L.M., which regulated intestinal inflammation through its specific metabolites, indoleacetaldehyde (IAAld).

CONCLUSION: SJS improves SAII by orchestrating L.M. derived IAAld-mediated macrophage polarization through modulation of NF-κB and TGF-β signaling pathways.}, } @article {pmid41263913, year = {2025}, author = {Merrick, B and Prossomariti, D and Kertanegara, M and Wyatt, D and Goldenberg, S}, title = {Facilitators and barriers to recruitment and retention in a feasibility trial of encapsulated faecal microbiota transplant to eradicate carriage of antibiotic-resistant bacteria at an academic hospital in central London: a nested qualitative study.}, journal = {BMJ open}, volume = {15}, number = {11}, pages = {e104783}, doi = {10.1136/bmjopen-2025-104783}, pmid = {41263913}, issn = {2044-6055}, mesh = {Humans ; London ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; Feasibility Studies ; Middle Aged ; Qualitative Research ; Adult ; Focus Groups ; *Patient Selection ; COVID-19/epidemiology ; Aged ; *Carrier State/therapy ; }, abstract = {OBJECTIVES: This nested qualitative study (NQS) aimed to identify facilitators and barriers to the delivery of a substantive randomised controlled trial investigating the eradication of gastrointestinal tract carriage of antibiotic-resistant organisms using encapsulated faecal microbiota transplant (FMT).

DESIGN: NQS within a participant-blinded, randomised, placebo-controlled, single-centre, feasibility trial (RCT)-Feasibility of ERadicating gastrointestinal carriage of Antibiotic-Resistant Organisms (FERARO) (ISRCTN reg. no. 34 467 677)-with data collected via focus groups and analysed using thematic analysis.

SETTING: RCT participants were recruited from a large academic tertiary referral hospital in central London. Focus groups were held at the hospital or via videoconferencing for those unable to travel.

PARTICIPANTS: This study included 13 FERARO study participants across two focus groups. 11 participants were under RCT follow-up and unaware of their treatment allocation, two participants had completed 6-month follow-up and knew whether they had received FMT or matched placebo. Additional data were opportunistically collected on reasons for declining RCT participation.

RESULTS: Participants found FMT to be an acceptable and holistic management strategy and noted positive impacts from RCT participation including enhanced personal health awareness and valuable support from the research team. The time and travel commitment presented the most substantial barrier to RCT participation. Many participants were motivated by a desire to give something back to the UK National Health Service and/or research. Patients' current health status also influenced the decision-making process, and, while infrequently cited, the COVID-19 pandemic added extra complexity likely impacting individuals' willingness to participate.

CONCLUSIONS: While FMT is generally acceptable to participants, logistical barriers such as the time and travel commitment associated with RCT participation need consideration. Effective communication, personal connections and participant education on antimicrobial resistance are likely to be crucial for enhancing recruitment and retention in future trials.

TRIAL REGISTRATION NUMBER: ISRCTN registration number 34 467 677 and EudraCT number 2019-001618-41.}, } @article {pmid41263574, year = {2025}, author = {Tang, L and Xie, P and Wang, H and Hong, X and Gong, Z and Zhao, G and Yue, M}, title = {The sex hormone-gut microbiome axis: mechanistic drivers of sex-disparate bacterial infection outcomes and precision clinical interventions.}, journal = {Clinical microbiology reviews}, volume = {}, number = {}, pages = {e0023625}, doi = {10.1128/cmr.00236-25}, pmid = {41263574}, issn = {1098-6618}, abstract = {SUMMARYSex disparities in bacterial infections pose significant challenges in clinical microbiology, influencing diagnostic approaches, antimicrobial stewardship, and patient outcomes. Males frequently exhibit heightened severity in conditions like Helicobacter pylori-associated gastritis and Vibrio cholerae outbreaks, whereas females face amplified risks during reproductive phases for pathogens, such as Listeria monocytogenes and Salmonella spp. Beyond genetic and behavioral factors, the bidirectional sex hormone-gut microbiome axis emerges as a key mechanistic driver: estrogens bolster innate immunity and microbial diversity (e.g., enriching short-chain fatty acid-producing taxa like Bifidobacterium), while androgens and progesterone impose immunosuppressive effects, altering colonization resistance and virulence modulation. Microbial contributions-via β-glucuronidase-mediated hormone deconjugation, bile acid biotransformations, and metabolite signaling-further calibrate host responses, as evidenced in Clostridioides difficile recurrence and enterohemorrhagic Escherichia coli virulence upregulation. This review synthesizes epidemiological, preclinical, and emerging clinical data, highlighting the axis's role in pathogen-specific immune evasion and dysbiosis-driven exacerbations. Clinically, these insights advocate for sex-stratified microbiome diagnostics (e.g., 16S rRNA sequencing for risk profiling) and targeted therapies, including hormone-modulated probiotics to restore barrier function, fecal microbiota transplantation to curb antibiotic-associated vulnerabilities, and selective estrogen receptor modulators to enhance clearance in high-risk cohorts. Despite advances, gaps in human longitudinal studies and pathogen-strain interactions limit translation. Future research integrating multi-omics with clinical trials could refine precision interventions, optimizing infection management in diverse populations and aligning with evolving demands for personalized microbiology.}, } @article {pmid41263392, year = {2025}, author = {Zhao, R and Lu, Y and Xu, Q and Ren, H and Li, H and Gao, J and Cui, H and Yuan, Z and Cao, B and Wei, B}, title = {Gut blautia coccoides-derived 5Z-dodecenoic acid attenuates chronic psychological stress-induced gastric cancer progression.}, journal = {International journal of surgery (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1097/JS9.0000000000004080}, pmid = {41263392}, issn = {1743-9159}, abstract = {BACKGROUND: Chronic psychological stress is a critical oncogenic factor of gastric cancer (GC). However, the mechanisms underlying stress-induced malignant progression remain largely unknown. Gut microbiota dysregulation is tightly associated with cancer development and metabolism.

MATERIALS AND METHODS: Chronic unpredictable mild stress (CUMS) modeling was used to prepare mice suffering from chronic psychological stress. 16s rRNA sequencing and Q300 targeted metabolite quantification were jointly conducted to depict landscapes of gut microbiome and metabolomics of CUMS mice. Fecal microbiota transplantation was employed to investigate the functions of gut microbial communities in regulating CUMS-mediated GC growth. Drug affinity responsive target stability, surface plasmon resonance and molecular docking assays were performed to screen direct target proteins of 5Z-dodecenoic acid. The interactions between RIOK2 and BYSL were verified with co-immunoprecipitation and GST pull-down and fluorescent co-localization analysis. A series of experiments for malignant behaviors and glycolysis and subcutaneous tumor transplantation were employed to detect alterations of GC cell phenotypes ex vivo and in vivo, respectively.

RESULTS: Microbiome and metabolomics collectively demonstrated disrupted gut microbial communities and metabolic patterns. Particularly, Blautia coccoides-derived 5Z-dodecenoic acid was predominately declined by CUMS. Supplementation with Blautia coccoides or 5Z-dodecenoic acid effectively mitigated the negative effects of CUMS on glycolysis and malignancy. Mechanistically, 5Z-dodecenoic acid directly inhibits the functions of RIOK2, which maintained ectopic glycolysis and malignant behaviors. RIOK2 further interacted with BYSL and maintained its properties of potentiation of GC progression and metabolism.

CONCLUSION: Our findings advance the insights of Blautia coccoides-derived 5Z-dodecenoic acid implicated in chronic psychological stress-induced GC progression and provide novel strategies for dampening GC progression.}, } @article {pmid41263038, year = {2025}, author = {Wang, M and Sun, H and Wang, X and Zhang, X and Huang, Y and Cui, R and Sun, Y and Yao, H and Wan, JY}, title = {Tangerine Peel-Based Herbal Formula Ameliorates Metabolic Syndrome via Gut Microbiota-Mediated Bile Acid Remodeling and TGR5 Activation.}, journal = {The American journal of Chinese medicine}, volume = {}, number = {}, pages = {1-19}, doi = {10.1142/S0192415X25500946}, pmid = {41263038}, issn = {1793-6853}, abstract = {The growing global burden of metabolic syndrome (MetS), a key driver of multiple chronic diseases, highlights the limited treatment options for its multifactorial pathophysiology. Tanshi-Tiaoti Decoction (TTD), a Chinese herbal formula comprised of Citri Reticulatae Pericarpium (Tangerine peel), Coicis Semen (Raw coix seed/Job's tears), Raphani Semen (Radish seed), Nelumbinis Folium (Lotus leaf), Eckloniae/Laminariae thallus (Kelp), and Crataegi Fructus (Raw hawthorn fruit), demonstrates efficacy in the clinical management of MetS. However, its underlying molecular mechanisms remain incompletely elucidated. This study indicates that TTD restored gut microbiota homeostasis and bile acid (BA) profiles in high-fat diet (HFD)-induced MetS mice. TTD significantly attenuated body weight gain, fasting glucose levels, serum triglycerides, and hepatic steatosis. TTD corrected gut microbiota dysbiosis, most notably by reducing the Firmicutes/Bacteroidetes ratio. Fecal microbiota transplantation (FMT) validated the fact that the gut microbiome mediates TTD's therapeutic effects. TTD regulated BA biosynthesis through this microbial modulation, and thus specifically increased hyodeoxycholic acid (HDCA). HDCA, which has been identified as the signature BA during TTD treatment, phenocopied TTD's therapeutic effects against MetS by both activating the BA receptor TGR5 and subsequently promoting beige adipocyte browning. Collectively, TTD ameliorates MetS by reshaping microbial-mediated BA pools, and in particular elevates HDCA levels to thereby activate TGR5 and induce beige adipocyte browning. These findings support TTD as a promising herbal-based therapeutic strategy for the treatment of MetS.}, } @article {pmid41260222, year = {2025}, author = {Wang, Y and Wu, J and Yao, J and Chen, J and Cheng, KKY and Ho, MY and Lee, CH and Lam, KS and Tse, MA and Panagiotou, G and Xu, A}, title = {Gut microbiome-adipose crosstalk modulates soluble IL-6 receptor influencing exercise responsiveness in glycemic control and insulin sensitivity.}, journal = {Cell metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmet.2025.10.013}, pmid = {41260222}, issn = {1932-7420}, abstract = {Exercise is an effective intervention for the prevention and management of diabetes, but the high interpersonal variability in response to exercise impedes its widespread implementation. Herein, we identify adipocyte-derived soluble interleukin-6 receptor (sIL-6R) as a key exerkine determining exercise efficacy in improving metabolic health. In individuals with obesity who underwent a 12-week exercise intervention, circulating sIL-6R level exhibits dichotomous changes between exercise responders (Rs) and non-responders (NRs), in close association with exercise-mediated alterations in insulin sensitivity and glycemic control. Mechanistically, elevated gut microbiome-mediated leucine in NR acts on white adipocytes to promote disintegrin and metalloproteinase 17 (ADAM17)-mediated sIL-6R production via the mammalian target of rapamycin (mTOR)-hypoxia-inducible factor 1α (HIF1α) pathway, which in turn impairs the metabolic benefits of exercise through interleukin (IL)-6 trans-signaling-induced adipose inflammation. Adipocyte-selective ablation of ADAM17 prevents the effects of fecal microbiota transplantation from NR on elevation of sIL-6R, thereby restoring the efficacy of exercise-shaped gut microbiome in counteracting glucose intolerance and insulin resistance in obese mice. Thus, therapeutic interventions targeting adipocyte-derived sIL-6R represent a promising strategy for maximizing exercise efficacy in personalized diabetes prevention.}, } @article {pmid41258493, year = {2025}, author = {Xu, Q and Lin, A and Jiang, A and Chen, L and Zhu, L and Mou, W and Liu, Z and Zhang, J and Cheng, Q and Miao, K and Luo, P}, title = {Circadian rhythms as a modulator of gut microbiota-tumor microenvironment crosstalk.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {82}, number = {1}, pages = {409}, pmid = {41258493}, issn = {1420-9071}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Circadian Rhythm/physiology ; *Tumor Microenvironment ; Animals ; *Neoplasms/microbiology/pathology/therapy ; Dysbiosis/microbiology ; }, abstract = {Circadian rhythms play a pivotal role in regulating diverse physiological functions, notably the composition and activity of gut microbiota. Accumulating evidence indicates that circadian rhythm disruption can induce dysbiosis of the gut microbiome, which in turn is implicated in influencing the tumor microenvironment (TME) and facilitating cancer progression. This review integrates and analyzes recent advances elucidating the complex interplay where circadian rhythms modulate gut microbiota, and how these circadian-driven microbial changes affect the TME. This review analyzes recent advances in elucidating the complex interplay among circadian rhythms, gut microbiota, and the TME. We examine how circadian disruption modifies the diversity and metabolic functions of gut microbiota, resulting in alterations of microbial metabolites, including but not limited to short-chain fatty acids and secondary bile acids. These metabolic alterations have the potential to modulate immune cell function, vascular remodeling, and tumor cell metabolism within the TME. We investigate the potential mechanisms through which gut microbial dysbiosis induced by circadian misalignment could promote an immunosuppressive TME and accelerate tumor growth. Additionally, we evaluate emerging therapeutic strategies that leverage the circadian-microbiome axis, encompassing chronotherapy, probiotic supplementation, and fecal microbiota transplantation. The integration of circadian biology, microbiology, and cancer immunology presents promising avenues for the development of novel diagnostic and therapeutic approaches. However, significant challenges persist in translating these findings into viable clinical applications. Further research is imperative to elucidate the molecular pathways interconnecting circadian rhythms, gut microbiota, and the TME, and to develop personalized chronobiological interventions for cancer prevention and treatment.}, } @article {pmid41255657, year = {2025}, author = {Vaou, N and Zavras, N and Fessatou, S and Voidarou, CC and Vrioni, G and Tsakris, A and Vaos, G}, title = {Microbiota decolonization of bacterial pathogens in pediatric surgery-related intestinal disorders: Insights on current strategies and future outlook.}, journal = {World journal of clinical pediatrics}, volume = {14}, number = {4}, pages = {107722}, pmid = {41255657}, issn = {2219-2808}, abstract = {The significance of gut microbiota (GM) in human health is being increasingly researched. An imbalance in GM composition, known as dysbiosis, is linked to various and other health issues. In addition, antibiotics are the primary and most significant factors leading to major changes in the composition and function of the GM, which may result in colonization by antimicrobial-resistant (AMR) pathogens. Therefore, alternative antibiotic strategies for combating AMR pathogens are urgently needed. This narrative review highlights current knowledge regarding various pertinent strategies for decolonizing bacterial pathogens from GM and emphasizes decolonization therapies' critical role in pediatric surgical disorders. Strategies such as decontamination of the digestive tract utilizing antibiotics, the use of probiotics, and particularly fecal microbiota transplantation have introduced new options for clinical treatment. These treatments show the potential to restore GM balance and have demonstrated advantages for intestinal disorders related to pediatric surgery, including inflammatory bowel disease, neonatal necrotizing enterocolitis, Hirschsprung-associated enterocolitis, and short bowel syndrome. Despite GM therapeutics, recent strategies are still in their developmental phase and exhibit challenges that need further research. Thus, potential future directions for GM-targeted decolonization therapies are under consideration. Innovative alternative strategies to combat AMR though GM modulation in disorders related to pediatric surgery appear to be promising and should continue to be prioritized for further research and development.}, } @article {pmid41255529, year = {2025}, author = {Horiachok, M and Potapova, K and Ivanykovych, T and Yerokhovych, V and Ilkiv, Y and Sokolova, L}, title = {Integrating gut microbiota into multidisciplinary perspectives on diabetic neuropathy.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1710868}, pmid = {41255529}, issn = {1664-2392}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diabetic Neuropathies/microbiology/therapy/metabolism ; *Dysbiosis/microbiology ; Animals ; Probiotics/therapeutic use ; }, abstract = {Diabetic neuropathy (DN) is one of the most common and debilitating complications of diabetes mellitus, yet its precise pathogenesis remains incomplete. Emerging evidence highlights the gut microbiome as a key factor linking metabolic dysfunction, immune activation, and neuronal damage. Even minor dysbiosis may interfere with microbial metabolite balance and disrupt intestinal integrity, leading to local and, consequently, systemic inflammation, which in turn drives altered pain response via the gut-brain-immune axis. Recent clinical and preclinical data show that reduced short-chain fatty acid availability, altered bile acid and tryptophan metabolism, let alone expansion of pro-inflammatory species collaboratively contribute to DN onset and progression. Moreover, advances in metagenomics and metabolomics reveal reproducible microbiome-derived biomarkers that could predict neuropathy risk and pain phenotypes independent of glycemic control, supporting the microbiome as both a mechanistic driver and a measurable potential diagnostic tool. In the context of management, microbiota-affected interventions, such as probiotics, synbiotics, omega-3 supplementation, and fecal microbiota transplantation, show early promise in alleviating symptoms and improving nerve function. This mini-review synthesizes current evidence on the microbiome's role in DN, emphasizing its dual potential as a biomarker for early diagnosis and a therapeutic target for precision microbiome-based interventions.}, } @article {pmid41255078, year = {2025}, author = {Ghoshal, UC and Ramakrishna, BS and Rathi, PM and Shukla, A and Panigrahi, MK and Jain, S and Saha, I and Chakravartty, K and Singh, M and Mustafa, U and Sahu, S and Ghoshal, U and Chandnani, S and Goenka, MK and Mitra, M}, title = {Probiotic Blend of Lactobacillus acidophilus LA-5 and Bifidobacterium animalis ssp. Lactis BB-12 in Non-constipated Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.70137}, pmid = {41255078}, issn = {1440-1746}, support = {//Zydus Healthcare Limited and Shanti Public Educational and Development Society/ ; }, abstract = {BACKGROUND: As dysregulated gut microbiota is known in irritable bowel syndrome (IBS) and probiotics may improve it, we investigated the efficacy and safety of a combination probiotic, Lactobacillus acidophilus LA-5 and Bifidobacterium animalis ssp. lactis BB-12 in non-constipated IBS.

METHODS: Two hundred non-constipated IBS patients were randomized to the above-mentioned probiotic and placebo for 84 days. The outcome measures included IBS-Global Improvement Scale (IBS-GIS), IBS-Quality of Life (IBS-QoL), EAR3Q, IBS-Severity Scoring System (IBS-SSS), and patient-reported improvement. Fecal microbiota was evaluated in a subset.

RESULTS: Response in IBS-GIS was higher with probiotics than with placebo at days 28 (19.3% vs. 8.9%; p = 0.048), 56, and 84. Total and abdominal pain, distension, and QoL scores of IBS-SSS decreased at day 28 with probiotics that persisted till days 56 and 84. The percentage of patients with "severe" symptoms reduced from 20.8% at baseline to 3.9% at day 84, and the median IBS-QoL score decreased significantly at day 28; the beneficial effect on QoL was sustained till days 56 and 84 (p < 0.001). Improvement in abdominal pain, distension, urgency of defecation, bowel habit satisfaction, and stool frequency was noted earlier with probiotics than with placebo; 4.0% in the probiotic group and 0.9% in the placebo group had mild/moderate adverse events (p = 0.167). Symptom recurrence occurred in 3.0% in the probiotic group and 3.9% in the placebo group during follow-up of 180 days (p = 0.718). No difference was observed in the fecal microbiota between the two groups, but healthy genera were enriched with probiotics.

CONCLUSIONS: The probiotic blend studied was more effective than placebo in non-constipated IBS in adults.}, } @article {pmid41254951, year = {2025}, author = {González-Correa, C and Miñano, S and Moleón, J and Toral, M and Robles-Vera, I and Sánchez, M and Jiménez, R and Olivares, M and Martín-Morales, N and O'Valle, F and Guerra-Hernández, E and Romero, M and Gómez-Guzmán, M and Duarte, J}, title = {The probiotic Limosilactobacillus fermentum CECT5716 enhances the antihypertensive response to hydrochlorothiazide in spontaneously hypertensive rats.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2586324}, doi = {10.1080/19490976.2025.2586324}, pmid = {41254951}, issn = {1949-0984}, mesh = {Animals ; Rats, Inbred SHR ; *Hydrochlorothiazide/pharmacology/administration & dosage/therapeutic use ; *Probiotics/administration & dosage/pharmacology ; *Hypertension/drug therapy/microbiology/physiopathology ; Gastrointestinal Microbiome/drug effects ; Rats ; *Antihypertensive Agents/pharmacology/administration & dosage/therapeutic use ; Male ; *Limosilactobacillus fermentum/physiology ; Blood Pressure/drug effects ; Fecal Microbiota Transplantation ; }, abstract = {Limosilactobacillus fermentum CECT5716 (LC40) consumption reduces hypertension and improves endothelial dysfunction in spontaneously hypertensive rats (SHRs). The diuretic hydrochlorothiazide (HCTZ) lowers blood pressure in SHR but disrupts the gut microbiota balance. In this study, we investigated whether the LC40 could enhance the antihypertensive effects of HCTZ. Interestingly, we found that coadministration of LC40 with HCTZ potentiated the beneficial effects of HCTZ on endothelial dysfunction and blood pressure without altering plasma HCTZ concentrations or exacerbating electrolyte imbalances. These protective effects were associated with normalization of microbiota alterations, including a reduction in the Firmicutes/Bacteroidota ratio, suppression of lipopolysaccharide biosynthesis, and an increase in acetate-producing bacteria. Additionally, LC40 reduced intestinal pathology and endotoxemia. Furthermore, the HCTZ + LC40-treated rats exhibited reduced neuroinflammation and sympathetic activity, along with an immunoregulatory effect characterized by increased regulatory T cell infiltration and a reduction of vascular oxidative stress in the aorta. The beneficial effects of LC40 in HCTZ-treated rats appeared to be microbiota dependent, as they were replicated through fecal microbiota transplantation in germ-depleted normotensive rats. Our findings identify the gut microbiota as a novel therapeutic target to enhance the antihypertensive effects of diuretics. The coadministration of LC40 with HCTZ modulates immune responses, providing a promising strategy to improve hypertension management.}, } @article {pmid41253445, year = {2025}, author = {Chen, YL and Meng, LL and Wu, JY and Yang, XY and Ouyang, L and Wu, BF and Xu, HX and Gu, JL and Wang, YL and Jing, XY and Lu, SF and Fu, SP}, title = {Electroacupuncture Reprograms Gut Microbiota and Confers Cerebral Protection After Stroke through Enhanced Regulatory T Cell Response.}, journal = {The American journal of Chinese medicine}, volume = {}, number = {}, pages = {1-24}, doi = {10.1142/S0192415X25500855}, pmid = {41253445}, issn = {1793-6853}, abstract = {Ischemic stroke seriously endangers both the health and quality of life of patients. The gut microbiota, which plays a crucial role in modulating communication between the gut and the nervous system, has emerged as a promising target for therapeutic interventions in stroke. Electroacupuncture (EA), which is associated with intestinal immunity, has been proven to exert significant beneficial effects in ischemic stroke, but its exact mechanism remains unclear. In this study, we investigated the regulatory mechanism of EA on the microbiome-gut-brain axis following ischemic stroke. In rat models of ischemic stroke, EA treatment significantly reduced cerebral infarct volume and neuronal damage following cerebral ischemia-reperfusion injury, and also modulated the composition, diversity, and taxonomic distribution of the gut microbiota. Fecal microbiota transplantation from EA-treated donors significantly reduced cerebral infarct volume and neuronal damage in the ischemic hemisphere of recipient mice, and likewise upregulated Treg cell expression to suppress immune-inflammatory responses in the brain. These results indicate that, through modulation of the gut microbiota, which in turn regulates Treg-mediated immune-inflammatory responses, EA ameliorates cerebral ischemic injury to thereby improve the prognosis of ischemic stroke patients. This study provides new perspectives on the efficacy of EA in the treatment of ischemic stroke.}, } @article {pmid41253270, year = {2025}, author = {Ding, L and Xu, JY and Zhang, LL and Liu, Y and Gu, KT and Liang, YZ and Hidayat, K and Wan, Z and Chen, GC and Qin, LQ}, title = {Lactoferrin alleviates non-alcoholic steatohepatitis via remodeling gut microbiota to regulate serotonin-related pathways.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.11.034}, pmid = {41253270}, issn = {2090-1224}, abstract = {INTRODUCTION: Lactoferrin (LF), a multifunctional glycoprotein, has been implicated in the regulation of glucose and lipid metabolism.

OBJECTIVES AND METHODS: This study employed in vivo and in vitro models to investigate the direct effects of LF on non-alcoholic steatohepatitis (NASH) and to elucidate its underlying mechanisms.

RESULTS: LF intervention alleviated hepatic lipid metabolic disorders and liver injury in high-fat, high-cholesterol cholate-containing diet (HFCCD)-fed mice by mitigating oxidative stress, suppressing the inflammatory cGAS/STING pathway, and reducing M1 proinflammatory macrophage polarization. These effects were validated in free fatty acid (FFA)-treated HepG2 cells and AML12 cells. Furthermore, LF ameliorated HFCCD-induced gut microbiota dysbiosis and increased short-chain fatty acid levels. The critical role of gut microbiota in mediating the hepatoprotective effects of LF was confirmed through antibiotic-induced microbiome depletion and fecal microbiota transplantation. Mechanistically, LF modulated gut-liver serotonin signaling and promoted fatty acid β-oxidation through the HTR2A-PPARα-CPT-1A pathway, an effect abolished by the HTR2A agonist DOI. In a co-culture system, LF treatment of the Caco-2/HT29 monolayer alleviated lipid accumulation and regulated the HTR2A-PPARα-CPT-1A pathway in FFA-treated HepG2 cells.

CONCLUSIONS: These findings indicate that LF attenuates NASH by remodeling gut microbiota to modulate microbiota-derived serotonin signaling and enhance fatty acid oxidation.}, } @article {pmid41252333, year = {2025}, author = {Bahji, A and Brietzke, E and Cooke, NCA and Clement, F and Frey, BN and Hofmeister, M and Kennedy, SH and Lam, R and Milev, R and Moinul, D and Parikh, SV and Patten, S and Ravindran, A and Rosenblat, JD and Samaan, Z and Schaffer, A and Saleem, A and Beaulieu, S and Tourjman, V and Van Ameringen, M and Vigod, S and Yatham, L and Taylor, V and , }, title = {The Canadian Network for Mood and Anxiety Treatments Task Force Recommendations for the Use of Probiotics, Prebiotics, Synbiotics, and Fecal Microbiota Transplants in Adults With Major Depressive Disorder: Recommandations du Groupe de travail du Réseau canadien pour le traitement des troubles de l'humeur et de l'anxiété (Canadian Network for Mood and Anxiety Treatments, CANMAT) concernant l'utilisation des probiotiques, des prébiotiques, des symbiotiques et de la transplantation de microbiote fécal chez les adultes atteints de trouble dépressif majeur.}, journal = {Canadian journal of psychiatry. Revue canadienne de psychiatrie}, volume = {}, number = {}, pages = {7067437251394363}, doi = {10.1177/07067437251394363}, pmid = {41252333}, issn = {1497-0015}, abstract = {BackgroundApproximately one-third of adults with major depressive disorder (MDD) experience limited response or intolerable side effects with existing pharmacotherapies. As such, innovative treatments targeting novel biological pathways are under investigation. One promising area of research is the gut microbiome and its influence on mood through the microbiota-gut-brain axis. Clinical studies have begun evaluating microbiome-targeted interventions such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) as potential treatments for MDD. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to evaluate the evidence for microbiome-targeted interventions in adults with MDD and to provide updated clinical recommendations.MethodsA systematic review of randomized controlled trials (RCTs) and meta-analyses was conducted, assessing interventions such as probiotics, prebiotics, synbiotics, and FMT in adults with MDD. The CANMAT methodology was used to determine levels of evidence and treatment line recommendations, which were presented in a question-and-answer format.ResultsTwenty-three RCTs and eight meta-analyses were included. Probiotics have been the most extensively studied and have demonstrated modest improvements in depressive symptoms, particularly when used in an adjunctive manner. However, recent high-quality trials yielded mixed results. Evidence for prebiotics and FMT was limited and inconclusive, while synbiotics were assessed in only one small RCT. Most interventions were well tolerated, with few serious adverse events.ConclusionsProbiotics may be cautiously considered as third-line adjunctive treatments for MDD, though findings remain inconsistent. There is currently insufficient evidence to recommend prebiotics, synbiotics, or FMT in clinical practice. Further large-scale, well-controlled trials are needed to clarify efficacy, safety, and optimal patient subgroups.}, } @article {pmid41252206, year = {2025}, author = {Moreau, GB and Tian, J and Natale, NR and Naz, F and Young, MK and Nayak, U and Tanyüksel, M and Rigo, I and Madden, GR and Abhyankar, MM and Hagspiel, N and Brovero, S and Worthington, M and Behm, B and Marie, C and Petri, WA and Ramakrishnan, G}, title = {FMT promotes type 2 mucosal immune responses with colonic epithelium proliferation in recurrent CDI patients.}, journal = {JCI insight}, volume = {}, number = {}, pages = {}, doi = {10.1172/jci.insight.195678}, pmid = {41252206}, issn = {2379-3708}, abstract = {BACKGROUND: Fecal Microbiota Transplantation (FMT) is the most effective therapy for recurrent Clostridioides difficile infection (rCDI), yet its mechanism of action remains poorly understood.

METHODS: We report the results of a clinical trial of subjects undergoing FMT therapy for rCDI (n=16), analyzing colon biopsies, plasma, peripheral blood mononuclear cells, and stool at the time of FMT and two-month follow-up. Plasma and colon biopsy samples were also collected from healthy controls for comparison with rCDI patients. Microbiome composition, colonic gene expression, and immune changes were evaluated through high-throughput sequencing and immunoprofiling via flow cytometry.

RESULTS: No subjects experienced recurrence at follow-up. FMT significantly altered the intestinal microbiome but had no significant impact on the systemic immune system. In contrast, FMT promoted broad changes in colonic transcriptional profiles compared to both pre-FMT and healthy control biopsies, inhibiting genes associated with pro-inflammatory signaling and upregulating type 2 immunity and proliferative pathways (Myc and mTORC1). FMT increased expression of IL-33 and the type 2 immune EGFR family ligand amphiregulin, potentially explaining upregulation of Myc and mTORC1 pathways. Spatial transcriptomics demonstrated that these changes were localized to the colonic epithelium. Comparison of transcriptional profiles with available single cell gene sets determined that post-FMT biopsies were enriched in signatures associated with proliferative cell types while repressing signatures of differentiated colonocytes.

CONCLUSIONS: We conclude that FMT promotes proliferation of the colonic epithelium in rCDI patients, which may drive regeneration and protect against subsequent CDI.

CLINICALTRIALS: gov NCT02797288.

FUNDING: NIH grants R01 AI152477, R01 AI124214, and K23 AI163368.}, } @article {pmid41250648, year = {2025}, author = {Yang, J and Tan, H and Peng, X and Nie, S}, title = {Tamarind Seed-Derived Xyloglucan Attenuates Insulin Resistance in Mice through Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c07829}, pmid = {41250648}, issn = {1520-5118}, abstract = {Xyloglucan (XG), a plant polysaccharide abundant in tamarind seeds, is FDA-approved for use as a food additive, stabilizer, thickener, or gelling agent. While its structural properties have been well-studied, its physiological effects remain unclear. This study employed a high-fat diet-induced insulin resistance mouse model to evaluate the effects of XG on metabolic disturbances, combining 16S rRNA sequencing and metabolomics to determine the role of gut microbiota. Results showed that XG intervention in HFD-fed mice improved glucose tolerance and liver function and reduced inflammation and oxidative stress, linked to altered carnitine and tryptophan metabolism. Gut microbiota analysis revealed selective enrichment of Bifidobacterium. Crucially, the benefit of XG was transferable via fecal microbiota transplantation but was abolished by antibiotic-induced microbiota depletion. This study demonstrates that tamarind seed-derived xyloglucan alleviates metabolic disturbances via a gut-microbiota-dependent mechanism, supporting its potential probiotic role in functional foods.}, } @article {pmid41250124, year = {2025}, author = {Huang, SW and Lin, CR and Chang, YH and Ni, YH and Chen, HL and Liu, HH}, title = {Cross-country multi-modal evidence links Aspergillus to biliary atresia.}, journal = {Gut pathogens}, volume = {17}, number = {1}, pages = {94}, pmid = {41250124}, issn = {1757-4749}, abstract = {BACKGROUND: Biliary atresia (BA) is the leading cause of pediatric liver transplantation. It is characterized by progressive extrahepatic bile duct obstruction in young infants. Inspired by the success of antifungal treatment in a newborn with BA-related obstructive cholangitis, we explored a potential link between BA and fungi, particularly Aspergillus. Fecal DNA was analyzed using 18S ribosomal sequencing and validated with a published fecal metagenomic dataset. Epidemiological data from the UK, Taiwan, and Japan were also examined.

RESULTS: Gut Aspergillus was exclusively detected in BA cases, suggesting it may be a potential trigger. Independent fecal metagenomic data from China and epidemiological correlations further supported this hypothesis. In the UK, BA presentations strongly correlated (r = 0.98, 95% CI [0.36, 1.0], p = 0.02) with Aspergillosis, but not with Candidiasis, during the COVID-19 lockdown. In Taiwan, a decade of data showed BA incidence was significantly associated (r = 0.78, 95% CI [0.29, 0.94], p = 0.01) with yearly Aspergillus-positive isolates among cancer-adjusted hospital admissions. In Japan, BA cases over 25 years correlated significantly (r = 0.85, 95% CI [0.37, 0.97], p = 0.01) with visceral Aspergillus burdens in autopsied cases, but not with other fungal infections.

CONCLUSIONS: The resolution of obstructive cholangitis in the antifungal-treated index case, together with multi-modal, cross-country evidence, highlights a potential link between gut Aspergillus and BA. Although limited by small sample size, retrospective design, and lack of mechanistic validation, the study may still be interpreted as hypothesis-generating and underscores the need for prospective studies to validate and extend these observations.}, } @article {pmid41249722, year = {2025}, author = {Xu, N and He, Y and Yang, G and Huang, X}, title = {Exploring the Role of Gut Microbiota in Chronic Spontaneous Urticaria: Mechanisms and Potential Therapeutic Implications.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {41249722}, issn = {1867-1314}, support = {no. 82103751//National Natural Science Foundation of China/ ; }, abstract = {Gut microbiota dysbiosis has emerged as a significant factor in the pathogenesis of chronic spontaneous urticaria (CSU), a condition characterized by immune dysregulation and skin inflammation. This review summarizes the current understanding of the role of gut microbiota in CSU pathogenesis, highlighting the alterations in microbial composition and function, the mechanisms by which dysbiosis triggers systemic inflammation and skin mast cell activation, and the impact of microbial metabolites. We critically evaluate the potential of gut microbiota-targeted therapies, such as probiotics, prebiotics, and fecal microbiota transplantation (FMT), as novel treatment strategies for CSU. Despite the evident promise of these approaches, significant challenges persist, including the necessity for personalized interventions, the collection of long-term efficacy and safety data, and a more profound understanding of the complex interplay between the gut and skin. Future research endeavors must prioritize the execution of clinical trials that evaluate the efficacy of gut microbiota modulation in CSU patients and the identification of biomarkers that can effectively predict treatment response.}, } @article {pmid41248567, year = {2025}, author = {Huang, F and Zhang, L and Cheng, S and Zhang, Z and Xiang, Q and Xiao, Z}, title = {Banxia Baizhu Tianma Decoction improves posterior circulation ischemia vertigo in rats via gut microbiota and TLR4-NF-κB-MyD88 pathway.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {149}, number = {}, pages = {157539}, doi = {10.1016/j.phymed.2025.157539}, pmid = {41248567}, issn = {1618-095X}, abstract = {BACKGROUND: Posterior circulation ischemia vertigo (PCIV) frequently presents with vestibular dysfunction in patients suffering from posterior circulation stroke. The conventional approaches often fail to address PCIV's complex pathophysiology, which involves neuroimmune dysregulation, hemodynamic abnormalities, and gut-brain axis disruption. Banxia Baizhu Tianma Decoction (BBTD), a traditional Chinese medicine, is employed in treating PCIV and vasogenic vertigo, but the mechanisms underlying its efficacy require further elucidation.

PURPOSE: This study examines the therapeutic mechanisms and efficacy of BBTD for PCIV, particularly focusing on its impacts on neuroinflammation, gut microbiota communities, and gut barrier using a rat model of PCIV.

METHODS: The chemical and bioactive constituents of BBTD were profiled using ULPLC-Q Exactive-Orbitrap-MS. The PCIV model was employed and treated with BBTD for 7 days. Neurological score was measured with balance beam test; cerebellar pathology was assessed by H&E and Nissl staining. The TTC staining was used to measure cerebral infarct volume. The levels of IL-6, IL-1β, and TNF-α in serum and cerebellar tissue was analyzed by ELISA. Its mechanisms were investigated by 16S rRNA sequencing, antibiotic antagonistic and fecal microbiota transplantation (FMT) experiments. Significant alterations in gut microbiota and their detailed mechanisms were identified. Intestinal barrier integrity was assessed by AB-PAS staining, tight junction proteins (MUC2, occludin, claudin-1, ZO-1), and colonic inflammatory cytokine levels. The levels of short-chain fatty acids in the cecal contents and cerebellar tissues of our experimental rats using gas chromatography-mass spectrometry (GC-MS).

RESULTS: Our findings demonstrated that BBTD significantly improved neurological function, ameliorates cerebral ischemia, and alleviated neuroinflammation in rats. Moreover, BBTD significantly modulated the diversity and composition of the gut microbiota, elevating Lactobacillus and Akkermansia, while reducing Clostridiales and Ruminococcaceae. The further antibiotic depletion and FMT experiments confirmed that gut microbiota was essential for BBTD-induced neuroinflammation and gut barrier protection in PCIV. BBTD ameliorated intestinal damage by enhancing acidic mucins and tight junction protein expression. BBTD treatment markedly increased the concentrations of propionic acid in intestinal fecal content and cerebellar tissue. Mechanistically, BBTD ameliorates ischemia-induced neuroinflammation and neuronal injury by modulating the TLR4-NF-κB-MyD88 pathway via the gut-brain axis.

CONCLUSION: BBTD ameliorates PCIV through gut-brain axis modulation, restoring gut barrier-microbiota balance and suppressing TLR4-NF-κB-MyD88 signaling. BBTD treatment and FMT may serve as an effective therapeutic strategy for mitigating posterior circulation ischemia progression.}, } @article {pmid41247394, year = {2025}, author = {Wu, Y and Chan, SSM and Leung, PWL and Lo, HHL and Ho, SWS and Mo, FYM and Ho, CSW and Shea, CKS and Su, Q and Leung, TF and Chan, FKL and Ng, SC and Wong, OWH}, title = {The Mediating Role of Eating Behaviors Between Autistic Symptoms and Dietary Issues Among Chinese Children With Autism.}, journal = {Journal of autism and developmental disorders}, volume = {}, number = {}, pages = {}, pmid = {41247394}, issn = {1573-3432}, support = {InnoHK , the Government of Hong Kong, Special Administrative Region of the People's Republic of China//InnoHK , the Government of Hong Kong, Special Administrative Region of the People's Republic of China/ ; InnoHK , the Government of Hong Kong, Special Administrative Region of the People's Republic of China//InnoHK , the Government of Hong Kong, Special Administrative Region of the People's Republic of China/ ; The D.H. Chen Foundation//The D.H. Chen Foundation/ ; The D.H. Chen Foundation//The D.H. Chen Foundation/ ; PF22-77807//The Hong Kong PhD Fellowship Scheme/ ; }, abstract = {PURPOSE: Eating and dietary challenges are common among children with autism, but their associations with clinical symptoms remain unclear. This study aims to describe dietary issues, including nutritional problems and overexposures to food additives in autistic children, and their associations with clinical symptoms.

METHODS: This case-control study involved 836 children (469 with autism and 367 without autism; mean age = 8.3 years) profiled on autistic symptoms, eating behaviors, and dietary patterns with parent-reported questionnaires. Nutritional insufficiencies, dietary quality and food additives exposures were compared using regression models adjusted for age and sex. Multivariate logistics or linear regression models were used to identify clinical symptoms that predict dietary issues, with mediation analyses examining eating behaviors' roles.

RESULTS: Autistic children had lower protein intake, more vitamin and mineral insufficiencies, higher exposure to food additives, and poorer diet quality. They consumed fewer fruits/vegetables and more animal-based fats, with 38.2% exceeding 125% of the Estimated Energy Requirement (vs. 22.9% controls), suggesting energy-dense, ultra-processed food preferences. Diminished food enjoyment and increased food fussiness mediated between low social motivation and nutritional insufficiencies, as well as poorer diet quality. Further, difficulties with food responsiveness and emotional eating patterns mediated between more restricted and repetitive behaviors and higher exposures to emulsifiers/thickeners.

CONCLUSION: Autistic children, especially those with severe core symptoms, are susceptible to multifaceted dietary issues such as preference for low-quality food and nutrient deficiencies. It is crucial to implement personalized treatment strategies that target their specific eating behaviors to effectively address dietary challenges.}, } @article {pmid41247324, year = {2025}, author = {Weagley, JS and Cárdenas, LAC and Romani, A and Sullender, ME and Aggarwal, S and Makimaa, H and Hogarty, MP and Rodgers, R and Kennedy, EA and Foster, L and Schriefer, LA and Baldridge, MT}, title = {Differential Microbial Community Assembly Following Co-housing versus Microbiota Transplant.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ismejo/wraf256}, pmid = {41247324}, issn = {1751-7370}, abstract = {Mouse models are vital tools for discerning the relative contributions of host and microbial genetics to disease, often requiring the transfer of microbiota between different mouse strains. Transfer methods include antibiotic treatment of recipients and colonization using either co-housing with donors or the transplantation of faecal or caecal donor material. However, the efficiency and dynamics of these methods in reconstituting recipients with donor microbes is not well understood. We thus directly compared co-housing, faecal transplantation, and caecal transplantation methods. Donor mice from Taconic Biosciences, possessing distinct microbial communities, served as the microbial source for recipient mice from Jackson Laboratories, which were treated with antibiotics to disrupt their native microbiota. We monitored bacterial and viral populations longitudinally over the course of antibiotics treatment and reconstitution using 16S rRNA gene sequencing, quantitative PCR, and shotgun sequencing of viral-like particles. As expected, antibiotic treatment rapidly depleted microbial biomass and diversity, with slow and incomplete natural recovery of the microbiota in non-transfer-recipient control mice. Although all transfer methods reconstituted recipient mice with donor microbiota, co-housing achieved this more rapidly for both bacterial and viral communities. Overall, faecal and caecal transplant resulted in highly similar colonization processes with some minor variation in enrichment for two specific bacterial families. This study provides valuable insights into microbial ecology, as well as the dynamics underlying experimental microbial transfer methods, enhancing reproducibility and informing best practices for microbiota transfer in mouse models.}, } @article {pmid41247039, year = {2025}, author = {Kelly, CR and Feuerstadt, P}, title = {Diagnosis and Management of C. difficile.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ajg.0000000000003844}, pmid = {41247039}, issn = {1572-0241}, abstract = {Clostridioides difficile infection (CDI) is challenging to diagnose and treat. Recently published studies and clinical observations have improved our understanding around diagnostic testing and positioning of antibiotics and microbiota-based therapies. This review synthesizes current evidence and guidelines on CDI diagnosis, highlighting the limitations of individual tests and the value of algorithmic approaches. Treatment paradigms are discussed across the spectrum of disease severity, with vancomycin and fidaxomicin as first-line therapies and the diminishing role of metronidazole. For recurrent CDI, newer fecal microbiota-based therapies, including Fecal Microbiota, live-jslm (Rebyota, RBL) and Fecal Microbiota Spores, live-brpk (Vowst, VOS), are reviewed. The role of conventional fecal microbiota transplantation (FMT), particularly in fulminant CDI, is also addressed, including challenges resulting from FDA policies around stool bank material. We aim to clarify diagnostic and therapeutic approaches and optimize care for patients with CDI.}, } @article {pmid41246810, year = {2025}, author = {Tan, H and Chen, M and Yao, H and Li, S and Nie, S}, title = {Dominant Gut Commensals Enriched by Pectin with Low Esterification Degree Orchestrate the Amelioration of Acute Ulcerative Colitis.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c09097}, pmid = {41246810}, issn = {1520-5118}, abstract = {Dietary fiber's health benefits are increasingly recognized as microbiota-dependent, with effects influenced by fiber structure. We previously observed that low-esterified pectin provides superior protection against DSS-induced colitis compared to its high-esterified form, but the mechanism was unknown. This study investigated the microbiota-dependent pathway underlying low-esterified pectin's anticolitic effect using FMT. By evaluating three pectin-induced bacteria (Bifidobacterium longum NSP002, Bacteroides xylanisolvens NSP003, Enterococcus faecium NSP004) individually and in a consortium, we found that the consortium exerted a significantly stronger protective effect, suggesting synergistic interactions and highlighting its potential as an FMT alternative. Mechanistically, this protection may involve three axes: (1) Gut microbiome remodeling (reduced Akkermansia, increased Bacteroides, elevated propionic acid). (2) Intestinal homeostasis modulation (reduced mme/calprotectin expression, activated PI3K/calcium signaling). and (3) Systemic metabolic reprogramming (increased serum phenylethylamine, enriched phenylalanine metabolism). These findings support the clinical potential of pectin for optimizing enteral nutrition and using pectin-enriched microbiota consortia to target IBD pathogenesis.}, } @article {pmid41246285, year = {2025}, author = {Ahmed, N and Gaur, V and Kamle, M and Chauhan, A and Chauhan, R and Kumar, P and Singh, NA}, title = {Microbiome-based therapeutics for metabolic disorders: harnessing microbial intrusions for treatment.}, journal = {Frontiers in medical technology}, volume = {7}, number = {}, pages = {1695329}, doi = {10.3389/fmedt.2025.1695329}, pmid = {41246285}, issn = {2673-3129}, abstract = {The rising global rates of metabolic disorders, such as obesity, type 2 diabetes, non-alcoholic fatty liver disease, and metabolic syndrome, call for new treatment methods beyond traditional drugs. The human gut microbiota, made up of trillions of microorganisms that plays a crucial role in maintaining metabolic balance through complex biochemical processes and interactions between hosts and microbes. Dysbiosis, which involves changes in microbial composition and a decrease in diversity, has become a major factor in metabolic problems. This disruption impacts the production of short-chain fatty acid, increase in permeability of intestine, and causes enduring low-grade inflammation. This review features into the potential of treatments based on microbiome for metabolic syndromes, focusing on probiotics, prebiotics, synbiotics, and postbiotics. It also encompasses innovative methods such as engineered microbial consortium, fecal microbiota transplantation (FMT), and vaginal microbiota transplantation (VMT). Probiotics show significant promise in improving blood sugar control and enhancing lipid levels. Prebiotics help bring about positive changes in microbial composition and the production of beneficial metabolites. Synbiotic combinations provide added benefits by helping good microbes thrive while supplying nutrients they can ferment. Postbiotics have recent research focus because they are safer, more stable, easier to store, and less likely to contribute to antibiotic resistance comparative to live probiotics. Even now there are substantial complications in translating microbiome research into standardized therapeutics despite of promising pre-clinical outcomes and some initial clinical data. These comprises individual variances, strain-specificity, dosage problems, regulation issues, and the necessity for personalised treatment strategies. Future success will depend upon personalized medicine, technological developments, and the incorporation of multi-omics strategy to generate metabolic health therapeutics depending on targeted microbiomes.}, } @article {pmid41245267, year = {2025}, author = {Makkar, SK and Bishnupuri, KS}, title = {The gut microbiome and gastrointestinal cancers: mechanisms, biomarkers and therapeutic opportunities.}, journal = {Frontiers in physiology}, volume = {16}, number = {}, pages = {1676796}, doi = {10.3389/fphys.2025.1676796}, pmid = {41245267}, issn = {1664-042X}, abstract = {Gastrointestinal (GI) cancers remain a leading global cause of cancer-related mortality, significantly impacting public health and healthcare systems worldwide. Emerging evidence underscores the critical role of gut microbiome dysbiosis-characterized by disrupted microbial diversity and function-in GI carcinogenesis. Utilizing recent advancements in multi-omics technologies and sophisticated computational biology, researchers have elucidated distinct microbial signatures associated with colorectal, gastric, hepatobiliary, pancreatic, and esophageal cancers. This review comprehensively analyzes the primary mechanisms through which gut microbes contribute to cancer development and progression, encompassing genotoxicity, chronic inflammation, metabolic dysregulation, epigenetic modifications, and immunomodulation. Moreover, we explore innovative microbiome-derived biomarkers for potential clinical applications, including early diagnosis, prognosis assessment, and therapeutic response prediction. The intricate interactions between microbiota and standard cancer therapies-chemotherapy, immunotherapy, and radiation therapy-are discussed, highlighting microbiome influences on therapeutic efficacy and adverse effect profiles. We also critically assess the impact of modifiable factors such as diet, medications, lifestyle, and environmental exposures on microbiome composition and cancer risk. The review evaluates emerging therapeutic interventions, including dietary modifications, probiotics, prebiotics, fecal microbiota transplantation (FMT), and engineered live biotherapeutics. Despite notable advancements, significant hurdles remain, including clarifying causality, methodological standardization, and equitable global research representation. Addressing these challenges, we propose a strategic research agenda aimed at harnessing microbiome insights to advance precision oncology and improve GI cancer outcomes globally.}, } @article {pmid41244880, year = {2025}, author = {Bautista, J and Hidalgo-Tinoco, C and Di Capua Delgado, M and Viteri-Recalde, J and Guerra-Guerrero, A and López-Cortés, A}, title = {The gut-brain-circadian axis in anxiety and depression: a critical review.}, journal = {Frontiers in psychiatry}, volume = {16}, number = {}, pages = {1697200}, doi = {10.3389/fpsyt.2025.1697200}, pmid = {41244880}, issn = {1664-0640}, abstract = {Anxiety and depressive disorders rank among the most prevalent psychiatric conditions worldwide, yet remission rates remain unsatisfactory despite advances in pharmacological and psychotherapeutic interventions. The gut-brain axis has emerged as a transformative framework for understanding these disorders, emphasizing bidirectional communication between the central nervous system, the enteric nervous system, the endocrine and immune systems, and the gut microbiota. Preclinical studies demonstrate that germ-free or dysbiotic states exaggerate hypothalamic-pituitary-adrenal (HPA) reactivity, remodel synaptic plasticity, and induce anxiety- and depression-like behaviors, while fecal microbiota transplantation confirms the causal influence of microbial communities. Mechanistically, neural (e.g., vagal), endocrine (e.g., cortisol), immune (e.g., cytokine), and metabolic (e.g., short-chain fatty acids, tryptophan metabolites, bile acids) pathways converge to regulate mood and stress resilience. An underappreciated yet critical dimension of this model is circadian rhythmicity. Both host endocrine cycles and microbial communities exhibit diurnal oscillations that synchronize metabolism, immune activity, and neural signaling. Disruption of these rhythms, through factors such as sleep disturbance, irregular feeding, or shift work, alters microbial diversity, dampens metabolite oscillations, destabilizes HPA regulation, and enhances neuroinflammation, thereby amplifying vulnerability to psychiatric disorders. Collectively, evidence supports a model in which anxiety and depression are systemic conditions arising from integrated neural, immune, endocrine, metabolic, and circadian dysregulation, rather than isolated brain-based pathologies. This reconceptualization positions microbial taxa and metabolites as candidate biomarkers and therapeutic targets. Precision interventions, ranging from diet and psychobiotics to fecal microbiota transplantation, chrononutrition, and immune-modulatory strategies, offer promising avenues for personalized psychiatry.}, } @article {pmid41244772, year = {2025}, author = {Li, Q and Song, XC and Li, K and Wang, J}, title = {Gut-lung immunometabolic crosstalk in sepsis: from microbiota to respiratory failure.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1685044}, doi = {10.3389/fmed.2025.1685044}, pmid = {41244772}, issn = {2296-858X}, abstract = {Sepsis is a systemic immune-metabolic disorder syndrome caused by infection, in which gut microbiota dysbiosis plays a central role in the occurrence and development of multi-organ dysfunction. This paper systematically elaborates on the bidirectional regulatory mechanism of the "gut-lung axis" in sepsis. Gut microbiota dysregulation damages the gut barrier function, reduces the production of short-chain fatty acids (SCFAs), and increases endotoxin translocation. Subsequently, it activates alveolar macrophage polarization, promotes the formation of neutrophil extracellular traps (NETs), and leads to an imbalance in the Treg/Th17 cell ratio, ultimately exacerbating the pathological process of acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Conversely, the pulmonary inflammatory response can also aggravate gut barrier damage through circulating inflammatory mediators, forming a vicious cycle. Mechanistically, HIF-1α, mTOR, and Sirtuins do not act in isolation. Instead, they jointly regulate the metabolic fate of immune cells through spatiotemporally dynamic interactions. During the evolution of sepsis, these signals exhibit opposite regulatory polarities during the hyper-inflammatory phase and the immunosuppressive phase, and mitochondrial dysfunction and oxidative stress further amplify the inflammatory cascade reaction. Preclinical research evidence shows that microbiota-based intervention measures (including probiotic preparations, fecal microbiota transplantation, and SCFA supplementation) and vagus nerve electrical stimulation can effectively alleviate sepsis-related lung injury and improve prognosis, but there is significant individual heterogeneity in their therapeutic effects. Future research should not be restricted to descriptive associations. Instead, it is essential to conduct in-depth analyses of the specific logic of the aforementioned signaling networks in terms of cell types, subcellular compartments, and disease course timings, and clarify their context-dependent controversies to promote the transformation of mechanistic understanding into precision treatment. Meanwhile, research efforts should focus on constructing a multi-omics dynamic biomarker system integrating metagenomics, metabolomics, and immunophenotyping analysis and designing clinical trials through precise patient stratification to facilitate the clinical translation of individualized treatment strategies based on gut-lung axis regulation.}, } @article {pmid41243436, year = {2025}, author = {Cen, Q and Cui, Y and Jin, J and Feng, J and Xin, Y and Zhang, Z and Li, J and Wang, J and Zhang, A}, title = {Unraveling multiple sclerosis: a hidden interaction between intestinal microbiota and host lipid metabolism.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2576657}, doi = {10.1080/19490976.2025.2576657}, pmid = {41243436}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Multiple Sclerosis/metabolism/microbiology/therapy ; *Lipid Metabolism ; Animals ; }, abstract = {Dysregulation of the structure of the gut microbiota is closely linked to the risk of onset and progression of multiple sclerosis. The intricate interaction between the gut microbiota and lipid metabolism likely serves as a crucial pathway mediating this relationship: the gut microbiota directly or indirectly modifies lipid metabolism (including cholesterol, sphingolipids, phospholipids, and fatty acids) by controlling the production of specific metabolites (such as short-chain fatty acids, tryptophan metabolites, bile acids, trimethylamine-N-oxide, and lipopolysaccharides), thereby impacting core pathological processes in multiple sclerosis. Therefore, elucidating the specific roles and mechanisms of the gut microbiota in modulating lipid metabolism in multiple sclerosis will accelerate the development of precision therapeutic strategies. In this review, we conduct an in-depth exploration of the interaction between the gut microbiota and lipid metabolism in the context of multiple sclerosis and provide a comprehensive summary of existing strategies targeting the gut microbiota and lipid metabolism for treating multiple sclerosis (including microbiota-based therapies, pharmacotherapy, and lifestyle modifications). Finally, we outline the present challenges in this field and offer an in-depth prospect for future directions.}, } @article {pmid41243097, year = {2025}, author = {Hang, WJ and Yin, R and Kang, XW and He, L and Cao, X and Chen, J}, title = {Berberine ameliorates high-fat diet-induced metabolic disorders through promoting gut Akkermansia and modulating bile acid metabolism.}, journal = {Chinese medicine}, volume = {20}, number = {1}, pages = {190}, pmid = {41243097}, issn = {1749-8546}, support = {82100402//National Natural Science Foundation of China/ ; 82370837//National Natural Science Foundation of China/ ; 2022CFB201//Bureau of Science and Technology of Hubei Province/ ; 2022YFE0209900//National Key Research and Development Program of China/ ; WZ21A02//Wuhan Municipal Health Commission's Scientific Research/ ; }, abstract = {BACKGROUND: Coptidis Rhizoma, the rhizome of Coptis chinensis Franch., has long been employed in the treatment of diabetes. Its active component, berberine, has been utilized in clinical practice; however, the underlying mechanisms of its protective effects remain to be fully elucidated.

METHODS: Metabolomics and lipidomics analyzed plasma metabolite and lipid changes in mice fed a high-fat diet and treated with 25 mg/kg/day berberine for three months. Metagenomics and microbiota transplantation identified gut microbiota responding to berberine. Co-administration of berberine and Akkermansia was studied for metabolic effects, analyzing plasma and fecal metabolomics.

RESULTS: Berberine reduced triglycerides and cholesterol, showing metabolic protective effects. Metagenomics identified Akkermansia as key to berberine's benefits, validated by microbiota transplantation. Berberine enhanced Akkermansia growth, preserving intestinal mucus and tight junctions. It promotes the conversion of cholesterol to bile acids by inhibiting adenosine 5 '-monophosphate -activated protein kinase (AMPK), which promotes the expression of cholesterol 7-alpha hydroxylase (CYP7A1). Co-administration of berberine and Akkermansia amplified these effects. Potential metabolites, including linoleic acid and N-acetylputrescine, contributed to the observed benefits.

CONCLUSION: Berberine, through Akkermansia, maintains intestinal integrity and reduces cholesterol, highlighting its potential as a therapeutic agent for metabolic disorders. Combining berberine with Akkermansia enhances its efficacy against hyperlipidemia.}, } @article {pmid41242566, year = {2025}, author = {Yousefi-Hashemabad, MJ and Hosseini Kakroudi, M and Pourashory, M and Forouzan, K and Yazdanpanah, N and Saleki, K and Rezaei, N}, title = {Intratumoral Bacterial Microbiota in Gastrointestinal Adenocarcinoma: From Computational Insights to Clinical Practice.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {108174}, doi = {10.1016/j.micpath.2025.108174}, pmid = {41242566}, issn = {1096-1208}, abstract = {Intratumoral microbiota refers to bacteria and other organisms residing within the tumor microenvironment and are intriguingly found throughout the TME, including in cancer cells, immune cells, and stromal components. Among these microbiota, bacteria have gained attention due to their emerging roles in tumor biology. Recent research has uncovered new pathophysiological and therapeutic roles for targeting intratumoral bacterial microbiota. Emerging evidence pointed out that certain taxa, including Fusobacterium nucleatum and Porphyromonas gingivalis, can drive tumorigenic activity, whereas taxa such as Lactobacillus spp. may act as a protective agent. Overall, bacteria can influence cancer progression through mechanisms including immune modulation, metabolic reprogramming, and genomic instability. Furthermore, advances in artificial intelligence (AI) and microbiome profiling have identified prognostic microbial signatures and markers of treatment response. In addition, the mediation of the tumor microbiota via probiotics, antibiotics, engineered microbes, and fecal transplants exhibits novel approaches in targeted cancer therapy. The present review captures the role of intratumoral bacterial microbiota in adenocarcinomas and their significance in cancer development and progression as evidenced by experimental and clinical research.}, } @article {pmid41241915, year = {2025}, author = {Preetham, K and Chatterjee, J}, title = {Research trend on the emerging role of the microbiome in idiopathic male infertility.}, journal = {Antonie van Leeuwenhoek}, volume = {118}, number = {12}, pages = {193}, pmid = {41241915}, issn = {1572-9699}, mesh = {Male ; Humans ; *Infertility, Male/microbiology/etiology ; *Microbiota ; Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; Oxidative Stress ; }, abstract = {Idiopathic male infertility remains a major challenge in reproductive medicine despite extensive diagnostic workups, prompting research into novel etiologies and interventions. Emerging evidence highlights the microbiome's role in modulating male reproductive health. This study analyzes global research trends on idiopathic male infertility and associated microbial health over the past two decades using a structured bibliometric approach. Data extracted from Scopus were examined through Biblioshiny and VOSviewer. The analysis reveals a clear transition from traditional genetic and oxidative stress-based studies to microbiome-centered and multi-omics investigations. Increased Research output and citation rates in recent years, underscoring the growing relevance of microbiome studies. Key contributors like Agarwal A, Wang X, Zhang H, and Lundy SD advanced understanding from genetic and oxidative causes to gut-testis and semen microbiome interactions. Leading contributors and countries, particularly China and the USA dominate collaborative networks. Key themes link microbial dysbiosis, oxidative stress, inflammation, and hormonal imbalance with impaired spermatogenesis. Environmental and lifestyle factors, including diet, alcohol, antibiotics, endocrine disruptors, and microplastics, were increasingly recognized as influencing microbiome-mediated fertility. Mechanistic insights into the gut-testis axis, endotoxemia, immune modulation, and nutrient metabolism suggest avenues for diagnostics and microbiome-based interventions, including probiotics, nutritional modulation, and fecal microbiota transplantation.}, } @article {pmid41241335, year = {2025}, author = {Xu, Y and Ni, Y and Zhou, M and Gou, X}, title = {Qushi Huayu decoction alleviates NAFLD in mice by regulating gut microbiota homeostasis in the gut-liver axis via the pregnane X receptor.}, journal = {European journal of pharmacology}, volume = {1008}, number = {}, pages = {178366}, doi = {10.1016/j.ejphar.2025.178366}, pmid = {41241335}, issn = {1879-0712}, abstract = {BACKGROUND: Qushi Huayu decoction (QHD) is a traditional Chinese medicine formula with clinical experience in the treatment of non-alcoholic fatty liver disease (NAFLD). The gut-liver axis is directly connected via the portal vein, making gut microbiota dysbiosis and endotoxin circulation key drivers in the development and progression of NAFLD. However, the regulation of the gut-liver axis by QHD in NAFLD remains unreported, and its target mechanisms have yet to be elucidated.

MATERIALS AND METHODS: NAFLD was induced in male C57BL/6J mice via high-fat diet feeding, followed by 4 weeks of QHD administration. Comprehensive evaluation included serum biochemical analysis, liver histopathology examination, and quantification of proinflammatory enzyme activity. Mechanism studies were conducted via 16S rRNA sequencing, transcriptomics analysis, SCFAs analysis, RT-qPCR, Western blotting and ELISA techniques.

RESULTS: QHD therapy effectively ameliorates hepatic steatosis and lipid accumulation in a mouse model of NAFLD. In addition, QHD significantly increases intestinal tight junction proteins, thereby restoring intestinal barrier integrity and alleviating inflammatory responses. Transcriptomics revealed that QHD regulates multiple biological functions through multiple genes, in which inflammatory responses may play a key role. Simultaneously, QHD exerts beneficial modulation of the gut microbiota, increasing beneficial bacteria, particularly Akkermansia, while decreasing the prevalence of harmful microorganisms, such as Desulfovibrio. Fecal microbiota transplantation experiments demonstrates that gut microbiota remodeling partially mediates pharmacological efficacy of QHD against NAFLD. Notably, subsequent investigations identified that QHD altered the composition of the gut microbiota and the levels of acetic acid, propionic acid, and valeric acid in SCFAs in a PXR-dependent manner.

CONCLUSIONS: QHD exerts therapeutic effects on NAFLD by regulating the gut-liver axis. The mechanism by which QHD intervention ameliorates gut microbiota dysbiosis in NAFLD mice is associated with its regulation of PXR. This provides further scientific evidence and support for QHD's efficacy in improving NAFLD.}, } @article {pmid41239321, year = {2025}, author = {Alkuwaiti, SH and Skrabulyte-Barbulescu, J and Yassin, LK and Almazrouei, S and Aldhaheri, D and Alderei, M and BaniYas, S and Alshamsi, SH and Alnuaimi, A and Saeed, S and Alawadhi, M and Rutkowska-Gauvry, P and Ismail, FY and Hamad, MIK}, title = {Harnessing the microbiota-gut-brain axis to prevent and treat pediatric neurodevelopmental disorders: translational insights and strategies.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {1286}, pmid = {41239321}, issn = {1479-5876}, abstract = {BACKGROUND: Pediatric neurodevelopmental and neuropsychiatric disorders, including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), Rett syndrome (RTT), Tourette syndrome (TS), Down syndrome (DS), Fragile X syndrome (FXS), Prader–Willi syndrome (PWS), fetal alcohol spectrum disorder (FASD), pediatric epilepsy, congenital Zika syndrome (CZS), Wilson’s disease (WD), and cerebral palsy (CP), are associated with long-term impairments and high societal burden. Emerging evidence implicates the microbiota–gut–brain axis (MGBA) in early neurodevelopment with factors, such as maternal microbiota, birth mode, antibiotics, and infant diet shaping microbial colonization and influencing developmental outcomes.

OBJECTIVE: This review aims to synthesize current translational evidence from animal and human studies to address the following research questions: (1) How do disruptions in the MGBA contribute to the pathophysiology of pediatric neurodevelopmental disorders? (2) What microbiome alterations are consistently associated with these conditions? and (3) What ethical and safety considerations should be addressed in implementing early-life microbiome-based interventions? We also assess emerging microbiota-based interventions, including probiotics, prebiotics, dietary strategies, fecal microbiota transplantation, and traditional therapies, and their potential to modulate disease outcomes.

CONCLUSION: The MGBA presents a promising, yet currently preliminary, target for early intervention in pediatric neurodevelopmental disorders. There is emerging evidence that therapies targeting the microbiota could have an effect on neurodevelopment and outcomes of health and disease; however, most of the findings are in the initial stages, and the evidence is still inconsistent. Therefore, the findings must be translated into mechanisms of action over extended periods with longitudinal multi-omic studies to identify possible intervention windows, optimize personalized therapies, and evaluate the safety and efficacy of interventions targeting the microbiome. Till that point, these microbiota-targeted approaches should be approached cautiously and treated as experimental in the realm of pediatric interventions, given the present-day state of evidence.}, } @article {pmid41241180, year = {2025}, author = {Han, H and Park, J and Zhang, R and Subramaniyam, N and Das, S and Ge, X and Babu Komakula, SS and Wang, C and Desert, R and Chen, W and Song, Z and Athavale, D and Anwar, A and Lantvit, D and Guzman, G and Frutos, MD and Ramos-Molina, B and Nieto, N}, title = {INTESTINAL EPITHELIAL CELL-DERIVED OSTEOPONTIN PROTECTS AGAINST METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS BY MODULATING BILE ACID COMPOSITION AND THE GUT MICROBIOME.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {}, number = {}, pages = {101678}, doi = {10.1016/j.jcmgh.2025.101678}, pmid = {41241180}, issn = {2352-345X}, abstract = {BACKGROUND & AIMS: The gut-liver axis plays a critical role in metabolic dysfunction‒associated steatohepatitis (MASH). Osteopontin (OPN, encoded by SPP1) is implicated in chronic liver disease; however, its expression in intestinal epithelial cells (IECs) and role in MASH remain unclear.

METHODS: We evaluated intestinal OPN expression during MASH progression in patients. To determine the function of IEC-derived OPN, we generated Spp1 knock-in (Spp1[KI IEC]) and knock-out (Spp1[ΔIEC]) mice and fed them a high-fat, high-fructose, high-cholesterol diet to induce MASH.

RESULTS: IEC OPN expression decreased with MASH progression and was inversely associated with liver injury. Loss of Spp1 in IECs exacerbated MASH, whereas overexpression or oral OPN administration was protective. Spp1[ΔIEC] mice exhibited increased hepatic inflammation, disrupted IEC morphology, elevated IEC apoptosis, reduced epithelial cell turnover, and heightened intestinal permeability. They also showed hepatic 16s rRNA presence and elevated conjugated bile acids (BAs), particularly taurocholic acid (TCA) and taurodeoxycholic acid (TDCA), in portal serum. These BAs promoted hepatocyte injury and activated liver macrophages, enhancing inflammation both in vitro and in vivo. Fecal microbiome analysis revealed reduced abundance of bile salt hydrolase (BSH)-expressing bacteria. Fecal microbiota transplantation from Spp1[ΔIEC] mice or treatment with a BSH inhibitor further worsened MASH.

CONCLUSION: IEC-derived OPN protects against MASH by modulating BA composition and shaping the gut microbiome.}, } @article {pmid41241177, year = {2025}, author = {Rinaldi, M and Gatti, M and Giannella, M}, title = {Avoiding resistance development to newer drugs: open research lines.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2025.11.009}, pmid = {41241177}, issn = {1469-0691}, abstract = {BACKGROUND: The spread of multidrug-resistant Gram-negative bacteria (MDR-GNB), particularly those with carbapenem-resistant (CR) or difficult-to-treat resistance (DTR) phenotypes, is a major public health threat. New agents offer potent therapeutic options but carry the challenge of preserving their effectiveness against resistance.

OBJECTIVE: This narrative review summarizes antimicrobial and non-antimicrobial strategies to prevent or mitigate resistance development to novel agents.

SOURCES: We searched PubMed-MEDLINE for English-language articles published in the last five years.

CONTENT: Among antimicrobial strategies, we reviewed the role of optimizing pharmacokinetic/pharmacodynamic (PK/PD) targets for novel beta-lactam/beta-lactamase inhibitor combinations (BL/BLIc) and the impact of combination versus monotherapy regimens. Achieving aggressive joint PK/PD targets may help prevent resistance, supported by approaches such as continuous infusion of time-dependent agents and therapeutic drug monitoring. Current evidence does not demonstrate a routine benefit of combination therapy over monotherapy for novel drugs; however, available studies are limited in size and quality, and resistance emergence has rarely been a primary endpoint. Non-antimicrobial strategies reviewed include fecal microbiota transplantation (FMT), phage therapy, and active or passive immunization. These approaches may reduce the burden of MDR-GNB, particularly in high-risk populations such as immunocompromised patients, those undergoing invasive procedures, or patients with foreign bodies. By lowering pathogen load and transmission, these interventions could enhance the effectiveness of current drugs and limit further resistance development.

IMPLICATIONS: Prevention of resistance to novel BL/BLIc currently relies on optimized dosing and infusion strategies. The benefit of combination regimens remains uncertain and warrants further investigation, ideally with resistance emergence as a defined endpoint and addressed with appropriate analysis. Non-antimicrobial interventions show promise as adjunctive tools in high-risk settings and merit integration into broader resistance prevention frameworks.}, } @article {pmid41240539, year = {2025}, author = {Ma, J and Li, Y and Yang, Y and Zhao, L and Jiang, Y and Wong, TW and Zhang, D}, title = {Gut-liver axis mechanisms of Hippophae rhamnoides L. in non-alcoholic fatty liver disease prevention.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {149}, number = {}, pages = {157517}, doi = {10.1016/j.phymed.2025.157517}, pmid = {41240539}, issn = {1618-095X}, abstract = {BACKGROUND: Phytosterol-rich Hippophae rhamnoides L. can ameliorate abnormal blood lipids in patients with non-alcoholic fatty liver disease (NAFLD). Its gut microbiota modulatory roles along gut-liver axis are not known.

OBJECTIVE: This study explored the preventive roles of H. rhamnoides L. against NAFLD and the associated gut-liver axis mechanisms.

METHODS: Sterols were extracted from H. rhamnoides L. seed oil (SHR) and subjected to LC-MS analysis. Their effects on body/liver/epididymal fat mass, intestinal microbiota, metabolites (DAO, D-LA, LPS) and SCFAs secretion, intestinal barrier (claudin-1, ZO-1) and liver lipid composition and molecular biology (AST, ALT, TC, TG, LDL-C, HDL-C, SREBP1c, SCD1, FAS, LXRα, PPARα) were examined in vivo against normal and high-fat diet mice. The modulatory action of microbiota on liver dysfunction was further verified through SHR-fed fecal transplantation into antibiotic-pretreated mice.

RESULTS: β-sitosterol, campesterol, stigmasterol, and ergosterol were the primary active constituents of SHR. With reference to high fat diet mice, SHR increased intestinal tight junction functionality, reducing inflammatory LPS migration to liver and hepatic lipid synthesis. SHR raised the relative abundance of Alloprevotella and Lachnospiraceae_NK4A136_group, and Bacteroides/Firmicutes ratio leading to increased SCFA secretion that strengthened intestinal barrier and reduced hepatic hyperlipidemia.

CONCLUSION: SHR effectively mitigated NAFLD by reducing hepatic lipid expression via regulating intestinal microbiota, its SCFA secretion and intestinal barrier.}, } @article {pmid41239983, year = {2025}, author = {Gabriel-Segard, T and Heberden, C and Mondot, S and Duquesnoy, M and Dicembre, M and Naudon, L and Philippe, C and Maximin, E and Blais, A and Jacota, M and Lapaque, N and Blottière, HM and Paul, S and Doré, J and Rabot, S and Hanachi, M}, title = {Anorexia nervosa symptoms are induced after specific gut microbiota dysbiosis transfer in germ-free mice.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2563701}, doi = {10.1080/19490976.2025.2563701}, pmid = {41239983}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Anorexia Nervosa/microbiology/therapy/physiopathology ; *Dysbiosis/microbiology ; *Fecal Microbiota Transplantation ; Mice ; Mice, Inbred BALB C ; Female ; Disease Models, Animal ; Humans ; Germ-Free Life ; Feces/microbiology ; Adult ; Male ; }, abstract = {Anorexia nervosa (AN) is the most severe and life-threatening eating disorder. Its pathophysiology remains largely unknown, and no effective treatment currently exists for severe forms of the disease. Gut microbiota (GM) dysbiosis has been consistently reported in AN; however, no study has yet considered the role of the microbiota within the full spectrum of AN symptoms. To investigate the direct involvement of the microbiota in disease symptoms, we developed a murine model of fecal microbiota transplantation (FMT), using germ-free BALB/c mice colonized with fecal samples from well-characterized AN patients and healthy controls. Physiological, organ, and behavioral parameters were systematically monitored. We found that key AN-related features (including food restriction, anxiety-like behavior, physical hyperactivity, and elevated inflammatory responses) were transmitted to germ-free mice following transplantation with AN-derived microbiota. Likewise, organ-specific alterations associated with AN, such as liver dysfunction and disruption of ovarian follicles, were also reproduced. In conclusion, we demonstrate that the transfer of AN microbiota induces behavioral, physiological, and organ-level alterations reminiscent of the human disease. These findings highlight a major role of the gut microbiota in the symptomatology and progression of AN and open new therapeutic perspectives targeting this ecosystem.}, } @article {pmid41239968, year = {2025}, author = {Kim, MS and Bisanz, JE}, title = {Design and application of synthetic human gut microbial communities.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2575923}, doi = {10.1080/19490976.2025.2575923}, pmid = {41239968}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation/methods ; Dysbiosis/therapy/microbiology ; Inflammatory Bowel Diseases/therapy/microbiology ; Host Microbial Interactions ; Bacteria/genetics/classification ; Animals ; }, abstract = {The gut microbiome shapes host health through a complex network driven by both host‒microbe and microbe‒microbe interactions. Disruption of these interactions, often referred to as dysbiosis, is associated with a range of infectious and chronic diseases. Owing to the success of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridioides difficile infection, FMT has been explored as a therapeutic option for a range of microbiota-associated conditions, including inflammatory bowel disease and obesity. However, the microbial diversity that is the greatest strength of FMT is also its greatest liability. Concerns relating to reliance on human donors, potential for transmission of multidrug-resistant organisms or undesirable phenotypes demonstrate a need for alternate approaches, including the generation of synthetic alternatives to FMT, which can be built in the laboratory from individual strains. Furthermore, these communities are powerful tools for conducting mechanistic research allowing for the generation of 'knockout' communities, which are not possible when working with undefined fecal transplants. This review examines strategies for designing synthetic microbial communities that represent a new generation of microbiome-derived therapies. We highlight how synthetic microbial communities are being used to answer mechanistic questions about host-microbiome interactions relevant to health and disease. Finally, we examine the current clinical translation of these communities as live biotherapeutic products (LBPs). While the regulatory frameworks for LBPs continue to evolve, early clinical successes illuminate the potential for synthetic microbial communities to treat complex human diseases through targeted manipulation and restoration of the gut microbiome.}, } @article {pmid41238277, year = {2025}, author = {Pai, N and Sainath, NN}, title = {Diagnosis and Management of Small Intestinal Bacterial Overgrowth in Pediatric Short Bowel Syndrome.}, journal = {Gastroenterology clinics of North America}, volume = {54}, number = {4}, pages = {805-821}, doi = {10.1016/j.gtc.2025.07.005}, pmid = {41238277}, issn = {1558-1942}, mesh = {Humans ; *Short Bowel Syndrome/microbiology/complications/therapy ; *Intestine, Small/microbiology ; Child ; Anti-Bacterial Agents/therapeutic use ; Gastrointestinal Microbiome ; Breath Tests ; *Blind Loop Syndrome/diagnosis/therapy ; }, abstract = {This article explores the diagnosis and management of small intestinal bacterial overgrowth in children with short bowel syndrome, a population affected by altered anatomy, dysmotility, and medication-related risk factors. Diagnostic accuracy is limited by the feasibility, and specificity of breath testing and small bowel aspirates. While antibiotics are commonly used, concerns about recurrence and antibiotic resistance remain significant. Emerging nutritional strategies and precision-based, microbiome-targeted therapies offer promising adjunctive treatment options.}, } @article {pmid41238092, year = {2025}, author = {Ye, M and Ju, H and Ren, G and Hu, J}, title = {The Role of Microbiome in Immunotherapy: Insights and Perspectives.}, journal = {Seminars in cancer biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2025.11.001}, pmid = {41238092}, issn = {1096-3650}, abstract = {The intricate interplay between the gut microbiome and the host immune system has been recognized as a pivotal determinant of clinical outcomes in cancer immunotherapy. Mounting evidence suggests that specific microbial communities are associated with both the efficacy and toxicity of immune checkpoint inhibitors in diverse malignancies, underscoring the microbiome's role in modulating systemic and tumour-localized immunity. Mechanistically, the microbiome shapes antitumour immunity by affecting antigen presentation, activation of effector cells, immunosuppression and adverse effects. Key microbial components and metabolites present in distinct anatomical niches have been identified as promoters or inhibitors of therapeutic responsiveness via multiple pathways. Harnessing this knowledge, microbiome-targeted strategies such as antibiotic, probiotic, fecal microbiota transplantation, and dietary modulation are regarded as potential adjuvant therapies to enhance the efficacy of anti-tumour therapies. Although significant progress has been achieved in preclinical studies, challenges persist in translating these findings into standardized clinical applications.}, } @article {pmid41237834, year = {2025}, author = {Yang, J and Li, J}, title = {Nanotechnology-Microbiota Synergy in Cancer Immunotherapy.}, journal = {Critical reviews in oncology/hematology}, volume = {}, number = {}, pages = {105018}, doi = {10.1016/j.critrevonc.2025.105018}, pmid = {41237834}, issn = {1879-0461}, abstract = {The global burden of cancer continues to escalate, yet the efficacy of current targeted therapies and immune checkpoint inhibitors (ICIs) is often hampered by drug resistance and immune escape. The gut microbiota orchestrates tumor progression and ICI efficacy bidirectionally via the "microbiota-immune-tumor" axis. However, traditional interventions, including fecal microbiota transplantation and antibiotics, are limited by inherent drawbacks such as poor targeting. Nanotechnology can overcome this limitation: it not only enables precise targeting of the gut microbiota and reshapes the tumor immune microenvironment to synergistically enhance ICI efficacy but also reverses drug resistance in tumor chemotherapy, radiotherapy, and targeted therapy through multiple strategies. Additionally, it can synergize with probiotics, extracellular vesicles, and other agents to achieve tumor therapy. This review synthesizes current understanding of gut microbiota-immune crosstalk, the microbiota's role in regulating ICI efficacy, and the central applications of nanotechnology, thereby proposing novel synergistic strategies for cancer treatment.}, } @article {pmid41237775, year = {2025}, author = {Van Hul, M and Cani, PD}, title = {From microbiome to metabolism: Bridging a two-decade translational gap.}, journal = {Cell metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmet.2025.10.011}, pmid = {41237775}, issn = {1932-7420}, abstract = {The mapping of the human genome sparked high expectations for biomedical breakthroughs, yet attention has since shifted toward the human microbiome as a key player in health and disease. Pioneering studies revealed striking inter-individual variability and numerous associations between gut microbiota and a wide range of conditions (i.e., obesity, diabetes, cardiovascular and inflammatory bowel diseases, autism, allergies, neurodegenerative diseases, and cancers). However, the field has faced a deluge of correlative "dysbiosis" studies with limited causal evidence. Although animal models have provided crucial mechanistic insights, translating these findings to humans has proven challenging. Interventions such as fecal microbiota transplantation, prebiotics, probiotics, and postbiotics often yield inconsistent or modest effects in clinical trials. This gap highlights the need for precision, functional profiling, and integration of multi-omics , for instance, through artificial intelligence. In this perspective, we discuss what microbiome research offers as a transformative shift and how we conceptualize disease, favoring systems biology and personalized interventions over reductionist approaches.}, } @article {pmid41236646, year = {2025}, author = {Ochi, T and Takeda, M and Asahara, T and Kurita, A and Ogata, Y and Suzuki, M and Takei, H and Nittono, H and Miyano, G and Koga, H and Lane, GJ and Okazaki, T and Saiura, A and Mizuta, K and Kasahara, M and Yamataka, A and Yamashiro, Y}, title = {Postoperative gut dysbiosis in biliary atresia patients treated by portoenterostomy or liver transplantation.}, journal = {Pediatric surgery international}, volume = {42}, number = {1}, pages = {9}, pmid = {41236646}, issn = {1437-9813}, support = {22K11861//Japan Society for the Promotion of Science KAKENHI grant/ ; }, mesh = {Humans ; *Biliary Atresia/surgery ; *Dysbiosis/microbiology/etiology ; *Liver Transplantation/adverse effects ; Male ; Female ; *Portoenterostomy, Hepatic/adverse effects ; *Gastrointestinal Microbiome ; *Postoperative Complications/microbiology ; Infant ; Feces/microbiology/chemistry ; Bile Acids and Salts/analysis ; Case-Control Studies ; }, abstract = {PURPOSE: To assess how surgery and management protocols affect gut microbiota in postoperative biliary atresia (BA) patients by comparing survivors with native livers (NL) or transplanted livers (TL) with healthy non-surgical controls (CL).

METHODS: Subjects were 62 post-portoenterostomy BA patients divided into 2 groups (NL and TL) and CL. All subjects were clinically stable with no dietary restrictions throughout the study period. Stool samples were compared for gut microbiota, organic acids, and fecal bile acids, while blood samples were compared for serum biochemistry and serum bile acids.

RESULTS: Stool samples from CL (n = 30) were normal while NL (n = 31) and TL (n = 31) showed gut dysbiosis with significantly decreased total bacteria and reduced predominance of obligate anaerobes, and an abundance of Clostridioides difficile, Enterobacteriaceae, and Enterococcus. The latter two were more abundant in TL than NL. Biochemistry was normal in TL. In NL, elevated AST/ALT correlated with increased Clostridioides difficile, decreased Bacteroides fragilis group, and decreased Lactobacilli. Fecal secondary bile acids were lower and serum primary and secondary bile acids were higher in NL and TL compared with CL.

CONCLUSION: Gut dysbiosis was present in both NL and TL. Pathogenic florae were more abundant in TL despite TL biochemistry being normal.}, } @article {pmid41235136, year = {2025}, author = {Wu, Y and Pan, S and Yin, C and Kong, Y and Huo, W and Wang, Q and Wu, J and Li, L and Wei, J and Lu, C and Han, L and Lu, Y}, title = {PSORI-CM02 Restores Epidermal Differentiation in Psoriasis via the Gut Microbiota-Sphingolipid Axis.}, journal = {Drug design, development and therapy}, volume = {19}, number = {}, pages = {9993-10010}, pmid = {41235136}, issn = {1177-8881}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Psoriasis/drug therapy/metabolism/pathology ; Mice ; Humans ; *Cell Differentiation/drug effects ; *Sphingolipids/metabolism ; *Epidermis/drug effects/pathology/metabolism ; Keratinocytes/drug effects/metabolism ; }, abstract = {BACKGROUND: Psoriasis is linked to gut dysbiosis and disturbed sphingolipid metabolism. PSORI-CM02 improves epidermal differentiation, yet its impact on the microbiota-sphingolipid axis remains unknown.

METHODS: Transcriptomics of patient keratinocytes, Carmofur inhibition in IMQ mice, and multi-omics (metabolomics, metagenomics) of skin, lymph nodes and gut were combined. SPF, PGF and GF mice underwent FMT to test microbiota dependency.

RESULTS: Psoriatic lesions showed sphingolipid pathway enrichment. Carmofur enhanced differentiation. PSORI-CM02 lowered PASI, spleen index, and tissue levels of ceramide, S1P, C1P and sphingomyelin while restoring Flg, Krt10 and Krt14. It reduced Turicibacter, Bacteroides, Bifidobacterium and Acetobacter. PSORI-CM02-derived microbiota reproduced therapeutic effects in all FMT settings.

CONCLUSION: PSORI-CM02 reshapes gut microbiota, normalizes sphingolipid metabolism and improves epidermal differentiation to treat psoriasis.}, } @article {pmid41234596, year = {2025}, author = {Du, Y and Li, Y and Yu, M and Yu, Y and Zhang, Y and Wang, X and He, J and Lin, L and Shen, B and Gong, Y and Zhu, J and Zou, B and Liu, Y and Huang, M and Lu, Y}, title = {Fecal microbiota transplantation plus immune checkpoint inhibitor rechallenges in patients with advanced non-small cell lung cancer: a single-arm exploratory study.}, journal = {Translational lung cancer research}, volume = {14}, number = {10}, pages = {4541-4559}, pmid = {41234596}, issn = {2218-6751}, abstract = {BACKGROUND: The management of advanced non-small cell lung cancer (NSCLC) after progression on initial immunotherapy represents a significant clinical challenge. Immune checkpoint inhibitor (ICI) rechallenge is a considered option, yet its efficacy remains limited. Strategies to enhance the efficacy of ICI rechallenge are urgently needed. There is a pressing need for novel strategies to sensitize tumors to ICI rechallenge. Previous studies have established a correlation between the gut microbiota and the tumor response to immunotherapy, and have explored the application of fecal microbiota transplantation (FMT) in modifying the immune response by restoring the gut microbiota. However, the potential of FMT from healthy donor to reverse immunotherapy resistance in patients with NSCLC has not been previously investigated. This preliminary study aimed to provide initial insights into the safety, tolerability, and potential efficacy of the combined therapy of FMT from healthy donor with immunotherapy rechallenge in NSCLC patients.

METHODS: In this single-arm exploratory study, patients with advanced NSCLC who progressed after prior immunotherapy were screened and enrolled based on predefined eligibility criteria, including prior response to ICIs and adequate organ function. Eligible patients received oral FMT capsules from healthy donors followed by rechallenge with camrelizumab. The primary endpoint was safety and feasibility [incidence of adverse events (AEs) graded by CTCAE v5.0]. Secondary end points included the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Fecal and blood samples were collected for exploratory analyses of microbiota, metabolome, and T cell receptor (TCR) repertoire.

RESULTS: Seven patients (all male, median age 55 years) were enrolled and constituted the analysis population. The majority (5/7) had received three or more prior lines of therapy. During the follow-up period, none experienced grade 4 or higher AEs. The treatment-related AEs were mainly associated with immunotherapy, and only grade 1 FMT-related AEs (e.g., nausea, diarrhea, bloating, and constipation) were reported. One patient achieved a partial response (PR) and one achieved stable disease (SD) with PFS times of 14.6 and 8.1 months, respectively. The median PFS was 1.5 months [95% confidence interval (CI): 1.24-1.75], and the OS was 12.1 months (95% CI: 0.3-23.9) for all patients. Moreover, the treatment modulated the composition of the intestinal flora in all patients, with alpha diversity increasing in responders and decreasing in non-responders.

CONCLUSIONS: The results indicated that the combined therapy of FMT and immunotherapy rechallenge was feasible and demonstrated a tolerable safety profile in this small cohort. The observed clinical activity is preliminary. These findings support the need for larger, controlled trials to assess the efficacy of this approach.}, } @article {pmid41234231, year = {2025}, author = {Huang, L and Wang, S and Zhang, H and Feng, S and Zhong, H and Chen, J and Xie, W and Wu, L and Zhang, T and He, X and Yang, J}, title = {Clinical efficacy evaluation of washed microbiota transplantation treatment for metabolic related fatty liver disease and its impact on tongue coating microorganisms.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1684173}, pmid = {41234231}, issn = {1664-2392}, mesh = {Humans ; Animals ; *Tongue/microbiology ; Mice ; Male ; Female ; Middle Aged ; *Microbiota ; *Fecal Microbiota Transplantation/methods ; Adult ; Mice, Inbred C57BL ; Treatment Outcome ; RNA, Ribosomal, 16S/genetics ; *Non-alcoholic Fatty Liver Disease/therapy/microbiology ; }, abstract = {OBJECTIVE: The present study aims to explore the impact of washed microbiota transplantation (WMT) on the tongue microbiota composition of individuals with metabolic-associated fatty liver disease (MAFLD) and elucidate its biological correlations.

METHODS: We conducted a comprehensive analysis of hepatic fat deposition and characterized the tongue coating microbiota using 16S rRNA gene sequencing in MAFLD patients before and after undergoing WMT treatment. Furthermore, a MAFLD mouse model was established for additional validation.

RESULTS: At the genus level, significant differences in tongue coating microbiota structure were observed between MAFLD patients and HC. Specifically, Neisseria positively correlated with the BARD score, Porphyromonas and Rhodococcus positively correlated with fat decay, and Petostreptococcus, a conditionally pathogenic bacterium, exhibited a significantly higher relative abundance in MAFLD patients compared to HC. Conversely, Actinomyces positively correlated with the FIB-4 score, Megasphaera negatively correlated with the APRI score, and Subdoligulum negatively correlated with low-density lipoprotein levels. Notably, following effective WMT treatment, patients exhibited improved symptoms, with a significant reduction in the relative abundance of Petostreptococcus and an increase in potential probiotics such as Lachnospiraceae and Bifidobacterium in their tongue coating microbiota. Additionally, structural differences in the tongue coating microbiota were identified at the genus level between MAFLD model mice and HC mice. After WMT treatment, the relative abundance of conditionally pathogenic bacteria like Enterococcus was significantly decreased in MAFLD model mice.

CONCLUSIONS: WMT not only significantly ameliorates liver fat deposition in MAFLD patients but also alters the tongue coating microbial structure associated with disease severity, thereby potentially mitigating adverse patient outcomes.}, } @article {pmid41232540, year = {2025}, author = {Wieringa, JW and Binyamin, D and Jankelowitz, IA and Schweitzer, R and Turjeman, S and Khatib, S and Esser, MJ and van der Woude, CJ and Fuhler, GM and Koren, O}, title = {Intestinal barrier alterations in mice following fecal microbiota transplant from children of IBD-affected mothers.}, journal = {Med (New York, N.Y.)}, volume = {}, number = {}, pages = {100915}, doi = {10.1016/j.medj.2025.100915}, pmid = {41232540}, issn = {2666-6340}, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) carries a hereditary risk, which is higher through maternal, rather than paternal, inheritance. Like their mothers, children born to mothers with IBD have an altered microbiome shortly after birth.

METHODS: To investigate whether this altered microbiome persists later in life and affects the intestinal mucosa, the fecal microbiome was analyzed in samples from 44 infants ranging from 0 to 10 years of age born to 26 women with IBD. Forty-four age-matched children of 29 women without IBD served as controls. Fecal microbiota transplantation (FMT) to germ-free mice was carried out from 4-year-olds born to mothers with IBD and controls. Markers of inflammation, barrier function, and metabolic changes were investigated.

FINDINGS: Intestinal microbiomes were more similar between women with IBD and their children than between control mothers and their offspring. Microbial changes were noticeable in children from mothers with IBD from the age of 4 years compared to children of controls. No inflammatory response was present in the mucosa of mice receiving FMT from children of mothers with IBD; however, mesenteric lymph node enlargement and decreased expression of barrier genes Zo1 and Ocln were seen in mice receiving FMT from these children compared to controls. Additionally, reduced colonic expression of the immunological tolerance enzyme Ido1 coincided with decreased serum kynurenine/tryptophan ratios.

CONCLUSIONS: Fecal microbiomes of children of mothers with IBD exhibit characteristics that reduce epithelial tight junction barrier genes and tolerogenic tryptophan metabolism. Microbiome-induced gut barrier disruptions may contribute to an enhanced IBD predisposition in infants of mothers with IBD.

FUNDING: This work was funded by ZonMw.}, } @article {pmid41161092, year = {2025}, author = {Gu, M and Peng, X and Dai, X and Ma, X and Ge, W and Yang, S and Wei, W}, title = {Tannic acid decreased the synthesis and secretion of sIgA in the small intestine of Brandt's voles (Lasiopodomys brandtii) by modifying gut microbiota.}, journal = {Biochemical and biophysical research communications}, volume = {789}, number = {}, pages = {152846}, doi = {10.1016/j.bbrc.2025.152846}, pmid = {41161092}, issn = {1090-2104}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Arvicolinae/microbiology/immunology ; *Intestine, Small/drug effects/microbiology/metabolism/immunology ; *Tannins/pharmacology ; *Immunoglobulin A, Secretory/metabolism/biosynthesis ; Male ; Fecal Microbiota Transplantation ; Polyphenols ; }, abstract = {Tannic acid (TA), a representative plant secondary metabolite, impairs intestinal immune function and alters intestinal microbiota abundance of Brandt's voles. Whether TA reduces intestinal immune function by modifying the gut microbiota remains unknown. In this study, Brandt's voles were divided into three groups for microbiota transplantation (FMT): normal saline (Ab), microbiota from normal saline administration (R-Con), and microbiota from TA administration (R-TA). Then, the intestinal morphology, immune indices, gut flora, and microbiota metabolites were measured after FMT. The findings showed that the sIgA content of small intestine of voles in the R-TA group were lower than in the R-con group. Additionally, the voles in the R-con group exhibited higher mRNA levels of PIgR, J-chain, BAFF, and APRIL than in the R-TA group. The ANOSIM results showed significant structural differentiation, reflecting that the β-diversity of the cecal microbiome was altered. Moreover, the voles in the R-con group had a higher concentration of butyric acid in the cecum compared to both the Ab and R-TA groups. In the experiment 2, the sIgA content in the duodenum and ileum of Brandt's voles in the TBA group (1200 mg•kg[-1]d[-1] TA + butyrate) was significantly higher than that in the TNS group (1200 mg•kg[-1]d[-1] TA + normal saline). To summarize, the "TA microbiota" decreased the slgA secretion and synthesis in the small intestine by reducing butyric acid content, thus lowering the intestinal immune capacity of Brandt's voles. The findings provide the experimental basis to prove the critical role of gut microorganisms in controlling animal physiological processes.}, } @article {pmid41232361, year = {2025}, author = {Bishoyi, AK and Al-Hasnaawei, S and Salem, KH and Ganesan, S and Shankhyan, A and Nanda, A and Sinha, A and Ray, S and Nathiya, D and Hammady, FJ}, title = {Gut microbiome metabolites in lung cancer: The emerging importance of short-chain fatty acids.}, journal = {International immunopharmacology}, volume = {168}, number = {Pt 1}, pages = {115821}, doi = {10.1016/j.intimp.2025.115821}, pmid = {41232361}, issn = {1878-1705}, abstract = {Short-chain fatty acids (SCFAs), which are produced from the fermentation by the gut microbiota of dietary fiber, are now proven to play a vital role in the growth control of lung cancer and drug response. SCFAs have mechanisms of action, including the inhibition of histone deacetylases, activation of G-protein-coupled receptors, and metabolic reprogramming. SCFAs suppress tumor growth, induce apoptosis, suppress angiogenesis, and modulate epithelial-mesenchymal transition. Besides the above direct antitumor effects, SCFAs enhance the therapeutic effect of immune checkpoint inhibitors and reduce the toxicity of radiotherapy and chemotherapy by maintaining the mucosal barrier and restoring systemic immune homeostasis. Butyrate function is highly dualistic; it is usually protective but may confer multidrug resistance under certain therapeuticconditions. To reconcile these opposing effects is akey challenge in the translation of microbiota-based therapeutics and interventions. Therapies such as probiotics, fecal microbiota transplantation, and designed microbial consortia all target SCFAs as central mediators of microbiome-host communication. Overall, SCFAs are candidate metabolic co-adjuvants that can maximize therapeutic efficacy, suppress unacceptable side effects, and redirect therapeutic approaches to lung cancer.}, } @article {pmid41229982, year = {2025}, author = {Chen, Z and Li, L and Jin, D and Zhao, Y and Malard, F and Huang, H and Ye, Y and Mohty, M}, title = {Gut microbiota and acute graft-versus-host disease.}, journal = {Chinese journal of cancer research = Chung-kuo yen cheng yen chiu}, volume = {37}, number = {5}, pages = {657-666}, pmid = {41229982}, issn = {1000-9604}, abstract = {Acute graft-versus-host disease (aGVHD) is an important complication which critically impacts the prognosis of patients undergoing allogeneic hematopoietic stem cell transplantation. Increasing evidence suggests that dysbiosis of the gut microbiota plays a key role in aGVHD pathogenesis. The biological process involves compromised intestinal barrier integrity, amplified inflammation driven by the translocation of microbial products like lipopolysaccharide, and finally the dysregulated immune response centralized by T cell activation and differentiation. Meanwhile, certain microbial metabolites such as short-chain fatty acids and secondary bile acids exert protective effects. The clinical relevance of these findings is underscored by studies establishing that specific gut microbial signatures, such as low diversity and single pathogen dominance, independently predict aGVHD morbidity and mortality. From a therapeutic perspective, the microbiome has emerged as an important therapeutic target for aGVHD. Fecal microbiota transplantation has shown significant efficacy in clinical trials for prophylaxis and treatment of aGVHD, providing definitive proof-of-concept for ecological restoration. This review synthesizes these foundational mechanistic insights, from metabolic disruption to host-microbe crosstalk at the mucosal barrier, and details the rapidly advancing clinical landscape of microbiome-targeted diagnostics and therapeutics for aGVHD.}, } @article {pmid41229686, year = {2025}, author = {Tian, R and Chong, CJ and Bai, YY and Chen, N and Qiao, RR and Wang, K and Wang, YW and Zhao, P and Zhao, CB and Tang, YP and Zhang, L and Zhang, Q}, title = {The role of gut microbiota in diarrhea and its alleviation through microbiota-targeted interventions.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1630823}, pmid = {41229686}, issn = {1664-302X}, abstract = {Diarrhea is a common gastrointestinal disease and closely related to the balance of the gut microbiota (GM). In turn, dysregulation of the GM can affect the onset and progression of diarrhea through regulating the metabolism, intestinal immune function, intestinal barrier function and changes in the brain-gut axis of host. Although increasing evidence suggests that GM is associated with gastrointestinal homeostasis and disease, the underlying mechanisms are not fully understood. GM disorder was often accompanied by diarrhea patients and animals, and the diarrhea caused by GM imbalance mainly involved the effects on short chain fatty acids (SCFAs), bile acids (BAs), intestinal barrier, immune system, and brain-gut microbiota axis (BGMA). In addition, intervening in the GM (probiotics, fecal microbiota transplantation and bacteriophage therapy) has been shown to be an effective way to alleviate diarrhea. In this review, the mechanism of diarrhea occurrence, probiotics, fecal microbiota transplantation and bacteriophage therapy intervene in diarrhea by regulating GM from basic and clinical research were summarized and discussed. We aim to provide the latest reference for studying the mechanism of treating diarrhea from the perspective of GM, and provide data support for clinical treatment of diarrhea.}, } @article {pmid41229548, year = {2025}, author = {Xiao, Y and Wei, L and Yu, J and Liu, Y}, title = {Fecal Microbiota Transplantation for Attention-Deficit/Hyperactivity Disorder: Mechanisms, Evidence, and Future Directions.}, journal = {International journal of general medicine}, volume = {18}, number = {}, pages = {6757-6767}, pmid = {41229548}, issn = {1178-7074}, abstract = {Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition characterized by inattention, hyperactivity, and impulsivity. While pharmacological and behavioral therapies remain first-line treatments, their limitations in efficacy, tolerability, and long-term adherence underscore the need for innovative interventions. Growing evidence highlights the role of the microbiota-gut-brain axis (MGBA) in ADHD pathophysiology, particularly involving immune dysregulation, neurotransmitter imbalance, metabolic disruption, and epigenetic alterations. Fecal microbiota transplantation (FMT), as a microbiota-based intervention, has shown promise in restoring MGBA homeostasis and modulating neural function through multiple mechanisms. This review summarizes current preclinical and clinical research on FMT in ADHD, covering its effects on neuroinflammation, neurotransmitter pathways, vagus nerve and HPA axis signaling, and epigenetic reprogramming. Although preclinical models and early human data indicate potential behavioral benefits and mechanistic plausibility, methodological heterogeneity, limited sample sizes, and incomplete mechanistic validation pose significant challenges. Future research should prioritize protocol standardization, randomized controlled trials, biomarker discovery, and ethical regulation to facilitate the safe and effective clinical translation of FMT in ADHD treatment.}, } @article {pmid41228422, year = {2025}, author = {Diotaiuti, P and Misiti, F and Marotta, G and Falese, L and Calabrò, GE and Mancone, S}, title = {The Gut Microbiome and Its Impact on Mood and Decision-Making: A Mechanistic and Therapeutic Review.}, journal = {Nutrients}, volume = {17}, number = {21}, pages = {}, doi = {10.3390/nu17213350}, pmid = {41228422}, issn = {2072-6643}, support = {MUR Decree n. 105123.06.2022 PNRR Missione 4 Componente 2 Investimento 1.5-CUP H33C22000420001//Project ECS0000024 "Ecosistema dell'innovazione-Rome Technopole" financed by EU NextGeneration EU plan/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Affect/physiology ; *Decision Making/physiology ; Animals ; Cognition ; Probiotics ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; }, abstract = {Background/Objectives: The gut microbiome is increasingly recognized as a key modulator of central nervous system function through the gut-brain axis. Dysbiosis has been associated with neuropsychiatric disorders such as depression, anxiety, impulsivity, cognitive decline, and addiction. This review aims to synthesize mechanistic insights and therapeutic perspectives on how gut microbiota influence mood regulation, decision-making, and cognitive processes. Methods: A comprehensive narrative review was conducted using peer-reviewed articles retrieved from PubMed, Scopus, and Web of Science up to August 2025. Studies were included if they explored microbiota-related effects on behavior, mood, cognition, or decision-making using human or animal models. Emphasis was placed on molecular mechanisms, microbiome-targeted therapies, and multi-omics approaches. Results: Evidence indicates that gut microbiota modulate neurochemical pathways involving serotonin, dopamine, GABA, and glutamate, as well as immune and endocrine axes. Microbial imbalance contributes to low-grade systemic inflammation, impaired neuroplasticity, and altered stress responses, all of which are linked to mood and cognitive disturbances. Specific microbial taxa, dietary patterns, and interventions such as probiotics, prebiotics, psychobiotics, and fecal microbiota transplantation (FMT) have shown promise in modulating these outcomes. The review highlights methodological advances including germ-free models, metagenomic profiling, and neuroimaging studies that clarify causal pathways. Conclusions: Gut microbiota play a foundational role in shaping emotional and cognitive functions through complex neuroimmune and neuroendocrine mechanisms. Microbiome-based interventions represent a promising frontier in neuropsychiatric care, although further translational research is needed to define optimal therapeutic strategies and address individual variability.}, } @article {pmid41226824, year = {2025}, author = {de Groen, P and Blok, LCHM and Fuhri Snethlage, CM and Hanssen, NMJ and Rampanelli, E and Nieuwdorp, M}, title = {Unraveling Type 1 Diabetes: Integrating Microbiome, Metabolomics, and Immunomodulation for Next-Generation Therapies.}, journal = {International journal of molecular sciences}, volume = {26}, number = {21}, pages = {}, doi = {10.3390/ijms262110788}, pmid = {41226824}, issn = {1422-0067}, support = {09150182010020//Personal NWO-VICI grant 2020/ ; 101141346//ERC Advanced grant/ ; 4-SRA-2025-1766-M-B//BREAKTHROUGH T1D Grant/ ; 09150172210050//ZonMw-VIDI grant 2023/ ; 2021T055//Senior Clinical Dekker grant by the Dutch Heart Foundation/ ; 09150172210019//ZONMW-VIDI grant 2023/ ; }, mesh = {Humans ; *Diabetes Mellitus, Type 1/therapy/immunology/metabolism/microbiology ; *Gastrointestinal Microbiome/immunology ; *Metabolomics/methods ; *Immunomodulation ; Animals ; Fecal Microbiota Transplantation ; Autoimmunity ; }, abstract = {Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by T-cell-mediated destruction of pancreatic beta cells, resulting in insulin deficiency. Both genetic predisposition and environmental factors contribute to T1D development, with growing evidence implicating the gut microbiome as a critical environmental modulator in disease pathogenesis. Gut microbial composition and derived metabolites influence immune homeostasis and autoimmunity. This review summarizes recent advances elucidating immune dysregulations in T1D and novel therapeutic strategies to preserve beta cell function. We discuss approaches such as immune cell engineering, including CAR-Treg therapy, and targeted modulation of immune signaling pathways like JAK-STAT. Furthermore, we explore the role of the gut microbiota and its metabolites in modulating host immunity and describe emerging microbiome-targeting interventions, including fecal microbiota transplantation and metabolite supplementation. These interventions show promise in modulating disease progression in preclinical and early clinical studies. An integrated understanding of immune and microbiome-related mechanisms is critical for developing next-generation therapies. Further research and clinical trials are needed to optimize these approaches and translate them into durable, personalized treatments for individuals with T1D.}, } @article {pmid41223655, year = {2025}, author = {Chen, J and Gu, M and Zhang, M and Wang, S and Zhang, X and Zhu, Z and Gan, Q}, title = {Stage-specific gut microbial restructuring drives estrous transition in rabbits.}, journal = {Animal bioscience}, volume = {}, number = {}, pages = {}, doi = {10.5713/ab.250529}, pmid = {41223655}, issn = {2765-0189}, abstract = {OBJECTIVE: This study aimed to investigate the relationship between colonic microbiota and estrous cycle transition in rabbits by integrating 16S rRNA gene sequencing and metabolomic analyses, and to identify key microbial taxa and metabolites involved in estrus regulation.

METHODS: Female New Zealand white rabbits were divided into diestrus and early estrus groups based on vulvar mucosa color and serum estradiol (E2) concentration. Colonic microbiota dynamics were assessed via 16S rRNA sequencing, while metabolomes of colonic contents were profiled using UHPLC-MS/MS. Fecal microbiota transplantation (FMT) was performed by orally administration of colonic contents from diestrus or early estrus rabbits to mice with disrupted estrous cycles, to evaluate the regulatory effects of microbiota. Exogenous indole-3-acetic acid (IAA) was administered to both mice and rabbits to assess its role in estrus onset and cyclicity restoration.

RESULTS: Colonic microbial composition differed significantly between diestrus and early estrus rabbits. The genera Anaerostipes and Ruminiclostridium were enriched in early estrus, while the genera Oscillospirales UCG_010 and UCG_005 were more abundant in diestrus. FMT from early estrus donors restored cyclicity in mice with disrupted cycles, whereas diestrus FMT did not. Metabolomics identified IAA as a key elevated metabolite in early estrus, and this metabolite accelerated estrus onset and restored cyclicity in both mice and rabbits.

CONCLUSION: These findings demonstrate that gut microbiota restructuring regulates the estrous transition of rabbits, providing a basis for developing microbiota-targeted strategies to enhance reproductive efficiency in rabbit production and optimize animal reproductive management.}, } @article {pmid40751372, year = {2025}, author = {Bryant, JA and Straub, TJ and Pardi, DS and Litcofsky, KD and Kelly, CR and Chafee, ME and Cohen, SH and Khanna, S and Berenson, CS and Wortman, J and Sims, M and Ford, CB and Lombardo, MJ and McGovern, BH and von Moltke, L and Kraft, CS and Henn, MR and Hasson, BR}, title = {Comparability of Gastrointestinal Microbiome and Bile Acid Profiles in Patients With First or Multiply Recurrent Clostridioides difficile Infection.}, journal = {The Journal of infectious diseases}, volume = {232}, number = {5}, pages = {e733-e740}, doi = {10.1093/infdis/jiaf408}, pmid = {40751372}, issn = {1537-6613}, support = {//Seres Therapeutics/ ; }, mesh = {Humans ; *Bile Acids and Salts/analysis/metabolism ; *Gastrointestinal Microbiome ; *Clostridium Infections/microbiology/drug therapy/therapy ; Male ; Female ; Feces/microbiology/chemistry ; Middle Aged ; *Clostridioides difficile ; Aged ; Recurrence ; Anti-Bacterial Agents/therapeutic use ; Adult ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) treatment guidelines suggest varied approaches for patients with first (frCDI) or multiply recurrent CDI (mrCDI). Low microbial diversity, elevated primary bile acids (BA), and low secondary BA concentrations favor germination of C. difficile spores into toxin-producing bacteria and are believed to increase rCDI risk. Greater understanding of the gastrointestinal (GI) microbiome in rCDI may inform management of the disease. We describe a post hoc comparison of GI microbiome and bile acid profiles between patients with frCDI and mrCDI in a Phase 3 open-label trial, ECOSPOR IV, of fecal microbiota spores, live-brpk (VOWST®; VOS, formerly SER-109), an orally-administered live microbiome therapeutic.

METHODS: Patients received VOS following symptom resolution after standard-of-care antibiotics. Pretreatment baseline (within 3 days following antibiotic completion) and Week 1 post-dosing stool samples were collected for whole metagenomic sequencing and metabolomics. Diversity was calculated from MetaPhlAn2 species profiles. Concentrations of primary and secondary BAs were measured via targeted LC-MS/MS.

RESULTS: rCDI rates through Week 8 were similarly low in both frCDI and mrCDI patients (6.5% versus 9.7%, respectively). Baseline microbial diversity was similarly low between frCDI and mrCDI subgroups (P > .05). Diversity and secondary BA concentrations increased in both subgroups, whereas primary BA concentrations declined following VOS dosing, leading to few differences between subgroups at Week 1.

CONCLUSIONS: These data suggest commonalities in microbiome disruption in patients with frCDI and mrCDI that contribute to recurrence and suggest that antibiotics followed by a live microbiome therapy may be an optimal treatment strategy for rCDI, regardless of number of prior CDI recurrences.}, } @article {pmid41223536, year = {2025}, author = {Toresson, L and Ludvigsson, U and Olmedal, G and Hellgren, J and Toni, M and Giaretta, PR and Suchodolski, JS and Blake, AB}, title = {Repeated fecal microbiota transplantation in dogs with chronic enteropathy can decrease disease activity and corticosteroid usage.}, journal = {Journal of the American Veterinary Medical Association}, volume = {}, number = {}, pages = {1-10}, doi = {10.2460/javma.25.08.0563}, pmid = {41223536}, issn = {1943-569X}, abstract = {OBJECTIVE: Evaluate clinical and fecal parameters in dogs with refractory chronic enteropathy (CE) treated with repeated fecal microbiota transplantation (FMT) as adjunct treatment.

METHODS: This was a prospective longitudinal observational study from September 25, 2021, to June 20, 2024. Thirty-nine dogs received 2 to 3 rectal FMTs over 1 month. Canine inflammatory bowel disease activity index (CIBDAI) and fecal samples were assessed for 6 months. Fecal samples were analyzed for dysbiosis index, bile acids, and calprotectin.

RESULTS: 28 of 39 dogs responded to FMT. Eight dogs had a short-lasting response. Before FMT, baseline CIBDAI was equivalent in responders and nonresponders. Responders had a significantly decreased CIBDAI at 1 month, which remained unaltered at 6 months in long-lasting responders (LLRs). Baseline dysbiosis index (mean [95% CI]) was significantly lower in LLRs (-0.02 [-3.3 to 2.7]) versus nonresponders and short-lasting responders combined (N/SRs; 2.9 [-0.2 to 6.0]). Baseline percentage of secondary unconjugated fecal bile acids was higher in LLRs (65 [41 to 89]) versus N/SRs (30 [6 to 54]). Dysbiosis index decreased significantly at the time point for the third FMT in LLRs (-2.4 [-3.9 to 2.2]) but not in N/SRs (3.3 [-0.4 to 5.7]). Corticosteroid tapering was achieved in 13 responders. Mild adverse events were noted in 4 dogs.

CONCLUSIONS: This repeated FMT protocol was an effective adjunct treatment in refractory CE dogs, especially in dogs with no or mild dysbiosis. Marked dysbiosis and BA dysmetabolism before and after FMT appeared associated with no clinical response or a short-lasting response to FMT, potentially requiring repeated FMT.

CLINICAL RELEVANCE: Repeated FMT could reduce disease activity and corticosteroid usage in dogs with refractory CE.}, } @article {pmid41220843, year = {2025}, author = {Kwon, K and Kim, M and Jung, Y and Yoon, MY and Lee, JY and Yoon, SS and Rho, M and Chung, YW and Ryu, JH}, title = {Intestinal Dysbiosis Caused by Epithelial Fabp6 Gene Disruption Exacerbates Gut Inflammatory Disease.}, journal = {Immune network}, volume = {25}, number = {5}, pages = {e35}, pmid = {41220843}, issn = {1598-2629}, abstract = {Ileal lipid binding protein (Ilbp), encoded by Fabp6 gene, plays a critical role in intracellular transport of bile acids (BAs) from apical to basolateral side of ileal enterocytes, maintaining BA homeostasis within enterohepatic circulation. However, pathophysiological consequences of Ilbp deficiency remain largely unexplored. Here, we demonstrate that disruption of BA balance, caused by intestinal epithelial cell (IEC)-specific Fabp6 gene knockout (Fabp6 [ΔIEC]), exacerbates dextran sulfate sodium (DSS)-induced gut inflammation. Fecal microbiota transplantation from Fabp6 [ΔIEC] mice to germ free recipient mice replicated the adverse effects observed in Fabp6 [ΔIEC] mice, which were mitigated when these mice were co-housed with control (Fabp6 [f/f]) mice. Metagenomic analysis identified Ligilactobacillus murinus as a primarily diminished strain in Fabp6 [ΔIEC] mice. Oral administration of L. murinus isolated from feces of Fabp6 [f/f] mice ameliorated DSS-induced colitis in Fabp6 [ΔIEC] mice by restoring epithelial barrier integrity and lowering pro-inflammatory cytokines IL-1β, IL-6 and TNF-α. Furthermore, daily administration of taurodeoxycholic acid-one of the BAs reduced in Fabp6 [ΔIEC] mice and that promotes the growth of L. murinus in an in vitro growth assay-also exhibited a protective effect against DSS-induced colitis through a similar mechanism. These findings suggest that deficiency of specific BAs due to epithelial Fabp6 deletion leads to gut dysbiosis, predisposing the host to inflammatory disease.}, } @article {pmid41219783, year = {2025}, author = {Sami, A and Ashraf, R and Nisar, S and Mustehsan, ZH and Javed, MA and Ozsahin, DU and Waheed, Y}, title = {A comprehensive narrative review on precision medicine approach to hypertension: exploring the role of genetics, epigenetics, microbiome, and artificial intelligence.}, journal = {Journal of health, population, and nutrition}, volume = {44}, number = {1}, pages = {394}, pmid = {41219783}, issn = {2072-1315}, abstract = {Hypertension (HTN) impacts approximately 1.28 billion individuals globally and poses a great burden of disease. The objectives of this study are to explore the role of genetics, epigenetics, microbiome, and artificial intelligence (AI) in the management of HTN. A thorough literature search was conducted across various databases including PubMed, Google Scholar, Web of Science (WoS), and Medline to retrieve articles related to the role of genetics, epigenetics, microbiome, and AI in the precision medicine of HTN. Genes-including ACE, NOS3, ADD1, CYP11B2, NPPA, and NPPB-have a profound impact on blood pressure (BP) regulation in our body and polymorphism in these key genes can lead to HTN. Up or down-regulation of genes by epigenetic factors such as miRNA-155, miRNA-210, and miRNA-122 can significantly contribute to the development of HTN. These genetic and epigenetic factors can also be used as specific targets for gene editing and gene therapy for long-term management of HTN. However, the implementation of these techniques has not been possible in clinical settings due to lack of human studies and safety concerns related to unpredictable DNA alterations, nucleotide deletions, and loss of allele-specific chromosomes. Modulation of gut microbiome through oral supplements, fecal microbiota transplant (FMT), and dietary interventions has emerged as one the most effective and safe techniques for managing HTN in human models. AI-based cutting-edge models have helped curate personalized diet plans based on an individual's unique microbiome, genomic information, and physiological conditions leading to a reduction in BMI, fat, BP, and heart rate while improving overall cardiac health and gut microbial diversity. Despite the significant advantages offered by AI-based medicine, ethical concerns-related to data privacy, bias, and discrimination-and ineffective models have led to limited integration of AI in precision medicine of HTN. The integration of genetics, epigenetics, microbiome, and AI-based models can play a key role in improving the current landscape of precision medicine of HTN. These cutting-edge techniques can lead to a shift from the current one-size-fits all approach to more personalized treatment plan however further research in human models is needed to determine the safety and true efficacy of these techniques. Additionally, new AI-models need to be developed that address ethical concerns and are effective in real-world clinical settings.}, } @article {pmid41219653, year = {2025}, author = {Lamba, JK and Tandon, C and Tandon, S}, title = {Gut Microbiota and Chronic Kidney Disease: A Complex Interplay with Implications for Diagnosis and Treatment.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {41219653}, issn = {1867-1314}, abstract = {Chronic kidney disease (CKD) progresses over the years with a steady loss of renal function, often culminating in renal failure. While diabetes and hypertension are the major drivers, the exact underlying molecular mechanism for CKD remains only partially understood. Emerging research has revealed a new paradigm, linking microbiota imbalance or dysbiosis with CKD. Dysbiosis leads to the development of uremic toxins, which aggravate kidney damage, inflammation, and metabolic disruptions that accelerate disease progression. This review explores the complex interactions between dysbiosis, uremic toxins, and the major risk factors, namely, diabetes and hypertension. Microbiome-targeted interventions, such as dietary interventions, probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), are discussed with an emphasis on their therapeutic relevance in influencing renal health. Additionally, the potential of genetic engineering, particularly CRISPR-based systems, to develop 'smart bacteria' designed to restore gut health is also examined. Future perspectives highlight the need for personalized therapies targeting the gut-kidney axis. Incorporating microbiome modulation into standard CKD treatments holds the potential to slow disease progression, enhance recovery, and improve the quality of life for patients.}, } @article {pmid41217998, year = {2025}, author = {Wei, Q and Rui, M and Wang, Y and Ng, SC and You, JHS}, title = {Cost-effectiveness analysis of fecal microbiota transplantation for patients with irritable bowel syndrome.}, journal = {Digestion}, volume = {}, number = {}, pages = {1-21}, doi = {10.1159/000549485}, pmid = {41217998}, issn = {1421-9867}, abstract = {BACKGROUND AND AIM: Studies have demonstrated clinical benefits of fecal microbiota transplantation (FMT) for treatment of irritable bowel syndrome (IBS). This study aimed to evaluate the cost-effectiveness of FMT versus standard drug treatment for patients with moderate-to-severe IBS who failed to respond to first-line therapy from the US payer's perspective.

METHODS: Two one-year Markov models were developed to examine the outcomes of FMT versus standard drug treatment in patients with constipation-predominant IBS (IBS-C) and diarrhea-predominant IBS (IBS-D). The primary model outcomes included direct medical cost and quality-adjusted life-years (QALYs) gained. Model inputs were obtained from literature and public data. Sensitivity analyses were performed to examine the robustness of model results.

RESULTS: In the base-case analysis, FMT gained higher QALYs (by 0.0159 QALYs for IBS-C and 0.0166 QALYs for IBS-D) with cost-savings (USD7,813 for IBS-C and USD8,979 for IBS-D) when compared to standard drug treatment. Key influential parameters identified by one-way sensitivity analysis were response probabilities of FMT and first-line treatment, the utility values of therapeutic response and nonresponse, and FMT cost. The probabilities of FMT to be accepted as the preferred strategy at a willingness-to-pay threshold of 50,000 USD/QALY were 99.91% and 99.89% for IBS-C and IBS-D, respectively.

CONCLUSIONS: FMT appears to be cost-effective for patients with moderate-to-severe IBS who failed to respond to first-line therapy from the US payer's perspective.}, } @article {pmid41216880, year = {2025}, author = {Gu, C and Xu, R and Yin, B and Wu, R and Wei, Y and Wang, D and Wei, W}, title = {Sex-Specific Involvement of Gut Microbiota in Behavioral and Endocrine Responses to Chronic Predator Odor in Brandt's Voles.}, journal = {Integrative zoology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1749-4877.13014}, pmid = {41216880}, issn = {1749-4877}, support = {32401290//National Natural Science Foundation of China/ ; 31770422//National Natural Science Foundation of China/ ; //the Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; }, abstract = {Predator cues have profound impacts on the behavior and physiology of prey animals. However, the mechanisms underlying stress responses induced by chronic exposure to predator cues in mammals, particularly the role of the gut microbiota, remain insufficiently understood. This study investigated how gut microbiota contributes to behavioral and physiological responses in Brandt's voles (Lasiopodomys brandtii) under chronic predator odor exposure. Adult voles were repeatedly exposed to cat feces odor (CO) for 18 days (1 h/day), followed by behavioral tests to assess anti-predator and anxiety-like behaviors, hormonal measurements to evaluate basal hypothalamic-pituitary-adrenal (HPA) axis activity, and 16S rRNA sequencing to analyze gut microbiota composition. The results showed that repeated CO exposure increased anxiety-like behaviors and basal HPA axis activity in both sexes. However, anti-predator behaviors exhibited sex-specific responses: Males were habituated to repeated CO exposure by reducing freezing and alerting behaviors, whereas females consistently displayed concealing strategies, reflecting different adaptive strategies to prolonged predator threats. While CO exposure did not alter the α-diversity of gut microbiota, it significantly affected the β-diversity in females, including a reduction in the relative abundance of Treponema and Quinella. Cecal microbiota transplantation from female CO-exposed voles to naive recipients increased anxiety-like behaviors and basal HPA levels but did not alter anti-predator behaviors in the recipients. In contrast, male recipients showed no significant behavioral or physiological changes. These findings suggest that gut microbiota is involved in regulating anxiety-like behavior and HPA axis activity in female voles but has a limited regulating role in male voles.}, } @article {pmid41214728, year = {2025}, author = {Tang, X and You, X}, title = {Progress and prospects of gut microbiota-targeted therapy for primary biliary cholangitis.}, journal = {Gut pathogens}, volume = {17}, number = {1}, pages = {86}, pmid = {41214728}, issn = {1757-4749}, abstract = {Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune disease. Current therapeutic options are limited, with some patients responding poorly to first-line treatment with ursodeoxycholic acid. However, second-line drugs are difficult to develop. There are no drugs available to treat liver dysfunction. Currently, the etiology of PBC is unknown, and the intestinal flora affects the liver through the gut‒liver axis. The hypothesis of intestinal dysbiosis has gradually been accepted and involves mechanisms such as leaky gut, abnormal bile acids metabolism, and dysregulated immune tolerance. We found that gut microbiota-targeted therapy, including antibiotics, dietary regulation, probiotic supplementation, and fecal microbiota transplantation, can effectively improve liver function, remodel the intestinal microbiota, and alleviate symptom. However, this therapy has limitations, such as large individual differences and unknown long-term efficacy and safety. Large-scale and long-term clinical studies are expected to promote the broad application of gut microbiota-targeted therapy in the clinic.}, } @article {pmid41212912, year = {2025}, author = {Zhao, C and Ming, S and Zhang, J and Huang, T and Du, Y and Liu, J and Zong, S}, title = {Alleviative Effect of Stropharia rugosoannulata Exopolysaccharide on d-Galactose-Induced Gut Inflammation and Oxidative Stress by Modulating Gut Microbiota.}, journal = {Chemistry & biodiversity}, volume = {}, number = {}, pages = {e02918}, doi = {10.1002/cbdv.202502918}, pmid = {41212912}, issn = {1612-1880}, support = {137012023//Yangzhou University/ ; BY20221437//Joint Project of Industry-University-Research of Jiangsu Province/ ; }, abstract = {The exopolysaccharide SREP-1, purified from the fermentation broth of Stropharia rugosoannulata, exhibited antiaging potential. As aging significantly alters gut structure and function, protective effect of SREP-1 was investigated using a d-galactose-induced aging mouse model. SREP-1 administration reversed D-galactose-induced body weight loss and colon damage, as evidenced by improved histopathology. SREP-1 mitigated weight loss and colon damage, enhanced the activities of antioxidants (SOD, GSH-Px, and CAT), and reduced the level of MDA. It decreased proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and elevated IL-10 in colon tissue, while boosting serum immunoglobulins (IgG and IgM). Crucially, these effects were abolished by antibiotic pretreatment, highlighting the role of gut microbiota in SREP-1 bioactivity. This role was further confirmed through fecal microbiota transplantation (FMT) and fecal supernatant transplantation (FST) experiments. Based on 16S rRNA sequencing, SREP-1 restored gut microbial diversity, increased beneficial genera (e.g., Faecalibacterium, Akkermansia, Lactobacillus, and Bacteroides), and decreased harmful bacteria (e.g., Escherichia-Shigella and Collinsella). Furthermore, short-chain fatty acids (SCFAs) levels were elevated in the SREP-1 group, which might regulate GPCRs/NF-κB/Nrf2 signaling pathways and exert biological activity. This study revealed the potential of SREP-1 to alleviate aging-related intestinal dysfunction and underscored the crucial role of gut microbiota in mediating these effects.}, } @article {pmid41211636, year = {2025}, author = {Wu, L and Zhang, Q and Tang, Z and Li, Y and Wu, T and Chen, L and Tan, C and Zhang, L and Ji, X and Zhang, S and Wu, Y and Bozec, A and Zaiss, MM and Luo, Y}, title = {Gut microbiota-derived tryptophan indole metabolites ameliorate collagen-induced arthritis in mice via aryl hydrocarbon receptor activation in T cells and intestinal epithelial cells.}, journal = {Arthritis & rheumatology (Hoboken, N.J.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/art.43430}, pmid = {41211636}, issn = {2326-5205}, abstract = {OBJECTIVE: To investigate the specific role of tryptophan metabolism, especially that of microbiome-derived metabolites, in the development of rheumatoid arthritis (RA).

METHODS: We employed metabolomics to profile metabolites in 53 high-risk for RA individuals (PreRAs), 30 established RA patients and 38 healthy individuals. Fecal microbiota transplantation (FMT) and collagen-induced arthritis (CIA) mouse models were used to investigate the impact of gut microbiome on arthritis severity, gut barrier function, and metabolic change. Treg cell differentiation and epithelial cells' barrier function were assessed by flow cytometry, immunofluoresence staining and western blotting. Co-immunoprecipitation and luciferase were applied for molecular mechanism studies.

RESULTS: Dysregulated tryptophan metabolism exists in RA and PreRA individuals, as well as in FMT mice, characterized by a shift toward the kynurenine pathway and reduced activity of serotonin and indole pathways. Indole-3-lactic acid (ILA) and indole-3-acetic acid (IAA) significantly alleviated arthritis in CIA mice by expanding Treg cells via the classical aryl hydrocarbon receptor (AhR)-aryl hydrocarbon receptor nuclear translocator (ARNT)-xenobiotic response element (XRE) signaling pathway. Moreover, ILA repaired the leaking gut by increasing Zo-1 and occludin expression in Caco-2 cells, which was blocked by AhR antagonist CH223191. Moreover, CH223191 treatment could significantly reverse the improving effects of ILA and IAA on arthritis in mice.

CONCLUSION: These findings indicate that Trp indole metabolites may play a negative regulatory role in the progression of RA by affecting Treg cell development and intestinal gut barrier function.}, } @article {pmid41208872, year = {2025}, author = {Sun, J and Chen, J and Shen, Y and Yao, X and Sun, H and Chen, B and Feng, J}, title = {Diabetes mellitus-driven pulmonary injury: multidimensional mechanisms linking metabolic dysregulation to gut-lung axis and promising therapies.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1689522}, pmid = {41208872}, issn = {1663-9812}, abstract = {Diabetes mellitus (DM), a globally prevalent metabolic disorder, poses a significant public health threat due to its systemic complications. Recent studies have increasingly recognized the lung as a target organ in diabetic pathology. However, owing to the respiratory system's complex physiology, the mechanisms underlying DM-associated lung injury remain poorly understood and require further investigation. This review systematically elucidates the multifaceted effects of DM-induced metabolic disturbances on the lung, with a focus on four key pathophysiological axes triggered by hyperglycemic homeostasis, including chronic inflammation, oxidative stress imbalance, endocrine network disruption, and intestinal dysbiosis. Building upon the "metabolism-microbiota-immune" axis framework, this study demonstrates that: persistent hyperglycemia induces pulmonary tissue damage and immune microenvironment disruption through metabolite accumulation and mitochondrial dysfunction; DM-associated intestinal dysbiosis amplifies pulmonary inflammation via the gut-lung axis, mediated by metabolic reprogramming and immune cell trafficking; and metabolic aberration-driven dysregulation of innate/adaptive immunity serves as the pivotal mediator for progressive lung injury. Building on this mechanistic framework, we discuss emerging therapeutic avenues that target metabolic reprogramming, modulation of the gut microbiota, and restoration of immune homeostasis. Promising strategies include repurposed antidiabetic drugs (e.g., SGLT-2 inhibitors, GLP-1 receptor agonists), microbiome-targeted therapies (e.g., fecal microbiota transplantation), and novel immunomodulatory agents. These therapies are offering a new shift towards multi-target treatments for diabetic pulmonary complications.}, } @article {pmid41208121, year = {2025}, author = {Calhoun, AC and Shosanya, T and Long, BK and Rehberger, JK and Sadd, BM}, title = {Host-associated beneficial gut microbiota boosts induced immunity and limits immune deployment costs in bumblebees.}, journal = {The Journal of animal ecology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1365-2656.70180}, pmid = {41208121}, issn = {1365-2656}, support = {F22AP02271//U.S. Fish and Wildlife Service/ ; R15GM12968/NH/NIH HHS/United States ; }, abstract = {Ecological immunology posits that variation in host resistance to infection may be attributed partly to the ecological and evolutionary costs of immunity. While the deployment of immune defence is necessary to combat pathogenic infection, hosts pay energetic and other costs for activation. Host-associated beneficial microbiota have been shown to affect multiple host traits, including immunity, but how interactions with these microbial communities may mitigate the costs of immune activation remains an open question. For apid bees, including eusocial bumblebees, core members of the adult gut microbiota contribute to a variety of fitness-relevant traits and provide a key ecological and evolutionary relationship contributing to ecological success. Here we test the hypothesis that the host-associated microbiota provides benefits to bumblebee immunity, including the mitigation of the costs associated with inducible immune responses. Freshly emerged germ-free adult workers were supplemented with their native microbiota via experimental faecal transplants from nestmates or kept deprived of their native microbiota inoculum. We assessed functional measures of induced immunity and assessed the costs of non-pathogenic immune activation for survival. In support of our hypothesis, we find that microbiota supplementation strengthened functional antibacterial immunity. Moreover, although we observed a cost of immune activation for survival, the cost was much greater for bees deprived of their native gut microbiota compared to those supplemented. Thus, we provide evidence that in addition to other roles, the microbiota mitigates costs of immune deployment. This demonstrates a key role for host-associated microbiota in the realization of induced immune defence, and contributes more broadly to our understanding of microbiota-immune interactions in the context of ecological immunology.}, } @article {pmid41207269, year = {2025}, author = {Xu, M and Fu, Q and Liu, J and Chen, J and Zhai, X and Wang, C and Xu, W and Li, L and Wang, K and Si, H}, title = {Shouhui Tongbian capsule promotes calcium absorption by regulating gut microbiota and protects against osteoporosis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {149}, number = {}, pages = {157520}, doi = {10.1016/j.phymed.2025.157520}, pmid = {41207269}, issn = {1618-095X}, abstract = {BACKGROUND: Postmenopausal osteoporosis (OP) is a global health problem whose occurrence is strongly associated with intestinal flora dysbiosis. Shouhui Tongbian Capsule (SH) regulates gut microbiota for constipation/obesity, but its role, ability to counter calcium's side effects, and OP-related mechanism remain unclear.

PURPOSE: This study aimed to investigate the therapeutic effect of SH on OP and elucidate its mechanism in improving bone metabolism via gut microbiota regulation.

METHODS: Ovariectomized (OVX) mice received SH and/or calcium supplements. Gut microbiota profiles were analyzed via 16S rRNA sequencing, and functional annotations were performed using the Kyoto Encyclopedia of Genes and Genomes database. Gut barrier function was assessed through histology, tight junction protein expression, and serum biomarkers. Micro-CT was used to quantify the bone microstructure. Fecal microbiota transplantation (FMT) validated the microbiota-dependent effects. Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was assessed by calcium deposition staining and western blotting.

RESULTS: SH restored gut barrier integrity, reduced systemic inflammation, and alleviated constipation. SH reshaped the gut microbiota composition, enriched Lactobacillus, Lachnospiraceae, and Akkermansia, and strengthened metabolic pathways related to mineral absorption. SH synergized with calcium supplementation to significantly enhance bone mass in OVX mice. FMT experiments recapitulated the osteoprotective effects of SH, with calcium supplementation being a necessary factor in this process. SH potentiated the osteogenic capacity of BMSCs while having no effect on osteoclast differentiation.

CONCLUSION: SH ameliorates OP via the "microbiota-mineral absorption-osteogenesis" network by alleviating calcium-induced intestinal dysbiosis and promoting bone formation. This study is the first to confirm SH's synergistic regulation of gut microbiota and calcium metabolism against OP, offering novel insights for gut-bone axis-based OP therapies and highlighting traditional Chinese medicine's innovative potential in metabolic bone diseases.}, } @article {pmid41206510, year = {2025}, author = {Fang, J and Fang, J}, title = {A Review of Recent Advances in Fecal Microbiota Transplantation for the Treatment of Hepatic Encephalopathy.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {31}, number = {}, pages = {e949286}, doi = {10.12659/MSM.949286}, pmid = {41206510}, issn = {1643-3750}, abstract = {Hepatic encephalopathy (HE) results from a debilitating complication of liver cirrhosis and acute liver failure, characterized by neuropsychiatric abnormalities ranging broadly from mild cognitive impairment to respiratory failure to coma. The pathogenesis of HE is multifactorial, with gut-derived toxins, particularly ammonia, playing a central role. Recent advances in understanding the gut-liver-brain axis have revealed the importance of gut microbiota and dysbiosis in the development and progression of HE. Fecal microbiota transplantation (FMT), a clinical procedure that is performed to transfer fecal microbiota from a healthy donor to a patient with HE (recipient), has emerged as a promising therapeutic strategy for modulating gut microbiota and ameliorating HE. FMT facilitates the restoration of gut microbiota composition with increased microbial alpha diversity, reestablishment of the balance between beneficial and pathogenic bacteria, reduction in the production of gut-derived toxins, and improvement of intestinal barrier function. It also modulates immune and inflammatory responses, alleviating hepatocyte and biliary injury. FMT has also demonstrated efficacy in improving cognitive function and reducing hospitalizations in HE patients and can maintain a stable donor-like microbiota profile for up to 12 months post-transplantation. FMT is generally well-tolerated, with most adverse events reported to be mild and transient, providing a desirable option for HE treatment. This review provides a comprehensive overview of the current understanding of the role of gut microbiota in the pathogenesis of HE, the mechanisms underlying the therapeutic effects of FMT, and the clinical evidence supporting its use in HE. We will also discuss the limitations, challenges, and future prospects for FMT in the treatment of HE.}, } @article {pmid41206275, year = {2025}, author = {Hattoufi, K and Raji, F and Tligui, H and Benlhachemi, S and Heikel, J and Aguenaou, H and Barkat, A}, title = {Association of gut microbiota and type of feeding: Molecular analysis of a cohort of preterm moroccan newborns.}, journal = {Pediatrics and neonatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pedneo.2025.04.008}, pmid = {41206275}, issn = {2212-1692}, abstract = {BACKGROUND: We assessed the newborns' intestinal microbiota during the first three weeks of life using molecular biology techniques to understand colonization patterns according to feeding type.

METHODS: We conducted a prospective, observational descriptive study at the National Reference Centre for Neonatology and Nutrition, in collaboration with the research laboratory of the Children's Hospital at the University Hospital Centre Ibn Sina in Rabat. Stool samples were collected from 29 preterm newborns upon admission to the neonatal unit and subsequently twice weekly over a three-week period. Microbial composition was analyzed using real-time polymerase chain reaction (RT-qPCR), targeting four phyla: Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria.

RESULTS: The gestational age of the included preterm infants ranged from 28 to 36 weeks of amenorrhea. Enteral nutrition was initiated between the second and sixth days after birth. None of the infants was nursed immediately after birth or during their hospitalization. However, in 79 % of cases, breast milk was collected at home for later use in feeding the newborns, and among these, 21 % received more than 50 % of the collected breast milk. Over the first two weeks of life, Lactobacillus spp. was only detected in infants nursed by both breast milk and formula milk. Enterococcus spp. was present in all breastfed infants. Clostridium difficile and Clostridium perfringens were found in 83 % of formula-fed newborns in the second week of life and in all newborns by the end of the third week.

CONCLUSION: Promoting breastfeeding whenever possible is crucial for fostering a healthy gut microbiota. When breastfeeding is not feasible, incorporating infant formulas supplemented with probiotics and/or prebiotics can help establish a microbiota similar to that of breastfed infants. Additional preventive strategies, such as vaginal or fecal microbiota transplantation, may be considered, particularly for infants born via caesarean section.}, } @article {pmid41206121, year = {2025}, author = {Dong, PY and Chen, Y and Li, L and Zhai, CL and Yan, YC and Bai, Y and Li, YY and Dong, Y and Liu, J and Zhang, M and Liu, YH and Zhang, XF}, title = {Deoxynivalenol Disrupts Male Mice Reproduction through Gut-Testis Axis Dysregulation and Metabolic Alterations.}, journal = {Toxicological sciences : an official journal of the Society of Toxicology}, volume = {}, number = {}, pages = {}, doi = {10.1093/toxsci/kfaf155}, pmid = {41206121}, issn = {1096-0929}, abstract = {The mycotoxin deoxynivalenol (DON) is a widespread contaminant that threatens male reproductive health, though the systemic mechanisms involving the gut-testis axis remain incompletely understood. We employed a multi-omics approach-integrating transcriptomics, 16S rRNA sequencing, and serum metabolomics-in a mouse model to investigate these mechanisms. Oral exposure to DON (2 mg/kg/day for two weeks) induced testicular damage and disrupted the blood-testis barrier, marked by the downregulation of Occludin and GJA1, alongside the suppression of steroidogenesis-related genes and proteins including StAR and CYP17A1. Concurrently, DON triggered gut microbiota dysbiosis, characterized by an increased abundance of Desulfovibrio and a decline in beneficial bacteria. Serum metabolomics further identified a significant depletion of key fatty acids and the cholesterol precursor 5Alpha-Cholestanol. Crucially, fecal microbiota transplantation from DON-treated mice reproduced testicular damage and suppressed steroidogenesis in recipient animals, directly establishing the causal role of gut microbiota in DON-induced reproductive toxicity. These findings collectively demonstrate that DON impairs male reproductive function by inducing gut microbiota dysbiosis and associated metabolic alterations. This work advances our understanding of the gut-testis axis in toxicology and provides mechanistic insights for mitigating mycotoxin-induced reproductive dysfunction.}, } @article {pmid41206012, year = {2025}, author = {Tan, EK and Wang, JDJ and Pettersson, S and Wang, Q and Takahashi, R and Poewe, W and Jankovic, J and Rascol, O}, title = {Faecal microbiota transplant for Parkinson's disease: promises and future directions.}, journal = {Brain : a journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/brain/awaf419}, pmid = {41206012}, issn = {1460-2156}, abstract = {There is considerable evidence linking alterations in gut microbiome composition with Parkinson's disease (PD), leading to several recent randomized controlled fecal microbiota transplantation (FMT) trials in PD patients targeting gut dysbiosis with the aim to modulate the gut-brain axis. Some FMT trials have observed motor and non-motor symptoms improvements in PD patients, possibly through microbiota linked enhanced short-chain fatty acid or other metabolite effects and reduced systemic inflammation. While the findings are exciting and can potentially open a new treatment paradigm, crital questions on donor selection, the optimal screening and selection of the donor microbiome, delivery routes and the timing and frequency of transplantation need to be addressed. We suggest that future FMT trials should incorporate blood, metabolites, urine and functional neuroimaging biological markers and control dietary, lifestyle comorbidities, medication intake and/or other potential variables, and to ensure optimal evaluation of interactions between the gut microbes and brain outcomes prospectively over a longer time frame.}, } @article {pmid41205107, year = {2025}, author = {Caron, B and Sequier, L and Dignass, A and Ghosh, S and Hart, A and Jairath, V and Kobayashi, T and Kotze, PG and Lakatos, PL and Louis, E and Magro, F and Sebastian, S and Solitano, V and Sidhu, S and Danese, S and Peyrin-Biroulet, L}, title = {Management of Patients with Ulcerative Proctitis: A Global Survey.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {41205107}, issn = {1573-2568}, abstract = {UNLABELLED: BACKGROUND AND AIM: Ulcerative proctitis affects approximately 30% of patients with ulcerative colitis. Disease control is essential to maintain quality of life and to prevent disability and disease progression. The aim of this study was to investigate current practice on isolated proctitis management across the globe.

METHODS: Physicians with experience in treating inflammatory bowel diseases (IBD) were invited to participate in an anonymous, multiple-choice survey between January and February 2025.

RESULTS: The survey included 460 physicians from 66 countries. Most participants (87.9%) assessed clinical activity of isolated proctitis within 3 months of treatment initiation, 75.9% used fecal calprotectin, and 67.1% used C-reactive protein to measure disease activity. Endoscopic assessment was performed 3 to 6 months (34.2%) or 6 to 12 months (48.4%) after treatment induction. In this survey, 49% of participants were more reluctant to begin an advanced therapy in patients with isolated proctitis compared to pancolitis or left-sided colitis. About two-thirds of participants were less likely to use biologics in combination with immunosuppressants in isolated proctitis compared to left-sided or pancolitis. Anti-TNF (tumor necrosis factor) was the preferred choice in first-line advanced therapy after failing conventional treatment (48.4%).

CONCLUSION: This study highlighted differences in management of isolated proctitis compared to left-sided colitis or pancolitis. This is likely explained by the fact that isolated proctitis patients were historically excluded from clinical trials; therefore, management relied on extrapolation of data from studies on more extensive disease.}, } @article {pmid41204332, year = {2025}, author = {Pala, B and Frank, G and Pennazzi, L and Di Renzo, L and Gualtieri, P and Tocci, G and Rubattu, S}, title = {The role of gut microbiota in hypertension-mediated organ damage (HMOD): a systematic review.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {1242}, pmid = {41204332}, issn = {1479-5876}, support = {PNRR-MAD-2022-12376295, CUP: F33C22001010006.//Seventh Generation Fund for Indigenous Peoples/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Hypertension/microbiology/complications/pathology/physiopathology ; Animals ; Dysbiosis ; }, abstract = {Hypertension (HTN), a multifactorial condition and major modifiable risk factor for cardiovascular disease, has been increasingly linked to gut microbiota (GM) alterations, encouraging investigation into its potential role in the progression of hypertension-mediated organ damage (HMOD). This systematic review aims to evaluate the role of GM in HTN pathophysiology and its contribution to HMOD, with the aim of identifying potential microbiota-related targets for personalized therapeutic strategies. The study, registered in PROSPERO and conducted according to PRISMA guidelines, involved a comprehensive search of five databases up to January 2025, selecting human and complementary animal studies investigating the relationship between GM, HTN, and HMOD. While few studies directly assessed HMOD, emerging evidence suggests a protective role of GM and its metabolites against cardiovascular, cerebral and renal injury. Heterogeneity in design, small sample sizes and a lack of standardized methodologies limited comparability therefore we did not perform a meta-analysis. In conclusion, GM dysbiosis and its metabolites are increasingly recognized as key providers to HMOD, offering encouraging targets for future preventive and therapeutic strategies. A substantial proportion of the available evidence originates from preclinical animal studies. While these findings provide valuable mechanistic insights, further longitudinal and interventional research in human populations is warranted to confirm their translational relevance.}, } @article {pmid41203044, year = {2025}, author = {Jagwani, S and Musumeci, L and Flores, L and Mackenzie, GG and Amiji, MM}, title = {Strategic modulation of the gastrointestinal microbiome to enhance pancreatic cancer immunotherapy.}, journal = {Drug discovery today}, volume = {}, number = {}, pages = {104528}, doi = {10.1016/j.drudis.2025.104528}, pmid = {41203044}, issn = {1878-5832}, abstract = {Pancreatic cancer (PC) remains one of the most lethal malignancies, characterized by aggressive progression, late detection, and limited response to current therapies. Recent research has revealed that the gastrointestinal and intratumoral microbiomes are key modulators of immune regulation, metabolism, and epigenetic pathways, influencing tumor progression and therapeutic efficacy. This review summarizes the complex microbiome-PC interplay, emphasizing microbial modulation of inflammation, immunity, and treatment resistance. We also highlight microbiome-targeted strategies, such as probiotics, prebiotics, postbiotics, and fecal microbiota transplantation, along with advanced drug-delivery platforms - including nanoparticles, engineered bacteria, and stimuli-responsive systems - for precise microbiome modulation. Integrating microbiome science with immunotherapy, nanotechnology, and epigenetic reprogramming offers promising opportunities to improve outcomes in PC.}, } @article {pmid41202150, year = {2025}, author = {Champagne-Jorgensen, K and Gommerman, JL}, title = {Two of a kind, one with MS: Gut microbes tip the balance.}, journal = {Science immunology}, volume = {10}, number = {113}, pages = {eaed4910}, doi = {10.1126/sciimmunol.aed4910}, pmid = {41202150}, issn = {2470-9468}, mesh = {*Gastrointestinal Microbiome/immunology ; Humans ; Animals ; *Multiple Sclerosis/immunology/microbiology ; Mice ; Fecal Microbiota Transplantation ; }, abstract = {An MS twin study links ileal Lachnospiraceae to spontaneous CNS autoimmunity in mice receiving a human microbiome transplant.}, } @article {pmid41201220, year = {2025}, author = {Wang, W and Li, J and Mu, L and Bai, Y and Zhu, M and Zhao, Y and Hu, S and Wang, J and Shao, P and Su, X}, title = {Vitamin K2 Alleviates Metabolic Dysfunction-Associated Steatotic Liver Disease Through Mitochondrial Dysfunction Modulation via Gut Microbiota.}, journal = {International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition}, volume = {95}, number = {5}, pages = {37275}, doi = {10.31083/IJVNR37275}, pmid = {41201220}, issn = {0300-9831}, support = {82103810//National Natural Science Foundation of China/ ; 4457475042JZ2300U0//Outstanding Young Director in Air Force Medical University/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice, Inbred C57BL ; Mice ; Diet, High-Fat/adverse effects ; Male ; *Vitamin K 2/pharmacology/administration & dosage ; Liver/pathology/drug effects/metabolism ; *Fatty Liver/drug therapy ; *Mitochondria/drug effects ; Disease Models, Animal ; *Non-alcoholic Fatty Liver Disease/drug therapy ; Dysbiosis ; }, abstract = {INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately one-third of the global population. Meanwhile, the development of MASLD is related to dysbiosis of the gut microbiota (GM). Our previous studies have shown that Vitamin K2 (VK2) has considerable potential to ameliorate mitochondrial dysfunction in mice fed a high-fat diet (HFD); however, the mechanism through which VK2 improves mitochondrial function and mitigates MASLD remains unclear.

OBJECTIVE: This study aimed to elucidate the mechanism through which VK2 modulates MASLD.

METHODS: A total of 80 C57BL/6J mice (4-5 weeks old) were fed a HFD for 16 weeks to establish the MASLD animal model. Additionally, VK2 was administered at a dose of 120 mg/kg/day for the last 8 weeks; 30 mice were fed a normal diet for the entire 24-week period. Mice were randomly divided into groups according to different experimental protocols. Hematoxylin and Eosin (H&E) staining, Oil Red O staining, and Cluster of Differentiation 11b (CD11b) immunofluorescence staining were used to detect liver histology and inflammatory cell infiltration in the mouse liver tissues. Moreover, 16S rRNA gene sequencing, antibiotic treatment, and fecal microbiota transplantation (FMT) were employed to investigate the microbiota-mediated anti-MASLD effects of VK2. Adeno-associated virus 9 (AAV9) was used to elucidate the mechanism through which VK2 regulates MASLD severity.

RESULTS: VK2 significantly reduced hepatic lipid (triacylglycerol (TG) and total cholesterol (TC)) levels, as well as serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in HFD-fed mice (p < 0.05). VK2 also significantly suppressed inflammatory responses (p < 0.05), oxidative stress (p < 0.05), and improved mitochondrial dysfunction (p < 0.05) in a GM-dependent manner. Furthermore, VK2 restored the balance in the intestinal microbiota primarily through regulating Lactobacillus spp. abundance, and markedly alleviated MASLD via a GM-dependent manner. VK2 notably upregulated the expression of SIRT3 signaling pathway proteins (p < 0.05), thereby reducing MASLD-associated mitochondrial dysfunction (p < 0.05).

CONCLUSIONS: VK2 exerts promising therapeutic effects mainly through enhancing intestinal Lactobacillus abundance and ameliorating mitochondrial dysfunction.}, } @article {pmid41199753, year = {2025}, author = {Zulfatim, HS and Afrina, V and d'Arqom, A and Sutantyo, QE and Amornsupak, K and Nualkaew, T}, title = {Anti-Inflammatory Drugs for Alcoholic Liver Disease: A Systematic Review on Survival and Adverse Events.}, journal = {International journal of hepatology}, volume = {2025}, number = {}, pages = {8535952}, pmid = {41199753}, issn = {2090-3448}, abstract = {AIM: Alcoholic liver disease (ALD) is a major global health burden, with alcoholic hepatitis (AH) and severe alcoholic hepatitis (SAH) contributing significantly to mortality. Inflammation plays a central role in disease progression, and various anti-inflammatory therapies, particularly corticosteroids, have been employed to improve survival. However, clinical outcomes across different treatments vary. This systematic review is aimed at evaluating the effectiveness of anti-inflammatory pharmacological therapies compared to corticosteroids in improving short-term survival at 1, 3, and 6 months and to assess the incidence of adverse events in patients with ALD.

METHODS: The review followed PRISMA guidelines. A comprehensive literature search was conducted in PubMed, Scopus, ScienceDirect, and Clarivate Web of Science using MeSH terms. Inclusion criteria consisted of full-text, open-access, English articles (2014-2024) that reported survival outcomes and adverse events in patients with ALD treated with corticosteroids versus alternative or adjunctive anti-inflammatory therapies. Studies lacking a corticosteroid comparator were excluded.

RESULTS: Nine randomized controlled trials (RCTs) involving patients with AH and SAH were included. The interventions compared to corticosteroids included pentoxifylline, anakinra, metadoxine, S-adenosylmethionine (SAMe), granulocyte colony-stimulating factor (G-CSF), rifaximin, and fecal microbiota transplantation (FMT) as monotherapies or combination regimens. Among anti-inflammatory therapies, combination therapy with corticosteroids and metadoxine significantly improves 3- and 6-month survival rates in patients with ALD. Similarly, corticosteroids combined with SAMe demonstrate efficacy in enhancing 1- and 6-month survival rates. Notably, the metadoxine-based combination regimen exhibited a superior safety profile, with fewer adverse events compared to other anti-inflammatory therapies evaluated in this review.

CONCLUSIONS: Even though corticosteroids remain the current standard of care for severe AH, this review suggests that certain combination therapies, particularly those involving metadoxine or SAMe, may offer some survival benefits. FMT also shows promise by potentially improving survival while maintaining a favorable safety profile. Among these, the metadoxine-based regimen has been explored as a promising therapeutic strategy in some contexts. However, these findings must be interpreted with caution. The evidence is limited by significant study heterogeneity and a lack of high-quality RCTs. These limitations underscore the critical need for well-powered, rigorous RCTs with standardized survival and safety outcomes.}, } @article {pmid41199348, year = {2025}, author = {Ghozlane, A and Thirion, F and Plaza Oñate, F and Gauthier, F and Le Chatelier, E and Annamalé, A and Almeida, M and Ehrlich, SD and Pons, N}, title = {Accurate profiling of microbial communities for shotgun metagenomic sequencing with Meteor2.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {227}, pmid = {41199348}, issn = {2049-2618}, support = {ANR-11-DPBS-0001//Metagenopolis/ ; }, mesh = {*Metagenomics/methods ; Animals ; Mice ; Humans ; *Microbiota/genetics ; *Bacteria/genetics/classification ; *Metagenome ; *Gastrointestinal Microbiome/genetics ; *Software ; Computational Biology/methods ; }, abstract = {BACKGROUND: The characterization of complex microbial communities is a critical challenge in microbiome research, as it is essential for understanding the intricate relationships between microorganisms and their environments. Metagenomic profiling has advanced into a multifaceted approach, combining taxonomic, functional, and strain-level profiling (TFSP) of microbial communities. Here, we present Meteor2, a tool that leverages compact, environment-specific microbial gene catalogues to deliver comprehensive TFSP insights from metagenomic samples.

RESULTS: Meteor2 currently supports 10 ecosystems, gathering 63,494,365 microbial genes clustered into 11,653 metagenomic species pangenomes (MSPs). These genes are extensively annotated for KEGG orthology, carbohydrate-active enzymes (CAZymes) and antibiotic-resistant genes (ARGs). In benchmark tests, Meteor2 demonstrated strong performance in TFSP, particularly excelling in detecting low-abundance species. When applied to shallow-sequenced datasets, Meteor2 improved species detection sensitivity by at least 45% for both human and mouse gut microbiota simulations compared to MetaPhlAn4 or sylph. For functional profiling, Meteor2 improved abundance estimation accuracy by at least 35% compared to HUMAnN3 (based on Bray-Curtis dissimilarity). Additionally, Meteor2 tracked more strain pairs than StrainPhlAn, capturing an additional 9.8% on the human dataset and 19.4% on the mouse dataset. Furthermore, in its fast configuration, Meteor2 emerges as one of the fastest available tools for profiling, requiring only 2.3 min for taxonomic analysis and 10 min for strain-level analysis against the human microbial gene catalogue when processing 10 M paired reads - operating within a modest 5 GB RAM footprint. We further validated Meteor2 using a published faecal microbiota transplantation (FMT) dataset, demonstrating its ability to deliver an extensive and actionable metagenomic analysis. The unified database design also simplifies the integration of TFSP outputs, making it straightforward for researchers to interpret and compare results.

CONCLUSIONS: These results highlight Meteor2 as a robust and versatile tool for advancing microbiome research and applications. As an open-source, easy-to-install, and accurate analysis platform, Meteor2 is highly accessible to researchers, facilitating the exploration of complex microbial ecosystems.}, } @article {pmid41197688, year = {2025}, author = {Mela, V and Ortiz Samur, NS and Vijaya, AK and Gálvez, VJ and García-Martín, ML and Bandera, B and Martínez-Montoro, JI and Gómez-Pérez, AM and Moreno-Indias, I and Tinahones, FJ}, title = {Ketogenic diet is less effective in ameliorating depression and anxiety in obesity than Mediterranean diet: A pilot study for exploring the GUT-brain axis.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {106167}, doi = {10.1016/j.bbi.2025.106167}, pmid = {41197688}, issn = {1090-2139}, abstract = {Obesity is associated with depressive symptoms due to biological and psychological factors. Dietary interventions, including the Ketogenic (Keto) and Mediterranean (Med) diets, impact weight loss and mental health differently. While the Keto diet promotes rapid weight loss by increasing ketone body levels, its effects on mental health, particularly in individuals with obesity, remain unclear. This exploratory pilot study explores the impact of both diets on depression and impulsiveness, focusing on the gut-brain axis. Sixty-four participants (Body Mass Index 30-45 kg/m[2], ages 18-65) were randomly assigned to follow one of the two diets for three months. Due to attrition, 37 participants (Med n = 23; Keto n = 14) completed the study. Depression and impulsivity scores were evaluated before and after the intervention. Stool samples were collected for microbiota analysis, and faecal transplants were performed in healthy mice. Brain and serum metabolites in recipient mice were analysed using High-Resolution Magic Angle Spinning (HR-MAS) and Proton Nuclear Magnetic Resonance ([1]H NMR) spectroscopy. The Med diet showed greater improvement in depression scores compared to the Keto diet, while the latter was associated with reductions in impulsivity (urgency subscale). However, faecal transplants from the Keto group induced anxiety-like behaviours in recipient mice, which correlated with significant microbiota and metabolite changes. The Keto group exhibited increased levels of taurine, alanine, and betaine in the brain, and threonine levels were correlated with behavioural changes. These findings suggest that the Med diet offers more consistent short-term benefits related to depressive symptoms, while the Keto diet modulated impulsivity. The animal model findings highlighted the role of diet-induced microbiota changes and metabolite alterations in the gut-brain axis. Long-term studies in a larger population are needed to tailor dietary interventions, essential for optimizing mental and physical health in obesity.}, } @article {pmid41196658, year = {2025}, author = {Verna, G and De Santis, S and Islam, BN and Sommella, EM and Licastro, D and Zhang, L and De Almelda Celio, F and Miller, EN and Merciai, F and Caponigro, V and Xin, W and Campiglia, P and Pizarro, TT and Chieppa, M and Cominelli, F}, title = {A missense mutation in Muc2 promotes gut microbiome- and metabolome-dependent colitis-associated tumorigenesis.}, journal = {The Journal of clinical investigation}, volume = {}, number = {}, pages = {}, doi = {10.1172/JCI196712}, pmid = {41196658}, issn = {1558-8238}, abstract = {Colitis-associated cancer (CAC) arises from a complex interplay between host and environmental factors. In this report, we investigated the role of the gut microbiome using Winnie mice, a UC-like model with a missense mutation in the Muc2 gene. Upon rederivation from a conventional (CONV) to a specific-pathogen-free (SPF) facility, Winnie mice developed severe colitis and, notably, spontaneous CAC that progressively worsened over time. In contrast, CONV Winnie showed only mild colitis but no tumorigenesis. By comparison, when rederived into germ-free (GF) conditions, SPF Winnie mice were protected from colitis and colon tumors, indicating an essential role for the gut microbiome in the development of CAC in these mice. Using shotgun metagenomics, metabolomics, and lipidomics, we identified a distinct pro-inflammatory microbial and metabolic signature that potentially drives the transition from colitis to CAC. Fecal microbiota transplantation (FMT), using either SPF Winnie or WT (Bl/6) donors into GF Winnie recipients, demonstrated that while colitis developed regardless of the donor, only FMT from SPF Winnie donors resulted in CAC. Our studies present a relevant model of CAC, providing strong evidence that the microbiome plays a key role in its pathogenesis, thereby challenging the concept of colon cancer as a strictly non-transmissible disease.}, } @article {pmid41196286, year = {2025}, author = {Ni, Z and Ye, D}, title = {The impact of gut microbiota modulation on responses to immune checkpoint inhibitors in cancer.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {}, number = {}, pages = {}, doi = {10.1556/030.2025.02719}, pmid = {41196286}, issn = {1588-2640}, abstract = {The gut microbiota has emerged as a critical determinant of antitumor immunity and a potential modulator of responses to immune checkpoint inhibitors (ICIs). Although pre-clinical and clinical studies suggest that specific bacterial taxa may influence both efficacy and immune-related adverse events (irAEs). However, the magnitude and consistency of these associations remain unclear. A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted through March 2025. Eligible studies evaluated baseline gut microbiota composition, fecal microbiota transplantation (FMT), probiotic/prebiotic interventions, or antibiotic exposure in cancer patients treated with ICIs. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for response rates and irAEs, were estimated using random-effects models. Across 38 studies involving 5,642 patients were included. Pooled analysis demonstrated that enrichment of Akkermansia muciniphila, Bifidobacterium longum and Faecalibacterium prausnitzii was significantly associated with improved OS (HR 0.62, 95% CI 0.51-0.76) and PFS (HR 0.69, 95% CI 0.55-0.83). Conversely, antibiotic exposure before or during ICI treatment was associated with worse OS (HR 1.84, 95% CI 1.45-2.34). Patients undergoing FMT from responders exhibited higher objective response rates (OR 2.91, 95% CI 1.48-5.73). Microbiota diversity indices were consistently higher in responders than in non-responders. Collectively, gut microbiota composition and its modulation significantly impact the therapeutic efficacy and toxicity profile of ICIs. These findings highlight the translational potential of microbiome-based biomarkers and interventions in optimizing immunotherapy.}, } @article {pmid41195402, year = {2025}, author = {Ruohan, Z and Ruting, W and Hongxi, W and Zhenjin, H and Jiale, L and Rongxin, Z and Feng, J and Yuanbo, S}, title = {Gut microbiota as a novel target for treating anxiety and depression: from mechanisms to multimodal interventions.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1664800}, pmid = {41195402}, issn = {1664-302X}, abstract = {The global prevalence of depression and anxiety continues to rise, with major depressive disorder and anxiety disorders estimated to affect approximately 3.1 and 4.8% of the world's population. Yet current pharmacological treatments demonstrate limited efficacy. This limitation has spurred extensive research into alternative treatment methods. Emerging evidence highlights a complex correlation between gut microbiota (GM) imbalance and mental health disorders. Disruptions in GM may trigger or exacerbate symptoms of anxiety and depression by interfering with communication pathways between the gut and brain. These pathways include neural signaling through the vagus nerve, hormone regulation via the hypothalamic-pituitary-adrenal (HPA) axis, immune responses involving pro-inflammatory cytokines, and metabolic processes related to short-chain fatty acids (SCFAs). Preclinical studies and initial clinical trials indicate promising results for therapeutic interventions targeting gut microbiota. Given that current evidence remains constrained by insufficient depth of understanding regarding underlying mechanisms, this review explores the intricate interactions among the gut microbiota, and brain, highlighting opportunities for advanced therapeutic approaches, focusing on probiotics, prebiotics, postbiotics, synbiotics, dietary modifications, fecal microbiota transplantation (FMT), fecal virome transplantation (FVT), and traditional Chinese medicine (TCM). It elucidates the role of gut microbiota in depression/anxiety and advances therapeutic approaches.}, } @article {pmid41194539, year = {2025}, author = {Rolhion, N and Sokol, H}, title = {Targeting the gut microbiome in inflammatory bowel disease: from concept to clinical reality.}, journal = {Intestinal research}, volume = {23}, number = {4}, pages = {396-404}, doi = {10.5217/ir.2025.00104}, pmid = {41194539}, issn = {1598-9100}, support = {ERC-2021-COG-101043802/ERC_/European Research Council/International ; //MSDAVENIR/ ; }, abstract = {The gut microbiota, a complex community of trillions of microorganisms inhabiting the human gastrointestinal tract, has emerged as a critical regulator of immune homeostasis and gastrointestinal health. In the context of inflammatory bowel disease (IBD), comprising primarily Crohn's disease and ulcerative colitis, disruptions to this microbial ecosystem-collectively termed dysbiosis-have been increasingly recognized as central to disease pathogenesis. Recent research has established that alterations in gut microbiota not only reflect disease states but may actively drive immune dysregulation, barrier dysfunction, and mucosal inflammation. This review synthesizes current knowledge on the role of the gut microbiota in IBD and evaluates the therapeutic landscape of microbiota-modulating strategies using selected examples. Fecal microbiota transplantation, while offering proof-of-concept validation, is hindered by standardization challenges and variable clinical outcomes. As a response, microbiome-based therapeutics have evolved toward defined live biotherapeutic products including bacterial consortia and single-strain products, postbiotics, and metabolite-centered approaches targeting specific pathways. Groundbreaking research into rationally designed synthetic microbiomes and next-generation probiotics is driving a paradigm shift in microbiota-based treatment for IBD from empirical to precision-guided interventions.}, } @article {pmid41192778, year = {2025}, author = {Tabata, K and Ikarashi, N and Yoshida, R and Shinozaki, Y and Kato, Y and Kon, R and Iwasaki, Y and Yokoyama, K and Saito, R and Sakai, H and Hosoe, T}, title = {High-fat diet exacerbates atopic dermatitis through alterations in the gut microbiome.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {110164}, doi = {10.1016/j.jnutbio.2025.110164}, pmid = {41192778}, issn = {1873-4847}, abstract = {Atopic dermatitis (AD) is a chronic, relapsing skin disorder characterized by pruritic eczema. In addition to genetic predispositions, environmental factors such as diet are thought to contribute to the exacerbation of AD. The aim of this study was to provide scientific evidence on how environmental factors, particularly a high-fat diet (HFD), influence the pathogenesis of AD. AD was induced in NC/Nga mice fed an HFD through the application of 2,4-dinitrochlorobenzene. In the AD-HFD group, the expression levels of inflammatory markers (Tnfa, Il1b, Ptgs2, and Nos2) and AD-related factors (Il4, Ccl17, and Tslp) in the skin were significantly elevated compared with those in the AD group (mice fed a normal diet). Alteration of gut microbiota was observed in the AD-HFD group, characterized by a reduction in the abundances of Bacteroides acidifaciens and Parabacteroides distasonis, bacteria involved in short-chain fatty acid (SCFA) production. Moreover, the levels of acetate, propionate, and butyrate in the cecal contents were significantly decreased in the AD-HFD group. Fecal microbiota transplantation experiments revealed that alterations in the gut microbiota were associated with the exacerbation of AD symptoms. Furthermore, the administration of acetate alleviated the increase in the expression of skin inflammation markers and AD-related factors and the overall exacerbation of AD-like symptoms induced by the HFD. HFD intake exacerbates AD-like symptoms, and this exacerbation is linked to alteration of gut microbiota and a decrease in SCFA levels. These results suggest that acetate and acetate-producing bacteria may serve as potential tools for the prevention and treatment of AD.}, } @article {pmid41192727, year = {2025}, author = {Lai, J and Yang, B and Ju, P and Sun, Y and Sun, X and Cheng, W and Chen, J}, title = {Gut microbiota from adolescents with social anxiety disorder is associated with behavioral alterations and metabolic changes in the medial prefrontal cortex.}, journal = {Journal of affective disorders}, volume = {}, number = {}, pages = {120597}, doi = {10.1016/j.jad.2025.120597}, pmid = {41192727}, issn = {1573-2517}, abstract = {BACKGROUND: Social anxiety disorder (SAD) is a prevalent and burdensome neuropsychiatric disorder characterised by pronounced and persistent fear and anxiety in social situations. While evidence links gut microbiota to neuropsychiatric disorders, its role in SAD remains poorly understood.

AIM: In this study, we aimed to investigate the potential involvement of gut microbiota in SAD pathophysiology through fecal microbiota transplantation.

METHOD: We collected demographic data and fecal samples from 40 first-episode, comorbidity-free, and drug-naive adolescent patients with SAD, along with 32 demographically matched healthy controls. Fecal samples underwent 16S rDNA amplicon sequencing and were pooled for transplantation into neonatal rats from postnatal day 1 through late adolescence. Recipient rats were evaluated with behavioral tests, microbiota detection, and non-targeted metabolomics of the medial prefrontal cortex.

RESULT: Patients with SAD displayed alterations in gut microbiota composition. Rats colonized with SAD-associated microbiota exhibited anxiety-like behaviors and reduced social novelty preference, alongside microbial profiles partially overlapping with those of patients. These behavioral changes were correlated with microbiota differences, and distinct metabolic alterations were detected in the medial prefrontal cortex of SAD-colonized rats.

CONCLUSION: Gut microbiota from adolescents with SAD is associated with behavioral and metabolic alterations in a rodent model, suggesting a potential role of the gut-brain axis in SAD. Further studies are warranted to establish causality and elucidate underlying mechanisms.}, } @article {pmid41191115, year = {2025}, author = {Habeeb, TAAM and Hussain, A and Bueno-Lledó, J and Giménez, ME and Aiolfi, A and Chiaretti, M and Kryvoruchko, IA and Manangi, MN and Elias, AA and Adam, AAM and Gadallah, MA and Ahmed, SMA and Khyrallh, A and Alsayed, MH and Awad, ETK and Ibrahim, EA and Elshafey, MH and Labib, MF and Badawy, MHM and Teama, SRA and Seleem, A and Abo Alsaad, MI and Ali, AK and Elbelkasi, H and Abou Zaid, MA and Mohamed, BA and Alwadees, A and El-Taher, AK and Mansour, MI and Yassin, MA and Arafa, AS and Lotfy, M and Atef, B and Elnemr, M and Khairy, MM and Abdelwanis, AH and Abdelaziz, AM and Mostafa, A and Hamed, AM and Wasefy, T and Heggy, IA and Nawar, AMH}, title = {COVID-19-specific risk factor for early post-appendectomy complications (EPAC) in older patients: a retrospective study.}, journal = {Techniques in coloproctology}, volume = {29}, number = {1}, pages = {188}, pmid = {41191115}, issn = {1128-045X}, mesh = {Humans ; Retrospective Studies ; *COVID-19/complications/epidemiology/diagnosis ; *Appendectomy/adverse effects ; Male ; Female ; Risk Factors ; Aged ; *Postoperative Complications/epidemiology/etiology ; Middle Aged ; Incidence ; *Appendicitis/surgery ; SARS-CoV-2 ; Age Factors ; Surgical Wound Infection/epidemiology ; Aged, 80 and over ; }, abstract = {BACKGROUND: The incidence of acute appendicitis in older patients significantly varies from that in younger adults. The coronavirus disease 2019 (COVID-19) pandemic has increased the risk of early post-appendectomy complications (EPAC). This study aimed to investigate the incidence and risk factors associated with EPAC in older patients after appendectomy and to define active COVID-19 infection during surgery as an associated risk factor for EPAC.

METHODS: We conducted a retrospective multicenter analysis of older patients aged ≥ 60 years who underwent appendectomy between April 2020 and December 2024. Logistic regression identified the risk factors associated with EPAC.

RESULTS: A total of 585 patients aged ≥ 60 years were divided into the EPAC (n = 32) and no EPAC (n = 553) groups. The incidences of EPAC was 5.5% (32/585), including superficial incisional surgical site infections (SSI) (9/32, 28.1%), deep incisional SSI (2/32, 6.3%), organ/space infection (2/32, 6.3%), intra-abdominal abscess (9/32, 28.1%), ileus (2/32, 6.3%), pneumonia (3/32, 9.4%), acute myocardial infraction (MI) (2/32, 6.3%), fecal fistula (2/32, 6.3%), and acute adhesive intestinal obstruction (1/32, 3.1%). Multivariable analysis identified that active COVID-19 infection during surgery (odds ratio (OR) = 25.9; 95% confidence interval (CI) 4.8-139.1; p < 0.001), American Society of Anesthesiologists (ASA) score ≥ II (OR = 4.5; 95% CI 1.2-17.07; p = 0.02), open approach (OR = 30.6; 95% CI 8.1-115.3; p < 0.001), and high-grade appendicitis ≥ IV (OR = 63.06; 95% CI 7.5-526.4; p < 0.001) were significant associated risk factors for EPAC.

CONCLUSIONS: The incidence of EPAC in older patients after appendectomy is 5.5%. Active COVID-19 infection during surgery is strongly associated with an increased risk of EPAC. COVID-19 should be considered in perioperative risk assessment of EPAC.

TRIAL REGISTRATION: This study was registered as a clinical trial (NCT06787573). Retrospectively registered.}, } @article {pmid41190061, year = {2025}, author = {Ma, C and Wang, J and Song, X and Wang, X and Zong, S}, title = {Molecular mechanisms and clinical applications of gut microbiota-derived bioactive compounds in metabolic dysfunction-associated fatty liver disease.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1682755}, pmid = {41190061}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome ; Animals ; Probiotics ; Dysbiosis/metabolism ; Fecal Microbiota Transplantation ; Prebiotics ; *Non-alcoholic Fatty Liver Disease/metabolism/therapy/microbiology ; Lipid Metabolism ; Bile Acids and Salts/metabolism ; }, abstract = {Metabolic (dysfunction)-associated fatty liver disease (MAFLD) has emerged as a leading cause of chronic liver disease worldwide. Its pathogenesis is closely associated with gut microbiota dysbiosis and metabolic disturbances. In recent years, numerous studies have demonstrated that bioactive compounds produced by gut microbial metabolism-such as short-chain fatty acids, secondary bile acids, tryptophan derivatives, and bacterial extracellular vesicles-play critical roles in the development and progression of MAFLD by modulating hepatic lipid metabolism, inflammatory responses, and epigenetic regulation. The characteristic expression patterns of these gut microbiota-derived bioactive compounds provide novel options for differential diagnosis of the disease. Moreover, elucidation of the underlying pathological mechanisms has paved novel avenues for MAFLD treatment. Strategies including dietary interventions, prebiotics, probiotics, and other microbiota-targeted therapies are considered potential approaches to modulate MAFLD progression. This review systematically summarizes the molecular mechanisms underlying the development of MAFLD influenced by gut microbiota-derived bioactive compounds. It also explores the feasibility of utilizing specific gut microbial metabolite profiles for MAFLD diagnosis and highlights potential therapeutic strategies targeting microbiota-host metabolic interactions, including the use of engineered bacteria to produce specific metabolites, probiotic/prebiotic interventions, and the clinical prospects of fecal microbiota transplantation.}, } @article {pmid41189901, year = {2025}, author = {Bautista, J and Maldonado-Noboa, I and Maldonado-Guerrero, D and Reinoso-Quinga, L and López-Cortés, A}, title = {Microbiome influence in gastric cancer progression and therapeutic strategies.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1681824}, pmid = {41189901}, issn = {2296-858X}, abstract = {Gastric cancer (GC) remains a major global health burden, ranking as the fifth most commonly diagnosed malignancy and the fourth leading cause of cancer-related death worldwide. While Helicobacter pylori is established as the primary microbial risk factor, emerging evidence underscores the broader oncogenic potential of gastric microbiome dysbiosis. This review synthesizes recent advances in understanding how microbial communities, both within the stomach and along the gut-stomach axis, contribute to gastric carcinogenesis. We explore how alterations in microbial diversity, virulence, and metabolic output disrupt mucosal homeostasis, drive chronic inflammation, and reshape local immune surveillance. Special attention is given to the molecular mechanisms by which H. pylori virulence factors cytotoxin-associated gene A (CagA) and VacA, vacuolating cytotoxin, induce epithelial transformation, immune evasion, and epigenetic reprogramming. We also highlight the oncogenic roles of non-H. pylori taxa such as Fusobacterium nucleatum, Streptococcus anginosus, and Lactobacillus fermentum, which synergize with host and environmental factors to sustain tumor-promoting microenvironments. Multi-omics studies reveal microbial signatures predictive of disease progression, therapeutic response, and prognosis, laying the foundation for microbiome-informed precision oncology. Furthermore, we examine how microbiota-targeted interventions, probiotics, prebiotics, dietary modulation, and fecal microbiota transplantation, can enhance chemotherapy and immunotherapy efficacy while mitigating treatment-related toxicity. Lastly, we discuss the implications of early H. pylori eradication, the impact of antibiotic resistance, and the need for global surveillance strategies.}, } @article {pmid41189008, year = {2025}, author = {Cho, HW and Byeon, HW and Park, SO and Uyangaa, E and Choi, JY and Kim, K and Eo, SK}, title = {The gut microbiota limits systemic inflammation during neurotrophic viral CNS infection by priming tonic type I interferon signaling.}, journal = {Journal of neuroinflammation}, volume = {22}, number = {1}, pages = {259}, pmid = {41189008}, issn = {1742-2094}, support = {RS-2025-00513722//National Research Foundation of Korea/ ; RS-2021-NF000550//Korea Basic Science Institute/ ; HI22C0591//Korea Health Industry Development Institute/Republic of Korea ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology/immunology/drug effects ; *Interferon Type I/metabolism/immunology ; Mice ; Mice, Inbred C57BL ; *Signal Transduction/physiology ; Fecal Microbiota Transplantation ; Inflammation/microbiology/immunology ; Male ; Encephalitis Virus, Japanese ; *Encephalitis, Japanese/immunology ; Neuroinflammatory Diseases ; }, abstract = {Neurotropic viruses, such as Japanese encephalitis virus (JEV), trigger central nervous system (CNS) inflammation primarily through disruption of the blood-brain barrier (BBB) and infiltration of peripheral immune cells. Although the gut microbiota is known to regulate diverse immunopathological processes, its contribution to CNS neuroinflammation and systemic immune responses during neurotropic viral infection remains poorly understood. Here, we show that depletion of gut microbiota by antibiotic cocktail treatment markedly increases susceptibility to CNS neuroinflammation following JEV infection. Loss of microbiota promoted viral dissemination into extraneural tissues, aggravated systemic inflammation and organ damage, and impaired tonic type I interferon (IFN-I) responses and hematopoietic differentiation during disease progression. Remarkably, fecal microbiota transplantation (FMT) restored resistance to CNS neuroinflammation, highlighting the protective role of the microbiota. Moreover, ampicillin-mediated depletion of specific gram-positive bacteria-including Bifidobacterium, Faecalibaculum, Ligilactobacillus, and Turicibacter-was associated with enhanced viral spread, systemic inflammation, and organ injury, accompanied by distinct shifts in fecal metabolites. Collectively, these findings demonstrate that gut microbiota-driven tonic IFN-I responses limit viral dissemination in extraneural tissues, thereby attenuating systemic inflammation and protecting against CNS neuroinflammation, particularly viral encephalitis.}, } @article {pmid41181931, year = {2025}, author = {Khoruts, A}, title = {The challenges and opportunities in the expanding horizons of microbiota transplant therapies.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2559032}, pmid = {41181931}, issn = {1949-0984}, } @article {pmid41188912, year = {2025}, author = {Li, X and Hou, M and Lyu, J and Min, X and Han, X and Wang, X and Liu, Z and Leng, Y}, title = {Gut microbiota-derived arginine metabolism mitigates intestinal ischemia-reperfusion injury.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {1215}, pmid = {41188912}, issn = {1479-5876}, support = {82260381//Natural Science Foundation of china/ ; }, } @article {pmid41187620, year = {2025}, author = {Tian, J and Cheng, J and Yang, H and Niu, Z and Zhao, L and Guan, L and Liu, N and Rong, S and Wang, C and Shi, D and Zheng, H and Cao, N and Li, R and Zhang, Y and Ren, C and Zhang, Z}, title = {Unveiling the gut-vascular connection: Gut microbiota regulates cardiovascular toxicity induced by combined exposure to PM2.5 and high-fat diet via butyric acid/NLRP3 pathway.}, journal = {Journal of hazardous materials}, volume = {499}, number = {}, pages = {140334}, doi = {10.1016/j.jhazmat.2025.140334}, pmid = {41187620}, issn = {1873-3336}, abstract = {Environmental particulate matter and dietary factors have been found to induce gut microbiota dysbiosis and exert an impact on cardiovascular toxicity. However, the underlying biological connections among them remain unclear. Our results indicated co-exposure to PM2.5 and high-fat diet (HFD) notably elevated blood pressure and blood lipid in mice and serum nitric oxide and endothelin-1 were abnormal. Meanwhile, vascular diameter and end-diastolic velocity (EDV) decreased, while resistance index (RI) increased. There was a synergistic effect of co-exposure on EDV and RI. Furthermore, significant damage to colon was observed. 16S rDNA sequencing of fecal microbiota indicated PM2.5 and HFD led to gut microbiota dysbiosis. Desulfovibrio was positively correlated with blood pressure, while Parabacteroides was negatively correlated. Fecal microbiota transplantation from donor mice exposed to hazardous substances successfully exacerbated cardiovascular toxicity in recipient mice. Further analysis of short chain fatty acids using metabolomics showed exposure to PM2.5 and HFD decreased serum butyric acid. Supplementation with sodium butyrate (SB) successfully alleviated the damage to cardiovascular system. Both in vivo and vitro experiments demonstrated SB supplementation significantly inhibited NLRP3 inflammasome. These findings indicate that modulating gut microbiota and its metabolite butyric acid may prevent the adverse cardiovascular effects of environmental PM2.5 exposure and HFD.}, } @article {pmid41186720, year = {2025}, author = {Aijaz, M and Ahmad, M and Ahmad, S and Afzal, M and Kothiyal, P}, title = {The gut-brain axis: role of gut microbiota in neurological disease pathogenesis and pharmacotherapeutics.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {41186720}, issn = {1432-1912}, abstract = {The gut-brain axis is a highly complex, bidirectional communication link between the gut and the central nervous system (CNS), mainly through neural, endocrine, immunological, and metabolic pathways. This review outlines the growing contribution of gut microbiota in the remediation of neurological health and also emphasizes the controlling role of gut microbiota on the synthesis of neurotransmitters. Emerging evidence indicates that dysbiosis of the gut is related to a variety of neurodegenerative and neuropsychiatric diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), autism spectrum disorders (ASD), depression, and glioblastoma. Mechanistic understandings show that gut microbes critically contribute to neuroimmune and blood-brain barrier (BBB) signaling. The peripheral association of gut microflora, networked with inflammasome activation, nuclear factor kappa B (NF-κB), and type-I IFN pathways highlights their role in CNS inflammation. Microbiota-targeted interventions with probiotics, prebiotics, synbiotics, antibiotics, dietary modifications, and fecal microbiota transplantation are examined for their therapeutic potential. These strategies appear to be promising to reinstate microbial balance, enhance neuroplastic responses, and ameliorate the disease symptoms. The review highlights personalized microbiome-based algorithms, underpinned by integrated multi-omics technologies and machine-learning-driven diagnostics. Future research should address underlying microbial mechanisms and perform large, randomized controlled trials in order to establish microbiota-based therapies for neurological disorders.}, } @article {pmid41185751, year = {2025}, author = {Huang, Y and Zhang, Z and Xue, L and Zhang, X and He, C}, title = {Advances in Nanomedicine-Mediated Modulation of the Microbiome for Cancer Therapy.}, journal = {International journal of nanomedicine}, volume = {20}, number = {}, pages = {13079-13096}, pmid = {41185751}, issn = {1178-2013}, mesh = {Humans ; *Neoplasms/therapy/microbiology/drug therapy ; *Nanomedicine/methods ; Tumor Microenvironment/drug effects ; Animals ; Probiotics/therapeutic use/administration & dosage ; Fecal Microbiota Transplantation/methods ; *Microbiota/drug effects ; Liposomes/chemistry ; Drug Delivery Systems ; Antineoplastic Agents/administration & dosage ; Gastrointestinal Microbiome/drug effects ; }, abstract = {The microbiome is closely related to the development of cancer, and it is feasible to modulate the microbiome for cancer therapy. Strategies based on the modulation of the microbiome, such as probiotic therapy and fecal microbiota transplantation (FMT), have achieved certain results in cancer therapy. However, poor targeting and low survival rate of the microbiome limited their further application in cancer therapy. Nanomaterials such as liposomes and micelles are widely used as carriers for drug delivery due to their good biocompatibility and stability. The latest evidence indicates that some nanomedicines can reverse cancer-promoting effects (such as promoting cell proliferation and accelerating tissue inflammation) by eliminating cancer-related microbiota, or increase the proportion of beneficial bacteria, which further enhance the production of beneficial metabolites, facilitate immune cell infiltration, and reshape the tumor microenvironment (TME), thereby inhibit tumor growth. Thus, it is promising to enhance the efficacy of cancer therapy by regulating microbiota through nanomedicines. This review highlights recent advances in the integration of nanomedicine and microbiota modulation for cancer treatment, aiming to provide insights into the design of innovative therapeutic strategies and broaden treatment options for cancer patients.}, } @article {pmid41184709, year = {2025}, author = {Kiecka, A and Szczepanik, M}, title = {Dietary modulation of the gut microbiome as a supportive strategy in the treatment of amyotrophic lateral sclerosis - a narrative review.}, journal = {Pharmacological reports : PR}, volume = {}, number = {}, pages = {}, pmid = {41184709}, issn = {2299-5684}, abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease leading to permanent damage to the central and peripheral motor neurons. Currently, there is no effective treatment for ALS, and therapy focuses solely on slowing the progression of the disease. Recent studies show that gut microbiota plays an important role in the development of neurodegenerative diseases. Altered gut microbiota has also been found in ALS. These changes have prompted the search for alternative forms of ALS treatment, focusing on changing the microbial composition of the gut. It has been noted that diet, probiotics, prebiotics and vitamins can all influence the course of ALS. Another interesting issue is fecal microbiota transplantation, which is already used in the treatment of certain intestinal diseases and could potentially be useful in the treatment of ALS. This review summarizes current knowledge on the impact of gut microbiota on the neurodegenerative process in ALS, with particular emphasis on the role of diet and probiotics. It also discusses potential mechanisms and highlights future research directions in this emerging field.}, } @article {pmid41183735, year = {2025}, author = {He, J and Lin, Z and Lin, X and Wang, C and Cao, M and Xia, R and Hong, W}, title = {Targeted fecal microbiota transplantation ameliorates autism-like behaviors via gut-brain axis and excitatory/inhibitory balance restoration in a propionic acid mouse model.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {106162}, doi = {10.1016/j.bbi.2025.106162}, pmid = {41183735}, issn = {1090-2139}, abstract = {Autism spectrum disorder (ASD) is characterized by social interaction deficits, repetitive behaviors, and restricted interests. Emerging evidence suggests a role for the gut microbiota in ASD pathophysiology, with fecal microbiota transplantation (FMT) emerging as a potential therapeutic strategy. This study investigated the effects of targeted FMT using processed fecal suspensions from rigorously screened healthy human donors, selected by 16S rRNA sequencing for high Lactobacillus abundance, on a propionic acid (PPA)-induced ASD mouse model. PPA-exposed mice exhibited ASD-like behaviors, including anxiety, repetitive grooming, and social interaction deficits, along with alterations in gut microbiota composition, SCFA levels, and neurotransmitter profiles. Donor selection based on 16S rRNA gene sequencing revealed that FMT from donors with high Lactobacillus abundance was more effective in improving social interaction deficits compared to donors with lower Lactobacillus levels. Targeted FMT intervention restored gut microbiota diversity and enriched beneficial taxa, such as Lactobacillus, Roseburia, and Blautia. Furthermore, targeted FMT reduced PPA levels in both feces and the prefrontal cortex (PFC), and normalized the Glu/GABA ratio in the PFC, suggesting a restoration of E/I balance. Electrophysiological recordings confirmed that FMT corrected the E/I imbalance in PFC pyramidal neurons by reducing sEPSC frequency and increasing sIPSC frequency. These findings demonstrate that FMT can ameliorate ASD-like behaviors in a PPA-induced mouse model by modulating gut microbiota and restoring E/I balance in the brain. Our study provides foundational evidence for the potential of targeted FMT as a therapeutic strategy for ASD, highlighting the importance of donor selection based on gut microbiota composition.}, } @article {pmid41181478, year = {2025}, author = {Singhal, R and Ghadvaje, G and Karra, N and Gadde, ST and Chandra, P and Voruganti, BKT and Doddareddy, NP and Iftikhar, S and Patel, T}, title = {A narrative review on fecal microbiota transplantation routes in ulcerative colitis: identifying the optimal approach across key parameters.}, journal = {Annals of medicine and surgery (2012)}, volume = {87}, number = {10}, pages = {6599-6611}, pmid = {41181478}, issn = {2049-0801}, abstract = {Fecal microbiota transplantation (FMT) has gained increasing attention as a novel therapeutic approach for treating ulcerative colitis (UC), a chronic inflammatory bowel disease that causes an imbalance in the gut microbiota. Although FMT has demonstrated the potential to induce remission in UC patients, the most effective route of administration remains an area of active investigation. This narrative review provides a comprehensive comparison of different FMT delivery methods, such as oral capsules, enemas, colonoscopy, and nasogastric or nasoenteric tubes, across a range of clinically relevant parameters, including efficacy, safety, patient satisfaction, microbiota changes, pretreatment protocols, and cost-effectiveness. Furthermore, we examined how post-FMT dietary interventions may influence microbial engraftment and improve the long-term outcomes in patients with UC. In addition to assessing these practical and clinical factors, this review highlights the importance of patient-centered considerations, such as the tolerability and convenience of each administration route. The integration of these findings can provide valuable insights into how different FMT routes affect disease outcomes and guide clinicians in optimizing the treatment for individual patients. By synthesizing current evidence on these key variables, we aimed to identify the most effective and feasible FMT approach for UC. Establishing standardized protocols for FMT administration, informed by this analysis, will be crucial for ensuring consistency in clinical practice, improving patient outcomes, and minimizing adverse events. The insights from this review will help pave the way for more targeted and individualized FMT strategies, ultimately enhancing the therapeutic landscape of UC management.}, } @article {pmid41181343, year = {2025}, author = {Jeyaraman, N and Jeyaraman, M and Dhanabal, P and Ramasubramanian, S and Ambrosio, L and Vadalà, G and Muthu, S}, title = {Implications of the gut microbiome in spinal cord injuries.}, journal = {Frontiers in surgery}, volume = {12}, number = {}, pages = {1668225}, pmid = {41181343}, issn = {2296-875X}, abstract = {Spinal cord injuries (SCIs) present complex challenges in medical treatment and rehabilitation, profoundly affecting the patient's physiological and neurological status. Emerging research on the gut microbiome has unveiled its potential role in influencing SCI outcomes and recovery. The gut microbiome undergoes significant changes following SCIs, which influence systemic inflammation and increase susceptibility to secondary complications, such as infections and chronic pain. These effects are linked to altered permeability, immune system dysregulation, and activation of the gut-brain axis, which represent promising therapeutic targets for the treatment of these conditions. Insights into the mechanisms underlying these effects were explored, highlighting the roles of microbial-derived metabolites like short-chain fatty acids, which have been shown to possess anti-inflammatory properties and support neuroprotective responses. The implications of these findings are significant, suggesting that interventions aimed at modulating the gut microbiome, such as the use of probiotics, prebiotics, and faecal microbiota transplantation, could complement existing SCI treatments and support recovery processes. This review aims to synthesise current knowledge on the interplay between the gut microbiome and SCIs, exploring how this relationship can influence immune modulation, inflammation, and neuroplasticity, thereby affecting recovery trajectories and the necessity for interdisciplinary research approaches that integrate neurology, microbiology, and nutrition to develop holistic, effective treatment strategies for SCI patients.}, } @article {pmid41180995, year = {2025}, author = {Anis, MA and Shahid, Y and Majeed, AA and Abid, S}, title = {Microbiome and gut-liver interactions: From mechanisms to therapies.}, journal = {World journal of gastroenterology}, volume = {31}, number = {40}, pages = {111409}, pmid = {41180995}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/physiology/drug effects ; *Dysbiosis/therapy/microbiology/immunology ; *Liver/microbiology/immunology/metabolism/pathology ; Probiotics/therapeutic use ; *Liver Diseases/microbiology/therapy/immunology ; Fecal Microbiota Transplantation ; Bile Acids and Salts/metabolism ; Anti-Bacterial Agents/therapeutic use ; Precision Medicine/methods ; Animals ; Host Microbial Interactions/immunology ; }, abstract = {The gut-liver axis represents a bidirectional and dynamic communication system between the gastrointestinal tract and liver, critically modulated by gut microbiota, bile acids, immune responses, and metabolic pathways. Disruption of this finely tuned axis contributes to the pathogenesis of several liver diseases, including alcohol-associated hepatitis, metabolic dysfunction-associated steatotic liver disease, cirrhosis, hepatic encephalopathy, and cholangiopathies like primary biliary cholangitis and primary sclerosing cholangitis. Dysbiosis, marked by reduced microbial diversity and dominance of pathogenic species, alters bile acid metabolism, increases gut permeability, and fuels hepatic inflammation. In cholangiopathies, the gut microbiome modulates immune dysregulation and fibrosis through complex microbial-host interactions. Emerging therapies targeting the microbiota, such as fecal microbiota transplantation, antibiotics (e.g., rifaximin, vancomycin), bile acid modulators, and probiotics, show promise in restoring microbial equilibrium, improving liver biochemistry, and reducing disease progression. Precision medicine strategies integrating genomics, metabolomics, and microbiomics offer a tailored approach for therapy and prognosis. This review highlights the central role of the gut-liver axis in liver diseases and the potential of microbiome-based interventions to shift management from symptomatic relief toward disease modification and personalized hepatology, underscoring a new frontier in liver disease therapeutics.}, } @article {pmid41179483, year = {2025}, author = {Fanous, N and Talley, NJ and Chaemsupaphan, T and Lee, E and Rayamajhee, B and Baradaran Ghavami, S and Kazemifard, N and Asadzadeh Aghdaei, H and Chuang, E and Leong, RW}, title = {Microbiota-targeted strategies in IBD: therapeutic promise of 2'-fucosyllactose and beyond.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848251386319}, pmid = {41179483}, issn = {1756-283X}, abstract = {Inflammatory bowel diseases (IBD) are chronic and recurrent conditions of the gastrointestinal tract. IBD is often challenging to manage due to the complex etiology and involvement of multiple dysregulated immune pathways. Current treatments, including biologics and immunosuppressants, are associated with significant risks and side effects, highlighting the need for safer alternatives. Human milk oligosaccharides (HMOs), a group of bioactive carbohydrates found in human breast milk, play a crucial role in shaping the infant gut microbiome, modulating microbial metabolism and immune responses, and reducing inflammation. Notably, HMOs have no nutritional value for the infant and travel undigested through the upper gastrointestinal tract, serving as selective substrates for beneficial gut bacteria and supporting intestinal epithelial health. Among these, 2'-fucosyllactose (2'-FL) is the most abundant and well-studied HMO, functioning as a trisaccharide prebiotic. Emerging evidence suggests that the benefits of HMOs extend beyond infancy, with potential therapeutic applications in modulating immune responses, promoting epithelial health, and reducing inflammation in IBD. This review summarizes current research on the role of 2'-FL in inflammation and colitis, exploring its potential role in treating IBD.}, } @article {pmid41178925, year = {2025}, author = {Pacheco-Barcia, V and Mariño-Mendez, A and Hernandez-Jimenez, E and Jimenez-Fonseca, P and Muñoz Martín, AJ and Custodio-Cabello, S and Palka-Kotlowska, M and Gonzalez-Diaz, I and Cabezon-Gutierrez, L}, title = {Gut microbiome and nutritional strategies in gastrointestinal cancers: Clinical implications and therapeutic perspectives.}, journal = {World journal of clinical oncology}, volume = {16}, number = {10}, pages = {107877}, pmid = {41178925}, issn = {2218-4333}, abstract = {Gastrointestinal malignancies, particularly pancreatobiliary and gastroesophageal cancers, are associated with poor prognosis due to their frequent late-stage diagnosis. Many of these tumors contribute to anorexia-cachexia syndrome and malnutrition, further exacerbating disease progression. Inflammation plays a crucial role in tumor proliferation, and growing evidence suggests that gut microbiome significantly influence inflammatory responses and clinical outcomes in these patients. Additionally, the gut microbiome contributes to carcinogenesis through multiple mechanisms, including DNA damage, activation of oncogenic pathways, and modulation of immune responses. The emerging field of nutritional interventions highlight the microbiome's impact on anticancer drug responses, affecting both chemotherapy and molecular-targeted treatments. Given its pivotal role, microbiome modulation through probiotics, fecal microbiome transplantation, and antibiotics represents a promising approach for cancer prevention and treatment. In this review, we explore the intricate interplay between gut microbiome, inflammation, and nutritional status in gastrointestinal cancers, emphasizing potential therapeutic strategies to improve patient outcomes.}, } @article {pmid41177416, year = {2025}, author = {Bashir, B and Gulati, M and Vishwas, S and Hussain, MS and Gupta, G and Kumar, P and Negi, P and Mittal, N and Dua, K and Singh, SK}, title = {Bridging the gap in the management of Alzheimer's disease using fecal microbiota transplantation.}, journal = {Molecular and cellular neurosciences}, volume = {}, number = {}, pages = {104052}, doi = {10.1016/j.mcn.2025.104052}, pmid = {41177416}, issn = {1095-9327}, abstract = {Alzheimer's disease (AD) is a neurodegenerative disease that greatly impairs the health status of human beings and creates significant burdens on individuals, families, and society. AD is characterized by the buildup of pathological proteins and glial cell dysregulated activity. Additional hallmark features include oxidative stress, neuroinflammation, impaired autophagy, cellular senescence, mitochondrial dysfunction, epigenetic alterations, reduced neurogenesis, increased blood-brain barrier permeability, and age-inappropriate intestinal dysbiosis. There is significant evidence that shows that microbiota in the gut affects the development and progression of AD. As a result, gut microbiota modulation has been identified as a new method of clinical management of AD, and more and more efforts have been devoted to identifying new methodologies for its prevention and treatment. This paper will discuss the role of gut microbiome in the etiopathogenesis of AD and consider the possibilities of fecal microbiota extract (FME) supplementation, commonly referred to as fecal microbiota transplantation (FMT). It is both a prophylactic and curative approach. The FMT therapy is grounded on the premise that anti-inflammatory effects, modifications of amyloid β, improved synaptic plasticity, short-chain fatty acids, and histone acetylation are the principles behind the enhancement of AD. The current review will present an overview of the linkage between FMT and AD as well. It further examines and evaluates the effects of FMT on aging-based mechanisms that support the development of AD. It also provides a broad description of the recent clinical and preclinical evidence on the application of FMT to AD.}, } @article {pmid39882797, year = {2025}, author = {Steinsbø, Ø and Aasprong, OG and Aabakken, L and Karlsen, LN and Grimstad, T}, title = {Fecal Calprotectin Correlates With Disease Extent but Remains a Reliable Marker of Mucosal Healing in Ulcerative Colitis.}, journal = {The American journal of gastroenterology}, volume = {120}, number = {11}, pages = {2623-2631}, pmid = {39882797}, issn = {1572-0241}, support = {//AbbVie, Tillotts Pharma/ ; }, mesh = {Humans ; *Leukocyte L1 Antigen Complex/analysis/metabolism ; *Colitis, Ulcerative/pathology/metabolism/diagnosis ; *Feces/chemistry ; Male ; Female ; *Intestinal Mucosa/pathology ; Middle Aged ; Biomarkers/analysis/metabolism ; Adult ; Severity of Illness Index ; Colonoscopy ; Aged ; }, abstract = {INTRODUCTION: Fecal calprotectin (FC) is a marker of mucosal inflammatory activity in ulcerative colitis (UC). FC levels may also be influenced by the extent of disease. We aimed to examine the relationships between FC, mucosal activity, and disease extent and to assess how disease extent affects the diagnostic accuracy of FC.

METHODS: We conducted a single-center observational study of patients with UC. Mucosal inflammatory activity was rated by the Mayo Endoscopic Score (MES) and Nancy Histological Index (NHI). The endoscopic and histological extents of disease were categorized by the Montreal classification and colorectal distribution of histologically active inflammation (NHI ≥ 2), respectively. FC was measured by EliA Calprotectin Enzyme fluoroimmunoassay (Phadia).

RESULTS: A total of 518 visits by 254 patients were analyzed. In endoscopically active UC (MES ≥ 2), FC levels were significantly lower in proctitis (440 [interquartile range (IQR) 175-1,350] mg/kg) as compared with left-sided colitis (840 [IQR 298-2,011] mg/kg, P = 0.048) or pancolitis (1,690 [IQR 723-2,582] mg/kg, P = 0.00005). In MES ≤1, FC levels were significantly higher in pancolitis (85 [IQR 43-350] mg/kg) as compared with proctitis (24 [IQR 15-116] mg/kg, P = 0.00032) or left-sided colitis (40 [IQR 15-160] mg/kg, P = 0.012). However, FC remained a reliable marker of mucosal healing across all disease extents, with area under the receiver-operating characteristic curve ranging from 0.878 to 0.915, and no significant differences between the extent categories (DeLong test, P ≥ 0.2919).

DISCUSSION: FC showed a significant association with disease extent yet remained a reliable surrogate marker for mucosal healing across all disease extents.}, } @article {pmid41177025, year = {2025}, author = {Singh, DP and Bijalwan, V and Poonam, J and Lal, R and Palkhade, R and Viramgami, A and Vidhani, H and Kumar, A and Bishnoi, M and Das, S}, title = {Bisphenol-A at an environmentally plausible dose caused gut microbiota-led impaired cognitive performances in adult mice.}, journal = {Journal of hazardous materials}, volume = {499}, number = {}, pages = {140254}, doi = {10.1016/j.jhazmat.2025.140254}, pmid = {41177025}, issn = {1873-3336}, abstract = {Omnipresent Bisphenol-A (BPA) exposure is linked to neurobehavioral deficits and gut dysbiosis. However, studies assessed its impact on cognitive performance at environmentally unrealistic doses. Nevertheless, the exact mechanism underlying the neurobehavioral phenotype, linking the role of gut microbiota is poorly understood. Here, we evaluated the effects of environmentally plausible dose of BPA-exposure on cognitive task performances with the functional analysis of gut metagenome to elucidate the role of microflora-gut-brain axis in behavioural regulation. Swiss albino mice were exposed to BPA for 5 weeks assessed for working and spatial navigation task performances. qRT-PCR based gene expression, histological investigation, gut permeability, molecular and biochemical markers of neuro-inflammation, leaky gut, oxido-nitrosative stress and 16 s rRNA gene based metagenomics with functional analysis were performed. BPA exposure altered the cognitive task performances (mean difference for transfer latency in elevated plus maze 20.84 ± 5.64 sec in and -13.12 ± 3.53 in Morris' water maze), changed serotonin levels (-70.95 ± 21.43) and acetylcholinesterase activity (0.0032 ± 0.0008), enhanced ileal permeability (12.36 ± 3.56) and systemic and tissue level inflammation (increased brain LPS, TNF-a, IL-1b, IL-6 and circulating TNF-a and IL-1b), coupled with reduced SCFAs levels (acetate; 32.48 ± 8.48, and butyrate; 28.16 ± 9.86). Faecal microbial transplant cohort replicated similar behavioural, biochemical and molecular patterns, suggesting the role of gut-microbiota in the phenotype determination. Functional pathways prediction suggested altered serotonin, dopamine, SCFAs metabolism and LPS biosynthesis. BPA at a much lower but environmentally relevant dose altered the cognitive performances, which has potential linkage to gut-microbiota mediated pathways.}, } @article {pmid41176272, year = {2025}, author = {Gilbert, MS and Cai, Y and Minderhoud, R and Edens, MGJ and Folkerts, G and Braber, S and Gerrits, WJJ}, title = {Effects of galacto-oligosaccharides and microbiota transfer on lung health and performance of calves.}, journal = {Journal of dairy science}, volume = {}, number = {}, pages = {}, doi = {10.3168/jds.2025-27121}, pmid = {41176272}, issn = {1525-3198}, abstract = {Bovine respiratory disease is a major multifactorial health issue in calves. Our objective was to evaluate the effects of galacto-oligosaccharide supplementation, microbiota transfer, and their interaction on lung health and performance of calves. A total of 180 male Holstein-Friesian calves at 18 ± 3.6 d of age received 1 of 4 treatments according to a 2 × 2 factorial design for 8.5 wk (period 1). Calves received galacto-oligosaccharides (GOS) via the milk replacer or not (CON) and received a microbiota transfer (MT) or not (MOCK). The MT strategy consisted of a combination of an oral rumen microbiota transfer and a fecal microbiota transfer supplied orally and rectally. The MT or MOCK procedure was applied 3 times in the first week after arrival and was repeated within a week after a group antimicrobial treatment. Clinical health was scored weekly, and BW was measured every 4 wk. Bronchoalveolar lavage fluid (BALF) and blood samples were collected biweekly from a subset of calves (n = 108). After period 1, all calves received the same control milk replacer for 4 wk (period 2), during which performance and clinical health were measured. Clinical scores increased from wk 1 to 3, and BALF IL-8 concentrations increased with time in period 1. This high infection pressure resulted in a requirement of 6 group antimicrobial treatments (supplied to all calves). Supplementation with GOS increased the ADG adjusted to equal solid feed intake (+27 g/d) in period 1 and tended to increase it (+45 g/d) in period 2. Supplementation with GOS decreased clinical scores in wk 1 and 3 (in the absence of MT) but tended to increase it in wk 6. Furthermore, GOS tended to decrease rectal temperature in period 2. Cytokine concentrations in BALF and blood were not affected by GOS, but the percentage of lymphocytes in BALF was increased by GOS, accompanied by a decrease in lymphocyte and an increase in neutrophil percentage in plasma. Microbiota transfer reduced plasma white blood cell concentration, related to a relative decrease in plasma neutrophils. Microbiota transfer reduced the percentage of BALF lymphocytes, and in wk 5, it also reduced the BALF concentration of TNFα. However, MT did not affect performance. At the start of period 2, MT even increased clinical scores in the absence of GOS, resulting in a higher individual antimicrobial treatment supply to MT calves in period 2, ultimately reducing the rectal temperature of MT calves at the end of period 2. Hardly any interactions between GOS and MT occurred, suggesting the absence of an additive relation. In conclusion, GOS improved performance and even tended to increase it after GOS supplementation ended, but this was not related to lung health. Microbiota transfer affected some inflammatory parameters, pointing toward reduced systemic and respiratory inflammation, but this was not reflected in clinical health, which even decreased in the carry-over period.}, } @article {pmid41175891, year = {2025}, author = {Minari, TP and Pisani, LP}, title = {The Role of Gut Microbiota in Chronic Noncommunicable Diseases: An Overview of the Last Decade.}, journal = {Nutrition reviews}, volume = {}, number = {}, pages = {}, doi = {10.1093/nutrit/nuaf200}, pmid = {41175891}, issn = {1753-4887}, abstract = {The gut microbiota has emerged as a key modulator of various health outcomes, including chronic noncommunicable diseases (NCDs). Obesity, diabetes, and hypertension represent important clinical challenges. Recent research suggests that gut dysbiosis may contribute to the pathophysiology of NCDs through metabolic and inflammatory pathways. This narrative review evaluates current scientific evidence on the role of gut microbiota in NCDs, examining its impact on blood pressure, glucose regulation, and weight control. It also explores interactions with medications, prebiotics, probiotics, fecal transplants, and lifestyle changes while identifying research gaps to advance understanding and inform innovative therapeutic strategies. An extensive review was conducted across multiple scientific databases, including PubMed, Web of Science, CrossRef, Google Scholar, and Scopus. Articles published between 2015 and 2025 were collected. A total of 115 relevant studies were identified and analyzed. The findings demonstrate consistent associations between gut dysbiosis and NCDs. Genera such as Akkermansia muciniphila, Faecalibacterium prausnitzii, and Fusicatenibacter were depleted in disease states, while Prevotella and Clostridium sensu stricto 1 were often enriched in obesity, diabetes, and hypertension. Microbial imbalances, including altered Bacillota/Bacteroidota ratios and reduced short-chain fatty acid production, were implicated in low-grade inflammation and metabolic disruption. Current findings suggest that fecal transplantation, prebiotics, postbiotics (bioactive compounds resulting from probiotic activity), and probiotics have limited effectiveness in improving gut microbiota, emphasizing the need for further human studies. Several drugs can positively or negatively alter the composition of the microbiota. Gut microbiota imbalances contribute meaningfully to the onset and progression of major NCDs. Although emerging therapies offer promise, clinical translation requires more robust, longitudinal studies integrating microbiome profiling, metabolic outcomes, and personalized strategies. Advancing microbiota-targeted approaches may help bridge current gaps in NCD prevention and management.}, } @article {pmid41175586, year = {2025}, author = {Shang, Z and Zhou, L and Liu, Y and Yang, X and Yao, D and Zhai, F and Liu, B and Chen, Y and Zhu, X and Liu, D and Yi, B}, title = {Tongxie Yaofang attenuates ulcerative colitis by modulating gut microbiota and IL-10RA/NF-κB-mediated macrophage polarization.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {148}, number = {}, pages = {157459}, doi = {10.1016/j.phymed.2025.157459}, pmid = {41175586}, issn = {1618-095X}, abstract = {BACKGROUND: Tongxie Yaofang (TXYF), a traditional Chinese herbal formula, has shown therapeutic potential in gastrointestinal disorders. However, its mechanism in ulcerative colitis (UC) remains unclear. This study provides new insights into immune-microbiota crosstalk as a key mechanism driving the protective effects of TXYF.

METHODS: A DSS-induced colitis mouse model was used to evaluate TXYF's efficacy. Gut microbiota was profiled by 16S rRNA sequencing, while transcriptomics and network pharmacology identified core pathways. In vivo and in vitro assays examined immune regulation and epithelial barrier function. A THP-1/Caco-2 co-culture system explored IL-10RA-dependent immune-epithelial crosstalk, and fecal microbiota transplantation (FMT) tested the functional role of microbial remodeling.

RESULTS: TXYF alleviated colitis symptoms, improved colon histology, and reduced pro-inflammatory cytokines. It reshaped gut microbiota by enriching SCFA-producing beneficial taxa and suppressing pathogenic bacteria. Transcriptomic analyses identified IL-10RA/NF-κB as a novel regulatory axis, and TXYF enhanced IL-10RA expression, inhibited NF-κB activation, and promoted M2 macrophage polarization. The co-culture model revealed IL-10RA-dependent macrophage-epithelial signaling that strengthened tight junction integrity. Importantly, FMT from TXYF-treated donors yielded these therapeutic benefits, reinforcing the evidence for microbiota-driven causality.

CONCLUSION: This study is the first to identify IL-10RA/NF-κB as a key immunoregulatory pathway of TXYF, uncover IL-10RA-dependent immune-epithelial communication, and validate gut microbiota as a functional mediator through FMT. Collectively, these findings demonstrate the innovative potential of TXYF as a multi-target herbal therapy for UC.}, } @article {pmid41175583, year = {2025}, author = {Ning, F and Luo, S and Nong, T and Lu, L and Yin, Z and Qin, Z and Huang, M and Jin, J}, title = {Total tanshinones extract alleviates chronic prostatitis/chronic pelvic pain syndrome by modifying intestinal flora and suppressing the LPS-TLR4 axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {148}, number = {}, pages = {157458}, doi = {10.1016/j.phymed.2025.157458}, pmid = {41175583}, issn = {1618-095X}, abstract = {BACKGROUND: Total tanshinones (T-Tan) extract, a class of lipophilic abietane diterpenes isolated from Salvia miltiorrhiza Bunge, exhibits anti-inflammatory effects. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male urologic disorder. Dysbiosis of gut microbiota is closely related to CP/CPPS. However, whether T-Tan extract can regulate the intestinal flora to improve CP/CPPS remains unclear.

PURPOSE: The aim of this study was to investigate the effect of T-Tan extract on CP/CPPS and elucidate the mechanisms through which T-Tan extract modulates gut microbiota to ameliorate CP/CPPS.

METHODS: The pseudo-germ-free model was established by administering antibiotics (abx) water, and the experimental autoimmune prostatitis (EAP) model was induced via subcutaneous injections of prostate protein extract emulsified with Freund's adjuvant. The 16S rDNA method was used to analyze the structure and differential species of rat intestinal flora. Chronic pelvic pain was assessed by applying von Frey filaments. Inflammatory factors were detected by ELISA, qPCR and IHC. HE staining was used to evaluate histopathology. Immune cell markers were localized using IF. The expression levels of TLR4 pathway were detected by WB, IHC and qPCR. The graphical abstract is made by Figdraw.

RESULTS: T-Tan extract and its major compound tanshinone IIA (Tan IIA) alleviated abnormal pain and reduced inflammation. Moreover, they restored intestinal flora composition, reduced LPS levels, and downregulated the TLR4 pathway. In addition, fecal microbiota transplantation (FMT) preserved the protective effects of T-Tan extract, reduced inguinal pain, attenuated inflammatory responses, and inhibited the LPS-TLR4 signaling axis. Besides, we further confirmed that the role of intestinal flora in the treatment of CP/CPPS.

CONCLUSION: T-Tan extract could alleviate CP/CPPS by modulating the intestinal flora and then inhibiting the LPS-TLR4 axis, which is helpful for developing novel, microbiota-focused therapeutic strategies to treat CP/CPPS.}, } @article {pmid41174753, year = {2025}, author = {Xing, Y and Liu, C and Zhang, C and Zhou, D and Hu, B and Jiang, Q and Chen, J and Lin, Z and Wang, T and Yan, H and Liu, A and Lu, W and Ben, X and Yang, K and Yuan, JX and Zhan, W and Wang, J}, title = {Antibiotic-driven and microbiota-targeted therapy for advanced management of pulmonary hypertension.}, journal = {Respiratory research}, volume = {26}, number = {1}, pages = {303}, pmid = {41174753}, issn = {1465-993X}, support = {82120108001//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Hypertension, Pulmonary/drug therapy/microbiology/physiopathology ; *Anti-Bacterial Agents/therapeutic use/pharmacology/administration & dosage ; Male ; Retrospective Studies ; Rats ; Humans ; Middle Aged ; Female ; *Gastrointestinal Microbiome/drug effects/physiology ; Aged ; Rats, Sprague-Dawley ; *Disease Management ; Cohort Studies ; *Microbiota/drug effects ; }, abstract = {BACKGROUND: Pulmonary hypertension (PH), particularly secondary to hypoxic lung diseases like chronic obstructive pulmonary disease (COPD), lacks effective targeted therapies. Emerging evidence suggests that microbiota imbalances contribute to PH progression, raising the possibility of microbiome-targeted interventions. This study explores the role of antibiotics in modulating microbiota and ameliorating PH.

METHODS: A retrospective cohort analysis was conducted using the Medical Information Mart for Intensive Care (MIMIC) database to assess changes in mean pulmonary artery pressure (mPAP) after antibiotic treatment. Subsequently, clinical data of 220 PH patients (including group 1, 3, and 4 PH) from single clinical center were analyzed, with 16S rRNA sequencing performed on pharyngeal and fecal samples to evaluate microbiota composition. A hypoxia-induced PH rat model was used to investigate the effects of antibiotic treatment on hemodynamics, pulmonary vascular remodeling, and gut microbiota.

RESULTS: Antibiotic use was associated with reduced mPAP in PH patients, particularly in hypoxic associated PH. Microbiota diversity decreased with antibiotic treatment, but probiotic species like Lactobacillus were enriched. In hypoxia-induced PH rats, antibiotics attenuated right ventricular systolic pressure (RVSP), reduced pulmonary vascular thickening, and preserved gut villi integrity. Lactobacillus and Anaerostipes correlated negatively with PH severity, suggesting a protective role.

CONCLUSION: Antibiotic-driven microbiota modulation may alleviate PH progression by targeting dysbiosis and reducing inflammation. These findings support further investigation into optimized antibiotic regimens as a therapeutic strategy for PH, particularly in hypoxic lung disease-associated cases.}, } @article {pmid41172243, year = {2025}, author = {Hovmand, KA and Nielsen, FD and Jochumsen, EA and Kjeldsen, J and Holm, DK and Nilsson, AC and Justesen, US and Kragsnaes, MS}, title = {Impact of storage conditions on live bacteria in partially processed faecal microbiota transplantation products using culturomics.}, journal = {Letters in applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/lambio/ovaf126}, pmid = {41172243}, issn = {1472-765X}, abstract = {Faecal microbiota transplantation (FMT) is an effective treatment for Clostridioides difficile infection, but current FMT product manufacturing protocols are time-sensitive, labour-intensive, and require specialised staff. Delays can compromise microbial viability and product quality. Efficient storage methods for partially processed FMT material could therefore improve flexibility and streamline production. Therefore, this feasibility study evaluated the impact of storage conditions on live bacteria in partially processed donations containing glycerol as a cryoprotectant. Using culturomics, we assessed the concentration and composition of live bacteria immediately after half-way processing (reference, 0 h) or after storage at 5°C (refrigerator) or -80°C (freezer) for up to 72 h. Each FMT product was initially processed from one faecal donation provided by one of four screened donors. Storage at -80°C preserved the amount and composition of live bacteria in partially processed products. In contrast, storage at 5°C led to reduced bacterial concentrations and compositional shifts, particularly affecting the abundance of Bacteroides spp. These results highlight the potential adverse effects of refrigerator storage on bacterial viability, suggesting it may not be suitable for maintaining the quality of partially processed encapsulated FMT products. Freezer storage, however, emerged as a reliable method to preserve the content of live bacteria for at least 72h.}, } @article {pmid41171386, year = {2025}, author = {Singh, S and Kriti, M and Sharma, P and Pal, N and Sarma, DK and Verma, V and Tiwari, RR and Kumar, M}, title = {From Gut to Reproductive Health: Exploring Microbiome Interactions and Future Interventions.}, journal = {Reproductive sciences (Thousand Oaks, Calif.)}, volume = {}, number = {}, pages = {}, pmid = {41171386}, issn = {1933-7205}, abstract = {Recent advances in microbiome research have illuminated the complex bidirectional interactions between gut health and reproductive well-being. Understanding the gut microbiome's influence on the reproductive system and vice versa reveals how both of them can affect hormone production, immune function, and ultimately overall reproductive health. Dysbiosis, an imbalance in the gut microbial community, has been linked with a range of reproductive issues, including decreased sperm count and motility, erectile dysfunction, polycystic ovary syndrome (PCOS), endometriosis, infertility, and adverse pregnancy outcomes. This review critically evaluates emerging therapeutic interventions aimed at restoring microbial balance and enhancing reproductive health, such as use of prebiotics, probiotics, bacteriophage therapy, and fecal microbiota transplantation (FMT). By exploring the intricate interplay between gut microbiota and reproductive health, this review also emphasizes the need for integrated approaches in research and clinical practice to develop effective microbiome-based therapies for better reproductive health outcomes.}, } @article {pmid41171006, year = {2025}, author = {Zhou, Y and Wang, B and Wang, Q and Wang, F and Mou, X and Gong, L and Li, W}, title = {Lactobacillus plantarum Lac16 alleviates dextran sodium sulfate-induced colitis in mice by suppressing NLRP3 inflammasome overactivation through microbiota-derived isobutyric acid.}, journal = {mBio}, volume = {}, number = {}, pages = {e0239225}, doi = {10.1128/mbio.02392-25}, pmid = {41171006}, issn = {2150-7511}, abstract = {UNLABELLED: Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disorder characterized by immune dysregulation. Therapeutic strategies targeting gut microbiota modulation have been proven to be effective against IBD. This study sought to explore the protective effects of Lactobacillus plantarum Lac16 against dextran sulfate sodium (DSS)-induced colitis and to elucidate its underlying mechanisms. Results illustrated that Lac16 administration significantly ameliorated colitis symptoms, as evidenced by reduced weight loss, attenuated colon shortening, and decreased disease activity index scores. Furthermore, Lac16 treatment restored intestinal barrier integrity, modulated inflammatory cytokine levels, promoted macrophage polarization toward an anti-inflammatory phenotype, and suppressed NOD-like receptor protein 3 (NLRP3) inflammasome overactivation in the colon. Lac16 treatment effectively remodeled gut microbiota composition by significantly increasing the abundance of beneficial bacteria, particularly Alloprevotella and Dubosiella, while reducing the abundance of potentially pathogenic bacteria such as Bacteroides and Helicobacter. It also elevated acetic acid and isobutyric acid levels among microbiota-derived short-chain fatty acids. The pseudo-germ-free mouse model confirmed that Lac16 inhibits NLRP3 inflammasome overactivation and ameliorates colitis symptoms by modulating the gut microbiota. Moreover, the fecal microbiota transplantation (FMT) mouse model demonstrated that these protective benefits are transferable through FMT. Subsequently, isobutyric acid was found to suppress NLRP3 inflammasome overactivation and ameliorate colitis in vivo while also attenuating inflammatory injury in vitro. Collectively, these findings illustrate that Lac16 alleviates colitis and provides gastrointestinal protection by suppressing NLRP3 inflammasome overactivation through a gut microbiota-dependent mechanism, with microbiota-derived isobutyric acid identified as the pivotal mediator in this protective process.

IMPORTANCE: This study establishes that Lactobacillus plantarum Lac16 alleviates DSS-induced colitis through gut microbiota-dependent mechanisms. Lac16 administration significantly ameliorated colitis symptoms while restoring intestinal barrier integrity, promoting anti-inflammatory macrophage polarization, and suppressing NLRP3 inflammasome overactivation. The pseudo-germ-free mouse model provided definitive evidence that Lac16's suppression of NLRP3 inflammasome overactivation requires gut microbiota. Fecal microbiota transplantation verified the causal role of microbiota in mediating Lac16's therapeutic benefits. Notably, Lac16 reshaped microbial composition, elevating beneficial genera (Alloprevotella and Dubosiella) while suppressing pathogenic genera (Bacteroides and Helicobacter). Crucially, Lac16 increased microbiota-derived short-chain fatty acids, particularly isobutyric acid. Both in vivo and in vitro experiments confirmed that isobutyric acid significantly contributes to anticolitic effects and suppresses NLRP3 activation. These findings elucidate a novel mechanism by which Lac16 ameliorates colitis via (i) microbiota-dependent NLRP3 inflammasome modulation and (ii) isobutyric acid-mediated protective effects. This work provides important insights into probiotic mechanisms and supports targeting microbial metabolic networks for IBD intervention.}, } @article {pmid41170420, year = {2025}, author = {Guo, Y and Zhang, N and Pei, D}, title = {Gut microbiota heterogeneity in non-alcoholic fatty liver disease: a narrative review of drivers, mechanisms, and clinical relevance.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1645298}, pmid = {41170420}, issn = {1664-302X}, abstract = {Non-alcoholic fatty liver disease (NAFLD), a prevalent metabolic disorder, is increasingly recognized as a complex condition influenced by gut microbiota dysbiosis. However, the heterogeneity in findings across studies has hindered the clinical translation of microbiota-based interventions. In this narrative review, we synthesize current evidence on gut microbial alterations in patients with NAFLD, with a focus on the sources of variability that contribute to inconsistent results. We included human studies (2000-2024) that compared gut microbiota profiles between NAFLD patients and healthy controls using 16S rRNA or metagenomic sequencing; key drivers of microbial changes include clinical factors (metabolic comorbidities, disease progression), biological variables (diet, genetics), and methodological biases (sequencing platform differences, diagnostic criteria variability). Emerging evidence highlights the role of non-bacterial components (fungi, viruses) in modulating bacterial communities and disrupting host metabolic pathways, exacerbating hepatic inflammation and lipid accumulation. To overcome current limitations, we propose integrating multi-omics approaches (metagenomics, metabolomics, and proteomics) with a longitudinal study design to capture dynamic microbiota-host interactions. Precision microbiota therapies, including strain-specific probiotics, engineered microbial consortia, and fecal microbiota transplantation tailored to individual dysbiosis profiles, are emerging as promising strategies for targeted interventions. Addressing these challenges is essential to identifying reliable microbial biomarkers and developing personalized strategies for NAFLD prevention and treatment. Future research should harmonize methodologies, validate causal mechanisms, and optimize microbiota-based therapies to bridge experimental findings and clinical application.}, } @article {pmid41169365, year = {2025}, author = {Fu, W and Peng, N and Geng, Y}, title = {Fecal microbiota transplantation as salvage therapy for disseminated strongyloidiasis in an immunosuppressed patient: a case report.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1676906}, pmid = {41169365}, issn = {1664-3224}, mesh = {Humans ; *Strongyloidiasis/therapy/immunology ; Male ; *Fecal Microbiota Transplantation/methods ; Aged ; *Immunocompromised Host ; Animals ; *Strongyloides stercoralis ; *Salvage Therapy/methods ; Treatment Outcome ; Diarrhea/therapy ; }, abstract = {BACKGROUND: Disseminated strongyloidiasis carries high mortality in immunosuppressed populations. We report a case of refractory Strongyloides stercoralis-induced severe diarrhea and sepsis successfully treated with fecal microbiota transplantation (FMT).

CASE PRESENTATION: A 68-year-old male with nephrotic syndrome on long-term glucocorticoids developed hyperinfection syndrome manifesting as septic shock, multiorgan dysfunction, and intractable diarrhea (>30 episodes/day). Conventional therapies including antiparasitics (albendazole), antibiotics, and probiotics failed. FMT achieved rapid symptom resolution and microbiota restoration.

CONCLUSION: This case highlights FMT's potential in modulating gut-parasite interactions and suggests its role as adjunctive therapy for parasitic hyperinfection syndromes.}, } @article {pmid41168195, year = {2025}, author = {Shan, L and Guo, X and Hu, Y and Zhou, H and Meng, X and Liu, K and Shi, L and Hu, F and Liu, Y and Zhang, T and Zhou, Y}, title = {L-citrulline protects testicular Sertoli cell function by mitigating DNA damage via the gut-testis axis of sheep fed a high-concentrate diet.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {202}, pmid = {41168195}, issn = {2055-5008}, support = {YLXKZX-ND-029//Inner Mongolia Autonomous Region Department of Education first-class scientific research project/ ; YLXKZX-ND-029//Inner Mongolia Autonomous Region Department of Education first-class scientific research project/ ; YLXKZX-ND-029//Inner Mongolia Autonomous Region Department of Education first-class scientific research project/ ; 2022JBGS0024//the Inner Mongolia Autonomous Region Open Competition Projects/ ; 2022JBGS0024//the Inner Mongolia Autonomous Region Open Competition Projects/ ; 2022JBGS0024//the Inner Mongolia Autonomous Region Open Competition Projects/ ; 2023ZD0407504//Biological Breeding-National Science and Technology Major Project/ ; 2023ZD0407504//Biological Breeding-National Science and Technology Major Project/ ; 2023YFHH0114//Inner Mongolia Autonomous Region Science and Technology Plan/ ; 32260180//the National Natural Science Foundation of China/ ; 32260181//the National Natural Science Foundation of China/ ; 2024SKYPT0068//the Science and Technology Major Project of Inner Mongolia Autonomous Region of China to the State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock/ ; }, mesh = {Male ; Animals ; *DNA Damage/drug effects ; *Sertoli Cells/drug effects/metabolism/physiology ; *Gastrointestinal Microbiome/drug effects ; *Citrulline/metabolism/pharmacology ; Sheep ; *Testis/drug effects ; Fecal Microbiota Transplantation ; Blood-Testis Barrier/drug effects ; Metabolomics ; *Diet/adverse effects ; Infertility, Male ; Dysbiosis ; }, abstract = {Mounting evidence underscores that high-concentrate diets (HCD) significantly impair male reproductive health, leading to infertility, and are closely associated with dysregulation of the gut microbiome and metabolome. However, effective therapeutic strategies targeting these alterations remain elusive. Notably, compelling evidence implicates the gut-testis axis as a critical mediator in the etiology of poor semen quality. Gut-derived metabolites, as key players in the gut-testis axis, warrant in-depth investigation as potential therapeutic targets for addressing male infertility caused by environmental factors, particularly dietary stressors. In this study, through an integrated multi-omics approach employing 10× Genomics single-cell mRNA sequencing, 16S ribosomal DNA sequencing and metabolomic profiling, we demonstrate that HCD induces DNA damage in Sertoli cells and disrupts the integrity of the blood-testis barrier (BTB), resulting in a significant decline in spermatozoa quality. Moreover, HCD impairs gut microbiota homeostasis and arginine biosynthesis, particularly leading to a remarkable decrease in L-citrulline levels. Additionally, fecal microbiota transplantation (FMT) experiments confirm that gut microbiota dysbiosis contributes to Sertoli cell DNA damage and BTB dysfunction. Interestingly, the effect of HCD-induced aberrant Sertoli cells function can be rescued by supplementation with L-citrulline. Collectively, these findings highlight the therapeutic potential of L-citrulline in protecting male reproductive health under dietary stress conditions, particularly through its action on the gut-testis axis.}, } @article {pmid41168141, year = {2025}, author = {Vollebregt, PF and Baeten, CIM and Drewes, AM and Marinello, F and Martelluci, J and Mekhael, M and Nugent, K and Rink, AD and Rosen, H and Scott, SM and Slattenschek, PE and Zerbib, F and Christensen, P and , }, title = {Transanal irrigation: Bridging the gap in treatment for chronic constipation and/or faecal incontinence-A systematic review and management guidance.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {27}, number = {11}, pages = {e70274}, doi = {10.1111/codi.70274}, pmid = {41168141}, issn = {1463-1318}, support = {//Coloplast/ ; }, mesh = {Humans ; *Constipation/therapy ; *Fecal Incontinence/therapy ; *Therapeutic Irrigation/methods/standards ; Chronic Disease/therapy ; Treatment Outcome ; Anal Canal ; Female ; Practice Guidelines as Topic ; Male ; Quality of Life ; }, abstract = {AIM: The aims of the study were to: (1) update a systematic review on the efficacy of transanal irrigation (TAI) in patients with chronic constipation (CC) and/or faecal incontinence (FI); (2) provide guidance on the position of TAI in the treatment pathway of CC and FI; and (3) discuss knowledge gaps and areas of future research.

METHOD: A collaborative of 11 experts (gastroenterologists, colorectal surgeons, and clinical scientists) from eight European countries was established. The expert group was divided into three main groups, with each group leading a specific section (systematic review, treatment pathway, and knowledge gaps). A previously published systematic review on TAI was updated by conducting an additional search on 12 April 2025. Studies on TAI in specific subgroups (neurogenic bowel dysfunction, low anterior resection syndrome) were excluded.

RESULTS: Sixteen studies involving 1567 (range 16-507) patients were included. Only one underpowered randomised trial was performed, which demonstrated that high-volume TAI may be more effective than low-volume TAI in patients with CC. Most other studies (observational) showed improvement in symptoms and/or quality of life to some extent, with a large variation in outcomes used. Treatment discontinuation was reported in 3-57% of patients. The position of TAI in the treatment pathway of CC and FI was proposed, and 13 knowledge gaps were provided.

CONCLUSION: TAI may be an effective treatment in patients with CC and/or FI. There is a need for randomised controlled trials to study its efficacy and current knowledge gaps.}, } @article {pmid41167427, year = {2025}, author = {Prossomariti, D and Merrick, B and Goldenberg, SD}, title = {Should Faecal Microbiota Transplant (FMT) donors be screened for Candidozyma auris?.}, journal = {The Journal of hospital infection}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhin.2025.10.015}, pmid = {41167427}, issn = {1532-2939}, } @article {pmid41166910, year = {2025}, author = {Mao, YQ and Song, SY and Xu, Q and Zang, TT and Wang, LS and Shen, L and Ge, JB}, title = {Dietary fiber pectin supplement attenuates atherosclerosis through promoting Akkermansia-related acetic acid metabolism.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {148}, number = {}, pages = {157373}, doi = {10.1016/j.phymed.2025.157373}, pmid = {41166910}, issn = {1618-095X}, abstract = {BACKGROUND: Atherosclerosis (AS) is a vascular disease caused by chronic inflammation, and its incidence and mortality rates are still on the rise. Recent studies have revealed that the structure and function of gut microbiota are significantly correlated with the occurrence and development of AS, providing novel insights into the mechanisms of cardiovascular diseases. Multiple studies have clarified that dietary fiber pectin alter the structure and function of the gut microbiota. At the same time, it has also been found that dietary fiber pectin can alleviate atherosclerosis.

PURPOSE: The aim is to explore whether the gut microbiota mediates the anti-atherosclerotic effects of pectin, and to elucidate the underlying molecular mechanisms.

METHODS: We established an atherosclerosis model in ApoE[-/-] mice by feeding a high-fat and high-cholesterol diet. We combined antibiotic depleted gut microbiota and transplanted the fecal microbiota to demonstrate that the effect of dietary fiber pectin in alleviating atherosclerosis depends on the gut microbiota. Subsequently, we explored the material basis of the anti-atherosclerotic effect mediated by the gut microbiota through 16 s rRNA sequencing, targeted metabolomics detection, and bacterial culture methods.

RESULTS: We conducted experiments on ApoE[-/-] mice to deplete gut microbiota with antibiotics and then perform fecal microbiota transplantation, and the results showed that supplementation with dietary fiber pectin attenuates atherosclerosis in a gut microbiome dependent manner. Through 16S rRNA sequencing, we found that supplementation of dietary fiber pectin could enrich the abundance of Akkermansia (Akk). In addition, administration with Akk was sufficient to prevent the progression of atherosclerosis in a diet-induced model. Mechanistically, Akk produced acetic acid through fermentation of pectin, and then inhibited the proliferation of Lactococcus lactis (l.lactis) in arterial plaque to exert anti-atherosclerosis effect.

CONCLUSIONS: Our results suggest that dietary fiber pectin enriches the abundance of Akk, which inhibits the proliferation of the atherosclerotic-related bacterium, l.lactis, by producing acetic acid in ApoE[-/-] mice. Our findings first reveal that pectin prevents the development of atherosclerosis through gut microbiota. Additionally, based on the theory of the "gut-vessel" axis, we demonstrate that dietary fiber pectin enriched the abundance of Akk in the gut, which elevated the level of acetic acid and further inhibit the abundance of l. within atherosclerotic plaques. These data provide new clues and strategies for the clinical treatment of atherosclerosis.}, } @article {pmid41164289, year = {2025}, author = {Mishra, P and Logan, AC and Prescott, SL}, title = {Reimagining criminal accountability: microbial and omics perspectives in the evolution of legal responsibility.}, journal = {Journal of law and the biosciences}, volume = {12}, number = {2}, pages = {lsaf022}, doi = {10.1093/jlb/lsaf022}, pmid = {41164289}, issn = {2053-9711}, abstract = {Recent advances in microbiome science and omics technologies are reshaping our understanding of human behavior, suggesting that microbial communities significantly influence cognition, impulse control, and aggression. Emerging studies in neuromicrobiology, including fecal transplant studies, are pointing toward a causal role for gut microbes and their metabolites in human cognition and behavior. This essay introduces the legalome-a framework integrating microbial perspectives, including microbiome and omics sciences, into the courts and larger criminal justice system. We argue that the legalome is on a trajectory that will move the field of neurolaw forward, and challenge traditional doctrines of mens rea and culpability. Drawing on recent court decisions related to auto-brewery syndrome, and neuro-microbiological research, we examine how subtle biological processes influence behavior in ways overlooked by current legal standards. Recent findings raise questions about criminal intent, biological determinism, and equitable access to scientific defenses. At the same time, emergent research also suggests potential for microbiome-based rehabilitative interventions. Despite methodological challenges, we advocate for interdisciplinary collaboration to harmonize biological research with legal principles, creating a more nuanced framework for justice in the twenty-first century. The legalome provides concrete implementation protocols and assessment tools that demonstrate practical utility for courts, practitioners, and policymakers.}, } @article {pmid41164228, year = {2025}, author = {Wei, S and Yin, H and Hu, X and Chi, Y and Zhang, L and Zhang, B and Qian, K and Xu, W}, title = {Detection of antimicrobial peptides from fecal samples of FMT donors using deep learning.}, journal = {Frontiers in veterinary science}, volume = {12}, number = {}, pages = {1689589}, pmid = {41164228}, issn = {2297-1769}, abstract = {INTRODUCTION: Antimicrobial peptides (AMPs) represent a class of short peptides that are widely distributed in organisms and are regarded as an effective means to tackle bacterial resistance, potentially functioning as substitutes for onventional antibiotics.

METHODS: We employed metagenomics in combination with deep learning to mine AMPs from the 120 fecal microbiota transplantation (FMT) donor metagenome. Subsequently, a comprehensive analysis of the candidate AMPs was conducted through metaproteomic cross-validation, solubility analysis, cross-validation with other prediction tools, correlation analysis, and molecular dynamics simulations. Finally, four candidate AMPs were selected for chemical synthesis, and experimental validation identified two with broad-spectrum antimicrobial activity. Furthermore, molecular docking was utilized to further analyze the antimicrobial mechanisms of the candidate AMPs.

RESULTS: Our approach successfully predicted 2,820,488 potential AMPs. After a comprehensive analysis, four candidate AMPs were selected for synthesis, two of which exhibited broad-spectrum antimicrobial activity. Molecular docking provided further insight into the binding mechanisms of these peptides.

DISCUSSION: This study demonstrates the feasibility of discovering functional AMPs from the human fecal microbiome using computational and experimental approaches, highlights the potential of mining novel AMPs from the fecal microbiome, and provides new insights into the therapeutic mechanisms of FMT.}, } @article {pmid41163775, year = {2025}, author = {Ma, J and Gao, H and Zeng, G and Huda, N and Jiang, Y and Thoudam, T and Yang, Z and Liangpunsakul, S}, title = {Alcohol-Associated Hepatitis: Translating Pathophysiology into Targeted Clinical Trials.}, journal = {Current hepatology reports}, volume = {24}, number = {1}, pages = {34}, pmid = {41163775}, issn = {2195-9595}, abstract = {PURPOSE OF REVIEW: Alcohol-associated hepatitis (AH) is a severe manifestation of alcohol-associated liver disease with high short-term mortality and limited treatment options. This review synthesizes mechanistic insights into AH pathogenesis and evaluates both failed and emerging clinical trials to guide targeted therapeutic development.

RECENT FINDINGS: AH arises from intertwined mechanisms including hepatotoxicity, oxidative stress, inflammation, impaired regeneration, and gut-liver axis disruption. Trials targeting inflammatory cytokines or apoptosis pathways have not demonstrated survival benefit and raised safety concerns. Current investigations emphasize therapies that mitigate oxidative stress, enhance hepatocyte regeneration, and restore gut-liver integrity. Novel agents such as interleukin-22 (IL-22), granulocyte colony-stimulating factor (G-CSF), probiotics, fecal microbiota transplantation (FMT), larsucosterol, and farnesoid X receptor (FXR) agonists are under evaluation.

SUMMARY: Although no effective pharmacologic therapy is yet available, advances in understanding AH biology provide a framework for mechanism-based strategies. Integrating hepatology with addiction medicine and incorporating stratified trial designs will be essential to advance effective therapies.}, } @article {pmid41163076, year = {2025}, author = {Xu, B and Qin, W and Chen, Y and Yan, Z and Tang, Y and Zhou, S and Huang, J and Ma, L and Yan, X}, title = {Gut microbiota-derived short-chain fatty acids promote follicular maturation via gWAT-ovary axis in mammals.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {220}, pmid = {41163076}, issn = {2049-2618}, support = {LQN25C170003//Zhejiang Provincial Natural Science Foundation of China/ ; 2024LFR079//Research and Development Project of Zhejiang Agricultural and Forestry University/ ; 32230099//National Natural Science Foundation of China/ ; 2021hszd018//Foundation of Hubei Hongshan Laboratory/ ; 2022YFD130015//National Key Research and Development Program of China/ ; 2662023DKPY002//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Female ; Swine ; *Fatty Acids, Volatile/metabolism ; *Ovarian Follicle/growth & development/metabolism ; Fecal Microbiota Transplantation ; Bacteria/classification/metabolism/genetics/isolation & purification ; *Ovary/metabolism ; Receptors, G-Protein-Coupled/metabolism ; }, abstract = {BACKGROUND: Previous studies have demonstrated that gut microbiota regulates reproductive performance in mammals. Our prior research identified the gut microbiota-ovary axis as an important contributor to the superior follicular development observed in Chinese indigenous Meishan sows, yet the underlying mechanisms remain unclear. This study aims to elucidate the mechanism through which gut microbiota regulates follicular development.

RESULTS: Fecal microbiota transplantation (FMT) from Meishan sows promoted follicular maturation in recipient Landrace × Yorkshire sows, evidenced by increased numbers of antral follicles, secondary follicles, and corpora lutea, accompanied by decreased atretic follicles. Additionally, FMT altered reproductive hormone profiles, significantly elevating estradiol secretion during the estrous cycle prior to sampling. Multi-omics analyses identified four key bacterial species of Fibrobacter intestinalis, Lactobacillus mucosae, Bifidobacterium thermophilum, and Ruminococcin flavefaciens, along with short-chain fatty acids (SCFAs), that are closely associated with follicular maturation. These microbial species and their shared metabolites SCFAs promoted follicular maturation and ovulation rate by inhibiting apoptosis of ovarian granulosa cells, thus reducing follicular atresia. Mechanistically, SCFAs activated G-protein-coupled receptor 43 (GPR43), which is highly expressed in peri-ovarian gonadal white adipose tissue (gWAT). This SCFAs-mediated activation of GPR43 stimulated leptin secretion from gWAT in a concentration-dependent manner, consequently suppressing granulosa cell apoptosis and promoting follicular maturation. Furthermore, in a large-scale validation trial, dietary SCFAs supplementation increased litter size by approximately 5.91%.

CONCLUSION: Collectively, gut microbiota-derived SCFAs promote follicular maturation and increase litter size in sows by stimulating leptin secretion from peri-ovarian gWAT, thus providing novel insights into enhancing reproductive outcomes in mammals. Video Abstract.}, } @article {pmid41161186, year = {2025}, author = {He, J and Lian, H and Wang, J and Wu, B and Liu, X and Zhang, Z and Yin, W and Gao, P and Wu, X and Cao, J and Li, H and Huang, X and Wang, S}, title = {Xiaoer Qixing Cha alleviates functional constipation via regulating gut microbiota and short-chain fatty acids in mice.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {148}, number = {}, pages = {157417}, doi = {10.1016/j.phymed.2025.157417}, pmid = {41161186}, issn = {1618-095X}, abstract = {BACKGROUND: Constipation is a prevalent gastrointestinal disorder associated with gut microbiota dysbiosis. Conventional pharmacological treatments, while effective for short-term symptom relief, are limited by adverse effects, high recurrence rates after discontinuation, and risks of dependency with prolonged use. Xiaoer Qixing Cha (XQC), a well-established Chinese herbal prescription, is widely utilized in pediatric care for addressing dyspepsia, diminished appetite, and constipation. However, its therapeutic mechanisms remain poorly elucidated.

PURPOSE: This study was designed to comprehensively explore the therapeutic efficacy and elucidate the mechanistic basis of XQC in murine constipation models.

STUDY DESIGN AND METHODS: The chemical composition of XQC was comprehensively characterized using high-resolution mass spectrometry. The therapeutic efficacy of XQC (200, 400, and 800 mg/kg) was investigated in loperamide-induced constipated mice. Changes in fecal microbiota were evaluated via 16S rRNA sequencing. Both untargeted and targeted metabolomic analyses were carried out to explore the metabolomic profiles of mice treated with XQC. Additionally, fecal microbiota transplantation (FMT) was performed to evaluate the functional role of gut microbiota mediated by XQC in constipation.

RESULTS: High-resolution mass spectrometry identified 141 distinct compounds in XQC. Oral administration of XQC significantly alleviated loperamide-induced constipation in mice, as evidenced by improved fecal output, increased fecal water content, enhanced intestinal motility, accelerated whole-gut transit, and modulated inflammatory cytokine levels and mucin 2 expression. Furthermore, XQC selectively restored the gut microbiota, reversing loperamide-induced microbial dysbiosis and enriching beneficial bacterial taxa, including norank_f__Muribaculaceae and Bacteroides. FMT experiments confirmed that the therapeutic effects of XQC were at least partially mediated by gut microbiota. Notably, XQC restored short-chain fatty acid (SCFA) levels, particularly butyrate and isobutyrate. Exogenous butyrate supplementation further alleviated constipation symptoms in mice, supporting its role in XQC's mechanism of action.

CONCLUSION: These findings underscore XQC's dual therapeutic role in mitigating constipation and restoring gut microbial balance, positioning it as a viable alternative to conventional therapies. Furthermore, this study establishes a theoretical foundation and clinical framework for the evidence-based application of XQC in constipation management, advancing its rational integration into pediatric and gastroenterological practice.}, } @article {pmid41160345, year = {2025}, author = {Beswick, G and Major, N and Hendrickson, C and Kumar, V and Waller, M and Durrani, Z and Hotchkiss, S and Bala, A and Taylor, VH}, title = {A Scoping Review on the Role of the Microbiome as a Factor in the Bidirectional Association Between Obesity and Depression.}, journal = {Current diabetes reports}, volume = {25}, number = {1}, pages = {56}, pmid = {41160345}, issn = {1539-0829}, mesh = {Humans ; *Obesity/microbiology/complications ; *Gastrointestinal Microbiome/physiology ; *Depression/microbiology ; Inflammation/microbiology ; }, abstract = {PURPOSE OF REVIEW: Obesity is a chronic illness highly comorbid with mental health conditions, particularly depression. Among the factors involved in this association, inflammation is a consistently identified link. This review explores the emerging role of the gut microbiota as a modulator of inflammation and its potential involvement in the pathophysiological processes linking obesity and depression.

RECENT FINDINGS: Chronic low-grade inflammation is observed in both obesity and depressive disorders. Alterations in gut microbiota are increasingly implicated in inflammatory mechanisms, including increased intestinal permeability, immune activation, and short-chain fatty acid (SCFA) production, influencing leukocyte function and cytokine production. Additionally, both obesity and depression are associated with altered microbial composition. The gut microbiome contributes to chronic inflammation relevant to the pathophysiology of both obesity and depression. Accumulating evidence highlights the need for further research into how gut microbiota influences inflammatory mechanisms observed in both obesity and depression.}, } @article {pmid41160105, year = {2025}, author = {Singh, LS and Singha, LS and Singh, WS and Singh, YR and Marak, GK}, title = {Microbiome modulation as a therapeutic strategy for alcohol-induced gut dysbiosis and associated disorders.}, journal = {Antonie van Leeuwenhoek}, volume = {118}, number = {12}, pages = {182}, pmid = {41160105}, issn = {1572-9699}, mesh = {*Dysbiosis/therapy/microbiology/chemically induced ; Humans ; *Gastrointestinal Microbiome/drug effects ; Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; *Ethanol/adverse effects ; *Alcoholism/microbiology/therapy ; }, abstract = {Chronic alcohol consumption alters the composition of the gut microbiota, leading to dysbiosis, increased intestinal permeability, and systemic inflammation, which collectively contribute significantly to the pathogenesis of alcohol-related disorders, encompassing hepatic disease, metabolic abnormalities, immune dysfunction, and neuropsychiatric conditions. The complex interactions of alcohol with the gut ecosystem illuminate the fundamental mechanisms that result in the disruption of the gut-liver axis, the imbalance of microbial metabolites, and the emergence of leaky gut syndrome. The bidirectional gut-brain axis is similarly impaired, intensifying concerns related to addiction and cognitive deficits. Therapeutic strategies, encompassing probiotics, prebiotics, synbiotics, postbiotics, dietary alterations, and fecal microbiota transplantation, offer promising modalities for reinstating microbial balance and alleviating alcohol-induced damage. Cutting-edge treatments such as paraprobiotics and bacteriophage therapy further highlight the potential of microbiome modulation as a viable therapeutic strategy. This review underscores the urgent need for precision-targeted, microbiota-based interventions and calls for expanded clinical research to translate these insights into effective treatments for alcohol-associated disorders.}, } @article {pmid41157257, year = {2025}, author = {Eghdami, S and Saeidi, M and Gunturu, S and Boroon, M and Shalbafan, M}, title = {Gut Microbiota and Obsessive-Compulsive Disorder: A Systematic Review of Mechanistic Links, Evidence from Human and Preclinical Studies, and Therapeutic Prospects.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {10}, pages = {}, doi = {10.3390/life15101585}, pmid = {41157257}, issn = {2075-1729}, abstract = {Obsessive-compulsive disorder (OCD) is a multifactorial condition, and interest in gut-brain interactions is increasing. We conducted a systematic two-step review, registered in PROSPERO (CRD420251083936). Step 1 mapped core OCD biology to gut-relevant pathways, including neuroimmune activation, epithelial barrier function, microbial metabolites, and stress circuitry, to clarify plausible mechanisms. Step 2 synthesized evidence from human and preclinical studies that measured or manipulated microbiota. Searches across PubMed, EMBASE, Web of Science, PsycINFO, and Cochrane (September 2025) yielded 357 biological and 20 microbiota-focused studies. Risk of bias was assessed using the Joanna Briggs Institute checklist for human studies and SYRCLE's tool for animal studies. Although taxonomic findings in human cohorts were heterogeneous, functional patterns converged: reduced short-chain fatty acid capacity, enrichment of pro-inflammatory pathways, and host markers of barrier disruption and inflammation correlating with OCD severity. Transferring patient microbiota to mice induced OCD-like behaviors with neuroinflammatory changes, partly rescued by metabolites or barrier-supporting strains. Mendelian randomization suggested possible causal contributions at higher taxonomic levels. Diet, especially fiber intake, and psychotropic exposure were major sources of heterogeneity. Evidence supports the microbiota as a modifiable co-factor in a subset of OCD, motivating diet-controlled, stratified clinical trials with composite host-microbe endpoints.}, } @article {pmid41156796, year = {2025}, author = {Chukhlovin, AB and Goloshchapov, OV and Shchukina, OB and Kharitidis, AM and Zhloba, AA and Subbotina, TF and Kusakin, AV and Kosarev, OV and Tsai, VV and Kalinin, RS and Eismont, YA and Glotov, OS}, title = {Changes in Gut Phageome and Bacteriome Following Fecal Microbiota Transfer in Patients with Intestinal Graft-Versus-Host Disease and Crohn's Disease.}, journal = {Microorganisms}, volume = {13}, number = {10}, pages = {}, doi = {10.3390/microorganisms13102337}, pmid = {41156796}, issn = {2076-2607}, abstract = {Intestinal bacterial dysbiosis develops in a number of immune-mediated disorders. Fecal microbiota transfer (FMT) is considered a potentially efficient tool for restoration of the patient's gut microbiota. The aim of our study was to trace the time course of dominant bacterial populations and some Enterobacteria phages in patients with GVHD and Crohn's disease after FMT procedure. Patients and methods: We observed 12 patients with intestinal graft-versus-host disease (GVHD), and 15 persons with Crohn's disease after massive anti-infectious treatment. FMT was performed by a standard protocol using oral capsules administered for 2 days. Fecal bacteriome was assessed by 16S rRNA sequencing. Viral sequences were identified by NGS with a customized primer set. Plasma citrulline levels were measured in order to assess enterocyte damage in the patients. Results: Complete clinical response to FMT was observed in 5 of 12 GVHD patients and 10 of 15 Crohn's disease cases. Before FMT, most anaerobic Bacillota were exhausted in both Crohn's disease patients and GVHD. Following FMT, Akkermansia ratios tended to decrease within 30 days in Crohn's disease, along with higher Faecalibacteria, Romboutsia, and Dialister ratios than in GVHD, thus suggesting lesser damage to anaerobic microbiota in Crohn's disease. Increased contents of facultative anaerobes (Enterococcus and E. coli) was detected in GVHD patients after FMT. Fecal virome changes in Crohn's disease after FMT included early transient decrease in Caudoviricetes with a rise in Lederbergvirus and Eganvirus ratios at later terms. In GVHD patients, reverse correlations were revealed between E. coli and E. coli-hosted Eganvirus species. Intestinal damage assessed by low plasma citrulline levels was associated with fecal Klebsiella expansion, being more pronounced in GVHD than in Crohn's disease. Clinical response to FMT in GVHD patients correlated with increased plasma citrulline and lower Eganvirus abundance. Future studies will concern specific relations between fecal bacteriome and virome reconstitution following FMT in gut GVHD and other immune-mediated intestinal disorders.}, } @article {pmid41156706, year = {2025}, author = {Borrego-Ruiz, A and Borrego, JJ}, title = {The Gut Microbiome in Enteric Viral Infections: Underlying Mechanisms and Therapeutic Approaches.}, journal = {Microorganisms}, volume = {13}, number = {10}, pages = {}, doi = {10.3390/microorganisms13102247}, pmid = {41156706}, issn = {2076-2607}, abstract = {Despite growing recognition of the role of the gut microbiome in host health and in modulating pathogen activity, the dynamic and reciprocal relationship between enteric viruses and the gut microbial ecosystem remains insufficiently defined and requires further exploration. This comprehensive review examines the bidirectional interplay between the gut microbiome and enteric viral infections by addressing (i) viruses associated with gastrointestinal alterations, (ii) how enteric viral infections alter the composition and function of the gut microbiome, (iii) how the gut microbiome modulates viral infectivity and host susceptibility, and (iv) current microbial-based approaches for preventing or treating enteric viral infections. Gastrointestinal viral infections induce gut microbiome dysbiosis, marked by reductions in beneficial bacteria and increases in potentially pathogenic populations. Specific gut microorganisms can modulate host susceptibility, with certain bacterial genera increasing or decreasing infection risk and disease severity. Pattern recognition receptors in the intestinal epithelium detect microbial signals and trigger antimicrobial peptides, mucus, and interferon responses to control viral replication while maintaining tolerance to commensal bacteria. The gut microbiome can indirectly facilitate viral infections by creating a tolerogenic environment, suppressing antiviral antibody responses, and modulating interferon signaling, or directly enhance viral replication by stabilizing virions, promoting host cell attachment, and facilitating coinfection and viral recombination. In turn, commensal gut bacteria can inhibit viral entry, enhance host antiviral responses, and strengthen mucosal barrier function, contributing to protection against gastrointestinal viral infections. Probiotics and fecal microbiota transplantation constitute potential microbial-based therapeutics that support antiviral defenses, preserve epithelial integrity, and restore microbial balance. In conclusion, the role of the gut microbiome in modulating enteric viral infections represents a promising area of future investigation. Therefore, integrating microbiome insights with virology and immunology could enable predictive and personalized strategies for prevention and treatment.}, } @article {pmid41156627, year = {2025}, author = {Rodak, K and Mnichowska-Polanowska, M and Waloryszak, A and Ptaszyński, K and Wójcik, J and Wojtyś, ME}, title = {An Unusual Case of Anterior Mediastinal Cystic Echinococcosis Successfully Resolved with Multidisciplinary Approach.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {10}, pages = {}, doi = {10.3390/pathogens14101016}, pmid = {41156627}, issn = {2076-0817}, mesh = {Humans ; *Echinococcosis/diagnosis/parasitology/pathology/drug therapy ; Animals ; Male ; *Mediastinum/parasitology/pathology/diagnostic imaging ; Echinococcus granulosus/isolation & purification ; Echinococcus multilocularis/isolation & purification ; }, abstract = {Human echinococcosis is a zoonotic disease caused by accidental ingestion of tapeworm eggs of the genus Echinococcus, shed in the feces of animal definitive host. In the human duodenum, these eggs release oncospheres, which penetrate the intestinal wall and via the bloodstream reach the liver-the most common site for development of cysts. However, it is important to remember that any other organ can be affected via the bloodstream, due to larvae size. In Europe, the most diagnostically relevant species are Echinococcus granulosus, with a median incidence of 0.6 cases per 100,000 inhabitants, and Echinococcus multilocularis, with 0.1 cases per 100,000 inhabitants. This article aims to describe an exceptionally unusual location of human cystic echinococcosis in the anterior mediastinum. We describe the role of multidisciplinary diagnostics in establishing the definitive diagnosis. The pathomorphological examination, radiological imaging and serological testing for diagnosing cystic echinococcosis are hereby described. It is particularly important to avoid reporting unspecified Echinococcus (NOS) if possible, as the management and treatment of patients with echinococcosis varies depending on the species.}, } @article {pmid41156565, year = {2025}, author = {Komorniak, N and Gaweł, K and Deskur, A and Pawlus, J and Stachowska, E}, title = {The Impact of Diet on the Fecal Microbiota Transplantation Success in Patients with Gastrointestinal Diseases-A Literature Review.}, journal = {Nutrients}, volume = {17}, number = {20}, pages = {}, doi = {10.3390/nu17203314}, pmid = {41156565}, issn = {2072-6643}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Gastrointestinal Diseases/therapy/microbiology ; *Diet ; Dietary Fiber/administration & dosage ; Treatment Outcome ; Feces/microbiology ; }, abstract = {Background: Fecal microbiota transplantation (FMT) is a therapeutic method involving the administration of appropriately prepared feces from a healthy donor to the gastrointestinal tract of a recipient. This literature review aims to summarize and critically evaluate the available evidence on the impact of different dietary patterns and nutrients on the efficacy of FMT. Methods: The present literature review focuses on the impact of diet on the gut microbiota in the context of the effectiveness of fecal microbiota transplantation. A literature review was conducted based on the PubMed Database. Results: More and more data confirm the close link between diet and gut microbiota and suggest that proper nutrition before and after FMT may support the effectiveness of this procedure. It appears that increased fiber intake significantly delays the loss of diversity in the transplanted microbiota, thereby enhancing the beneficial clinical effects following FMT. Additionally, the use of an anti-inflammatory components in the diet combination with FMT could be effective in achieving clinical remission in patients with ulcerative colitis. Conclusions: Based on the literature review, it appears that the most optimal nutritional model (through its beneficial effect on the composition of the gut microbiota, short-chain fatty acids production, and intestinal barrier integrity) to support the effectiveness of FMT is an anti-inflammatory diet rich in dietary fiber (for both the donor and the recipient).}, } @article {pmid41155411, year = {2025}, author = {Caliman-Sturdza, OA and Hamamah, S and Iatcu, OC and Lobiuc, A and Bosancu, A and Covasa, M}, title = {Microbiome and Long COVID-19: Current Evidence and Insights.}, journal = {International journal of molecular sciences}, volume = {26}, number = {20}, pages = {}, doi = {10.3390/ijms262010120}, pmid = {41155411}, issn = {1422-0067}, support = {760073/23.05.2023, code 285/30.11.2022, within Pillar III, Component C9, Investment 8.//Romania's National Recovery and Resilience Plan/ ; 760073/23.05.2023, code 285/30.11.2022, within Pillar III, Component C9, Investment 8.//Romania's National Recovery and Resilience Plan/ ; }, mesh = {Humans ; *COVID-19/microbiology/complications ; *Gastrointestinal Microbiome ; SARS-CoV-2 ; Dysbiosis/microbiology ; Post-Acute COVID-19 Syndrome ; Probiotics/therapeutic use ; *Microbiota ; }, abstract = {Long COVID, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent multi-systemic symptoms such as fatigue, cognitive impairment, and respiratory dysfunction. Accumulating evidence indicates that gut and oral microbiota play an important role in its pathogenesis. Patients with long COVID consistently exhibit reduced microbial diversity, depletion of beneficial short-chain fatty acid (SCFA)-producing species such as Faecalibacterium prausnitzii and Bifidobacterium spp. and enrichment of proinflammatory taxa including Ruminococcus gnavus, Bacteroides vulgatus, and Veillonella. These alterations may disrupt intestinal barrier integrity, sustain low-grade systemic inflammation, and influence host immune and neuroendocrine pathways through the gut-brain and gut-lung axes. Distinct microbial signatures have also been associated with symptom clusters, including neuropsychiatric, respiratory, and gastrointestinal manifestations. Proposed mechanisms linking dysbiosis to long COVID include impaired SCFA metabolism, tryptophan depletion, microbial translocation, and interactions with host immune and inflammatory responses, including autoantibody formation and viral antigen persistence. Preliminary interventional studies using probiotics, synbiotics, and fecal microbiota transplantation suggest that microbiome-targeted therapies may alleviate symptoms, although evidence remains limited and heterogeneous. This review synthesizes current literature on the role of gut and oral microbiota in long COVID, highlights emerging microbial biomarkers, and discusses therapeutic implications. While causality remains to be firmly established, restoring microbial balance represents a promising avenue for diagnosis, prevention, and management of long COVID.}, } @article {pmid41155291, year = {2025}, author = {Watai, K and Taniguchi, M and Azuma, K}, title = {The Gut-Brain-Immune Axis in Environmental Sensitivity Illnesses: Microbiome-Centered Narrative Review of Fibromyalgia Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and Multiple Chemical Sensitivity.}, journal = {International journal of molecular sciences}, volume = {26}, number = {20}, pages = {}, doi = {10.3390/ijms26209997}, pmid = {41155291}, issn = {1422-0067}, mesh = {Humans ; *Fibromyalgia/microbiology/immunology/therapy ; *Fatigue Syndrome, Chronic/microbiology/immunology/therapy ; *Gastrointestinal Microbiome/immunology ; *Multiple Chemical Sensitivity/microbiology/immunology/therapy ; *Brain/immunology/metabolism ; Animals ; *Brain-Gut Axis/immunology ; }, abstract = {Environmental sensitivity illnesses-including fibromyalgia syndrome (FMS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and multiple chemical sensitivity (MCS)-are chronic, disabling disorders characterized by hypersensitivity to environmental stimuli, persistent fatigue, widespread pain, and neurocognitive and autonomic dysfunction. Although their diagnostic criteria differ, increasing evidence suggests overlapping clinical features and shared biological mechanisms. A unifying hypothesis highlights the gut-brain-immune axis, where alterations in the intestinal microbiome, epithelial barrier dysfunction, and aberrant immune signaling interact with central sensitization and systemic metabolic dysregulation. Recent studies demonstrate reduced microbial diversity, depletion of anti-inflammatory taxa (e.g., Faecalibacterium prausnitzii, Bifidobacterium), and enrichment of pro-inflammatory Clostridium species across these conditions. These shifts likely alter production of short-chain fatty acids, amino acid metabolites, and complex lipids, with downstream effects on mitochondrial function, neuroinflammation, and host energy metabolism. Moreover, emerging clinical interventions-including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation-suggest a potential role for microbiome-targeted therapies, though controlled evidence remains limited. This review synthesizes current knowledge on microbiome alterations in FMS, ME/CFS, and MCS, emphasizing their convergence on metabolic and immune pathways. By integrating microbial, immunological, and neurophysiological perspectives, we propose a microbiome-centered framework for understanding environmental sensitivity illnesses and highlight avenues for translational research and therapeutic innovation.}, } @article {pmid41154477, year = {2025}, author = {Hsu, CN and Hou, CY and Tzeng, HT and Wu, KLH and Lee, WC and Chang-Chien, GP and Lin, SF and Tain, YL}, title = {Maternal Fecal Microbiota Transplantation Mitigates Hypertension in Offspring Exposed to a High-Fructose Diet.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {10}, pages = {}, doi = {10.3390/antiox14101168}, pmid = {41154477}, issn = {2076-3921}, support = {CMRPG8M0711, CMRPG8M0721, and CORPG8P0533//Kaohsiung Chang Gung Memorial Hospital, Taiwan/ ; }, abstract = {Excessive maternal fructose intake contributes to the developmental programming of hypertension in offspring, partly via gut microbiota dysbiosis and oxidative stress. Fecal microbiota transplantation (FMT) may restore microbial balance and modulate short-chain fatty acid (SCFA) production. We investigated whether maternal FMT from healthy donors could prevent hypertension in offspring exposed to a high-fructose (HF) diet. Pregnant Sprague Dawley rats (n = 12) were fed normal chow (ND) or a 60% HF diet from mating to delivery. Cross-FMT was performed: HF dams received FMT from ND donors, and ND dams received FMT from HF donors. Male offspring (n = 8/group) were assigned to ND, HF, ND + HF-FMT, or HF + ND-FMT groups. Offspring of HF dams developed higher systolic blood pressure (+13 mmHg vs. ND, p < 0.05). Maternal FMT from ND donors reduced this elevation by ~8 mmHg (p < 0.05). Protective effects were accompanied by higher plasma butyrate, increased expression of SCFA receptors (GPR41, GPR43), reduced renal oxidative stress markers (8-OHdG), and distinct gut microbiota profiles. Maternal FMT generated four enterotypes in offspring, each associated with differential blood pressure outcomes. These findings suggest that maternal microbiota-targeted interventions, such as FMT, can mitigate hypertension of developmental origin by restoring gut microbial and metabolic homeostasis.}, } @article {pmid41153953, year = {2025}, author = {Zhang, Z and Chen, K and Zhang, S and He, Y and Lei, G and Zhao, Y and Liang, J}, title = {Identification of Fecal Microbiota and Related Metabolites Associated with Feed Efficiency in DLY Pigs.}, journal = {Animals : an open access journal from MDPI}, volume = {15}, number = {20}, pages = {}, doi = {10.3390/ani15203026}, pmid = {41153953}, issn = {2076-2615}, abstract = {Improving feed efficiency (FE) is essential for enhancing productivity, reducing production costs, and minimizing environmental impacts in the swine industry. Fecal microbiota and their metabolites play important roles in nutrient metabolism and energy utilization. This study aimed to investigate the fecal microbiota and associated metabolites in pigs with divergent feed conversion ratios (FCR). Fecal samples were collected from 20 Duroc × (Landrace × Yorkshire) (DLY) commercial pigs exhibiting extremely high (HFCR, n = 10) and low (LFCR, n = 10) FCR for analysis using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS). The microbiota analysis revealed significantly higher abundances of Ruminococcus, Prevotella, Akkermansia, and Eubacterium in LFCR pigs (p < 0.05), while pathogenic bacteria predominated in HFCR pigs (p < 0.05). LC-MS metabolomics identified significant variations in metabolites involved in steroid hormone biosynthesis and primary bile acid metabolism between the two groups (p < 0.05). Spearman correlation analysis further demonstrated significant positive correlations between Ruminococcaceae_NK4A214_group and [Eubacterium]_coprostanogenes_group with bile acid metabolites, as well as between Akkermansia and steroid hormone synthesis (p < 0.05). These findings suggest a potential role for specific microbes and metabolites that are associated with feed efficiency, and warrant validation in pig feeding trials and fecal microbiota transplantation (FMT).}, } @article {pmid41153659, year = {2025}, author = {Lagoa, T and Martins, L and Queiroga, MC}, title = {Microbiota Modulation as an Approach to Prevent the Use of Antimicrobials Associated with Canine Atopic Dermatitis.}, journal = {Biomedicines}, volume = {13}, number = {10}, pages = {}, doi = {10.3390/biomedicines13102372}, pmid = {41153659}, issn = {2227-9059}, support = {UIDB/05183/2020 and LA/P/0121/2020//FCT - Fundação para a Ciência e a Tecnologia, Portugal/ ; }, abstract = {Modern lifestyle factors-such as dietary changes, reduced microbial exposure, and genetic susceptibility-profoundly influence the composition and function of the commensal microbiota. Additionally, dysregulation of the gut microbiota has been linked to impaired immune responses and an increased prevalence of skin disorders, including allergies and inflammatory conditions, thereby underscoring the importance of the gut-skin axis. Chronic gastrointestinal and dermatological manifestations frequently lead to excessive antimicrobial use, which in turn fosters the selection and colonization of multidrug-resistant organisms, most notably methicillin-resistant Staphylococcus pseudintermedius (MRSP) in companion animals. Furthermore, the growing threat of antimicrobial resistance (AMR) to both human and animal health reinforces the urgent need for alternative strategies like modulating the gut microbiota, which also contributes to the prevention and management of skin conditions. Against this backdrop, the present review aims to evaluate microbiota modulation as an alternative and complementary approach to antimicrobial therapy, focusing on its ability to restore microbial balance, strengthen epithelial barrier integrity, and improve overall health outcomes in dogs affected by atopic dermatitis (cAD). Promising interventions-including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation-are highlighted for their potential role in mitigating AMR and warrant further investigation as sustainable therapeutic strategies.}, } @article {pmid41148805, year = {2025}, author = {Baum, S and Hamedi, K and Loftus, C and Loftus, G and Zhou, ER and Arce, S}, title = {From Cytokines to Biomarkers: Mapping the Immunopathology of Inflammatory Bowel Disease.}, journal = {Cells}, volume = {14}, number = {20}, pages = {}, pmid = {41148805}, issn = {2073-4409}, mesh = {Humans ; *Inflammatory Bowel Diseases/immunology/pathology/genetics ; *Biomarkers/metabolism ; *Cytokines/metabolism ; Animals ; Genetic Predisposition to Disease ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic immune-mediated condition of the gastrointestinal tract, characterized by dysregulated inflammatory responses throughout the gastrointestinal tract. It includes two major phenotypes, Crohn's disease (CD) and ulcerative colitis (UC), which present with varying gastrointestinal and systemic symptoms. The pathophysiology of IBD is multifactorial including genetic predisposition, mucosal and epithelial dysfunction, environmental injury, and both innate and adaptive immune response abnormalities. Several predisposing genetic factors have been associated with IBD explaining the strong hereditary risk for both CD and UC. For example, Caspase Recruitment Domain 9 (CARD9) variant rs10781499 increases risk for IBD, while other variants are specific to either CD or UC. CD is related to loss-of-function mutations in the nucleotide oligomerization domain containing the protein 2 (NOD2) gene and Autophagy-Related 16-like 1 (ATG16L1) gene. UC risk is increased particularly in Chinese populations by the A-1661G polymorphism of the Cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene. This abnormal CTLA-4 interferes with B- and T-cell responses causing predisposition to autoimmune conditions. Previous studies suggested that IBD results from breakdown of the adaptive immune system, primarily of T-cells. However, new evidence suggests that a primary breakdown of the innate immune system in both CD and UC increases susceptibility to invasion by viruses and bacteria, with a compensatory overactivation of the adaptive immune system as a result. When this viral and microbial invasion continues, further damage is incurred, resulting in a downward cycle of further cytokine activation and epithelial damage. Released biomarkers also affect the permeability of the epithelial membrane, including lactoferrin, nitric oxide (NO), myeloperoxidase (MPO) and its activation of hypochlorous acid, matrix metalloproteinases (MMPs), especially MMP-9, omentin-1, and others. Increased macrophage and dendritic cell dysfunction, increased neutrophil activity, increased numbers of innate lymphoid cells, increased T-cells with decreased regulatory T-cells (Tregs), and changes in B-cell populations and immunoglobulin (Ig) functions are all associated with IBD. Finally, treatment of IBD has typically consisted of medical management (e.g., aminosalicylates and corticosteroids) and lifestyle modification, and surgical intervention in extreme cases. New classes of medications with more favorable side effect profiles include anti-integrin antibodies, vedolizumab, etrolizumab, and carotegrast methyl. Additionally, fecal microbiota transplant (FMT) is a newer area of research for treatment of IBD along with TNF-blockers, JAK inhibitors, and S1PR modulators. However, expense and long preparation time have limited the usefulness of FMT.}, } @article {pmid41148568, year = {2025}, author = {Che, Y and Shi, Y and Xu, Y and Guo, S and Liu, H and Yang, J and Liu, J and Niu, J and Shi, W and Guo, L and Wang, X and Zhang, F and Fan, W}, title = {Gut Microbiota Dysbiosis and LPS/NLRP3/GSDMD Pyroptosis Drive Hepatic Fibrosis: Therapeutic Potential of a Synbiotic Intervention.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {41148568}, issn = {1867-1314}, support = {202203021211239//Shanxi Provincial Natural Fund Project/ ; 202303021211126//Shanxi Provincial Natural Fund Project/ ; BYJL045//Shanxi Province Higher Education "Billion Project" Science and Technology Guidance Project/ ; }, abstract = {Hepatic fibrosis (HF) is the inevitable course from chronic hepatitis to liver cirrhosis with limited treatment options. Our previous studies have found that a synbiotic alleviates autoimmune hepatitis in mice by improving the gut microbiota. However, whether this synbiotic can prevent the progression of HF and its underlying mechanism remains unclear. Therefore, we explored the effects and mechanism of this synbiotic on concanavalin A (ConA)-induced HF in mice. We found that the synbiotic not only reshaped the gut microbiota by increasing beneficial bacteria such as Bifidobacterium and reducing harmful bacteria such as Allobaculum and Dubosiella but also strengthened the intestinal barrier, reduced the hepatic transfer of lipopolysaccharide (LPS), and inhibited the LPS/NLRP3/GSDMD pyroptosis pathway. It also decreased collagen deposition and alleviated HF in mice in vivo and in LX2 cells in vitro. Fecal microbiota transplantation (FMT) experiments showed that microbiota from fibrotic mice exacerbated gut barrier dysfunction and promoted the LPS-induced pyroptosis pathway. In contrast, microbiota depletion with antibiotics alleviated these effects. In conclusion, our study indicates that gut microbiota dysbiosis and the subsequent activation of the LPS/NLRP3/GSDMD pyroptosis pathway are important factors in the progression of HF. The synbiotic, by regulating the gut microecology and inhibiting the LPS-induced pyroptosis pathway, provides a promising therapeutic strategy for inhibiting HF.}, } @article {pmid41148459, year = {2025}, author = {Liang, M and Li, L and Fan, J}, title = {Multi-target Effects of Short-Chain Fatty Acids for Obesity-Related Asthma: Interventional Potential and Challenges.}, journal = {Clinical reviews in allergy & immunology}, volume = {68}, number = {1}, pages = {97}, pmid = {41148459}, issn = {1559-0267}, mesh = {Humans ; *Asthma/etiology/metabolism/therapy/epidemiology ; *Obesity/complications/metabolism ; *Fatty Acids, Volatile/metabolism/therapeutic use ; Gastrointestinal Microbiome ; Animals ; Dysbiosis ; Fecal Microbiota Transplantation ; }, abstract = {In recent years, the prevalence of obesity and asthma has risen steadily, emerging as two major chronic diseases threatening public health. These conditions exert mutual promotion and may induce pathological superposition effects in obesity-related asthma. Obesity-related asthma represents a distinct asthma phenotype, with pathogenesis involving chronic low-grade inflammation, metabolic dysregulation, mechanical constraints, and genetic predispositions. Critically, four core components, including adipose dysfunction with metabolic dysregulation, gut microbiota dysbiosis with intestinal barrier impairment, systemic chronic inflammation, and pulmonary inflammation with airway hyperresponsiveness, interlock into a self-reinforcing cycle that synergistically amplifies disease progression. Accordingly, obesity-related asthma exhibits a greater clinical burden than classical asthma, including more severe symptoms, higher exacerbation rates, and poorer therapeutic responsiveness. As key metabolites derived from gut microbiota, short-chain fatty acids (SCFAs) demonstrate potential to disrupt this pathological cycle in obesity-related asthma through anti-inflammatory actions, immune-metabolic modulation, and epithelial barrier protection. Furthermore, SCFA levels can be effectively modulated through dietary interventions, microbial preparation supplementation, and fecal microbiota transplantation, positioning them as promising translational targets for obesity-related asthma.}, } @article {pmid41148447, year = {2025}, author = {Choo, JM and Kang, WX and Le Leu, R and Manning, SK and Elms, L and Watson, N and Mukherjee, M and Trimingham, C and Coates, PT and Jesudason, S and Rogers, GB and Meade, A}, title = {The capacity of gastrointestinal microbiota in kidney transplant recipients to ferment prebiotic starch.}, journal = {Journal of nephrology}, volume = {}, number = {}, pages = {}, pmid = {41148447}, issn = {1724-6059}, support = {(2019/07-QA25217)//Kidney Transplant & Diabetes Research Australia/ ; APP1155179//National Health and Medical Research Council/ ; }, abstract = {BACKGROUND: Disruption of the gut microbiota in kidney transplant recipients has been linked to an increased risk of post-transplant infections and gastrointestinal symptoms, including diarrhoea. Dietary supplementation with resistant starch may mitigate these risks by promoting the growth of commensal gut bacteria that produce beneficial bioactive metabolites.

METHODS: Faecal microbiome profiles, gastrointestinal symptoms, and dietary habits were assessed in 13 individuals with kidney failure before and after transplantation, using 16S rRNA V4 amplicon sequencing, a modified Gastrointestinal Symptom Rating Scale (mGSRS) and a food frequency screener. The effect of resistant starch supplementation on the gut microbiota pre- and post-transplant was evaluated using a preclinical in vitro fermentation model with high amylose maize starch.

RESULTS: Gut microbiota diversity (based on richness and Shannon diversity index) declined significantly following kidney transplantation. This loss correlated with a higher frequency of gastrointestinal symptoms, including rectal pain. Significant shifts in microbiota composition were observed, including depletion of butyrate-producing Lachnospiraceae species, a change previously associated with post-transplant diarrhoea. These microbiota changes occurred independently of dietary patterns, which remained consistent throughout the study. Fermentation of high amylose maize starch in vitro by pre- or early post-transplant gut microbiota did not result in significant expansion of commensal bacterial populations.

CONCLUSIONS: Alterations in the gut microbiota following kidney transplantation are associated with gastrointestinal symptoms. High amylose maize starch supplementation did not produce beneficial effects on the gut microbiota in preclinical model studies, either before or after transplantation.}, } @article {pmid41146499, year = {2025}, author = {Lang, Q and Zeng, Y and Yao, H and Dai, N and Fu, X and Fu, B}, title = {[Gut microbiota: new perspective on the treatment of acute pancreatitis and clinical application prospects].}, journal = {Zhonghua wei zhong bing ji jiu yi xue}, volume = {37}, number = {9}, pages = {797-801}, doi = {10.3760/cma.j.cn121430-20240903-00744}, pmid = {41146499}, issn = {2095-4352}, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis ; *Pancreatitis/therapy/microbiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Acute Disease ; Anti-Bacterial Agents/therapeutic use ; Enteral Nutrition ; }, abstract = {Acute pancreatitis (AP) is a severe inflammatory disease characterized by self-digestion of pancreatic tissue and inflammatory responses. Recent studies have revealed a close connection between gut microbiota and AP. The gut microbiota community, a complex ecosystem composed of trillions of microorganisms, is closely associated with various physiological activities of the host, including metabolic processes, immune system regulation, and intestinal structure maintenance. However, in patients with AP, dysbiosis of the gut microbiota are believed to play a key role in the occurrence and progression of the disease. This dysbiosis not only impairs the integrity of the intestinal barrier, but may also exacerbate inflammatory responses through multiple mechanisms, thereby affecting the severity of the disease and patient' clinical prognosis. This article reviews the mechanisms of action of gut microbiota in AP, explores how gut microbiota dysbiosis affects disease progression, and evaluates current clinical treatment methods to regulate intestinal flora, including probiotic supplementation, fecal microbiota transplantation, antibiotic therapy, and early enteral nutrition. In addition, this article discusses the efficacy and safety of the aforementioned therapeutic approaches, and outlines future research directions, aiming to provide novel perspectives and strategies for the diagnosis, treatment and prognostic evaluation of AP. Through in-depth understanding the interaction between gut microbiota and AP, it is expected that more precise and personalized therapeutic regimens will be developed to improve patients' quality of life and clinical outcomes.}, } @article {pmid41145520, year = {2025}, author = {Suzuki, TA and Tanja, AS and Waters, JL and Jakob, D and Vu, DL and Ballinger, MA and Di Rienzi, SC and Chang, H and de Araujo, IE and Tyakht, AV and Ley, RE}, title = {Selection and transmission of the gut microbiome alone can shift mammalian behavior.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {9482}, pmid = {41145520}, issn = {2041-1723}, support = {101142834//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology/genetics ; Male ; Mice ; *Behavior, Animal/physiology ; Feces/microbiology ; *Selection, Genetic ; Locomotion ; Lactobacillus/metabolism ; Mice, Inbred C57BL ; Germ-Free Life ; Fecal Microbiota Transplantation ; }, abstract = {Animals live in partnership with their gut microbiota, and these microbial communities often shift when hosts adapt to new environments. While it is well known that the microbiome can influence traits ranging from metabolism to behavior, a key question remains unresolved: can host traits under natural selection be transmitted solely through the microbiome, without changes to the host genome? Here we experimentally demonstrate that selection on a behavioral trait in mice significantly shifts the host trait over time through microbiome transmission alone. We first identify locomotor activity as transmissible through the gut microbiome, using fecal transfers from wild-derived mouse strains into germ-free male recipients. Building on this, we carry out four rounds of one-sided microbiome selection, serially transferring microbiomes from low-activity donors to independently bred male germ-free mice. Only this selection line, not the randomly chosen control line, shows a decrease in locomotion toward the end of the experiment. Reduced activity is linked to enrichment of Lactobacillus and its metabolite indolelactic acid, and administration of either alone is sufficient to suppress locomotion. These findings demonstrate that microbiome selection and transmission can shape mammalian behavior, independent of host genomic evolution. Our work highlights the role of microbiome-mediated trait inheritance in shaping host ecology and evolution.}, } @article {pmid41145481, year = {2025}, author = {Yu, Y and Zheng, Y and Zhang, H and Fan, X and Guo, J and Sun, L and Tang, L and Ta, D}, title = {Abdominal LIPUS ameliorates simulated microgravity induced skeletal muscle atrophy via the gut-muscle axis.}, journal = {NPJ microgravity}, volume = {11}, number = {1}, pages = {73}, pmid = {41145481}, issn = {2373-8065}, support = {2025JC-YBMS-046//Natural Science Foundation of Shaanxi Province/ ; 12374442, 11974233//National Natural Science Foundation of China/ ; 12034005//National Natural Science Foundation of China/ ; }, abstract = {Study investigated if abdominal low-intensity pulsed ultrasound (LIPUS) alleviates simulated microgravity (hindlimb unloading, HU)-induced skeletal muscle atrophy by restoring gut microbiota. Mice were divided into control (NC), HU, and HU with daily abdominal LIPUS (HU + LIPUS) groups. Fecal microbiota transplantation (FMT) from LIPUS-treated mice to HU mice was also performed. After 28 days, abdominal LIPUS partially reversed HU-induced gut dysbiosis, restored intestinal barrier integrity, and increased short-chain fatty acid (SCFAs) levels. LIPUS downregulated muscle atrophy genes (MSTN, ActRIIB) and upregulated growth genes (Akt, mTOR) in HU mice, preventing muscle loss. SCFAs levels positively correlated with muscle function. HU mice receiving FMT from LIPUS-treated donors showed similar gut and muscle improvements as direct LIPUS treatment. Results demonstrate abdominal LIPUS ameliorates muscle atrophy by modulating the gut-muscle axis, offering a potential non-invasive strategy for astronauts and patients.}, } @article {pmid41144719, year = {2025}, author = {Liu, M and Sun, J and Jia, Z and Cui, Y and Zhu, X and Wang, Z and Sun, H and Liu, B and Shi, Y}, title = {Medicago Sativa L. Saponin-Driven Lactobacillus Intestinalis Restores Intestinal Stemness in Naturally Aged Mice via the Bile Acid-FXR-Wnt Signaling Axis.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e15370}, doi = {10.1002/advs.202515370}, pmid = {41144719}, issn = {2198-3844}, support = {CARS-34//Modern Agro-industry Technology Research System of China/ ; 244200510010//Science and Technology Innovation Leading Talent in Central Plains/ ; }, abstract = {Aging is recognized as a significant risk factor for chronic diseases. The decline in intestinal stem cells function is a critical contributor to intestinal aging, resulting in impaired intestinal homeostasis and increased vulnerability to age-related diseases. Medicago sativa L. (alfalfa) saponin are plant-derived bioactive compounds that are shown to have benefits in regulating oxidative stress and gut microbiota. However, the potential of alfalfa saponin (AS) to modulate intestinal aging and enhance intestinal stemness to maintain homeostasis remains insufficiently explored. In this study, the effects of AS on intestinal stemness in naturally aged mice and its underlying mechanisms involving gut microbiota regulation are examined. Antibiotic-mediated depletion of intestinal bacteria and fecal microbiota transplantation are employed to determine the specific role of the gut microbiota in mediating the effects of AS. Comprehensive multi-omics analyses revealed that AS significantly increased the abundance of Lactobacillus intestinalis (L. intestinalis). Notably, L. intestinalis is found to possess bile acids metabolic capabilities, producing ursodeoxycholic acid, which functions as an FXR antagonist to activate the Wnt signaling pathway and enhance intestinal stemness, thereby supporting intestinal homeostasis. These findings are validated in both intestinal organoids and naturally aged mice models. This study provides the first identification of a complete functional axis by which the metabolites of AS and L. intestinalis modulate intestinal stemness to mitigate intestinal aging, offering insights for the development of innovative natural product-based therapeutic strategies to promote healthy aging.}, } @article {pmid41144632, year = {2025}, author = {Vermeijden, NK and Oorthuys, A and Groen, J and Thapar, N and Vlieger, A and Puoti, MG and Borrelli, O and Benninga, M}, title = {Current and novel therapeutic strategies in pediatric irritable bowel syndrome and functional abdominal pain-not otherwise specified.}, journal = {Expert opinion on pharmacotherapy}, volume = {}, number = {}, pages = {}, doi = {10.1080/14656566.2025.2582017}, pmid = {41144632}, issn = {1744-7666}, abstract = {INTRODUCTION: Irritable bowel syndrome (IBS) and functional abdominal pain - not otherwise specified (FAP-NOS) are amongst the most common disorders affecting children worldwide, often associated with a lower quality of live, anxiety, and depression. The underlying mechanisms of these conditions remain poorly understood, posing significant challenges to effective treatment. Consequently, many children receive inadequate care. This highlights the urgent need for accessible and effective treatment strategies.

AREA COVERED: Data were identified using CENTRAL, MEDLINE, and PUBMED databases up to 1 December 2024. This review will explore existing treatment approaches, from first-line reassurance to a spectrum of non-pharmacological and pharmacological interventions. We also discuss emerging therapies and future directions.

EXPERT OPINION: IBS and FAP-NOS are now named disorders of gut-brain interaction in the Rome IV criteria, highlighting the complex interplay between central and peripheral gastrointestinal alterations. Psychological interventions, such as cognitive behavior therapy and gut hypnotherapy, have proven to be the most successful therapies in pediatric IBS and FAP-NOS, whilst the evidence for the efficacy of pharmacological interventions is mostly lacking due to poor quality of available studies and high placebo responses. Future studies are needed to investigate the value of novel treatment strategies such as fecal microbiota transplantation and open label placebo's.}, } @article {pmid41144501, year = {2025}, author = {Jiang, T and Li, C and Pan, Z and Wang, Y and Chen, X and Song, J and Zhu, K and Yang, Y and Hou, Y and Sun, L and Zhao, H and Liu, J and Gu, Y and Tao, B}, title = {Gut Microbiota-Decanoic Acid-Interleukin-17A Axis Orchestrates Hyperglycemia-Induced Osteoporosis in Male Mice.}, journal = {Diabetes}, volume = {}, number = {}, pages = {}, doi = {10.2337/db25-0471}, pmid = {41144501}, issn = {1939-327X}, support = {22YF1440000//Shanghai Sailing Program/ ; 82070865//National Natural Science Foundation of China/ ; 82201396//National Natural Science Foundation of China/ ; 82270931//National Natural Science Foundation of China/ ; 82301005//National Natural Science Foundation of China/ ; }, abstract = {UNLABELLED: Hyperglycemia (HG) is a well-established risk factor for secondary osteoporosis, primarily due to suppressed osteoblast activity. While gut microbiota (GM) dysbiosis has been implicated in various diseases, its role in HG-induced osteoporosis remains poorly understood. Here, we demonstrate that HG mice develop low-turnover osteoporosis accompanied by reduced GM diversity. Fecal microbiota transplantation (FMT) from HG mice (GMHG-FMT) induced osteoporosis in recipient mice, independent of blood glucose levels. A depletion of Bifidobacterium pseudolongum was associated with bone loss, whereas supplementation with either microbiota of normoglycemic mice or B. pseudolongum alleviated osteoporosis in HG mice. Both HG and GMHG-FMT recipient mice exhibited elevated serum interleukin-17A (IL-17A) levels, and anti-IL-17A antibody treatment mitigated osteoporosis in the GMHG-FMT model. Furthermore, decanoic acid levels were elevated in the feces of HG mice and the serum of GMHG-FMT recipients. Decanoic acid promoted the differentiation of naive CD4+ T cells into T helper17 cells, leading to increased IL-17A production. These findings reveal a microbiome dysbiosis-driven decanoic acid/IL-17A axis in HG-induced osteoporosis and highlight the therapeutic potential of microbiome-associated targets.

ARTICLE HIGHLIGHTS: This study investigated the role of gut microbiota dysbiosis in hyperglycemia-induced osteoporosis, a condition with unclear mechanisms. We explored whether gut microbiota dysbiosis drives bone loss in hyperglycemia and identified key microbial and molecular pathways. Hyperglycemic mice showed disturbed gut microbiota symbiosis, decreased Bifidobacterium pseudolongum, and elevated decanoic acid, which promoted T helper 17 differentiation and interleukin-17A (IL-17A) production, leading to osteoporosis. Fecal microbiota transplantation from control mice, B. pseudolongum supplementation, and IL-17A blockade alleviated bone loss, highlighting both B. pseudolongum supplementation and IL-17A inhibition as potential therapeutic strategies for hyperglycemia-induced osteoporosis.}, } @article {pmid41143926, year = {2025}, author = {Shi, Y and Ma, H and Li, H and Wang, Y and Wang, C and Zhang, N and Luo, G and Wang, Y and Gao, X}, title = {Sennoside A alleviating cognitive impairment in APP/PS1 mice via balancing microbiome metabolism.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {}, number = {}, pages = {13872877251389922}, doi = {10.1177/13872877251389922}, pmid = {41143926}, issn = {1875-8908}, abstract = {BackgroundThe progression of Alzheimer's disease (AD) is associated with constipation, potentially mediated by gut microbiota. Laxatives have shown potential in improving the cognitive function of AD, but the specific mechanism remains underexplored. Sennoside A (SA), a well-established laxative, is commonly used for treating constipation.ObjectiveThis work used SA as a probe to explore the therapeutic effects and potential mechanisms of laxatives on AD via the gut-brain axis.MethodsFollowing a two-month treatment, behavioral experiments were used to assess the cognitive function. The central pathologies and neuroinflammation were evaluated by histopathology and ELISA. 16S rRNA sequencing, fecal microbiota transplantation and antibiotic treatment were conducted to verify whether SA exerts anti-AD effects via gut microbiota. Further, non-targeted metabolomics coupled with Spearman correlation analysis was employed to elucidate the underlying mechanisms.ResultsSA significantly countered cognitive dysfunction and central pathological damage in APP/PS1 mice. Besides, SA ameliorated gut dysbiosis and affected the metabolic functions of the flora. Furthermore, the therapeutic effects of SA decrease with the depletion of gut microbes and could be transferred with the microbiota. Intriguingly, amino acid metabolism and aminoacyl-tRNA biosynthesis were the main metabolic pathways regulated by SA, consistent with the predicted functions of gut bacteria. Finally, correlation analysis revealed a strong correlation between gut microbes, fecal metabolites, and cognitive ability affected by SA.ConclusionsThe study investigated the efficacy and mechanisms of laxatives represented by SA for AD from the perspective of the gut-brain axis.}, } @article {pmid41140755, year = {2026}, author = {Santos-Ferreira, N and Zhang, X and Corneillie, L and Van Dycke, J and Chiu, W and Montpellier, C and Neyts, J and Cocquerel, L and Kaptein, SJF and Rocha-Pereira, J}, title = {Proliferative Cell Targeting and Epithelial Cell Turnover Fuels Hepatitis E Virus Replication in Human Intestinal Enteroids.}, journal = {Gastro hep advances}, volume = {5}, number = {1}, pages = {100769}, pmid = {41140755}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: Hepatitis E virus (HEV) is a leading pathogen causing acute viral hepatitis globally. While HEV is primarily spread fecal-orally, the role of the gut in HEV pathogenesis remains largely unexplored, including how HEV disseminates from gut to liver, and whether the gut is an HEV reservoir. We here aimed to illuminate HEV biology in the gut using human intestinal enteroids (HIEs).

METHODS: Three strategies were explored to establish an HEV-HIE model - three-dimensional (3D) HIEs, two-dimensional HIEs in transwell, and HEV RNA-electroporated HIEs. HEV particles produced by electroporated HIEs were characterized by western blot and gradient centrifugation. The intestinal tropism of HEV was investigated through confocal fluorescent microscopy and gene expression analysis.

RESULTS: HEV infection in 3D-HIEs and two-dimensional-HIEs showed limited replication, whereas HIEs electroporation led to a sustained increase in the release of nonenveloped infectious virions. These virions could reinfect new 3D-HIEs, yielding a ∼2 log10 increase in HEV RNA over time. In electroporated HIEs, high expression of the infectious open reading frame 2 capsid form was observed in the supernatant. Importantly, 70% of all HEV-infected cells were identified as proliferative cells (leucine-rich-repeat-containing G-protein-coupled receptor 5 intestinal stem cells and transit-amplifying progenitor cells). Open reading frame 2 staining was also observed in absorptive enterocytes, goblet, and enteroendocrine cells.

CONCLUSION: Overall, we established a robust HEV-HIE model that yields high titers of infectious nonenveloped virions. Proliferative cells and the fast intestinal epithelial cell turnover are important features that facilitate efficient HEV replication, and likely also its dissemination. This study suggests that the gut is an HEV reservoir, capable of producing some of the nonenveloped HEV shed in the feces.}, } @article {pmid41140407, year = {2025}, author = {Li, D and Li, Z and Liu, W}, title = {The gut-kidney axis in urolithiasis: roles of gut microbiota, metabolites, and therapeutic implications.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1655808}, pmid = {41140407}, issn = {1664-302X}, abstract = {Urolithiasis affects 2-20% of the global population and recurs frequently. Emerging evidence positions the gut-kidney axis as a central driver of stone formation. This review synthesizes epidemiological data, comparative metagenomic analyzes, and mechanistic studies to demonstrate that stone formers exhibit reduced α-diversity, depletion of oxalate-degrading taxa (e.g., Oxalobacter, Lactobacillus, Bifidobacterium), and enrichment of pro-inflammatory genera (Escherichia, Bacteroides). Microbial metabolites-oxalate, short-chain fatty acids, p-cresol, and secondary bile acids-modulate intestinal oxalate transport, systemic inflammation, and renal crystal nucleation. Therapeutic modulation via targeted probiotics, prebiotics, engineered Lactobacillus, or fecal microbiota transplantation restores oxalate homeostasis and attenuates nephrolithiasis in rodent models; however, human efficacy remains preliminary. Large-scale multi-omics cohorts and randomized controlled intervention trials are imperative to translate gut-centric strategies into precision urology.}, } @article {pmid41140403, year = {2025}, author = {Scarpellini, E and Abenavoli, L and Falalyeyeva, T and Kobyliak, N and Bendriss, G}, title = {Editorial: Fecal Microbiota Transplants: challenges in translating microbiome research to clinical applications.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1704947}, pmid = {41140403}, issn = {1664-302X}, } @article {pmid41140006, year = {2025}, author = {Shearer, J and Scantlebury, MH and Erome-Utunedi, O and Choudhary, A and Thompson, JA and Ohland, C and McCoy, KD and Mu, C}, title = {Role of Acid-Sensing Ion Channels 1a in the Regulation of Obesity and the Gut Microbiota.}, journal = {Obesity (Silver Spring, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/oby.70059}, pmid = {41140006}, issn = {1930-739X}, support = {RGPIN-2018-04238//Natural Sciences and Engineering Research Council of Canada/ ; //Cumming School of Medicine Research Enhancement Program/ ; }, abstract = {OBJECTIVE: Acid-sensing ion channels are proton-activated ion channels predominantly found in the nervous system. They are well known to affect metabolic and neurological health, yet their role in obesity and gut physiology remains unclear. This study investigates how systemic deletion of Asic1a influences obesity, metabolic, and gut-based outcomes.

METHODS: Employing male and female rats with systemic Asic1a deletion (Asic1a[-/-]), metabolic, gut, and fecal microbiota (16S rRNA sequencing) measures were assessed following chow diet or high-fat diet administration for 8 weeks. Fecal microbiota transplantation into germ-free mice was carried out as a proof-of-concept approach to assess the gut microbiota's direct impact.

RESULTS: On a chow diet, Asic1a deletion resulted in significant gains in body weight, fat mass, glucose intolerance, and insulin resistance in both male and female rats compared to wild-type controls. These effects were exacerbated with high-fat diet administration. Asic1a[-/-] reshaped the gut microbiota, characterized by the enrichment of Bacteroides and Akkermansia. Microbiota transplantation from Asic1a[-/-] rats to recipient germ-free mice increased body weight gain relative to those from wild-type rats, implicating the potential role of gut microbiota.

CONCLUSIONS: Results provide evidence that ASIC1a plays a role in regulating metabolic homeostasis and the gut microbiota impacting body composition.}, } @article {pmid41137517, year = {2025}, author = {Bayne, J and Charavaryamath, C and Hu, Y and Yousefi, F and Murphy, M and Law, A and Michael, A and Muyyarikkandy, MS and Nibbering, B and Smits, WK and Kuijper, E and Opriessnig, T and Sauer, M and Scaria, J and Sponseller, B and Ramirez, A and Mooyottu, S}, title = {The swine IsoLoop model of the gut host-microbiota interface enables intra-animal treatment comparisons to advance 3R principles.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2568706}, doi = {10.1080/19490976.2025.2568706}, pmid = {41137517}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Swine ; Ileum/microbiology/surgery ; *Host Microbial Interactions ; Humans ; Feces/microbiology ; Clostridioides difficile/physiology ; Fecal Microbiota Transplantation ; Bacteria/classification/genetics/isolation & purification ; Models, Animal ; Disease Models, Animal ; }, abstract = {Understanding gut-host microbiota interactions requires models that replicate human physiology while providing region-specific resolution, translational precision, and minimal animal use. To this end, we developed the IsoLoop model, a swine gut loop platform enabling intra-animal, multi-treatment comparisons. Microbiota-depleted ileal loops were surgically created in pigs, maintaining neurovascular integrity while isolating them from the anastomosed digestive tract. In Experiment 1, loops were inoculated with human fecal microbiota (HFM) or HFM combined with Peptacetobacter hiranonis. In Experiment 2, they were inoculated with Clostridioides difficile. Host-microbiota interactions were compared with respective controls in each experiment. The IsoLoop model reduced animal use by 75% compared to conventional whole-animal designs. Following antibiotic-induced depletion, loops re-established microbial diversity by day 5, despite reduced richness and loss of taxa, including Lactobacillus. HFM transplantation in microbiota-depleted loops induced robust transcriptomic recovery, enriched Akkermansia and Bifidobacterium, and restored specific metabolic pathways, although taxonomic and metabolic restoration remained incomplete and divergent. P. hiranonis promoted normal ileum-like metagenomic functional convergence, activated epithelial repair pathways, and increased specific secondary bile acids. C. difficile challenge recapitulated early infection pathology in IsoLoops. The IsoLoop model offers an ethical and precise platform for investigating host-microbiota crosstalk, localized enteric pathologies, and therapeutic interventions.}, } @article {pmid41136355, year = {2025}, author = {Chen, D and Yang, X and Jiao, D and Chen, X and Xiao, W and Zheng, J and Li, YX and Bao, C and Li, Y and Xu, B and Yuan, M}, title = {Electroacupuncture ameliorates Autism Spectrum Disorder via modulating the gut-brain axis depending on the integrity of vagus nerve.}, journal = {Translational psychiatry}, volume = {15}, number = {1}, pages = {428}, pmid = {41136355}, issn = {2158-3188}, mesh = {Animals ; *Autism Spectrum Disorder/therapy/chemically induced ; *Electroacupuncture ; *Gastrointestinal Microbiome/physiology ; Mice ; *Vagus Nerve/physiopathology ; Disease Models, Animal ; Male ; Microglia/metabolism ; Female ; *Brain-Gut Axis/physiology ; Behavior, Animal/physiology ; Mice, Inbred C57BL ; Brain ; Fecal Microbiota Transplantation ; }, abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by behavioral and neurological abnormalities. Numerous pieces of evidence indicate a strong association between ASD and neuroinflammation mediated by gut microbiota and microglial activation. Previous studies have shown that the therapeutic effects of an acupuncture protocol targeting the bacteria-gut-brain axis in a well-established ASD mouse model induced by prenatal exposure to valproic acid (VPA). We demonstrated that electroacupuncture significantly alleviates behavioral symptoms in VPA model. However, the precise mechanisms remain insufficiently elucidated. In this study, we confirmed that electroacupuncture markedly improved behavioral symptoms in ASD mice. We conducted gut microbiota transplantation from electroacupuncture-treated mice to untreated ASD mice, improving behavioral outcomes in untreated ASD mice. Conversely, by transplanting gut microbiota from ASD mice into electroacupuncture-treated mice, we successfully mitigated the beneficial behavioral effects of acupuncture. We analyzed inflammatory markers in the microglial activation from cerebral cortex and hippocampus tissues, revealing that acupuncture exerts robust anti-neuroinflammatory effects in ASD mice. To further validate the mechanism, we performed vagotomy in ASD mice, which abolished the therapeutic benefits of acupuncture. Our findings establish that the behavioral improvements observed in ASD mice are intricately linked to the diversity and abundance of gut microbiota. Furthermore, regulatory effects of electroacupuncture on ASD behaviors are mediated via bacteria-gut-brain axis, dependent on intact vagus nerve signaling. This study provides compelling evidence for the potential of acupuncture to modulate central neuroinflammation through vagus nerve-mediated gut microbiota regulation, offering novel avenue into its therapeutic application for neurodevelopmental disorders such as ASD.}, } @article {pmid41133518, year = {2025}, author = {Abdullah, IA and Khan, S and Hassan, FE}, title = {Gut-Brain Axis and Perioperative Gut Microbiome in Postoperative Cognitive Dysfunction: Implications for Neurosurgical Patients.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {13}, number = {4}, pages = {}, doi = {10.3390/medsci13040236}, pmid = {41133518}, issn = {2076-3271}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Postoperative Cognitive Complications/microbiology/etiology/prevention & control ; *Brain ; *Neurosurgical Procedures/adverse effects ; Dysbiosis ; Animals ; Probiotics/therapeutic use ; }, abstract = {Background: Postoperative cognitive dysfunction (POCD) is a common postoperative condition after neurosurgery, and in patients of advancing age, with far-reaching implications for recovery and quality of life. Current evidence points to the gut-brain axis as the main mechanism for the regulation of perioperative neuroinflammation and cognition. Objective: The aim of this review is to consolidate the existing evidence for perioperative gut microbiome dysbiosis in POCD, specifically in neurosurgical patients. Methods: A review of preclinical and clinical evidence on the gut microbiome, surgical stress, and cognitive recovery was conducted. Both mechanistic and therapeutic evidence were examined. Results: Surgery and anesthesia enhance gut microbial diversity, intestinal permeability, and systemic inflammation, thereby compromising neuroplasticity and the integrity of blood-brain barriers. Preclinical models show that interventions to reestablish microbial homeostasis with probiotics, prebiotics, or fecal microbiota transplantation decrease postoperative cognition. Clinical studies offer evidence supporting the associations between decreased short-chain fatty acid-producing bacteria and POCD risk. Randomized controlled trials have demonstrated that perioperative probiotics lower the incidence and markers of POCD. Multi-omic approaches to integrating microbiome, metabolome, and neuroimaging signatures are being engineered to discern recovery phenotypes prior to surgery. Conclusions: Perioperative gut microbiota are a modifiable target for the optimization of cognitive recovery from neurosurgery. The inclusion of microbiome treatments and diagnostics into standard surgical care pathways is one potential pathway to POCD minimization, but large randomized trials will be necessary to establish this.}, } @article {pmid41133095, year = {2025}, author = {Cui, X and Yuan, Q and Long, J and Zhou, J}, title = {Recent advances in gut microbiota-mediated regulation of fat deposition and metabolic disorders.}, journal = {Microbiome research reports}, volume = {4}, number = {3}, pages = {31}, pmid = {41133095}, issn = {2771-5965}, abstract = {The gut microbiota critically regulates lipid metabolism through microbial metabolites and host signaling pathways. Short-chain fatty acids (SCFAs), derived from dietary fiber fermentation, suppress hepatic lipogenesis via inhibition of SREBP-1c and enhance mitochondrial β-oxidation through GPR41/43 activation. Microbial enzymes convert primary bile acids into secondary bile acids, which activate FXR to inhibit lipogenesis and TGR5 to promote adipose thermogenesis. Lipopolysaccharide (LPS) from dysbiotic microbiota triggers TLR4-NF-κB signaling, exacerbating insulin resistance and adipose inflammation. Branched-chain amino acids (BCAAs), metabolized by gut microbes, drive adipogenesis via mTORC1-PPARγ signaling, with elevated circulating BCAAs linked to obesity. In livestock, microbiota modulation optimizes fat deposition: probiotics in pigs enhance intramuscular fat via Lactobacillus-enriched communities, while dietary succinate or coated sodium propionate reduces abdominal fat in broilers by reshaping cecal microbiota. Fecal microbiota transplantation confirms microbial causality in transferring fat phenotypes. Dysbiosis-associated mechanisms are conserved across species, where SCFAs and bile acids ameliorate metabolic inflammation, whereas LPS and BCAA imbalances worsen lipid dysregulation. Metabolic disorders, including obesity, type 2 diabetes (T2D), and non-alcoholic fatty liver disease (NAFLD), are tightly linked to gut microbiota perturbations. Dysbiosis drives LPS translocation and barrier impairment. These changes, along with altered metabolites, promote inflammation and fat deposition. Future strategies should integrate multi-omics and precision engineering of microbial consortia to advance therapies for both livestock and human metabolic health.}, } @article {pmid41133047, year = {2025}, author = {Al-Juhani, A and Desoky, MS and Almuhaimid, AA and Zaheer, M and Alhaqbani, HF and Abalkhail, EA and Alanazi, SA and Alzahrani, RS and Alrefaai, M and Desoky, R}, title = {Efficacy of Gut Microbiome-Targeted Therapies in Modulating Systemic Inflammation and Low-Grade Chronic Inflammatory States in Adults With Metabolic Disorders: A Systematic Review.}, journal = {Cureus}, volume = {17}, number = {9}, pages = {e92881}, pmid = {41133047}, issn = {2168-8184}, abstract = {Gut microbiome-targeted therapies have shown promise in promoting the outcomes of metabolic inflammation-related disease management. This review aims to assess the effectiveness of microbiome-targeted interventions and pinpoint the most promising therapies for clinical implementation. Following the PRISMA 2020 standards, we searched four main databases: PubMed, EMBASE, Scopus, and the Cochrane Library. We integrated medical subject headings (MeSH) and free-text keywords search pertinent to gut microbiome-targeted interventions, along with related outcomes such as inflammation and insulin resistance. English studies were conducted on primary adults with a metabolic disease diagnosis or deemed a high risk, and were mandated to report at least one outcome pertinent to metabolic health or systemic inflammation. To assess the risk bias, data were extracted, and the Cochrane Risk of Bias (RoB) 2.0 tool was employed. Fifteen studies fulfilled the inclusion criteria. A narrative synthesis was conducted. We found that probiotics significantly enhanced insulin resistance (HOMA-IR), reduced circulating endotoxin levels, decreased visceral fat, BMI, and fat mass, and increased beneficial taxa with obesity-associated bacteria reduction. However, inconsistent outcomes were shown for lipid parameters. Prebiotic therapies showed significant decreases in fasting glucose in overweight people, and insulin levels and HOMA-IR in patients with metabolic syndrome, enhanced anti-inflammatory effects (31% C-reactive protein (CRP) reduction, decreased interleukin (IL)-6, tumor necrosis factor-alpha (TNF)-α, and lipopolysaccharide (LPS) levels), and promoted butyrate-producing bacteria. Synbiotic interventions showed complementary benefits for glucose metabolism and body composition. Fecal microbiota transplantation (FMT) studies indicated improved insulin sensitivity and donor microbiota engraftment in responders. Fiber-rich diet trials markedly improved HbA1c levels in diabetic and prediabetic individuals. In conclusion, prebiotics demonstrated the most consistent metabolic and anti-inflammatory benefits across multiple parameters. Probiotics showed targeted effects on insulin resistance and body composition but inconsistent lipid outcomes. FMT and synbiotics require further investigation to establish clinical efficacy. This evidence supports prebiotics as a priority intervention for metabolic disease management through microbiome modulation.}, } @article {pmid41132656, year = {2025}, author = {Hu, Y and Yang, Y and Li, Y and Zhang, Q and Zhang, W and Jia, J and Han, Z and Wang, J}, title = {Th17/Treg imbalance in inflammatory bowel disease: immunological mechanisms and microbiota-driven regulation.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1651063}, pmid = {41132656}, issn = {1664-3224}, mesh = {Humans ; *Th17 Cells/immunology/metabolism ; *T-Lymphocytes, Regulatory/immunology/metabolism ; *Gastrointestinal Microbiome/immunology ; *Inflammatory Bowel Diseases/immunology/microbiology/therapy/metabolism ; Animals ; Dysbiosis/immunology ; Cytokines/metabolism ; }, abstract = {Inflammatory bowel disease (IBD) is a group of conditions characterized by chronic and recurrent intestinal inflammation, primarily including Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis of IBD is closely linked to abnormal immune responses, particularly T-cell mediated immune reactions. Th17 cells promote persistent intestinal inflammation by secreting pro-inflammatory cytokines such as IL-17, while regulatory T (Treg) cells help maintain immune homeostasis by secreting anti-inflammatory cytokines like IL-10 and TGF-β. In patients with IBD, Th17 cell function is enhanced, whereas Treg cell function is impaired or their numbers are reduced, leading to an imbalance in the immune system and exacerbating intestinal inflammation. The gut microbiota plays a crucial role in the immune regulation of IBD. Dysbiosis can lead to excessive activation of Th17 cells and suppression of Treg cell function, further aggravating clinical symptoms. Studies have shown that restoring gut microbiota balance through probiotics, antibiotics, dietary interventions, or fecal microbiota transplantation can not only improve immune responses but also restore the balance between Th17 and Treg cells, which has a positive impact on IBD treatment. This review summarizes how gut microbiota modulates the Th17/Treg cell balance to influence IBD immune responses and explores therapeutic strategies targeting Th17/Treg balance, including cytokine antagonists and immunosuppressive agents, which provide new directions and approaches for clinical IBD treatment.}, } @article {pmid41132492, year = {2025}, author = {Zhang, L and Xu, T and Chen, W and Chai, Y and Wu, Y and Du, X}, title = {The potential of the microbiome as a target for prevention and treatment of carbapenem-resistant Enterobacteriaceae infections.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1674534}, pmid = {41132492}, issn = {2235-2988}, mesh = {Humans ; *Carbapenem-Resistant Enterobacteriaceae/drug effects/physiology ; *Enterobacteriaceae Infections/prevention & control/microbiology/therapy ; *Gastrointestinal Microbiome/drug effects ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use/administration & dosage ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Animals ; Dysbiosis ; Carbapenems/pharmacology ; Fatty Acids, Volatile ; }, abstract = {Carbapenem-resistant Enterobacteriaceae (CRE) present an escalating threat to global health due to their high transmissibility, limited treatment options, and high mortality rates. The gastrointestinal tract serves as both a major reservoir and a transmission hub for CRE, especially under conditions of antibiotic-induced dysbiosis. This review highlights the growing interest in the gut microbiome as a potential target for preventing and managing CRE infections. Building upon the understanding of CRE pathogenesis, we examine how commensal microbiota contribute to colonization resistance through mechanisms such as nutrient competition, spatial niche exclusion, immune modulation, and the production of antimicrobial metabolites. We further discuss microbiome-based therapeutic strategies, including probiotic administration, fecal microbiota transplantation (FMT), and supplementation with short-chain fatty acids (SCFAs), that have shown encouraging results in reducing intestinal CRE colonization. In addition, we explore emerging microbiome engineering approaches, particularly CRISPR-Cas9-mediated systems, which enable the selective elimination of resistant strains while maintaining microbial homeostasis. Current microbiome-based approaches have shown promise in the treatment and prevention of CRE infections, but further research is still needed to clarify their mechanisms, evaluate long-term safety, and determine their effectiveness in different clinical settings. With continued studies and thoughtful integration into existing infection control and antibiotic stewardship practices, these strategies may gradually contribute to a more practical and sustainable way to manage CRE.}, } @article {pmid41131460, year = {2025}, author = {Li, G and Hou, Y and Zhang, L and Chen, L and Yang, Y and Yu, D}, title = {Gut microbiota and metabolomic profiles of tacrolimus-induced DILI in renal transplant recipients: a population-based case control study.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {684}, pmid = {41131460}, issn = {1471-2180}, support = {2025ZNSFSC0718//Sichuan Science and Technology Support Program/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Kidney Transplantation/adverse effects ; Male ; Female ; Middle Aged ; *Tacrolimus/adverse effects ; Case-Control Studies ; Adult ; *Immunosuppressive Agents/adverse effects ; *Bacteria/classification/genetics/metabolism/isolation & purification ; Transplant Recipients ; *Chemical and Drug Induced Liver Injury/microbiology/metabolism/etiology ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Metabolomics ; *Metabolome ; Aged ; }, abstract = {BACKGROUND: In clinical practice, cases of drug-induced liver injury (DILI) often occur in renal transplant recipients treated with tacrolimus (Tac) as an immunosuppressive therapy. Numerous studies have confirmed the close relationship between gut microbiota (GM) and DILI. However, systematic studies on the GM and metabolomic characteristics of Tac-associated DILI are lacking, and the role of GM and its metabolites in DILI remains incompletely understood.

METHODS: Renal transplant recipients receiving Tac at the Organ Transplantation Center of Sichuan Provincial People's Hospital were enrolled. Patients with DILI were assigned to the DILI group, and those with stable liver function to the control group. Stool samples were analyzed by 16 S rRNA gene sequencing and LC-MS non-targeted metabolomics, and blood samples were collected to measure Tac trough concentrations.

RESULTS: Seventy-two renal transplant recipients were included, comprising 32 DILI patients and 40 controls. Oscillibacter and Ruminococcus gnavus group were significantly enriched in the DILI group, whereas Bacteroides, Lachnospiraceae NK4A136 group, Anaerostipes, Subdoligranulum, Eubacterium coprostanoligenes group, and Megamonas were significantly decreased in the DILI group. Metabolites such as icosadienoic acid and 1-acyl-sn-glycerol-3-phosphate were significantly elevated in the DILI group, while glycyrrhetinate, S-adenosylmethionine, and other related metabolites were significantly reduced.

CONCLUSIONS: In renal transplant recipients, distinct GM and enteric metabolic profiles differentiate patients with DILI from those with stable liver function. Key microbial taxa-including Oscillibacter, Bacteroides, Ruminococcus gnavus group, and Lachnospiraceae NK4A136 group-potentially contribute to DILI pathogenesis through modulation of bile acid metabolism and inflammatory signaling pathways.}, } @article {pmid41130540, year = {2025}, author = {Li, J and Yue, Y and Pan, J and Liang, F}, title = {Research progress on gut microbiota in colorectal cancer immunotherapy.}, journal = {Biochimica et biophysica acta. Reviews on cancer}, volume = {1880}, number = {6}, pages = {189476}, doi = {10.1016/j.bbcan.2025.189476}, pmid = {41130540}, issn = {1879-2561}, abstract = {Immune checkpoint inhibitors (ICIs) have demonstrated significant clinical benefits in treating various malignancies. However, their therapeutic efficacy exhibits considerable interindividual variability in patients with colorectal cancer (CRC). In recent years, growing attention has been focused on the regulatory role of the gut microbiota and its metabolic microenvironment in modulating ICIs responses. This article systematically reviews key advances in understanding how the gut microbiota and its metabolites influence ICIs efficacy. For example: Specific bacterial species (e.g., Lactobacillus paracasei and Fusobacterium nucleatum) may regulate ICIs efficacy by modulating antigen presentation or the tumor immune microenvironment. Microbial metabolites, such as short-chain fatty acids (SCFAs), can enhance immune function and thereby improve ICIs outcomes. Potential microbiome-targeted interventions-including probiotic/prebiotic combinations, optimized antibiotic administration timing, refined fecal microbiota transplantation (FMT) protocols, and engineered synthetic biology-based bacterial therapies-are also discussed. By synthesizing current evidence, this review provides a theoretical foundation for developing novel personalized immunotherapy strategies for CRC, with a focus on microbiome modulation to optimize ICIs treatment efficacy.}, } @article {pmid41130528, year = {2025}, author = {Wang, J and Luo, Y and Wang, S and Zhou, Y and Gan, G and Xie, J and Cheng, ASK}, title = {Gut microbiota and late-life depression: from mechanistic insights to clinical rehabilitation.}, journal = {Life sciences}, volume = {}, number = {}, pages = {124041}, doi = {10.1016/j.lfs.2025.124041}, pmid = {41130528}, issn = {1879-0631}, abstract = {Emerging evidence identifies the gut microbiota as a promising therapeutic target for late-life depression, yet its mechanisms and clinical applications remain insufficiently defined in aging populations. This review synthesizes findings from animal studies and clinical trials to examine how the gut microbiota contributes to late-life depression and to evaluate potential intervention. We first outline the association between microbial ecosystem alterations and mental health, emphasizing their relevance for late-life depression. Mechanistic pathways are then discussed in sequence: disruption of intestinal microbial networks that impair barrier integrity, dysregulation of microbial metabolites that disturb gut-brain communication, and maladaptive immune activation and signal transduction at the host-microbe interface. Building on these insights, we assess the therapeutic approaches, including dietary interventions, probiotics, prebiotics, postbiotics, and fecal microbiota transplantation. Recovery outcomes are also summarized, covering microbial composition, metabolite changes, neurological biomarkers and neuroimaging findings. Finally, we address major translational challenges, including individual variability, dynamic monitoring, technological limitations, and safety concerns. We highlight the methodological gaps that limit current research and propose future directions to advance mechanistic understanding and clinical translation. By integrating ecological balance with personalized strategies, gut microbiota-based interventions hold potential to improve prevention and treatment of late-life depression.}, } @article {pmid41129310, year = {2025}, author = {Mao, ZH and Liu, Y and Pan, S and Zhang, Q and Qiao, Y and Zhang, X and Li, D and Chen, J and Liu, D and Feng, Q and Liu, Z}, title = {The Gut-Kidney Dialogue: Unraveling the Microbial Symphony in Renal Fibrosis.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {39}, number = {20}, pages = {e71179}, doi = {10.1096/fj.202502675R}, pmid = {41129310}, issn = {1530-6860}, support = {U21A20348//National Natural Science Foundation of China (NSFC)/ ; 82200796//National Natural Science Young Scientists Foundation of China/ ; LHGJ20230165//Medical Science and Technology Research Project of Henan Province/ ; LHGJ20240215//Medical Science and Technology Research Project of Henan Province/ ; 252300421112//Natural Science Foundation of Henan Province/ ; YQRC2024011//Young and Middle-aged Innovation Talents of Health Science and Technology Project in Henan Province/ ; 242102310009//Key R&D and Promotion Special Projects of Henan Province/ ; 242102310098//Key R&D and Promotion Special Projects of Henan Province/ ; //Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; Animals ; Fibrosis/microbiology ; *Renal Insufficiency, Chronic/microbiology/pathology ; *Kidney/pathology/microbiology ; *Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Mice ; Probiotics/therapeutic use ; }, abstract = {Renal fibrosis is a maladaptive pathological endpoint common to the diverse etiologies of chronic kidney disease (CKD), resulting in irreversible nephron loss and functional decline. Emerging evidence has highlighted the potential role of the gut microbiota in renal fibrosis through bidirectional interactions between the gut and kidney. In animal models, broad-spectrum antibiotic regimens have been confirmed to attenuate renal fibrosis, whereas fecal microbiota transplantation from fibrotic donors transmits renal disease in recipient germ-free mice, providing rudimentary evidence of microbial causality. Human-based studies have demonstrated that, in patients with CKD exhibiting progressive fibrosis, there are modifications in the composition of the gut microbiota, including decreased microbial variety and shifts in the distribution of specific bacterial groups. Furthermore, metabolomic profiling revealed that the severity of fibrosis was independently predicted by increased levels of circulating trimethylamine N-oxide and indoxyl sulfate. Preliminary clinical studies exploring the therapeutic potential of regulating the gut microbiota have demonstrated promising results. Interventions, such as high-purity probiotic formulations, result in improved renal function and decreased levels of fibrotic markers. These findings suggest a potential correlation between gut microbiota dysbiosis and renal fibrosis. However, further research is necessary to determine the causal correlations, elucidate the underlying mechanisms, and identify specific microbial species and metabolites related to the regulation of renal fibrosis. This review provides a systematic summary of the current understanding of the important connection between gut microbiota dysbiosis and renal fibrosis. Understanding the influence of gut microbiota on renal fibrosis may open new avenues for the development of innovative therapeutic strategies to prevent or manage renal fibrosis and its associated complications.}, } @article {pmid41128412, year = {2025}, author = {Peng, L and Song, H and Shi, H and Wu, L and Ma, Y and Fan, X and Wu, M and Duan, L and Li, Z and Yuan, H}, title = {Oral Multi-Enzymatic Manganese-Carbon Dots Alleviate Sepsis-Associated Lung Injury via the Gut-Lung Axis.}, journal = {ACS nano}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsnano.5c10625}, pmid = {41128412}, issn = {1936-086X}, abstract = {Sepsis-induced pulmonary injury represents a life-threatening global health challenge due to poorly defined pathological mechanisms. The gut-lung axis has been proven to be widely involved in sepsis-induced lung injury, yet effective interventions targeting gut microbiota homeostasis remain unknown. Single-cell sequencing revealed increased alveolar apoptosis and impaired macrophage efferocytosis during sepsis pathogenesis. Thus, we designed oral manganese-doped carbon dots (Mn-CDs) to alleviate septic lung injury by remodeling gut microbiota homeostasis and targeting the gut-lung axis. Biochemical characterization demonstrated Mn-CDs possess multienzyme mimetic activities (SOD-, CAT-, POD-, GPx-like) and potent ROS scavenging capacity. In murine sepsis models, Mn-CDs significantly improved systemic indices and were associated with macrophage anti-inflammatory states with enhanced efferocytosis, as evidenced by transcriptomic profiling. Integrated metagenomic/metabolomic analyses identified Mn-CDs-mediated enrichment of g_Clostridium and g_Bacteroides, concomitant with elevated indole-3-propionic acid (IPA) production. Subsequent in vitro studies demonstrate that IPA likely binds primarily to the aryl hydrocarbon receptor (AHR), promoting both efferocytosis and anti-inflammatory polarization in macrophages, thereby mitigating septic lung injury. Notably, the fecal microbiota transplantation (FMT) from Mn-CDs-treated mice not only alleviated systemic symptoms but also effectively promoted efferocytic polarization of pulmonary macrophages in septic mice. Depletion of the gut microbiota resulted in a significant loss of the protective efficacy of Mn-CDs in a murine model of septic lung injury. Collectively, the gut-lung axis mediated by microbiota-derived IPA and macrophage efferocytosis contributes to the remediation of septic lung injury, highlighting the potential of Mn-CDs in microbiome-directed critical care.}, } @article {pmid41126840, year = {2025}, author = {Liu, T and Li, Y and Xiong, X and Lai, X and Xu, X}, title = {The Microbiota-gut-brain axis in vascular cognitive impairment: unraveling the mysterious link and therapeutic prospects.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1648800}, pmid = {41126840}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Brain/metabolism ; *Cognitive Dysfunction/microbiology/therapy/etiology ; *Brain-Gut Axis ; *Dementia, Vascular/microbiology/therapy/etiology ; Medicine, Chinese Traditional ; Animals ; }, abstract = {BACKGROUND: Vascular cognitive impairment (VCI) exhibits particularly high prevalence in East Asian populations. However, its pathogenesis remains elusive due to its multifactorial and complex nature. Emerging evidence highlights the microbiota-gut-brain axis as a novel and promising paradigm for elucidating VCI mechanisms and developing therapeutic interventions. This systematic review aims to synthesize recent advances in this field, offering critical perspectives to guide future research on VCI through the lens of gut-brain interactions. Notably, given Traditional Chinese Medicine's (TCM) holistic and multi-target therapeutic advantages, we incorporate TCM studies to complement conventional approaches.

METHODS: We systematically searched PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang database for relevant studies from their inception to March 31, 2025, and conducted a comprehensive review.

RESULTS: A total of 22 relevant studies were included in the final review. Current research primarily focused on analyzing the altered gut microbiota in VCI patients, with findings indicating significant changes in both the structure and abundance of gut microbiota. Enterobacteriaceae exhibited potential as a diagnostic biomarker for post-stroke cognitive impairment (PSCI) (AUC=0.629), while distinct microbial signatures involving Bifidobacterium, Lactobacillus gasseri, and Anaerostipes hadrus may effectively differentiated PSCI patients from stroke survivors without cognitive deficits (AUC values of 0.785, 0.792, and 0.750, respectively). Furthermore, multiple interventional studies from both basic and clinical research systematically explored the microbiota-gut-brain axis as a promising therapeutic target for VCI. They evaluated the efficacy of diverse approaches-such as fecal microbiota transplantation, aerobic exercise, pharmacological interventions, and acupuncture-on key outcome including gut microbiota composition, cognitive function, hippocampal integrity, and inflammatory markers. Basic experimental studies revealed that Prevotella histicola, Clostridium butyricum, aerobic exercise, and TCM improved cognitive function, whereas trimethylamine N-oxide exacerbated cognitive impairment. The efficacy of TCM was further confirmed by clinical studies.

CONCLUSION: Research is in its early stages, but the microbiota-gut-brain axis already offers promising prospects for a deeper understanding and discovery of potential new therapeutic targets for VCI.

https://www.crd.york.ac.uk/prospero, identifier CRD42024560293.}, } @article {pmid41126356, year = {2025}, author = {Ba, F and Wang, W and Huang, Y and Zhang, S and Qiu, B and Xie, S and Xu, L and Gao, W and Zhang, X and Wen, Z and Wang, Q and Gao, H and Sheng, G and Berglund, B and Li, P and Li, L and Yao, M}, title = {Improving fecal transplantation precision for enhanced maturation of intestinal function in germ-free mice through microencapsulation and probiotic intervention.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {212}, pmid = {41126356}, issn = {2049-2618}, support = {2024YFA1307100//National Key Research and Development Program of China/ ; 2023YFC2506005, 2022YFA1303801//National Key Research and Development Program of China/ ; LR22C200005//Outstanding Youth Project of Zhejiang Natural Science Foundation/ ; SYS202202//Shandong Provincial Laboratory Project/ ; 2019-I2M-5-045//CAMS Innovation Fund for Medical Sciences/ ; 32372339//National Natural Science Foundation of China/ ; LY22C200014//Zhejiang Provincial Natural Science Foundation of China/ ; 2025ZFJH03//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Probiotics/administration & dosage/pharmacology ; Mice ; *Gastrointestinal Microbiome ; Feces/microbiology ; Germ-Free Life ; Bacteria/classification/genetics/isolation & purification ; Pediococcus pentosaceus/physiology ; Male ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has emerged as a widely used treatment for various diseases. While previous efforts have focused on selecting "super donors", the precise modulation of donor microbiota to enhance FMT efficacy remains a critical challenge. This study aimed to develop strategies to modify donor microbiota to promote gastrointestinal development and maturation in germ-free mice. Probiotic Pediococcus pentosaceus Li05 (Li05) was used as gut microbiota modulator to establish a healthier donor fecal microbiota, and a microencapsulation method was applied to ensure high bacterial viability during gastrointestinal tract transition.

RESULTS: Probiotic intervention initially altered the stability of the gut microbiota but eventually fostered a more complex bacterial interaction network and established a new equilibrium within 14 days. Transplantation of encapsulated Li05-modulated fecal microbiota significantly promoted epithelial development, improved barrier function, and altered the colonic transcriptome profile. These effects were found to be more dependent on the abundance of some bacterial genera instead of their co-occurrence network, and the key functional bacterial genera associated with these benefits were believed to be Parabacteroides, Parasutterella, Lachnoclostridium, Muribaculum and Desulfovibrio. Notably, both encapsulation and probiotic modulation played critical roles in enhancing the functional efficacy of these key bacterial genera, and the community composed of key functional bacteria demonstrated an antagonistic relationship with other bacterial communities. Moreover, encapsulated Li05-modulated fecal microbiota induced dramatical changes in host lipid metabolism, especially the bile acids and their derives. Sporobiota gained the function of promoting epithelium development gene expression only after Li05-modulation since high abundance of Lachnoclostridium was introduced.

CONCLUSION: These findings underscore the importance of encapsulation and donor microbiota modulation in FMT and provide valuable strategies for improving transplantation precision and outcomes.}, } @article {pmid41125958, year = {2025}, author = {Fan, Y and Ni, M and Aggarwala, V and Mead, EA and Ksiezarek, M and Cao, L and Kamm, MA and Borody, TJ and Paramsothy, S and Kaakoush, NO and Grinspan, A and Faith, JJ and Fang, G}, title = {Long-read metagenomics for strain tracking after faecal microbiota transplant.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {41125958}, issn = {2058-5276}, support = {R35 GM139655/GM/NIGMS NIH HHS/United States ; }, abstract = {Accurate tracking of bacterial strains that stably engraft in faecal microbiota transplant (FMT) recipients is critical for understanding the determinants of strain engraftment, evaluating correlations with clinical outcomes and guiding the development of therapeutic consortia. While short-read sequencing has advanced FMT research, it faces challenges in strain-level de novo metagenomic assembly. Here we describe LongTrack, a method that uses long-read metagenomic assemblies for FMT strain tracking. LongTrack shows higher precision and specificity than short-read approaches, especially when multiple strains co-exist in the same sample. We uncovered 648 engrafted strains across six FMT cases involving patients with recurrent Clostridioides difficile infection and inflammatory bowel disease. Furthermore, long reads enabled assessment of the genomic and epigenomic stability of engrafted strains at the 5-year follow-up timepoint, revealing structural variations that may be associated with strain adaptation in a new host environment. Our findings support the use of long-read metagenomics to track microbial strains and their adaptations.}, } @article {pmid41123871, year = {2025}, author = {Krawczyk, A and Kasperski, T and Gosiewski, T and Nikiforuk, A and Potasiewicz, A and Arent, Z and Salamon, D}, title = {Effects of fecal microbiota transplantation on the abundance and diversity of selected fungal and archaeal species in the gut microbiota in the rat model of schizophrenia.}, journal = {Pharmacological reports : PR}, volume = {}, number = {}, pages = {}, pmid = {41123871}, issn = {2299-5684}, abstract = {BACKGROUND: The gut microbiome has been increasingly recognized for its potential role in schizophrenia through gut-brain interactions involving immune, neural, and metabolic pathways. This pilot study evaluated the impact of fecal microbiota transplantation (FMT) on the abundance and variability of selected fungal and archaeal species in the gut microbiota in the rat model of schizophrenia.

METHODS: Sprague-Dawley rats using as a prenatal methylazoxymethanol acetate (MAM-E17) model of schizophrenia underwent FMT or placebo. Fecal DNA was extracted and analyzed via quantitative Real-Time PCR (qPCR) to quantify selected fungi (Candida tropicalis, Malassezia spp., Cryptococcus neoformans) and archaea (Methanobrevibacter smithii, Methanosphaera stadtmanae) before and after intervention RESULTS: A slightly higher prevalence of C. tropicalis was noted in MAM-exposed rats compared to healthy controls (19% vs. 10%). Post-FMT, C. tropicalis colonization increased to nearly 100% across all groups, irrespective of transplantation source, indicating natural microbiome maturation rather than FMT effect. Malassezia spp. were commonly present before treatment, with their abundance significantly declining after both FMT and placebo administration, suggesting procedural impacts rather than specific FMT effects. C. neoformans and methanogenic archaea were absent.

CONCLUSIONS: Overall, the results suggest that FMT has limited impact on gut fungal populations, possibly due to the developmental stage of microbiome maturation or procedural interventions. The absence of archaea underscores the complexity of the microbiome's role in neurodevelopmental disorders, highlighting the necessity for continued research into microbial influences on schizophrenia pathophysiology.}, } @article {pmid41123835, year = {2025}, author = {Saha, J and Goswami, R}, title = {Modulation of Innate Immunity by Short-Chain Fatty Acids in Probiotic and Fecal Microbiota Transplantation Therapies for the Treatment of Colon Disorders.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {41123835}, issn = {1867-1314}, abstract = {Short-chain fatty acids (SCFAs) are produced by microbes in the gut from macronutrient fermentation. As the key bacterial metabolites, three SCFAs-acetate, propionate, and butyrate-are abundant in the gut and are presently linked to a number of homeostatic and pathophysiologic immune regulatory processes. The significance of these metabolites in the control of numerous immunological processes is currently being closely examined especially in gut immunity in gut-liver and gut-brain axes. Besides affecting cell metabolism and functions that confer immunity to the host, interestingly, SCFAs are currently in the spotlight for their role in innate immune cell maturation and differentiation having potential translational benefits. Dysbiosis in the gut leading to alterations of gut microbe population affects wide array of physiologic functions including both local and systemic immune regulation. Affecting millions worldwide, inflammatory bowel disease (IBD) and colorectal cancer (CRC) are the major gut diseases where the etiology can be partially attributed to gut dysbiosis and short-chain fatty acid alterations. We closely monitored the impact of intervention strategies of IBD and CRC by alteration of gut microbiota through probiotic administration and fecal microbiota transplantation on innate immunity. Although ongoing studies underscore the implications of these strategies in combatting gut inflammation but the importance of SCFA metabolism on innate immunity needs to be addressed. With the current narrative, we aim to connect the dots and find any missing links, between how probiotic administration and fecal microbiota transplantation as therapies impact gut inflammation via innate immune cell regulation through SCFAs as gut microbial metabolites.}, } @article {pmid41123566, year = {2025}, author = {Omar, TM and Al-Hussainy, AF and Jyothi, SR and Priyadarshini Nayak, P and Bethanney Janney, J and Singh, G and Polatova, D and Sameer, HN and Salih, RM and Adil, M and Salajegheh, P}, title = {Invisible influencers: the tumor microbiome's impact on immunotherapy in colorectal cancer (CRC).}, journal = {Expert review of anticancer therapy}, volume = {}, number = {}, pages = {}, doi = {10.1080/14737140.2025.2579656}, pmid = {41123566}, issn = {1744-8328}, abstract = {INTRODUCTION: The tumor microbiome, a diverse microbial community within the tumor microenvironment (TME), significantly influences cancer progression and immunotherapy outcomes in colorectal cancer (CRC). Understanding its role in modulating immune responses and therapeutic resistance is critical for advancing precision oncology.

AREAS COVERED: This review examines the tumor microbiome's impact on CRC immunotherapy, focusing on immune checkpoint inhibitors (ICIs) like anti-PD-1/PD-L1 and anti-CTLA-4. It explores microbial composition, their immune-modulatory mechanisms, and metabolite-driven resistance pathways, including short-chain fatty acids and polyamines. Emerging strategies such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and targeted antibiotics are discussed, alongside challenges in personalizing microbiome-based therapies. Literature was sourced from peer-reviewed studies on tumor microbiome dynamics and immunotherapy resistance.

EXPERT OPINION: The tumor microbiome shapes CRC immunotherapy efficacy by modulating immune evasion and TME dynamics. Targeted interventions like FMT and probiotics show promise in enhancing ICI responses, but challenges include microbial variability, safety concerns, and ethical considerations. Future research should prioritize personalized microbiome profiling and standardized protocols to optimize therapeutic outcomes and overcome resistance in CRC.}, } @article {pmid41123497, year = {2025}, author = {Mali, J and Salusjärvi, J and Leppäniemi, A and Mentula, P and Sallinen, V}, title = {Comparison of classification systems for acute diverticulitis and updating of Helsinki staging.}, journal = {The journal of trauma and acute care surgery}, volume = {}, number = {}, pages = {}, doi = {10.1097/TA.0000000000004795}, pmid = {41123497}, issn = {2163-0763}, abstract = {BACKGROUND: Helsinki classification for acute colonic diverticulitis, based on radiological and clinical parameters, stratifies patients according to their prognosis and recommended treatment into five stages. This study aims to update Helsinki classification to improve it in patients with abscesses and peritonitis and validate the classification by comparing it with other classifications of diverticulitis.

METHODS: This was a retrospective cohort study. Patients treated for acute colonic diverticulitis of any stage between 2011 and 2017 and for stages 4 and 5 between 2006 and 2017 in Helsinki University Hospital were included. Performance of classifications was tested with area under the receiver operating characteristic curve analysis.

RESULTS: In total, 2,361 patients were included. Receiver operating characteristic curve analysis showed the highest specificity and sensitivity for abscess cutoff point 50 mm in intensive care unit (ICU) admissions, discharge within 14 days, and operative treatment. Patients with Helsinki stage 4 fecal peritonitis had significantly more ICU admissions (38% vs. 12%, p = 0.005) and less ICU-free days (median, 24 vs. 26; p < 0.03), and fewer were discharged within 14 days (48% vs. 72%, p = 0.03) than patients with Helsinki stage 4 purulent peritonitis. Outcomes were similar between stage 4 fecal subgroup and stage 5 patients. Based on these findings, in the updated Helsinki 2.0 classification, abscess diameter cutoff between Helsinki stages 2 and 3 was changed to 50 mm, and fecal peritonitis was defined as belonging to Helsinki stage 5 diverticulitis. Helsinki 2.0 classification had generally at least equal area under the curve (AUC) values (AUC, 0.89-0.95) for mortality and morbidity compared with other classifications of diverticulitis (AUC, 0.83-0.95).

CONCLUSION: Updated Helsinki 2.0 classification is an easy-to-use robust pre- and intraoperative classification for acute diverticulitis accurately predicting outcomes and guiding treatment choices.

LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.}, } @article {pmid41122746, year = {2025}, author = {Zhang, X and Li, Y and Guo, Y and Sun, J and Yang, Y}, title = {Clinical efficacy of fecal microbiota transplantation in alleviating depressive symptoms: a meta-analysis of randomized trials.}, journal = {Frontiers in psychiatry}, volume = {16}, number = {}, pages = {1656969}, pmid = {41122746}, issn = {1664-0640}, abstract = {BACKGROUND: Depressive symptoms are common in neuropsychiatric disorders, significantly affecting quality of life and posing challenges to treatment. While pharmacological and psychological therapies remain standard, many patients show limited response. Fecal microbiota transplantation (FMT), which aims to restore gut microbial balance, has emerged as a novel approach for alleviating depressive symptoms by modulating the gut-brain axis. This study aims to conduct a comprehensive synthesis and quantitative evaluation of current evidence to elucidate the therapeutic potential of FMT in the management of depressive symptomatology.

METHODS: Following PRISMA guidelines, we conducted a systematic search across PubMed, Embase, Web of Science, the Cochrane Library, and CINAHL from January 1, 2000, to December 31, 2024. 12 randomized controlled trials (RCTs) with 681 participants were included. The standardized mean difference (SMD) was calculated to evaluate FMT's effect on depressive symptoms. Subgroup analyses examined effects by delivery routes, follow-up duration, and clinical population.

RESULTS: FMT significantly reduced depressive symptoms (SMD = -1.21; 95% CI: -1.87 to -0.55; p = 0.0003). Sensitivity analysis confirmed statistical significance (SMD = -0.56; 95% CI: -0.86 to -0.26; p = 0.001). Both oral capsule and direct gastrointestinal administration were effective, with greater effects seen in direct gastrointestinal delivery (SMD = -1.06 vs. -1.29). Improvements were most notable in the short- to mid-term; effects diminished by 6 months. Subgroup analysis showed stronger effects in patients with irritable bowel syndrome (IBS) (SMD = -1.06) than in those with neurological/psychiatric-related conditions (SMD = -0.67), with moderate heterogeneity (I² = 47%).

CONCLUSIONS: This meta-analysis supports FMT as an effective adjunctive therapy for depressive symptoms, especially in individuals with IBS. Endoscopic or enema routes appear more efficacious than oral capsules. While short- and mid-term benefits are evident, sustained effects require further investigation through long-term, high-quality RCTs.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42025638185.}, } @article {pmid41120147, year = {2025}, author = {Takeshige-Amano, H and Igami, E and Okuzumi, A and Kamo, R and Iseki, M and Tsuyama, K and Wakamori, R and Okada, H and Taniguchi, D and Ueno, SI and Oji, Y and Ishikawa, KI and Nishikawa, N and Orikasa, M and Odakura, R and Koma, M and Maruyama, T and Nomura, K and Ishikawa, D and Shibuya, T and Nagahara, A and Teramoto, H and Yanagisawa, N and Hatano, T and Hattori, N}, title = {Randomised, double-blind, placebo-controlled, parallel-group study to assess the efficacy and safety of antibiotic faecal microbiota transplantation in patients with Parkinson's disease (FLORA-PD): a study protocol.}, journal = {BMJ open}, volume = {15}, number = {10}, pages = {e102851}, doi = {10.1136/bmjopen-2025-102851}, pmid = {41120147}, issn = {2044-6055}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Parkinson Disease/therapy/microbiology ; Double-Blind Method ; *Anti-Bacterial Agents/therapeutic use ; Randomized Controlled Trials as Topic ; *Gastrointestinal Microbiome ; Treatment Outcome ; Male ; Middle Aged ; Female ; }, abstract = {INTRODUCTION: The intestinal microbiota of people with Parkinson's disease (PwP) differs significantly from that of healthy individuals. Given that altered microbiota may play a role in the pathogenesis of Parkinson's disease, faecal microbiota transplantation (FMT) has been proposed as a potential therapeutic approach. However, the efficacy of FMT in improving motor symptoms in PwP has been inconclusive in some pilot randomised controlled trials (RCT). Previous RCTs on PwP employed simple FMT, but our modified approach-pretreatment with antibiotics before FMT (A-FMT)-has been shown to improve the engraftment rate of given species and the beneficial effects of FMT. This study aims to evaluate the efficacy and safety of A-FMT for PwP, particularly in those with motor fluctuations.

METHODS AND ANALYSIS: This study is a randomised, double-blind, placebo-controlled, parallel-group study with an 8-week observation period following a single A-FMT. Thirty clinically established PwP with prominent motor fluctuation episodes will be randomised 1:1 to FMT or placebo. Participants in both groups will receive antibiotic treatment prior to colonoscopy for FMT or placebo treatment. Primary and secondary endpoints will include subjective and objective evaluations of motor and non-motor symptoms and will be evaluated before and after antibiotic treatment and at 4 and 8 weeks after the procedure. Exploratory endpoints will include blood and faecal sample analyses, advanced brain MRI and pharmacokinetic assessment of levodopa concentrations during a levodopa challenge test.

ETHICS AND DISSEMINATION: This study has been approved by the ethical committee of Juntendo University in August 2024 (J24-005) and will be conducted in accordance with the Declaration of Helsinki, the Japan Ministry of Health, Labour and Welfare Clinical Trials Act and related laws and regulations. All patient data will be anonymised to protect privacy and used solely for study purposes. Results will be published in academic journals and presented at conferences.

TRIAL REGISTRATION NUMBER: jRCTs031240344.}, } @article {pmid41120029, year = {2025}, author = {Liu, J and Bian, X and Bian, X and Zhang, J and Li, Z and Liu, H and Wu, J and Sun, X}, title = {The main active component Kaji-ichigoside F1 of the ethnic medicine Rosa roxburghii Tratt prevents acetaminophen-induced acute liver injury by modulating microbial metabolism.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {120767}, doi = {10.1016/j.jep.2025.120767}, pmid = {41120029}, issn = {1872-7573}, abstract = {Kaji-ichigoside F1 (KF1), the main active component of the Guizhou ethnic medicinal material Rosa roxburghii Tratt, is widely used in China due to its anti-inflammatory properties. However, the protective effects of KF1 against drug-induced liver injury and its potential mechanisms are not yet understood.

AIM OF THE STUDY: We aimed to investigate the effects of KF1 on acute liver injury (ALI) and explore its underlying mechanisms, particularly its role in modulating the gut microbiota to inhibit ALI development.

MATERIALS AND METHODS: KF1 was prepared via 80% ethanol extraction, silica gel column chromatography, and Sephadex LH-20 column chromatography. Mouse models of ALI were established using acetaminophen (APAP) treatment, with or without KF1 (5 and 10 mg/kg). 16S rRNA gene sequencing, metabolomics, and transcriptomics approaches were employed to explore the inhibitory effect of KF1 on ALI. Additionally, the role of the gut microbiota was investigated through antibiotic treatment and fecal microbiota transplantation experiments.

RESULTS: Treatment with KF1 significantly altered the gut microbiota composition, notably increasing the abundance of the probiotic Akkermansia muciniphila (A. muciniphila). Furthermore, A. muciniphila enhanced the levels of beneficial metabolites, including inosine. Notably, inosine significantly suppressed inflammatory factors and improved APAP-induced ALI. Transcriptomic analysis revealed that inosine inhibited key signaling pathways, including MAPK, PI3K-AKT, JAK-STAT3, IL-17, TNF, and cytokine-cytokine receptor interactions. Importantly, the preventive effect of KF1 is dependent on microbial mechanisms.

CONCLUSION: KF1 protects against ALI by modulating the gut microbiota and associated metabolites, thereby promoting a more favorable state and inhibiting pro-inflammatory pathways.}, } @article {pmid41118252, year = {2025}, author = {Qi, X and Li, Y and Zhu, Y and Shen, R and Xie, Z}, title = {Rebuilding the gut ecosystem: Emerging strategies targeting the microbiota in antibiotic-associated diarrhea.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {}, number = {}, pages = {}, doi = {10.1556/030.2025.02690}, pmid = {41118252}, issn = {1588-2640}, abstract = {Antibiotic-associated diarrhea (AAD) is a prevalent iatrogenic complication of antibiotic therapy, primarily triggered by dysbiosis and loss of intestinal homeostasis. The traditional interventions, such as empirical probiotic use, have shown a modest and a heterogeneous efficacy. This review integrates the current mechanistic understanding of AAD through the lens of the microbiota-mucosal-immune axis and provides a comprehensive overview of emerging therapeutic strategies. By integrating evidence from metagenomics, metabolomics, and immunology, we highlight next-generation approaches, including rationally engineered probiotics, standardized fecal microbiota transplantation (FMT), and synthetic-biology-derived interventions. Recent progress in multi-omics technologies and machine learning has enabled patient-stratified modulation of the gut microbiota, moving beyond empirical supplementation toward precision ecological reprogramming. These advanced therapies demonstrate superior outcomes in restoring microbial diversity, strengthening epithelial barrier function, and re-establishing immunological homeostasis. Ultimately, the management of AAD requires a systems-biology strategy that leverages real-time microbiome analytics for targeted, accurate, and sustainable restoration of gut health.}, } @article {pmid41115965, year = {2025}, author = {Göttert, S and Thiele Orberg, E and Fan, K and Heinrich, P and Matthe, DM and Khalid, O and Klostermeier, L and Suriano, C and Strieder, N and Gebhard, C and Vonbrunn, E and Mamilos, A and Hirsch, D and Meedt, E and Kleigrewe, K and Hiergeist, A and Schwarz, A and Gläsner, J and Ghimire, S and Joachim, L and Voll, F and Neuhaus, K and Janssen, KP and Perl, M and Pielmeier, F and Ruland, J and Kreutz, M and Weber, D and Schmidl, C and Köhler, N and Tschurtschenthaler, M and Hoffmann, P and Edinger, M and Wolff, D and Bassermann, F and Rehli, M and Haller, D and Evert, M and Hildner, K and Büttner-Herold, M and Herr, W and Gessner, A and Heidegger, S and Holler, E and Poeck, H}, title = {The microbial metabolite desaminotyrosine protects against graft-versus-host disease via mTORC1 and STING-dependent intestinal regeneration.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {9282}, pmid = {41115965}, issn = {2041-1723}, support = {324392634//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, mesh = {Animals ; *Graft vs Host Disease/prevention & control ; *Mechanistic Target of Rapamycin Complex 1/metabolism ; *Gastrointestinal Microbiome/drug effects ; Mice ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; *Intestines/physiology/drug effects ; *Membrane Proteins/metabolism/genetics ; *Regeneration/drug effects ; Mice, Inbred C57BL ; *Tyrosine/analogs & derivatives/pharmacology/metabolism ; Male ; Female ; Fecal Microbiota Transplantation ; Transplantation, Homologous ; }, abstract = {Changes in the intestinal microbiome and microbiota-derived metabolites predict clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, we report that desaminotyrosine (DAT), a product of bacterial flavonoid metabolism, correlates with improved overall survival and reduced relapse rates in patients receiving allo-HSCT. In preclinical mouse models, treatment with synthetic DAT prevents graft-versus-host disease by protecting the intestinal barrier and promoting intestinal regeneration and contributes to graft-vs.-leukemia responses. DAT´s beneficial effects on intestinal regeneration remain effective despite broad-spectrum antibiotics-induced dysbiosis, also when administered by fecal microbiota transfer with flavonoid-degrading F. plautii. Mechanistically, DAT promotes mTORC1-dependent activation and proliferation of intestinal stem cells, with concomitant engagement of the innate immune receptor STING required to mitigate metabolic stress and maintain an undifferentiated stem cell state independently of type-I interferon responses. Additionally, DAT can skew T cells towards an effector phenotype to modulate graft-versus-leukemia responses. Our data uncover DAT's dual, tissue- and immune-modulating properties and underscore its potential in precision microbiome-based therapies to improve tissue regeneration and minimize immune-mediated side effects.}, } @article {pmid41115539, year = {2025}, author = {Meng, M and Zhao, L and Liu, W and Yi, G and Song, Y and Gan, Z and Tan, X and Dou, H and Liu, Y and Zhang, Y}, title = {Effect of polysaccharides from Aconitum pendulum Bush on rheumatoid arthritis.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {148405}, doi = {10.1016/j.ijbiomac.2025.148405}, pmid = {41115539}, issn = {1879-0003}, abstract = {The Tibetan people of China have used the roots of Aconitum pendulum Bush as a folk remedy for rheumatoid arthritis (RA). In this study, we investigated the effects of A. pendulum polysaccharides (APPs) on RA. Chemical analysis revealed that APPs were mostly composed of galacturonic acid, glucose, and glucuronic acid. Structural characterization showed that it is an α-glucan with (1 → 4) and (1 → 3,6) glycosidic linkages. Furthermore, we examined the therapeutic potential of APPs (100 and 400 mg/kg) in a rat model of bovine collagen-induced arthritis (CIA). Results indicated that APP administration markedly reduced the critical characteristics of CIA, including foot swelling, thymic and splenic indices, and serum concentrations of pro-inflammatory cytokines. Histopathological analysis further validated that APPs mitigated vascular opacities and synovial inflammation in the ankle joints. Moreover, initial analysis of fecal samples revealed changes in the abundance of specific intestinal microbial taxa after APP treatment. These findings collectively establish an experimental basis for the potential of APPs as adjunctive therapeutic agents for RA. However, additional research, encompassing fecal microbiota transplantation and studies in germ-free models, is essential to clarify the potential causal relationship between the observed alterations in gut microbiota and the anti-arthritic effects of APPs.}, } @article {pmid41114583, year = {2025}, author = {Xia, Y and Yang, J and Lu, S and Cheng, W and Ren, M and Liu, Z and Yang, L and Shen, Q and Liang, Y and Huang, H and Chen, M and Zhou, X and Yu, M and Ji, F and Xu, C}, title = {Microbial changes resulting from VSG attenuate MASLD by modulating bile acid metabolism and the intestinal FXR-FGF19 axis.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0063425}, doi = {10.1128/msystems.00634-25}, pmid = {41114583}, issn = {2379-5077}, abstract = {UNLABELLED: Vertical sleeve gastrectomy (VSG) is a highly effective intervention for metabolic dysfunction-associated steatotic liver disease (MASLD) and is associated with significant alterations in the gut microbiota. However, the precise mechanisms underlying its metabolic benefits remain poorly understood. In this study, we revealed that VSG mitigates MASLD by reshaping gut microbiota-mediated bile acid metabolism. Through integrated 16S rRNA sequencing, targeted metabolomics, and functional validation experiments, we demonstrated that VSG markedly enhances bile salt hydrolase (BSH) activity within the gut microbiota, resulting in elevated levels of unconjugated bile acids. These unconjugated bile acids serve as potent agonists for the intestinal farnesoid X receptor (FXR), thereby activating the intestinal FXR-fibroblast growth factor 19 signaling pathway. This activation leads to significant improvements in metabolic health, including enhanced glucose regulation and attenuated hepatic lipid accumulation. Fecal microbiota transplantation (FMT) from VSG-treated rats replicated these metabolic improvements, whereas antibiotic treatment abolished these beneficial effects, highlighting the indispensable role of the gut microbiota in mediating the anti-MASLD effects of VSG. Importantly, inhibition of intestinal FXR signaling negated the metabolic benefits of FMT, further emphasizing the critical role of the gut microbiota-BSH-FXR axis. Our findings reveal a novel mechanism by which VSG alleviates MASLD through gut microbiota-dependent activation of intestinal FXR, offering new perspectives for microbiome-targeted therapeutic strategies in MASLD.

IMPORTANCE: Fecal transplantation from bariatric surgery patients and mice to germ-free mice has shown that the gut microbiota may contribute to metabolic benefits after bariatric surgery. However, the mechanisms by which the gut microbiota contributes to metabolic benefits after bariatric surgery require further investigation. To address this gap, we investigated the effects of the vertical sleeve gastrectomy (VSG) gut microbiota on metabolic dysfunction-associated steatotic liver disease (MASLD) in vivo and elucidated its underlying mechanisms. Our study demonstrated that VSG significantly improved the gut microbiota, especially by increasing bile salt hydrolase (BSH) activity, in MASLD rats. Increased BSH activity significantly increased the proportion of FXR-agonistic bile acids and further activated the intestinal FXR-FGF19 axis, thereby improving MASLD. These findings explored the key roles and mechanisms of the gut microbiota in the metabolic benefits of VSG, offering new microbiome-based treatment strategies.}, } @article {pmid41114530, year = {2025}, author = {Xiao, Y and Zhang, X and Shao, B and Wu, Z and Li, X and Yi, D and Li, T and Yang, T and Zhu, J and Huang, T and Deng, Y and Qiu, T and Yang, G and Sun, X and Wang, N}, title = {Hydroxytyrosol Improves Metabolic Dysfunction-Associated Fatty Liver Disease Dependent on the Modulation of Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c07003}, pmid = {41114530}, issn = {1520-5118}, abstract = {The global threat of metabolic dysfunction-associated fatty liver disease (MAFLD) is significant, but effective measures are still lacking. To explore the potential impact of hydroxytyrosol (HT), a plant polyphenol, in the metabolic outcomes of MAFLD and the mediating role of the gut microbiota, we performed an 8-week randomized placebo-controlled clinical trial in MAFLD patients and collected fecal bacteria for metagenomics analysis and targeted metabolomics. In this population-based trial, we have revealed that HT mitigates liver injury and steatosis in patients with MAFLD, as well as systemic glucolipid metabolism disorder. Through analysis of the differences in bacterial taxon and functional profiles, as well as correlation analysis between species and metabolic indicators, it was found that Fusicatenibacter saccharivorans (F. saccharivorans), the microbial species with the greatest difference after HT intervention, was also the most significantly correlated with metabolic parameters of MAFLD and showed a significant positive correlation with the content of fecal butanoic acid. Butanoic acid was further associated with MAFLD-related metabolic indexes. To confirm the potential causal relationship between alterations in gut microbiota induced by HT intervention and improved MAFLD metabolic phenotypes, fecal microbiota transplantation (FMT) was conducted using a model of pseudogerm-free mice. We have further demonstrated that the fecal microbiota from donors of MAFLD patients receiving HT supplementation can ameliorate liver and systemic phenotypes in western-diet-induced MAFLD mice, interpreting the robust action of gut microbiota remodeled by HT in improving MAFLD. Consequently, HT supplementation may represent a tactic for improving MAFLD by modulating the composition and functionality of the gut microbiota.}, } @article {pmid41114029, year = {2025}, author = {Li, X and Liu, Q and Wang, Y and Zhang, H and Wu, Z and Fan, R and Ma, Y and Gong, W and Li, X}, title = {Two modified colonoscopically guided fecal microbiota transplantation catheter placement methods: a retrospective study (with video).}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1641325}, pmid = {41114029}, issn = {2296-858X}, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) transfers fecal microbiota from a healthy person into a patient for the treatment of various diseases. This study introduces two modified colonoscopically guided fecal microbiota transplantation catheter placement methods and evaluates their effectiveness and safety in clinical use.

METHODS: This study retrospectively reviewed medical records and corresponding endoscopist operational records of FMT patients at Shenzhen Hospital, Southern Medical University, from January 13, 2022, to July 26, 2024. The study analyzed 117 cases, divided into the Direct Loop Clamping (DLC) group and the Clip Loop Binding (CLB) group. The primary outcome was the catheter placement success rate. The secondary outcomes were operation-related times and adverse events.

RESULTS: Both groups achieved a 100% success rate in catheter placement. The two methods showed no significant differences in cecal intubation time, withdrawal time, and total operation time. What's more, the CLB group had a slightly shorter time for the first endoscopic clip securement (median 1.8 min vs. 3.7 min, P = 0.006). There were no significant differences in the incidence of adverse events between the two groups, and no severe adverse events were reported.

CONCLUSION: Both modified colonoscopically guided fecal microbiota transplantation catheter placement methods demonstrated safety and effectiveness in securing the FMT catheter, meeting the needs of patients requiring multiple FMT treatments over a short period. However, further validation through large-scale randomized controlled trials is needed.}, } @article {pmid41113141, year = {2025}, author = {Waseem, MH and Abideen, ZU and Shoaib, A and Rehman, N and Osama, M and Sajid, B and Ahmad, R and Fahim, Z and Ansari, MW and Aimen, S and Cheema, AH and Thada, PK}, title = {Fecal Microbiota Transplantation for Treatment of Parkinson's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.}, journal = {Journal of central nervous system disease}, volume = {17}, number = {}, pages = {11795735251388781}, pmid = {41113141}, issn = {1179-5735}, abstract = {BACKGROUND: Emerging evidence has indicated gut dysbiosis as a potential modifiable contributor to the pathogenesis of Parkinson's disease (PD). Fecal microbiota transplantation (FMT), a microbiome-centric model aimed at modulating the intestinal microbial taxa, represents a novel therapeutic approach. However, its safety and efficacy profile in improving PD symptoms remains inadequately researched.

METHODS: PubMed, ScienceDirect, and the Cochrane Central Registry were searched to retrieve relevant articles from inception till February 2025. Risk ratios (RR) and Mean differences (MD), along with 95% confidence intervals (CI), were pooled under the random-effect model for dichotomous and continuous outcomes, respectively. The primary outcomes of interest were change in Movement Disorder Society Unified Parkinson's Disease Rating Scale part 1 (MDS-UPDRS 1), change in MDS-UPDRS 2. Secondary endpoints of interest were change in MDS-UPDRS 3 (on medication), change in MDS-UPDRS 3 (off medication), change in MDS-UPDRS 4, change in Irritable Bowel Severity Scoring System (IBS-SSS), change in Montreal Cognitive Assessment (MoCA), change in Parkinson Disease Questionnaire Summary Index (PDQ-39 SI), and GI adverse events. The Cochrane Risk of Bias 2.0 (RoB 2.0) tool was used for the quality assessment of the included randomized controlled trials (RCTs). A Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessment was done for the certainty of evidence.

RESULTS: This systematic review and meta-analysis included 145 patients across 3 RCTs. FMT and placebo were comparable regarding the primary outcomes that include MDS-UPDRS Part I (MD = -0.36; 95% CI:[-2.18,1.45]; P = .70; I[2] = 33%), Part II (MD = -0.46; 95% CI:[-1.91,0.99]; P = .53; I[2] = 0%). The secondary outcomes, involving MDS-UPDRS Part III on-medication (MD = 1.41; 95% CI:[-2.14,4.42]; P = .50; I[2] = 17%), Part III off-medication (MD = 1.26; 95% CI:[-2.27,4.79]; P = .48; I[2] = 0%), and Part IV (MD = -0.39; 95% CI:[-1.63,0.85]; P = .54; I[2] = 24%) were also comparable between the two groups. No significant changes were observed in IBS-SSS (MD = -15.91; 95% CI:[-63.17,31.89]; P = .51; I[2] = 76%), PDQ-39 SI (MD = -2.13, 95% CI:[-5.62,1.36]; P = .23; I[2] = 0%), and MOCA scores (MD = 0.11; 95% CI:[-1.34,1.57]; P = .88; I[2] = 68%). However, the FMT group had more frequent adverse gastrointestinal events (RR = 3.32; 95% CI: [1.01,10.87]; P = .05; I[2] = 39%).

CONCLUSION: FMT shows no evidence of superiority compared to placebo. Variations in the findings of existing studies suggest that donor fecal composition, host-microbiota interactions, and methodological heterogeneity may determine outcomes. Further RCTs employing tailored microbiota and standardized endpoint metrics are required to establish a correlation between FMT and PD.}, } @article {pmid41112298, year = {2025}, author = {Ma, T and Zhang, T and Peng, C and Liu, K and Xiong, Y and Chen, K and Peng, N and Wei, Z and Kuang, J and Ou, L}, title = {Immune cells: the key mediator between the gut microbiota and osteoporosis.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1680021}, pmid = {41112298}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Osteoporosis/immunology/microbiology/metabolism/therapy/etiology ; Animals ; Bone and Bones/immunology/metabolism ; Probiotics ; }, abstract = {As the body's largest immunological interface, the intestine harbors a complex ecosystem of gut microbiota (GM) that orchestrates mucosal immune maturation while sustaining local immunological equilibrium. Emerging evidence reveals the gut's influence on skeletal homeostasis via neuro-immune-endocrine pathways-termed the gut-bone axis-though its mechanistic intricacies remain incompletely defined. Since the concept of osteoimmunology was proposed in 2000 by Arron & Choi, immune-skeletal interactions have garnered significant research traction. Immune cells primarily contribute to the maintenance of bone homeostasis through the release of pro- and anti-inflammatory factors. Consequently, the immune system represents a crucial intermediary in understanding the relationship between GM and metabolic bone diseases. This review synthesizes the interrelationships among gut microbiota, immune cells, and osteoporosis, and elucidates how GM modulate bone metabolism in osteoporosis through this critical intermediary. Furthermore, building upon the microbiome-immune-bone axis, we highlight several emerging microbiota-targeted interventions-such as probiotics, prebiotics, dietary modifications, fecal microbiota transplantation, and engineered microbes-and evaluate their clinical translational potential, with the aim of advancing diagnostic and therapeutic strategies for metabolic bone disorders.}, } @article {pmid41112050, year = {2025}, author = {Wang, W and Bu, N and Cao, H and Chen, N and Chen, W and Cheng, L and Cui, B and Dai, L and Gao, H and Guo, M and He, X and Hu, J and Jiang, C and Jiang, X and Li, J and Li, P and Li, W and Liao, W and Liu, H and Liu, J and Liu, L and Liu, S and Liu, X and Lv, M and Ma, Y and Man, C and Pi, Z and Ren, Q and Sang, L and Sun, Z and Suo, H and Tan, Y and Tao, W and Wang, G and Wang, J and Wang, L and Wang, X and Wang, X and Wang, Y and Wu, K and Wu, R and Wu, Z and Xiao, X and Xiang, B and Yang, S and Yi, H and Yu, H and Yu, J and Zeng, Y and Zhai, H and Zhai, Q and Zhang, C and Zhang, G and Zhang, J and Zhang, W and Zhao, F and Zhao, L and Zhou, H and Zhu, L and Lan, C and Zhang, H and Zhu, S and Zhang, F}, title = {Shaping the future of probiotics, live biotherapeutic products, and fecal microbiota transplantation: 30 scientific recommendations from the CHINAGUT Conference.}, journal = {iMeta}, volume = {4}, number = {5}, pages = {e70083}, pmid = {41112050}, issn = {2770-596X}, abstract = {The 2025 CHINAGUT Conference has assembled a panel of 63 experts (30 scientists, 26 physicians, and 7 corporate R&D personnel) collaborated in three groups to present 30 scientific recommendations to advance probiotics, live biotherapeutic products, and fecal microbiota transplantation, addressing key issues on standardization, translation, supervision, regulation, and regulatory harmonization. These interdisciplinary guidelines aim to synthesize cutting-edge knowledge and practical needs to transform microbiota-based treatments from applications into precision-driven medical solutions, and serve as reference by scientific researchers, medical educators, pharmaceutical enterprises, clinicians, food and drug administrations, policymakers, and patients.}, } @article {pmid41112042, year = {2025}, author = {Lin, A and Xiong, M and Jiang, A and Huang, L and Wong, HZH and Feng, S and Zhang, C and Li, Y and Chen, L and Chi, H and Zhang, P and Ye, B and Zhang, H and Zhang, N and Zhu, L and Mou, W and Shen, J and Li, K and Xu, W and Ying, H and Zhang, C and Zeng, D and Xie, J and Deng, X and Wang, Q and Xu, J and Shi, W and Qi, C and Qu, C and Huang, X and Hajdu, A and Li, C and Peng, C and Cao, X and Pei, G and Zhang, L and Huo, Y and Xu, J and Glaviano, A and Szöllősi, AG and Bian, S and Li, Z and Tang, H and Tang, B and Liu, Z and Zhang, J and Miao, K and Cheng, Q and Wei, T and Yuan, S and Luo, P}, title = {The microbiome in cancer.}, journal = {iMeta}, volume = {4}, number = {5}, pages = {e70070}, pmid = {41112042}, issn = {2770-596X}, abstract = {The human microbiome is now recognized as a central regulator of cancer biology, intricately shaping tumor development, immune dynamics, and therapeutic response. This comprehensive review delineates the multifaceted roles of bacteria, viruses, and fungi in modulating the tumor microenvironment and systemic immunity across diverse cancer types. We synthesize current evidence on how microbial dysbiosis promotes carcinogenesis via chronic inflammation, metabolic reprogramming, genotoxic stress, immune evasion, and epigenetic remodeling. This review emphasizes organ-specific microbiome signatures and highlights their potential as non-invasive biomarkers for early detection, treatment stratification, and prognosis. Furthermore, we explore the impact of intratumoral microbiota on cancer therapies, uncovering how microbial metabolites and host-microbe interactions shape therapeutic efficacy and resistance. Finally, advances in microbiome-targeted strategies, such as probiotics, fecal microbiota transplantation, and engineered microbes offer new avenues for adjunctive cancer therapy. This review provides a roadmap for future investigation and underscores the transformative promise of microbiome modulation in cancer prevention and treatment.}, } @article {pmid41111893, year = {2025}, author = {Fu, Z and Yu, T and Meng, C and Zhang, G and Huang, S and Li, Y and Fu, L and Deng, Z}, title = {Tortoise Oligopeptides Augment Cyclophosphamide's Antitumor Activity Through Dual Modulation of Therapeutic Efficacy and Hematologic Toxicity.}, journal = {Food science & nutrition}, volume = {13}, number = {10}, pages = {e71078}, pmid = {41111893}, issn = {2048-7177}, abstract = {Cyclophosphamide (CTX) is a widely used chemotherapeutic agent, but its efficacy is often limited by leukopenia, a common adverse effect for which effective preventive strategies are currently lacking. In this study, oligopeptides were prepared from a blend of three edible tortoise species (Cuora trifasciata, Mauremys mutica, and Chinemys reevesii) and evaluated for their potential to alleviate CTX-induced leukopenia. The resulting Tortoise Oligopeptides (TOPs) were characterized primarily as small molecules with molecular weights under 5 kDa and peptide lengths between 4 and 15 amino acids, rich in glycine, glutamic acid, and proline. In a mouse model, TOPs administration significantly ameliorated CTX-induced leukopenia in a dose-dependent manner, attenuated pathological damage in the spleen and femur, and correlated with elevated serum levels of IL-4, IL-1β, TNF-α, and IFN-γ. In CTX-treated tumor-bearing mice, TOPs not only reduced leukopenia but also enhanced the antitumor efficacy of CTX. Correlation analyses linked leukocyte recovery to increased relative abundance of gut microbiota genera such as Colidextribacter, Tyzzerella, Prevotellaceae_UCG_001, and Rikenella. KEGG pathway analysis and fecal microbiota transplantation (FMT) experiments indicated that TOPs alleviate CTX-induced granulocytopenia partly through modulation of the gut microbiota. Additionally, LC-MS/MS sequencing combined with bioinformatic prediction and molecular docking identified several peptides-including PAIPAPPVGPGPK, FSFPTLPF, and PGLPFHP-with high binding affinity to key tumor targets (BCL-2, MDM2, EGFR), suggesting intrinsic antitumor properties. These findings indicate that TOPs may serve as a specialized medical food to mitigate CTX-induced leukopenia through multimodal mechanisms involving immunonutrition, gut microbiota regulation, and direct antitumor peptide effects.}, } @article {pmid41111149, year = {2025}, author = {Cai, K and Chen, Z and Wu, J and Wang, Q and Zhou, X and Pan, B and Xie, Z and Li, P and Chen, F and Chen, H and Liao, Q}, title = {Qing-Kai-Ling oral liquid alleviates non-alcoholic fatty liver disease via remodeling gut microbiota and activating AMPK/ACC1 axis.}, journal = {Chinese medicine}, volume = {20}, number = {1}, pages = {177}, pmid = {41111149}, issn = {1749-8546}, support = {2023B03J1382//Guangzhou Science and Technology Program/ ; 2022ZD004//Nansha Science and Technology Program/ ; 2024A1515011747//Guangdong Basic and Applied Basic Research Foundation/ ; }, abstract = {BACKGROUND: Qing-Kai-Ling (QKL) oral liquid, evolving from a classical Chinese formula known as An-Gong-Niu-Huang pills, has demonstrated hepatoprotective, lung-protective, and gut microbiota-modulating properties. However, its efficacy in preventing high fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and its relationship with gut microbiota and hepatic inflammation remain unclear.

PURPOSE: The study aims to investigate whether QKL can prevent HFD-induced NAFLD, focusing on the mechanistic role of gut microbiota, microbial metabolites, and hepatic inflammation.

METHODS: QKL was subjected to extraction and chemical profiling to identify its active compounds. In vivo studies were conducted in HFD-fed mice to assess the effects of QKL on hepatic lipid accumulation, inflammation, gut microbiota composition, SCFAs production, intestinal permeability, body weight, and fat mass.

RESULTS: Chemical analysis revealed that the major components of QKL are gallic acid, corilagin, and chebulagic acid. QKL administration (12.33 and 24.66 mL/kg) for 8 weeks significantly reduced hepatic steatosis, serum lipid profiles (TG, LDL-C), and body weight in high-fat diet-induced NAFLD mice, while improving glucose tolerance and intestinal barrier integrity. Gut microbiota analysis revealed QKL enriched beneficial taxa (e.g., Akkermansia, Bacteroides) and suppressed pathobionts (e.g., Lachnospiraceae NK4A136_group), effects replicated through faecal microbiota transplantation from QKL-treated donors. QKL upregulated intestinal gene GPR41/43 and hepatic protein GPR135 expression, enhanced SCFAs production (acetic, propionic, and butyric acids), and activated AMPK/ACC1 signaling to suppress lipogenesis and promote lipid oxidation. Untargeted metabolomics demonstrated QKL restored hepatic fatty acid metabolism by reducing palmitic acid and arachidonic acid accumulation.

CONCLUSION: These findings established QKL as a microbiota-modulating therapeutic agent for NAFLD through SCFA-AMPK/ACC1 axis activation, providing a foundation for developing QKL-based treatments.}, } @article {pmid41110523, year = {2025}, author = {Li, R and Liu, J and Ye, F and He, S and Huang, J and Zhou, M and Xie, Q and Liu, Z and Cheng, W and Wang, G and Deng, W and Wang, X and Yang, T and Liang, Z and Hu, F and Huang, W and Cai, M and Xie, L and Zhang, W and Gong, S and Chen, Y and Wang, Y and Lin, L and Zhu, K}, title = {Microbial metabolism dysfunction induced by transarterial chemoembolization aggravates postprocedural liver injury in HCC.}, journal = {Journal of hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhep.2025.10.008}, pmid = {41110523}, issn = {1600-0641}, abstract = {BACKGROUND & AIMS: Transarterial chemoembolization (TACE) is widely used for treating unresectable hepatocellular carcinoma (HCC). Liver injury induced by TACE (TACE-LI) is the most common complication of TACE which limits long-term outcomes of HCC. Beyond traditional cognition of the direct damage induced by TACE on normal liver tissue, deeper mechanism underlying TACE-LI remains unclear. We aimed to further elucidate the unclear relationship between gut microbiota disturbances and TACE-LI.

METHODS: Microbial multi-omics analysis, genetically engineered bacteria and transcriptomics were used to study microbiota disturbances and host responses in TACE-LI.

RESULTS: Rats with gut microbiota depleted by antibiotics and rats that received fecal transplants from donor rats or HCC patients that had undergone TACE showed more severe TACE-LI. Limosilactobacillus reuteri (L. reuteri) abundance was significantly reduced in TACE-treated rats and patients with HCC. Reduced L. reuteri abundance after TACE led to decreased levels of tryptophan metabolite indole-3-lactic acid (ILA), while administration of live L. reuteri or ILA provided effective protection against TACE-LI. Mechanistically, L. reuteri relied on the key enzyme phenyllactate dehydrogenase (fldH) to generate ILA, which inhibited the ATPase activity of heat shock protein 90 to deactivate NOD-like receptor protein 3-inflammasome in macrophages and suppressed hepatic pro-inflammatory response. Reduced levels of L. reuteri and ILA were correlated with aggravated LI and poor overall survival in TACE-treated patients with HCC.

CONCLUSIONS: This is the first study to identify gut microbiota disturbance, i.e., deficiency of L. reuteri metabolite ILA, as significant cause of TACE-LI. L. reuteri and ILA administration serves as promising therapeutic approach for TACE-LI, which is crucial for reducing TACE adverse effects to achieve better prognosis in HCC.

IMPACT AND IMPLICATIONS: The majority of patients with hepatocellular carcinoma (HCC) are diagnosed losing the chance of surgical resection. Transarterial chemoembolization (TACE) is widely used for treating unresectable HCC; however, its long-term outcome is significantly limited by its main complication, i.e., liver injury (LI). In addition to traditional cognition of the direct liver damage of the ischemic necrosis or regional chemotherapy induced by TACE, the deeper mechanisms underlying TACE-induced LI (TACE-LI) remain largely unclear. Gut microbiota can modulate various liver diseases but its exact role in TACE-LI has not been reported. We found that TACE could disturb the gut microbiota. This disturbance was characterized by reduced levels of Limosilactobacillus reuteri (L. reuteri) and its metabolite indole-3-lactic acid (ILA), which were correlated with aggravated TACE-LI and poor overall survival in HCC. Administration of L. reuteri or ILA significantly improved TACE-LI by inhibiting the inflammation of macrophages. Our study is the first report highlighting gut microbiota disturbances as an important cause of TACE-LI; administration of L. reuteri or ILA represents a viable and secure strategy for preventing TACE-LI, thereby reducing the adverse effects of TACE and yielding better prognoses in patients with HCC.}, } @article {pmid41110352, year = {2025}, author = {Yuan, Y and Hu, J and Lu, X and Han, H and Wang, M and Zhang, W and Jiao, Y and Li, Y and Lin, Z and Liang, C and Yu, Y and Xie, C and Li, J and Mao, T}, title = {Oral rhein attenuate nonalcoholic steatohepatitis in mice through the modulation of gut microbiota and Th17 cell differentiation.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {148}, number = {}, pages = {157409}, doi = {10.1016/j.phymed.2025.157409}, pmid = {41110352}, issn = {1618-095X}, abstract = {BACKGROUND: Non-alcoholic steatohepatitis (NASH) is an important clinical issue and a challenge in the field of global public health. However, there are very few clinically approved drugs that can effectively treat NASH. Rhein is a natural organic compound with anti-inflammatory and antioxidant properties, but the specific role and mechanism on NASH remain unexplored.

PURPOSE: This study investigated the role and associated mechanism of rhein in NASH mice.

METHODS: The effects of rhein on lipid accumulation were evaluated in NASH mice through systemic signs of obesity, biochemical parameters, and histological changes. Network pharmacology was employed to determine the main bioactive compounds and key targets of rhein for the NASH treatment. Additionally, antibiotics treatment and fecal microbiota transplantation (FMT) were performed to investigate the role of microbiota in the treatment of NASH with rhein. Bacterial 16S rRNA amplicon sequencing, LC-MS/MS analysis and flow cytometric were employed to investigate the mechanisms underlying rhein's regulatory effects on gut microbiota, BA metabolism and immune balance. Finally, in vitro cell experiments were conducted to explore the effects of metabolites on Th17 cell differentiation.

RESULTS: Our results showed that mice treated with rhein showed a significant alleviating effect from high-fat diet (HFD)-induced liver lipid accumulation and pathological changes compared to those in HFD group. The protective effects of rhein are gut microbiota dependent, as demonstrated by fecal microbiome transplantation and antibiotics treatment. Microbiota transferred from rhein-treated mice displayed a similar role in attenuating hepatic lipid deposition as rhein on NASH in mice, and depletion of the gut microbiota through antibiotics treatments diminished the protective effects of rhein on NASH mice. Moreover, the results from bacterial 16S rRNA sequencing suggested that rhein partially attenuated HFD-induced gut dysbiosis in NASH mice. Network pharmacology analyses was implemented and showed that Th17 cell differentiation might be the potential target in the treatment of rhein against NASH, which was confirmed by flow cytometric analysis showing markedly decrease of the percentage of Th17 cells, corresponded with upregulated Treg cells in rhein-treated NASH mice. Furthermore, targeted bile acid metabolomics analysis showed that supplement with rhein greatly increased the levels of primary bile acids β-MCA and AlloLCA, positively correlated with the relative abundances of Bifidobacterium_choerinum, which may play the key role by which rhein-altered gut microbiota promoted the restoration of Th17/Treg balance in NASH mice. Subsequent in vitro experiments confirmed that AlloLCA directly inhibits Th17 cell differentiation, with suppression of glycolysis potentially serving as the underlying mechanism for the immunomodulatory effects of AlloLCA.

CONCLUSIONS: Collectively, our results suggested that orally administrated rhein reduced hepatic lipid deposition through the modulation of dysregulated gut microbiota and bile acids metabolism, thus regulating Th17/Treg immune balance. This study uncovers a novel mechanistic axis in NASH pathogenesis and providing new research directions for microbiota-targeted clinical strategies.}, } @article {pmid41109696, year = {2025}, author = {Bunchorntavakul, C and Reddy, KR}, title = {Current Status and Future Directions in the Pharmacologic Management of Cirrhosis.}, journal = {Clinics in liver disease}, volume = {29}, number = {4}, pages = {657-672}, doi = {10.1016/j.cld.2025.06.003}, pmid = {41109696}, issn = {1557-8224}, mesh = {Humans ; *Liver Cirrhosis/drug therapy/complications ; Adrenergic beta-Antagonists/therapeutic use ; Angiotensin Receptor Antagonists/therapeutic use ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Anticoagulants/therapeutic use ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Fecal Microbiota Transplantation ; Albumins/therapeutic use ; Rifaximin ; }, abstract = {In recent years, the necessity for pharmacologic treatments to mitigate the risk of hepatic decompensation has been highlighted, with non-selective beta-blockers identified as the most effective option. However, a significant therapeutic gap persists, and additional or alternative treatments have been proposed, including statins, rifaximin, albumin, anticoagulants, angiotensin receptor blockers, granulocyte-colony stimulating factor, and fecal microbial transplant. According to the data from limited clinical trials, these pharmacotherapies offer promising possibilities; nonetheless, additional investigations, particularly randomized controlled trials, are required, in some instances, prior to their incorporation into routine clinical practice.}, } @article {pmid41109693, year = {2025}, author = {Wagh, RS and Shasthry, SM and Sarin, SK}, title = {New Approaches to Alcohol-Associated Hepatitis.}, journal = {Clinics in liver disease}, volume = {29}, number = {4}, pages = {595-626}, doi = {10.1016/j.cld.2025.06.012}, pmid = {41109693}, issn = {1557-8224}, mesh = {Humans ; *Hepatitis, Alcoholic/therapy ; Liver Transplantation ; Fecal Microbiota Transplantation ; Plasma Exchange ; Granulocyte Colony-Stimulating Factor/therapeutic use ; }, abstract = {Severe alcohol-associated hepatitis (SAH) remains a difficult-to-treat severe liver ailment with limited therapeutic options and high mortality. The article reviews new data to help identify the steroid non-responders at the baseline to reduce the risk of infections and increased mortality. New information on the use of growth factors, such as granulocyte-colony stimulating factor, plasma exchange, and fecal microbiota transplantation, has been provided to choose as a monotherapy or with steroids for SAH. Early selection for liver transplantation after careful ethical considerations and risks of recidivism post-transplant can help improve survival upto 70% to 80%.}, } @article {pmid41109415, year = {2025}, author = {Alasbly, G and Alotaishan, S and Algindan, Y and Khattab, R}, title = {Risk Factors for Nosocomial Clostridioides Difficile Infection-Induced Diarrhea in Patients Receiving Enteral Feeding: A Scoping Review.}, journal = {The Journal of hospital infection}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhin.2025.10.005}, pmid = {41109415}, issn = {1532-2939}, abstract = {BACKGROUND: Nosocomial Clostridioides difficile infection (CDI)-induced diarrhea is a major healthcare-associated infection, particularly in critically ill patients. Antibiotic use and disruptions in gut microbiota are known risk factors, and the role of enteral feeding (EF) requires further exploration.

AIM: To examine risk factors for nosocomial CDI-induced diarrhea in hospitalized patients receiving enteral feeding and assess the impact of EF-related factors on CDI outcomes.

METHODS: This scoping review synthesized evidence from recent studies evaluating CDI risk in hospitalized patients on EF, focusing on antibiotic exposure, hospitalization duration, EF type, and gut microbiota alterations.

FINDINGS: Key risk factors identified include prolonged hospitalization, antibiotic use, and feeding tube placement, all of which may facilitate C. difficile colonization. Altered gut microbiota, characterized by reduced bacterial diversity, was associated with prolonged EF and lack of fiber in formulas. Fiber-enriched and polymeric formulas may support microbial balance, while the effects of probiotics on CDI prevention were inconsistent. Management strategies emphasized include antibiotic stewardship, infection control, and optimized nutrition. Fecal microbiota transplantation and bezlotoxumab show promise in reducing recurrence. However, evidence remains limited on whether specific EF modalities (e.g., continuous vs. intermittent feeding, polymeric vs. elemental formulas) directly affect CDI risk.

CONCLUSION: EF may contribute to CDI risk through its impact on gut microbiota and related factors. While certain EF strategies show potential benefits, further research is needed to determine their role in CDI prevention and to develop evidence-based nutritional guidelines for at-risk patients.}, } @article {pmid41108334, year = {2025}, author = {Chang, A and Oh, J and Shin, A and Oser, M and Manitius, N and Ghaffari, A and Limketkai, BN}, title = {Similar Symptoms, Distinct Syndromes: Multi-modal Approach to the Patient with an IBD-IBS Overlap.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {41108334}, issn = {1573-2568}, abstract = {Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are distinct gastrointestinal conditions, but they frequently share overlapping clinical symptoms such as abdominal pain, bloating, and altered bowel habits. IBD is defined by the presence of chronic immune-mediated inflammation, and IBS is characterized by gastrointestinal symptoms in the absence of endoscopic and histologic inflammation. When patients with IBD continue to experience IBS-like symptoms despite remission of inflammation, this phenomenon is commonly referred to as IBD-IBS overlap. These patients pose diagnostic and therapeutic challenges, as symptom persistence may reflect lingering immune activation, disrupted barrier function, visceral hypersensitivity, gut-brain axis dysfunction, or microbiome alterations. This review synthesizes emerging evidence on the shared mechanisms underlying IBD and IBS and outlines a multimodal treatment approach that includes pharmacologic management, dietary interventions, mind-body therapies, and microbiome-directed strategies such as probiotics and fecal microbiota transplantation.}, } @article {pmid41107170, year = {2025}, author = {Taylor, NA and Sivam, S and van Dorst, J and Coffey, MJ and Visser, S and Haber, P and Volovets, A and Ooi, CY}, title = {Stool and symptom testing in ColoREctal Evaluation for Neoplasia in Cystic Fibrosis (SCREEN-CF).}, journal = {Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jcf.2025.09.008}, pmid = {41107170}, issn = {1873-5010}, abstract = {BACKGROUND: People with cystic fibrosis (pwCF) have increased colorectal cancer (CRC) risk. Colonoscopy is recommended, yet CF comorbidities increase complexity and risk.

METHODS: We conducted a prospective, observational study of pwCF meeting colonoscopy screening guidelines at an Australian centre (2019 - 2023). Immunochemical faecal occult blood test (iFOBT), faecal calprotectin (FC), and faecal tumour pyruvate kinase isoenzyme type M2 (TuM2-PK) were evaluated for detecting adenomatous polyps and malignant ileocolonic lesions in pwCF. Stools were collected within 3 months of colonoscopy. Diagnostic performance and optimal cut-offs were calculated.

RESULTS: Among 49 participants [mean (SD) age 47.8 (8.2) years; 53 % female], 12 (24.5 %) were post-solid organ transplant, 10 (20.4 %) had > 3 months of triple modulator therapy at stool testing, 12 (24.5 %) had adenomatous polyps and 2 (4 %) had ileocolonic malignancy. Malignancies were in non-transplanted individuals, in the terminal ileum (age 43) and hepatic flexure/ascending colon (age 48). Higher BMI (>23.5 kg/m²) was associated with abnormal colonoscopy (p = 0.03). iFOBT, FC and TuM2PK demonstrated excellent predictive performance for malignancy (AUC 0.93, 1.00, 0.83; all p < 0.05). Only FC had acceptable predictive performance for pre-malignant lesions (AUC 0.73; p = 0.008). For adenomatous polyps, FC ≤100 µg/g achieved a sensitivity of 91.7 % and an NPV of 95.5 %. For ileocolonic malignancy, FC ≥1000 µg/g showed 100 % sensitivity and specificity (p = 0.0009).

CONCLUSION: CRC screening in pwCF is critical given the high prevalence of neoplasia. Alternative non-invasive screening may support risk stratification among individuals with comorbidities, or reluctance, though performance could be influenced by CFTR modulator therapy.}, } @article {pmid41106539, year = {2025}, author = {Wang, R and Tang, D and Wu, L and Ou, L and Ding, L and Jiang, J and Wu, Y}, title = {Bielong Ruangan decoction inhibits tumor growth and improves immune response in a hepatocellular carcinoma mouse model through gut microbiota.}, journal = {The international journal of biochemistry & cell biology}, volume = {}, number = {}, pages = {106873}, doi = {10.1016/j.biocel.2025.106873}, pmid = {41106539}, issn = {1878-5875}, abstract = {Hepatocellular carcinoma (HCC) is a leading cause of cancer fatality worldwide. It is closely linked to the gut-liver axis, which plays a crucial role in nutrient metabolism, immune responses, and the biotransformation of bacterial metabolites. Traditional Chinese Medicine (TCM), as an adjuvant treatment, is important in the treatment course of HCC. This study aimed to explore the effects of Bielong Ruangan decoction (BLRG) on HCC. It is a traditional Chinese medicine formula used for liver fibrosis and cancer. The study focuses on its impact on gut microbiota and associated mechanisms. An orthotopic liver transplantation model was established in mice in the presence or absence of BLRG treatment, and the therapeutic effects of BLRG were evaluated. BLRG significantly inhibited tumor growth in an orthotopic liver transplantation mouse model, by reducing tumor size, liver weight, volume, Ki-67, and serum AFP levels. It also enhanced intestinal barrier functions by lowering serum LPS levels, increasing intestinal mucus thickness, and boosting ZO-1 and occludin mRNA levels. Moreover, BLRG modulated immune responses, decreasing inflammatory cytokines (IL-10 and IL-1β) while increasing anti-tumor cytokines (IFN-α, IFN-γ, and IL-2). A notable shift in gut microbiota composition was observed, accompanied by a decrease in Mucispirillum_sp. and Helicobacter_typhlonius post-treatment. Serum metabolomic profiling confirmed these findings and revealed a positive correlation between Mucispirillum and triglycerides (TG). Fecal Microbiota Transplantation (FMT) experiments further highlighted the gut microbiota's role in mediating BLRG's anti-tumor effects, demonstrating decreased tumor metrics and improved serum AFP levels, intestinal permeability, and immune responses in recipient mice. These results underscore BLRG's potential as an adjunctive therapeutic agent in liver cancer, demonstrating its ability to modulate tumor growth, gut microbiota, and immune responses, thereby potentially reshaping the HCC therapeutic landscape.}, } @article {pmid41106199, year = {2025}, author = {Yu, Z and Wu, J and Han, J and Wang, L and Lu, R and Chen, J and Wang, K and Shi, Z}, title = {Triclosan induced obesity via gut microbiota dysbiosis and butyrate reduction.}, journal = {Ecotoxicology and environmental safety}, volume = {305}, number = {}, pages = {119227}, doi = {10.1016/j.ecoenv.2025.119227}, pmid = {41106199}, issn = {1090-2414}, abstract = {Triclosan (TCS) can influence energy metabolism and is a potential obesogen. However, its underlying mechanisms remain largely unknown. This study investigated how low-dose TCS exposure (0.5 mg/kg/day) disrupts energy metabolism in Sprague-Dawley rats. TCS increased body weight, visceral fat, liver lipid accumulation, and serum triglyceride levels. It also promoted hyperphagia by altering hypothalamic appetite regulation, activating orexigenic neuropeptide Y neurons and suppressing anorexigenic pro-opiomelanocortin neurons. Furthermore, TCS may reduce brown adipose tissue thermogenesis, as indicated by decreased mitochondrial uncoupling protein 1 and tyrosine hydroxylase. These metabolic effects were blocked by subdiaphragmatic vagotomy, confirming gut-brain neural circuit involvement. Mechanistically, TCS reduced gut microbial diversity and butyrate levels. Crucially, both fecal microbiota transplantation from control rats and butyrate supplementation reversed TCS-induced metabolic dysregulation. These findings reveal that TCS-induced gut dysbiosis and butyrate reduction as key drivers of metabolic disturbances and offer insights into the role of environmental chemicals in obesity and potential therapeutic strategies targeting the gut microbiota and butyrate.}, } @article {pmid41105383, year = {2025}, author = {Carlsen, A and Steinsbø, Ø and Kvaløy, JT and Aabakken, L and Bolstad, N and Warren, DJ and Karlsen, L and Lundin, KEA and Omdal, R and Grimstad, T}, title = {Optimizing serum adalimumab levels in maintenance therapy via proactive therapeutic drug monitoring improves markers of disease activity in Crohn's disease.}, journal = {Scandinavian journal of gastroenterology}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/00365521.2025.2573725}, pmid = {41105383}, issn = {1502-7708}, abstract = {OBJECTS: The benefit of a proactive therapeutic drug monitoring (TDM) strategy in patients with inflammatory bowel disease receiving biological therapy remains disputed. We aimed to evaluate whether optimizing serum adalimumab levels (s-ADL), guided by proactive TDM, is associated with improved markers of disease activity in patients with Crohn's disease.

MATERIALS AND METHODS: In this longitudinal cross-sectional study, 72 patients receiving adalimumab maintenance therapy from our outpatient clinic, were included. Patients underwent five study visits at 3-month intervals over one year. Disease activity was assesed using the Harvey-Bradshaw Index, plasma C-reactive protein (CRP), and fecal calprotectin. s-ADL levels were measured at each visit, and dosing was adjusted to maintain a therapeutic target range of 5.0-12.0 mg/L.

RESULTS: At baseline, subtherapeutic s-ADL levels were associated with higher CRP levels (p = 0.03), and in these patients' drug levels increased significantly over the study (p = 0.001), whereas CRP levels decreased (p = 0.03). Longitudinal analysis demonstrated that higher s-ADL levels (≥5.0 mg/L) were associated with lower CRP levels (p = 0.008) and lower HBI scores (p = 0.03). Additionally, lower CRP- and fecal calprotectin levels at any visit were associated with higher s-ADL levels at the preceding visit (p = 0.04 for both). Lower CRP levels were also associated with higher s-ADL levels using 7.0 mg/L as the therapeutic threshold in longitudinal analyses (p = 0.003).

CONCLUSION: Proactive TDM-guided optimization of s-ADL levels in Crohn's disease patients on adalimumab maintenance therapy was associated with the modest but significant improvements in markers of disease activity over one year of follow-up.}, } @article {pmid41104042, year = {2025}, author = {Yassin, LK and Skrabulyte-Barbulescu, J and Alshamsi, SH and Saeed, S and Alkuwaiti, SH and Almazrouei, S and Alnuaimi, A and BaniYas, S and Aldhaheri, D and Alderei, M and Shehab, S and Hamad, MIK}, title = {The microbiota-gut-brain axis in mental and neurodegenerative disorders: opportunities for prevention and intervention.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1667448}, pmid = {41104042}, issn = {1663-4365}, abstract = {The microbiota-gut-brain axis (MGBA) is increasingly recognized as a critical regulator of brain health, influencing both neurodevelopment and age-related neurological decline. Disruptions in this axis, driven by gut dysbiosis, have been implicated in the pathogenesis of a wide range of neurodegenerative and neuropsychiatric disorders. This review synthesizes current evidence linking microbiota alterations to Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and stroke-including post-stroke cognitive impairment (PSCI), as well as major depressive disorder (MDD), bipolar disorder (BD), anxiety disorders, post-traumatic stress disorder (PTSD), and chronic fatigue syndrome (CFS). Common findings include reduced microbial diversity, depletion of short-chain fatty acid (SCFA)-producing genera, and enrichment of pro-inflammatory taxa. These changes contribute to neuroinflammation, blood-brain barrier (BBB) dysfunction, microglial activation, and neurotransmitter imbalances. The review further explores the neurotoxic effects of external factors such as radiation and xenobiotics on the MGBA. Despite disorder-specific variations, shared microbial and immunological mechanisms emerge across the spectrum of conditions. Importantly, we present current and emerging strategies aimed at restoring gut-brain communication, including dietary interventions such as fiber-rich and Mediterranean diets, SCFA supplementation, probiotics, and fecal microbiota transplantation (FMT). These approaches show promise in alleviating cognitive and emotional symptoms, modulating immune responses, and potentially slowing disease progression. By integrating mechanistic insights with therapeutic perspectives, this review underscores the gut microbiota as a modifiable factor in neuropsychiatric and neurodegenerative disease. Targeting the MGBA offers a novel, translational approach to intervention that may ultimately contribute to healthier brain aging and improved outcomes across the lifespan.}, } @article {pmid41103946, year = {2025}, author = {Zhou, L and Li, B and Ren, J and Wang, S and Wang, J}, title = {Microbiome-mediated regulation of chemoradiotherapy response.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1659467}, pmid = {41103946}, issn = {2234-943X}, abstract = {The gut microbiota critically influences patient responses to chemoradiotherapy through bidirectional interactions with host physiology, modulating both therapeutic efficacy and toxicity. Radiotherapy and chemotherapy disrupt microbial homeostasis, exacerbating intestinal damage, systemic inflammation, and immune dysfunction, while specific commensals and metabolites enhance treatment response via metabolic reprogramming, DNA repair regulation, and immune activation. Key mechanisms include microbiota-mediated TLR/NF-κB signaling, SCFA-dependent epigenetic modifications, and microbial enhancement of immune checkpoint inhibitors. Clinical interventions such as probiotics, fecal microbiota transplantation, and targeted antibiotics demonstrate potential to mitigate toxicity and overcome resistance. This review summarizes emerging evidence on how microbial dysbiosis induced by radiotherapy and chemotherapy exacerbates intestinal damage, systemic inflammation, and immune dysfunction, while specific commensals and metabolites enhance chemoradiotherapy response via metabolic reprogramming, DNA repair modulation, and immune activation. These findings underscore the gut microbiota as a critical determinant of chemoradiotherapy precision, offering actionable targets for microbiome-guided therapeutic optimization.}, } @article {pmid41102296, year = {2025}, author = {Udomkarnjananun, S and Chuaypen, N and Metta, K and Dissayabutra, T and Sodsai, P and Kittiskulnam, P and Tangkijvanich, P}, title = {Dietary composition modulate gut microbiota and related biomarkers in patients with chronic kidney disease.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {36274}, pmid = {41102296}, issn = {2045-2322}, support = {PMU-B, grant number B36G660010//the NSRF via the Program Management Unit for Human Resources & Institutional Development, Research and Innovation (PMU-B, grant number B36G660010)/ ; }, mesh = {Humans ; *Renal Insufficiency, Chronic/microbiology/blood ; *Gastrointestinal Microbiome ; Male ; Female ; *Biomarkers/blood ; Middle Aged ; Methylamines/blood ; Cross-Sectional Studies ; Aged ; Cytokines/blood ; Feces/microbiology ; *Diet ; Dietary Fiber ; Adult ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Emerging evidence indicates gut microbiota is essential to chronic kidney disease (CKD) progression. This study investigated the association between gut microbiota profiles, plasma trimethylamine-N-oxide (TMAO), and circulating inflammatory markers in CKD patients according to dietary patterns, particularly low-protein, high-fiber (LP-HF) versus high-protein, low-fiber (HP-LF) diet. In this cross-sectional study, patients with non-dialysis CKD and healthy subjects were enrolled. Dietary patterns among participants were assessed using three-day diet records with detailed nutrient analysis. The 16 S ribosomal RNA sequencing was conducted to examine fecal gut microbiota composition. Plasma samples were analyzed for TMAO concentration and cytokine levels. A total of 135 CKD patients were recruited. A distinct shift in gut microbiota composition in CKD patients was observed compared to 19 healthy controls, particularly a significant reduction of short-chain fatty acid (SCFA)-producing bacteria. TMAO and several cytokine levels were significantly elevated in CKD patients compared to healthy subjects. Within CKD, patients with LP-HF diet displayed a greater abundance of SCFA-producing bacteria, such as the Lachnospiraceae NK4A136 group and Eubacterium ruminantium group, than those with the HP-LF diet. The HP-LF subgroup showed enriched proteolytic bacterial genera such as Klebsiella. The HP-LF subgroup also exhibited significantly higher plasma levels of TMAO, interleukin (IL)-18, and monocyte chemoattractant protein-1 (MCP-1). CKD patients displayed marked alterations in gut bacterial composition compared to healthy controls. Our results also highlighted the potential advantages of adopting a high fiber-rich and low-protein diet intake in reducing gut dysbiosis in CKD patients.}, } @article {pmid41101217, year = {2025}, author = {Liu, XL and Wu, SY and Zou, ZP and Xian, X and Wang, J and Min, L and Zhou, Y and Houf, K and Yu, Z}, title = {Characterization and intestinal pathogenicity of Proteus mirabilis isolated from broiler carcasses and processing environments.}, journal = {International journal of food microbiology}, volume = {445}, number = {}, pages = {111487}, doi = {10.1016/j.ijfoodmicro.2025.111487}, pmid = {41101217}, issn = {1879-3460}, abstract = {Proteus mirabilis, a well-known urinary tract pathogen, is increasingly recognized as a food safety concern due to its frequent detection in meat products, particularly poultry. Sporadic reports indicate gastrointestinal symptoms linked to P. mirabilis, but the relationship between its genome, antibiotic resistance, and variable pathogenicity remains unclear. In this study, 142 P. mirabilis isolates were collected from broiler carcasses and processing environments in wet markets and industrial facilities to assess contamination levels. Thirty-six representative isolates were characterized for genomic heterogeneity, antibiotic resistance, and virulence gene profiles using whole-genome sequencing and phenotypic susceptibility testing. Selected strains were further assessed for intestinal pathogenicity in a murine model. Broiler carcasses from wet markets had significantly higher contamination rates (80.77 %, 21/26) than industrial sources (41.67 %, 5/12), with all wet market samples (13/13) testing positive. Overall, 94.4 % of isolates were multidrug-resistant, with carcass isolates showing higher resistance than environmental isolates. Animal experiments demonstrated variable pathogenicity, including intestinal injury, villus disruption, epithelial shedding, goblet cell loss, inflammatory cytokine elevation, and gut dysbiosis. Dysbiosis induced by certain strains (e.g., R638) was linked to intestinal injury, as confirmed by fecal microbiota transplantation. These findings highlight P. mirabilis as a highly heterogeneous foodborne pathogen, emphasizing the need for targeted hygiene practices, particularly in wet market processing environments.}, } @article {pmid41100443, year = {2025}, author = {Shi, F and Zou, D and Zhang, L and Guo, N and Yu, J and Degen, AA and Tang, X and Ren, S and Ru, Y and Zheng, S and Zhang, Y and Wang, D}, title = {Increased urea nitrogen salvaging by a remodeled gut microbiota helps nonhibernating pikas maintain protein homeostasis during winter.}, journal = {PLoS biology}, volume = {23}, number = {10}, pages = {e3003436}, doi = {10.1371/journal.pbio.3003436}, pmid = {41100443}, issn = {1545-7885}, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; *Nitrogen/metabolism ; *Urea/metabolism ; Seasons ; *Lagomorpha/metabolism/microbiology/physiology ; Homeostasis ; *Proteostasis/physiology ; Feces/microbiology ; Diet, Protein-Restricted ; Male ; Liver/metabolism ; Herbivory ; Fecal Microbiota Transplantation ; }, abstract = {Nitrogen balance is a major challenge for herbivores when consuming a low-nitrogen diet. Gut microbiota-mediated urea nitrogen recycling facilitates protein homeostasis during times of nitrogen deficiency, yet its relevance to wild nonhibernating small mammals remains unclear. Here, through a combination of isotope tracing, metagenomics, targeted short-chain fatty acid analysis, and fecal microbiota transplantation, we investigated the effects of protein restriction in winter on urea nitrogen recycling in plateau pikas (Ochotona curzoniae) of the Qinghai-Tibetan Plateau. Hepatic urea-cycle metabolism was downregulated during winter protein restriction, accompanied by increases in beneficial bacteria with ureolytic capacity (such as the genus Alistipes), gut urease activity, and urea transporters, and acetate production, with a consequent increase in nitrogen reincorporation into the pika's protein pool. Critically, supplementing a low-protein diet with yak fecal microbiota enhanced the ureolytic capacity by increasing Alistipes abundance, revealing a critical mechanism whereby interspecies horizontal microbial transfer between sympatric species enhances host protein homeostasis. Our results reveal a functional role for the gut microbiota in urea nitrogen recycling to maintain protein balance in winter-active herbivorous small mammals and contribute to our understanding of species coexistence and mammalian adaptation to high-altitude environments. Our findings establish that microbiota-driven urea nitrogen recycling is a key adaptive strategy for protein homeostasis in winter-active herbivores. This work provides new insights into the mechanisms of mammalian adaptation to high-altitude environments and the dynamics of interspecies coexistence.}, } @article {pmid41098769, year = {2025}, author = {Li, Y and Xin, Y and Zong, W and Li, X}, title = {The role of oral microbiota in digestive system diseases: current advances and perspectives.}, journal = {Journal of oral microbiology}, volume = {17}, number = {1}, pages = {2566403}, pmid = {41098769}, issn = {2000-2297}, abstract = {The oral microbiota is intimately linked to human health and various disease states. With the advent of the Human Microbiome Project, our comprehension of the oral microbiota has substantially improved. This microbial community is not only associated with a range of oral diseases, such as dental caries and periodontal diseases, but also with numerous digestive disorders, as demonstrated by recent clinical studies. Specific bacteria residing in the oral cavity, such as Porphyromonas gingivalis, Fusobacterium species and Streptococcus species, have been shown to translocate to the gastrointestinal tract, thereby establishing a potential connection between the oral and gut microbiota. The transfer and ectopic colonization of oral microbiota within the gastrointestinal tract may contribute to both the onset and exacerbation of gastrointestinal diseases. Following the principles of dysregulation characteristics, mechanism research and innovative treatment, this paper systematically reviews the association between the oral microbiota and various digestive system diseases. This paper explores how specific oral microbiota drive digestive system diseases mechanisms and evaluates treatments including probiotics, prebiotics, fecal microbiota transplantation, and targeted antimicrobial therapies. By clarifying the oral-gut microbiota-disease link, it highlights oral microbiota monitoring as a promising tool for early detection, diagnosis, and therapy.}, } @article {pmid41097970, year = {2025}, author = {Ma, Y and Huang, J and Zhuo, Q and Shen, S and Zhang, B and Wang, H and Zhang, J and Wang, O}, title = {[Impact of high-fat diet on intestinal fat absorption and fatty acid metabolism in rats transplanted with gut microbiota from hypertriglyceridemic individuals].}, journal = {Wei sheng yan jiu = Journal of hygiene research}, volume = {54}, number = {5}, pages = {757-762}, doi = {10.19813/j.cnki.weishengyanjiu.2025.05.008}, pmid = {41097970}, issn = {1000-8020}, mesh = {Animals ; Male ; *Diet, High-Fat/adverse effects ; Rats ; *Gastrointestinal Microbiome/physiology ; Rats, Sprague-Dawley ; *Fatty Acids/metabolism ; *Fecal Microbiota Transplantation ; *Intestinal Absorption ; *Hypertriglyceridemia/metabolism/microbiology ; Fatty Acids, Volatile/metabolism ; Humans ; Feces/microbiology ; Lipid Metabolism ; }, abstract = {OBJECTIVE: To investigate the effects of fecal microbiota transplantation on fat absorption rate, fatty acid metabolic flux, and short-chain fatty acid production in germ-free Sprague-Dawley(SD) rats.

METHODS: Ten-week-old male germ-free SD rats were randomly grouped(5-6 rats/group) by body weight. Blank control: saline gavaged + germ-free basal diet. Normal control: colonized with normal-TG(≤1.7 mmol/L) human gut microbiota + germ-free basal diet. Two other groups: colonized with high-TG(>1.7 mmol/L) human gut microbiota, one on germ-free basal diet and the other on high-fat diet(40.5% fat energy). Day 0 marked colonization start. On Days 0, 2, 4, rats were gavaged with fecal bacteria(1 mL/100 g body weight). After 10-day adaptation, high-fat group started high-fat diet on Day 14. Feces were induced and collected aseptically on Days 0, 14, 21, 56, 77 for total fat(fat absorption rate), fatty acid profile, and short-chain fatty acids like butyric acid.

RESULTS: On Day 77, compared to blank control, normal control had lower body weight, fat absorption rate, and fecal palmitoleic and linoleic acids(P<0.05), but higher butyric, palmitic, arachidic, oleic, DHA, and stearic acids(P<0.05). High-TG group had higher body weight, fat absorption rate, and fecal palmitoleic and linoleic acids than normal control(P<0.05), with lower butyric, three saturated, and oleic acids(P<0.05). High-fat group had higher body weight, fat absorption rate, and fecal fatty acids than high-TG group(P<0.05). After Day 21, α-linolenic acid was undetectable in all groups.

CONCLUSION: In contrast to the positive regulation of lipid metabolism in rats by colonization with non-high-TG microbiota, colonization with high-TG microbiota disrupts lipid metabolism balance, inhibits the excretion of saturated fatty acids and oleic acid, reduces butyrate production, increases fat absorption rate, elevates the risk of obesity, and may synergize with a high-fat diet to exacerbate intestinal lipid metabolism disorders.}, } @article {pmid41097199, year = {2025}, author = {Dey, P}, title = {All That Glitters Ain't Gold: The Myths and Scientific Realities About the Gut Microbiota.}, journal = {Nutrients}, volume = {17}, number = {19}, pages = {}, doi = {10.3390/nu17193121}, pmid = {41097199}, issn = {2072-6643}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; Dysbiosis/microbiology ; Probiotics ; Diet ; Fecal Microbiota Transplantation ; }, abstract = {Gut microbial modulation through diet is central to human health and disease. Despite tremendous effort in understanding the impact of nutrients and drugs on the gut microbiota, and attempts to develop dietary strategies that facilitate gut-beneficial effects, several erroneous gut microbiota-associated concepts remain prevalent in popular belief. This article discusses widespread misconceptions about the gut microbiota, contrasting them with contemporary scientific facts. In this article, ten prevalent myths, including the obsolete 10:1 bacteria-to-human-cell ratio, the reductive categorization of microbes as 'good' or 'bad', and the discredited universal biomarker status of the Firmicutes/Bacteroidetes ratio in relation to metabolic diseases, have been debunked. Essential facts highlighting the context-dependency of the microbiome, considerable inter-individual heterogeneity, and dynamic reactivity to dietary changes are discussed. This questions the assumptions that increased diversity always signifies health, that probiotics are intrinsically safe, that fecal microbiota transplantation is a universal remedy, or that leaky gut syndrome constitutes a clearly defined diagnosis. It is highlighted that eubiosis and dysbiosis do not possess uniform criteria, and microbiome-drug interactions are extremely individualized. The gut microbiota operates as a dynamic, adaptive ecosystem, necessitating sophisticated, evidence-based methodologies for study and therapeutic application, transcending simplistic misconceptions in favor of tailored insights and therapies.}, } @article {pmid41096928, year = {2025}, author = {Yang, B and Wu, J and Hou, X and Bai, T and Liu, S}, title = {Memory in Misfire: The Gut Microbiome-Trained Immunity Circuit in Inflammatory Bowel Diseases.}, journal = {International journal of molecular sciences}, volume = {26}, number = {19}, pages = {}, doi = {10.3390/ijms26199663}, pmid = {41096928}, issn = {1422-0067}, support = {2022YFC2504005//National Key Research and Development Program of China/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Inflammatory Bowel Diseases/immunology/microbiology/therapy ; Animals ; *Immunologic Memory ; Immunity, Innate ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Trained Immunity ; }, abstract = {Inflammatory bowel disease (IBD) demonstrates chronic relapsing inflammation extending beyond adaptive immunity dysfunction. "Trained immunity"-the reprogramming of innate immune memory in myeloid cells and hematopoietic progenitors-maintains intestinal inflammation; however, the mechanism by which gut microbiome orchestration determines protective versus pathological outcomes remains unclear. Microbial metabolites demonstrate context-dependent dual effects along the gut-bone marrow axis. Short-chain fatty acids typically induce tolerogenic immune memory, whereas metabolites like succinate and polyamines exhibit dual roles: promoting inflammation in certain contexts while enhancing barrier integrity in others, influenced by cell-specific receptors and microenvironmental factors. Interventions include precision probiotics and postbiotics delivering specific metabolites, fecal microbiota transplantation addressing dysbiotic trained immunity, targeted metabolite supplementation, and pharmacologic reprogramming of pathological myeloid training states. Patient stratification based on microbiome composition and host genetics enhances therapeutic precision. Future research requires integration of non-coding RNAs regulating trained immunity, microbiome-immune-neuronal axis interactions, and host genetic variants modulating microbiome-immunity crosstalk. Priorities include developing companion diagnostics, establishing regulatory frameworks for microbiome therapeutics, and defining mechanistic switches for personalized interventions.}, } @article {pmid41095952, year = {2025}, author = {Soares Ferreira Júnior, A and Rodrigues da Silva, BF and Luiz da Silva, J and Trovão da Silva, M and Feliciano, JVP and Colturato, I and Barros, GMN and Scheinberg, P and Chao, NJA and de Oliveira, GLV}, title = {Unraveling the Intestinal Microbiota Conundrum in Allogeneic Hematopoietic Stem Cell Transplantation: Fingerprints, Clinical Implications and Future Directions.}, journal = {Journal of clinical medicine}, volume = {14}, number = {19}, pages = {}, doi = {10.3390/jcm14196874}, pmid = {41095952}, issn = {2077-0383}, support = {#2022/12989-6//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; #2023/08142-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; #313190/2021-6//National Council for Scientific and Technological Development/ ; Finance Code 001//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; }, abstract = {Intestinal dysbiosis represents a critical determinant of clinical outcomes in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Distinct microbiota patterns represent potential prognostic biomarkers and therapeutic targets. However, the exponential growth in microbiota research and analytical complexity has created significant interpretive challenges for clinicians. This review provides a synthesis of current literature examining microbiota fingerprints and their clinical implications. We analyzed key studies evaluating the clinical implications of intestinal microbiota fingerprints in allo-HSCT. Additionally, we examined current therapeutic strategies for microbiota modulation and approaches for translating research findings into clinical practice. We identified three major microbiota fingerprints: (1) decreased intestinal microbiota diversity, (2) reduced abundance of short-chain fatty acid-producing bacteria, and (3) Enterococcus domination. These fingerprints are associated with critical clinical outcomes including overall survival, Graft-versus-host disease, transplant-related mortality, and infection-related complications. While fecal microbiota transplantation and dietary interventions appear promising, current studies suffer from limited sample sizes and lack standardized protocols. Despite significant advances in microbiota research, biological, methodological, and logistical challenges continue to hinder its clinical translation. Understanding microbiota fingerprints represents a promising avenue for improving allo-HSCT outcomes. However, successful clinical implementation requires standardized methodologies, mechanistic studies, and multi-center collaborations to translate research into actionable clinical tools.}, } @article {pmid41094491, year = {2025}, author = {Wang, Z and Zhou, L and Zheng, Y and Zhong, X and Huang, R and Sun, W and Wang, S and Li, W}, title = {Nuclear receptor Nr1d1 links sleep deprivation to intestinal homeostasis via microbiota-derived taurine.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {1106}, pmid = {41094491}, issn = {1479-5876}, support = {2023YFC2705400//National Key R&D Rrogram of China/ ; 2021B1515420004//Guangdong Basic and Applied Basic Research Foundation/ ; 2025A03J4164//Huadu District Basic and Applied Basic Research Joint Funding Project/ ; GKLBCN-202501-01//Open Project Program of Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University/ ; 202201020363//Science and Technology Projects in Guangzhou/ ; 2020A1515011031//Natural Science Foundation of Guangdong Province/ ; }, mesh = {Animals ; *Sleep Deprivation/microbiology/metabolism ; *Homeostasis/drug effects ; *Gastrointestinal Microbiome/drug effects ; *Taurine/metabolism/pharmacology ; *Nuclear Receptor Subfamily 1, Group D, Member 1/metabolism ; Male ; Mice, Inbred C57BL ; Intestinal Mucosa/pathology/metabolism ; *Intestines/microbiology/pathology ; Mice ; Fecal Microbiota Transplantation ; Colon/pathology ; }, abstract = {BACKGROUND: Sleep deficiency significantly compromises human health, with the gut being particularly susceptible. However, the molecular mechanisms by which gut microbiota mediate sleep deprivation-induced intestinal dysfunction remain largely undefined. In this study, we employed a chronic sleep deprivation (CSD) mouse model to investigate the impact of sleep loss on intestinal integrity and microbial composition.

METHODS: The CSD mouse model was established using the modified multiple platform (rotating rod) method. Colon histomorphology was assessed by hematoxylin and eosin (HE) staining. Expression levels of barrier proteins (Occludin, Claudin-1) and circadian regulators (Nr1d1, Bmal1) were evaluated via Western blot or immunohistochemistry (IHC). Gut microbiota composition and stability were analyzed by 16S rRNA gene sequencing, and the causal role of microbiota in CSD-induced barrier damage was assessed through fecal microbiota transplantation (FMT). RNA sequencing (RNA-seq) of intestinal epithelial tissues identified differentially expressed genes and enriched pathways. Untargeted metabolomics was employed to investigate key differential metabolites (Taurine). Additionally, taurine was supplemented in vivo to explore its efficacy and mechanism in alleviating intestinal barrier damage in CSD mice.

RESULTS: CSD led to pronounced colon shortening and significant downregulation of the epithelial barrier proteins Occludin and Claudin-1, indicative of impaired intestinal barrier function. Moreover, CSD exacerbated symptoms of chemically induced colitis and induced gut microbiota dysbiosis. Mechanistically, FMT from CSD mice into antibiotic-treated recipients recapitulated intestinal inflammation, confirming the pathogenic role of the altered microbiota. Transcriptomic analysis revealed significant enrichment of genes involved in circadian rhythm pathways, notably a marked suppression of the circadian nuclear receptor Nr1d1, a key regulator of intestinal homeostasis. Complementary untargeted metabolomic profiling identified taurine as a microbiota-derived metabolite significantly reduced by CSD. In vivo taurine supplementation restored Nr1d1 expression, reinforced epithelial barrier integrity, and decreased pro-inflammatory cytokine production.

CONCLUSION: Together, these findings reveal a gut microbiota-taurine-Nr1d1 axis underlying sleep deprivation-induced intestinal barrier dysfunction, and suggest that therapeutic modulation of taurine levels or circadian pathways may offer novel strategies to prevent or treat sleep-related gastrointestinal disorders.}, } @article {pmid41090775, year = {2025}, author = {Baek, JS and Ma, X and Park, HS and Lee, DY and Kim, DH}, title = {Bifidobacterium longum P77 and Lactiplantibacillus plantarum P72 and Their Mix-Live or Heat-Treated-Mitigate Sleeplessness and Depression in Mice: Involvement of Serotonergic and GABAergic Systems.}, journal = {Cells}, volume = {14}, number = {19}, pages = {}, doi = {10.3390/cells14191547}, pmid = {41090775}, issn = {2073-4409}, support = {RS-2024-00486802//the Commercialization Promotion Agency for R&D Outcomes (COMPA) grant/ ; 2017R1A5A2014768//National Research Foundation of Korea/ ; }, mesh = {Animals ; *Depression/therapy ; Mice ; *Serotonin/metabolism ; Humans ; Male ; *Bifidobacterium longum/physiology ; Probiotics/pharmacology ; Anxiety ; Hot Temperature ; gamma-Aminobutyric Acid/metabolism ; Mice, Inbred C57BL ; Stress, Psychological ; }, abstract = {Sleeplessness (insomnia) is a significant symptom associated with stress-induced depression/anxiety. In the present study, we selected Bifidobacterium longum P77, which increased serotonin production in corticosterone-stimulated SH-SY5Y cells, from the fecal bacteria collection of healthy volunteers and examined the effects of B. longum on depression, anxiety, and sleeplessness induced by immobilization stress or by transplantation of cultured fecal microbiota (cFM) from patients with depression. Orally administered B. longum P77 decreased depression/anxiety- and sleeplessness-like behaviors in immobilization stress-exposed mice. B. longum P77 reduced immobilization stress-induced corticosterone, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 expression and the cell population of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)[+] in the prefrontal cortex, while the expression levels of immobilization stress-suppressed IL-10, γ-aminobutyric acid (GABA), its receptor GABAARα1, serotonin, and its receptor 5-HT1AR increased. B. longum P77 also alleviated immobilization stress-induced colitis: it decreased TNF-α and IL-6 expression and increased IL-10 expression in the colon. Furthermore, B. longum P77, Lactiplantibacillus plantarum P72, and their combination decreased cFM- or immobilization stress-induced depression-, anxiety-, and sleeplessness-like behaviors. They also decreased cFM-induced, corticosterone, TNF-α, and IL-6 expression levels in the prefrontal cortex and colon, while increasing cFM- or immobilization stress-suppressed GABA, GABAARα1, serotonin, and 5-HT1AR expression levels in the prefrontal cortex. In particular, the combination of B. longum P77 and L. plantarum P72 (P7277) additively or synergistically alleviated depression-, anxiety-, and sleeplessness-like behaviors, along with their associated biomarkers. Heat-killed P7277 also alleviated immobilization stress-induced depression/anxiety- and sleeplessness-like symptoms. These results imply that L. plantarum P72 and/or B. longum P77 can mitigate depression/anxiety and sleeplessness by upregulating GABAergic and serotonergic systems, along with the suppression of NF-κB activation.}, } @article {pmid41090697, year = {2025}, author = {Moore, JE and Millar, BC}, title = {Improving health literacy and patient-directed knowledge of fecal microbiota transplantation (FMT) through analysis of readability: a cross sectional infodemiology study.}, journal = {Expert opinion on biological therapy}, volume = {}, number = {}, pages = {}, doi = {10.1080/14712598.2025.2576509}, pmid = {41090697}, issn = {1744-7682}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is increasingly used in geriatric medicine, including intestinal decolonization of antimicrobial-resistant bacterial pathogens and the treatment of inflammatory bowel disease, graft versus host disease and autism spectrum disorders. The aim of this study was to examine readability of patient-facing FMT information.

RESEARCH DESIGN AND METHODS: Readability was calculated using Readable software, examining (i) Flesch Reading Ease (FRE), (ii) Flesch-Kincaid Grade Level (FKGL), (iii) Gunning Fog Index and (iv) SMOG Index and two text metrics [words/sentence, syllables/word] for 234 sources of FMT information, from four categories (abstracts/hospital information/patient-facing information/clinical trials).

RESULTS: Mean readability scores of FMT information for FRE and FKGL were 22.2 ± 1.2 (SEM)) (target > 60) and 14.8 ± 0.2 (target < 8), respectively, with mean words/sentence and syllables/word of 19.2 ± 0.4 and 2.0, respectively. There was no significant difference in readability between scientific abstracts and lay summaries. No information was found that had a readability of less than 7th grade (12-13 year olds).

CONCLUSION: Readability of FMT information for patients is poor, not reaching readability reference standards. Authors of FMT information should consider using readability calculators when preparing FMT information, so that the final material is within recommended readability reference parameters, to support the health literacy and treatment adherence of readers.}, } @article {pmid41089557, year = {2025}, author = {Chen, N and Zhang, M and Shi, B and Luo, X and Huang, R and Luo, Z and He, J and Xue, S and Li, N and Ling, Z and Guo, H and Xu, R and Liu, Y}, title = {Tirzepatide, a dual GLP-1 and GIP receptor agonist, promotes bone loss in obese mice via gut microbial-related metabolites.}, journal = {Journal of orthopaedic translation}, volume = {55}, number = {}, pages = {280-292}, pmid = {41089557}, issn = {2214-031X}, abstract = {BACKGROUND: As a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist, Tirzepatide (TZP) is a recently approved medication for treating type 2 diabetes mellitus (T2DM) and obesity; however, the effect of TZP in bone remodeling remains unclear.

METHODS: 1. The effect of Tirzepatide on osteoblasts and osteoclasts was observed by inducing differentiation of bone marrow mesenchymal cells (BMSCs) in vitro. 2. Db/db mice were used as a pathological model to investigate the role of TZP on bone metabolism. After TZP intervention, the feces in the intestinal tract of mice were collected for 16s rRNA gene sequencing to select the candidate gut microbiota most related to bone mass, and the effects of gut microbiota on bone metabolism were verified through subsequent microbiota supplementation experiments. 3. Metabolomics was used to analyze the difference of fecal metabolites between mice with the candidate microbiota supplement and those without, and the effect of candidate metabolites on bone metabolism was verified by the in vitro intervention of differential metabolites in BMSCs induction differentiation experiments.

RESULTS: We found that TZP intervention resulted in a significant decrease in bone mass accrual in vivo. TZP was not indispensable to the differentiation of osteoblasts and osteoclasts in vitro. Bone and fat homeostasis were modulated by gut microbiota. We further demonstrated that the biodiversity of the gut microbiota in db/db mice was strikingly altered after TZP treatment. Lachnospiraceae, a key pro-osteogenic component of gut microbiota was significantly reduced. As a main metabolite of Lachnospiraceae, evodiamine played a role in suppressing osteoclastogenesis in vitro. Based on this, the transplantation of the Lachnospiraceae effectively ameliorated bone loss that was seen in db/db mice due to TZP treatment.

CONCLUSION: TZP administration leads to bone loss in the context of diabetes and obesity, and targeting the composition of gut microbiota may provide a potential way to protect bone health in type 2 diabetic patients treating with TZP.

This study indicates that TZP has a negative impact on bone mass, suggesting that clinical attention should be paid to the risk of further decline in bone mass after Tirzepatide treatment, and it is necessary to follow up on their bone metabolism. Additionally, the gut microbiota plays an important role in bone metabolism regulation, and supplementing with certain probiotics may have a preventive effect on bone mass reduction associated with TZP treatment. Our research provides a reference for the prevention and treatment of drug-related osteoporosis in patients with T2DM in the future.}, } @article {pmid41089551, year = {2025}, author = {Hearn, J and Malik, G and Stukalin, I and Panaccione, R and Ingram, RJM and Ma, C}, title = {Refractory Immune Checkpoint Inhibitor Colitis Treated With Biologics, Janus Kinase Inhibition, Plasma Exchange, and Fecal Microbiota Transplantation.}, journal = {ACG case reports journal}, volume = {12}, number = {10}, pages = {e01847}, pmid = {41089551}, issn = {2326-3253}, abstract = {Enterocolitis is a common immune-related adverse event associated with cancer immunotherapy. Current guidelines inform first-line pharmacologic management of immune checkpoint inhibitor-related enterocolitis; however, treatment in refractory cases is uncertain. We present a case of a 45-year-old woman with refractory immune checkpoint inhibitor-related enterocolitis requiring treatment with a combination of janus kinase inhibition, therapeutic plasma exchange, and fecal microbiota transplantation after failure of several lines of therapy. This is the first report of the combination of upadacitinib, plasma exchange, and fecal microbiota transplant for refractory enterocolitis.}, } @article {pmid41089403, year = {2025}, author = {Wang, J and Zhang, X and Cui, C and Li, M and Xie, Z and Yang, L and Ding, D and Li, X and Zhao, M}, title = {Gut Microbiota and Metabolite Changes Induced by Tacrolimus: Implications for Skin Transplant Immunology in Mice.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {14059-14073}, pmid = {41089403}, issn = {1178-7031}, abstract = {BACKGROUND: Tacrolimus is the most widely used immunosuppressive therapy in solid organ transplantation. However, whether it can inhibit transplant graft rejection by altering the composition and metabolism of gut microbiota remains unclear.

METHODS: In this study, a skin transplantation mouse model was established to explore the effects of tacrolimus on gut microbiota and its metabolites. Additionally, we investigated the protective effect and potential mechanism of feces from mice treated with tacrolimus on skin allografts.

RESULTS: Tacrolimus did not significantly affect gut microbiota α-diversity but altered β-diversity, with specific changes in microbial composition. LEfSe analysis identified 19 microbial taxa with reduced and 12 with elevated relative abundance in the Tac group (mice treated with tacrolimus) compared to the Ctrl group (mice with no treatment). Metabolomic analysis identified 33 differential fecal metabolites (17 upregulated and 16 downregulated) in the Tac group compared to the Ctrl group. FMT from tacrolimus-treated mice significantly prolonged skin allograft survival, reduced inflammatory cell infiltration, and improved graft histopathology. This protective effect was associated with increased Treg cell proportions and decreased Th17 cell proportions in draining lymph nodes and mesenteric lymph node.

CONCLUSION: Overall, our data may provide a basis for establishing gut microbiota-based therapies for allograft rejection.}, } @article {pmid41088420, year = {2025}, author = {Zhu, JH and Wu, LP and Deng, L and Zang, SG and Li, XB and Chen, X and Yu, JX}, title = {Gut microbiota and metabolism in systemic lupus erythematosus: from dysbiosis to targeted interventions.}, journal = {European journal of medical research}, volume = {30}, number = {1}, pages = {971}, pmid = {41088420}, issn = {2047-783X}, support = {No.YK2023130//The Medical Research Project of Yancheng Health Commission/ ; No.2024LZ006//The Special Scientific Research Fund for Clinical Medicine of Nantong University/ ; 2024LZ008//The Special Scientific Research Fund for Clinical Medicine of Nantong University/ ; No.YCBE202475//The Special Fund Project of Yancheng Science and Technology Bureau/ ; }, mesh = {Humans ; *Lupus Erythematosus, Systemic/metabolism/microbiology/therapy ; *Gastrointestinal Microbiome ; *Dysbiosis/therapy/metabolism/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multiorgan involvement, with pathogenesis closely linked to that of gut dysbiosis and metabolic disturbances. Studies indicate that SLE patients exhibit significantly reduced gut microbial diversity, increased abundance of pathogenic bacteria, and decreased beneficial bacteria. Dysbiosis exacerbates disease progression by disrupting the intestinal barrier, triggering autoimmune responses, and promoting proinflammatory cytokine release. Metabolomic analyses further reveal that SLE is associated with dysregulated amino acid metabolism, reduced short-chain fatty acids, and disrupted lipid homeostasis, which correlate with disease activity, renal injury, and increased atherosclerosis risk. Emerging microbiota-targeted interventions, such as fecal microbiota transplantation (FMT), probiotics/prebiotics, phage therapy, and dietary modifications, demonstrate promising therapeutic potential by restoring microbial balance, enhancing immune regulation, and improving metabolic homeostasis. This review systematically summarizes the alterations in gut microbiota and metabolism in SLE, their critical roles in disease progression, diagnosis, and pathogenesis, and explores the clinical value of microbial-targeted strategies in improving SLE outcomes.}, } @article {pmid41087864, year = {2025}, author = {Chen, H and Wang, Z and Su, W and Li, S and Ye, Q and Zhang, G and Zhou, X}, title = {Helicobacter pylori infection impairs glucose homeostasis through gut microbiota dysbiosis.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {663}, pmid = {41087864}, issn = {1471-2180}, support = {82100594//National Natural Science Foundation of China,China/ ; }, abstract = {BACKGROUND: Epidemiological data show that Helicobacter pylori (H. pylori) infection is not only the most important risk factor for gastric cancer, but is also associated with poor glycemic control in patients with diabetes. However, the direct causal and functional relationship between H. pylori infection and dysglycemia is unclear.

METHOD: A retrospective cohort study was conducted to examine the association between H. pylori infection and glycemic levels in individuals with Type 2 diabetes. C57BL/6 diabetic mice were infected with H. pylori, and the resulting changes in colonic inflammation and intestinal Glucagon-like peptide-1 (GLP-1) secretion were thoroughly examined using immunohistochemistry, RNA sequencing, metagenomic sequencing, and targeted metabolomics. The microbial and metabolomics profiles were analyzed and compared in antibiotic-treated mice through fecal transfer experiments.

RESULTS: H. pylori infection aggravated insulin resistance in diabetic individuals and mice. We identified a unique H. pylori-induced epithelial inflammation and reduced intestinal GLP-1 secretion in the colon. H. pylori infection also interrupts the normal microbial composition in the colon, leading to a decrease in SCFA-producing bacteria and a reduction in acetic and propionate acids. Similar changes were observed in antibiotic-treated mice after receiving fecal transplants from H. pylori-infected diabetic mice. In vitro studies revealed that the intestinal flora of H. pylori-positive diabetic mice inhibited proglucagon transcription, cAMP levels, and GLP-1 secretion in colonic endocrine cells, with SCFA supplementation reversing this effect on GLP-1 production. These microbial, metabolic, and GLP-1 alterations were also seen in antibiotic-treated mice after receiving fecal transplants from H. pylori-infected diabetic mice. H. pylori eradication with antibiotics improved glucose metabolism and GLP-1 secretion to levels comparable to uninfected controls.

CONCLUSION: Our studies offer evidence that H. pylori infection significantly contributes to the progression of glucose impairment and insulin resistance. Therefore, incorporating H. pylori status into preventive strategies for diabetes should be taken into account. (Chinese Clinical Trial Registry Center, ChiCTR2200063489, Registered 08 September 2022, https://www.chictr.org.cn/showproj.html?proj=178102).}, } @article {pmid41087029, year = {2025}, author = {Tu, D and Lu, C and Guo, J and Chen, Q and Li, X and Wang, Y and Cheng, L and Jiang, H and Jian, J and Ge, Y and Hou, Z and Feng, X and Feng, Y and Zhou, J and Lei, Y and Diao, H and Ran, L and Zhou, Y and Xu, Z and Zhou, J and Tang, B and Yang, S}, title = {Gut microbiota-mediated berberine metabolism ameliorates cholestatic liver disease by suppressing 5-HT production.}, journal = {Clinical and molecular hepatology}, volume = {}, number = {}, pages = {}, doi = {10.3350/cmh.2025.0577}, pmid = {41087029}, issn = {2287-285X}, abstract = {BACKGROUND/AIMS: Cholestatic liver disease (CLD) is a pathological condition characterized by impaired bile formation, secretion, and excretion. However, the key pathophysiological mechanisms of CLD remain elusive, and therapeutic efficacy is unsatisfactory.

METHODS: We administered berberine (BBR) or dihydroberberine (dhBBR) in bile duct ligation-, ANIT-, and mdr2-/- CLD mouse models to evaluate the anti-CLD effect. We conducted fecal microbiota transplantation to determine the role of gut microbiota in BBR's effect. We conducted a randomized, controlled clinical trial to evaluate the effects of BBR in patients with CLD.

RESULTS: Oral BBR alleviates cholestatic liver injury in multiple mouse models. Gut microbes can transform BBR into dhBBR, which suppresses 5-HT production in gut enterochromaffin cells by antagonizing tryptophan hydroxylase 1 (TPH1) activity and downregulating Tph1 transcription. This further ameliorates CLD by interrupting the 5-HT/5HTR axis. A clinical study validated that BBR improved blood biochemical indicators in patients with CLD and decreased 5-HT levels.

CONCLUSIONS: BBR is transformed by gut microbiota to ameliorate CLD via inhibiting 5-HT, suggesting potential novel strategies for further clinical use.}, } @article {pmid41086122, year = {2025}, author = {Peng, W and Fan, X and Shi, H and Jiang, Y and Fan, L and Xing, Y and Peng, Y and He, Y and Zou, W and Jiang, M}, title = {Gut Microbiota and Chemotherapy-Induced Gastrointestinal Toxicity: Mechanisms and Intervention Strategies.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {}, number = {}, pages = {1-22}, doi = {10.1159/000548922}, pmid = {41086122}, issn = {1421-9875}, abstract = {BACKGROUND: Cancer remains a leading cause of mortality worldwide. Chemotherapy serves as a cornerstone of cancer treatment, providing significant benefits in tumor control and survival. However, its therapeutic efficacy is often compromised by gastrointestinal toxicity, which impairs quality of life and may necessitate treatment modifications. Disruption of the gut microbiota has been recognized as a key factor in the development of these toxicities.

SUMMARY: This review synthesizes evidence on how chemotherapeutic agents disrupt gut microbial balance and exacerbate gastrointestinal toxicity through epithelial barrier damage, inflammatory activation, and metabolic disturbance. It also examines diverse interventions, including dietary modifications, probiotics, prebiotics, synbiotics, traditional herbal medicines, and fecal microbiota transplantation, that aim to restore microbial homeostasis and reduce gastrointestinal injury.

KEY MESSAGES: This review provides a symptom‑oriented framework linking specific clinical manifestations of chemotherapy‑related gastrointestinal toxicity with underlying microbial alterations. It further integrates emerging evidence across nutritional, microbial, and herbal approaches, emphasizing shared therapeutic pathways and highlighting prospects for personalized microbiota‑based strategies to improve treatment tolerance and patient outcomes.}, } @article {pmid41085348, year = {2025}, author = {Zhang, S and Wu, Z and Zhang, S and Ru, Y and Wang, Q and Tong, H and Qin, Q and Yan, Q and Li, Z and Wu, G}, title = {The intricate microbial-gut-brain axis in Alzheimer's disease: a review of microbiota-targeted strategies.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d5fo03139g}, pmid = {41085348}, issn = {2042-650X}, abstract = {The microbiome-gut-brain axis (MGBA) has emerged as a potential focus for the enhancement of cognitive abilities and the improvement of Alzheimer's disease (AD). Probiotics and prebiotics can improve the imbalance of gut microbiota to alleviate AD symptoms. Current research on probiotics/prebiotics and brain function mainly focuses on metabolic pathways such as those involving microbial metabolites like lipopolysaccharides and short-chain fatty acids, as well as immune pathways that regulate inflammation in the gut and brain. However, the roles played by endocrine and neural pathways remain less explored and warrant further attention. This review explores the intricate mechanisms of gut-brain communication within the MGBA, and especially systematically elaborates on the specific mechanisms of the endocrine pathway (impact of gut-derived and exogenous hormones on brain function) and the neural pathway (regulation of brain function by the sympathetic and parasympathetic systems). It also emphasizes the specific changes in gut microbiota noted in individuals with AD. Additionally, it examines the beneficial effects of probiotics, prebiotics, synbiotics, and postbiotics for cognitive function, reviewing their advancements in preclinical research, clinical trials, and commercial applications. Furthermore, this review delves into novel gut microbiota-related strategies to promote brain health, including antibiotics, certain gut-targeted inhibitors or agonists, fecal microbiota transplantation, whole microbiome transplantation, viral microbiota transplantation, genetically engineered bacteria, and bacteriophage-based in situ intestinal microbiome engineering. Ultimately, this review aims to advance the therapeutic application of gut microbiota-targeted strategies in AD.}, } @article {pmid41081988, year = {2025}, author = {Bhat, A and Mansoor, A and Fatima, M and Kumar, A and Mari, T and Ali, A and Bakht, K and Dad, A and Zahra, R and Makhija, V and Southwick, FS}, title = {Safety and efficacy of fecal microbiota transplantation versus antibiotics for treating clostridioides difficile infection: systematic review and meta-analysis.}, journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {}, number = {}, pages = {}, pmid = {41081988}, issn = {1435-4373}, abstract = {BACKGROUND: Recurrent Clostridioides difficile infection (CDI) is a persistent clinical challenge due to the high rate of relapse following treatment with standard antibiotics. Fecal microbiota transplantation (FMT) has emerged as a promising alternative, with comparable results. Aiming to restore intestinal microbial balance and reduce recurrence. Comparative evidence on the efficacy and safety of FMT versus antibiotics remains variable across studies, warranting a comprehensive synthesis to guide clinical decision-making.

AIM: This systematic review and meta-analysis aims to present an updated comparison of the effectiveness and safety of FMT versus Vancomycin/ fidaxomicin in patients with CDI.

METHODS: A comprehensive search of PubMed, Embase, and the Cochrane Library was conducted to identify randomized controlled trials comparing FMT with standard antibiotic therapy for recurrent CDI. Primary outcomes included resolution of infection, recurrence, mortality, and adverse events. A random-effects model was used to calculate risk ratios with 95% confidence intervals. Statistical heterogeneity was assessed using the I-squared statistic. The quality of the included studies was evaluated using the Cochrane Risk of Bias version 2 and ROBINS-1 tools.

RESULTS: A total of 9 clinical trials involving 759 patients were included. FMT was significantly more effective in resolving CDI compared to antibiotic therapy, with a risk ratio (RR) of 1.51 (95% CI: 1.29 to 1.78). Recurrence rates were significantly lower in the FMT group, with a RR of 0.38 (95% CI: 0.29 to 0.50). Mortality did not differ significantly between groups (RR = 0.95). Adverse events (AEs) were comparable between FMT and antibiotics, and no serious AEs directly related to FMT were reported. In the subgroup analysis, the lower GI route adminstration showed significant results (p = 0.02) for both recurrence and resolution of CDI.

CONCLUSION: FMT is more effective than standard antibiotic therapy for achieving resolution and reducing recurrence in patients with recurrent CDI.}, } @article {pmid41081080, year = {2025}, author = {Bzdyra, M and Tulewicz-Marti, EM and Przepióra, A and Lewandowski, K and Rydzewska, G}, title = {Efficacy and safety of faecal microbiota transplantation (FMT) in recurrent Clostridioides difficile infection: results of a single-centre retrospective study.}, journal = {Przeglad gastroenterologiczny}, volume = {20}, number = {3}, pages = {330-334}, pmid = {41081080}, issn = {1895-5770}, abstract = {INTRODUCTION: Studies have indicated the high effectiveness of faecal microbiota transplantation (FMT) in the treatment of recurrent Clostridioides difficile infection (rCDI). However, there is still a lack of data from different subpopulations regarding FMT and the factors related to it.

AIM: The aim of the study was to retrospectively evaluate the efficacy and safety of FMT in rCDI.

MATERIAL AND METHODS: In all cases, FMT was performed using a nasoenteric tube. A good response following a single FMT was considered an improvement, whereas requiring more than one FMT was considered a suboptimal response.

RESULTS: In the analysed period, FMT was performed on a total of 98 patients, including 74 with rCDI (of whom 23 received 2 FMTs, 6 received 3 FMTs, and 1 received 5 FMTs). The average age of the patients was 68 years. 42 (56%) patients were women, 41 (55.4%) had previously used antibiotics, 2 (2.7%) had used steroids, and 4 (5.4%) had used proton pump inhibitors (PPI). Following the first FMT procedure, clinical improvement was observed in 44 (59.4%) patients. The odds of a suboptimal effect of the therapy (needing more than 1 FMT) were associated with prior use of metronidazole. Among all analysed factors, cardiovascular risk factors (such as hypertension and hyperlipidaemia) were associated with a threefold increased likelihood of requiring more than 1 FMT (p = 0.038).

CONCLUSIONS: In our study, FMT was found to be an effective and safe treatment of recurrent CDI. Use of metronidazole was identified as a risk factor for a suboptimal response to FMT in the studied cohort.}, } @article {pmid41080577, year = {2025}, author = {Wang, Z and Yu, J and Liu, Y and Gong, J and Hu, Z and Liu, Z}, title = {Role of the microbiota-gut-lung axis in the pathogenesis of pulmonary disease in children and novel therapeutic strategies.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1636876}, pmid = {41080577}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; Child ; *Lung/immunology/microbiology/metabolism ; *Lung Diseases/therapy/microbiology/immunology/etiology/metabolism ; Dysbiosis ; Animals ; Fatty Acids, Volatile/metabolism ; }, abstract = {Emerging evidence highlights the microbiota-gut-lung axis (MGLA) as a pivotal regulator of pediatric respiratory health, yet mechanistic insights are lacking and therapeutic applications remain unclear. This review synthesizes cutting-edge findings to delineate how gut microbiota-derived metabolites, particularly short-chain fatty acids (SCFAs), orchestrate pulmonary immunity and disease pathogenesis in children. Leveraging multi-omics integration (metagenomics, metabolomics, transcriptomics), emerging studies have uncovered novel microbe-host interactions driving immune dysregulation in asthma, pneumonia, and cystic fibrosis. A comprehensive map of gut-lung crosstalk has been established across these conditions. Current studies suggest that early-life gut dysbiosis, shaped by delivery mode, antibiotics, and diet, disrupts SCFA-mediated immune homeostasis, amplifying T-helper 2 cell inflammation and impairing alveolar macrophage function. Crucially, we identified disease-specific microbial signatures (e.g., depletion of Lachnospira and Faecalibacterium in asthma) and demonstrated that fecal microbiota transplantation and probiotic interventions restore microbial balance, attenuating airway inflammation in preclinical models. This work pioneers the translation of MGLA insights into precision medicine strategies, highlighting dietary modulation and microbial therapeutics as viable alternatives to conventional treatments. By bridging microbial ecology and immune dynamics, our findings provide actionable biomarkers for early diagnosis and personalized interventions, addressing critical gaps in pediatric respiratory disease management. The integration of multi-omics frameworks not only advances mechanistic understanding but also positions the MGLA as a transformative target in reducing global childhood morbidity. Future research must prioritize longitudinal studies and clinical trials to validate these innovations, ultimately redefining therapeutic paradigms for GLA-driven pathologies.}, } @article {pmid41080562, year = {2025}, author = {Zhu, Z and Cheng, Y and Liu, X and Xu, X and Ding, W and Ling, Z and Liu, J and Cai, G}, title = {The microbiota-gut-brain axis in depression: unraveling the relationships and therapeutic opportunities.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1644160}, pmid = {41080562}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Depression/therapy/microbiology/metabolism/etiology ; *Brain/metabolism ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; *Brain-Gut Axis ; }, abstract = {Depression, a highly prevalent and relapsing mental disorder, exacts profound personal and socioeconomic tolls globally, warranting urgent scientific and clinical attention. Emerging evidence from both preclinical models and human clinical investigations has established the microbiota-gut-brain axis (MGBA) as a critical determinant in depression pathogenesis. This intricate bidirectional network integrates gut microbiota with central nervous system function, influencing mental health through mechanisms previously underrecognized. This review systematically synthesizes gut microbiota alterations associated with depression and their impacts on neuroendocrine, neuroimmune, and metabolic pathways. Advanced therapeutic strategies targeting the MGBA are discussed, including probiotics, fecal microbiota transplantation, and artificial intelligence-enabled microbiome interventions for depression management. While challenges in standardization, mechanistic understanding, efficacy and safety remain, MGBA-centered approaches offer a promising shift toward microbiota-based diagnostics and personalized treatments for depression.}, } @article {pmid41080326, year = {2025}, author = {Qureshi, U and Bajwa, A and Aslam, Z and Aggrey, A and Nawaz, UH and Ul Ain, Q}, title = {Gut Microbiota Modulation in Type 2 Diabetes and Cardiometabolic Risk: A Systematic Review.}, journal = {Cureus}, volume = {17}, number = {9}, pages = {e92020}, pmid = {41080326}, issn = {2168-8184}, abstract = {Cardiometabolic complications related to type 2 diabetes mellitus (T2DM) are often due to changes in the gut microbiota. The review analyzed studies looking at the effects of probiotics, prebiotics, high-fiber diets, and fecal microbiota transplantation (FMT) on glucose levels and heart and metabolic health in individuals either having T2DM or being at risk. The review followed the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. The literature was searched using text terms and controlled vocabulary, employing Boolean operators "AND," "OR," and various combinations across PubMed, Embase, and the Cochrane Library. Open-access, full-text English papers from 2005 to 2025, including those authored by people, were searched. The quality was assessed using the Risk of Bias 2.0 (RoB 2.0) tool, and the evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Fifteen randomized controlled trials (RCTs) were analyzed for methodological quality, with three categorized as having a high risk of bias (RoB). The GRADE tool categorized two high RoB RCTs as "low quality." However, two RCTs had low RoB and were classified as "high quality." Ten RCTs had uncertain RoB, lowering the evidence by one point to "moderate quality." A comprehensive review of RCTs was conducted to assess outcomes related to glycemic parameters (e.g., glycated hemoglobin (HbA1c), fasting glucose), lipid profiles, inflammatory markers, anthropometric measures, and gut microbiota composition. Interventions included probiotic and prebiotic supplementation, high-fiber or Mediterranean-style diets, and FMT. Probiotic yogurt containing Lactobacillus acidophilus and Bifidobacterium lactis significantly improved lipid profiles by reducing low-density lipoprotein cholesterol (LDL-C) and total cholesterol. High-fiber diets consistently lowered fasting blood glucose, HbA1c, triglycerides, and LDL-C while elevating high-density lipoprotein cholesterol (HDL-C) and beneficial short-chain fatty acid (SCFA)-producing bacteria. Anti-inflammatory effects were observed across interventions, notably with probiotics and polyphenol-rich Mediterranean diets, which reduced tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and other inflammatory cytokines. The Green-Mediterranean diet significantly improved weight, insulin resistance, and Framingham risk scores. Novel mechanisms involving SCFAs and bile acid metabolism were also identified as key modulators of host metabolic response. Microbiota-based interventions offer promising avenues for glycemic control and cardiometabolic risk reduction in patients with T2DM.}, } @article {pmid41080149, year = {2025}, author = {Xu, H and Li, S and Liu, S and Zuo, YG}, title = {A Conceptual Review of Gut, Skin, and Oral Microbiota in Autoimmune Bullous Diseases: From Dysbiosis to Therapeutic Potential.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {13925-13943}, pmid = {41080149}, issn = {1178-7031}, abstract = {Autoimmune bullous diseases (AIBDs), including pemphigus and bullous pemphigoid, are chronic inflammatory skin disorders characterized by dysregulated immune responses mediated by autoantibodies that target adhesion molecules in the skin and mucous membranes. Emerging evidence highlights the pivotal role of host microbiota dysbiosis in AIBDs pathogenesis, offering novel insights into disease mechanisms and therapeutic strategies. This review systematically synthesizes the current findings on gut, skin, and oral microbiota alterations in AIBDs, emphasizing their contributions via the gut-skin axis, microbial metabolites, and pathogen-host interactions. Key innovations include uncovering how specific pathogenic and commensal microbiota influence disease progression through intriguing skin inflammation and direct barrier impairment. Notably, while some microbiota changes overlap with other dermatoses, AIBDs exhibit distinct microbial signatures associated with their unique autoimmune mechanisms targeting adhesion molecules. Furthermore, we explore microbiota-targeted therapies, such as antibiotics, probiotics, and fecal microbiota transplantation, and demonstrate their potential to restore microbial homeostasis and improve clinical outcomes. By integrating multi-omics evidence and clinical data, this review bridges mechanistic insights with translational applications, proposing microbiota modulation as a promising adjunctive therapy for AIBDs. Our analysis identifies critical research gaps, including the need for longitudinal studies and personalized microbial interventions, positioning this review at the forefront of microbiome-inflammation-autoimmunity research.}, } @article {pmid41078532, year = {2025}, author = {Taha, H and Issa, A and Muhanna, Z and Al-Shehab, M and Wadi, T and Awamleh, S and Ateiwi, YA and Abusido, M and Berggren, V}, title = {Microbiota-based interventions for autism spectrum disorder: a systematic review of efficacy and clinical potential.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1648118}, pmid = {41078532}, issn = {1664-302X}, abstract = {PURPOSE: Autism spectrum disorder (ASD) is increasingly linked to gut microbiota imbalances, influencing both behavioral and gastrointestinal (GI) symptoms. This systematic review assesses the efficacy of microbiota-based interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), in improving ASD-related symptoms, aiming to provide insights into their therapeutic potential and inform future clinical applications.

METHODS: A comprehensive systematic review was conducted following PRISMA guidelines and registered in PROSPERO (CRD42024615043). A structured literature search was performed in PubMed, Cochrane Library, and Scopus to identify peer-reviewed English-language studies. Eligible studies included randomized controlled trials (RCTs), non-randomized trials (NRTs), and retrospective studies assessing the impact of microbiota-based interventions on ASD-related behavioral and GI outcomes. Two independent reviewers conducted study selection, data extraction, and quality assessment using standardized risk-of-bias tools.

RESULTS: 33 studies were included, consisting of 16 RCTs, 14 NRTs, and 3 retrospective studies. Among them, 15 assessed probiotics, 4 prebiotics, 5 synbiotics, and 9 FMT. Probiotics showed moderate behavioral improvements in ASD, with multi-strain formulations being more effective than single strains. Prebiotics and synbiotics yielded mixed results, with some studies indicating benefits in behavioral and GI symptoms. FMT demonstrated the most consistent and sustained improvements in both ASD-related behaviors and GI function. Adverse events were minimal, primarily involving transient GI symptoms.

CONCLUSION: Microbiota-targeted interventions, particularly FMT, hold promise for managing ASD symptoms, though probiotics, prebiotics, and synbiotics present variable efficacy. Standardized protocols, larger controlled trials, and personalized microbiome-based approaches are necessary to refine these therapeutic strategies and enhance clinical applicability.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42024615043, identifier CRD42024615043.}, } @article {pmid41078530, year = {2025}, author = {Li, R and Hu, Y and Liu, Y and Tan, X}, title = {Fecal microbiota transplantation augments 5-fluorouracil efficacy in pancreatic cancer via gut microbiota modulation.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1548027}, pmid = {41078530}, issn = {1664-302X}, abstract = {BACKGROUND: Pancreatic cancer is a highly aggressive malignancy with limited therapeutic options due to rapid tumor progression and poor prognosis. Fecal Microbiota Transplantation (FMT) has emerged as a promising approach to modulate gut microbiota, potentially enhancing the efficacy of conventional treatments.

OBJECTIVES: This study evaluates the combined effects of FMT and 5-fluorouracil (5FU) on gut microbiota composition, pancreatic tumor growth, and systemic immune responses in a murine model.

METHODS: One hundred female C57BL/6 mice aged 6-8 weeks were randomly divided into five groups (n = 20 each): Sham, Model, FMT, 5FU, and FMT + 5FU. Pancreatic tumors were induced via orthotopic implantation of Pan02 cells. FMT was administered orally (0.2 g fecal material) three times per week, starting 2 weeks before tumor implantation. 5FU was administered intraperitoneally at 25 mg/kg body weight twice weekly, beginning one-week post-tumor implantation. Gut microbiota was analyzed via 16S rRNA gene sequencing of fecal samples after 10-week cell implantation. Tumor volumes were measured, and serum cytokine levels were assessed. Short-chain fatty acids (SCFAs) in blood and feces using gas chromatography-mass spectrometry (GC-MS).

RESULTS: The FMT + 5FU group exhibited the smallest average tumor volume, significantly smaller than the Model (p < 0.0001) and 5FU groups (p = 0.005). FMT alone reduced tumor volume compared to the Model group (p < 0.0001). Gut microbiota analysis revealed increased α diversity in the FMT group compared to the Model group (p < 0.0001). The FMT + 5FU group showed a significant reduction in cytokine levels, including TNF-α (p = 0.0001) and IL-6 (p = 0.012) and increased IL-10 level (p < 0.001), compared to the Model group. Plasma and fecal SCFA concentrations were significantly higher in both FMT and FMT + 5FU groups relative to the Model group (p < 0.001). Additionally, the FMT + 5FU group had the highest survival rate (50%) after 10-week cell implantation, compared to the Model group (15%).

CONCLUSION: FMT significantly enhances the efficacy of 5FU in reducing pancreatic tumor growth through gut microbiota modulation.}, } @article {pmid41078364, year = {2025}, author = {Yu, J and Liu, Z and Wang, Y and Zhou, Y and Liu, W and Wang, T and Xie, Q and Tian, H and Xu, Y and Wang, M and Zhao, F and Wang, L and Zhang, G and Chen, D and Gao, L and Pan, T}, title = {Propionic acid mediates the renoprotective effects of fecal microbiota transplantation against ischemia-reperfusion injury via upregulating GPR43.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1616164}, pmid = {41078364}, issn = {2235-2988}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Rats, Sprague-Dawley ; *Reperfusion Injury/therapy/prevention & control ; *Propionates/metabolism/pharmacology ; *Receptors, G-Protein-Coupled/metabolism/genetics ; Gastrointestinal Microbiome/drug effects ; Rats ; Disease Models, Animal ; Kidney/pathology ; Male ; Guinea Pigs ; *Acute Kidney Injury/therapy/prevention & control ; Apoptosis/drug effects ; Up-Regulation ; Signal Transduction ; }, abstract = {INTRODUCTION: Kidney ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), characterized by aggravated inflammation and apoptosis following reperfusion. This study aimed to investigate the protective effects and mechanisms of fecal microbiota transplantation (FMT) in a rat model of kidney IRI.

METHODS: Sprague-Dawley rats(SDRs) subjected to 45 minutes of bilateral renal ischemia followed by reperfusion were prophylactically treated with FMT derived from guinea pigs or supplemented with propionic acid. Renal function, histopathology, inflammatory markers, apoptosis, proliferation, and gut microbiota composition were systematically evaluated.

RESULTS: The results demonstrated that FMT attenuated kidney IRI by remodeling the gut microbiota to enhance propionic acid production, which subsequently modulated inflammation and apoptosis via GPR43 signaling.

CONCLUSIONS: These findings provide novel insights into microbiota-targeted therapeutic strategies for kidney IRI and highlight propionic acid as a potential therapeutic agent.}, } @article {pmid41078360, year = {2025}, author = {Gu, X and Tang, J and Chen, C}, title = {Efficacy of gut microbiota-targeted therapies in Parkinson's disease: a systematic review and meta-analysis of randomized controlled trials.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1627406}, pmid = {41078360}, issn = {2235-2988}, mesh = {Humans ; *Parkinson Disease/therapy/microbiology ; *Gastrointestinal Microbiome/drug effects ; Randomized Controlled Trials as Topic ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Treatment Outcome ; Anti-Bacterial Agents/therapeutic use ; Synbiotics/administration & dosage ; }, abstract = {OBJECTIVE: This study aimed to investigate the efficacy of gut microbiota (GM)-targeted therapies in treating Parkinson's disease (PD).

METHODS: Randomized controlled trials (RCTs) were retrieved from PubMed, Embase, Cochrane, and WOS from database inception to June 2025. The eligible RCTs employed GM-targeted therapies, including antibiotics, probiotics, synbiotics, or fecal microbiota transplantation (FMT), as adjunct treatments for PD. Data were pooled using a random-effects model, and the effect sizes were expressed as standardized mean differences (SMDs). In addition, the quality of evidence for all outcomes was assessed using the GRADE framework.

RESULTS: This study demonstrated that GM-targeted therapies significantly improved PD outcomes, including Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) III (SMD: -0.34, 95%CI: -0.57 to -0.11, P = 0.004), bowel movements (BMs) (SMD: 1.27, 95%CI: 0.35 to 2.2), use of laxatives (SMD: -0.33, 95% CI: -0.65 to -0.02), malondialdehyde (MDA) (SMD: -0.69, 95%CI: -1.23 to -0.15) indicators. However, there were no significant improvements in MDS-UPDRS I (SMD: -0.64, 95%CI: -1.42 to 0.13), MDS-UPDRS II (SMD: -0.28, 95%CI: -0.70 to 0.14), MDS-UPDRS IV (SMD: -0.08, 95% CI: -0.82 to 0.66), Mini-Mental State Examination (MMSE) (SMD: -0.01, 95% CI: -0.30 to 0.29), Montreal Cognitive Assessment (MoCA) (SMD: 0.04, 95%CI: -0.53 to 0.60), non-motor symptom scale (NMSS) (SMD: -0.11, 95%CI: -0.94 to 0.72), Parkinson's Disease Questionnaire-39 (PDQ-39) (SMD: -0.19, 95%CI: -0.58 to 0.20), total antioxidant capacity (TAC) (SMD: 0.29, 95%CI: -0.04 to 0.62), glutathione (GSH) (SMD: 0.51, 95%CI: -0.02 to 1.03), and Geriatric Depression Scale-15 (GDS-15) (SMD: -0.37, 95%CI: -0.87 to 0.12).

CONCLUSION: GM-targeted therapies may improve motor symptom scores (as measured by MDS-UPDRS III), alleviate constipation, and reduce blood malondialdehyde levels in PD patients. However, they did not significantly impact the scores for cognitive function, PD neuropsychiatric, behavioral, and emotional symptoms, and activities of daily living in this analysis. Given the inherent limitations of the included studies (such as small sample sizes and heterogeneity), future large-scale and rigorously designed RCTs are needed to validate these preliminary findings.

https://www.crd.york.ac.uk/prospero/, identifier CRD42024606415.}, } @article {pmid41078065, year = {2025}, author = {Doukas, PG and Doukas, SG and Broder, A}, title = {Effectiveness and Safety of Fecal Microbiota Transplantation for Ulcerative Colitis Treatment: A Systematic Review and Meta-Analysis.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {}, number = {}, pages = {1-22}, doi = {10.1159/000548568}, pmid = {41078065}, issn = {1421-9875}, abstract = {Despite advances in pharmaceuticals, managing ulcerative colitis (UC) remains challenging. Interest in fecal microbiota transplantation (FMT) for UC is growing, but varying formulations and endpoints in trials complicate safety and efficacy assessment. This systematic review and meta-analysis offer a validated, up-to-date overview of FMT's efficacy and safety in UC. We searched four electronic databases and analyzed only randomized clinical trials (RCT) that investigated the clinical and endoscopic efficacy of FMT in UC, regardless of administration route or dose. Clinical and endoscopic remission was assessed by comparing the odds ratio (OR) and 95% confidence interval (CI). The initial search yielded 6737 studies with 15 meeting inclusion criteria after duplicate removal and screening. The meta-analysis showed clinical remission in 62% receiving FMT vs. 50.5% in controls (OR 2.65; [1.76; 4.00]). The endoscopic response was 42% in the FMT group vs. 22% in controls (OR 2.00; [1.09; 3.68]). Heterogeneity was assessed as low (by I2 index and τ2). Our data show that FMT significantly improves clinical and endoscopic remission rates, offering a promising non-pharmacological option for UC patients unresponsive to conventional treatments. Further prospective studies are needed to optimize the formulation and dosing while also addressing the safety profile of FMT in UC.}, } @article {pmid41077748, year = {2025}, author = {Lee, HK and Shin, CM and Chang, YH and Jo, H and Choi, J and Choi, Y and Jun, YK and Yoon, H and Park, YS and Kim, N and Lee, DH}, title = {Predictors of Treatment Response to Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Pilot Study.}, journal = {Journal of neurogastroenterology and motility}, volume = {31}, number = {4}, pages = {462-476}, doi = {10.5056/jnm24183}, pmid = {41077748}, issn = {2093-0879}, abstract = {BACKGROUND/AIMS: We aim to investigate the effectiveness, safety, and predictors of treatment response to fecal microbiota transplantation (FMT) in Korean irritable bowel syndrome (IBS) patients.

METHODS: Patients with moderate to severe diarrhea-predominant IBS (IBS-D) or mixed-type IBS (IBS-M) received FMT from one healthy donor via esophagogastroduodenoscopy. IBS-symptom severity score (IBS-SSS), Bristol stool form scale (BSFS), IBS Quality of Life (IBS-QoL) questionnaires, Hospital Anxiety and Depression Scale (HADS), and gut microbiome profiles were assessed at baseline, 4 weeks and 12 weeks post-FMT.

RESULTS: Among the 46 enrolled IBS patients, 37 patients (IBS-D:IBS-M = 28:9) completed a 12-week follow-up. Significant improvements were observed in IBS-SSS, IBS-QoL, and BSFS after 12 weeks. FMT led to increased microbial diversity and a sustained increase in beneficial bacterial genera, including Holdemanella, Ruminococcus, and Faecalibacterium. In terms of β-diversity, the distance between the patient's gut microbiome and that of the donor decreased after FMT; greater reduction in distance to donor microbiota was associated with greater symptom improvement (Unweighted UniFrac distance, P < 0.05). Responders (IBS-SSS reduction > 50 points) exhibited lower baseline relative abundances of Roseburia and Subdoligranulum, and more profound microbiome shifts toward the donor profile after FMT.

CONCLUSIONS: FMT appears to be a potentially effective treatment for moderate to severe IBS, with significant symptom relief and gut microbiota changes. Lower baseline abundances of Roseburia and Subdoligranulum and greater shifts of gut microbiome profile toward donor microbiota after FMT may predict favorable FMT response. Long-term follow-up is on the way to assessing the durability of these effects.}, } @article {pmid41077742, year = {2025}, author = {Gweon, TG}, title = {Is Fecal Microbiota Transplantation Applicable for the Treatment of Irritable Bowel Syndrome? Time for Precision Medicine.}, journal = {Journal of neurogastroenterology and motility}, volume = {31}, number = {4}, pages = {403-404}, doi = {10.5056/jnm25146}, pmid = {41077742}, issn = {2093-0879}, } @article {pmid41077430, year = {2025}, author = {Polster, SP}, title = {The Role of the Microbiome and the Neurovascular Unit.}, journal = {The Surgical clinics of North America}, volume = {105}, number = {5}, pages = {857-869}, doi = {10.1016/j.suc.2025.06.008}, pmid = {41077430}, issn = {1558-3171}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Blood-Brain Barrier ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {The gut-brain axis plays a crucial role in neurovascular diseases, linking gut microbiota to blood-brain barrier integrity, neuroinflammation, and disease progression. Conditions such as cerebral cavernous malformations, traumatic brain injury, radiation-induced damage, and stroke exhibit microbiome-driven modulation that may be relevant to explain disease variance. Microbial metabolites have been shown to influence endothelial function and secondary brain injury mechanisms. Emerging interventions of dietary modifications, probiotics, fecal microbiota transplantation, and metabolite-based therapies show promise in mitigating neurovascular damage. Future research should focus on microbiome-targeted treatments, biomarker discovery, and personalized strategies to optimize neurovascular health through gut microbiome modulation.}, } @article {pmid41076929, year = {2025}, author = {Shi, W and Xi, M and Zhang, K and Yang, J and Cheng, X and Zang, H and Fan, W}, title = {Gut microbiota as a central mediator in hydrogen gas-induced alleviation of colitis via TLR4/NF-κB and Nrf2 pathway regulation.}, journal = {International immunopharmacology}, volume = {167}, number = {}, pages = {115671}, doi = {10.1016/j.intimp.2025.115671}, pmid = {41076929}, issn = {1878-1705}, abstract = {Inflammatory bowel disease (IBD) is a chronic and relapsing autoimmune disorder of the gastrointestinal tract with incompletely elucidated pathogenesis and limited therapeutic options. Although hydrogen gas (H2) has demonstrated therapeutic efficacy in various diseases including IBD, its mechanisms of action, particularly its interaction with the gut microbiota, remain poorly characterized. This study reveals that H2 inhalation effectively reversed dextran sulfate sodium (DSS)-induced dysbiosis by suppressing the expansion of potential pathogenic bacteria (e.g., Enterobacteriaceae and Escherichia-Shigella) and promoting potential beneficial microbes (e.g., Bacteroides and Lactobacillaceae), thereby restoring microbial homeostasis. Furthermore, H2 inhalation enhanced goblet cell density and mucus production, upregulated tight junction proteins (ZO-1 and occludin), and repaired intestinal barrier integrity. It also rebalanced the Treg/Th17 cell ratio, correcting immune dysregulation. At the molecular level, H2 inhalation suppressed the TLR4/NF-κB signaling pathway and activated the Keap1/Nrf2 antioxidant axis, leading to reduced production of pro-inflammatory cytokines and oxidative stress markers, alongside elevated antioxidant enzymes, collectively ameliorating colonic injury. In brief, the ameliorative effects of H2 are likely mediated through remodeling of the gut microbiota, restoration of the epithelial barrier, suppression of inflammatory signaling, and activation of antioxidant pathways. These findings were further validated by fecal microbiota transplantation (FMT) experiments. Collectively, this study links the therapeutic effects of H2 to structural and functional reprogramming of the gut microbiome, indicating that microbial ecological restoration is a central mechanism through which H2 alleviates colitis, thereby providing a mechanistic foundation for the therapeutic application of H2 inhalation in IBD.}, } @article {pmid41076730, year = {2025}, author = {Hull, MA and Sun, H}, title = {Omega-3 polyunsaturated fatty acids and gut microbiota.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {}, number = {}, pages = {}, pmid = {41076730}, issn = {1473-6519}, abstract = {PURPOSE OF REVIEW: Oral intake of n (omega)-3 polyunsaturated fatty acids (PUFAs) is associated with changes to gut microbiota. We review recent findings from 2024 onwards, which build the scientific case that changes to bacterial abundance, and their metabolites, contribute to the health benefits associated with n-3 PUFAs.

RECENT FINDINGS: There are now multiple studies in rodent disease models that demonstrate that n-3 PUFAs do not significantly alter bacterial diversity but, instead, alter abundance of several species that are implicated in short-chain fatty acid synthesis, in a model-specific manner. Limited intervention studies in humans, backed by larger observational studies, concur with the preclinical findings. Importantly, faecal transplantation experiments have confirmed that n-3 PUFA-induced changes to gut microbiota are causally related to reversal of the disease phenotype in two rodent models. In-vitro colonic models are now being used to understand the mechanism(s) underlying n-3 PUFA-induced changes to the gut microbiota and metabolome.

SUMMARY: Despite emerging proof that the gut microbiota contributes to n-3 PUFA activity in animal models, human data are sparse. It remains unclear how n-3 PUFAs affect changes to the gut microbiota or whether n-3 PUFA metabolism by gut microbes contributes to the host metabolome.}, } @article {pmid41075966, year = {2025}, author = {Wang, T and Huang, X and Lu, L and Luo, X and Wang, Y and Ma, Y and Tong, X and Zou, H and Gu, J and Liu, X and Bian, J and Liu, Z and Yuan, Y}, title = {The dysbiosis of gut microbiota attributes to the impairment of blood-brain barrier in rats triggered by cadmium.}, journal = {Toxicology}, volume = {}, number = {}, pages = {154303}, doi = {10.1016/j.tox.2025.154303}, pmid = {41075966}, issn = {1879-3185}, abstract = {Cadmium (Cd) is a non-biodegradable heavy metal with a long biological half-life that is detrimental to human health. As Cd can increase blood-brain barrier (BBB) permeability and disturb the gut microbiota, the relationship between the BBB and gut microbiota disturbance induced by Cd consumption remains unclear. This study aims to identify whether Cd-induced gut microbiota dysbiosis is associated with rat BBB injury and investigate the possible mechanism. Here, we conducted analyses of variations in the composition of the gut microbiota and its metabolites, as well as BBB permeability and the results of the Morris water maze test, in rats treated with Cd by gavage. Fecal microbiota transplantation was performed to verify the role of the microbiota in altering BBB permeability induced by Cd. The results showed that Cd disturbed the gut microbiota, decreasing the levels of short-chain fatty acids (SCFAs). Furthermore, Cd-induced BBB permeability was substantiated by FITC-dextran leakage, ultrastructural observations, and diminished Claudin-5, Occludin, and ZO-1 protein expression, all of which were mitigated by FMT. In vitro, sodium butyrate (SOB) alleviated Cd-induced oxidative stress and increased the expression levels of GPX4 and FTH. Taken together, these findings suggest that Cd disrupts the microbiota and SCFAs components in rats, thereby contributing to BBB damage. SOB prevents Cd-induced BBB damage by suppressing ferroptosis in microvascular endothelial cells. This exhaustive study considerably enhances our comprehension of the health hazards posed by Cd to the central nervous system via the gut-brain axis.}, } @article {pmid41075893, year = {2025}, author = {Huang, J and Yu, L and Zhang, C and Fang, Y and Zhou, X and Wang, R and Xing, L and Wang, L and Yu, N and Peng, D and Chen, W and Zhang, Y and Wang, Y}, title = {Water-soluble Poria cocos polysaccharide improves alcoholic liver disease via modulation of gut microbiota-mediated intestinal bile acids-farnesoid X receptor.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {148202}, doi = {10.1016/j.ijbiomac.2025.148202}, pmid = {41075893}, issn = {1879-0003}, abstract = {Alcoholic liver disease (ALD) is characterized by gut microbiota dysbiosis. This study aimed to elucidate the mechanism by which water-soluble Poria cocos polysaccharide (PCP) ameliorates ALD through modulation of the gut microbiota. PCP administration alleviated hepatic injury, reduced lipid accumulation, and attenuated inflammation in ALD mice. It also enhanced intestinal barrier integrity, as indicated by upregulation of tight junction proteins (ZO-1, Occludin, Claudin-1) and reduced lipopolysaccharide (LPS) levels. Additionally, PCP treatment remodeled the gut microbiota profile, characterized by a marked enrichment of Parabacteroides distasonis, which is associated with bile acid metabolism. Targeted metabolomics revealed PCP increased intestinal chenodeoxycholic acid (CDCA) and cholic acid (CA) levels, activating the intestinal farnesoid X receptor/fibroblast growth factor 15 (FXR/FGF15) axis while suppressing hepatic Cholesterol 7α-hydroxylase (CYP7A1), ultimately reducing systemic bile acids. Fecal microbiota transplantation confirmed gut microbiota-mediated protection, while intestinal FXR inhibition with glycine-β-muricholic acid (Gly-β-MCA) abolished PCP's therapeutic effects. These findings reveal that PCP ameliorates ALD by regulating the gut microbiota-bile acid-FXR axis, PCP as a promising natural therapeutic for ALD.}, } @article {pmid41075520, year = {2025}, author = {Gong, S and Xu, Y and Zhao, R and Yu, J and Bao, L and Zhang, Y and Li, F and Jiao, L and Kou, J}, title = {Xinqingning tablet attenuates ischemic stroke complicated by gut dysbiosis through regulating the miR-126-driven gut-brain axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {148}, number = {}, pages = {157356}, doi = {10.1016/j.phymed.2025.157356}, pmid = {41075520}, issn = {1618-095X}, abstract = {BACKGROUND: Ischemic stroke (IS), the predominant clinical stroke subtype, is increasingly linked to dysregulation of the gut-brain axis (GBA)-a bidirectional neuroendocrine-immune interface connecting intestinal homeostasis with cerebrovascular pathophysiology. Xinqingning Tablet (XQNT) demonstrates neuroprotective potential in IS complicated by gut dysbiosis (GD), yet its mechanisms of GBA modulation remain unclear.

METHODS: A dual-hit IS-GD mouse model was established via fecal slurry transplantation and permanent middle cerebral artery occlusion (pMCAO) surgery. Gut function was evaluated by constipation indices and histopathological changes, while the neuroprotective efficacy of XQNT (0.36, 0.48, and 0.61 g kg⁻¹) was assessed via TTC staining, neurological deficit scores, cerebral water content, and Evans blue (EB) extravasation assays. Additionally, Western blot was employed to quantify blood-brain barrier (BBB) and inflammation-associated proteins. microRNA sequencing was used to screen the differentially expressed miRNAs. miR-126 expression levels were measured by RT-qPCR, while concentrations of LPS, IL-6 and IL-10 were determined by ELISA. Finally, mechanistic validation employed intravenous miR-126 agonism/antagonism coupled with phenotypic rescue experiments.

RESULTS: XQNT conferred robust survival benefits, while concurrently ameliorating intestinal dysfunction and neurovascular injury. Mechanistically, XQNT elevated miR-126 expression, suppressing NF-κB-driven neuroinflammation. Additionally, miR-126 agonism phenocopied XQNT efficacy, whereas miR-126 inhibition abrogated therapeutic benefits.

CONCLUSIONS: This study provides early evidence that XQNT functions as a dual-target GBA modulator that alleviates IS with GD via regulation of the miR-126/NF-κB axis. By simultaneously promoting barrier restoration and inflammatory resolution, XQNT offers a promising therapeutic approach that links regulation of the gastrointestinal system with cerebrovascular protection.}, } @article {pmid41074196, year = {2025}, author = {Liu, Y and Dong, B and Yang, YL and Zhang, YQ and Zhang, Y and Pan, D and Du, EZ and Zhu, SJ and Wang, B and Huang, YW}, title = {Intestinal microbiota dynamics in piglets: the interplay with swine enteric coronavirus infections and implications for disease control.}, journal = {Animal microbiome}, volume = {7}, number = {1}, pages = {107}, pmid = {41074196}, issn = {2524-4671}, support = {32302873//National Natural Science Foundation of China/ ; U22A20521//National Natural Science Foundation of China/ ; }, abstract = {Infections of swine enteric coronavirus (SECoV), including porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV), cause severe diarrhea in piglets and result in substantial losses to the pig industry. The intestinal microbiota plays a crucial role in SECoV disease progression and outcomes, yet current research largely focuses on specific age groups or intestinal segments. This review provides a comprehensive analysis of the dynamic microbiota changes in piglets after SECoV infections across different ages and intestinal regions. It discusses differential microbiota analyses, functional changes, metabolic products, alongside their effects on immune responses. Additionally, we explore fecal bacterial transplantation as a potential intervention and highlight the role of the microbiota in either promoting or inhibiting SECoV infections. The development of advanced research tools, including culturomics, sequencing technologies, and multi-omics approaches, is pivotal in understanding the intricate relationship between the porcine intestinal microbiota and SECoV infections, offering potential strategies for preventing and controlling SECoV-related diseases.}, } @article {pmid41072839, year = {2025}, author = {Yu, G and Xie, W and Xiang, J and Ke, Y and Wang, Z and Tu, F and Wu, W and Hong, H and Lin, X}, title = {Gut microbiota remodelling alleviates elderly sepsis by microbiota-derived acetic acid via FFAR2/NLRP3 pathway.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {178229}, doi = {10.1016/j.ejphar.2025.178229}, pmid = {41072839}, issn = {1879-0712}, abstract = {BACKGROUND: Elderly patients with sepsis have higher morbidity, mortality, and susceptibility than adults. Young-donor faecal microbiota transplantation (FMT) can remodel and improve intestinal dysbiosis to alleviate age-related diseases via microbiota-derived acetic acid and may be a treatment option for elderly sepsis. This study aimed to elucidate the influence of remodelling of the elderly gut microbiota on sepsis via acetic acid and explore the underlying mechanism. We analyzed the gut microbiota and plasma acetic acid in elderly patients with sepsis, performed young-donor FMT, and acetic acid supplementation in a caecum ligation and puncture-induced aged septic model mice, and assessed the effects of acetic acid on the septic myocardium by examining NLRP3 inflammasome in FFAR2 knockdown mice.

RESULTS: Elderly sepsis had higher mortality, reduced gut microbiota diversity, increased Escherichia-Shigella abundance, and reduced plasma acetic acid levels. Young-donor FMT improved the gut microbiota, increased the abundance of the probiotic genus Akkermansia and faecal acetic acid levels in the gut, and improved colon barrier function and outcomes. Intestinal acetic acid intervention improved age-related intestinal dysbiosis, organ dysfunction, and adverse effects in aged septic mice. These beneficial effects on the myocardium were mediated by activation of the FFAR2/NLRP3 axis, as evidenced by the finding that FFAR2 knockdown abrogated the amelioration of acetic acid. The elderly gut microbiota is fragile, which is related to the severity and poor prognosis of elderly sepsis.

CONCLUSION: Gut microbiota remodelling improves elderly sepsis via acetic acid, which can inhibit inflammatory reactions to alleviate myocardial damage by FFAR2/NLRP3 inflammasome inactivation.}, } @article {pmid41072600, year = {2025}, author = {Wang, Y and Wang, X and Gan, B and Jia, T and Xu, T and Xu, H}, title = {The "Butterfly Effect" of Heart Failure: Induced by the Combination of Polylactic Acid Nanoplastics and Copper from the Perspective of Gut Microbiome.}, journal = {Chemico-biological interactions}, volume = {}, number = {}, pages = {111769}, doi = {10.1016/j.cbi.2025.111769}, pmid = {41072600}, issn = {1872-7786}, abstract = {Plastic and heavy metal pollution have received extensive attention, but there is relatively little research on the damage to the gut-heart axis induced by the co-exposure to plastics and heavy metals. This study investigated the impact of the co-exposure of Polylactic acid nanoplastics (PLA-NPs) and copper (Cu) on heart failure (HF) in mice and explored the role of the gut microbiota in mediating this adverse outcome. Male C57BL/6J mice were divided into four groups: the Control group, the PLA-NPs group, the Cu group, and the Co-exposure group (PLA-NPs+Cu group). A 28-day exposure experiment was conducted. The research results indicate that, compared with the Single-exposure groups (PLA-NPs and Cu groups), the mice of Co-exposure group exhibited more severe toxic effects, including more pronounced myocardial hypertrophy and more severe myocardial fibrosis. These damages might be caused by increasing the heart's sensitivity to ferroptosis. Additionally, the co-exposure caused significant damage to the gut barrier and remarkable dysbiosis in the gut microbiota, such as a reduction in the abundances of beneficial bacteria like Lactobacillus. The fecal Microbiota Transplantation experiment confirmed that the alterations in gut microbiota play a pivotal role in the synergistic toxicity induced by PLA-NPs and Cu. This study for the first time reveals the mechanism of the combined effect of PLA-NPs and Cu on cardiac damage and emphasizes the crucial role of gut microbiota in this process.}, } @article {pmid41071393, year = {2025}, author = {Wasim, R}, title = {The gut immune axis in ulcerative colitis: insights from microbiome research.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {1006}, pmid = {41071393}, issn = {1573-4978}, mesh = {Humans ; *Colitis, Ulcerative/microbiology/immunology/therapy ; *Gastrointestinal Microbiome/immunology ; Fecal Microbiota Transplantation/methods ; Dysbiosis/microbiology/immunology ; Probiotics/therapeutic use ; Intestinal Mucosa/immunology/microbiology ; Prebiotics ; Animals ; }, abstract = {Ulcerative colitis (UC) is a chronic, recurrent inflammatory bowel disease (IBD) marked by inflammation of the colonic mucosa. While its precise aetiology remains unclear, emerging evidence underscores the pivotal role of gut microbiota in UC pathogenesis. In healthy individuals, the gut microbiota contributes to immune modulation, nutrient absorption, and maintenance of intestinal barrier integrity. In contrast, individuals with UC exhibit gut dysbiosis-characterized by a reduction in beneficial bacteria such as Faecalibacterium prausnitzii and Bifidobacterium, and an increase in potentially pathogenic microbes like Escherichia coli. This microbial imbalance disrupts mucosal homeostasis, promotes persistent inflammation, and impairs epithelial healing. Contributing factors include genetic predisposition, antibiotic exposure, diet, and environmental influences. Novel microbiota-targeted interventions-such as probiotics, prebiotics, dietary modifications, and faecal microbiota transplantation (FMT)-are being actively explored, with promising preliminary outcomes in symptom relief and microbiome restoration. However, challenges persist in defining a "healthy" microbiome and standardizing therapeutic protocols. This study highlights the potential of microbiome modulation as a transformative approach in UC management and calls for further research into host-microbe interactions to advance precision-based, microbiota-oriented therapies.}, } @article {pmid41067318, year = {2025}, author = {Zhao, H and Li, Y and Liu, N and Chen, P and Yu, X and Li, G and Deng, B and Li, D and Yang, F and Wang, G}, title = {Ganoderma lucidum polysaccharides alleviate non-alcoholic fatty liver disease by modulating gut microbiota against TLR4/NF-κB/MAPK pathway and activating AMPK pathway.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {120723}, doi = {10.1016/j.jep.2025.120723}, pmid = {41067318}, issn = {1872-7573}, abstract = {Ganoderma lucidum (Leyss. ex Fr.) Karst has been a revered traditional Chinese medicinal herb, widely used in folk medicine to treat various metabolic diseases due to its remarkable bioactivities. Among its active components, G. lucidum polysaccharides are particularly recognized as one of the main contributors to its therapeutic effects. However, the therapeutic efficacy of G. lucidum polysaccharides against non-alcoholic fatty liver disease (NAFLD) and its underlying mechanisms remain to be elucidated.

AIMS OF THE STUDY: This study aimed to assess the therapeutic efficacy of a novel polysaccharide (EPGLa) derived from G. lucidum in the treatment of NAFLD and to elucidate its underlying mechanisms.

MATERIALS AND METHODS: The chemical characterization of the isolated and purified EPGLa was conducted using monosaccharide composition analysis, Fourier-transform infrared (FT-IR) spectroscopy, molecular weight determination, methylation analysis, and 1D/2D nuclear magnetic resonance (NMR) spectroscopy. Following the establishment of a NAFLD mouse model, the therapeutic effect of EPGLa on NAFLD was assessed, and its underlying mechanism was clarified.

RESULTS: The backbone of EPGLa consists of the following glycosidic linkages: →6)-β-D-Glcp-(1→, →3)-β-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, →3,6)-β-D-Manp-(1→, →2)-α-D-Manp-(1→, and →4)-β-D-Galp-(1→. Its branches are composed of β-D-Glcp-(1→, β-D-Glcp-(1→3)-β-D-Glcp-(1→, and α-L-Fucp-(1→. In vivo results demonstrated that EPGLa effectively alleviated NAFLD by promoting the growth of beneficial gut bacteria to repair the intestinal barrier against Lipopolysaccharides (LPS)/toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB)/mitogen-activated protein kinase (MAPK) pathways, and simultaneously enhancing short-chain fatty acid (SCFA) production to activate the AMP-activated protein kinase (AMPK) pathway. To further validate these findings, we employed fecal microbiota transplantation (FMT), which confirmed the role of EPGLa in modulating gut microbiota against NAFLD.

CONCLUSION: Our study provides compelling evidence that EPGLa holds promise as a potential therapeutic agent for the intervention of NAFLD, and our findings also offer novel insights into the therapeutic targets of other bioactive polysaccharides.}, } @article {pmid41067200, year = {2025}, author = {Ding, L and Li, Q and Qi, K and Chen, Y and Hu, N and Hu, S and Fang, T and Guan, S and Wang, J and Qiu, J and Deng, X and Xu, L}, title = {Phloretin alleviates Salmonella pullorum infection by modulating gut microbiota-derived 3-phenylpropionic acid and AhR/IL-22/STAT-3 axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {148}, number = {}, pages = {157350}, doi = {10.1016/j.phymed.2025.157350}, pmid = {41067200}, issn = {1618-095X}, abstract = {BACKGROUND: Salmonella pullorum (S. pullorum) is an enteric pathogen that impairs growth performance, leading to substantial economic losses. Evidence demonstrates that the natural flavonoid phloretin can modulate gut microbiota functionality, and which underpins its therapeutic efficacy in ameliorating gastrointestinal disorders. However, the protective effects of phloretin against S. pullorum infections and underlying mechanisms remain unelucidated.

PURPOSE: This study aimed to elucidate the protective effects and mechanisms of phloretin in improving defense against S. pullorum infection by modulating gut microbiota in chicks.

METHODS: H&E staining, RT-qPCR and ELISA assays were used to assess the protective potentials of phloretin in S. pullorum-infected chicks. Then, 16S rRNA gene sequencing and untargeted metabolomics were employed to identify key microbiota and metabolites regulating the intestinal microenvironment. Moreover, fecal microbiota transplantation (FMT) and dietary metabolite supplementation were conducted to reshape the gut microbiota, elucidate the interaction between the microbiota and S. pullorum infection.

RESULTS: Phloretin treatment alleviated intestinal injury and enhanced growth performance in S. pullorum-infected chicks via improved intestinal barrier integrity, suppression of inflammatory responses, and restructuring of gut microbial composition. Additionally, these beneficial effects were also observed following FMT from phloretin-treated donors. Subsequent microbial and untargeted metabolomic analysis revealed that phloretin significantly enriched abundance of the functional bacterium Faecalibacterium, and the microbiota-derived phenylalanine metabolites 3-phenylpropionic acid (3-PPA). Importantly, 3-PPA supplementation attenuates S. pullorum-induced intestinal barrier damage and inflammation in chicks through modulation of the AhR/IL-22/STAT-3 signalling axis.

CONCLUSION: These findings provide new insights into the therapeutic potentials of phloretin for S. pullorum-infected chicks.}, } @article {pmid41066868, year = {2025}, author = {Zeng, Z and Li, H and Yang, W and Li, L and Ni, P and Chen, Q and Zhou, W and Peng, J and Huang, L}, title = {Probiotic VSL#3 alleviates intrahepatic cholestasis of pregnancy by upregulating farnesoid X receptor-fibroblast growth factor 15 through regulation of the gut microbiota.}, journal = {Journal of reproductive immunology}, volume = {172}, number = {}, pages = {104653}, doi = {10.1016/j.jri.2025.104653}, pmid = {41066868}, issn = {1872-7603}, abstract = {Intrahepatic cholestasis of pregnancy (ICP) poses significant risks to both maternal and fetal health, and treatment options remain limited. This study investigated the efficacy and underlying mechanisms of VSL#3 in alleviating ICP. Clinical fecal and blood samples were collected from 26 patients with ICP and 21 healthy pregnant women. The gut microbiota composition was analyzed using 16S rRNA sequencing. To further explore causality, we established a fecal microbiota transplantation-ICP mouse model using fecal samples from ICP patients, as well as an estrogen-induced ICP mouse model. Compared with healthy pregnant women, ICP patients exhibited a distinct gut microbiota profile, characterized by an increased abundance of Bacteroides and Alistipes. Serum FGF19 levels were significantly lower in ICP patients, showing a negative correlation with liver function markers, such as serum total bile acid (TBA), and a positive correlation with beneficial genera including Bifidobacterium, Ruminococcus, Blautia, Dorea, Eubacterium (hallii group) and Ruminococcus (torques group). VSL#3 treatment in mice alleviated ICP manifestations by improving liver histopathology, reducing TBA and alanine aminotransferase levels, increasing FGF15 concentrations, and enhancing fetal outcomes. These beneficial effects were abolished by co-administration of the FXR antagonist Z-guggulsterone, confirming the role of FXR signaling. In conclusion, VSL#3 alleviated ICP by modulating the gut microbiota to activate the FXR-FGF15 axis, thereby reducing bile acid synthesis and improving maternal and fetal outcomes.}, } @article {pmid41065216, year = {2025}, author = {Heer, P and Fernandez Elviro, C and Koutsokera, A and Mornand, A and Rochat, I and Regamey, N and Blanchon, S}, title = {Identification of early changes in multiple biomarkers following CFTR modulator initiation in patients with cystic fibrosis.}, journal = {Therapeutic advances in respiratory disease}, volume = {19}, number = {}, pages = {17534666251376211}, doi = {10.1177/17534666251376211}, pmid = {41065216}, issn = {1753-4666}, mesh = {Humans ; *Cystic Fibrosis/drug therapy/physiopathology/diagnosis/genetics/metabolism ; *Cystic Fibrosis Transmembrane Conductance Regulator/genetics/metabolism/drug effects ; Male ; Female ; *Aminophenols/therapeutic use/adverse effects ; *Benzodioxoles/therapeutic use/adverse effects ; *Quinolones/therapeutic use/adverse effects ; Prospective Studies ; Child ; Biomarkers/metabolism/blood ; Adolescent ; Treatment Outcome ; *Aminopyridines/therapeutic use ; Time Factors ; *Indoles/therapeutic use/adverse effects ; *Chloride Channel Agonists/therapeutic use/adverse effects ; Drug Combinations ; Young Adult ; *Pyrazoles/therapeutic use ; Sweat/chemistry ; Adult ; Pyrrolidines/therapeutic use ; }, abstract = {BACKGROUND: There are currently no early parameters that allow prediction of long-term responses to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator treatment on an individual level.

OBJECTIVES: To identify early parameters measured within 7 to 14 days after initiation of treatment with a CFTR modulator to assess CFTR modulator efficacy.

STUDY DESIGN: Prospective observational study of patients diagnosed with CF who begin elexacaftor/tezacaftor/ivacaftor (ETI) therapy at 3 CF clinics in Switzerland (Geneva, Lausanne, Lucerne).

METHODS: Standardized measurements were taken within 2 months prior to and 7 to 14 days after starting CFTR modulator treatment.

RESULTS: ETI treatment was started on 47 patients [median age: 12 years] of whom 12 (26%) were switching from lumacaftor/ivacaftor (n = 8) or tezacaftor/ivacaftor (n = 4) to ETI. A significant early treatment effect was observed for BMI z-score (p < 0.001) and inflammatory parameters (white blood cells (p = 0.006), neutrophils (p = 0.006), immunoglobulin G (p = 0.012), and fecal calprotectin (p = 0.002)). In CFTR functional assays, sweat chloride concentration and nasal potential difference testing [Δlow-chloride+isoproterenol, Sermet score, and Wilschanski index] improved significantly (all p < 0.001). Improvement was also observed in lung function (FVC, FEV1, MMEF25-75, LCI2.5%) (all p < 0.001). No changes were found for blood pressure, SpO2, respiratory rate, erythrocyte sedimentation rate, C-reactive protein, and fecal elastase.

CONCLUSION: This study identified clinical, biologic, and functional parameters showing treatment effect early after initiation of CFTR modulator therapy. These parameters may serve as potential predictors of long-term responses to CFTR modulator treatment.}, } @article {pmid41064515, year = {2025}, author = {Aumpan, N and Chonprasertsuk, S and Pornthisarn, B and Siramolpiwat, S and Bhanthumkomol, P and Issariyakulkarn, N and Gamnarai, P and Bongkotvirawan, P and Wongcha-Um, A and Mahachai, V and Vilaichone, RK}, title = {Efficacy of encapsulated fecal microbiota transplantation and FMT via rectal enema for irritable bowel syndrome: a double-blind, randomized, placebo-controlled trial (CAP-ENEMA FMT Trial).}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1648944}, pmid = {41064515}, issn = {2296-858X}, abstract = {INTRODUCTION: Irritable bowel syndrome (IBS) is a functional bowel disorder. Gut dysbiosis involves in pathogenesis of IBS. Limited studies compared efficacy of fecal microbiota transplantation (FMT) via different routes of administration. This study aimed to compare efficacy of encapsulated FMT, FMT via rectal enema, and placebo in IBS patients.

METHODS: In this double-blind, randomized, placebo-controlled study, we enrolled patients aged 18-70 years with IBS defined by Rome IV criteria at Thammasat university, Thailand. Patients were randomized into three groups: (1) encapsulated FMT (six capsules twice daily for two consecutive days, total 50 g of stool), (2) FMT via rectal enema (50 g of stool in 200 mL of isotonic saline), or (3) placebo. Primary endpoint was clinical response defined by ≥50-point decrease in IBS-symptom severity score (IBS-SSS) at 4 weeks. Secondary outcomes were quality of life and changes of fecal microbiota composition after treatment. The study was registered with ClinicalTrials.gov, number NCT06201182.

RESULTS: From August 20, 2020, to February 15, 2024, 45 patients were randomized to receive encapsulated FMT (n = 15), FMT via rectal enema (n = 15), or placebo (n = 15). There was no difference in patient characteristics and baseline IBS-SSS between groups. Encapsulated FMT provided significantly improved IBS-SSS (166.7 ± 73.7 vs. 269.3 ± 69.5, p = 0.001), clinical response (86.7 vs. 26.7%, p = 0.001), and quality of life (31.7 ± 4.8 vs. 25.1 ± 5.2, p < 0.001) at 4 weeks compared with placebo. FMT via rectal enema demonstrated better IBS-SSS (168.7 ± 101.9 vs. 269.3 ± 69.5, p = 0.004), clinical response (73.3 vs. 26.7%, p = 0.011), and quality of life (30.2 ± 5.0 vs. 21.0 ± 7.4, p < 0.001) than placebo. Clinical response and quality of life between encapsulated FMT and FMT via rectal enema were not different. No serious adverse event was observed. Minor adverse events such as bloating and diarrhea were not different between all groups.

CONCLUSIONS: Higher clinical response and quality of life were demonstrated in both FMT groups than placebo. Either encapsulated FMT or FMT via rectal enema was safe and could provide favorable outcomes for IBS patients.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT06201182, Identifier: NCT06201182.}, } @article {pmid41063317, year = {2025}, author = {Gong, K and Zhang, S and Pan, Y and Cai, Q and Wu, M and Yin, X and Ma, J and Ji, H and Wang, Z and Wu, W and Zheng, H}, title = {Alternate day fasting alleviates neuroinflammation in diabetic mice by regulating δ-valerobetaine-carnitine-microglia axis via enrichment of Akkermansia muciniphila.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {202}, pmid = {41063317}, issn = {2049-2618}, support = {22074106//National Natural Science Foundation of China/ ; LY23H090008//Zhejiang Provincial Natural Science Foundation of China/ ; }, mesh = {Animals ; Mice ; *Carnitine/metabolism ; Gastrointestinal Microbiome/physiology ; *Fasting ; *Microglia/metabolism ; Akkermansia ; *Neuroinflammatory Diseases/metabolism ; *Diabetes Mellitus, Type 1/microbiology/metabolism ; *Verrucomicrobia ; Mice, Inbred C57BL ; *Diabetes Mellitus, Experimental/microbiology ; Male ; *Betaine/metabolism/analogs & derivatives ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Alternate day fasting (ADF) as a healthy dietary pattern has been reported to improve brain functions and behaviors, but the effect of ADF on diabetes-related brain disorders and the potential mechanisms remain unclear. In this study, we investigated the impact of ADF on neuroinflammation and exploratory behavior in type 1 diabetic (T1D) mice and explored the specific molecular mechanisms from the perspective of the gut microbiota and host metabolism.

RESULTS: ADF can effectively relieve neuroinflammation and exploratory behavioral disorders in T1D mice. According to fecal microbiota transplant and bacterial supplementation, we demonstrated that ADF-driven enrichment of Akkermansia muciniphila (AKK) was necessary for boosting exploratory behavior in T1D mice. The gut microbiota-derived metabolite δ-valerobetaine (VB) reduced hepatic carnitine synthesis by inhibiting BBOX, and caused exploratory behavioral disorders in mice. In vitro and in vivo studies revealed that AKK bacteria had the ability to consume VB, and thereby increased systemic carnitine level. In addition, carnitine was found to deplete lipid droplet accumulation in microglia by enhancing fatty acid oxidation and lipolysis, reduce neuroinflammation and neuron injury, and then increase exploratory behavior in T1D mice.

CONCLUSIONS: Our study sheds light on the gut-liver-brain metabolic axis mechanism on the protective role of ADF in T1D-associated neuroinflammation and exploratory behavioral disorders and AKK bacteria exert as a key mediator. Video Abstract.}, } @article {pmid41061446, year = {2025}, author = {Zhang, J and Lv, Y and Yang, S and Li, H and Luo, Y and Tang, X and Xu, J and Liu, X}, title = {Deciphering the regulatory role of selenium on cadmium bioavailability and toxicity: From the perspective of gut microbiota.}, journal = {Ecotoxicology and environmental safety}, volume = {305}, number = {}, pages = {119193}, doi = {10.1016/j.ecoenv.2025.119193}, pmid = {41061446}, issn = {1090-2414}, abstract = {Residents in areas naturally rich in cadmium (Cd) and selenium (Se) frequently exhibit exceptional longevity, raising intriguing questions about the interplay between the two elements. However, whether co-exposure affects the bioavailability of Cd remains unclear. Meanwhile, it is necessary to unclose the antagonistic mechanisms between Se and Cd. Here, a mouse bioassay was conducted to assess the impact of Se addition at low (0.1 mg/kg), medium (0.5 mg/kg) and high (2 mg/kg) doses, and duration (10 and 30 d) on Cd bioavailability of rice and Cd-induced hepatic toxicity. Results showed that Se cannot reduce Cd bioavailability. Medium Se addition for a duration of 10 days (MSe10) exhibited the highest efficacy in attenuating hepatic inflammation, as evidenced by augmented antioxidant enzyme activity, alleviated pathological damage, and increased levels of anti-inflammatory metabolites within the liver. The benefit was associated with its restoration of the gut microbiota and changes in key metabolic pathways. Notably, MSe10 increased the abundance of Faecalibaculum and Dubosiella, and enhanced the levels of secondary bile acids. Neither 0.1 mg/kg, 2 mg/kg nor long time addition of Se was beneficial for liver recovery. The hepatic lesions were fecal microbiota-dependent, as supported by fecal microbiota transplantation. Microbiota from MSe10 were capable to ameliorate hepatic inflammation, strengthen the intestinal barrier, and inhibit lipopolysaccharides (LPS) accumulation in blood. Additionally, the study provided insights into Se as an intervention for Cd toxicity, highlighting the appropriate dosage and its potential to reduce health risks.}, } @article {pmid41061376, year = {2025}, author = {Wekking, D and Ende, TVD and Bijlsma, MF and Vidal-Itriago, A and Nieuwdorp, M and van Laarhoven, HWM}, title = {Fecal microbiota transplantation to enhance cancer treatment outcomes across different cancer types: A systematic literature review.}, journal = {Cancer treatment reviews}, volume = {140}, number = {}, pages = {103025}, doi = {10.1016/j.ctrv.2025.103025}, pmid = {41061376}, issn = {1532-1967}, abstract = {BACKGROUND: The gut microbiome is increasingly recognized as a critical modulator of cancer therapy response. This systematic review evaluates Fecal Microbiota Transplantation (FMT)'s impact on cancer treatment outcomes and treatment-related toxicity and explores its mode of action.

METHODS: A systematic search was conducted for prospective or retrospective clinical studies published until May 2025 that investigated FMT in cancer patients undergoing immunotherapy, chemotherapy, radiotherapy, targeted therapy, or a combination regimen.

RESULTS: 45 studies were included. No large-scale RCTs with published efficacy data were available, and most findings were derived from studies that lacked statistical power to assess efficacy. The majority of the articles demonstrated the safety and feasibility of FMT. Most toxicities reported were grade 1 or 2. Mechanistically, donor FMT restores gut microbiota diversity and reprograms the gut ecosystem, with increases in tumor-infiltrating lymphocytes and lower levels of regulatory T cells being observed. Furthermore, studies reported clinical improvement and endoscopic and/or histologic remission of treatment-induced colitis following FMT, alongside decreased colonic CD8+ T cell infiltration.

CONCLUSION: Donor FMT appears to be a safe and feasible adjunctive strategy during both first and later-line therapy and has potential for managing treatment-related colitis; however, its efficacy and its role in preventing immune-related adverse events remain to be elucidated in RCTs, as well as its application for graft-versus-host disease. The variability in clinical outcomes and context-dependent microbiota-host interactions that result in inconsistent findings underscores the complexity of FMT as a therapeutic modality. Furthermore, subclassifying recipient cancer patients could (based on gut microbiome ecosystem features) enhance biomarker identification for treatment responses.}, } @article {pmid41059058, year = {2025}, author = {Wang, Y and Bai, Z and Liu, Y and Wang, Y and Xu, J and Lai, Z}, title = {Influence of the gut microbiota on the pharmacokinetics of tacrolimus in liver transplant recipients: insights from microbiome analysis.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1616985}, pmid = {41059058}, issn = {1664-302X}, abstract = {INTRODUCTION: Tacrolimus is crucial for immunosuppression after liver transplantation, but its pharmacokinetics vary markedly among individuals. Emerging evidence suggests that the gut microbiota may influence its metabolism, although the underlying mechanisms remain unclear.

METHODS: This study analyzed the fecal microbiota from 38 postliver transplant patients and 31 healthy controls via 16S rDNA amplicon and shotgun metagenomic sequencing. Patients were stratified into three groups on the basis of oral tacrolimus dosage and blood concentration: LDLBC (low dose, low blood concentration), LDHBC (low dose, high blood concentration), and SDLBC (standard dose, low blood concentration).

RESULTS: Posttransplant patients presented significantly reduced gut microbial diversity. Specific bacterial taxa, including Enterococcus raffinosus, Intestinibacter bartlettii, and Bacteroides fragilis, were enriched in patients with lower tacrolimus blood concentrations. In contrast, Phascolarctobacterium faecium and Streptococcus salivarius were associated with increased drug levels. Functional analysis revealed differences between patient subgroups in ATP-binding cassette (ABC) transporters and drug efflux pumps, suggesting a potential microbial influence on tacrolimus absorption and metabolism. Additionally, antibiotic resistance genes were more abundant in patients with lower tacrolimus blood concentrations, particularly in the Escherichia coli-enriched groups.

DISCUSSION: These findings underscore the influence of the gut microbiota on tacrolimus pharmacokinetics and support the potential of microbial composition as a biomarker for optimizing immunosuppressive therapy.}, } @article {pmid41057955, year = {2025}, author = {Chen, W and Liu, C and Li, X and Yang, X and Liu, Y and Qin, M and Jiang, W and Wang, Y and Sun, H and Li, G and Wen, B and He, S}, title = {5,7-dimethoxyflavone inhibits hepatocellular carcinoma progression via increasing intestinal Akkermansia muciniphila and hepatic CD8[+] T cell infiltration.}, journal = {Chinese medicine}, volume = {20}, number = {1}, pages = {170}, pmid = {41057955}, issn = {1749-8546}, support = {82405072//National Natural Science Foundation of China/ ; 82304927//National Natural Science Foundation of China/ ; 82274286//National Natural Science Foundation of China/ ; 2023A1515110041//Joint Funds of Basic and Applied Basic Research Fund of Guangdong/ ; 2023M741596//China Postdoctoral Science Foundation/ ; }, abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) mainly develops in cases of fibrosis and cirrhosis and is accompanied by intestinal flora disorder. HCC also affects CD8[+] T cell immune function. 5,7-Dimethoxyflavone (DMF), an active flavonoid with anti-tumor effect, is found in Kaempferia parviflora. However, whether DMF can treat HCC remains unclear. This study aims to investigate the effect of DMF on HCC and to explore its possible mechanism, focusing on the gut microbiota regulation and the effect of CD8[+] T cells in a murine model.

METHODS: The HCC mouse model was induced with diethylnitrosamine/carbon tetrachloride and orally administered DMF. DMF effects on HCC progression were assessed using hematoxylin and eosin staining, immunohistochemistry, and serum biochemical marker levels. The causal relationship between gut microbes and HCC was explored using 16S rRNA genome-derived taxonomic profiling, microbial transplantation, fecal high-throughput targeted metabolomics, and untargeted serum metabolomic analyses. Transcriptome analysis, molecular docking, quantitative real-time polymerase chain reaction, and Western blot were applied to study the genes targeted by DMF. CD8[+] T cell infiltration and tumor-killing factors were studied using flow cytometry and immunofluorescence staining.

RESULTS: DMF reduced the number of tumors, the largest tumor size, and the liver-to-body ratio while also improving liver function. An antibiotic cocktail lowered the anti-tumor effect of DMF, indicating that DMF inhibition of HCC is partially dependent on the gut microbiota. DMF considerably upregulates Akkermansia muciniphila during chemical hepatocarcinogenesis in mice. DMF-upregulated A. muciniphila leading to intestinal barrier repair, which inhibited HCC progression by enhancing antioxidant capacity through glutathione regulation and 11,12-DIHETrE down-regulation. An untargeted serum metabolomic analysis showed that there existed additional mechanisms underlying DMF anti-tumor effect following its absorption into the bloodstream. DMF enhances the infiltration effect of CD8[+] T cells and upregulates interferon-gamma expression in HCC tissue. Overall, 822 genes, including chemokine (C-C motif) ligand 2 (CCL2), were significantly downregulated by DMF treatment in HCC cells. Notably, DMF binds strongly with nuclear factor kappa-B (NF-κB) and inhibits NF-κB p65 phosphorylation, sequentially suppressing the expression of downstream protein CCL2, which mediate the crosstalk between tumor cells and CD8[+] T cells.

CONCLUSION: DMF improves A. muciniphila-mediated intestinal barrier repair and inhibits the NF-κB/CCL2 pathway in HCC cells, enhancing the immunity of CD8[+] T cells in the liver. Hence, it may serve as a potential candidate for HCC treatment.}, } @article {pmid41055380, year = {2025}, author = {Du, J-Y and Zhang, Z-J and Tan, L and Yang, J-Y and Yang, R-N and Chen, Y-L and Tan, G-F and Li, J and Li, W-J and Yang, L and Cai, J and Shen, D-L and Zhu, H-R and Fan, Z-X and Yuan, M-L and Zhang, W}, title = {Gut microbiota dysbiosis and metabolic perturbations of bile/glyceric acids in major depressive disorder with IBS comorbidity.}, journal = {mBio}, volume = {}, number = {}, pages = {e0244725}, doi = {10.1128/mbio.02447-25}, pmid = {41055380}, issn = {2150-7511}, abstract = {Major depressive disorder (MDD) and irritable bowel syndrome (IBS) exhibit high comorbidity, yet their shared pathophysiology remains unclear. Previous studies have primarily focused on the psychological health in the IBS population, without considering psychiatric diagnoses or stratifying different psychological states, potentially leading to biased findings. This study employed multi-omics approaches to characterize gut microbiota and serum metabolites in 120 MDD patients (47 with IBS and 73 without IBS) and 70 healthy controls (HCs). MDD with IBS patients showed significantly higher depression (Hamilton depression scale [HAMD-17]) and anxiety (Hamilton anxiety scale [HAMA-14]) scores than MDD-only patients (P < 0.05). Metagenomic sequencing of fecal samples revealed increased alpha diversity (Chao1/Shannon indices) and Firmicutes dominance in both MDD groups vs HC, while Actinobacteria enrichment specifically marked MDD with IBS. Functionally, MDD with IBS uniquely activated D-amino acid/glycerolipid metabolism pathways (Kyoto Encyclopedia of Genes and Genomes). Serum metabolomics identified comorbid-specific perturbations: downregulation of bile acids (CDCA, GCDCA, GCDCA-3S) and upregulation of glyceric acid/glutaconic acid. Our study also found that Eggerthella lenta and Clostridium scindens are differentially abundant bacteria that are involved in bile acid metabolism, and that microbial genes (e.g., K03738) are associated with glyceric acid production. These findings implicate gut microbiota-driven bile acid/glyceric acid dysregulation in MDD with IBS comorbidity, supporting the gut-brain axis as a therapeutic target for probiotics or microbiota transplantation.IMPORTANCEMajor depressive disorder (MDD) exhibits a high comorbidity rate with irritable bowel syndrome (IBS). Our study, conducted on 120 MDD patients (47 of whom were comorbid with IBS) and a control group of 70 individuals, revealed that MDD-IBS comorbid patients demonstrated significantly higher depression/anxiety scores. Multi-omics analysis indicated substantial alterations in the gut microbiota (e.g., Firmicutes, Actinobacteria) and serum metabolites (e.g., bile acids, glyceric acid) among MDD-IBS patients, which were associated with specific metabolic pathways. Therefore, the new aspect of this study was the inclusion of patients with MDD but without IBS symptoms, which provided a deeper understanding of the intestinal microbiota dysregulation associated with comorbid IBS and MDD. These findings suggest that there may be involvement of the gut-brain axis, providing new research directions for potential therapeutic targets.CLINICAL TRIALSThis study is registered with the Chinese Clinial Trial Registry as ChiCTR2100041598.}, } @article {pmid41052982, year = {2025}, author = {Cao, Y and Fan, X and Zang, T and Qiu, T and Fang, Q and Bai, J and Liu, Y}, title = {Prenatal depression-associated gut microbiota induces depressive-like behaviors and hippocampal neuroinflammation in germ-free mice.}, journal = {Translational psychiatry}, volume = {15}, number = {1}, pages = {383}, pmid = {41052982}, issn = {2158-3188}, support = {2023AFB710//Natural Science Foundation of Hebei Province (Hebei Provincial Natural Science Foundation)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Female ; *Hippocampus/metabolism/pathology/immunology ; Mice ; Pregnancy ; Fecal Microbiota Transplantation ; *Depression/microbiology/metabolism ; *Dysbiosis/microbiology/complications ; Humans ; Lipopolysaccharides/blood ; Germ-Free Life ; *Neuroinflammatory Diseases/metabolism/microbiology ; Microglia ; *Pregnancy Complications/microbiology ; Disease Models, Animal ; Behavior, Animal ; Interleukin-6/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Numerous studies have described the role of the microbiome-gut-brain axis in depression. However, the molecular mechanisms underlying the involvement of gut microbiota in the development of prenatal depression are limited. In this study, fecal microbiota from women with prenatal depression was transplanted into germ-free mice to investigate the potential causal relationships between the gut microbiota and depressive phenotypes. Shotgun metagenomic sequencing and untargeted metabolomics approaches were used to investigate the characteristics of gut microbiota and microbial metabolites. The levels of neuroinflammation in the brain were detected using immunofluorescence and real-time quantitative PCR. We found significant changes in gut microbiota composition and metabolites in mice with fecal microbiota transplantation (FMT) from women with prenatal depression, including decreased Ligilactobacillus, increased Akkermansia, and abnormal glycerophospholipid metabolism. Besides, significant increase in plasma lipopolysaccharide (LPS) levels and significant proliferation of microglia in the hippocampus were observed in mice receiving FMT from women with prenatal depression, accompanied by a significant increase in the expression of nuclear factor-κB (NF-κB) p65, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA. The gut microbiota and its metabolites were strongly associated with depressive-like behaviors, plasma LPS and neuroinflammation. Our study collectively demonstrates that dysbiosis of the gut microbiota may play a causal relationship in the development of prenatal depression. This process potentially involves the activation of neuroinflammation through the LPS-NF-κB signaling pathway.}, } @article {pmid41052746, year = {2025}, author = {Chen, Y and Yu, L and Zhang, L and Liu, C and You, Y and Guo, H and Li, Z and Yin, X and Hong, T and Ding, L and Fang, Q}, title = {Gut microbiota dysbiosis exacerbates post-stroke depression via microglial NLRP3 inflammasome activation.}, journal = {Experimental neurology}, volume = {}, number = {}, pages = {115488}, doi = {10.1016/j.expneurol.2025.115488}, pmid = {41052746}, issn = {1090-2430}, abstract = {BACKGROUND: Post-stroke depression (PSD) is a neuropsychiatric complication prevalent among stroke survivors. Emerging evidence suggests that dysregulation of the microbiota-gut-brain axis is implicated in the pathogenesis of PSD. However, the exact mechanism is not clear and further research is necessary.

METHODS: Initially, Sprague-Dawley (SD) rats were randomly allocated into three experimental groups: Sham, Middle Cerebral Artery Occlusion (MCAO), and PSD. Behavioral tests were conducted to evaluate depressive-like behavior. Fecal samples from all groups underwent 16S rRNA sequencing for comprehensive gut microbiota analysis. Colonic tissues were collected from rats and subjected to immunohistochemical analysis for quantification of tight junction proteins (ZO-1, Occludin, and Claudin). Peripheral blood plasma was obtained for the determination of IL-1β, IL-6, TNF-α, and IL-18 levels using enzyme-linked immunosorbent assay (ELISA). Lastly, hippocampus tissues were harvested for molecular characterization of Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation and inflammatory cytokines expression through tripartite methodology: Reverse Transcription quantitative PCR (RT-qPCR), Western blot, and immunofluorescence. Concurrently, hippocampal concentrations of 5-HT, BDNF, and PSD-95 were also measured by ELISA. Subsequently, Fecal Microbiota Transplantation (FMT) was performed by administering fecal suspensions from PSD and Sham donor rats to healthy SD recipients via oral gavage. Then, use the above methods to test the same indicator.

RESULT: Comparative analyses showed that microbial species richness and diversity indices were significantly reduced in PSD model rats, along with a compositional imbalance of the gut microbiota. Concurrently, reduced expression of the colonic tight junction proteins ZO-1, Occludin, and Claudin was observed, accompanied by elevated levels of peripheral inflammatory cytokines. In PSD rats, NLRP3 inflammasome activation was detected in the ischemic hippocampus, along with increased expression of the inflammatory cytokines IL-18 and IL-1β, and decreased levels of 5-HT, BDNF, and PSD-95. Subsequently, using FMT technology, PSD rat feces were innovatively prepared into a fecal suspension and administered to healthy SD rats. Analysis revealed that FMT-PSD rats exhibited a disrupted gut microbiota structure, impaired colonic barrier integrity, activation of the hippocampal NLRP3 inflammasome, elevated inflammatory cytokine levels, and reduced neurotransmitter expression.

CONCLUSION: In summary, these data demonstrate that dysbiosis of the intestinal microbiota compromises gut barrier integrity and elicits systemic inflammation, which may subsequently activate the NLRP3 inflammasome in hippocampal microglia. This activation promotes the release of pro-inflammatory cytokines IL-18 and IL-1β, and coincides with dysregulation of emotion-related neurotransmitters, collectively contributing to the pathogenesis of PSD.}, } @article {pmid41052446, year = {2025}, author = {Sacks, HS and , }, title = {In primary CDI, fecal microbiota transplantation was noninferior to vancomycin for clinical cure at 14 d without recurrence at 60 d.}, journal = {Annals of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.7326/ANNALS-25-03648-JC}, pmid = {41052446}, issn = {1539-3704}, abstract = {GIM/FP/GP: [Formula: see text] Gastroenterology: [Formula: see text] Infectious Disease: [Formula: see text].}, } @article {pmid41048505, year = {2025}, author = {Yang, W and Jin, Q and Xiao, D and Li, X and Huang, D}, title = {Interaction mechanism and intervention strategy between metabolic dysfunction-associated steatotic liver disease and intestinal microbiota.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1597995}, pmid = {41048505}, issn = {1664-302X}, abstract = {The interaction between metabolic dysfunction-associated seatotic liver disease (MASLD) and gut microbiota regulates hepatic metabolic homeostasis through the gut-liver axis, and its mechanisms involve intestinal dysbiosis (decreased bacteroidetes, increased ratio of firmicutes/proteobacteria), bile acid metabolism reprogramming (secondary bile acids inhibit FXR signaling), short-chain fatty acid (SCFAs) deficiency, and endotoxin-mediated inflammatory activation (TLR4/NF-κB pathway). Among the intervention strategies, probiotics (such as Bifidobacteria) improved inflammation by regulating microbiota structure and intestinal barrier function, prebiotics such as resistant starch enriched butyric acid-producing bacteria and reduced liver lipid deposition, fecal microbiota transplantation (FMT) could remodel the microbiota but needed to optimize safety, restricted fructose intake and Mediterranean diet reduced liver damage by regulating microbiota metabolism, and metabolic surgery improved fibrosis through microbiota remodeling and bile acid signaling. In the future, it is necessary to combine multi-omics technology to analyze the microbiota-host interaction network, develop precision therapies such as phage targeted clearance or engineering bacterial delivery of metabolites, and promote the clinical transformation of personalized intervention programs.}, } @article {pmid41047993, year = {2025}, author = {Paaske, SE and Baunwall, SMD and Rubak, T and Rågård, N and Kelsen, J and Hansen, MM and Lødrup, AB and Lyhne, S and Glavind, E and Fernis, CMC and Hald, S and Erikstrup, LT and Vinter-Jensen, L and Lal, S and Mikkelsen, S and Erikstrup, C and Dahlerup, JF and Hvas, CL}, title = {Improving Clinical Outcomes of Encapsulated Faecal Microbiota Transplantation for Clostridioides difficile Infection Through Empirical Donor Selection and Optimised Dosing: A Quality Improvement Study.}, journal = {Alimentary pharmacology & therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/apt.70395}, pmid = {41047993}, issn = {1365-2036}, support = {8056-00006B//Innovationsfonden/ ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is effective for Clostridioides difficile infection (CDI), but real-world effectiveness data are warranted to refine treatment algorithms. We previously found that FMT effectiveness varied with donors, and the effect of a single capsule FMT administration was lower than expected.

AIMS: To improve FMT outcomes through empirical donor exclusion and application of an optimised capsule FMT dosing regimen.

METHODS: In this multi-site Danish quality improvement study, we included patients with CDI treated with capsule-based FMT from 24 June 2019 to 30 September 2024. The primary outcome was cure of C. difficile-associated diarrhoea (CDAD) 8 weeks after FMT. We assessed this using statistical process control charts monitored separately for the primary FMT centre and the external FMT sites. We used multivariable, mixed-effect logistic regression analysis to evaluate the impact of FMT dosing while adjusting for patient, donor and CDI-related factors.

RESULTS: We included 1176 patients (1707 FMT treatments). At external FMT sites, the cure rate from one FMT treatment changed from 50% (95% confidence interval (CI): 45%-56%) to 59% (55%-63%) following the exclusion of three low-performing donors in November 2022. After implementing a two-dose capsule FMT dosing regimen in February 2024, the cure rate increased to 72% (65%-77%). The impact of the two-dose capsule FMT dosing regimen remained statistically significant after adjustment (odds ratio 1.22; 95% CI 1.16-1.28; p < 0.001).

CONCLUSION: Empirical donor selection and a two-dose capsule FMT regimen improved clinical outcomes in a large-scale system treating patients with CDI.}, } @article {pmid41047724, year = {2025}, author = {de Groen, P and Fuhri Snethlage, CM and Wortelboer, K and Tokgöz, S and Davids, M and Verdoes, X and Westerbeke, FHM and Meijer, RI and Gotthardt, M and de Vos, WM and Herrema, H and Nieuwdorp, M and Hanssen, NMJ}, title = {Autologous fecal microbiota capsules are safe and potentially preserve beta-cell function in individuals with type 1 diabetes.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2563155}, doi = {10.1080/19490976.2025.2563155}, pmid = {41047724}, issn = {1949-0984}, mesh = {Humans ; *Diabetes Mellitus, Type 1/therapy ; *Insulin-Secreting Cells/physiology/metabolism ; Male ; Female ; Adult ; *Feces/microbiology ; Pilot Projects ; Capsules/administration & dosage ; *Fecal Microbiota Transplantation/adverse effects/methods ; Young Adult ; Middle Aged ; C-Peptide/blood/metabolism ; Adolescent ; Gastrointestinal Microbiome ; }, abstract = {This study investigated the safety and feasibility of daily ingestion of autologous lyophilized fecal microbiota capsules (a-LFMCs) for preserving beta-cell function in individuals with type 1 diabetes (T1D). We evaluated a-LFMC in an open-label, single-arm pilot study (NCT05323162) with 10 individuals with T1D. The study included a 3-month run-in period, 3 months of daily a-LFMC treatment, and a 3-month follow-up. Beta-cell function was assessed using mixed-meal stimulated C-peptide area under the curve (AUC). During the run-in period, beta-cell function significantly declined (mean ΔAUC -12.02 ± 5.09 nmol/L*min, p = 0.025). There was no decrease in beta-cell function during the a-LFMC treatment period (mean ΔAUC 0.76 ± 5.09 nmol/L*min, p = 0.88) and the follow-up period (mean ΔAUC 0.96 ± 5.09 nmol/L*min, p = 0.85). No serious adverse events occurred, though constipation increased during the treatment period (0% vs. 30%, p = 0.021). a-LFMC treatment was found to be safe and potentially contributes to preserving beta-cell function in T1D patients. A larger randomized placebo-controlled trial is needed to confirm these promising findings.}, } @article {pmid41046337, year = {2025}, author = {Vogel, GF and Kathemann, S and Pietrobattista, A and Maggiore, G and Aldrian, D and Sciveres, M and Verkade, HJ and Sokal, E and Jannone, G and Salcedo, M and Rauschkolb, P and Maucksch, C and Valcheva, V and Lainka, E}, title = {Odevixibat after liver transplant in patients with progressive familial intrahepatic cholestasis type 1: A case series.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/jpn3.70227}, pmid = {41046337}, issn = {1536-4801}, support = {//Ipsen/ ; }, abstract = {OBJECTIVES: Patients with progressive familial intrahepatic cholestasis type 1 (PFIC1) who have undergone liver transplantation (LT) may have unmet needs and impacts on daily life due to post-LT complications, including diarrhea and hepatic steatosis. Here, we describe the effects of the ileal bile acid transporter inhibitor odevixibat on diarrhea and hepatic steatosis in a cohort of patients with PFIC1 post-LT.

METHODS: Treating physicians from six centers retrospectively collected data through July 2023 on patients with PFIC1 who received odevixibat post-LT. Data collected included demographics, medical history, and symptom presentation, characteristics of diarrhea, and liver imaging and/or histopathology.

RESULTS: Overall, nine male patients with PFIC1 (seven aged <18 years at initial completion of the case report form) were included. In most patients, the primary indication for odevixibat treatment was diarrhea and/or steatosis post-LT. Odevixibat was initiated at a daily dose of 30-120 µg/kg (median exposure: 13 months). All patients had post-LT diarrhea, which was generally associated with negative impacts on daily life (e.g., ability to attend school, needing to wear diapers due to fecal urgency). After odevixibat initiation, most patients had improved diarrhea and positive impacts on daily life. Among five patients with post-LT steatosis and data available before and after odevixibat initiation, steatosis appeared to improve in three and did not change in two.

CONCLUSIONS: Overall, the majority of patients with PFIC1 post-LT complications in this case series experienced improvements in diarrhea and daily activities with odevixibat. Treatment with odevixibat following LT also appeared to reduce steatosis in some patients. Further studies, particularly those with a prospective design, are needed to confirm these findings.}, } @article {pmid41046274, year = {2025}, author = {Sadeghloo, Z and Ebrahimi, S and Hakemi-Vala, M and Totonchi, M and Sadeghi, A and Fatemi, N}, title = {Fusobacterium nucleatum and non-coding RNAs: orchestrating oncogenic pathways in colorectal cancer.}, journal = {Gut pathogens}, volume = {17}, number = {1}, pages = {78}, pmid = {41046274}, issn = {1757-4749}, abstract = {Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with mounting evidence implicating the gut microbiome in its pathogenesis. Among the microbial agents, Fusobacterium nucleatum has emerged as a prominent contributor, frequently detected in CRC tissues and associated with advanced disease stages and poor prognosis. This review highlights the complex interplay between F. nucleatum and host non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in modulating CRC biology. F. nucleatum influences the expression of several ncRNAs, which in turn regulate key signaling pathways such as Wnt/β-catenin (e.g., miR-1246, miR-135b), PI3K/AKT (e.g., miR-22, miR-135b), and TLR4/NF-κB (e.g., miR-31, lnc-NEAT1). Through these mechanisms, F. nucleatum contributes to tumor cell proliferation, immune evasion, metastasis, and chemoresistance. Additionally, its impact on ncRNA expression is implicated in reduced efficacy of standard chemotherapy. Emerging microbiota-based therapies, including probiotics and fecal microbiota transplantation, show promise in modulating gut flora and potentially reversing ncRNA dysregulation; however, their mechanistic effects on the F. nucleatum-ncRNA axis require further investigation. This review underscores the critical role of F. nucleatum-regulated ncRNAs in CRC and presents new opportunities for biomarker discovery and targeted therapeutics.}, } @article {pmid41045390, year = {2025}, author = {Senthilkumar, H and Chauhan, SC and Arumugam, M}, title = {Unraveling the multifactorial pathophysiology of polycystic ovary syndrome: exploring lifestyle, prenatal influences, neuroendocrine dysfunction, and post-translational modifications.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {980}, pmid = {41045390}, issn = {1573-4978}, mesh = {Humans ; *Polycystic Ovary Syndrome/physiopathology/metabolism/genetics/etiology ; Female ; *Protein Processing, Post-Translational ; Life Style ; Pregnancy ; Neurosecretory Systems/metabolism/physiopathology ; Insulin Resistance/physiology ; Animals ; Oxidative Stress ; }, abstract = {Polycystic ovary syndrome (PCOS) is a complex, multifactorial metabolic and endocrine disorder in reproductive-age women. This review discusses the interlinked roles of lifestyle, metabolic dysregulation, insulin resistance, neuroendocrine impairment, genetic predisposition, and post-translational modifications (PTMs) in PCOS pathogenesis. Lifestyle components, especially those leading to obesity and insulin resistance, worsen the hyperandrogenism, ovulatory dysfunction, and inflammation. Dietary treatments such as, DASH diet and caloric restriction, particularly along with metformin, have been proven to improve metabolic and reproductive parameters. Environmental toxins, such as endocrine-disrupting chemicals (EDCs) and advanced glycation end-products (AGEs), further compromise ovarian function and hormone regulation. Oxidative stress and insulin resistance, driven by mitochondrial malfunction and chronic inflammation, create a self-perpetuating vicious cycle that compromises oocyte quality and worsens metabolic imbalance. Neuroendocrine disruption, characterized by increased GnRH and LH pulsatility, is initiated by dysregulated kisspeptin, dynorphin, and neurokinin B signaling in KNDy neurons, modified GABAergic input, and increased AMH and androgens. PTMs such as phosphorylation, methylation, acetylation, and ubiquitination also play essential roles in granulosa cell function, AR signaling, insulin sensitivity, and oocyte maturation. Current and novel treatment options vary from lifestyle modifications and pharmacological interventions (e.g., metformin, GLP-1 receptor agonists, myoinositol, vitamin D, and statins) to regenerative measures like mesenchymal stem cells and fecal microbiota transplantation. Newer therapies focusing on PTMs and neuroendocrine regulators remain the future hope. Multidisciplinary individualized management is critical for successful PCOS therapy and averting long-term complications.}, } @article {pmid41039216, year = {2025}, author = {Ma, Y and Wang, D and Yu, X and Fan, Y and Yang, Z and Gao, X and Huang, X and Meng, J and Cheng, P and Liu, X and Liu, Z and Li, X}, title = {Moderate altitude exposure induced gut microbiota enterotype shifts impacting host serum metabolome and phenome.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {591}, pmid = {41039216}, issn = {1471-2180}, support = {2023YFE0114300//National key research and development program intergovernmental key projects/ ; No.2024A1515012697//Guangdong Provincial Basic and Applied Basic Research Fund Project/ ; No. 202206010044//Science and Technology Program of Guangzhou, China/ ; No. U24A20652//The Joint Funds of the Natural Science Foundation of China/ ; No. 82272246//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Consistent patterns of gut microbiota variations, particularly in relative abundance, have been identified in the adult human gut. Enterotype, another general measure of the gut microbiota, is a valuable approach for categorizing the human gut microbiota into distinct clusters. The impact of different enterotypes on human health varies, and the changes induced by moderate altitude exposure remain unclear. This study aimed to conduct a comprehensive investigation of the cascade effects triggered by enterotype shifts following moderate altitude exposure.

RESULTS: Using shotgun metagenome sequencing, participants before and after moderate-altitude exposure were classified into cluster BL (dominated by Blautia) and cluster BA (dominated by Bacteroides). Relative to cluster BL, cluster BA consisted predominantly of individuals exposed to moderate altitude. Compared to cluster BL, Cluster BA exhibited rewired metabolism of serum metabolites (i.e., amino acids, fatty acids and bile acids) and gut microbiota, lower inflammatory factor levels (i.e., tumor necrosis factor-α (TNF-α)), and sparser correlations among these parameters. Individuals with baseline BL enterotype who transitioned to the BA enterotype following moderate-altitude exposure showed prominent improvement in fasting blood glucose (FBG) levels, with higher abundance of Bacteroidetes species (e.g., Bacteroides thetaiotaomicron, and Bacteroides uniformis), but lower Proteobacteria species abundance (e.g., Escherichia coli) and decreased L-Glutamic acid levels. Furthermore, fecal microbiota transplantation (FMT) from moderate-altitude exposed individuals to high-fat diet (HFD) fed mice confirmed increased Bacteroides abundance shifts associated with improvements in glucose homeostasis regulation and rewired amino acid metabolism. In addition, significant increases in alanine aminotransferase (ALT) levels but decreased serum creatinine (Scr), arterial oxygen saturation (SaO2), 4-Hydroxyproline, L-Glutamic acid, L-Asparagine, L-Threonine, L-Citrulline, L-Lysine and Isovaleric acid levels were identified as potentially important signals for individuals upon moderate altitude exposure, regardless of the gut microbiota enterotype.

CONCLUSIONS: Moderate altitude exposure could induce enterotype switching, and a Bacteroides-dominant enterotype may be a beneficial pattern of the gut microbiome related to host metabolism. Moderate-altitude exposure has potential implications for glycemic control, suggesting new avenues for managing FBG levels in future.

GRAPHICAL ABSTRACT: [Image: see text]

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-025-04245-4.}, } @article {pmid41043596, year = {2025}, author = {Nasare, D and Bagade, S}, title = {The Gut-Lung Axis in Tuberculosis: A New Frontier in Immunomodulation and Microbiota-Directed Therapeutic Strategies.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {108087}, doi = {10.1016/j.micpath.2025.108087}, pmid = {41043596}, issn = {1096-1208}, abstract = {Tuberculosis (TB) is a transmissible disease that contributes to the global health burden due to drug resistance. The gut-lung axis is an emerging and promising frontier for understanding Mycobacterium tuberculosis (MTB) pathogenesis and disease progression via gut and lung bidirectional communication. Increasing evidence highlights that regulation in gut and lung microbial communities, termed dysbiosis, influences homeostatic conditions, innate and adaptive responses, and susceptibility to TB. Growing research has witnessed a paradigm shift toward the immunological interplay between gut microbiota and lung microbiota, and modulation in TB. This review deals with the interplay of immune cells and gut microbiota in TB, highlighting the importance of innate and adaptive responses in stabilizing the dysbiosis and inflammation. Host-directed therapies such as probiotics, prebiotics, synbiotics, short-chain fatty acids (SCFAs), and fecal microbiota transplantation support the stabilization of gut microbiota and maintain the disease severity. Moreover, personalized microbiota therapies, such as bacteriophage therapy, diagnostic agents, and biomarkers, are explored for their several roles in maintaining the eubiosis condition. We also highlight the future perspective of addressing the knowledge gap to develop a personalized and combined approach to novel drug delivery systems and host-directed therapies. This review provides an in-depth outline of the gut-lung axis as a potential therapeutic intervention, offering a conceptual framework for developing next-generation, microbiota-directed therapies to suppress and combat MTB infection.}, } @article {pmid41043575, year = {2025}, author = {Ahmed, LA and Al-Massri, KF}, title = {Insights into the Role of Gut Microbiota Modulation in the Management of Various Cardiovascular Diseases: A New Approach for Improving the Efficacy of Current Cardiovascular Medications.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {178210}, doi = {10.1016/j.ejphar.2025.178210}, pmid = {41043575}, issn = {1879-0712}, abstract = {Gut microbiome is an emerging contributor to various cardiovascular diseases (CVDs) where gut dysbiosis increases the risk of development and progression of atherosclerosis, coronary artery diseases, hypertension, and heart failure. Microbiota can also affect the metabolism of medications including cardiovascular drugs, resulting in alteration of their pharmacokinetics and pharmacodynamics or producing metabolites which can interfere with response of these drugs. Importantly, CVDs require prolonged pharmacological interventions with medications which may have impacts on the diversity and composition of gut microbiota. Gut microbiota modulation using diets, prebiotics, probiotics, fecal microbiota transplantation, and microbial trimethylamine-lyase inhibitors, has also shown benefits in the management of CVDs where gut microbiota and their metabolites have recently been studied as potential targets for the management of these diseases. Specifically, using innovative microbiota therapies in combination with traditional pharmacological agents have been evaluated for additional benefits in various CVDs. However, assessing the interactions among host factors, gut microbiome, and drug response will be essential for the development of new therapeutic targets for cardiovascular disorders, ultimately hoping better prognosis and patient's quality of life for those affected with CVDs.}, } @article {pmid41043062, year = {2025}, author = {Malogan, J and Hallowell, HA and Francis, B and Suez, J}, title = {Supplementation and Elimination of Microbiome-Produced Metabolites in the Treatment of Human Disease.}, journal = {Annals of the New York Academy of Sciences}, volume = {}, number = {}, pages = {}, doi = {10.1111/nyas.70103}, pmid = {41043062}, issn = {1749-6632}, abstract = {The human gut microbiome has a complex and influential relationship with host physiology that is governed through commensal-derived metabolites, small molecules, and endogenous microbial patterns. Indeed, microbial metabolites from the gut microbiome have been implicated in promoting health as well as contributing to the pathogenesis of microbiome-associated diseases. Live microbial therapeutics, such as probiotics and fecal microbiota transplantations, have been extensively utilized to establish health-promoting assemblages of bacteria and their associated beneficial metabolites. However, broad clinical use of live microbial therapeutics is limited by efficacy, specificity, and safety concerns. To circumvent this, a postbiotic approach can be taken, in which a beneficial effect may be achieved by direct administration of bacterially derived bioactive molecules. Alternatively, in cases where microbiome-derived metabolites drive disease, specific oral inhibitors can be used to restrict compound production. In this review, we examine the use of postbiotics to alleviate disease and highlight recent translational successes. Additionally, we discuss emerging approaches for precision elimination of disease-causing metabolites, as well as the exciting possibility of utilizing bacteriophages to modulate the production of metabolites in the microbiome.}, } @article {pmid41041846, year = {2025}, author = {Zhao, Y and Yu, C and Zhang, J and Yao, Q and Zhu, X and Zhou, X}, title = {The gut‑skin axis: Emerging insights in understanding and treating skin diseases through gut microbiome modulation (Review).}, journal = {International journal of molecular medicine}, volume = {56}, number = {6}, pages = {}, doi = {10.3892/ijmm.2025.5651}, pmid = {41041846}, issn = {1791-244X}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Skin Diseases/therapy/microbiology ; *Skin/microbiology/pathology ; Probiotics/therapeutic use ; Animals ; Prebiotics ; }, abstract = {Emerging evidence indicates a significant association between the composition and functionality of the gut microbiome and various skin disorders, including psoriasis, atopic dermatitis, acne and several dermatological conditions. The gut‑skin axis theory describes a complex bidirectional communication network between the gut and the skin, providing mechanistic insights into the pathogenesis of certain cutaneous diseases. Specifically, the gut microbiome influences skin health through the regulation of systemic immunity, inflammatory responses and metabolic pathways. Advances in high‑throughput sequencing and bioinformatics technologies have substantially enhanced the understanding of the role of the gut microbiome in skin pathology. Clinical and preclinical studies have demonstrated that restoring gut microbial homeostasis via interventions such as faecal microbiota transplantation, probiotics and prebiotics can ameliorate symptoms of skin diseases. Furthermore, personalized microbiome‑based therapies, next‑generation probiotics and dietary modifications hold promise for refining gut‑skin interactions and advancing precision medicine in dermatology. Therapeutic strategies targeting the gut‑skin axis offer novel avenues for innovative dermatological treatments, with future breakthroughs potentially involving microbial community engineering, postbiotics and artificial intelligence in microbiome‑related diagnostics. This narrative review summarizes recent advances in gut‑skin axis research, explores its potential in the prevention and management of selected dermatoses and discusses future trends and scientific developments in the field.}, } @article {pmid41041667, year = {2025}, author = {Tariq, H and Ramakrishnan, M and Portocarrero, P and Gupta, M and Herrera, N and Klein, J and Gupta, A and Cibrik, D}, title = {Fecal Impaction: An Unusual Cause of Acute Kidney Injury in a Kidney Transplant Recipient.}, journal = {Case reports in transplantation}, volume = {2025}, number = {}, pages = {5726025}, pmid = {41041667}, issn = {2090-6943}, abstract = {Acute kidney injury (AKI) is common in kidney transplant recipients, and the etiology varies depending on the time since transplantation. We present an uncommon case of AKI from obstructive uropathy 7 years posttransplant in a 47-year-old Caucasian male with moderate intellectual disability and end-stage kidney disease secondary to glomerulonephritis who received a deceased donor kidney transplant. He presented with abdominal pain, lethargy, hypercalcemia, and AKI. However, though his serum calcium level improved with intravenous fluid resuscitation, the AKI did not improve. Kidney transplant ultrasound showed hydronephrosis of the transplant ureter, and a noncontrast abdominal and pelvic computed tomography scan showed fecal impaction as the cause of obstruction of the transplanted ureter. The patient underwent fecal disimpaction resulting in the resolution of his hydronephrosis and return of his kidney function to baseline. Although a few case reports have been published of fecal impaction causing AKI due to obstruction of native ureters, to our knowledge, this is the first case describing AKI from fecal impaction in an adult kidney transplant recipient.}, } @article {pmid41041075, year = {2025}, author = {Zhu, S and Li, X and Yu, Y and Han, X and Yang, F and Lu, M and Dai, G and Guo, L and Xu, D}, title = {EZH2-mediated H3K27me3 links microbial inosine loss to depression: a gut-brain epigenetic switch.}, journal = {Theranostics}, volume = {15}, number = {18}, pages = {9969-9986}, pmid = {41041075}, issn = {1838-7640}, mesh = {Animals ; *Gastrointestinal Microbiome/genetics/physiology ; Mice ; *Enhancer of Zeste Homolog 2 Protein/metabolism/genetics ; *Epigenesis, Genetic ; *Depression/microbiology/metabolism/genetics ; *Histones/metabolism ; *Inosine/metabolism ; *Brain/metabolism ; Male ; Mice, Knockout ; Mice, Inbred C57BL ; Disease Models, Animal ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Apoptosis ; }, abstract = {Background: Depression, the second most prevalent neurological disorder globally, affects over 300 million people and presents an urgent public health challenge. While gut microbiota dysbiosis is increasingly recognized as a key contributor to depression, the molecular mechanisms linking microbial imbalance to brain dysfunction remain poorly defined. Methods: We investigated the role of EZH2 in gut microbiota-induced depressive behaviors in mice using the chronic unpredictable mild stress (CUMS), fecal microbiota transplantation, and conditional knockout of EZH2. CUT&Tag sequencing was employed to analyze EZH2-mediated H3K27me3 epigenetic reprogramming. Untargeted metabolomics and luciferase reporter assays were used to identify metabolites that upregulate EZH2 expression. 16S rRNA sequencing combined with metabolic tracing was conducted to trace the microbial origin of inosine. Additionally, natural compound screening identified coumaric acid (CA) as a novel EZH2-targeting degrader. Results: Conditional knockout of neuronal Ezh2 abolishes microbiota-induced depressive behaviors and neuronal apoptosis. Mechanistically, reduced abundance of specific microbiota (f_Lachnospiraceae, f_Oscillospiraceae, and f_Erysipelotricaceae) leads to inosine depletion. This depletion subsequently elevates EZH2 transcriptional activity by increasing H3K9ac modification at its locus, mediated through attenuation of the A2aR-cAMP-PKA-CREB-HDAC3 signaling axis. Subsequently, EZH2 silences serotonergic synapse-related genes (e.g., Tph2, Htr2a, Htr6) via H3K27me3 reprogramming, ultimately driving depressive behaviors and neuronal apoptosis in mice. Importantly, CA is identified as a first-in-class EZH2 degrader that binds lysine residues K623/K646 and recruits UBE3A for proteasomal degradation. CA treatment restores synaptic integrity and reverses depressive behaviors with minimal toxicity. Conclusions: Collectively, these findings define a novel "microbiota-inosine-EZH2" axis in depression pathogenesis and highlight EZH2 degradation as a promising therapeutic strategy for microbiota-associated neuropsychiatric disorders.}, } @article {pmid41040884, year = {2025}, author = {Zhang, S and Zhang, T and Zhang, Y and Ye, C and Mu, L and He, Q and Huang, T and Wang, G and Li, Y and Xie, S and Tang, X}, title = {Akkermansia muciniphila regulates the gut microenvironment and alleviate periodontal inflammmation in mice with periodontitis.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1643691}, pmid = {41040884}, issn = {1664-302X}, abstract = {OBJECTIVE: Akkermansia muciniphila (A. muciniphila) is an emerging gut commensal known for its roles in host metabolism and immune modulation. While its involvement in metabolic and inflammatory disorders is well characterized, its potential association with oral diseases such as periodontitis remains poorly understood. This study aimed to explore whether modulation of the gut microbiota via fecal microbiota transplantation (FMT) from periodontally healthy donors could influence the abundance of A. muciniphila and contribute to the alleviation of periodontitis.

METHODS: Fecal samples were collected from human donors, including periodontally healthy individuals (H group, n = 16), untreated patients with severe periodontitis (P group, n = 12), and the same patients at two weeks (P2W) and three months (P3M) after periodontal therapy. Quantitative PCR was used to assess A. muciniphila abundance in these human samples. A germ-free mouse model of periodontitis was then established, and the mice received FMT using samples from human donor groups (P-PBS, P-H, and P-P). Gut microbiota composition, periodontal inflammation, gut barrier proteins (MUC2, ZO-1), and inflammatory cytokines (IL-6, TNF-α) were evaluated in the mice.

RESULTS: Compared to groups H, P2W, and P3M, the abundance of A. muciniphila in the gut was significantly lower in patients with severe periodontitis, but it was increased after periodontal therapy. In mice, FMT from healthy donors (P-H group) significantly enriched A. muciniphila, improved expression of gut barrier proteins, reduced inflammatory cytokine levels, and alleviated periodontal inflammation compared to other groups.

CONCLUSION: These findings suggest a previously underrecognized link between gut microbial composition particularly A. muciniphila and periodontal health. Targeting the gut microbiota via FMT may represent a novel strategy for modulating systemic and oral inflammation and supporting the prevention or adjunctive treatment of periodontitis.}, } @article {pmid41039491, year = {2025}, author = {Song, J and Yang, X and Liu, X and Li, J}, title = {Gut bacteria: protective mediators, pathogenic contributors and novel therapeutic targets in Candida albicans infections.}, journal = {Gut pathogens}, volume = {17}, number = {1}, pages = {77}, pmid = {41039491}, issn = {1757-4749}, support = {24QNMP087//Health Commission of Sichuan Province Medical Science and Technology Program/ ; 24QNMP087//Health Commission of Sichuan Province Medical Science and Technology Program/ ; 24QNMP087//Health Commission of Sichuan Province Medical Science and Technology Program/ ; 24QNMP087//Health Commission of Sichuan Province Medical Science and Technology Program/ ; 2024ZYD0146//Central Government-Directed Project for Local Science and Technology Development/ ; 2024ZYD0146//Central Government-Directed Project for Local Science and Technology Development/ ; 2024ZYD0146//Central Government-Directed Project for Local Science and Technology Development/ ; 2024ZYD0146//Central Government-Directed Project for Local Science and Technology Development/ ; Q2024024//The Sichuan Medical Association Youth Innovation Project/ ; Q2024024//The Sichuan Medical Association Youth Innovation Project/ ; Q2024024//The Sichuan Medical Association Youth Innovation Project/ ; Q2024024//The Sichuan Medical Association Youth Innovation Project/ ; }, abstract = {Candida albicans is an opportunistic pathogen that resides in the human gut alongside a diverse array of microorganisms, including enteric bacteria, archaea, and viruses, which collectively form the gut microbiota. Recent studies have shown that the development of Candida albicans infections involves both weakened host immunity and enhanced invasiveness of Candida albicans, with intestinal microecology serving as a critical mediator of these processes. It has been demonstrated that disturbances in the gut microbiome can potentiate the invasive capacity of Candida albicans. Moreover, a compromised immune system, along with the use of antibiotics and immunosuppressive drugs, can lead to gut microbiome imbalances. Consequently, modulators of the intestinal microecology represent promising therapeutic interventions for managing Candida albicans infections. In this review, we examine the mechanisms underlying the increased invasiveness of Candida albicans following significant disruption of intestinal bacteria and highlighting the interplay among immune dysfunction, antibiotic use, and their effects on gut microbiome imbalance and Candida albicans infection. Additionally, we summarize the roles of microbiome-based therapies, such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation (FMT), in addressing Candida albicans infections. This review provides a theoretical foundation and practical guidance for the development of more effective microecological therapeutic strategies in the future.}, } @article {pmid41039079, year = {2025}, author = {Barkai, T and Yakubovsky, O and Korem Kohanim, Y and Bahar Halpern, K and Shir, S and Oren, N and Fine, M and Kelmer, P and Talmon, A and Israeli, A and Pencovich, N and Pery, R and Nachmany, I and Itzkovitz, S}, title = {Transcriptomic profiling of shed cells enables spatial mapping of cellular turnover in human organs.}, journal = {Molecular systems biology}, volume = {}, number = {}, pages = {}, pmid = {41039079}, issn = {1744-4292}, support = {768956//EC | ERC | HORIZON EUROPE European Research Council (ERC)/ ; 908/21//Israeli Science Foundation/ ; 3663/21//Israeli Science Foundation/ ; }, abstract = {Single-cell atlases provide valuable insights into gene expression states but lack information on cellular dynamics. Understanding cell turnover rates-the time between a cell's birth and death-can shed light on stemness potential and susceptibility to damage. However, measuring turnover rates in human organs has been a significant challenge. In this study, we integrate transcriptomic data from both tissue and shed cells to assign turnover scores to individual cells, leveraging their expression profiles in spatially resolved expression atlases. By performing RNA sequencing on shed cells from the upper gastrointestinal tract, collected via nasogastric tubes, we infer turnover rates in the human esophagus, stomach, and small intestine. In addition, we analyze colonic fecal washes to map turnover patterns in the human large intestine. Our findings reveal a subset of short-lived, interferon-stimulated colonocytes within a distinct pro-inflammatory microenvironment. Our approach introduces a dynamic dimension to single-cell atlases, offering broad applicability across different organs and diseases.}, } @article {pmid41038971, year = {2025}, author = {Bahar Halpern, K and Kent, I and Yakubovsky, O and Ben-Moshe, S and Barkai, T and Fine, M and Novoselsky, R and Israeli, A and Nachmany, I and Itzkovitz, S}, title = {Stool shed cell transcriptomics mirrors tumor biology and enables colorectal cancer diagnosis.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {34413}, pmid = {41038971}, issn = {2045-2322}, support = {768956/ERC_/European Research Council/International ; }, mesh = {Humans ; *Colorectal Neoplasms/diagnosis/genetics/pathology ; *Feces/cytology ; Female ; *Transcriptome ; Male ; *Gene Expression Profiling/methods ; Aged ; Middle Aged ; Biomarkers, Tumor/genetics ; Case-Control Studies ; Gene Expression Regulation, Neoplastic ; Adult ; Early Detection of Cancer/methods ; }, abstract = {Screening and molecular characterization of human intestinal pathologies such as colorectal cancer (CRC) currently depends on colonoscopy, an invasive procedure associated with risks and poor adherence. A non-invasive method that captures host molecular changes could improve early detection and monitoring of intestinal diseases. Transcriptomic profiling of shed intestinal cells in stool has shown potential in neonates but is limited in adults by the dominance of bacterial RNA. To address this, we combined microbial ribosomal RNA (rRNA) depletion with unique molecular identifier (UMI)-based RNA sequencing to enrich and quantify human transcripts in stool. Applying this method to samples from 54 CRC patients and 24 healthy controls, we profiled thousands of human genes per sample. Stool-derived gene expression distinguished CRC from control samples with high accuracy (AUC = 0.86) and strongly correlated with matched tumor tissue signatures. Notably, stool transcriptomes reverted to control-like patterns after tumor resection. Our approach offers a powerful, non-invasive alternative to current CRC diagnostics and enables molecular insights into tumor biology. This method could complement or replace existing screening tools and may be applicable to other gastrointestinal diseases.}, } @article {pmid41038411, year = {2025}, author = {Taoum, C and Devaux, A and Rouanet, P and Colombo, PE and Boucher, D and Bonnet, M}, title = {Gut microbiota and chemoradiotherapy response in rectal cancer: biomarker opportunities.}, journal = {Critical reviews in oncology/hematology}, volume = {}, number = {}, pages = {104974}, doi = {10.1016/j.critrevonc.2025.104974}, pmid = {41038411}, issn = {1879-0461}, abstract = {The gut microbiota is increasingly recognized as a key factor in rectal carcinogenesis. This review synthesizes current clinical and preclinical evidence linking specific microbial signatures, such as Fusobacterium nucleatum, Duodenibacillus massiliensis and colibactin-producing Escherichia coli (CoPEC) to chemoradiotherapy (CRT) treatment efficacy and resistance. Microbiota-driven mechanisms include immune modulation, inflammation, and drug metabolism. We highlight emerging microbial biomarkers and therapeutic strategies such as antibiotics, probiotics, and fecal microbiota transplantation. Integrating microbiome profiling into clinical workflows could refine patient stratification and enhance CRT efficacy in rectal cancer. Ongoing clinical trials aim to validate these associations and establish robust microbial biomarkers for CRT response prediction in rectal cancer.}, } @article {pmid41038146, year = {2025}, author = {Du, Y and Xu, J and Jia, J and Nong, Y and Lin, Y and Ye, Y and Zhong, Y and Tan, Q and Wei, Y and Huang, G and Mao, D and Huang, G and Lu, L and Peng, Y and Huang, H and Huang, J}, title = {Yuzhuo Zhixiao pill can treat non-alcoholic steatohepatitis through modulation of gut microbiota, bile acid and short-chain fatty acid metabolism.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {148}, number = {}, pages = {157348}, doi = {10.1016/j.phymed.2025.157348}, pmid = {41038146}, issn = {1618-095X}, abstract = {BACKGROUND: Yuzhuo Zhixiao Pill (YZZXP), a formulation in traditional Chinese medicine (TCM), exhibits therapeutic potential in non-alcoholic steatohepatitis (NASH). However, the mechanisms underlying its effects, particularly those involving gut microbiota-bile acid-short-chain fatty acid (GM-BA-SCFA) interactions, remain unclear. Current therapies present notable side effects and inadequately address the multifactorial etiology of NASH.

PURPOSE: To evaluate the anti-NASH efficacy of YZZXP and elucidate its mechanism, focusing on GM remodeling and BA/SCFA regulation.

STUDY DESIGN: This study established a NASH model in rats using a high-fat diet (HFD) and performed fecal microbiota transplantation (FMT) experiments.

METHODS: The therapeutic impacts of YZZXP on gut microbial structure (16S rDNA sequencing), SCFA concentrations, and BA profiles (analyzed by LC-MS and GC-MS) were assessed.

RESULTS: YZZXP administration alleviated HFD-induced obesity, hepatic steatosis, inflammatory responses, and disturbances in glycolipid metabolism. Microbial profiling via 16S rDNA sequencing revealed restored gut microbial diversity, marked by increased Akkermansia, Bacteroides, and Roseburia abundance. PROB and FMT interventions validated GM modulation as central to YZZXP 's effects. Targeted metabolomic analyses demonstrated elevated levels of SCFAs (notably butyrate and acetate) and substantial shifts in BA composition, accompanied by downregulation of intestinal FXR-FGF19 signaling and enhanced cholesterol excretion.

CONCLUSIONS: YZZXP exerts anti-NASH activity through a synergistic mechanism comprising GM restoration, BA metabolic reprogramming via FXR pathway inhibition, and SCFA-driven metabolic modulation. In contrast to monotherapy approaches, the multi-target strategy of YZZXP prevents compensatory dysbiosis and yields more durable metabolic benefits than PROB or FMT alone. By integrating microbiota-metabolite interplay into therapeutic design, YZZXP introduces a novel paradigm in traditional medicine for NASH management, addressing the limitations of synthetic agents while promoting metabolic homeostasis.}, } @article {pmid41038145, year = {2025}, author = {Guo, L and Yi, J and Zhang, A and Zheng, X and Wang, M and Yang, F and Kong, X and Meng, J}, title = {Zhenqi Fuzheng Granule targets the SCFAs-GPR109A axis to enhance PD-1 antibody efficacy via immunometabolic remodeling in colorectal cancer.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {148}, number = {}, pages = {157312}, doi = {10.1016/j.phymed.2025.157312}, pmid = {41038145}, issn = {1618-095X}, abstract = {BACKGROUND: Immune checkpoint inhibitors (ICIs), particularly PD-1 antibodies, represent a breakthrough in colorectal cancer (CRC) treatment. However, their clinical efficacy remains limited by tumour-induced immunosuppression. Traditional Chinese medicine (TCM) has attracted growing interest as a potential adjuvant to immunotherapy. Zhenqi Fuzheng Granule (ZQFZ) is a clinically approved herbal prescription widely used as an adjuvant therapy for CRC, yet its mechanistic underpinnings remain elusive.

OBJECTIVE: To investigate how ZQFZ improves the efficacy in CRC, with emphasis on gut microbiota modulation, SCFAs production, and downstream immunometabolic pathways involving GPR109A, and confirms that butyrate plays an important role in colorectal cancer inhibition.

METHODS: Phytochemical analysis of ZQFZ was conducted using LC-MS/MS and UPLC-MS/MS, identifying and quantifying seven major compounds. In vivo experiments, AOM/DSS-induced CRC mouse models were treated with ZQFZ, PD-1 antibody, or their combination. Tumour progression, body weight, and survival were monitored. Gut microbial composition and colonic SCFAs levels were assessed via 16S rRNA sequencing and gas chromatography. RT-qPCR was employed to validate the expression of key genes associated with the GPR109A/AKT/mTOR/HIF-1α signaling pathway. Molecular changes in the GPR109A/AKT/mTOR/HIF-1α pathway were evaluated through Western blotting, transcriptomic, and proteomic analyses. Immune cell infiltration and phenotypes were analyzed by flow cytometry. Molecular docking and molecular dynamics simulations were conducted to predict the binding affinity and structural stability between GPR109A and AKT1. The interactions between GPR109A and AKT1, as well as between butyrate and GPR109A, were further validated in vitro using microscale thermophoresis (MST) assays. To evaluate the microbial basis of ZQFZ activity, antibiotic-pretreated mice received ZQFZ-derived fecal microbiota transplantation (FMT). In vitro experiments, to investigate the mechanism by which sodium butyrate (NaB), the major gut microbial metabolite of ZQFZ, inhibits glycolysis in colorectal cancer under hypoxic conditions, CCK-8 assays, flow cytometry, lactate measurements, and Western blotting were performed to assess cell viability, apoptosis, lactate production, and the expression of AKT/mTOR/HIF-1α and glycolysis-related proteins.

RESULTS: LC-MS/MS profiling identified multiple bioactive constituents in ZQFZ. Targeted UPLC-MS/MS quantification revealed that the formulation contained Adenosine (0.87mg/g), Salidroside (0.11 mg/g), Astragaloside IV (0.07 mg/g), Calycosin (0.03 mg/g), Formononetin (6.7 μg /g), Chlorogenic acid (1.4 μg/g), Apigenin (0.5 μg/g). In vivo studies, both ZQFZ and PD-1 antibody inhibited tumour growth, with the combination treatment exerting the most pronounced antitumour effects. ZQFZ reshaped the gut microbiota, increased the levels of short-chain fatty acids (SCFAs), particularly butyrate, and activated the GPR109A pathway, leading to downregulation of the AKT/mTOR/HIF-1α signaling axis, suppression of HK2 expression and lactate production, and consequent inhibition of glycolysis. Immune remodeling was also observed, including reduced infiltration of myeloid-derived suppressor cells (MDSCs), polarization of macrophages toward the M1 phenotype, restoration of the CD4⁺/CD8⁺ T cell ratio, and modulation of serum cytokines including upregulation of IL-2, IL-12, and IFN-γ, along with downregulation of IL-4 and IL-10. ZQFZ-derived FMT significantly inhibited tumour growth, suppressed glycolysis-related markers (PKM2, GLUT1, HIF-1α, LDHA), and remodeled the immune microenvironment by reducing MDSCs and enhancing M1 macrophages and CD8⁺ T cell infiltration. In hypoxia-mimicking in vitro experiments, sodium butyrate (NaB), the principal gut microbial metabolite of ZQFZ, suppressed colorectal cancer cell viability and induced apoptosis. Through activation of GPR109A, NaB inhibited the AKT/mTOR/HIF-1α pathway and glycolysis-related enzymes, reduced lactate production, and further suppressed glycolysis. Molecular docking and dynamics simulations suggested a stable interaction between GPR109A and AKT1, which was confirmed in vitro by MST showing high-affinity binding (Kd=74.5 ± 20.8 nM); MST also verified moderate-affinity binding between GPR109A and sodium butyrate (Kd=43.3 ± 6.5 μM), supporting a dual interaction model wherein butyrate activates GPR109A, which in turn directly binds AKT1 to inhibit downstream glycolytic signaling.

CONCLUSION: This study uncovers a novel integrated mechanism whereby ZQFZ enhances PD-1 antibody efficacy via the gut microbiota-SCFAs-GPR109A axis, and NaB-mediated glycolysis inhibition under hypoxia further confirms its immunometabolic mechanism against CRC.}, } @article {pmid41037658, year = {2025}, author = {Sun, W and Ma, L and Feng, X and Fan, Y and Cai, Y and Li, X}, title = {Efficacy of gut microbiota-based therapy for autism Spectrum Disorder and attention Deficit Hyperactivity Disorder: a systematic review and meta-analysis.}, journal = {Psychology, health & medicine}, volume = {}, number = {}, pages = {1-25}, doi = {10.1080/13548506.2025.2565181}, pmid = {41037658}, issn = {1465-3966}, abstract = {The gut-brain axis is an emerging therapeutic target for neurodevelopmental conditions such as Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). However, the overall efficacy of gut microbiome-based interventions remains unclear. This systematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, aimed to synthesize the evidence on these interventions. Fifteen randomized controlled trials (RCTs) were identified from 1,080 records across PubMed, Embase, Web of Science, Cochrane, PsycInfo, MEDLINE, and ClinicalTrials.gov through August 2024. Interventions included probiotics, prebiotics, dietary changes, and fecal transplants. Using random-effects models, pooled analysis showed a small but significant overall benefit of gut microbiota-based interventions (Standardized Mean Difference, SMD = -0.12; 95% Confidence Interval, CI: -0.19 to -0.04), with low heterogeneity (I[2] = 5.9%). Effects differed by disorder: ADHD demonstrated greater improvement (SMD = -0.24; 95% CI: -0.42 to -0.06; I[2] = 50.4%) compared to ASD (SMD = -0.05; 95% CI: -0.15 to 0.04; I[2] = 0%). Duration-specific effects emerged: 8-week interventions showed significant outcomes (SMD = -0.32; 95% CI: -0.58 to -0.06), while shorter or longer durations lacked significance. Acceptability analysis from eight studies revealed comparable dropout rates between intervention and control groups (ASD: Risk Ratio, RR = 1.002; ADHD: RR = 0.943), with no serious adverse events reported. Subgroup analyses identified participant age, diagnosis type, and geographic location as heterogeneity sources. Despite methodological limitations and small sample sizes, findings suggest gut microbiome modulation may offer a safe adjunctive therapy, particularly for ADHD, with optimal effects emerging at 8 weeks. The gut-brain axis appears promising for neurodevelopmental disorders, but current evidence remains preliminary. Future research should prioritize large-scale RCTs with standardized protocols, mechanistic investigations, and long-term follow-up to establish clinical guidelines and clarify biological pathways. Findings underscore the need to tailor interventions to specific disorders and optimize treatment duration.}, } @article {pmid41036798, year = {2025}, author = {Nobel, YR and Park, H and Tillman, AM and Seeram, D and Moallem, DH and Intara, A and Nandakumar, R and Annavajhala, MK and Gomez-Simmonds, A and Verna, EC and Uhlemann, AC}, title = {Fecal Microbiota and Bile Acid Profiles in Early-Stage Hepatocellular Carcinoma: A Matched Case-Control Study.}, journal = {Clinical and translational gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ctg.0000000000000928}, pmid = {41036798}, issn = {2155-384X}, abstract = {INTRODUCTION: Early identification of hepatocellular carcinoma (HCC) is critical to reduce mortality. Diagnostic tools are limited for early disease. Intestinal microbiota may contribute to HCC risk directly and via metabolites, particularly bile acids (BA), offering potential noninvasive biomarkers.

METHODS: This was a case-control study of patients with cirrhosis with or without early-stage HCC, matched based on liver disease severity. Comprehensive analyses of fecal microbiota composition and function were performed.

RESULTS: There were 98 patients in the study (49 patients per group). Subjects with HCC were older (median 64 vs. 60 years, p<0.01) and more likely to have Hepatitis C (78% vs. 43%, p<0.01). Alpha diversity, beta diversity, and genes and pathways related to BA metabolism did not differ between groups overall, but alpha diversity did differ within the subset of patients with metabolic-associated steatotic liver disease (MASLD). There was differential abundance of multiple taxa between groups, including higher abundance of Klebsiella pneumoniae in cases. Increased concentration of secondary BA, which are microbiota-dependent, was associated with higher odds of HCC (adjusted OR 2.4, p=0.02); however, addition of microbial or BA features to a model with clinical data alone did not improve HCC prediction.

DISCUSSION: When accounting for liver disease severity, there were limited differences in intestinal microbiota composition and BA metabolism between subjects with or without early-stage HCC. Promising areas for future study of microbiota-based HCC biomarkers were identified, including a focus on the subpopulation of patients with MASLD.}, } @article {pmid41036738, year = {2025}, author = {Li, Y and Dong, J and Wang, S and Xiong, R and Kang, X}, title = {High flavonoid diet alleviates chronic stress in cancer patients by optimization of the gut microbiota.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d5fo02560e}, pmid = {41036738}, issn = {2042-650X}, abstract = {Scope: Cancer patients face long-term psychological stress due to the fear of death, economic burden, and pain caused by the disease. The aim of this study is to explore the effects of flavonoid diets on chronic stress in cancer patients. Methods and results: In this study, cancer patients were subjected to a high flavonoid diet (n = 15) or normal diet (n = 15). Their chronic stress status, quality of life and immune function were evaluated at the beginning and end of a 12-week diet intervention. The high flavonoid diet significantly alleviated anxiety, depression, and perceived stress in cancer patients (p < 0.05). The stress indicators in their plasma and saliva also decreased after the flavonoid diet (p < 0.05). The anxiety and depression behaviors of mice improved after receiving fecal microbiota transplantation from cancer patients receiving a high flavonoid diet (p < 0.05). The distribution of the gut microbiota changed, and butyric acid levels increased significantly in the FMT mice from the high flavonoid group (p < 0.05). The selected components of flavonoid (quercetin) caused similar changes in the behavioral experiments and gut microbiota of chronic stress mice. Conclusion: High levels of flavonoid intake can significantly improve the chronic stress status and quality of life of cancer patients, and the effects may be mediated by the optimization of the gut microbiota and their metabolites.}, } @article {pmid41036224, year = {2025}, author = {Liu, T and Ou, G and Wu, J and Wang, S and Wang, H and Wu, Z and Jiang, Y and Chen, Y and Xu, H and Deng, L and Chen, X and Xu, L}, title = {Pingwei Powder alleviates high-fat diet-induced colonic inflammation by modulating microbial metabolites SCFAs.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1628488}, pmid = {41036224}, issn = {2235-2988}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Diet, High-Fat/adverse effects ; *Fatty Acids, Volatile/metabolism ; Colon/pathology/drug effects/microbiology ; *Colitis, Ulcerative/drug therapy ; Male ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Mice ; Cytokines/metabolism ; Disease Models, Animal ; Signal Transduction/drug effects ; Powders ; Mice, Inbred C57BL ; Bacteria/metabolism/classification/genetics ; Inflammation/drug therapy ; RNA, Ribosomal, 16S/genetics ; TOR Serine-Threonine Kinases/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; }, abstract = {BACKGROUND: Pingwei Powder (PWP), a renowned traditional Chinese medicine (TCM) formula, it has demonstrated excellent therapeutic effects in ulcerative colitis (UC), yet its underlying pharmacological mechanisms remain unclear. This study aims to investigate the therapeutic effect of PWP on the aggravation of colonic inflammation induced by a high-fat diet and particularly focuses on its regulatory mechanisms on gut microbiota, which are closely related to UC.

METHODS: Network pharmacology analysis was employed to screen potential pharmacological targets of PWP for UC. Histological changes in colonic tissue were observed using hematoxylin and eosin (H&E) staining, and immunofluorescence staining was performed to evaluate the expression of tight junction proteins (ZO1 and Occludin). Western blotting was used to detect the expression levels of proteins related to the PI3K/AKT/mTOR pathway, ZO1, and Occludin. qRT-PCR was conducted to measure the relative expression of inflammatory cytokines (IL-1β, IL-17, IL-6, and TNF-α) in colonic tissue. Additionally, 16S rDNA sequencing was performed to analyze gut microbiota alterations, and GC/MS was used to quantify short-chain fatty acids (SCFAs) in gut contents. The gutMgene database was utilized to validate the mediating roles of gut microbiota metabolites in the pharmacological effects of PWP. And their mediating role in PWP efficacy was verified by fecal microbiota transplantation (FMT) and butyrate supplementation.

RESULTS: Network pharmacology analysis predicted that PWP may regulate the PI3K/AKT pathway to exert therapeutic effects in UC. Experimental validation showed that PWP significantly downregulated the levels of PI3K, pAKT/AKT, and pmTOR/mTOR in colonic tissue, thereby enhancing autophagy in colonic epithelial cells, as evidenced by decreased levels of P62 and increased LC3B-II/LC3B-I ratios. Furthermore, 16S rDNA sequencing combined with targeted SCFAs analysis of gut contents revealed that the pharmacological effects of PWP may be mediated by increasing the abundance of SCFAs-producing gut microbiota (Alistipes and Parabacteroides) and elevating the levels of SCFAs in the gut.

CONCLUSION: PWP enhances the abundance of SCFAs-producing bacteria (Alistipes and Parabacteroides) in the gut, increases the levels of butyrate, and inhibits the PI3K/AKT/mTOR pathway in the colon. These effects promote colonic autophagy and contribute to the resolution of colonic inflammation.}, } @article {pmid41035886, year = {2025}, author = {Tayyab, M and Zhao, Y and Zhang, Y}, title = {Microbiome engineering to enhance disease resistance in aquaculture: current strategies and future directions.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1625265}, pmid = {41035886}, issn = {1664-302X}, abstract = {Aquaculture, a cornerstone of global food security, faces critical threats from disease outbreaks, antimicrobial resistance, and ecological disruption. Through a narrative analysis of over 160 studies, this review synthesizes advances in microbiome engineering-a sustainable approach to enhancing disease resistance in aquatic animals-addressing key gaps: the inconsistent efficacy of conventional probiotics and prebiotics under field conditions, and the need for climate-resilient solutions. Critically, we highlight the emergence of precision microbiome engineering as a transformative paradigm. We integrate findings from genomics, metabolomics, clustered regularly interspaced short palindromic repeats, and artificial intelligence to identify microbial strategies that enhance host resilience. Genomic and multi-omics methods reveal health-associated microbes and metabolites, such as Vibrio-dominated dysbiosis markers in shrimp and butyrate-mediated immunity. Guided by these biomarkers, we describe precision-tailored probiotics-host-derived or genome-edited Bacillus subtilis strains whose adhesion factors, metabolic outputs (e.g., butyrate, bacteriocins), and heat stress tolerance are matched to the target species' gut niche. These are combined with complementary prebiotics (e.g., chitosan oligosaccharides) and synbiotics (e.g., Lactiplantibacillus plantarum plus king oyster mushroom extracts) that suppress pathogens through competitive exclusion and immune modulation. Ecologically rational innovations-interventions explicitly grounded in ecological theory (niche complementarity, K-selection) to stabilize resource-efficient microbiomes-such as fecal microbiota transplantation and synthetic consortia, demonstrate further disease control potential. Our synthesis reveals that translating microbiome engineering from laboratory to farm requires overcoming host-microbiome compatibility challenges and ecological risks. Policy alignment with the United Nations Sustainable Development Goals-Zero Hunger (Sustainable Development Goal 2), Climate Action (Sustainable Development Goal 13), and Life Below Water (Sustainable Development Goal 14)-is critical for sustainable adoption.}, } @article {pmid41035652, year = {2025}, author = {Kalopedis, EA and Zorgani, A and Zinovkin, DA and Barri, M and Wood, CD and Pranjol, MZI}, title = {Leveraging the role of the microbiome in endometriosis: novel non-invasive and therapeutic approaches.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1631522}, pmid = {41035652}, issn = {1664-3224}, mesh = {Humans ; *Endometriosis/therapy/microbiology/immunology/diagnosis/metabolism/etiology ; Female ; *Gastrointestinal Microbiome/immunology ; Dysbiosis/therapy/immunology/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Animals ; Lactobacillus ; Biomarkers ; }, abstract = {Endometriosis (EMS) is an oestrogen-dependent condition characterised by ectopic endometrial-like tissue growth with a chronic and inflammatory nature leading to severe symptoms and reduced quality of life. Emerging evidence implicates gut microbiome dysbiosis in EMS pathogenesis, driving chronic inflammation, immune dysfunction, and altered bacterial taxa within patient gut microbiome. This review examines the intricate relationship between gut dysbiosis and EMS, with a focus on immunomodulatory mechanisms and the downstream consequences of the bacterial contamination theory. It evaluates recent findings regarding microbial imbalances and microbial diversity, pinpointing gaps in current research that mandate further understanding. For example, while microbial markers like Lactobacillus depletion and elevated Escherichia coli have been observed in patients, their diagnostic potential remains poorly defined. Additionally, it addresses the broader implications of EMS, including its physical, mental and healthcare burdens. Simultaneously, critiquing current drawbacks in diagnostic and therapeutic strategies such as their invasiveness and limited efficacy. The review further evaluates novel microbiome-based strategies namely Lactobacillus-based probiotics and faecal microbiota transplantation (FMT), assessing their potential in modulating immune responses and alleviating EMS symptoms while considering associated challenges. Lastly, it highlights the emerging role of metabolomics in identifying non-invasive and diagnostic biomarkers like short-chain fatty acids (SCFAs), implicated in the interplay between microbial metabolites and immune signalling pathways in EMS.}, } @article {pmid41035378, year = {2025}, author = {Zhang, Q and Cui, J and Hou, Y and Guo, L and Li, H and Zhou, G and Wang, X and Zhu, B and Shi, K and Zhang, Y and Bi, Y and Li, Y and Sun, L and Feng, Y and Yuan, J and Wang, X}, title = {Alterations in Gut Microbiota and Metabolism in Cirrhotic Portal Hypertension: Implications for Disease Progression.}, journal = {Alimentary pharmacology & therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/apt.70392}, pmid = {41035378}, issn = {1365-2036}, support = {7232272//the Beijing Municipal Natural Science Foundation/ ; BJZYYB-2023-06//the Beijing Traditional Chinese Medicine Technology Development Fund Project/ ; 81774234//the National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Although gut microbiota has been implicated in various liver disorders, its relationship with cirrhotic portal hypertension (CPH) remains unclear.

AIMS: To investigate the structural and functional alterations of gut microbiota in patients with CPH and the potential role of these alterations in the progression of CPH.

METHODS: We collected faecal samples from 35 patients with CPH and 71 patients without CPH (controls) to conduct microbiome and metabolomic analyses. Gut microbes, faecal metabolites and their functional pathways associated with CPH were identified using multiple bioinformatics approaches. To understand the role of gut microbiota in the pathogenesis of CPH, we carried out faecal microbiota transplantation, CPH-characteristic bacterial transplantation and antibacterial experiments in mice.

RESULTS: Microbial diversity was diminished, and gut microbial structures were altered in patients with CPH compared to the controls, primarily manifested as increased abundance of lipopolysaccharide-producing bacteria and decreased abundance of anti-inflammatory bacteria. This dysbiosis of gut microbiota was accompanied by changes in the faecal metabolome, particularly in arginine biosynthesis and nitric oxide production. Transplantation of gut microbiota from CPH patients, as well as the transplantation of CPH-associated bacteria Veillonella nakazawae, was found to exacerbate CPH progression in mice. Antibiotic treatment significantly alleviated the CPH progression induced by N-dimethylnitrosamine in mice.

CONCLUSIONS: Our study reveals that gut microbiota dysbiosis is implicated in CPH progression, potentially providing new avenues for microbiome-based treatment for CPH.}, } @article {pmid41035224, year = {2025}, author = {Farini, A and Strati, F and Molinaro, M and Mostosi, D and Saccone, S and Tripodi, L and Troisi, J and Landolfi, A and Amoroso, C and Cassani, B and Blanco-Míguez, A and Leonetti, E and Bazzani, D and Bolzan, M and Fortunato, F and Caprioli, F and Facciotti, F and Torrente, Y}, title = {Immunoproteasome Inhibition Positively Impacts the Gut-Muscle Axis in Duchenne Muscular Dystrophy.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {16}, number = {5}, pages = {e70054}, doi = {10.1002/jcsm.70054}, pmid = {41035224}, issn = {2190-6009}, support = {M6/C2_CALL 2022//PNRR/ ; FRRB-2022//Unmet Medical Needs, Fondazione Regionale per la Ricerca Biomedica/ ; GJC21084//Cariplo Telethon Alliance GJC2021-2022/ ; //NextGenerationEU/ ; //MUR/ ; PR-0394//Gruppo familiari beta-sarcoglicanopatie/ ; PNC-E3-2022-23683266-CUP: C43C22001630001//Hub Life Science-Diagnostica Avanzata/ ; //Associazione Centro Dino Ferrari/ ; }, mesh = {Animals ; *Muscular Dystrophy, Duchenne/drug therapy/metabolism/pathology ; Mice ; Gastrointestinal Microbiome/drug effects ; *Proteasome Inhibitors/pharmacology/therapeutic use ; *Muscle, Skeletal/drug effects/metabolism ; Disease Models, Animal ; Mice, Inbred mdx ; Male ; *Proteasome Endopeptidase Complex/metabolism ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Duchenne Muscular Dystrophy (DMD) features immune-muscle crosstalk, where muscle fibre degeneration enhances pro-inflammatory macrophage infiltration, worsening inflammation and impairing regeneration.

METHODS: We investigated the impact of immunoproteasome (IP) inhibition on the gut-muscle axis in mdx mice, a well-established model of DMD. We employed microbiota perturbation models, including broad-spectrum antibiotic treatment (ABX) and faecal microbiota transplantation (FMT) from IP-inhibited mdx mice. IP inhibition effects were assessed by analysing gut microbiota composition, intestinal inflammation, muscle integrity and associated metabolic and inflammatory pathways.

RESULTS: IP inhibitor ONX-0914 significantly impacted the intestinal inflammatory microenvironment and gut microbiota of mdx mice. ONX-0914 treatment increased gastrointestinal transit (increased wet/dry faecal weights, p = 0.0486 and p = 0.0112, respectively) and partially restored intestinal barrier integrity (reduced FITC-dextran leakage, p = 0.0449). JAM-A was significantly upregulated (p < 0.0001). Colonic CD206+ M2 macrophages increased, while CD68 + M1 cells partially decreased. ONX-0914 downregulated IP isoforms in macrophages (PSMB8: p = 0.0022; PSMB9: p = 0.0186) as well as FOXO-1 (p = 0.0380) and TNF-α (p = 0.0487). Antibiotic-induced microbiota depletion abrogated these effects. Metagenomic analysis revealed significant differences in microbiota composition between C57Bl controls and mdx mice (PERMANOVA p < 0.001), with ONX-0914 inducing enrichment of stachyose degradation pathways. Metabolomic analysis showed enrichment of bacterial metabolites, fatty acid and sugar metabolism pathways, with increased glutathione, galactose, glycerol, glyceraldehyde and TCA cycle intermediates. ONX-0914 improved mitochondrial activity in skeletal muscle, as increased expression of ETC complexes (mdx vs. mdx+ONX: Complex II, p = 0.0338; Complex IV, p = 0.0023) and TCA enzymes (mdx vs. FTMmdx+ONX: IDH p = 0.0258; FH p = 0.0366). This led to a shift towards oxidative muscle fibres and improved muscle morphology (increased fibre size, p < 0.0001 mdx vs. mdx+ONX and mdx vs. FTMmdx+ONX). Muscle performance was enhanced with reduced CPK levels (p = 0.0015 mdx vs. mdx+ONX) and fibrosis (decreased TGFβ: mdx vs. mdx+ONX, p = 0.0248; mdx vs. FTMmdx+ONX, p = 0.0279). ONX-0914 reduced CD68+ (mdx vs. mdx+ONX, p = 0.0024; mdx vs. FTMmdx+ONX, p < 0.0001) and increased CD206+ (mdx vs. FTMmdx+ONX: p = 0.0083) macrophages in muscle, downregulated inflammatory genes (mdx vs. mdx+ONX: ccl2 p = 0.0327, vcam-1p = 0.0378) and reduced pro-inflammatory proteins (MCP1, mdx vs. mdx+ONX, p = 0.0442). Inflammatory cytokines and endothelial vessel density in ONX-0914 treated mdx were restored to wild type mice. These data demonstrate that ONX-0914 enhances muscle function through microbiota-dependent mechanisms.

CONCLUSIONS: Our study advances the understanding of the role of dysbiosis in DMD disease and identifies IP inhibition as a potential therapeutic strategy to modulate the dystrophic gut-muscle axis, offering new perspectives for microbiota-targeted therapies.}, } @article {pmid41033875, year = {2025}, author = {Kopple, JD and Bross, R and Ekramzadeh, M and Markovic, D and Lyzlov, A and Lodebo, BT and Mehrotra, R and Shah, AP}, title = {Lanthanum carbonate lowers serum phosphorus without altering body phosphorus burden in maintenance peritoneal dialysis patients: a randomized crossover trial.}, journal = {The American journal of clinical nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajcnut.2025.08.015}, pmid = {41033875}, issn = {1938-3207}, abstract = {BACKGROUND: Many studies show that intestinal phosphate binders reduce serum phosphorus concentrations in hyperphosphatemic patients with chronic kidney failure. To our knowledge, there are virtually no studies of the effect of these binders on fecal phosphate or body phosphate.

OBJECTIVES: This study examined the hypothesis that phosphate binders increase fecal phosphate and reduce body phosphorus burden.

METHODS: Seven adult patients undergoing maintenance peritoneal dialysis underwent full metabolic balance studies for phosphorus in a research ward while they ate a constant phosphorus diet. Patients were studied during a baseline period without phosphate binders and while they received, in random order, 3 doses of lanthanum carbonate (La2(CO3)3), 1.5, 3.0, and 4.5 g/d, in 3 divided daily doses for ∼12-14 d each. The total duration of study was 47-49 d in each patient. Dialysate, urine, and feces were collected continuously and serum intermittently for phosphorus measurements.

RESULTS: Serum phosphorus concentrations fell progressively and significantly as the La2(CO3)3 dose was increased (r = -0.47, P < 0.001). Fecal phosphorus concentrations rose progressively as La2(CO3)3 increased (r = 46.4, P < 0.001). However, there was a negative correlation between both dialysate (r = -17.2, P = 0.002) and urine (r = -18.5, P < 0.001) phosphorus and La2(CO3)3 dose. This decline in dialysate and urine phosphorus correlated with the fall in serum phosphorus concentration as the La2(CO3)3 dose increased. As the La2(CO3)3 dose rose, the increase in fecal phosphorus concentration was essentially counterbalanced by the fall in dialysate and urine phosphorus. Hence, body phosphorus balance did not change with increasing La2(CO3)3 doses.

CONCLUSIONS: La2(CO3)3 treatment lowered serum phosphorus concentration but did not change body phosphorus content. This trial was registered at clinicaltrials.gov as NCT01581996.}, } @article {pmid41033511, year = {2025}, author = {Bian, S and Zhu, S and Lu, J and Iqbal, M and Jamil, T and Kiani, FA and Dong, H and Dai, H and Zhang, X and Liu, F and Li, A}, title = {Targeting gut microbiota in non-alcoholic fatty liver disease (NAFLD): Pathogenesis and therapeutic insights: A review.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {147995}, doi = {10.1016/j.ijbiomac.2025.147995}, pmid = {41033511}, issn = {1879-0003}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by hepatic steatosis associated with insulin resistance, oxidative stress, inflammatory responses, and other factors. The precise pathogenesis of NAFLD remains unclear. Although it has emerged as a global health burden, current therapeutic options for example, probiotics, prebiotics, synbiotics and fecal microbiota transplantation (FMT) have shown promising but varied efficacy. Moreover, use of traditional Chinese medicine (TCM) in NAFLD patients, has gained growing attention for its multi-targeted regulatory properties and several natural product formulations and their beneficial impacts on gut microbiota, lipid metabolism and hepatic health. The article highlights the role of gut microbiota dysbiosis in the pathogenesis of NAFLD and explores the therapeutic strategies emphasizing the need of personalized multimodal approaches and robust clinical trials to validate these interventions.}, } @article {pmid41032750, year = {2025}, author = {Gurer Kluge, EE and Meedt, E and Feicht, J and Cao, K and Hiergeist, A and Mamilos, A and Hirsch, D and Hoepting, M and Kattner, AS and Matos, C and Bülow, S and Thiele Orberg, E and Beckhove, P and Kandulski, A and Evert, M and Hildner, K and Kreutz, M and Edinger, M and Wolff, D and Herr, W and Poeck, H and Gessner, A and Weber, DA and Kehr, B and Holler, E and Ghimire, S}, title = {Mucosal calprotectin is associated with severity of aGI-GVHD and poor outcomes after allogeneic stem cell transplantation.}, journal = {Blood}, volume = {}, number = {}, pages = {}, doi = {10.1182/blood.2025029402}, pmid = {41032750}, issn = {1528-0020}, abstract = {Calprotectin, a calcium- and zinc-binding protein composed of the subunits S100A8 and S100A9, has been extensively studied as a biomarker of gastrointestinal (GI) inflammation through fecal and serum analyses. However, its role in intestinal tissue remains poorly understood due to limited availability of biopsies. In this study, we analyzed S100A8 and S100A9 mRNA expression in 579 intestinal biopsies from allogeneic stem cell transplant (ASCT) patients and observed a strong association with acute GI graft-versus-host disease (aGI-GvHD) (p<0.001). Neutrophil infiltration correlated with the severity of aGI-GvHD (p<0.001), and calprotectin expression was strongly linked to Toll-like receptor 4 (TLR4) (p<0.001) and TLR2 (p<0.001) expression. TLR4 and aGI-GvHD were associated with elevated calprotectin mRNA levels (p<0.001). When patients received broad-spectrum antibiotics at disease onset, expression of calprotectin was suppressed (S100A8, p=0.001; S100A9, p=0.01). Gastrointestinal site-specific differences in calprotectin expression were identified: during severe aGI-GvHD, levels increased up to 30-fold in the small intestine and up to 5-fold in the large intestine with respect to mild/no aGI-GVHD, while under homeostasis, the large intestine exhibited higher baseline calprotectin (p=0.001). The high clinical relevance is evident from the observation that calprotectin expression was prognostic for transplant-related mortality (TRM). Our study suggests that (a) calprotectin is a potential biopsy biomarker in aGI-GvHD, (b) calprotectin expression and neutrophil infiltration possibly indicate translocation of microbiota, which (c) may be modulated by antibiotics.}, } @article {pmid41031618, year = {2025}, author = {Xu, F and Yue, Y and Sun, D}, title = {Mechanism of the AMPK/SIRT1 pathway in gut dysbiosis-mediated postoperative cognitive dysfunction in aged mice.}, journal = {The international journal of neuropsychopharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1093/ijnp/pyaf066}, pmid = {41031618}, issn = {1469-5111}, abstract = {OBJECTIVE: Postoperative cognitive dysfunction (POCD) is a prevalent complication in older patients who undergo surgery that requires anesthesia. This study explored the role of the AMPK/SIRT1 pathway in gut dysbiosis-mediated POCD in aged mice.

METHODS: POCD was induced in aged male mice via open tibial fracture surgery under isoflurane anesthesia. Mice then received the probiotic VSL#3, the SIRT1 inhibitor EX527, and the AMPK/SIRT1 activator resveratrol. Fecal microbiota transplantation was conducted in aged POCD mice. Mouse cognitive function was assessed using the Morris water maze and novel object recognition tests. Mouse histopathological changes were observed via HE staining. Iba1+/GFAP+ activation was assessed via immunofluorescence, and pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 [IL]-1β, IL-6) in the hippocampus were determined via ELISA. Gut microbiota compositions were detected via 16S rRNA sequencing. Hippocampal pAMPK/AMPK and SIRT1 levels were assessed by western blot.

RESULTS: Aged POCD mice exhibited prolonged escape latency, reduced platform crossings, and an impaired object discrimination rate on postoperative day 7. Severe hippocampal CA1 damage, increased Iba1+/GFAP+ cell numbers, elevated pro-inflammatory cytokines, and gut dysbiosis were also observed. The probiotic VSL#3 ameliorated gut dysbiosis, alleviated POCD, and reduced neuroinflammation. Gut microbiota from POCD mice exacerbated cognitive deficits and neuroinflammation in aged mice, while clearance of gut microbiota improved outcomes. VSL#3 improved POCD in aged mice by balancing gut microbiota through the AMPK/SIRT1 pathway. The AMPK/SIRT1 pathway activation mitigated POCD.

CONCLUSION: VSL#3 balanced gut microbiota and suppressed neuroinflammation in hippocampal CA1 region by activating the AMPK/SIRT1 pathway, thereby alleviating POCD in aged mice.}, } @article {pmid41030553, year = {2025}, author = {Xie, H and Zhu, S and Xue, P and Xie, F and Zhao, L and Chu, X}, title = {Yanggan Yizhong decoction prevents liver metastasis from colorectal cancer by targeting myeloid-derived suppressor cells through the regulation of bile acid metabolism in the gut microbiota.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1639442}, pmid = {41030553}, issn = {1664-302X}, abstract = {INTRODUCTION: Liver metastasis (LM) exhibits a high incidence in colorectal cancer (CRC), yet effective preventive therapies are still lacking. Based on the prophylactic principle of harmonizing the liver and spleen, Yanggan Yizhong (YGYZ) decoction has shown clinical effectiveness in preventing LM. This study aims to explore the active components and underlying mechanisms of YGYZ in the prevention and treatment of LM.

METHODS: The components of YGYZ were analyzed using Ultra-High Performance Liquid Chromatography coupled with High-Resolution Tandem Mass Spectrometry (UPLC-HR-MS/MS). The LM mouse model was established through intrasplenic injection of ct26-luc cells to evaluate the effect and safety of YGYZ on LM. Fecal microbiota transplantation (FMT) was performed to create microbiota-altered mice, and liver tissue morphology along with HE staining was utilized to dynamically monitor LM progression. Flow cytometry and inflammatory factor assays were conducted to assess the immune microenvironment (IME) of the liver pre-metastatic niche (PMN). Additionally, 16S rRNA sequencing and bile acid (BA) metabolomics were employed to investigate the role of YGYZ in modulating gut microbiota (GM) and BA. Western blot analysis was performed to identify key targets of YGYZ in the GM-BA-immunity pathway.

RESULTS: UPLC-HR-MS/MS analysis identified 95 compounds in YGYZ, Glycyrrhizic acid, Bergapten, and Icariin as the main compounds. YGYZ and its FMT inhibited LM of CRC with safety, inhibited CD11b+Ly6G+ and CD11b+Ly6C+ cells in the pre-metastatic stage, decreased CD11b+Ly6G+ cells in the metastatic stage, reduced immunosuppressive factors such as Arg-1, TGF-β, and IL-10, and improved the CD4+/CD8+ T-cell ratio, regulating liver PMN. YGYZ also improved the GM structure, particularly decreasing the abundance of Clostridium in the LM mice. For the hepatic BAs profile, YGYZ increased the content of primary BAs-Nor cholic acid (NorCA), Taurocholic acid, Taurochenodeoxycholic Acid, and Tauro β-Muricholic Acid, and secondary BAs-ursodeoxycholic acid (UDCA), with similar trends in FMT, while YGYZ decreased NorCA, α-Muricholic acid, Tauro α-Muricholic acid, and UDCA in the fecal BA profile. YGYZ and its FMT dampened the protein expression of IL-6, STAT3, and pSTAT3, but only YGYZ downregulated kruppel-like factor 15 (KLF15).

CONCLUSION: YGYZ may prevent LM by remodeling the GM and synergistically inhibiting KLF15 to regulate the enterohepatic BA cycle, and suppressing the proliferation and activation of myeloid-derived suppressor cells through the IL-6/STAT3 pathway, thereby improving IME of liver PMN.}, } @article {pmid41030253, year = {2025}, author = {Bautista, J and Villegas-Chávez, JA and Bunces-Larco, D and Martín-Aguilera, R and López-Cortés, A}, title = {The microbiome as a therapeutic co-driver in melanoma immuno-oncology.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1673880}, pmid = {41030253}, issn = {2296-858X}, abstract = {Melanoma, one of the most aggressive skin cancers, remains a major clinical challenge due to its high metastatic potential, therapy resistance, and rising global incidence. Although immune checkpoint inhibitors have transformed management, variable responses and acquired resistance limit durable benefit. Emerging evidence positions the microbiome as a pivotal determinant of melanoma biology and therapeutic outcomes. Dysbiosis in the skin, gut, and oral compartments fosters tumor-promoting inflammation, immune evasion, and oncogenic signaling, whereas enrichment of specific commensals, such as Akkermansia muciniphila and Faecalibacterium prausnitzii, enhances antigen presentation and effector T cell activity, improving ICI efficacy. Mechanistically, microbial metabolites, including short-chain fatty acids, tryptophan derivatives, and bile acids, modulate epigenetic programs, G-protein-coupled receptor signaling, and oncogenic cascades such as PI3K-AKT and RAS-RAF-MEK-ERK. Beyond the gut, cutaneous microbiota such as Staphylococcus epidermidis exert direct antitumor effects, while pathogenic oral taxa propagate systemic inflammation that shapes the melanoma tumor microenvironment. These insights are driving the development of microbiome-targeted interventions, including fecal microbiota transplantation, defined consortia, probiotics, and dietary modulation, with early clinical studies showing the potential to overcome resistance to immunotherapy. Integration of circadian biology further suggests that host-microbiome-immune interactions are temporally regulated, opening new dimensions for therapeutic optimization. By synthesizing mechanistic, clinical, and translational advances, this review highlights the microbiome as both a biomarker and a therapeutic axis in melanoma, underscoring its promise to transform precision immuno-oncology.}, } @article {pmid41028942, year = {2025}, author = {Ma, S and Li, X and Shang, S and Zhai, Z and Wu, M and Song, Q and Chen, D}, title = {Targeting gut microbiota and metabolites in cancer radiotherapy.}, journal = {Clinical and translational medicine}, volume = {15}, number = {10}, pages = {e70481}, doi = {10.1002/ctm2.70481}, pmid = {41028942}, issn = {2001-1326}, mesh = {Humans ; *Gastrointestinal Microbiome/radiation effects/drug effects/physiology/immunology ; *Neoplasms/radiotherapy ; *Radiotherapy/methods/adverse effects ; Probiotics/therapeutic use ; Prebiotics ; Fecal Microbiota Transplantation/methods ; }, abstract = {Radiotherapy (RT) is a cornerstone in cancer treatment, but often causes radiation-induced injury. Accumulating evidence points to the gut microbiota in modulating immune functions and maintaining intestinal integrity to impact RT efficacy. This review examines the current understanding of intestinal flora and their metabolites within the context of RT. We outlined the current research applications in how microbiota-targeted strategies such as probiotics, prebiotics, dietary interventions, and faecal microbiota transplantation could restore microbial balance, reduce toxicity, and improve patient prognosis. Microbial byproducts such as short-chain fatty acids, bile acids and tryptophan exhibit protective effects against radiation damage, supporting immune modulation and enhancing tumour radiosensitivity. These microbial products underscore the potential of gut microbiota-targeted therapies as adjunctive treatments in RT, with implications for reducing toxicity and personalizing cancer care. All these strategies targeting gut microbiota and metabolites potentially aim to develop innovative therapies that boost RT effectiveness while minimizing side effects, and finally revolutionizing personalized cancer treatment. KEY POINTS: RT alters gut microbiota composition and contributes to intestinal injury and systemic toxicity. Gut microbiota regulate mucosal integrity, immune responses and therapeutic outcomes of RT. Microbial metabolites, including SCFAs, BAs and tryptophan derivatives, protect against radiation injury and enhance tumour radiosensitivity. Microbiota-targeted interventions (e.g. probiotics, prebiotics, dietary strategies, FMT) show promise for reducing RT-related toxicity and improving patient prognosis.}, } @article {pmid41028744, year = {2025}, author = {Chen, C and Su, Q and Zi, M and Hua, X and Zhang, Z}, title = {Harnessing gut microbiota for colorectal cancer therapy: from clinical insights to therapeutic innovations.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {190}, pmid = {41028744}, issn = {2055-5008}, mesh = {Humans ; *Colorectal Neoplasms/therapy/microbiology ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Prebiotics/administration & dosage ; Fusobacterium nucleatum ; }, abstract = {Colorectal cancer (CRC) remains a leading cause of cancer morbidity and mortality worldwide, yet improvements in survival have been modest despite advances in conventional therapies. The gut microbiota has emerged as a critical player in CRC pathogenesis and a promising therapeutic target to enhance clinical outcomes. Mounting evidence implicates specific microorganisms, notably Escherichia coli, Fusobacterium nucleatum, and Bacteroides fragilis, in tumor initiation and progression through DNA damage, inflammatory modulation, and immunosuppressive mechanisms. Clinical trials investigating microbiome modulators-including faecal microbiota transplantation, probiotics, prebiotics, and engineered biotherapeutics-highlight their potential to augment chemotherapy, radiotherapy, immunotherapy, and surgical recovery, with encouraging preliminary efficacy in treatment-resistant CRC subtypes. Nonetheless, translating microbiome interventions into standardized clinical practice requires rigorous mechanistic validation, robust biomarker development, and careful management of safety concerns. Future research must focus on integrating high-resolution multi-omics, spatial microbiome mapping, artificial intelligence analytics, and innovative microbiome-targeted nanotechnologies to precisely reshape gut microbial communities, thereby ushering in a new era of precision oncology in colorectal cancer management.}, } @article {pmid41027059, year = {2025}, author = {Shan, R and Wang, K and Chen, Q and Bao, L and Wu, K and Zhao, Y and Han, Y and Gao, Y and Zhang, N and Hu, X and Fu, Y and Zhao, C and Bian, W}, title = {Phytosphingosine alleviates DSS-induced colitis by regulating the gut microbiota and inflammatory responses.}, journal = {International immunopharmacology}, volume = {166}, number = {}, pages = {115610}, doi = {10.1016/j.intimp.2025.115610}, pmid = {41027059}, issn = {1878-1705}, abstract = {Inflammatory bowel disease is becoming increasingly prevalent and represents a major concern in global public health. However, conventional therapies often come with various adverse effects. Phytosphingosine (PS), a key metabolite in sphingolipid metabolism, is widely found in plants and fungi and possesses notable anti-inflammatory properties. In this study, we aimed to evaluate the protective effects of PS against dextran sulfate sodium (DSS)-induced experimental colitis in mice and elucidate its underlying mechanisms. Our results showed that oral administration of PS significantly alleviated DSS-induced colonic injury and reduced levels of proinflammatory cytokines such as TNF-α and IL-1β. Additionally, PS improved intestinal barrier function disrupted by DSS, as indicated by increased expression of mucin-2 and tight junction proteins. Furthermore, PS suppressed the activation of the NF-κB signaling pathway, oxidative stress and enhanced PPARγ expression. We also observed that PS mitigated DSS-induced gut dysbiosis in mice, characterized by an increase in Bacteroidota and a decrease in Proteobacteria. To explore the role of the gut microbiota in PS-mediated protection against colitis, fecal microbiota transplantation (FMT) was conducted in DSS-treated mice. Recipients of FMT from PS-treated donors exhibited reduced inflammatory responses and improved intestinal integrity, accompanied by a higher abundance of Bacteroidota in the gut. Additionally, PS treatment modified the profile of short-chain fatty acids in the mice, with a notable increase in the levels of butyrate and propionate. Overall, our findings demonstrate that PS attenuates DSS-induced colitis in mice through modulation of the gut microbiota, providing a potential strategy for IBD intervention via microbiota regulation.}, } @article {pmid41024986, year = {2025}, author = {Singla, N and Singla, K and Attauabi, M and Aggarwal, D}, title = {Gut-skin axis: Emerging insights for gastroenterologists-a narrative review.}, journal = {World journal of gastrointestinal pathophysiology}, volume = {16}, number = {3}, pages = {108952}, pmid = {41024986}, issn = {2150-5330}, abstract = {The gut-skin axis (GSA) embodies a complex, bidirectional interaction between the gastrointestinal (GI) system and skin, driven by immune modulation, systemic inflammation, and gut microbiota dynamics. Disruptions in gut homeostasis, including dysbiosis and increased intestinal permeability, are increasingly recognized as contributing factors to dermatological conditions such as acne, psoriasis, and atopic dermatitis. For gastroenterologists, appreciating this interplay is essential, as diseases and their treatments frequently present with cutaneous manifestations, offering diagnostic and therapeutic insights. This review explores the underlying mechanisms of the GSA, focusing on the microbiome and its metabolites as key regulators of inflammation and immunity. It underscores the clinical importance of microbiome-targeted therapies, such as probiotics, prebiotics, and dietary modifications, in addressing both GI and dermatological disorders. Furthermore, the review examines the influence of GI conditions, including inflammatory bowel disease and celiac disease on skin health. This article seeks to equip gastroenterologists with practical insights for identifying, diagnosing, and managing skin conditions associated with GI health. The article also highlights the current limitations in knowledge regarding the GSA. The GSA represents a promising avenue for therapeutic advancements, encouraging interdisciplinary collaboration between gastroenterology and dermatology to optimize patient care.}, } @article {pmid41024984, year = {2025}, author = {Marano, G and Anesini, MB and Milintenda, M and Acanfora, M and d'Abate, C and Lisci, FM and Pirona, I and Traversi, G and Pola, R and Gaetani, E and Mazza, M}, title = {Discovering a new paradigm: Gut microbiota as a central modulator of sexual health.}, journal = {World journal of gastrointestinal pathophysiology}, volume = {16}, number = {3}, pages = {107823}, pmid = {41024984}, issn = {2150-5330}, abstract = {The gut microbiota plays a pivotal role in human health, influencing diverse physiological processes, including those related to sexual health. Emerging evidence suggests a bidirectional relationship between the gut microbiota and sexual health, mediated by its impact on systemic inflammation, hormonal regulation, and immune function. A balanced gut microbiota supports optimal levels of sex hormones, such as estrogen and testosterone, which are critical for sexual function and reproductive health. Additionally, gut-derived metabolites such as short-chain fatty acids contribute to maintaining mucosal barrier integrity and regulating immune responses, which are essential for protecting against infections that may impair sexual health. Conversely, dysbiosis, an imbalance in gut microbial composition, has been linked to conditions such as erectile dysfunction, polycystic ovary syndrome, and reduced libido, emphasizing its role in sexual dysfunction. Lifestyle factors, including diet, stress, and antibiotic use, can modulate the gut microbiota and, consequently, sexual health outcomes. Recent therapeutic approaches, such as probiotics, prebiotics, and fecal microbiota transplantation, offer potential for restoring gut balance and improving sexual health. This review highlights the central role of the gut microbiota in sexual health, emphasizing its importance as a target for therapeutic interventions to enhance overall well-being.}, } @article {pmid41024883, year = {2025}, author = {Abdelwahab, MM and Ghattas, AS and Tawheed, A}, title = {Implications of gut microbiota in hepatic and pancreatic diseases: Gut-liver-pancreas axis.}, journal = {World journal of hepatology}, volume = {17}, number = {9}, pages = {109965}, pmid = {41024883}, issn = {1948-5182}, abstract = {The gut-liver-pancreas axis (GLPA) is a critical network shaped by gut microbiota (GM) and their metabolites, essential for maintaining metabolic and immune balance. Disruption of this microbial equilibrium, known as dysbiosis, contributes to the development and progression of various hepatic and pancreatic diseases. Through mechanisms such as increased intestinal permeability and exposure to microbial products-including lipopolysaccharide, trimethylamine-N-oxide, and secondary bile acids-dysbiosis promotes inflammation, oxidative stress, insulin resistance, and carcinogenesis. These changes are linked to conditions including metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, cirrhosis, hepatocellular carcinoma, pancreatitis, pancreatic ductal adenocarcinoma, and diabetes. Emerging tools like stool metagenomics and serum metabolomics help identify microbial biomarkers for diagnosis and risk stratification. While interventions such as probiotics, dietary changes, and fecal microbiota transplantation aim to restore microbial balance, their success remains inconsistent. This work aims to highlight the pathogenic role of GM across the GLPA, with special emphasis on the underexplored gut-pancreas connection. Advancing our understanding of the GLPA can unlock novel microbiota-targeted approaches for early diagnosis and treatment of hepatopancreatic diseases.}, } @article {pmid41024876, year = {2025}, author = {Mishra, AK and Goel, A}, title = {Stratification and selection of therapies to improve survival in severe alcoholic hepatitis.}, journal = {World journal of hepatology}, volume = {17}, number = {9}, pages = {109118}, pmid = {41024876}, issn = {1948-5182}, abstract = {Severe alcoholic hepatitis (SAH) is associated with high short-term mortality. The SAH population exhibits extreme heterogeneity in disease severity, clinical presentation, decompensations, and outcomes. Nonetheless, improving outcomes and preventing adverse events is a major challenge when selecting an appropriate treatment for alcoholic hepatitis. Currently, steroids are the standard of care for SAH with Maddrey's discriminant function > 32 and model for end stage liver disease > 20; however, they have limited usage due to ineligibility in approximately two-third of such patients. Approximately 25% of patients do not respond to steroids and require alternative therapies. An array of evolving therapies, such as granulocyte colony-stimulating factors, plasma exchange, fecal microbiota transplantation, antibiotics, anti-cytokine therapies, and N-acetylcysteine, showing variable success, are emerging. Hence, it is also crucial to select appropriate therapy. The present review discusses the standard of care, the existing therapies, risk stratification for outcomes, and the selection of appropriate therapy to improve survival in SAH patients.}, } @article {pmid41024767, year = {2025}, author = {Ezzat, WM}, title = {Machine learning as an artificial intelligence application in management of chronic hepatitis B virus infection.}, journal = {World journal of gastroenterology}, volume = {31}, number = {35}, pages = {109776}, pmid = {41024767}, issn = {2219-2840}, mesh = {Humans ; *Hepatitis B, Chronic/therapy/microbiology/diagnosis/virology ; *Machine Learning ; *Gastrointestinal Microbiome ; *Hepatitis B virus/pathogenicity ; Algorithms ; Artificial Intelligence ; Antiviral Agents/therapeutic use ; Supervised Machine Learning ; }, abstract = {Let's review the role of gut microbiota in pathogenesis of chronic hepatitis B infection as addressed in by Zhu et al. Zhu et al used high-throughput technology to characterize the microbial ecosystems, which led to an explosion of various types of molecular profiling data, such as metagenomics, metatranscriptomics, and metabolomics. To analyze such data, machine learning (ML) algorithms have shown to be useful for identifying key molecular signatures, discovering potential patient stratifications, and, particularly, for generating models that can accurately predict phenotypes. Strong evidence suggests that such gut microbiome-based stratification could guide customized interventions to benefit human health. Supervised learning includes designing an algorithm to fix a pre-identified problem. To get an answer, ML software must access data that have been nominated. On the other hand, unsupervised learning does not address any pre-defined problems. Bias should be eliminated as much as possible. In unsupervised learning, an ML algorithm works to identify data patterns without any prior operator input. This can subsequently lead to elements being identified that could not be conceived by the operator. At the intersection between supervised and unsupervised learning is semi-supervised ML. Semi-supervised learning includes using a partially labeled data set. The ML algorithm utilizes unsupervised learning to label data (that has not yet been labelled) by drawing findings from the labeled data. Then, supervised techniques can be used to solve defined problems involving the labeled data. Reinforcement learning, which is similar to supervised learning in the meaning, is goal-oriented. Reinforcement learning does not need labeled data, instead, it is provided with a set of regulations on a problem. An algorithm will carry out operations to try to answer questions involving the problem. Based on obtained data of gut microbiota, various therapeutic modalities can be applied: Prebiotics, probiotics, postbiotics, engineered bacteria, bacteriophage, and novel microbe-materials therapeutic system and fecal transplantation. In conclusion, ML is an artificial intelligence application that helps in providing new perspectives on tailored therapy. Furthermore, assessing the impact of gut microbiota modification is a critical step in advanced liver disease management. These new artificial intelligence techniques although promising, still require further analysis and validation in future studies.}, } @article {pmid41024761, year = {2025}, author = {Quiñones-Calvo, M and Alvarado-Jara, R and García-Renedo, P and Stallings, E and Grifol-Clar, E and Fernández-Rodríguez, CM}, title = {Beyond corticosteroids: A systematic review of novel therapeutic strategies in severe alcoholic hepatitis and 90-day survival.}, journal = {World journal of gastroenterology}, volume = {31}, number = {35}, pages = {109987}, pmid = {41024761}, issn = {2219-2840}, mesh = {Humans ; *Hepatitis, Alcoholic/mortality/therapy ; Liver Transplantation ; *Adrenal Cortex Hormones/therapeutic use ; Treatment Outcome ; Severity of Illness Index ; Time Factors ; Nutritional Support/methods ; }, abstract = {BACKGROUND: Severe alcoholic hepatitis (SAH) carries a 90-day mortality rate approaching 50%. Management includes corticosteroids, nutritional support, and early liver transplantation in selected cases. However, the mid-term impact of available therapies remains unclear. This systematic review provides a critical evaluation of treatments for SAH, specifically focusing on survival or mortality at 90 days as an essential window that captures short- and mid-term outcomes. The 90-day window is clinically significant, as it reflects the remission of systemic inflammation, early liver recovery, and minimizes confounding long-term behaviors such as alcohol relapse.

AIM: To review the effect of different treatments for SAH on survival and mortality at 90 days.

METHODS: A systematic search of PubMed and EMBASE (last updated March 2025) was performed without language restrictions, focusing on studies published in the last decade. Study selection and data extraction were performed independently by at least two reviewers. Risk of bias was assessed using RoB 2.0 and Risk-of Bias in Non-Randomized Studies of Interventions tools. Due to heterogeneity in study designs and interventions, a meta-analysis was not feasible. A qualitative synthesis was conducted using narrative summaries and evidence tables.

RESULTS: Searches in the databases yielded 645 citations in PubMed and 1516 in EMBASE. Of these 2161 studies, 618 were duplicates and therefore removed. A total of eight studies were included in qualitative synthesis. Among the included publications, six were randomized control trials (RCT) and two were retrospective cohort studies. These studies evaluated 90-day mortality or survival in SAH patients treated with corticosteroids (n = 2), pentoxifylline (n = 1), anakinra plus zinc (n = 2), granulocyte colony-stimulating factor (n = 1), amoxicillin-clavulanate (n = 1), fecal microbiota transplantation (n = 1) or extracorporeal liver assist device (n = 1). While most studies were conducted in Western countries, two had a global scope.

CONCLUSION: Steroids remain the first-line therapy for SAH despite reports of them not having any 90-day survival benefit. These results highlight the need for multicenter, biomarker-guided RCTs evaluating emerging treatments to improve mid-term survival in SAH.}, } @article {pmid41024199, year = {2025}, author = {Yang, G and Gao, L and Liu, Y and Xu, X and Yang, W}, title = {The impact of altered intestinal microbiota on intestinal immune function after acute exhaustive exercise in mice.}, journal = {BMC sports science, medicine & rehabilitation}, volume = {17}, number = {1}, pages = {279}, pmid = {41024199}, issn = {2052-1847}, support = {ZL22018//2022 Campus-Level Talent Special Project/ ; }, abstract = {PURPOSE: Long-term training or intense exercise alters gut microbiota. This study aimed to determine the effects of microbiota on colonic permeability and immune function in mice subjected to acute exhaustive exercise.

METHODS: C57BL/6 mice were randomly divided into the blank control (C), no exercise experience (NE), under a training protocol (E), phosphate-buffered saline (PBS) transplantation (PT), and fecal microbiota transplantation (FMT) groups. The E group underwent 14 weeks of moderate intensity training. At the end of the 14th week, fecal suspensions were prepared from mice in Group E and transplanted into Group FMT via enema, while Group PT received PBS enemas twice daily for 7 days. Prior to transplantation, both Groups PT and FMT were gavaged with antibiotics for 7 days, followed by 3 days of polyethylene glycol bowel cleansing. The C group was euthanized after a rest period, and the other groups were euthanized after acute exhaustive exercise. Colonic zonulin, occludin, ZO-1, CD14, TLR-4, MD-2, and TNF-α protein levels were detected via western blot, and enzyme-linked immunosorbent assays were used to detect serum LPS, IL-6, and colonic sIgA.

RESULTS: Colonic zonulin protein expression was significantly higher (P < 0.01) and occludin and ZO-1 expression levels were significantly lower in the NE, PT, and FMT groups compared with the C group (P < 0.01). ZO-1 was significantly higher in the FMT group compared with the PT group (P < 0.05). Colonic MD-2, TLR-4, and CD14 expression levels were significantly lower in the FMT group compared with the PT group (P < 0.01, P < 0.05, and P < 0.05, respectively). Serum LPS and IL-6 expression levels were significantly lower in the FMT group compared with the PT group (P < 0.01). Colonic sIgA levels were significantly lower in the NE, E, PT, and FMT groups compared with the C group (P < 0.01), and levels in the FMT group were significantly higher than the levels in the PT group (P < 0.01).

CONCLUSION: Fecal microbiota transplantation attenuated the increased intestinal permeability, enhanced intestinal immune function, and reduced systemic inflammation induced by acute exhaustive exercise in mice without prior exercise experience.}, } @article {pmid41024120, year = {2025}, author = {Huang, J and Tang, J and Wang, Z and Zhang, H and Wang, F and Tang, X and Zhou, X}, title = {Efficacy and safety of fecal microbiota transplantation for ulcerative colitis: protocol for an umbrella review of systematic reviews.}, journal = {Systematic reviews}, volume = {14}, number = {1}, pages = {182}, pmid = {41024120}, issn = {2046-4053}, support = {YN2024GZRPY030//Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Systematic Reviews as Topic ; *Colitis, Ulcerative/therapy ; Research Design ; Meta-Analysis as Topic ; Treatment Outcome ; }, abstract = {INTRODUCTION: A growing number of systematic reviews and meta-analyses (SRs/MAs) based on randomized clinical trials have been carried out to assess the efficacy of fecal flora transplantation (FMT) in the treatment of ulcerative colitis (UC). An overview of SRs/MAs will be conducted with the aim of systematically compiling, evaluating, and synthesizing the evidence regarding FMT for UC. This is a protocol for an overview of SRs/MAs. We will search eight public electronic databases for the studies of FMT on UC. SRs/MAs of clinical trials evaluating the effect of FMT on UC will be included. Two independent authors will screen titles and abstracts retrieved in the literature search and select reviews meeting the eligibility criteria for full-text review. The methodological quality, reporting quality, and evidence quality of the included studies will be assessed, using, respectively, the AMSTAR-2 tool, PRISMA checklists, and GRADE system.

RESULTS: From this study, the methodological quality, reporting quality, and evidence quality of the included SRs/MAs will be evaluated. We will also evaluate the efficacy of FMT in patients with UC.

IMPLICATIONS: We will ascertain the efficacy of FMT in UC patients to provide evidence to guide the treatment of UC with FMT in the future.

ETHICS AND DISSEMINATION: As a secondary study based on SRs/MAs, this study does not contain any individual patient information or violate participant rights. It is therefore not necessary to obtain ethics approval. We will report our findings in peer-reviewed journals or disseminate them at relevant conferences.

TRAIL REGISTRATION: Systematic review registration. PROSPERO CRD42023388682.}, } @article {pmid41022353, year = {2025}, author = {Belvončíková, P and Gardlík, R}, title = {Faecal microbiota transplantation for urinary tract infections.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2025.09.018}, pmid = {41022353}, issn = {1469-0691}, abstract = {BACKGROUND: Recurrent urinary tract infections (rUTIs) are a major clinical burden, increasingly complicated by multidrug-resistant organisms (MDROs) and antibiotic overuse. Growing evidence implicates gut microbiota dysbiosis as a key contributor to UTI susceptibility, with the gastrointestinal tract acting as a reservoir for uropathogens.

OBJECTIVES: This review examines the emerging role of faecal microbiota transplantation (FMT) as a therapeutic strategy for rUTIs. We synthesize findings from human studies and case reports, evaluate microbiological and clinical outcomes post-FMT, and discuss mechanistic insights, safety concerns, and future research directions.

SOURCES: We reviewed peer-reviewed publications up to May 2025 using PubMed and Web of Science. Included sources comprised clinical trials, cohort studies, case reports, economic analyses, and expert reviews concerning FMT and UTIs.

CONTENT: FMT has shown promise in reducing rUTI episodes, particularly in patients with underlying gut dysbiosis or MDRO colonization. Clinical studies and case reports consistently report decreased UTI frequency, lower MDRO burden, and increased gut microbiota diversity post-FMT. Patients previously refractory to antibiotic prophylaxis achieved prolonged infection-free periods. Microbiome analyses often reveal reductions in uropathogen abundance and shifts toward donor-like microbial communities. However, outcomes vary and some patients experience persistence or transmission of uropathogens from donor stool, underscoring safety and screening concerns.

IMPLICATIONS: FMT represents a promising microbiome-based intervention for managing rUTIs, particularly in complex or antibiotic-resistant cases. Randomized controlled trials are needed to assess efficacy, define optimal protocols, and address safety concerns. Standardized practices will be essential to integrate FMT into routine UTI care.}, } @article {pmid40737907, year = {2025}, author = {Bilal, M and Si, W and Vitienes, I and El-Fateh, M and Ahmed, N and Lin, H and Willie, BM and Zhao, X}, title = {Cohousing-mediated microbiota transfer promotes bone health and modulates gut integrity, and immunity in young broiler chickens.}, journal = {Poultry science}, volume = {104}, number = {10}, pages = {105587}, pmid = {40737907}, issn = {1525-3171}, mesh = {Animals ; *Chickens/immunology/physiology/microbiology/growth & development ; *Gastrointestinal Microbiome ; *Bone and Bones/physiology ; Male ; *Fecal Microbiota Transplantation/veterinary ; *Animal Husbandry/methods ; Cytokines ; Random Allocation ; }, abstract = {The intestine hosts a complex microbiota, which plays a crucial role in health and development. This study investigated the impact of cohousing day-old broilers with 14-day-old (CH14) or 42-day-old (CH42) broiler chickens and their fecal material for a week, compared to a non-cohoused control group. Birds were raised for 42 days, and bone traits, gut integrity and microbiota, cytokine and antimicrobial peptide profiles, and T cell immunity subsets were assessed at days 14 and 42. Production parameters were recorded weekly, and mortality daily. Both treatment groups exhibited significantly improved tibial bone length, cortical bone volume, and mineral density, with reduced pore volume and diameter. These effects were more pronounced in CH42 birds at day 14. Pro-inflammatory (IL-6, IL-17, IL-1β, IL-2, AvBD-4, AvBD-7) and anti-inflammatory (IL-10, TGF-β) markers were monitored, with CH42 birds showing significantly higher levels of both IL-10 and TGF-β at day 42. CH42 birds had higher CD4+CD25+ T regulatory cells and lower CD4+ T cells, while CD8+ T cells remained unchanged. Gut integrity markers (Claudin-2, Occludin, ZO-1, JAM-2) were improved in both groups. CH42 birds showed increased microbiota alpha and beta diversity and Firmicutes dominance by day 42. Cohousing and fecal material transfer improved bone development, gut integrity and microbiota, and immune homeostasis, highlighting the potential of older birds' microbiota and inspiring the development of microbiota-based approaches to enhance poultry health, welfare, and management.}, } @article {pmid41020845, year = {2025}, author = {Borrego-Ruiz, A and Borrego, JJ}, title = {Microbial Metabolomes in Alzheimer's Disease: From Pathogenesis to Therapeutic Potential.}, journal = {Current issues in molecular biology}, volume = {47}, number = {9}, pages = {}, doi = {10.3390/cimb47090724}, pmid = {41020845}, issn = {1467-3045}, abstract = {BACKGROUND: Accumulating evidence underscores the potential role of the gut microbiome in the pathogenesis of Alzheimer's disease, but much remains to be clarified. This review examines current evidence linking gut microbiome dysbiosis to Alzheimer's disease, focusing on microbial metabolomes and their mechanistic role, as well as on the potential of therapeutic approaches targeting the gut microbiome.

METHODS: A narrative, non-systematic examination of the literature was conducted to provide a comprehensive overview of the subject under examination. Database searches were performed in PubMed, Scopus, and Web of Science between June and July 2025.

RESULTS: Alzheimer's disease is linked to reduced gut microbial diversity and altered bacterial taxa. Gut microbiome shifts correlate with inflammation and may drive Alzheimer's disease progression via the microbiota-gut-brain axis. Microbial amyloids and bacterial products can cross both the intestinal and blood-brain barrier, triggering neuroinflammation and promoting amyloid and tau pathologies. Short-chain fatty acids produced by the gut microbiome regulate neuroinflammation, lipid metabolism, and gene expression, impacting Alzheimer's disease pathology. Therapeutics targeting the gut microbiome, including probiotics, prebiotics, and fecal microbiota transplantation, show promise in modulating neuroinflammation, reducing amyloid and tau pathology, and improving cognitive function in Alzheimer's disease.

CONCLUSIONS: The gut microbiome significantly influences Alzheimer's disease pathogenesis, and its modulation offers potential to slow progression. However, further research is required to validate effective clinical interventions.}, } @article {pmid41019955, year = {2025}, author = {Hajjar, J and Voigt, AY and Conner, ME and Swennes, AG and Fowler, S and Calarge, C and Mendonca, DD and Armstrong, D and Chang, CY and Walter, JE and Butte, MJ and Savidge, T and Oh, J and Kheradmand, F and Petrosino, JF}, title = {Gut dysbiosis patterns in CVID patients with noninfectious complications observed in a germ-free mouse model through fecal microbiota transplantation.}, journal = {Journal of human immunity}, volume = {1}, number = {1}, pages = {}, pmid = {41019955}, issn = {3065-8993}, abstract = {Patients with common variable immunodeficiency (CVID) who develop noninfectious complications (NIC) have worse clinical outcomes than those with infections only (INF). While gut microbiome aberrations have been linked to NIC, reductionist animal models that accurately recapitulate CVID are lacking. Our aim in this study was to uncover potential microbiome roles in the development of NIC in CVID. We performed whole-genome shotgun sequencing on fecal samples from CVID patients with NIC, INF, and their household controls. We also performed fecal microbiota transplants from CVID patients to germ-free mice. We found potentially pathogenic microbes Streptococcus parasanguinis and Erysipelatoclostridium ramosum were enriched in gut microbiomes of CVID patients with NIC. In contrast, Fusicatenibacter saccharivorans and Anaerostipes hadrus, known to suppress inflammation and promote healthy metabolism, were enriched in gut microbiomes of INF CVID patients. Fecal microbiota transplant from NIC, INF, and their household controls into germ-free mice revealed gut dysbiosis patterns only in recipients from CVID patients with NIC, but not in those from INF CVID or household controls recipients. Our findings provide a proof of concept that fecal microbiota transplant from CVID patients with NIC to germ-free mice recapitulates microbiome alterations observed in the donors.}, } @article {pmid41019532, year = {2025}, author = {Li, Z and Zhang, L and Wan, Z and Liu, H and Zhang, T and Li, Y}, title = {Therapeutic potential of the gut commensal bacterium Parabacteroides goldsteinii in human health and disease treatment.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1618892}, pmid = {41019532}, issn = {1664-302X}, abstract = {The gut microbiota, as a critical guardian of human health, maintains physiological homeostasis, modulating immunity, and facilitates nutrient metabolism. Parabacteroides goldsteinii, a probiotic gut commensal, has garnered increasing scientific attention. This review systematically examines its biological characteristics, then analyzes mechanisms promoting health (immunomodulation, metabolic regulation, and intestinal barrier reinforcement), and finally evaluates disease associations (metabolic disorders, neurological diseases, inflammatory conditions, and malignancies). Current evidence shows that therapeutic efficacy against obesity, non-alcoholic fatty liver disease, inflammatory bowel disease, autism spectrum disorder, and colorectal cancer via short-chain fatty acids secretion, bile acid transformation, and host immunity modulation. Dietary factors (e.g., inulin), pharmacological agents (e.g., metformin, aspirin), and lifestyle interventions (e.g., exercise synbiotics) dynamically regulate its abundance, underscoring therapeutic potential. Despite translational challenges-like optimizing cultivation, dose-response characterization, and genetic tool development-emerging applications (engineered probiotics, fecal microbiota transplantation, and synthetic biology) highlight broad prospects. Future research should prioritize context-dependent mechanisms across diseases and refined translation strategies for microbiome-based precision medicine.}, } @article {pmid41018102, year = {2025}, author = {Wang, L and Qiao, W and Zhen, X and Zhang, Y and Dong, Z}, title = {Targeting the gut-liver axis in cholangiocarcinoma: mechanisms, therapeutic advances, and future directions.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1646897}, pmid = {41018102}, issn = {2234-943X}, abstract = {Cholangiocarcinoma (CCA), a highly aggressive biliary tract malignancy, exhibits rising incidence rates and an extremely poor prognosis. Recent studies reveal that gut-liver axis dysregulation drives CCA progression through gut microbiota dysbiosis, bile acid (BA) metabolic disturbances, and immune microenvironment remodeling. Clinical evidence highlights significant alterations in the gut and biliary microbial composition of CCA patients, which correlate with tumor stage, vascular invasion, and survival outcomes. Dysregulated BA metabolism in CCA, characterized by accumulation of primary conjugated BAs, promotes tumor invasiveness via interaction with specific BA receptors and fosters an immunosuppressive microenvironment. Emerging therapeutic strategies include antibiotics for pathogenic microbiota modulation, probiotics for microbial homeostasis restoration, fecal microbiota transplantation, and BA pathway modulators. Future directions necessitate integrating synthetic biology (engineered microbiota), multi-omics, and artificial intelligence to develop precision therapies. Targeting the gut-liver axis offers novel therapeutic perspectives for CCA; however, clinical translation demands deeper mechanistic insights and standardized protocols to address challenges such as microbiota heterogeneity and receptor signaling duality.}, } @article {pmid41017540, year = {2025}, author = {Ticinesi, A and Spaggiari, R and Passaro, A and Volpato, S}, title = {Gut microbiota dysbiosis and its relation to osteoporosis and sarcopenia in older people.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCO.0000000000001173}, pmid = {41017540}, issn = {1473-6519}, abstract = {PURPOSE OF REVIEW: Gut microbiome is increasingly recognized as a modulator of the biology of aging. Several preclinical studies suggest that dysbiosis, typically arising in the older age, is associated with osteoporosis and sarcopenia. This review examines the recent findings on the mechanistic aspects of the gut-bone and gut-muscle axes in aging and provides a critical overview on their translation to clinical practice.

RECENT FINDINGS: Gut microbiome can modulate the pathophysiology of osteoporosis and sarcopenia through multiple mechanisms, particularly involving the production of bioactive mediators such as short-chain fatty acids (SCFAs), bile acids and tryptophan metabolites. Dysbiosis increases the risk of osteoporosis, fragility fractures and muscle wasting, with possible sex-specific differences, but the definition of GM traits associated with each condition is inconsistent across studies. Short-term microbiome-modifying treatments, including probiotics and functional foods, slowed down the age-related decline in bone mineral density and improved muscle function in a handful of small-sized clinical studies.

SUMMARY: Gut microbiome remains a very promising therapeutic target against osteoporosis and sarcopenia, but no recommendations can be made for clinical practice at the current state-of-art. Microbiome-targeted strategies may soon emerge as valuable adjuvant therapies in the management of age-related musculoskeletal decline.}, } @article {pmid41017030, year = {2025}, author = {Jones, JC and García, OG and Villalba, JA and Hinojosa, R and Taylor, ML and Annambhotla, P and Kapturczak, MH and Mayes, B and Karpathy, SE and Gleaton, AN and Moon, L and Singleton, J and Basavaraju, SV and Paddock, CD}, title = {Organ Donor Transmission of Rickettsia typhi to Kidney Transplant Recipients, Texas, USA, 2024.}, journal = {Emerging infectious diseases}, volume = {31}, number = {10}, pages = {1893-1900}, doi = {10.3201/eid3110.250961}, pmid = {41017030}, issn = {1080-6059}, abstract = {Murine typhus, a fleaborne disease caused by the bacterium Rickettsia typhi, is found throughout temperate and tropical regions of the world. Transmission of R. typhi to humans involves several species of fleas, and most infections result from direct inoculation of R. typhi-infected flea feces into abrasions in the skin. We describe the transmission of R. typhi from an organ donor in Texas, USA, to 2 kidney transplant recipients. The donor and 1 recipient died from the infection. The occurrence of R. typhi transmission via transplantation is a harbinger for the reemergence of murine typhus in some of the most densely populated metropolitan areas of the United States. Our findings reinforce the need to improve healthcare provider and public awareness of this life-threatening but treatable infection.}, } @article {pmid41016812, year = {2025}, author = {Huang, L and Li, H and Yang, W and Huang, L and Chen, Q and Li, S and Zou, Z and Zhao, L and Zeng, Z}, title = {L-Theanine Ameliorates Metabolic Dysregulation and Adverse Fetal Outcomes in a Mice Model of Gestational Obesity: Association with FXR/FGF15 Signaling.}, journal = {Journal of microbiology and biotechnology}, volume = {35}, number = {}, pages = {e2504017}, doi = {10.4014/jmb.2504.04017}, pmid = {41016812}, issn = {1738-8872}, mesh = {Animals ; Female ; Pregnancy ; Mice ; Gastrointestinal Microbiome/drug effects ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; *Glutamates/pharmacology/therapeutic use ; *Fibroblast Growth Factors/metabolism/genetics ; *Receptors, Cytoplasmic and Nuclear/metabolism ; Signal Transduction/drug effects ; Pregnancy Outcome ; Humans ; *Pregnancy in Obesity/metabolism/drug therapy ; Mice, Inbred C57BL ; *Obesity/metabolism ; Mice, Obese ; Placenta ; }, abstract = {In this study, we investigated whether L-theanine (LTA) ameliorates adverse pregnancy outcomes in high-fat diet (HFD)-induced gestational obesity mice. Gestational obese mice models received HFD and fecal microbiota transplantation (FMT) from pregnant obese women, followed by LTA treatment. Gut microbiota DNA from six obese and six normal pregnant women was analyzed. Also assessed were lipid profiles, inflammatory factors, gut permeability, FXR/FGF15 expression, pup weight, and placental function. Alpha- and beta-diversity analyses showed reduced gut microbial diversity in the obese pregnant women. Postpartum hemorrhage, cholesterol, and triglycerides inversely correlated with Weissella, while BMI was positively associated with Escherichia-Shigella. Neonatal weight correlated positively with Subdoligranulum and negatively with Megamonas. Fasting glucose was significantly positively associated with Bacteroides vulgatus, whereas neonatal body weight inversely correlated with Eubacterium ramulus. In gestational obesity mice, LTA administration reduced weight gain, visceral/gonadal adiposity, metabolic markers (fasting glucose/insulin/cholesterol), gut barrier dysfunction (TNF-α, IL-6, IL-8, Claudin-2), and linked to FXR/FGF15 pathway alterations. Furthermore, LTA intervention suppressed MCP-1, IL-1β, F4/80 and hepatic lipid metabolism regulators (CD36, SREBP1c, SCD1, GLUT4, Cyp7a1, IRS-1), while also mitigating placental tissue junction zone abnormalities and pup weight. To sum up, LTA-mediated attenuation of adverse pregnancy outcomes associates with FXR/FGF15 pathway alterations, concomitant with restoration of metabolic homeostasis and inflammation suppression.}, } @article {pmid41016739, year = {2025}, author = {Zheng, D and Chen, S and Feng, H and Zhang, S and Zhang, C and Wang, Y and Tan, W and Qing, Q and Liu, L and Liu, X and Wang, Z and Liang, L and Sun, J and Chen, Y}, title = {Oral administration of low-molecular-weight heparin ameliorates colitis by enhancing the gut mucus barrier via microbial tryptophan metabolites.}, journal = {British journal of pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bph.70209}, pmid = {41016739}, issn = {1476-5381}, support = {2021YFA0717000//National Key R&D Program of China/ ; 81800460//National Natural Science Foundation of China/ ; 82270581//National Natural Science Foundation of China/ ; KCXFZ20211020163558024//Shenzhen Science and Technology Innovation Program/ ; ZDSYS20220606100800002//Shenzhen Key Laboratory of Gastrointestinal Microbiota and Disease/ ; }, abstract = {BACKGROUND AND PURPOSE: Previous studies have reported that oral low-molecular-weight heparin (LMWH) ameliorated colitis by undefined mechanisms in ulcerative colitis (UC) patients. Our study explored the mechanisms of LMWH on colitis from the perspective of gut microbiota and its metabolites.

EXPERIMENTAL APPROACH: Dextran sulfate sodium (DSS; 2.5%) was used to induce colitis in mouse model, and LMWH was administered by either oral gavage, intracolonic delivery or subcutaneous injection to compare their therapeutic effects. Pseudo-germ-free mice was established by using antibiotic cocktail, and faecal microbial transplantation (FMT) was performed to verify the role of microbiota in LMWH actions. Alcian blue staining, fluorescence in situ hybridization of EUB338 and immunohistochemical staining were performed to evaluate the integrity of gut mucus barrier. Amplicon sequencing, transcriptome sequencing and untargeted metabolome studies were used to explore LMWH mechanisms. The ameliorating effect of indole-3-propionic acid (IPA) was verified in vitro and in vivo.

KEY RESULTS: Oral, but not subcutaneous, administration of LMWH alleviated colitis and enhanced the gut mucus barrier. Pseudo-germ-free mice and FMT assays confirmed that therapeutic effects of oral LMWH were dependent on gut microbiota. Oral LMWH increased Firmicutes abundance and decreased Escherichia/Shigella abundance, subsequently increasing microbial tryptophan metabolites, especially IPA. The protective effects of oral LMWH were reproduced by IPA supplementation, with mucus barrier enhancing through regulating the Wnt/β-catenin pathway.

CONCLUSION AND IMPLICATIONS: The results provide new insights into the signalling mechanisms associated with the therapeutic potential of LMWH in colitis, and highlight the application of IPA for UC treatment.}, } @article {pmid41015495, year = {2025}, author = {Castells-Nobau, A and Fumagalli, A and Del Castillo-Izquierdo, Á and Rosell-Díaz, M and de la Vega-Correa, L and Samulėnaitė, S and Motger-Albertí, A and Arnoriaga-Rodríguez, M and Garre-Olmo, J and Puig, J and Ramos, R and Burokas, A and Coll, C and Zapata-Tona, C and Perez-Brocal, V and Ramio, L and Moya, A and Swann, J and Martín-García, E and Maldonado, R and Fernández-Real, JM and Mayneris-Perxachs, J}, title = {Gut microbial modulation of 3-hydroxyanthranilic acid and dopaminergic signalling influences attention in obesity.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-336391}, pmid = {41015495}, issn = {1468-3288}, abstract = {BACKGROUND: Obesity-related alterations in the gut microbiota have been linked to cognitive decline, yet their relationship with attention remains poorly understood.

OBJECTIVE: To evaluate the possible relationships among gut metagenomics, plasma metabolomics and attention.

DESIGN: We conducted faecal shotgun metagenomics and targeted plasma tryptophan metabolomics across three independent cohorts (n=156, n=124, n=804) with functional validations in preclinical models, including three faecal microbiota transplantation (FMT) experiments in mice and Drosophila melanogaster.

RESULTS: Obesity was consistently associated with reduced attention. Metagenomics analyses identified Proteobacteria species and microbial functions related to tryptophan biosynthesis from anthranilic acid (AA) as negatively associated with attention in obesity. Plasma tryptophan metabolic profiling and machine learning revealed that 3-hydroxyanthranilic acid (3-HAA) was positively associated with attention, particularly in obesity, while AA showed a negative association. Bariatric surgery improved attention and enriched microbial species linked to attention. In mice, diet-induced obesity (DIO) and microbiota depletion reduced 3-HAA and 5-hydroxy-indole acetic acid (5-HIAA) concentrations in the prefrontal cortex (PFC), which were restored by FMT. Global metabolic profiling (>600 metabolites) of PFC from the FMT group identified 3-HAA and the tryptophan and tyrosine pathways among the most significant in mice receiving microbiota from high-attention donors. A second FMT experiment also revealed a consistent enrichment of the tryptophan and tyrosine metabolism at the transcriptional level in the PFC, with Haao (3-hydroxyantrhanilic acid dioxygenase) and Aox4 (aldehyde oxidase 4), key in 3-HAA and 5-HIAA degradation, among the significantly regulated genes. In a third FMT study, attentional traits were transmitted from humans to mice alongside modulation of serotonergic and dopaminergic pathways. In Drosophila, mono-colonisation with Enterobacter cloacae and DIO induced attention deficit-like behaviours, which were mitigated by 3-HAA supplementation.

CONCLUSIONS: We have identified the microbiota and 3-HAA as potential therapeutic targets to improve attention, especially in obesity.}, } @article {pmid41013319, year = {2025}, author = {Igbo, CA and Ezeano, C and Adeniran, O and Taha, M and Annan, AA and Nriagu, VC and Boateng, S and Williams, MC and Onyali, C}, title = {The impact of fecal microbiota transplantation on refractory ulcerative colitis: A systematic review and Meta-Analysis of randomised controlled trials.}, journal = {BMC gastroenterology}, volume = {25}, number = {1}, pages = {654}, pmid = {41013319}, issn = {1471-230X}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Colitis, Ulcerative/therapy ; Randomized Controlled Trials as Topic ; Remission Induction ; Treatment Outcome ; }, abstract = {BACKGROUND: Refractory ulcerative colitis (UC), characterized by persistent disease activity despite optimized medical therapy, poses a significant therapeutic challenge. Fecal microbiota transplantation (FMT) has shown promise in inducing remission in active ulcerative colitis (UC) by restoring gut microbial balance; however, its efficacy in refractory cases remains unclear. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of FMT in achieving clinical and endoscopic remission in patients with refractory UC, based on evidence from randomized controlled trials (RCTs).

METHODS: We searched PubMed, Scopus, Google Scholar Cochrane CENTRAL, and Web of Science up to February 2025 for RCTs comparing FMT to placebo or standard care in adults with refractory UC (Mayo Score ≥ 3 despite treatment). Primary outcomes were clinical remission (Mayo Score ≤ 2, no subscore > 1) and endoscopic remission (Mayo endoscopic subscore ≤ 1). Data were pooled using a random-effects model, with heterogeneity assessed via I² and Q-tests. Subgroup analyses explored age at diagnosis and disease duration as moderators. The review followed PRISMA guidelines and was registered with PROSPERO (CRD420250651790).

RESULTS: Six RCTs were included. FMT showed no significant effect on clinical remission (pooled estimate - 0.2584; 95% CI - 0.9031 to 0.3863; p = 0.4321) or endoscopic remission (pooled estimate - 0.2229; 95% CI - 0.8811 to 0.4353; p = 0.5069), with no heterogeneity (I² = 0.00%). Subgroup analyses revealed no moderation by age or disease duration (p > 0.27). Adverse events were mild and transient.

CONCLUSION: FMT does not significantly improve clinical or endoscopic remission in refractory UC, suggesting limited efficacy in this population despite a favorable safety profile. Larger, standardized trials are warranted.}, } @article {pmid41012834, year = {2025}, author = {Liu, S and Zhou, B and Liu, L and Zhong, J and Zhang, X and Jiang, W and Liu, H and Zhou, Z and Peng, G and Zhong, Y and Zhang, K and Zhong, Z}, title = {Effects and Microbiota Changes Following Oral Lyophilized Fecal Microbiota Transplantation Capsules in Canine with Chronic Enteropathy After Parvovirus Infection: Case Report.}, journal = {Veterinary sciences}, volume = {12}, number = {9}, pages = {}, doi = {10.3390/vetsci12090909}, pmid = {41012834}, issn = {2306-7381}, support = {CGF2024001//the Study on Key Technologies for Conservation of Wild Giant Panda Populations and Its Habitats within Giant Panda National Park System/ ; }, abstract = {(1) Background: Chronic enteropathy (CE) in canines is associated with persistent microbiome dysbiosis, and conventional therapies (e.g., special diets, antimicrobials, and immunosuppressive drugs) are sometimes ineffective. Currently, fecal microbiota transplantation (FMT) has proven successful in treating CE in canines via invasive methods (e.g., enemas or endoscopy) or via oral frozen liquid capsules, which must be stored at -80 °C. However, due to the invasiveness of the administration methods and the storage constraints of the liquid capsules, FMT is not widely used in veterinary clinical practice. (2) Methods: The case of a four-year-old Siberian Husky with a three-year history of CE following canine parvovirus infection received lyophilized FMT capsules for thirty days. Stool samples were collected for metagenomic sequencing and quantification of fecal short-chain fatty acids (SCFAs), both pre- and post-FMT. Blood samples were analyzed using complete blood count (CBC) and biochemical testing. Ultrasound was used to assess the wall thickness of the stomach, duodenum, jejunum, and colon. (3) Results: Post-FMT, improvements in clinical outcomes were observed: fecal scores improved from 6 (unformed stools with mucus) to 2 (formed stool), and body weight increased by 8.3% (from 24.2 kg to 26.2 kg). Abnormal CBC and biochemical parameters were restored to reference ranges, including hematocrit (from 60.6% to 55.7%), hemoglobin (from 208 g/L to 190 g/L), creatinine (from 167 μmol/L to 121 μmol/L), and urea (from 11.9 mmol/L to 7.1 mmol/L). Ultrasound results showed that colonic wall thickness decreased from 0.23 ± 0.03 cm (pathological) to 0.18 ± 0.01 cm (physiological). Metagenomic analysis revealed that microbial richness (operational taxonomic units (OTUs) from 151 to 183) and diversity (Shannon and Simpson indices from 3.16 to 4.8 and from 0.87 to 0.94, respectively) all increased. The microbiota composition of the recipient exhibited a decline in the relative abundance of Firmicutes, falling from 99.84% to 35.62%, concomitant with an increase in Actinobacteria (from 0.08% to 4.78%), indicating a convergence toward a donor-like profile. Fecal SCFAs analysis revealed a 251.4% increase in propionate (from 0.0833 to 0.2929 mg/g) and elevated acetate (from 0.4425 to 0.4676 mg/g). These changes are functionally linked to enriched propanoate metabolism (Z = 0.89) in KEGG pathways. (4) Conclusions: Oral lyophilized FMT capsules resolved clinical signs of CE, enhanced microbial diversity and richness, and restored donor-like abundances of gut microbiota, particularly SCFA-producing taxa. Microbial restructuring increased microbial metabolite output, notably SCFA concentrations, and enriched functional metabolic pathways. Importantly, lyophilized FMT overcomes storage limitations and administration barriers, demonstrating its high clinical viability for treating canine CE.}, } @article {pmid41011544, year = {2025}, author = {Dai, K and Ding, L and Yang, X and Wang, S and Rong, Z}, title = {Gut Microbiota and Neurodevelopment in Preterm Infants: Mechanistic Insights and Prospects for Clinical Translation.}, journal = {Microorganisms}, volume = {13}, number = {9}, pages = {}, doi = {10.3390/microorganisms13092213}, pmid = {41011544}, issn = {2076-2607}, abstract = {Preterm birth remains a significant global health challenge and is strongly associated with heightened risks of long-term neurodevelopmental impairments, including cognitive delays, behavioural disorders, and emotional dysregulation. In recent years, accumulating evidence has underscored the critical role of the gut microbiota in early brain development through the gut-brain axis. In preterm infants, microbial colonisation is frequently delayed or disrupted due to caesarean delivery, perinatal antibiotic exposure, formula feeding, and prolonged stays in neonatal intensive care units (NICUs), all of which contribute to gut dysbiosis during critical periods of neurodevelopment. This review synthesises current knowledge on the sources, temporal patterns, and determinants of gut microbiota colonisation in preterm infants. This review focuses on the gut bacteriome and uses faecal-sample bacteriome sequencing as its primary method of characterisation. We detail five mechanistic pathways that link microbial disturbances to adverse neurodevelopmental outcomes: immune activation and white matter injury, short-chain fatty acids (SCFAs)-mediated neuroprotection, tryptophan-serotonin metabolic signalling, hypothalamic-pituitary-adrenal (HPA) axis modulation, and the integrity of intestinal and blood-brain barriers (BBB). We also critically examine emerging microbiota-targeted interventions-including probiotics, prebiotics, human milk oligosaccharides (HMOs), antibiotic stewardship strategies, skin-to-skin contact (SSC), and faecal microbiota transplantation (FMT)-focusing on their mechanisms of action, translational potential, and associated ethical concerns. Finally, we identify key research gaps, including the scarcity of longitudinal studies, limited functional modelling, and the absence of standardised protocols across clinical settings. A comprehensive understanding of microbial-neurodevelopmental interactions may provide a foundation for the development of targeted, timing-sensitive, and ethically sound interventions aimed at improving neurodevelopmental outcomes in this vulnerable population.}, } @article {pmid41011526, year = {2025}, author = {Roberts, JL and Park, CC}, title = {Emerging Roles of the Gut Microbiome in Musculoskeletal Injury and Repair.}, journal = {Microorganisms}, volume = {13}, number = {9}, pages = {}, doi = {10.3390/microorganisms13092193}, pmid = {41011526}, issn = {2076-2607}, support = {5P30AR003783-04/NH/NIH HHS/United States ; IK1RX003783//US Department of Veterans Affairs/ ; RFGA2024-022-010//Arizona Biomedical Research Centre/ ; }, abstract = {Over the past decade, significant attention has been directed toward understanding the role of the gut microbiome in health and disease. The gut microbiota, comprising a complex and diverse community of microorganisms, has been linked to numerous conditions, including metabolic disorders, gastrointestinal diseases, and inflammatory or autoimmune conditions. Recently, a growing body of evidence has revealed a compelling relationship between gut microbiota composition and musculoskeletal injury recovery, highlighting its potential as a novel therapeutic target. Musculoskeletal injuries, including fractures, post-traumatic osteoarthritis, and tendon or ligament injuries, commonly lead to changes in the community structure of the gut microbiota, intestinal permeability, and systemic inflammation, processes known to negatively influence tissue repair. Preclinical studies demonstrate that microbiota-targeted interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, effectively restore gut barrier integrity, modulate inflammation, and normalize gut-derived metabolite profiles. Despite these promising findings, critical gaps remain in translating these effects into clinical practice, particularly regarding the mechanisms linking specific microbiota changes to improved musculoskeletal healing outcomes. Future research incorporating rigorous clinical trials, multi-omics analyses, and advanced predictive tools, including artificial intelligence and microbiome-informed digital twins, is urgently needed to fully harness the therapeutic potential of microbiome-based interventions in musculoskeletal injury recovery. This narrative review provides insights into our evolving understanding of the relationship between the gut microbiota and musculoskeletal injury and explores the potential of gut microbiota-targeted therapies for improved healing outcomes.}, } @article {pmid41011482, year = {2025}, author = {Zhu, H and Yan, X and Shi, H and Chen, Y and Huang, C and Zhou, Y and Yan, S and Zhang, N and Wang, J and Zhang, J and Han, C and Chen, Q and Zhao, J and Cao, M}, title = {The Role of Gut Microbiota and Its Metabolites in Mitigating Radiation Damage.}, journal = {Microorganisms}, volume = {13}, number = {9}, pages = {}, doi = {10.3390/microorganisms13092151}, pmid = {41011482}, issn = {2076-2607}, support = {No. 2024ZYD0194//Central Guidance on Local Science and Technology Development Fund of Sichuan Province/ ; No. SZKF202309//Open Project Program of Panxi Crops Research and Utilization Key Laboratory of Sichuan Province/ ; No. 2024LQRD0045//Science and Technology Plan Project of Chengdu Longquanyi District/ ; }, abstract = {With the widespread use of ionizing radiation (IR) in medical and industrial settings, irradiation has become increasingly common, posing significant risks to human health. Among the various organs affected, the gut is particularly sensitive to radiation-induced damage, leading to conditions such as radiation-induced intestinal damage (RIID). Recent studies have emphasized the critical role of gut microbiota and its metabolites in mitigating radiation-induced injury. This review discusses the effects of IR on the mammalian and human gut microbiota. We examine the dynamics of gut microbiota composition during and after irradiation, and emphasize the protective role of the gut flora and the metabolites in the pathophysiological mechanisms exhibited during radiation injury. In addition, this article investigates how specific metabolites, such as short-chain fatty acids and indole derivatives, may contribute to the mitigation of inflammation and promotion of gut barrier integrity. In addition, various therapeutic strategies based on modulating the gut microbiota, such as probiotics, antibiotics, and fecal microbiota transplantation, are discussed to understand their potential to prevent or mitigate RIID. Understanding the interactions between IR, gut microbiota and their metabolites provides new avenues for developing innovative therapeutic approaches to improve patient outcomes during and after radiotherapy. Future research directions could focus on optimizing microbiota-based therapies and exploring the role of diet and lifestyle in enhancing intestinal health during irradiation.}, } @article {pmid41011478, year = {2025}, author = {Cortés, M and Olate, P and Rodriguez, R and Diaz, R and Martínez, A and Hernández, G and Sepulveda, N and Paz, EA and Quiñones, J}, title = {Human Microbiome as an Immunoregulatory Axis: Mechanisms, Dysbiosis, and Therapeutic Modulation.}, journal = {Microorganisms}, volume = {13}, number = {9}, pages = {}, doi = {10.3390/microorganisms13092147}, pmid = {41011478}, issn = {2076-2607}, support = {N° 21231033//Agencia Nacional de Investigación y Desarrollo/ ; }, abstract = {The human microbiome plays a central role in modulating the immune system and maintaining immunophysiological homeostasis, contributing to the prevention of immune-mediated diseases. In particular, the gut microbiota is a key ecosystem for immune system maturation, especially in early life. This review aimed to analyze the molecular and cellular mechanisms linking the microbiome to immune and neuronal functions, as well as the impact of dysbiosis and emerging therapeutic strategies targeting the microbiome. The analysis was based on scientific databases, prioritizing studies published since 2000, with special emphasis on the past decade. The microbiome influences immune signaling through microorganism-associated molecular patterns (MAMPs) and pattern recognition receptors (PRRs), including Toll-like receptors (TLRs). Additionally, microbial metabolites-such as short-chain fatty acids (SCFAs), tryptophan derivatives, and secondary bile acids-exert significant immunomodulatory effects. The intestinal epithelial barrier is also described as an active immunological interface contributing to systemic regulation. The literature highlights innovative therapies, including fecal microbiota transplantation (FMT), probiotics, and microbiome editing with CRISPR-Cas technologies. These strategies aim to restore microbial balance and improve immune outcomes. The growing body of evidence positions the microbiome as a valuable clinical and diagnostic target, with significant potential for application in personalized medicine.}, } @article {pmid41011464, year = {2025}, author = {Cano, Á and Ruiz Arabi, E and Ruiz, L and Nadales, BJ and Baumela, A and Recio, M and Machuca, I and Castón, JJ and Pérez-Nadales, E and Torre Cisneros, J}, title = {Compassionate Use of Encapsulated MKB-01 Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection: A Single-Center Experience.}, journal = {Microorganisms}, volume = {13}, number = {9}, pages = {}, doi = {10.3390/microorganisms13092134}, pmid = {41011464}, issn = {2076-2607}, abstract = {Fecal microbiota transplantation (FMT) is a safe and effective treatment for recurrent Clostridiodes difficile infection (rCDI). However, experience with the oral biologic product MKB-01 remains limited. We describe a series of 13 patients with rCDI treated with FMT using MKB-01 capsules administered orally. Each patient received a single dose of 4 capsules (≥2.1-2.5 × 10[11] microorganisms) with water after a 2 h fasting period. Antibiotic therapy was discontinued pre FMT. Clinical evaluation was performed at weeks 8 and 12. The mean number of prior recurrences was 1.5 (range: 1-3 episodes). In 12 patients (92.3%), FMT was administered after resolution of the current episode; in one patient (7%), it was administered on day 3 of fidaxomicin therapy, prior to symptom resolution. At week 8, clinical cure (Absence of baseline symptoms for at least 72 h) was achieved in 11 patients (84.6%). An additional patient (7%) responded to a second FMT. One recurrence occurred at 8 weeks and was resolved with a second FMT. Therefore, the overall clinical response rate after one or more FMTs was 12 out of 13 patients (92.3%). The procedure was well tolerated; only one patient experienced self-limited diarrhea. These findings support oral FMT with MKB-01 capsules as a safe and effective option for treating rCDI.}, } @article {pmid41011331, year = {2025}, author = {Alexandrescu, L and Tofolean, IT and Tofolean, DE and Nicoara, AD and Twakor, AN and Rusu, E and Preotesoiu, I and Dumitru, E and Dumitru, A and Tocia, C and Herlo, A and Alexandrescu, DM and Popescu, I and Cimpineanu, B}, title = {Ethanol-Induced Dysbiosis and Systemic Impact: A Meta-Analytical Synthesis of Human and Animal Research.}, journal = {Microorganisms}, volume = {13}, number = {9}, pages = {}, doi = {10.3390/microorganisms13092000}, pmid = {41011331}, issn = {2076-2607}, abstract = {BACKGROUND: Chronic ethanol consumption is a major global health concern traditionally associated with liver disease. Ethanol disrupts gut microbial communities, compromises intestinal barrier function, and contributes to hepatic, metabolic, and neurocognitive disorders.

METHODS: We conducted a systematic PubMed search and meta-analysis of 11 human and 19 animal studies evaluating ethanol-induced gut microbiota alterations. Studies were assessed for microbial diversity, taxonomic shifts, barrier integrity, and systemic effects. Effect sizes were calculated where possible, and interventional outcomes were examined.

RESULTS: Across species, ethanol exposure was consistently associated with reduced microbial diversity and depletion of beneficial commensals such as Faecalibacterium, Lactobacillus, Akkermansia, and Bifidobacterium, alongside an expansion of proinflammatory taxa (Proteobacteria, Enterococcus, Veillonella). Our analysis uniquely highlights discrepancies between human and animal studies, including opposite trends in specific genera (e.g., Akkermansia and Bifidobacterium) and the impact of confounders such as antibiotic exposure in human cohorts. We also demonstrate that microbiota-targeted interventions can partially restore diversity and improve clinical or behavioral outcomes.

CONCLUSIONS: This meta-analysis highlights reproducible patterns of ethanol-induced gut dysbiosis across both human and animal studies.}, } @article {pmid41011314, year = {2025}, author = {Meacci, D and Bruni, A and Cocquio, A and Dell'Anna, G and Mandarino, FV and Marasco, G and Cecinato, P and Barbara, G and Zagari, RM}, title = {Microbial Landscapes of the Gut-Biliary Axis: Implications for Benign and Malignant Biliary Tract Diseases.}, journal = {Microorganisms}, volume = {13}, number = {9}, pages = {}, doi = {10.3390/microorganisms13091980}, pmid = {41011314}, issn = {2076-2607}, abstract = {Next-generation sequencing has overturned the dogma of biliary sterility, revealing low-biomass microbiota along the gut-biliary axis with metabolic and immunologic effects. This review synthesizes evidence on composition, function, and routes of colonization across benign and malignant disease. In cholelithiasis, Proteobacteria- and Firmicutes-rich consortia provide β-glucuronidase, phospholipase A2, and bile salt hydrolase, driving bile supersaturation, nucleation, and recurrence. In primary sclerosing cholangitis, primary biliary cholangitis, and autoimmune hepatitis, intestinal dysbiosis and disturbed bile acid pools modulate pattern recognition receptors and bile acid signaling (FXR, TGR5), promote Th17 skewing, and injure cholangiocytes; bile frequently shows Enterococcus expansion linked to taurolithocholic acid. Distinct oncobiomes characterize cholangiocarcinoma subtypes; colibactin-positive Escherichia coli and intratumoral Gammaproteobacteria contribute to DNA damage and chemoresistance. In hepatocellular carcinoma, intratumoral microbial signatures correlate with tumor biology and prognosis. We critically appraise key methodological constraints-sampling route and post-sphincterotomy contamination, antibiotic prophylaxis, low biomass, and heterogeneous analytical pipelines-and outline a translational agenda: validated microbial/metabolomic biomarkers from bile, tissue, and stent biofilms; targeted modulation with selective antibiotics, engineered probiotics, fecal microbiota transplantation, and bile acid receptor modulators. Standardized protocols and spatial, multi-omic prospective studies are required to enable risk stratification and microbiota-informed therapeutics.}, } @article {pmid41011192, year = {2025}, author = {Cerrito, L and Galasso, L and Iaccarino, J and Pizzi, A and Termite, F and Esposto, G and Borriello, R and Ainora, ME and Gasbarrini, A and Zocco, MA}, title = {Present and Future Perspectives in the Treatment of Liver Fibrosis.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {9}, pages = {}, doi = {10.3390/ph18091321}, pmid = {41011192}, issn = {1424-8247}, abstract = {BACKGROUND/OBJECTIVES: Liver fibrosis is a progressive consequence of chronic liver injury that can evolve into cirrhosis, liver failure, or hepatocellular carcinoma, representing a major global health burden. Fibrogenesis is driven by hepatic stellate cell (HSC) activation, excessive extracellular matrix deposition, and structural disruption of liver tissue, with transforming growth factor-β (TGF-β) signaling and inflammatory mediators as central pathways. Current therapies primarily target the underlying causes, which may halt disease progression but rarely reverse established fibrosis. This review aims to outline current and emerging therapeutic strategies for liver fibrosis, informing both clinical practice and future research directions.

METHODS: A narrative synthesis of preclinical and clinical evidence was conducted, focusing on pharmacological interventions, microbiota-directed strategies, and innovative modalities under investigation for antifibrotic activity.

RESULTS: Bile acids, including ursodeoxycholic acid and derivatives, modulate HSC activity and autophagy. Farnesoid X receptor (FXR) agonists, such as obeticholic acid, reduce fibrosis but are limited by adverse effects. Fatty acid synthase inhibitors, exemplified by denifanstat, show promise in metabolic dysfunction-associated steatohepatitis (MASH). Additional strategies include renin-angiotensin system inhibitors, omega-3 fatty acids, and agents targeting the gut-liver axis. Microbiota-directed interventions-probiotics, prebiotics, symbiotics, antibiotics (e.g., rifaximin), and fecal microbiota transplantation-are emerging as potential modulators of barrier integrity, inflammation, and fibrogenesis, though larger clinical trials are required. Reliable non-invasive biomarkers and innovative trial designs, including adaptive platforms, are essential to improve patient selection and efficiently evaluate multiple agents and combinations.

CONCLUSIONS: Novel modalities such as immunotherapy, gene editing, and multi-targeted therapies hold additional potential for fibrosis reversal. Continued translational efforts are critical to establish safe, effective, and accessible treatments for patients with liver fibrosis.}, } @article {pmid41011021, year = {2025}, author = {Savvidis, C and Maggio, V and Rizzo, M and Zabuliene, L and Ilias, I}, title = {The Gut Microbiota Axis in Social Jetlag: A Novel Framework for Metabolic Dysfunction and Chronotherapeutic Innovation.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {9}, pages = {}, doi = {10.3390/medicina61091630}, pmid = {41011021}, issn = {1648-9144}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Circadian Rhythm/physiology ; *Jet Lag Syndrome/complications/physiopathology/microbiology/therapy ; *Metabolic Diseases/etiology ; *Chronotherapy/methods ; Melatonin/therapeutic use ; }, abstract = {Social jetlag, the misalignment between internal circadian rhythms and socially imposed schedules, is increasingly recognized as a risk factor for metabolic disorders such as obesity, type 2 diabetes (T2D), and cardiovascular disease. Recent evidence implicates the gut microbiota as a key mediator in this relationship, operating through a microbiota-gut-metabolic axis that influences host metabolism, immune function, and circadian regulation. Mechanistic studies reveal that social jetlag disrupts microbial rhythmicity, reduces short-chain fatty acid (SCFA) production, impairs intestinal barrier function, and promotes systemic inflammation, which contribute to insulin resistance and metabolic dysfunction. Clinical and preclinical interventions, including time-restricted feeding (TRF)/time-restricted eating (TRE), probiotics or melatonin supplementation, and fecal microbiota transplantation (FMT), demonstrate the potential to restore microbial and metabolic homeostasis by realigning host and microbial rhythms. This review synthesizes mechanistic insights with emerging human and clinical evidence, highlighting the gut microbiota as a novel target for chronotherapeutic strategies aimed at mitigating the metabolic consequences of circadian disruption. Recognizing and treating circadian-microbiome misalignment may provide a clinically actionable pathway to prevent or reverse chronic metabolic diseases in modern populations.}, } @article {pmid41010985, year = {2025}, author = {Petrelli, F and Ghidini, A and Dottorini, L and Ghidini, M and Zaniboni, A and Tomasello, G}, title = {Clinical Evidence for Microbiome-Based Strategies in Cancer Immunotherapy: A State-of-the-Art Review.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {9}, pages = {}, doi = {10.3390/medicina61091595}, pmid = {41010985}, issn = {1648-9144}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/immunology ; *Immunotherapy/methods ; *Neoplasms/therapy ; Immune Checkpoint Inhibitors/therapeutic use ; Probiotics/therapeutic use ; }, abstract = {The gut microbiome has emerged as a critical determinant of immune-checkpoint inhibitor (ICI) efficacy. A narrative review of 95 clinical studies (2015-2025) shows that patients with greater gut microbial diversity and relative enrichment of commensals such as Akkermansia, Ruminococcus, and other short-chain fatty acid producers experience longer progression-free and overall survival, particularly in melanoma and non-small-cell lung cancer. Broad-spectrum antibiotics given within 30 days of ICI initiation and over-the-counter mixed probiotics consistently correlate with poorer outcomes. Early phase I/II trials of responder-derived fecal microbiota transplantation in ICI-refractory melanoma achieved objective response rates of 20-40%, while pilot high-fiber or plant-forward dietary interventions improved immunologic surrogates such as CD8[+] tumor infiltration. Machine-learning classifiers that integrate 16S or metagenomic profiles predict ICI response with an area under the ROC curve of 0.83-0.92. Methodological heterogeneity across sampling, sequencing, and clinical endpoints remains a barrier, underscoring the need for standardization and larger, well-powered trials.}, } @article {pmid41010510, year = {2025}, author = {Petropoulos, A and Stavropoulou, E and Tsigalou, C and Bezirtzoglou, E}, title = {Microbiota Gut-Brain Axis and Autism Spectrum Disorder: Mechanisms and Therapeutic Perspectives.}, journal = {Nutrients}, volume = {17}, number = {18}, pages = {}, doi = {10.3390/nu17182984}, pmid = {41010510}, issn = {2072-6643}, support = {//Democritus University of Thrace/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Autism Spectrum Disorder/microbiology/therapy/physiopathology ; Dysbiosis/microbiology/therapy ; *Brain/physiopathology ; Animals ; *Brain-Gut Axis ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; Gastrointestinal Diseases/microbiology ; }, abstract = {Background/Objectives: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition often accompanied by gastrointestinal (GI) symptoms and gut microbiota imbalances. The microbiota-gut-brain (MGB) axis is a bidirectional communication network linking gut microbes, the GI system, and the central nervous system (CNS). This narrative review explores the role of the MGB axis in ASD pathophysiology, focusing on communication pathways, neurodevelopmental implications, gut microbiota alteration, GI dysfunction, and emerging therapeutics. Methods: A narrative review methodology was employed. We searched major scientific databases including PubMed, Scopus, and Google Scholar for research on MGB axis mechanisms, gut microbiota composition in ASD, dysbiosis, leaky gut, immune activation, GI disorders, and intervention (probiotics, prebiotics, fecal microbiota transplantation (FMT), antibiotics and diet). Key findings from recent human, animal and in vitro studies were synthesized thematically, emphasizing mechanistic insights and therapeutic outcomes. Original references from the initial manuscript draft were retained and supplemented for comprehensiveness and accuracy. Results: The MGB axis involves neuroanatomical, neuroendocrine, immunological, and metabolic pathways that enable microbes to influence brain development and function. Individuals with ASD commonly exhibit gut dysbiosis characterized by reduced microbial diversity (notably lower Bifidobacterium and Firmicutes) and overpresentation of potentially pathogenic taxa (e.g., Clostridia, Desulfovibrio, Enterobacteriaceae). Dysbiosis is associated with increased intestinal permeability ("leaky gut") and newly activated and altered microbial metabolite profiles, such as short-chain fatty acids (SCFAs) and lipopolysaccharides (LPSs). Functional gastrointestinal disorders (FGIDs) are prevalent in ASD, linking gut-brain axis dysfunction to behavioral severity. Therapeutically, probiotics and prebiotics can restore eubiosis, fortify the gut barrier, and reduce neuroinflammation, showing modest improvements in GI and behavioral symptoms. FMT and Microbiota Transfer Therapy (MTT) have yielded promising results in open label trials, improving GI function and some ASD behaviors. Antibiotic interventions (e.g., vancomycin) have been found to temporarily alleviate ASD symptoms associated with Clostridiales overgrowth, while nutritional strategies (high-fiber, gluten-free, or ketogenic diets) may modulate the microbiome and influence outcomes. Conclusions: Accumulating evidence implicates the MGB axis in ASD pathogenesis. Gut microbiota dysbiosis and the related GI pathology may exacerbate neurodevelopmental and behavioral symptoms via immune, endocrine and neural routes. Interventions targeting the gut ecosystem, through diet modification, probiotics, symbiotics, or microbiota transplants, offer therapeutic promise. However, heterogeneity in findings underscores the need for rigorous, large-scale studies to clarify causal relationships and evaluate long-term efficacy and safety. Understanding MGB axis mechanisms in ASD could pave the way for novel adjunctive treatments to improve the quality of life for individuals with ASD.}, } @article {pmid41010468, year = {2025}, author = {Forcina, G and Di Filippo, P and De Biasio, D and Cesaro, FG and Frattolillo, V and Massa, A and De Cesare, M and Marzuillo, P and Miraglia Del Giudice, E and Di Sessa, A}, title = {Targeting the Gut Microbiota in Pediatric Obesity: A Paradigm Shift in Prevention and Treatment? A Comprehensive Review.}, journal = {Nutrients}, volume = {17}, number = {18}, pages = {}, doi = {10.3390/nu17182942}, pmid = {41010468}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Pediatric Obesity/microbiology/therapy/prevention & control ; Probiotics/therapeutic use/administration & dosage ; Child ; Prebiotics/administration & dosage ; Fecal Microbiota Transplantation ; Dysbiosis/therapy ; Synbiotics/administration & dosage ; }, abstract = {Pediatric obesity represents a growing global health challenge, closely associated with increased cardiometabolic risk and long-term adverse outcomes. Although lifestyle modifications remain the cornerstone of treatment, sustained success is often limited. Emerging evidence suggests that the gut microbiota (GM) plays a pivotal role in the pathogenesis of obesity, influencing host metabolism, energy homeostasis, and systemic inflammation. This narrative review aims to provide a comprehensive and up-to-date overview of the complex interplay between GM and pediatric obesity, with a particular emphasis on microbiota-targeted interventions. These include probiotics, prebiotics, synbiotics, postbiotics, dietary modulation, and fecal microbiota transplantation (FMT). Findings from preclinical studies and early-phase clinical trials indicate that gut dysbiosis may contribute to obesity-related mechanisms, such as altered nutrient absorption, increased adiposity, and dysregulated appetite control. Interventions targeting the microbiota have shown promise in modulating inflammatory pathways and improving metabolic profiles. While preliminary findings underscore the potential of the GM as a novel adjunctive target in managing pediatric obesity, current evidence remains heterogeneous, and robust clinical pediatric data are limited. Further research is needed to clarify the therapeutic efficacy, safety, and long-term outcomes of microbiota-modulating strategies in children with obesity.}, } @article {pmid41010451, year = {2025}, author = {Jiang, Z and Zhu, J and Shen, Z and Gao, L and Chen, Z and Zhang, L and Wang, Q}, title = {The Microecological-Immune Axis in Pediatric Allergic Diseases: Imbalance Mechanisms and Regulatory Interventions.}, journal = {Nutrients}, volume = {17}, number = {18}, pages = {}, doi = {10.3390/nu17182925}, pmid = {41010451}, issn = {2072-6643}, support = {(2025KYCX1-A04//Wuhan Yaxin General Hospital Scientific Research and Innovation Fund Key Projects/ ; WCYY2022K02//Wuhan Wuchang Hospital Scientific Research and Innovation Fund Key Projects/ ; }, mesh = {Humans ; *Hypersensitivity/immunology/microbiology/therapy ; Child ; *Dysbiosis/immunology ; *Gastrointestinal Microbiome/immunology ; Probiotics/administration & dosage ; Prebiotics/administration & dosage ; *Microbiota/immunology ; Lung/immunology/microbiology ; Skin/immunology/microbiology ; Asthma/immunology/microbiology ; }, abstract = {In recent years, the global prevalence of pediatric allergic diseases-including atopic dermatitis, allergic rhinitis, and asthma-has increased significantly. Accumulating evidence underscores the pivotal role of the microbiota-immune axis in the regulation of immune tolerance, wherein microbial dysbiosis is a critical driver in the onset and progression of these conditions. Notably, reduced microbial diversity and imbalanced proportions can also cause immune dysregulation and cross-organ signaling. The skin-lung-gut axis has emerged as a key conduit for multi-organ immune communication. Microbial communities at barrier sites not only mediate local immune homeostasis but also influence distant organs through metabolite production and immune signaling pathways, forming a complex network of organ crosstalk. This mechanism is integral to the maintenance of both innate (e.g., epithelial barrier integrity and phagocytic activity) and adaptive (e.g., the Type 1/Type 2 cytokine balance and regulatory T cell function) immunity, thereby suppressing allergic inflammation. Early microbial colonization is crucial for immune system maturation, and its perturbation is strongly linked to abnormal allergic immune responses. As such, the skin-lung-gut axis functions as a cross-organ microecological-immune regulatory network that is particularly relevant in the context of infantile allergic disorders. Intervention strategies targeting the microbiota-including probiotics, prebiotics, synbiotics, and postbiotics-have demonstrated potential in modulating host immunity. Furthermore, emerging approaches such as engineered probiotics, advanced delivery systems, and fecal microbiota transplantation (FMT) offer promising therapeutic avenues. This review provides a comprehensive overview of microbiota development in early life, its association with allergic disease pathogenesis, and the current progress in microbiota-targeted interventions, offering a theoretical foundation for individualized prevention and treatment strategies.}, } @article {pmid41009869, year = {2025}, author = {Kocsis, B and Szabó, D and Sipos, L}, title = {Gut Microbiome and Intestinal Colonization with Multidrug-Resistant Strains of Enterobacterales: An Interplay Between Microbial Communities.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {9}, pages = {}, doi = {10.3390/antibiotics14090890}, pmid = {41009869}, issn = {2079-6382}, support = {No "0272//HUN-REN-SU, Human Microbiota Study Group/ ; Janos Bolyai Scholarship (BO/00286/22/5)//Hungarian Academy of Sciences./ ; 952491-AmReSu//European Union's Horizon 2020/ ; }, abstract = {Background: The intestinal tract is a host to a high number of diverse bacteria, and the presence of multidrug-resistant (MDR) Enterobacterales strains acts as a reservoir and a source of infection. The interactions between the intestinal microbiome and colonizer Enterobacterales strains influence long-lasting colonization. Aims: In this narrative review, we summarize available data about the intestinal colonization of MDR Enterobacterales strains and correlations between colonization and the intestinal microbiome. Results: Several endogenous and exogenous factors influence the intestinal colonization of MDR Enterobacterales strains. On the gut microbiome level, the intestinal microbial community is composed of the Lachnospiraceae family (e.g., Lachnoclostridium, Agathobacter, Roseburia, Tyzzerella), which indicates a protective role against colonizer MDR Enterobacterales strains; by contrast, a high abundance of Enterobacterales correlates with the colonization of MDR Enterobacterales strains. In specific patient groups, striking differences in microbiome composition can be detected. Among hematopoietic stem-cell-transplanted patients colonized by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales, a greater abundance of Bifidobacterium, Blautia, Clostridium, Coprococcus, L-Ruminococcus, Mogibacteriaceae, Peptostreptococceae and Oscillospira was observed compared to patients not colonized by ESBL-producing strains, who had a greater abundance of Actinomycetales. In liver transplant patients, a reduction in the alpha-diversity of the intestinal microbiome in fecal samples correlates with the carriage of MDR Enterobacterales. Conclusions: Intestinal colonization with MDR Enterobacterales is a multifactorial process that involves the MDR strain (e.g., its plasmids, fimbria), host and mucosal factors (e.g., IgA and defensin) and exogenous factors (e.g., use of antibiotics, hospitalization). On the gut microbiome level, the Lachnospiraceae family is dominant among intestines not colonized by MDR strains, but a high abundance of Enterobacterales was correlated with colonization with MDR Enterobacterales strains.}, } @article {pmid41009471, year = {2025}, author = {Miftode, IL and Vâţă, A and Miftode, RŞ and Oancea, AF and Pasăre, MA and Parângă, TG and Miftode, EG and Mititiuc, IL and Radu, VD}, title = {The Gut Microbiome and Colistin Resistance: A Hidden Driver of Antimicrobial Failure.}, journal = {International journal of molecular sciences}, volume = {26}, number = {18}, pages = {}, doi = {10.3390/ijms26188899}, pmid = {41009471}, issn = {1422-0067}, mesh = {*Gastrointestinal Microbiome/drug effects ; Humans ; *Colistin/pharmacology/therapeutic use ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; Animals ; *Drug Resistance, Bacterial/genetics ; Gene Transfer, Horizontal ; }, abstract = {Colistin, a polymyxin antibiotic reintroduced as a last-resort therapy against multidrug-resistant Gram-negative bacteria, is increasingly being compromised by the emergence of plasmid-mediated colistin resistance genes (mcr-1 to mcr-10). The human gut microbiota serves as a major reservoir and transmission hub for these resistance determinants, even among individuals without prior colistin exposure. This review explores the mechanisms, dissemination, and clinical implications of mcr-mediated colistin resistance within the gut microbiota, highlighting its role in horizontal gene transfer, colonization, and environmental persistence. A comprehensive synthesis of the recent literature was conducted, focusing on epidemiological studies, molecular mechanisms, neonatal implications and decolonization strategies. The intestinal tract supports the enrichment and exchange of mcr genes among commensal and pathogenic bacteria, especially under antibiotic pressure. Colistin use in agriculture has amplified gut colonization with resistant strains in both animals and humans. Surveillance gaps remain, particularly in neonatal populations, where colonization may occur early and persist silently. Promising interventions, such as fecal microbiota transplantation and phage therapies, are under investigation but lack large-scale clinical validation. The gut microbiome plays a central role in the global spread of colistin resistance. Mitigating this threat requires integrated One Health responses, improved diagnostics for gut colonization, and investment in microbiome-based therapies. A proactive, multisectoral approach is essential to safeguard colistin efficacy and address the expanding threat of mcr-mediated resistance.}, } @article {pmid41008952, year = {2025}, author = {Huang, W and Lv, Y and Zou, C and Ge, C and Zhan, S and Shen, X and Wu, L and Wang, X and Yuan, H and Lin, G and Yu, D and Liu, B}, title = {Mangosteen Pericarp Extract Mitigates Diquat-Induced Hepatic Oxidative Stress by NRF2/HO-1 Activation, Intestinal Barrier Integrity Restoration, and Gut Microbiota Modulation.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {9}, pages = {}, doi = {10.3390/antiox14091045}, pmid = {41008952}, issn = {2076-3921}, support = {32402779//National Natural Science Foundation of China/ ; ZCLMS25C1701//Zhejiang Provincial Natural Science Foundation/ ; 2024GZ39//Public Welfare and Applied Research Project of Huzhou Science and Technology Bureau/ ; }, abstract = {Poultry production exposes birds to diverse environmental and physiological stressors that disrupt redox balance, impair gut-liver axis function, and undermine health and productivity. This study investigated the hepatoprotective and antioxidative effects of mangosteen pericarp extract (MPE) in an experimental model of diquat-induced oxidative stress in laying hens. A total of 270 Hy-Line White laying hens were randomly assigned to three groups: control group (CON), diquat-challenged group (DQ), and MEP intervention with diquat-challenged group (MQ), with six replicates of 15 birds each. The results showed that MPE supplementation effectively mitigated the hepatic oxidative damage caused by diquat, as evidenced by the increased ALT and AST activity, improved lipid metabolism, and reduced hepatic fibrosis. Mechanistically, MPE activated the NRF2/HO-1 antioxidant pathway, thus enhancing the liver's ability to counteract ROS-induced damage and reducing lipid droplet accumulation in liver tissue. MPE supplementation restored intestinal barrier integrity by upregulating tight junction protein expression (Occludin-1 and ZO-1), enhancing MUC-2 expression, and thereby decreasing gut microbiota-derived LPS transferring from the intestine. Additionally, MPE also modulated gut microbiota composition by enriching beneficial bacterial genera such as Lactobacillus and Ruminococcus while suppressing the growth of potentially harmful taxa (e.g., Bacteroidales and UCG-010). Fecal microbiota transplantation (FMT) from MPE-treated donors into diquat-exposed recipients reproduced these beneficial effects, further highlighting the role of gut microbiota modulation in mediating MPE's systemic protective actions. Together, these findings demonstrated that MPE alleviated DQ-induced liver injury and oxidative stress through a combination of antioxidant activity, protection of intestinal barrier function, and modulation of gut microbiota, positioning MPE as a promising natural strategy for mitigating oxidative stress-related liver damage by regulating the gut microbiota and gut-liver axis in poultry.}, } @article {pmid41008344, year = {2025}, author = {Logan, AC and Cordell, B and Pillai, SD and Robinson, JM and Prescott, SL}, title = {From Bacillus Criminalis to the Legalome: Will Neuromicrobiology Impact 21st Century Criminal Justice?.}, journal = {Brain sciences}, volume = {15}, number = {9}, pages = {}, doi = {10.3390/brainsci15090984}, pmid = {41008344}, issn = {2076-3425}, abstract = {The idea that gut microbes or a "bacillus of crime" might promote criminal behavior was popularized in the early 20th century. Today, advances in neuromicrobiology and related omics technologies are lending credibility to the idea. In recent cases of dismissal of driving while intoxicated charges, courts in the United States and Europe have acknowledged that gut microbes can manufacture significant amounts of systemically available ethanol, without a defendant's awareness. Indeed, emergent research is raising difficult questions for criminal justice systems that depend on prescientific notions of free moral agency. Evidence demonstrates that gut microbes play a role in neurophysiology, influencing cognition and behaviors. This may lead to justice involvement via involuntary intoxication, aggression, anger, irritability, and antisocial behavior. Herein, we discuss these 'auto-brewery syndrome' court decisions, arguing that they portend a much larger incorporation of neuromicrobiology and multi-omics science within the criminal justice system. The legalome, which refers to the application of gut microbiome and omics sciences in the context of forensic psychiatry/psychology, will likely play an increasing role in 21st century criminal justice. The legalome concept is bolstered by epidemiology, mechanistic bench science, fecal transplant studies, multi-omics and polygenic research, Mendelian randomization work, microbiome signature research, and human intervention trials. However, a more robust body of microbiota-gut-brain axis research is needed, especially through the lens of prevention, intervention, and rehabilitation. With ethical guardrails in place, greater inclusion of at-risk or justice-involved persons in brain science and microbiome research has the potential to transform justice systems for the better.}, } @article {pmid41007859, year = {2025}, author = {Wang, J and Chao, J}, title = {Alveolar Epithelial Cell Dysfunction in Acute Respiratory Distress Syndrome: Mechanistic Insights and Targeted Interventions.}, journal = {Biomedicines}, volume = {13}, number = {9}, pages = {}, doi = {10.3390/biomedicines13092299}, pmid = {41007859}, issn = {2227-9059}, support = {82373547//National Natural Science Foundation of China/ ; BF2024054//Jiangsu Province Science and Technology Plan Project/ ; }, abstract = {Acute respiratory distress syndrome (ARDS) is a life-threatening condition with high mortality. A central driver in its pathogenesis is alveolar epithelial cell (AEC) dysfunction, which leads to disruption of the epithelial barrier, impaired fluid clearance, and dysregulated inflammatory responses. This review summarizes the key mechanisms underlying AEC injury, including programmed cell death (apoptosis, pyroptosis, necroptosis, ferroptosis), oxidative stress, mitochondrial dysfunction, epigenetic reprogramming (DNA methylation, histone modifications), metabolic rewiring (succinate accumulation), and spatiotemporal heterogeneity revealed by single-cell sequencing and spatial transcriptomics. Multicellular crosstalk involving epithelial-immune-endothelial networks and the gut-lung axis further shapes disease progression. Building on these mechanistic foundations, we evaluate emerging AEC-targeted interventions such as pharmacologic agents (antioxidants, anti-inflammatories), biologics (mesenchymal stem cells and engineered exosomes), and gene-based approaches (adeno-associated virus and CRISPR-Cas9 systems delivered via smart nanocarriers). Complementary strategies include microbiome modulation through probiotics, short-chain fatty acids, or fecal microbiota transplantation, and biomarker-guided precision medicine (e.g., sRAGE, exosomal miRNAs) to enable promise individualized regimens. We also discuss translational hurdles, including nanotoxicity, mesenchymal stem cell (MSC) heterogeneity, and gene-editing safety, and highlight future opportunities involving AI-driven multi-omics, lung-on-chip platforms, and epithelium-centered regenerative therapies. By integrating mechanistic insights with innovative therapeutic strategies, this review aims to outline a roadmap toward epithelium-targeted, precision-guided therapies for ARDS.}, } @article {pmid41007736, year = {2025}, author = {Borrego-Ruiz, A and Borrego, JJ}, title = {The Gut Microbiome in Human Obesity: A Comprehensive Review.}, journal = {Biomedicines}, volume = {13}, number = {9}, pages = {}, doi = {10.3390/biomedicines13092173}, pmid = {41007736}, issn = {2227-9059}, abstract = {An estimated 2.6 billion individuals are currently living with overweight or obesity, and this number is projected to exceed 4 billion by 2035. Consequently, unless this increasing trajectory is effectively addressed, the trend is expected to continue in the coming years. The gut microbiome has emerged as a central regulator of host metabolism and energy homeostasis, making its detailed characterization crucial for the advancement of innovative therapeutic strategies and for elucidating mechanisms underlying metabolic health and disease. This review examines human obesity through the lens of the gut microbiome, providing a comprehensive overview of its role by addressing gut microbiome alterations, microbiome-driven mechanisms, dietary influences, prebiotic effects, microbiome-based therapeutics, and other approaches in the treatment of obesity and related metabolic disorders. The composition of the gut microbiome is altered in obesity and characterized by reduced microbial diversity and inconsistent shifts in dominant bacterial phyla, which collectively contribute to metabolic dysregulation. The gut microbiome influences obesity through multiple mechanisms. These include regulating energy balance and insulin sensitivity via short-chain fatty acids, inducing chronic inflammation, modulating metabolic and appetite genes, altering bile acid signaling, and promoting fat storage by inhibiting fasting-induced adipose factor. Dietary patterns exert a profound influence on gut microbiome composition and function, with plant-based diets conferring protective effects against obesity and its comorbidities. Microbiome-based therapeutics, including probiotics, synbiotics, and fecal microbiota transplantation, have demonstrated potential in modulating key metabolic and inflammatory pathways associated with obesity. As the scientific understanding of the human gut microbiome continues to advance, the integration of microbiome-based therapies into standard clinical practice is poised to become increasingly feasible and therapeutically transformative, particularly for obesity, a complex condition that demands innovative and customized interventions.}, } @article {pmid41007706, year = {2025}, author = {Caserta, S and Alvaro, ME and Penna, G and Fazio, M and Stagno, F and Allegra, A}, title = {Gut Microbiota Dysbiosis and Dietary Interventions in Non-Hodgkin B-Cell Lymphomas: Implications for Treatment Response.}, journal = {Biomedicines}, volume = {13}, number = {9}, pages = {}, doi = {10.3390/biomedicines13092141}, pmid = {41007706}, issn = {2227-9059}, abstract = {Non-Hodgkin B-cell lymphomas are a heterogeneous group of lymphoid malignancies with variable biological behavior, clinical presentation and treatment response. While chemoimmunotherapy remains the cornerstone of their management, growing evidence implicates the gut microbiota as a critical modulator of both lymphomagenesis and therapeutic efficacy. Gut microbiota dysbiosis, characterized by reduced microbial diversity and pathogenic taxonomic shifts, has been observed also in newly diagnosed patients and not just after therapy. This microbial imbalance contributes to mucosal barrier disruption, systemic inflammation, and altered immune responses, affecting treatment outcomes and toxicity profiles. Antibiotic exposure, especially broad-spectrum agents, exacerbates dysbiosis and has been associated with inferior responses to immunochemotherapy and CAR T-cell therapy. Conversely, certain commensal taxa, like Faecalibacterium prausnitzii and Lactobacillus johnsonii, may exert protective effects by preserving mucosal homeostasis and promoting antitumor immunity. Targeted interventions, including prudent antibiotic stewardship, prebiotics, probiotics, dietary modulation, and fecal microbiota transplantation, are under investigation to restore eubiosis and improve clinical outcomes. Preliminary clinical trials suggest a strong correlation between baseline microbiome composition and therapeutic response. Further mechanistic studies and randomized trials are warranted to define the causal role of the microbiome in non-Hodgkin B-cell lymphomas pathophysiology and to develop personalized microbiome-modulating strategies as adjuncts to standard treatment.}, } @article {pmid41007667, year = {2025}, author = {Dziedziak, M and Mytych, A and Szyller, HP and Lasocka, M and Augustynowicz, G and Szydziak, J and Hrapkowicz, A and Dyda, M and Braksator, J and Pytrus, T}, title = {Gut Microbiota in Psychiatric and Neurological Disorders: Current Insights and Therapeutic Implications.}, journal = {Biomedicines}, volume = {13}, number = {9}, pages = {}, doi = {10.3390/biomedicines13092104}, pmid = {41007667}, issn = {2227-9059}, abstract = {Recent studies increasingly highlight the complex interaction between gut microbiota and mental health, drawing attention to the role of the microbiota-gut-brain axis (MGBA) in the pathophysiology of mental and neurodevelopmental disorders. Changes in the composition of the gut microbiota-dysbiosis-are associated with conditions such as depression, schizophrenia, bipolar disorder (BD), autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), and neurodegenerative diseases such as Parkinson's and Alzheimer's. These microbial imbalances can affect brain function through a variety of mechanisms, including activation of the immune system, alteration of intestinal permeability, modulation of the digestive and central nervous systems, and changes in the production of neuroactive metabolites such as short-chain fatty acids, serotonin, and tryptophan derivatives. The aim of this paper is to review the current state of knowledge on therapeutic strategies targeting the gut microbiome-including probiotics, prebiotics, synbiotics, personalized dietary interventions, and fecal microbiota transplantation (FMT)-which are becoming promising adjuncts or alternatives to conventional psychopharmacology, offering a forward-looking and individualized approach to mental health treatment. Understanding the bidirectional and multifactorial nature of MGBA may pave the way for new, integrative treatment paradigms in psychiatry and neurology, requiring further research and exploration of their scope of application.}, } @article {pmid40716981, year = {2025}, author = {Wang, Y and Bao, J and Chen, B and Zhang, F and Cui, B}, title = {Successful management of oral manifestations of Behcet's disease and Sjogren's disease using washed microbiota transplantation: a case report.}, journal = {Oral surgery, oral medicine, oral pathology and oral radiology}, volume = {140}, number = {5}, pages = {e147-e152}, doi = {10.1016/j.oooo.2025.06.017}, pmid = {40716981}, issn = {2212-4411}, mesh = {Humans ; *Behcet Syndrome/complications/therapy ; Female ; *Sjogren's Syndrome/complications/therapy ; Adult ; *Oral Ulcer/therapy/etiology/microbiology ; Xerostomia/therapy/etiology ; *Fecal Microbiota Transplantation ; Dry Eye Syndromes/therapy/etiology ; }, abstract = {Recurrent oral ulcers is a characteristic of Behcet's disease (BD), while xerostomia typifies Sjogren's disease (SD), with emerging evidence implicating gut dysbiosis in their pathogenesis through oral-gut axis interactions. This case report describes a 36-year-old woman with BD and SD who presented with refractory oral ulcers, xerostomia, and dry eyes. Despite conventional therapy, her symptoms persisted until she underwent washed microbiota transplantation (WMT) to address concurrent gut dysbiosis. Remarkably, within 3 months, the frequency of oral ulcers decreased with quicker healing, and dry eye symptoms resolved completely. Two years later, sustained improvement was confirmed, allowing for discontinuation of hydroxychloroquine. Microbial analyses showed a significant difference in the gut and oral microbiota before and after WMT. These findings suggest WMT may offer a novel therapeutic approach for refractory oral manifestations in BD and SD.}, } @article {pmid41006438, year = {2025}, author = {Prylińska-Jaśkowiak, M and Tabisz, H and Kujawski, S and Godlewska, BR and Słomko, J and Januszko-Giergielewicz, B and Murovska, M and Morten, KJ and Sokołowski, Ł and Zalewski, P}, title = {The gut microbial composition is different in chronic fatigue syndrome than in healthy controls.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {33075}, pmid = {41006438}, issn = {2045-2322}, abstract = {The pathogenesis of Chronic Fatigue Syndrome (CFS) is yet unknown. This study aimed to assess the gut microbial composition in CFS patients versus in healthy controls (HCs). The composition of fecal bacteria was examined in twenty-five CFS patients and sixteen HCs using Illumina sequencing of 16 S rRNA gene amplicons targeting the V3-V4 bacterial gene regions. 143 (46%) of the microbial genera were found only in the CFS. In addition, the gut microbial composition in the CFS patients contained a much higher proportion of the 10 most commonly found bacteria compared to the HCs group. A significantly lower observed number of operational taxonomic units (OTUs) was noted in CFS compared to HCs (p = 0.045). Significant between-group differences in the gut microbial composition in CFS compared to HCs were noted. The three most discriminating Amplicon Sequencing Variants (ASVs): ASV 191, ASV 44, and ASV 75, were identified as significantly more abundant in the healthy control group compared to the patient group. In addition, the Neural Network (multilayer perceptron) was able to discriminate gut microbial composition from CFS versus HCs with excellent performance (AUC = 0.935). The gut microbial composition is different in CFS patients compared to HCs. Further studies should assess the pathophysiological consequences of these differences as well as the effectiveness of therapies aimed at modifying the gut microbial composition in CFS patients.}, } @article {pmid41005300, year = {2025}, author = {Zhao, CN and Li, SS and Yau, T and Chen, WQ and Ji, R and Guan, XY and Kong, FS}, title = {Phocaeicola vulgatus induces immunotherapy resistance in hepatocellular carcinoma via reducing indoleacetic acid production.}, journal = {Cell reports. Medicine}, volume = {}, number = {}, pages = {102370}, doi = {10.1016/j.xcrm.2025.102370}, pmid = {41005300}, issn = {2666-3791}, abstract = {Immunotherapy has made remarkable achievements in various cancers, but response rates in hepatocellular carcinoma (HCC) remain highly variable. Understanding mechanisms behind this heterogeneity and identifying responsive patients are urgent clinical challenges. In this study, the metagenomic analysis of 65 HCC patients reveals distinct gut microbiota profiles distinguishing responders (Rs) from non-responders (NRs). These findings are further validated through fecal microbiota transplantation (FMT) in mouse models. Notably, Phocaeicola vulgatus (P. vulgatus) is enriched in NRs and diminishes anti-PD-1 efficacy in both syngeneic and orthotopic tumor models. Mechanistically, P. vulgatus suppresses the production of indoleacetic acid (IAA), thereby weakening interferon (IFN)-γ[+] and granzyme B (GzmB)[+]CD8[+] T cells and impairing the antitumor immune response. Furthermore, supplementation with IAA restores CD8[+] T cell cytotoxicity and counteracts the immune-suppressive effects of P. vulgatus. Our findings establish a causal relationship between P. vulgatus and anti-PD-1 resistance in HCC, highlighting IAA as a potential therapeutic target to enhance immunotherapy outcomes.}, } @article {pmid41005008, year = {2025}, author = {Jia, R and Xiao, CX and Zhang, YH and Hu, LY and Jun-Jun, Y and Zuo, R and Hu, YF and Xie, YH and Ma, XL and Li, Q and Hou, KJ}, title = {Microbiota in drug resistance.}, journal = {Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy}, volume = {84}, number = {}, pages = {101311}, doi = {10.1016/j.drup.2025.101311}, pmid = {41005008}, issn = {1532-2084}, abstract = {Drug resistance, particularly those of anticancer drugs and antibiotics, poses a significant challenge in the treatment of diseases, severely compromising therapeutic efficacy and patient survival rates. In recent years, an increasing number of studies have highlighted the dual role of microbiota in either promoting or mitigating drug resistance. The microbiome exists in symbiosis with the host, playing a crucial role in maintaining physiological functions and regulating immune responses. However, dysbiosis within the microbial community may induce or exacerbate drug resistance. While antibiotic-mediated depletion of gut microbiota has been proposed as a strategy to combat resistance, it may paradoxically lead to increased resistance or even worsen treatment outcomes. In this review, we focus on anticancer and antimicrobial agents as representative examples to elucidate the association of microbiome and drug resistance. We provide a detailed discussion on the mechanisms by which microbial dysbiosis contributes to development of drug resistance. Additionally, we systematically summarize the latest advancements in microbiota-targeted therapeutic strategies aimed at overcoming resistance, including fecal microbiota transplantation, probiotics and prebiotics, and bacterial engineering approaches. Finally, we discuss the potential clinical applications of microbiota-modulating strategies for overcoming drug resistance and examine the current challenges and future research directions in this field.}, } @article {pmid41004024, year = {2025}, author = {Longo, M and Rubio, T and Lamelas, A and Jericó, D and Rodenes-Gavidia, A and Cervero, J and Martínez-Blanch, J and Chenoll, E and Martorell, P and Paolini, E and Meroni, M and Riezu-Boj, JI and Solares, I and Sampedro, A and Urigo, F and Collantes, M and Battistin, M and Gatti, S and Quincoces, G and Peñuelas, I and Moreno-Aliaga, MJ and Ávila, MA and Di Pierro, E and Ramón, D and Milagro, FI and Dongiovanni, P and Fontanellas, A}, title = {Oral lipoteichoic and lipoic acids improve insulin resistance and body composition in porphyria mice on a high-carbohydrate diet.}, journal = {Journal of physiology and biochemistry}, volume = {}, number = {}, pages = {}, pmid = {41004024}, issn = {1877-8755}, abstract = {Acute intermittent porphyria (AIP) is a genetic metabolic disorder characterized by neurovisceral attacks. Although high-carbohydrate diets or intravenous glucose administration can help alleviate incipient attacks in patients, these interventions may also promote insulin resistance and increase metabolic risk. This study explored targeted dietary interventions to manage hyperinsulinemia and to enhance glucose uptake in insulin-sensitive organs under high-carbohydrate diet. Body composition and fecal microbiota profile were also investigated in a murine model of the disease. Wild-type and AIP mice (n = 6/group) were supplemented with tapioca maltodextrin in drinking water for 12 weeks, alongside heat-treated Bifidobacterium animalis subsp. lactis CECT-8145 (BPL1®HT), its by-product lipoteichoic acid (LTA), or the insulin-sensitizing agent α-lipoic acid (α-LA). Liver-targeted therapies, previously assessed in AIP mice, were also included in this study. AIP mice on a high-carbohydrate diet exhibited hyperinsulinemia and tissue-specific differences in glucose uptake compared to wild-type mice. Dysbiosis, marked by reduced fecal Dorea spp. and Adlercreutzia muris, alongside higher abundance of Escherichia coli, was also showed. Supplementation with α-LA and LTA revealed superior ability to improve glucose tolerance test and skeletal muscle glucose uptake, reduce hyperinsulinemia, and enhance body composition by increasing lean mass relative to fat, compared to gene therapy or liver-targeted insulin administration. Notably, LTA restored fecal microbiota profiles resembling those of wild-type mice. In conclusion, supplementation with LTA from BPL1®HT and α-LA may represent promising dietary interventions to manage glucose tolerance, improve insulin sensitivity in muscle and adipose tissues, and potentially ameliorate body composition in AIP patients under a high-carbohydrate diet.}, } @article {pmid41003873, year = {2025}, author = {Sadeghloo, Z and Sadeghi, A}, title = {Gut microbiota as a hidden modulator of chemotherapy: implications for colorectal cancer treatment.}, journal = {Discover oncology}, volume = {16}, number = {1}, pages = {1717}, pmid = {41003873}, issn = {2730-6011}, abstract = {Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality worldwide, with chemotherapy remaining a cornerstone of treatment. Emerging evidence reveals that the gut microbiota significantly influences the metabolism, efficacy, and toxicity of chemotherapeutic agents such as 5-fluorouracil, irinotecan, and oxaliplatin. Microbial enzymes-most notably β-glucuronidases-can reactivate drug metabolites, contributing to adverse effects like mucositis and diarrhea. Additionally, certain bacterial species promote chemoresistance by modulating host immune responses and tumor microenvironments. This review highlights the critical role of the gut microbiota in shaping the efficacy and toxicity of chemotherapy in colorectal cancer, with a focus on microbial metabolism, chemoresistance, and microbiota-targeted therapies. Microbiota-targeted interventions-including probiotics, prebiotics, fecal microbiota transplantation (FMT), and enzyme inhibitors-represent promising strategies to improve treatment outcomes and mitigate toxicity. Enhanced understanding of microbiota-drug interactions is crucial for personalizing chemotherapy regimens, optimizing therapeutic efficacy, and minimizing adverse effects. The gut microbiota thus serves as both a key modulator and a potential therapeutic target in CRC.}, } @article {pmid41002952, year = {2025}, author = {Ji, M and Ji, M and Zhong, Y and Shao, L}, title = {Gut Microbiota in Acute Myeloid Leukemia: From Biomarkers to Interventions.}, journal = {Metabolites}, volume = {15}, number = {9}, pages = {}, doi = {10.3390/metabo15090568}, pmid = {41002952}, issn = {2218-1989}, abstract = {Acute myeloid leukemia (AML), the most common acute leukemia among adults, poses significant therapeutic challenges due to diagnostic limitations and the frequent development of treatment resistance. While genomics-based approaches have advanced, DNA aberrations do not always reflect the expression levels of genes and proteins, which are more tightly connected to disease phenotypes. Recently, the role of the gut microbiota in AML has gained increasing attention. AML patients often exhibit gut microbiota dysbiosis, which is linked to disease progression and heightened infection risk. Mounting evidence indicates that gut microbiota metabolism influences hematopoiesis and immune function via the "gut-bone marrow axis," with microbiota composition and diversity significantly affecting treatment outcomes and prognosis. High-throughput sequencing and metabolomics have identified correlations between gut microbiota composition and its metabolic products with AML clinical characteristics, paving the way for new biomarkers in diagnosis and prognosis. Additionally, treatments such as fecal microbiota transplantation (FMT) show promise in enhancing chemotherapy efficacy and improving patient outcomes. This review highlights recent advances in understanding the role of the gut microbiota in AML and explores new perspectives for its diagnosis and treatment.}, } @article {pmid41001760, year = {2025}, author = {Jiang, L and Li, M and Zhao, Z}, title = {Intra-tumoral microbial heterogeneity of breast cancer: roles in tumorigenesis, therapeutic responses, and future directions.}, journal = {Journal of applied microbiology}, volume = {136}, number = {9}, pages = {}, doi = {10.1093/jambio/lxaf230}, pmid = {41001760}, issn = {1365-2672}, support = {82274296//National Natural Science Foundation of China/ ; 82473449//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Breast Neoplasms/microbiology/therapy/pathology ; Female ; *Carcinogenesis ; *Microbiota ; Tumor Microenvironment ; Dysbiosis/microbiology ; Probiotics/therapeutic use ; Gastrointestinal Microbiome ; }, abstract = {Recent advances in microbiome research have revealed that tumor-resident microbiota are not passive bystanders but active contributors to the progression of breast cancer. Similar to the well-characterized gut-breast microbiota axis, emerging evidence points to intricate interactions between intra-tumoral microbiota and breast cancer with implications for carcinogenesis, therapeutic response, and future directions. Intra-tumoral microbes have been shown to initiate inflammation, modulate tumor microenvironment, alter drug metabolism, and produce bioactive metabolites that influence tumor cell proliferation, apoptosis, and epithelial-mesenchymal transition. Distinct microbial signatures have been associated with specific molecular subtypes of breast cancer and may serve as predictive biomarkers for prognosis. Furthermore, dysbiosis within the tumor-resident microbiota has been linked to the development of treatment resistance, including chemotherapy, immunotherapy, and endocrine therapy. Preclinical studies support the feasibility of modulating the microbiota via using antibiotics, probiotics, fecal microbiota transplantation, or bacteriophage-based strategies to enhance antitumor efficacy and overcome resistance. This review summarizes current knowledge on the biological roles of tumor-resident microbiota in breast cancer, highlights subtype-specific microbial patterns and host-microbe interactions, and explores microbiota-targeted interventions as promising adjuncts in overcoming drug resistance.}, } @article {pmid41001122, year = {2025}, author = {Bahitham, W and Banoun, Y and Aljahdali, M and Almuaiqly, G and Bahshwan, SM and Aljahdali, L and Sanai, FM and Rosado, AS and Sergi, CM}, title = {"Trust your gut": exploring the connection between gut microbiome dysbiosis and the advancement of Metabolic Associated Steatosis Liver Disease (MASLD)/Metabolic Associated Steatohepatitis (MASH): a systematic review of animal and human studies.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1637071}, pmid = {41001122}, issn = {2296-861X}, abstract = {Metabolic Associated Steatosis Liver Disease (MASLD) and its advanced form, Metabolic Associated Steatohepatitis (MASH), represent growing global health concerns closely linked to obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. The gut microbiome has emerged as a key modulator in MASLD pathogenesis through the gut-liver axis, influencing hepatic fat accumulation, inflammation, and fibrosis via microbial metabolites and immune responses. Dysbiosis-characterized by altered microbial diversity and composition-contributes to hepatic lipid dysregulation, systemic inflammation, and impaired bile acid signaling. Metabolites such as short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), and ethanol play critical roles in disease progression. Recent innovations in precision medicine, including microbiome profiling, metabolomics, and genomics, offer promising diagnostic and therapeutic strategies. Targeted probiotics, fecal microbiota transplantation (FMT), and personalized dietary interventions are under investigation for modulating the gut microbiome. This systematic review, conducted in accordance with PRISMA 2020 guidelines, is the first to comprehensively integrate both animal and human studies on MASLD/MASH-related gut microbiome alterations. It uniquely synthesizes microbial taxa, functional metabolites, and region-specific patterns-including data from underrepresented MENA populations. Eligible studies from PubMed, Scopus, and Web of Science evaluated microbial composition, metabolite profiles, and associations with steatosis, inflammation, and fibrosis. The findings underscore the diagnostic and therapeutic potential of microbiome modulation and emphasize the need for longitudinal, mechanistically driven studies. This systematic review is the first to integrate both animal and human studies on MASLD/MASH-related gut microbiome alterations. Unlike previous reviews, it uniquely emphasizes microbial taxa, functional metabolites, and region-specific patterns, including underrepresented MENA populations. By synthesizing findings from diverse cohorts, this review highlights diagnostic and therapeutic opportunities while identifying persistent gaps in longitudinal data, regional representation, and multi-omics integration.}, } @article {pmid41000801, year = {2025}, author = {Soriano, S and Marshall, A and Holcomb, M and Flinn, H and Burke, M and Kara, G and Scalzo, P and Villapol, S}, title = {Sex-specific effects of fecal microbiota transplantation on TBI-exacerbated Alzheimer's pathology in mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.09.11.675717}, pmid = {41000801}, issn = {2692-8205}, abstract = {BACKGROUND: Traumatic brain injury (TBI) accelerates Alzheimer's disease (AD) pathology and neuroinflammation, potentially via gut-brain axis disruptions. Whether restoring gut microbial homeostasis mitigates TBI-exacerbated AD features remains unclear, particularly with respect to sex differences.

OBJECTIVE: The goal of our study was to test whether fecal microbiota transplantation (FMT) modifies amyloid pathology, neuroinflammation, gut microbial composition, metabolites, and motor outcomes in male and female 5xFAD mice subjected to TBI.

METHODS: Male and female 5xFAD mice received sham treatments or controlled cortical impact, followed 24 hours later by vehicle (VH) or sex-matched FMT from C57BL/6 donors. Assessments at baseline, 1, and 3 days post-injury included Thioflavin-S and 6E10 immunostaining for Aβ, Iba-1 and GFAP for glial activation, lesion volume, rotarod performance, 16S rRNA sequencing for microbiome profiling, serum short-chain fatty acids (SCFAs), and gut histology.

RESULTS: TBI increased cortical and dentate gyrus Aβ burden, with females showing greater vulnerability. FMT reduced Aβ deposition in sham animals and shifted plaque morphology but did not attenuate TBI-induced amyloid escalation. FMT differentially modulated glial responses by sex and region (reduced microgliosis in males) without altering lesion volume. Rotarod performance was better in sham females compared to males and declined in FMT-treated TBI females. Fecal microbiome alpha diversity and richness were unchanged, while beta diversity revealed marked, time-dependent community shifts after TBI that were slightly altered by FMT. Gut morphology remained broadly intact, but crypt width increased after TBI, particularly in males.

CONCLUSION: In 5xFAD mice, TBI drives sex-dependent worsening of amyloid pathology, neuroinflammation, and dysbiosis. Acute FMT partially restores microbial composition and plaque features in sham animals but fails to reverse TBI-induced neuroinflammation or motor deficits. These findings underscore the context- and sex-dependence of microbiome interventions and support longer-term, sex-specific strategies for AD with comorbid TBI.}, } @article {pmid41000396, year = {2025}, author = {Liu, C and Wang, J and Lei, L and Li, L and Yuan, X}, title = {Gut microbiota therapy for chronic kidney disease.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1660226}, pmid = {41000396}, issn = {1664-3224}, mesh = {Humans ; *Renal Insufficiency, Chronic/therapy/microbiology/etiology ; *Gastrointestinal Microbiome ; Dysbiosis/therapy ; *Fecal Microbiota Transplantation/methods ; Animals ; Probiotics/therapeutic use ; Prebiotics/administration & dosage ; }, abstract = {Chronic kidney disease (CKD), affecting 13% of the global population, is increasingly linked to gut microbiota dysbiosis, a condition driven by uremic toxins accumulation, metabolic alterations, and dietary factors. This mini review explores gut microbiota modulation as a therapeutic strategy to alleviate CKD symptoms, focusing on interventions that target gut microbiota composition and function. Prebiotics, such as resistant starch, have been shown to lower uremic toxins and reduce inflammation, while dietary adjustments, including low-protein and gluten-free diets, modulate microbial diversity and improve renal biomarkers. Fecal microbiota transplantation (FMT), which stabilizes creatinine levels and shifts gut microbiota toward beneficial taxa, represents another promising approach. However, limitations persist: synbiotics, which often induce gut microbiota shifts, frequently lack clinical impact; probiotics, which enhance glucose control and oxidative stress mitigation, exhibit variable efficacy; and interventions such as propolis or cranberry extract, which have been tested, prove ineffective. The causal relationship between gut microbiota dysbiosis and CKD progression, which remains unclear, is further complicated by methodological heterogeneity across studies. Emerging strategies, including phage therapy and artificial intelligence-driven multi-omics integration, which hold significant promise, require further validation. Future research must prioritize longitudinal studies, maternal gut microbiota optimization, and personalized approaches, which are essential for advancing CKD management. While gut microbiota modulations hold therapeutic potential, translating these findings into clinical practice demands rigorous trials to address inconsistencies and establish mechanistic links, ultimately shifting CKD management from reactive treatment to precision-based prevention.}, } @article {pmid40999363, year = {2025}, author = {Pan, Y and Luo, Y and Wu, G and Lu, Y and Yang, P and Kong, P and Zheng, C and Wang, C and Yang, L and Li, X}, title = {Gut microbiota dysbiosis promotes coronary heart disease comorbid with depression through lipopolysaccharides and Toll-like receptor 4.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {588}, pmid = {40999363}, issn = {1471-2180}, support = {2021GXNSFBA196059//the Guangxi Young Scientists Fund/ ; 2022GXNSFDA035086//the Key Project of the Guangxi Natural Science Foundation/ ; 82060835//the National Natural Science Foundation of China/ ; 82360900//the National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Toll-Like Receptor 4/metabolism/genetics ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology/complications ; *Lipopolysaccharides/metabolism ; Rats ; Male ; *Coronary Disease/microbiology/metabolism/etiology ; Fecal Microbiota Transplantation ; *Depression/microbiology/metabolism ; Disease Models, Animal ; Rats, Sprague-Dawley ; Diet, High-Fat/adverse effects ; Myeloid Differentiation Factor 88/metabolism ; Comorbidity ; NF-kappa B/metabolism ; Signal Transduction ; RNA, Ribosomal, 16S/genetics ; Sulfonamides ; }, abstract = {Coronary heart disease (CHD) and depression often coexist and complicate patient care. The gut microbiota plays a crucial role in overall health and is involved in both conditions. Dysbiosis, particularly, increased levels of lipopolysaccharides (LPSs), can activate the Toll-like receptor 4 (TLR4), triggering inflammatory pathways associated with CHD and depression. Although some associations have been observed, the direct mechanistic association among gut dysbiosis, LPSs, TLR4 activation, and comorbidity of CHD and depression remains unclear. Thus, in the present study, we aimed to explore this association and the potential of modulating gut microbiota as a therapeutic strategy. METHODS: A rat model of CHD and depression was established using a high-fat diet and chronic unpredictable mild stress and verified by electrocardiogram, behavioral assessments, and cardiac marker analysis. Fecal microbiota transplantation (FMT) was performed by transferring microbiota from diseased rats to healthy rats (FMT-Disease group); the fecal microbiota of the rats from the FMT-Disease and FMT-Normal groups were compared. The TLR4 inhibitor TAK-242 was administered, creating the Disease + TAK-242 and FMT-Disease-TAK-242 groups. Gut microbiota composition was analyzed using 16 S rRNA high-throughput sequencing; LPS levels were measured using enzyme-linked immunosorbent assay. Polymerase chain reaction and western blotting were used to detect the expression of genes and proteins related to the TLR4/MYD88/NF-κB pathway in the heart and hippocampus, respectively. RESULTS: We confirmed that in the FMT-Disease group, the gut microbiota of diseased rats altered the gut microbial composition of healthy rats in terms of β-diversity, α-diversity, and community structure. Notably, LPS levels in the serum of FMT-Disease rats were elevated, thereby activating the TLR4/MYD88/NF-κB inflammatory pathway and increasing susceptibility to CHD comorbid with depression. Additionally, after receiving fecal microbiota from healthy rats, the Disease group showed a restoration of gut microbiota balance, improvement in general condition, and normalization of pathological, biochemical, and inflammatory indicators, indicating a suppressive effect on the progression of CHD with depression. CONCLUSION: Our findings further clarify the interrelationship between gut microbiota and CHD comorbid with depression, enhancing our understanding of its pathogenesis. Moreover, we propose a potential novel therapeutic strategy that focuses on modulating gut microbiota composition to block the TLR4/MYD88/NF-κB inflammatory pathway.}, } @article {pmid40998619, year = {2025}, author = {Metri, AA and Faghih, M and Thompson, E and Noë, M and Mannan, R and Kalyani, R and Gunzelman, E and Afghani, E and Cheesman, L and Akshintala, VS and Gurakar, M and Yousefli, Z and Warren, D and Desai, NM and Sun, Z and Walsh, C and Makary, MA and Hruban, RH and He, J and Zaheer, A and Singh, VK}, title = {Clinical predictors of pancreatic fibrosis in patients with recurrent acute and chronic pancreatitis.}, journal = {Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pan.2025.09.021}, pmid = {40998619}, issn = {1424-3911}, abstract = {OBJECTIVES: Fibrosis is considered the criterion standard for diagnosing chronic pancreatitis (CP) but adequate tissue specimens are difficult to obtain, carry risk and are often obtained at the time of surgery in advanced stages of CP. Noninvasive biomarkers that correlate with fibrosis across the continuum of pancreatitis are needed. Our aim was to determine which clinical variables are associated with fibrosis in patients with recurrent acute pancreatitis (RAP) or CP undergoing total pancreatectomy with islet autotransplantation (TPIAT).

METHODS: The demographic, clinical and radiologic data for patients undergoing TPIAT for RAP or CP between 2011 and 2023 were reviewed. Excisional biopsies from the proximal and distal pancreas were each scored from 0 to 6 for both perilobular and intralobular fibrosis, and the score of each biopsy was the sum of perilobular and intralobular fibrosis (0-12). The fibrosis score (FS), ranging from 0 to 12, was the mean FS from the proximal and distal pancreas.

RESULTS: There were 88 patients with a mean age 38 ± 14 years and 46 (52.3 %) were female. There were 35 (39.8 %) and 53 (60.2 %) with RAP and CP, respectively. Genetic (52.3 %) and idiopathic (37.5 %) were the most common etiologies. The mean FS was 6.52 ± 3.53. Large duct CP (β = 3, p = 0.001), exocrine pancreatic insufficiency (EPI) (β = 1.5, p = 0.037) and a genetic etiology (β = 1.6, p = 0.03) were significant predictors of fibrosis after adjusting for age, BMI, disease duration and use of oral hypoglycemic drugs and/or insulin.

CONCLUSION: Large duct CP, genetic etiology and EPI are all independent predictors of pancreatic fibrosis in a cohort of patients undergoing TPIAT. Computed tomography (CT) imaging and fecal elastase-1 (FE-1) concentration may be sufficient to estimate fibrosis without acquisition of a tissue specimen.}, } @article {pmid40997947, year = {2025}, author = {Bonilla-Moreno, M and Medina-Gómez, C and Guevara-Núñez, D and Saiz-Escobedo, L and Martí, S and Domínguez, MÁ and Carrera-Salinas, A and Rodríguez-Sevilla, G}, title = {Assessing healthcare workers as potential stool donors for faecal microbiota transplantation: a cross-sectional study of antimicrobial-resistant gut bacteria and enteropathogenic microorganisms.}, journal = {The Journal of hospital infection}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhin.2025.09.004}, pmid = {40997947}, issn = {1532-2939}, abstract = {BACKGROUND: Faecal Microbiota Transplantation (FMT) is a procedure designed to modulate the gut microbiome, but identifying reliable stool donors remains challenging. We conducted a study at Bellvitge University Hospital to assess the prevalence of enteropathogenic microorganisms (EPs) and antimicrobial-resistant (AMR) gut bacteria among healthcare workers (HCWs) and evaluate their potential as stool donors.

METHODS: From November 2022 to April 2023, 106 HCWs were enrolled. Stool samples were tested for a range of EPs using real-time PCR and conventional methods, while AMR gut bacteria were screened using selective culture media. 16SrRNA sequencing was performed, and alpha-diversity was assessed using the Shannon index.

FINDINGS: EPs were found in 48.1% of samples (51/106), with protozoa being the most prevalent (37.7%, 40/106), followed by bacteria (10.4%, 11/106) and viruses (4.7%, 5/106). Blastocystis hominis (33%, 35/106) and Dientamoeba fragilis (18.8%, 20/106) were the most common protozoa, while Enteropathogenic Escherichia coli was the most frequent bacterial pathogen (3.8%, 4/106). Extended spectrum β-lactamase-producing E. coli was found in 2.8% of samples (3/106). Carbapenemase-producing bacteria, vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus or Clostridioides difficile were not present in any sample. HCWs with B. hominis had significantly higher Shannon alpha-diversity than those without (p < 0.01).

CONCLUSION: The prevalence of EPs and AMR gut bacteria among HCWs supports the inclusion of HCWs as potential stool donors for FMT, provided they meet health and screening criteria. This approach could help address the shortage of suitable stool donors for FMT programs.}, } @article {pmid40997843, year = {2025}, author = {Kao, D and Wong, K and Lee, C and Steiner, T and Franz, R and McDougall, C and Silva, M and Schmidt, TSB and Walter, J and Loebenberg, R and Monaghan, TM and Giebelhaus, RT and Harynuk, JJ and Xu, H and Yaskina, M and MacDonald, KV and Marshall, DA and Louie, T}, title = {Effects of lyophilised faecal filtrate compared with lyophilised donor stool on Clostridioides difficile recurrence: a multicentre, randomised, double-blinded, non-inferiority trial.}, journal = {The lancet. Gastroenterology & hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/S2468-1253(25)00190-6}, pmid = {40997843}, issn = {2468-1253}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is highly effective in preventing recurrent Clostridioides difficile infection. However, it is not known whether live microbes are necessary in mediating FMT efficacy. This study aims to determine whether lyophilised sterile faecal filtrate (LSFF), free of live bacteria, is non-inferior to lyophilised donor stool (LFMT) in efficacy.

METHODS: This multicentre, randomised, double-blinded, non-inferiority trial was done at four academic centres in Canada. Eligible patients were adults aged 18 years or older with recurrent C difficile infection (at least two recurrences). Eligible patients were randomly assigned (1:1 using a prespecified computer-generated randomisation list with permutation blocks of 2 and 4, stratified by age >65 years or <65 years) to receive oral LSFF or LFMT. Each treatment dose consisted of 15 capsules that appeared identical. Participants and investigators were masked to treatment allocation. The primary outcome was the proportion of participants without recurrent C difficile infection (absence of more than three Bristol type 6 or 7 bowel movements per 24 h persisting more than 2 consecutive days) at 8 weeks. Analysis was done in the per protocol population, in which participants with unknown outcome status at 8 weeks due to death or loss to follow-up were excluded. Non-inferiority was established if the lower bound of the one-sided 95% CI for the difference in proportions of participants without recurrent C difficile between the LSFF and LFMT groups was above the non-inferiority margin of -10%. This trial was registered at ClinicalTrials.gov, NCT03806803, and is complete.

FINDINGS: Between March 27, 2019, and Nov 6, 2023, we assessed 409 patients for eligibility. 271 were excluded and the remaining 138 were enrolled and randomly assigned to receive LSFF (n=72) or LFMT (n=66). Participants' mean age was 61·2 years (SD 18·6); 91 (66%) of 138 patients were women and 47 (34%) were male. 127 participants (92%) were White. 130 (94%) of 138 participants completed the trial. At the planned interim analysis, 47 (65%) of 72 participants in the LSFF group and 57 (88%) of 65 participants in the LFMT group did not have C difficile recurrence at 8 weeks (difference -23%, one-sided 95% CI -33·8% to infinity; p=0·96). Given the pre-specified non-inferiority margin of -10%, non-inferiority of LSFF to LFMT could not be established and the study was terminated at the recommendation of the data safety monitoring board. Serious adverse events included one death (LFMT group) and five hospitalisations (four unrelated, one possibly related to interventions [LSFF group]). One event occurred before treatment and all others 2-20 weeks after study intervention. The most common adverse events were abdominal discomfort (48 [67%] of 72 patients in the LSFF group and 36 (55%) of 66 patients in the LFMT group) and nausea (13 [18%] in the LSFF group and 21 [32%] in LFMT group).

INTERPRETATION: Among adults with recurrent C difficile infection, non-inferiority of LSFF to LFMT was not established for the prevention of recurrent C difficile infection over 8 weeks, supporting the crucial role of live microbes in mediating clinical efficacy.

FUNDING: Canadian Institutes of Health Research; University of Alberta Hospital Foundation; Alberta Health Services; Weston Foundation.}, } @article {pmid40996680, year = {2025}, author = {Luo, YM and Dong, L and Li, YL and Lin, M and Xie, DY and Gao, JM and Zhang, YD and Zhu, YZ and Gong, QH}, title = {Icariside II Ameliorates Depression Induced by High-Fat Diet via the Microbiota-Gut-Brain Axis in Mice.}, journal = {Phytotherapy research : PTR}, volume = {}, number = {}, pages = {}, doi = {10.1002/ptr.70103}, pmid = {40996680}, issn = {1099-1573}, support = {ZYSE-2022-02//Future techelite talent development program from Zunyi Medical University/ ; 82160756//Natural Science Foundation of China/ ; GCC[2023]042//hundred level of high-level innovative talents in Guizhou Province/ ; Zunshi Kehe HZ Zi (2023) 170. Qianke Platform Talent [2021] 1350-006//Zunyi Science and Technology and Big Data Bureau, Zunyi Medical University 2023 Science and Technology Joint Fund Project/ ; }, abstract = {Obesity can lead to depression via the microbiota-gut-brain axis. Icariside II (ICS II), a flavonoid compound derived from the traditional Chinese medicine Herbal Epimedium, exerts excellent neuroprotective effects. However, the pharmacological effects and underlying mechanisms of ICS II in obesity-induced depression remain unexplored. The present study aims to investigate whether ICS II can mitigate depression induced by a high-fat diet (HFD) in mice through modulating the microbiota-gut-brain axis. Metabolic parameters were reflected through changes in body weight and blood lipids, while depressive phenotypes were evaluated through behavioral tests and neurotransmitter analysis. The microbiota composition was analyzed by 16S ribosomal RNA gene sequencing, and short chain fatty acids (SCFAs) were detected by liquid chromatography-tandem mass spectrometry. The gut barrier and brain blood barrier (BBB) functions were observed by pathological methods. Fecal microbiota transplantation was used to demonstrate the causality of microbiota-mediated effects. The results showed that ICS II alleviated obesity status and depressive-like behaviors. ICS II reshaped gut microbiota and increased SCFAs. Meanwhile, ICS II relieved gut barrier impairment and systemic inflammation. In the brain, ICS II alleviated neuroinflammation and BBB injury. Intriguingly, fecal microbiota from ICS II-treated HFD mice improved depressive-like behaviors, intestinal barrier dysfunction, and BBB damage compared with those receiving microbiota from HFD mice. Our findings reveal for the first time that ICS II improves the obesity-related metabolic dysregulation and alleviates HFD-induced depression via the microbiota-gut-brain axis. Overall, this study indicates that ICS II is a potential candidate compound for treating obesity-related mental diseases.}, } @article {pmid40996271, year = {2025}, author = {Wong, MK and Armstrong, E and Heirali, AA and Schneeberger, PHH and Chen, H and Cochrane, K and Sherriff, K and Allen-Vercoe, E and Siu, LL and Spreafico, A and Coburn, B}, title = {Assessment of ecological fidelity of human microbiome-associated mice in observational studies and an interventional trial.}, journal = {mBio}, volume = {}, number = {}, pages = {e0190425}, doi = {10.1128/mbio.01904-25}, pmid = {40996271}, issn = {2150-7511}, abstract = {Composition and function of the gut microbiome are associated with diverse health conditions and treatment responses. Human microbiota-associated (HMA) mouse models are used to establish causal links for these associations but have important limitations. We assessed the fidelity of HMA mouse models in recapitulating ecological responses to a microbial consortium using stools collected from a human clinical trial. HMA mice were generated using different routes of consortium exposure, and their ecological features were compared to human donors by metagenomic sequencing. HMA mice resembled other mice more than their respective human donors in gut microbial composition and function, with taxa including Akkermansia muciniphila and Bacteroides spp. enriched in mouse recipients. A limited repertoire of microbes was able to engraft into HMA mice regardless of route of consortium exposure. In publicly available HMA mouse data sets from four distinct health conditions, we confirmed our observation that a taxonomically restricted set of microbes reproducibly engrafts in HMA mice and observed that stool microbiome composition of HMA mice was more like other mice than their human donor. Our data suggest that HMA mice are limited models for assessing the ecological impact of microbial consortia, with ecological effects in HMA mice being more strongly associated with host species than donor stool ecology or ecological responses to treatment in humans. Comparisons to published studies suggest this may be due to comparatively large host-species effects that overshadow ecological effects of treatments in humans that HMA models aim to recapitulate.IMPORTANCEHMA mice are models that better represent human gut ecology compared to conventional laboratory mice and are commonly used to test the effects of the gut microbiome on disease or treatment response. We evaluated the fidelity of using HMA mice as avatars of ecological response to a human microbial consortium, Microbial Ecosystem Therapeutic 4. Our results show that HMA mice in our cohort and across other published studies are more similar to each other than the human donors or inoculum they are derived from and harbor a taxonomically restricted gut microbiome. These findings highlight the limitations of HMA mice in evaluating the ecological effects of complex human microbiome-targeting interventions, such as microbial consortia.}, } @article {pmid40994135, year = {2025}, author = {Li, S and Li, Z and Tuo, Y and Mu, G and Jiang, S}, title = {Mechanisms of Casein-Derived Immunomodulatory Peptides Maintaining Immune Homeostasis via Regulating Gut Microbiota in a Cyclophosphamide-Induced Mouse Model.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c07986}, pmid = {40994135}, issn = {1520-5118}, abstract = {Two immunomodulatory signature peptides (PFPEVFG and SPAQILQW) were obtained from casein hydrolysates produced by Kluyveromyces marxianus JY-1 in our previous studies with the aid of virtual screening. However, their mechanisms for improving the composition of the gut microbiota in immunosuppressed mice remain unknown. The aim of this study was to reveal the mechanisms of immunomodulation and improvement of gut microbiota composition mediated by the casein peptides PFPEVFG and SPAQILQW through a cyclophosphamide (Cy)-induced immunosuppression and intestinal mucosal injury mouse model. The casein peptides PFPEVFG and SPAQILQW reversed Cy-induced intestinal structural damage and could correct for Cy-induced intestinal flora disorders. Importantly, fecal microbiota transplantation (FMT) confirmed that the casein peptides PFPEVFG and SPAQILQW attenuate immunosuppression by targeting participation in the dynamic balance of the gut microbiota. These results indicated that the casein peptides PFPEVFG and SPAQILQW have the potential to be used as natural medicines for the treatment of immunosuppression.}, } @article {pmid40993485, year = {2025}, author = {El-Mansoury, B and Esselmani, H and Merzouki, M and Devaraj, E and Hiba, OE and Ortega, A and Najimi, M}, title = {Current advances in the management of hepatic encephalopathy: an updated and critical review.}, journal = {Pharmacological reports : PR}, volume = {}, number = {}, pages = {}, pmid = {40993485}, issn = {2299-5684}, abstract = {Hepatic encephalopathy (HE) is a serious and potentially reversible neuropsychiatric syndrome resulting from severe liver insufficiency. HE is primarily considered a gliopathy in which astrocyte dysfunction is the main neuropathological hallmark, while recently microglia and neuronal alterations have been reported. It is believed that reversible factors trigger more than 80% of the cases. Several causative factors, including ammonia, inflammation, neuroinflammation, and oxidative stress, contribute to its pathogenesis, ultimately leading to abnormalities in neurotransmission and altered neuronal integrity. Current treatment strategies for managing HE include the primary use of rifaximin and lactulose, along with other pharmacological therapies that aim to reduce inflammation, neuroinflammation, and oxidative stress. However, liver transplantation remains the definitive curative treatment for end-stage liver diseases and associated encephalopathy. Recently, probiotics and fecal microbiota transplantation, as well as cell-based therapies, have shown promising results in both experimental studies and clinical trials. This review article highlights advances in understanding the complex pathophysiology of HE and assesses recent treatment strategies that aim to promote liver regeneration, target ammonia toxicity, and modulate immune responses.}, } @article {pmid40993162, year = {2025}, author = {Yang, R and Xu, Y and Xu, J and Huang, C and Zhu, F and Wang, T and Kong, R and Xiao, J and He, B and Gu, X and Wang, HL}, title = {Lacticaseibacillus rhamnosus GR-1 prevents autism-like behaviors by reshaping the maternal and offspring microbiome.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {187}, pmid = {40993162}, issn = {2055-5008}, support = {JZ2020HGTB0053//Fundamental Research Funds for the Central Universities/ ; 201904e01020001//Anhui Provincial Key Research and Development Plan/ ; 81673624//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Female ; Mice ; Pregnancy ; *Probiotics/administration & dosage ; Male ; *Lacticaseibacillus rhamnosus/physiology ; Gastrointestinal Microbiome ; Disease Models, Animal ; Behavior, Animal ; Fecal Microbiota Transplantation ; Vagina/microbiology ; *Autism Spectrum Disorder/prevention & control/microbiology ; *Autistic Disorder/prevention & control/microbiology ; Mice, Inbred C57BL ; *Microbiota ; Feces/microbiology ; }, abstract = {As a prevalent neurodevelopmental disease, whether ASD (autism spectrum disorder) can be ameliorated by the early use of a single microbe remains unknown. Here we used a lactobacillus strain, Lacticaseibacillus rhamnosus GR-1 (LGR-1), for prenatal intervention in autism-like mice with either environmental or idiopathic origins by exclusively administering to the pregnant dams at a dose of 10[9]/mouse/day, followed by offspring behavioral assessment with 3-chamber trial and marble burying test. The results revealed that LGR-1 prevented the occurrence of autism-like symptoms, as evidenced by the improved behaviors and restored E/I (excitatory-inhibitory) balance in the prefrontal cortex of male pups. In parallel, the offspring microbiome was reshaped by LGR-1 treatment, probably mediated by the vertical transmission of maternal microbiome, with its roles further unraveled by fecal microbiota transplant and cross-fostering experiments. In addition to gut commensals, the LGR-1-shaping vaginal microbiota also contributed to the establishment of "beneficial" microbiome. Regarding key taxa in offspring, Akkermansia muciniphila was influenced by LGR-1 and exerted impact on behaviors via pathways related to IL-17-producing lymphocytes. Our findings demonstrate that prenatal microbial administration protects offspring against autism-like behavioral phenotypes through microbiome transmission, highlighting a potential microbe-based therapeutic avenue to mitigate ASD risk.}, } @article {pmid40992605, year = {2025}, author = {Goetzl, EJ}, title = {Microbiomes in Health, Diseases and Therapeutics.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2025.09.002}, pmid = {40992605}, issn = {1555-7162}, abstract = {A microbiome is the aggregate of populations of bacteria, viruses and fungi in an organ system, of which the highly dominant numbers are in the gastrointestinal tract. Some of the bacteria, termed microbiota, support viability and functions of host cells directly by generating beneficial short-chain fatty acid components of dietary fibers and other metabolites of host compounds including secondary bile acids and indole derivatives of tryptophan. Short-chain fatty acids also recruit immune protective elements exemplified by IL-22, which has beneficial effects on intestinal epithelium by their IL-22 receptors. Other bacteria have detrimental effects on host cells through lipopolysaccharides and diverse toxins. An increased ratio of detrimental to beneficial microbiomal bacteria, a state termed dysbiosis, is observed in human diseases of many systems. Therapies for dysbiosis involve largely dietary manipulation and more recently fecal microbiota transplantation. Resistant and recurrent Clostridium difficile diarrhea responds dramatically to fecal microbiota transplantation, but this approach requires additional evaluation in other diseases. The potential prognostic value of microbiome characteristics suggests future uses in precision medicine.}, } @article {pmid40991236, year = {2025}, author = {Dobrila, HA and Hryckowian, AJ}, title = {The emerging view on the roles of butyrate in Clostridioides difficile pathogenesis.}, journal = {Infection and immunity}, volume = {}, number = {}, pages = {e0004725}, doi = {10.1128/iai.00047-25}, pmid = {40991236}, issn = {1098-5522}, abstract = {The Centers for Disease Control and Prevention classifies Clostridioides difficile as an urgent threat to the nation's health, as it causes 450,000 infections, 15,000 deaths, and 1 billion dollars in excess healthcare costs per year in the United States. Current treatments for C. difficile infections (CDIs) are antibiotics and, in recurrent cases, microbiome restoration therapy (MRT). Antibiotics contribute to antibiotic resistance and recurrent CDIs. Although MRTs (e.g., defined consortia of microbes or fecal transplant) are increasingly accessible, the long-term sustainability and accessibility of these treatments remain to be determined. These limitations highlight the need for more precise strategies for coping with CDI. Because a disrupted (dysbiotic) gut microbiome is the primary risk factor for CDI, a better understanding of the interactions between C. difficile, the microbiome, and the host will aid the development of such treatments. Butyrate is a prominent microbiome-host co-metabolite that is influenced by host dietary fiber intake and differentiates healthy from dysbiotic gut ecosystems. Emerging evidence supports that butyrate is a key determinant of C. difficile fitness and pathogenesis. Here, we review the current literature and gaps in knowledge about how butyrate-rich gut environments exclude C. difficile, and how butyrate impacts C. difficile growth, metabolism, toxin production/release, and sporulation. We further discuss the implications of continued study of butyrate's impacts on CDI, including the eventual development of new strategies to mitigate CDI in at-risk human populations.}, } @article {pmid40990659, year = {2025}, author = {Yan, ZB and Han, CL and Jia, JS and Li, H and Lu, DH and Cao, QH and Wang, YX and Jiao, KF and He, Q and Peng, SX and Zhang, DL and Wang, Q and Li, T}, title = {The landscape of gut microbiota in hepatocarcinogenesis: a comprehensive review of pathogenesis and therapeutic interventions.}, journal = {International journal of surgery (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1097/JS9.0000000000003511}, pmid = {40990659}, issn = {1743-9159}, abstract = {Primary liver cancer (PLC) represents a significant global health burden, with hepatocellular carcinoma (HCC) being its predominant subtype. The gut microbiota plays a crucial role in the pathogenesis, treatment, and postoperative recovery of HCC through its regulatory functions along the gut-liver axis. This review systematically elucidates the role of gut microbiota dysbiosis and associated metabolites in the pathogenesis of HCC, specifically addressing the underlying mechanisms whereby gut microbiota and their metabolites mediate hepatic metabolic reprogramming, remodel the immune microenvironment, and promote HCC progression through crosstalk with intratumoral bacteria. It further explores the impact of the gut microbiota on immunotherapy, molecular targeted therapy, conventional chemotherapy, and surgical outcomes. Additionally, the review comprehensively outlines therapeutic strategies targeting the gut microbiota, including oral probiotics, antibiotics, fecal microbiota transplantation (FMT), particular small molecules and traditional Chinese medicine. In summary, this review provides a comprehensive overview of how the gut microbiota influences the development and treatment of HCC and offers a theoretical foundation for targeting the microbiota to improve surgical prognosis in HCC patients.}, } @article {pmid40990473, year = {2025}, author = {Liu, X and Liu, C and Qian, X and Zhang, S and Yao, Z and Chai, Y and Shi, Q and Yang, W and Wang, Q and Zhang, L and Zeng, X and Liu, C and Wu, Y and Sun, Q}, title = {Fecal microbiota transplantation alleviated heat-induced colonic tissue damage, epithelial apoptosis, and oxidative stress.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {e0097625}, doi = {10.1128/aem.00976-25}, pmid = {40990473}, issn = {1098-5336}, abstract = {UNLABELLED: Exposure to high ambient temperatures can cause significant damage to the gastrointestinal tract; however, the therapeutic potential of fecal microbiota transplantation (FMT) in this context remains largely unexplored. We investigated whether FMT could alleviate heat-induced colonic injury in C57BL/6J mice. Mice were randomly divided into four groups: normal control (22°C only), normal-FMT (NF, 22 °C+ FMT), heat exposure (HE, 39°C only), and HE-FMT (HF, 39°C + FMT). The HE and HF groups were exposed to 39°C for 2 hours daily over 15 consecutive days. FMT (100 µL/day) was administered by oral gavage to the NF and HF groups for 15 days, starting after the first HE. Our results showed that FMT significantly modulated gut microbiota composition, increasing the relative abundance of Alistipes, Citrobacter, Parasutterella, Bifidobacterium, Lachnospiraceae_UCG-001, Raoultella, Woeseia, Prevotellaceae_UCG-001, and Christensenellaceae, while decreasing Clostridium_sensu_stricto_1, Eubacterium_xylanophilum_group, Clostridioides, Bilophila, GCA-900066575, and Peptococcus. Notably, FMT markedly restored epithelial integrity and enhanced mucus production, as shown by hematoxylin-eosin and periodic acid-Schiff staining. Moreover, FMT attenuated heat-induced epithelial cell apoptosis, evidenced by reduced apoptotic cells and downregulation of mitochondrial apoptotic markers, including Bax, Bak, cleaved Caspase-3, cleaved Caspase-9, and the phospho-P53/P53 ratio. In addition, FMT mitigated oxidative stress induced by HE, indicated by decreased 3-nitrotyrosine levels and normalization of antioxidant-related proteins, such as Nrf2, Sod1, Cat, and Gpx4. Collectively, these findings demonstrate that FMT alleviates heat-induced colonic injury by restoring mucosal barrier integrity, inhibiting apoptosis, and reducing oxidative stress, highlighting its potential as a promising therapeutic strategy for heat-related gastrointestinal disorders.

IMPORTANCE: This study is the first to demonstrate the protective role of fecal microbiota transplantation (FMT) against heat-induced colonic injury in a mouse model. We show that FMT mitigates colonic damage by restoring gut microbiota balance, preserving mucosal barrier integrity, inhibiting epithelial cell apoptosis, and reducing oxidative stress. These findings underscore the essential role of the gut microbiota in maintaining intestinal homeostasis under heat stress and highlight the therapeutic potential of microbiota-targeted strategies, such as FMT, in preventing or treating heat-related intestinal injury.}, } @article {pmid40990446, year = {2025}, author = {Xu, J and Li, J and Guo, X and Huang, C and Peng, Y and Xu, H and Li, Y and Xu, J and Hu, J and Liao, Y and Nie, Y and Zhou, Y}, title = {Secondary Bile Acids Modified by Odoribacter Splanchnicus Alleviate Colitis by Suppressing Neutrophil Extracellular Trap Formation.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e09073}, doi = {10.1002/advs.202509073}, pmid = {40990446}, issn = {2198-3844}, support = {82370552//National Natural Science Foundation of China/ ; 82470579//National Natural Science Foundation of China/ ; 2023A1515030214//Natural Science Foundation of Guangdong Province/ ; 2022-2023//Guangzhou Key Laboratory of Digestive Diseases/ ; KY17010003//Guangzhou Key Laboratory of Digestive Diseases/ ; }, abstract = {The gut microbiota contributes to inflammatory bowel disease (IBD) pathogenesis, yet the functional impact of specific bacterial species remains unclear. Here, Odoribacter splanchnicus (O. splanchnicus) is indentified as a taxon depleted in human IBD cohorts and demonstrated its protective effects in acute and chronic murine colitis models. In mice, O. splanchnicus administration alleviated colonic inflammation and preserved barrier integrity, accompanied by a restructured mucosal immune landscape and reduced neutrophil extracellular traps (NETs) formation. This inhibitory effect on NETs is lost in Pad4[-/-] mice, highlighting its dependence on NETs formation machinery. Metabolomic profiling showed that O. splanchnicus treatment elevated the secondary bile acid lithocholic acid (LCA). This increase is lost following antibiotic cocktail treatment and restored by fecal microbiota transplantation from O. splanchnicus-treated donors, demonstrating a requirement for an intact gut microbiota. Mechanistically, LCA supplementation recapitulated the anti-NETs formation phenotype and suppressed colonic inflamation by inhibiting the NLRP3-GSDMD signaling pathway. Together, these findings define a gut microbiota-metabolite-neutrophil axis in IBD pathogenesis, highlighting the microbiota-dependent regulation of LCA as a key protective mechanism of O. splanchnicus.}, } @article {pmid40988801, year = {2025}, author = {Ueno, S and Suzuki, T and Suzuki, M and Marubashi, S and Iseki, K}, title = {Effective Resolution of Postoperative Stoma Edema With Repeated Application of Topical 50% Glucose: A Case Report.}, journal = {Cureus}, volume = {17}, number = {8}, pages = {e90800}, pmid = {40988801}, issn = {2168-8184}, abstract = {Although glucose-induced osmotic gradients have been used to reduce intestinal edema, no standardized technique has been established. Repeated applications of this method have not been documented, and concerns remain regarding its potential effects on glycemic control. We present a case of a patient in his 20s admitted for treatment of an advanced pressure ulcer over the left greater trochanter. His medical history included spina bifida and type 2 diabetes mellitus. The ulcer was complicated by osteonecrosis of the left femur, and a left hip disarticulation was planned as a life-saving procedure. Before this procedure, a sigmoid colostomy was performed to divert the fecal stream. On postoperative day six following colostomy, the hip disarticulation was performed, and the patient's general condition gradually improved. However, persistent stoma edema was observed 12 days after surgery. Congestive discoloration of the stoma mucosa developed, and complications such as stomal outlet obstruction and abdominal distension were suspected. To address this complication, 20 mL of 50% glucose solution was applied topically to the intestinal mucosa eight times over five days. Following this treatment, a marked reduction in stomatal edema was observed. Notably, the procedure used in our case did not adversely affect perioperative glycemic control, suggesting its feasibility as a minimally invasive approach for managing acute-phase stoma edema.}, } @article {pmid40986483, year = {2025}, author = {Quigley, EMM}, title = {Gut power for better health: microbial therapeutics.}, journal = {Current opinion in gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MOG.0000000000001136}, pmid = {40986483}, issn = {1531-7056}, abstract = {PURPOSE OF REVIEW: To critically evaluate the literature over the past year on microbial therapeutics in the management of disorders of the large intestine. The primary focus is on disorders where the microbiome has been implicated in pathophysiology, and its modulation has been a therapeutic target.

RECENT FINDINGS: Though widely consumed, data on the impact of probiotics and prebiotics in gastrointestinal disorders continue to pose challenges in interpretation due to shortcomings in study design; postbiotics, meanwhile, because of some logistical and regulatory advantages, are attracting attention. Though time-honored for its role in infections due to Clostridioides difficile (CDI), FMT has encountered challenges in relation to regulation leading to the appearance of highly standardized, extensively screened and rigorously prepared microbial products [defined as live biotherapeutic products (LBP)], which show great promise; two have been approved by the FDA for prevention of recurrent CDI. Outside of CDI, efforts to define a role for FMT in the management of various diseases have met with mixed results.

SUMMARY: The translation of findings in studies of microbiome composition to successful therapies has proven disappointing to date, though attempts to develop selective and targeted microbial consortia show promise and may lead the way to personalized bacteriotherapy.}, } @article {pmid40984900, year = {2025}, author = {Weerakoon, S and Avula, S and Mandefro, BT and Sundara, SV and Lu, X and Busmail, H and Malasevskaia, IA}, title = {Microbiota-Based Therapies for Recurrent Clostridium difficile Infection: A Systematic Review of Their Efficacy and Safety.}, journal = {Cureus}, volume = {17}, number = {8}, pages = {e90737}, pmid = {40984900}, issn = {2168-8184}, abstract = {Recurrent Clostridium difficile infection (RCDI) remains a significant clinical challenge, with high recurrence rates following standard antibiotic therapy. Emerging evidence supports the role of fecal microbiota transplant (FMT) and standardized microbiome therapeutics (e.g., SER-109, RBX2660) in gut microbiota restoration and recurrence prevention. This systematic review evaluates the effectiveness and safety of these approaches in comparison to traditional therapies. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines, we searched the databases PubMed/MEDLINE, ScienceDirect, Cochrane Library, Europe PubMed Central (Europe PMC), ClinicalTrials.gov, Google Scholar, and Elicit AI for studies published between January 2015 and May 2025. Eligible studies included randomized controlled trials (RCTs), observational studies, and case series assessing FMT in adults with rCDI. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool (RoB 2) for RCTs and the Newcastle-Ottawa Scale (NOS) for cohort studies. Seven studies (six RCTs, one cohort; N=1,030 patients) were included. FMT demonstrated superior efficacy compared to antibiotics/placebo, with clinical cure rates ranging from 70% to 91% (versus 23% to 62%). Donor FMT outperformed autologous FMT (90.9% vs. 62.5%, p = 0.042) and standard therapies (71% resolution vs. 33% fidaxomicin/19% vancomycin, p < 0.01). Microbiota-based therapies (SER-109, RBX2660) demonstrated comparable efficacy (RRR up to 68%). Safety profiles were favorable, with predominantly mild gastrointestinal events and no increased risk detected for the specific outcomes measured over a five-year follow-up period. Heterogeneity existed in administration routes (colonoscopy/capsules) and donor material (fresh/frozen). FMT and standardized microbiome therapies are highly effective for treating rCDI, demonstrating robust short-term efficacy and favorable long-term safety. Donor-derived interventions and pharmaceutical-grade products (SER-109, RBX2660) represent promising alternatives to traditional antibiotics, particularly in recurrent or refractory cases. Future research should aim to standardize protocols and include more high-risk populations.}, } @article {pmid40983157, year = {2025}, author = {McGill, SK and Barlowe, TS}, title = {This Letter to the Editor is in response to: Response to Fulminant Clostridioides difficile Infection Following Fecal Microbiota Spores Compared to Fecal Microbiota Transplant.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2025.09.018}, pmid = {40983157}, issn = {1542-7714}, } @article {pmid40983156, year = {2025}, author = {Goldsmith, J and Nguyen, D and Delgado-Aros, S}, title = {Response to "Fulminant Clostridioides difficile Infection Following Fecal Microbiota Spores Compared to Fecal Microbiota Transplant".}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2025.09.017}, pmid = {40983156}, issn = {1542-7714}, } @article {pmid40983096, year = {2025}, author = {Yang, W and Zhang, Y and Xu, Y and Diao, J and Zheng, S and Yuan, C}, title = {Gut Microbial Metabolite Butyrate Regulates Treg/Th17 Cell Balance to Alleviate Diabetic Periodontitis.}, journal = {Journal of clinical periodontology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jcpe.70041}, pmid = {40983096}, issn = {1600-051X}, support = {2022YFE0118300//National Key Research and Development Program of China/ ; 2022YFA1206101//National Key Research and Development Program of China/ ; PKUSS-2024CRFG04//The Peking University School and Hospital of Stomatology Series of Clinical Research Projects/ ; }, abstract = {AIM: To investigate whether the gut microbiota-derived metabolite butyrate alleviates the progression of diabetic periodontitis by modulating the Treg/Th17 cell balance.

MATERIALS AND METHODS: A diabetic periodontitis mouse model was established to assess alveolar bone loss, Treg/Th17 cell subsets, colonic histopathology, faecal microbiota composition and short-chain fatty acid (SCFA) levels. To investigate microbial causality and therapeutic potential, faecal microbiota transplantation (FMT) and butyrate supplementation were conducted.

RESULTS: Mice with diabetic periodontitis exhibited a disrupted Treg/Th17 balance accompanied by colonic epithelial damage and a decreased abundance of SCFA-producing gut microbiota. Faecal SCFA levels showed a downward trend, although the reduction in butyrate was not significant. FMT from diabetic periodontitis mice aggravated periodontal destruction, impaired the colonic mucus barrier and further disturbed Treg/Th17 homeostasis in the recipient mice. These effects were associated with a decrease in SCFA-producing bacteria and faecal butyrate levels. Moreover, butyrate supplementation significantly alleviated periodontal destruction and restored the Treg/Th17 balance.

CONCLUSION: Gut microbiota dysbiosis contributes to diabetic periodontitis progression through disruption of the Treg/Th17 balance, whereas butyrate, as an immunomodulatory SCFA, may alleviate periodontal tissue destruction by restoring this balance.}, } @article {pmid40978956, year = {2025}, author = {Ray, R and Hack, SA and Vij, AK and Gbenla, KI and Khatri, S and Aravind Rongali, D and Khalid, A and Anjum, A and Fancy, RS and Mirza, MSS}, title = {Efficacy of Fecal Microbiota Transplantation (FMT) Versus Standard Antibiotic Therapy in Recurrent Clostridioides difficile (CDI/rCDI) Infection: A Systematic Review and Meta-Analysis.}, journal = {Cureus}, volume = {17}, number = {8}, pages = {e90614}, pmid = {40978956}, issn = {2168-8184}, abstract = {Repeated Clostridioides difficile infection (rCDI) is a hard clinical problem because normal antibiotic treatment usually doesn't stop relapses. Fecal microbiota transplantation (FMT) has come up as another way to try to fix the gut's microbial balance. This review and study looked at how well FMT works and how safe it is compared to normal antibiotic treatment for rCDI. We searched PubMed, Embase, and the Cochrane Library up to December 2023 to find trials and studies. We used a model to calculate risk ratios, and we also looked at subgroups based on how FMT was given and the patient's age. After checking fifteen studies with 1,452 patients, we found that FMT worked better than antibiotics [relative risk (RR) = 1.85, 95% confidence interval (CI): 1.62-2.11, p < 0.001], with recurrence rates of 16% versus 42%. Subgroup checks showed that FMT worked well no matter how it was given, whether by colonoscopy, tube, or capsules. Side effects were usually small and about the same for both FMT and antibiotics. In conclusion, FMT is safer and does a better job than normal antibiotics for rCDI and should be thought of as the main treatment after the first time the infection comes back.}, } @article {pmid40977983, year = {2025}, author = {Liu, H and Li, X and Shi, Y and Hong, K and Wang, X and Huang, C}, title = {Gut-brain axis in adolescent depression: a systematic review of psychological implications and behavioral interventions.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1644245}, pmid = {40977983}, issn = {2296-861X}, abstract = {BACKGROUND: Adolescent depression affects 13% of youths globally, with 30-40% exhibiting treatment resistance. Emerging evidence implicates gut microbiome dysbiosis in core behavioral symptoms (e.g., anhedonia, social withdrawal) via gut-brain axis (GBA) pathways. This systematic review synthesizes clinical and preclinical evidence (2014-2025) to delineate the microbiota-behavior interactions and evaluate microbiome-targeted interventions.

METHODS: Following PRISMA 2020 guidelines, 45 studies (29 clinical trials, 11 animal models, 5 meta-analyses) were analyzed from PubMed, Web of Science, and Embase. Data extraction focused on microbiome composition, neurobehavioral outcomes, and intervention efficacy. Random-effects meta-analyses pooled effect sizes (95% CIs).

RESULTS: Depressed adolescents showed reduced gut microbiota α-diversity (Shannon index SMD = -0.92; 95% CI: -1.24, -0.60) and altered taxa abundance (e.g., Bacteroidetes depletion: Δ = -32%). Dysbiosis correlated with anhedonia severity (r = 0.42; 95% CI: 0.28, 0.55) and impaired social functioning. Psychobiotics (e.g., Lactobacillus plantarum PS128) significantly reduced depressive symptoms (HAM-D Δ = -4.2; 95% CI: -5.1, -3.3) vs. placebo and improved emotion recognition (+18%; 95% CI: 2.1, 33.9). Sex-specific effects were prominent: Bifidobacterium breve enhanced reward responsiveness in females (SMD = 0.61; 95% CI: 0.22, 1.00). Current data lack large-scale RCTs for fecal microbiota transplantation (FMT) in adolescents.

CONCLUSION: Gut microbiome modulation shows promise as an adjunct to behavioral therapies (e.g., CBT). Bifidobacterium breve's female-predominant effects suggest hormonal modulation. Future research must address gaps in FMT safety, developmental mechanisms, personalized nutritional interventions.}, } @article {pmid40976345, year = {2025}, author = {Su, SH and Chen, M and Lu, DD and Fang Wu, Y and Huang, XS and Zhang, L}, title = {Fecal microbiota transplantation alleviates chronic cerebral hypoperfusion-induced axonal hypomyelination by regulating gut microbiota-derived metabolism and oligodendrogenesis.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {110122}, doi = {10.1016/j.jnutbio.2025.110122}, pmid = {40976345}, issn = {1873-4847}, abstract = {Fecal microbiota transplantation (FMT), aimed at rebuilding gut microbiota, has been proposed as a potential therapeutic approach to central nervous system (CNS) diseases. However, the therapeutic effects of FMT against demyelination-related white matter injury (WMI) have not yet been clarified under chronic cerebral hypoperfusion (CCH) condition. We therefore explored the potential roles and mechanisms of FMT on CCH-induced WMI, focusing on myelin integrity, axonal survival, and oligodendrogenesis. FMT restored mitochondrial electron transport chain (ETC) complex I-V activities and promoted the changes of pyruvate metabolism from lactate-generated to acetyl-CoA-generated mode, strengthening mitochondrial ATP production. Furthermore, FMT mitigated CCH-induced demyelination and axonal degeneration, effects mediated in part by oligodendrogenesis-dependent remyelination. Moreover, FMT altered CCH-induced gut microbiota composition by increasing the proportions of some bacterial groups including Verrucomicrobiae, Akkermansiaceae, Verrucomicrobiales, Verrucomicrobiota, Akkermansia, and Akkermansia_muciniphila. These gut microbiota were strongly associated with elevated fecal levels of L-tryptophan, 5-hydroxyindoleacetic acid, and N-a-acetylcitrulline, as well as with increased hippocampal concentrations of L-arginine, L-glutamine, N2-succinyl-L-ornithine, N-acetylornithine, indolepyruvate, indoleacetaldehyde, kynurenic acid, 11, 12-EET, 11, 12-DiHETrE and prostaglandin A2, which were almost involved in tryptophan and arginine related metabolism pathways. This study highlights the beneficial effects of FMT strategy in response to demyelination-mediated WMI under chronic cerebral ischemia condition.}, } @article {pmid40975229, year = {2025}, author = {Zhao, Y and Wang, B and Wei, X and Liu, D and Wang, R and Xie, S and Qiao, Z and Cui, D and Hou, S and Zhang, H}, title = {Impact of Gut Microbiota Dysbiosis on Intestinal Barrier Integrity and Systemic Inflammation in a Pre-Eclampsia Mouse Model.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {108053}, doi = {10.1016/j.micpath.2025.108053}, pmid = {40975229}, issn = {1096-1208}, abstract = {Pre-eclampsia is characterized by systemic inflammation and endothelial dysfunction, with growing evidence suggesting a significant role for gut microbiota in its pathogenesis. This study investigated the effects of fecal microbiota transplantation from pre-eclamptic and healthy donors on intestinal barrier integrity and systemic inflammation in a mouse model. Fecal bacteria solutions from pre-eclamptic and healthy pregnant women were transplanted into pseudo-sterile mice. The expression of ZO-1 and Occludin in colon tissue was assessed using PCR, Western Blot, and immunohistochemistry. Urinary protein content, serum lipopolysaccharide (LPS), TNF-α, and IL-6 levels were measured by ELISA. Fecal microbiota transplantation from pre-eclamptic and healthy donors did not affect tissue morphology in mice but significantly compromised intestinal barrier integrity in the pre-eclampsia model group (PET). This was indicated by reduced levels of the tight junction proteins TJP1 and Occludin. The PET group also exhibited elevated urinary protein levels (4456.24 ± 1509.05 μg/ml) and increased serum levels of LPS (10.26 ± 3.91 μg/ml), TNF-α (13.34 ± 1.07 pg/ml), and IL-6 (16.48 ± 5.33 pg/ml), underscoring systemic inflammation associated with gut microbiota dysbiosis in pre-eclampsia. This study indicates that the dysregulation of the intestinal microbiota in patients with preeclampsia may disrupt the intestinal barrier function and exacerbate systemic inflammation. However, due to the limited number of donors and experimental conditions, the specific mechanism still requires further investigation.}, } @article {pmid40974996, year = {2025}, author = {Liu, J and Sun, G and Zhang, H and Liu, H and Wang, X and Miao, Z}, title = {Glyphosate below no-observed-adverse-effect level exacerbates fatty liver hemorrhagic syndrome in laying hens.}, journal = {Poultry science}, volume = {104}, number = {11}, pages = {105847}, doi = {10.1016/j.psj.2025.105847}, pmid = {40974996}, issn = {1525-3171}, abstract = {Glyphosate (GLY) can disturb gut microbiota homeostasis through inhibiting bacterial shikimate pathway to pose a health challenge to animals and humans. But little information was reported about the influence of GLY on fatty liver hemorrhagic syndrome (FLHS) in laying hens, especially the exposure below no-observed-adverse-effect level. This study aimed to investigate the effects of GLY exposure on the progression of FLHS using a laying hen FLHS model induced by high-energy low-protein diet (HELPD). Ninety healthy Hyline brown laying hens were randomly allocated into 3 groups and subjected to the following feed for 6 weeks: Control group (fed with a basal diet), FLHS group (fed with HELPD), and FLHS + GLY group [fed with HELPD containing GLY (equal to 47 mg/kg body weight/d)]. Fresh feces were collected for microbiome and metabolome analysis, as well as fecal microbiota transplantation (FMT) experiments. The liver was collected for differentially expressed gene analysis and the colon for gut permeability determination. The results revealed that GLY exposure aggravated liver damage and lipid deposition by reshaping gut microbiota and increasing gut permeability in FLHS hens. Specifically, GLY exposure significantly elevated the relative abundance of Escherichia-Shigella, Bacteroides, Erysipelothrix, Desulfobvibrio, and Eggerthellain, while markedly decreased the relative abundance of Lactobacillus and Bifidobacterium, thus instigating the decline of certain tryptophan metabolites, including 3-hydroxyanthranilic acid, 5-hydroxyindoleacetic acid, kynurenic acid, 4-(2-aminophenyl)-2,4-dioxobutanoic acid, tryptamine, and indole-3-carboxylic acid in the gut, which inhibited aryl hydrocarbon receptor pathway to impair gut integrity. The impaired gut barrier led to the increase of serum LPS level, triggering inflammation and oxidative stress in the liver via activating TLR4/MyD88/NF-κB pathway and inhibiting Nrf2/Keap1 pathway. Furthermore, FMT experiments substantiated that GLY exposure aggravated FLHS in a gut microbiota-dependent manner. Collectively, these findings demonstrate that GLY exposure aggravates the progression of FLHS in laying hens through modulating the gut-liver axis. This study provides theoretical basis for assessing adverse effects of GLY exposure below no-observed-adverse-effect level on animal welfare.}, } @article {pmid40974374, year = {2025}, author = {Hemnani, M and Karatas, M and Cruz, AVS and da Silva, PG and Thompson, G and Poeta, P and Rebelo, H and Matthijnssens, J and Mesquita, JR}, title = {Metagenomic analysis of viral diversity in Portuguese bats.}, journal = {Veterinary research communications}, volume = {49}, number = {6}, pages = {319}, pmid = {40974374}, issn = {1573-7446}, mesh = {Animals ; *Chiroptera/virology ; Metagenomics ; Portugal/epidemiology ; Feces/virology ; *Coronavirus/genetics/isolation & purification/classification ; Spike Glycoprotein, Coronavirus/metabolism/genetics ; *Coronavirus Infections/veterinary/virology/epidemiology ; Phylogeny ; }, abstract = {Bats are highly diverse mammals and known reservoirs of numerous zoonotic viruses. Their role in the ecology of emerging infectious diseases continues to be of significant interest. This study aimed to evaluate the occurrence of coronaviruses (CoVs) in Portuguese bats and predict the affinity of their spike proteins with the aminopeptidase N (APN) receptor of several host species. The study also explored the viral diversity in bat samples using metagenomic sequencing. Ten bats (five Myotis myotis and five Miniopterus schreibersii) were captured at an underground roost in 2022 (Central Portugal), and fecal samples, oral, and anal swabs were collected (n = 27). A Pan-CoV nested RT-PCR was used for initial screening, followed by viral metagenomic sequencing of all fecal samples and one CoV-positive buccal swab. In silico protein docking studies were performed between a Portuguese bat CoV spike protein and APNs of bats, pigs, and humans. Pan-CoV nested RT-PCR identified three positive samples: two fecal samples and one buccal sample. Metagenomic sequencing allowed us to determine two near complete CoV genomes. Protein docking predicted strong binding of this spike protein to bat, porcine, and human APN receptors. Metagenomics also identified picornaviruses, adenovirus, and dependoparvovirus in fecal samples. This study reports the first near complete genome sequences of two members of the Alphacoronavirus genus from a Portuguese bat The identification of other viral families highlights the diverse virome of these cave-dwelling bat species. Protein docking studies suggest a potential for cross-species transmission of this bat CoV between bats, porcines and humans, though further research is needed to confirm these interactions.}, } @article {pmid40973482, year = {2025}, author = {Raja, SS and Costello, SP and Rayner, CK and Day, A and Portmann, L and Uylaki, W and Wheeler, R and Saxon, S and Tucker, EC and Fon, J and Edwards, S and Young, RB and Forster, SC and Goodsall, T and Bryant, RV}, title = {Examining the role of faecal microbiota transplantation for inducing remission in resistant ulcerative proctitis and distal ulcerative colitis (up-FMT).}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjaf169}, pmid = {40973482}, issn = {1876-4479}, abstract = {BACKGROUND: Resistant ulcerative proctitis (UP) represents a clinical conundrum, often necessitating the use of systemic therapy despite the disease being localised. Faecal microbiota transplantation (FMT) has proven efficacy for inducing remission in ulcerative colitis (UC) but has not been evaluated in UP.

AIMS: To undertake a pilot study examining the safety and efficacy of FMT enema therapy for management of resistant UP.

METHODS: Patients with mild-moderate active UP (total Mayo 3-10 with endoscopic Mayo subscore ≥ 1) were enrolled. After an initial conditioning phase of vancomycin and dietary education, participants received six anaerobically prepared single-donor FMT retention enemas over 8 weeks. The primary end point was safety and tolerability of FMT therapy. Secondary endpoints included combined clinical and endoscopic remission (Mayo Clinic score ≤2 with endoscopic subscore ≤1), histological remission, patient reported outcomes and exploratory microbial analysis.

RESULTS: 30 participants were enrolled (median age 41 years; 17 [57%] female). Serious adverse events occurred in 3 patients, including flare of UC (n = 2) and Clostridioides difficile colitis (n = 1). 18 patients (60%) reported mild-moderate adverse events, most commonly gastrointestinal symptoms. Combined clinical and endoscopic remission was achieved in 10 patients (33.3%). Higher baseline Mayo score (OR 0.28, p = 0.008) and faecal calprotectin (OR 0.66, p = 0.049) predicted failure to achieve remission. Participants demonstrated a decrease in Shannon diversity (p = 0.02) following the dual intervention of vancomycin conditioning and FMT.

CONCLUSIONS: Antibiotic conditioning followed by FMT enema therapy was well tolerated and demonstrated efficacy in inducing clinical remission in UP. Further controlled studies of FMT in UP are warranted alongside mechanistic assessment of both faecal and mucosa-associated microbiome.}, } @article {pmid40972731, year = {2025}, author = {Wang, T and Yang, D and Gao, R and Wen, Y and Liu, Z and Zhai, J and Li, S and Han, N and Yin, J}, title = {The discovery of the material basis and mechanism of gypsum as an antipyretic based on the theory of the diverse applications of raw and processed products.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {120623}, doi = {10.1016/j.jep.2025.120623}, pmid = {40972731}, issn = {1872-7573}, abstract = {Gypsum (CaSO4·2H2O), recognized as a classical mineral medicine in traditional Chinese medicine (TCM), has been traditionally used to treat fever. However, the specific bioactive constituents and the underlying molecular mechanisms of its action have yet to be fully elucidated.

AIM OF THE STUDY: To address this knowledge gap, we systematically elucidated the antipyretic material basis and underlying mechanisms of gypsum through integrating the analysis of metal profile, gut microbiota profiling, and serum metabolomics.

MATERIALS AND METHODS: Metal chemical profiling was firstly used to elucidate the antipyretic composition by comparing the serum composition of gypsum and calcined gypsum. Subsequently, this research investigated the differential antipyretic effects of gypsum, calcined gypsum and key elements in a lipopolysaccharide (LPS)-induced fever model in rats by monitoring changes in body temperature and inflammatory cytokines. Furthermore, the underlying mechanism was explored through western blotting (WB), quantitative real-time PCR (qPCR), and gut microbiota in conjunction with metabolomics.

RESULTS: The results reveal that Mg, Ca, Zn, and Mo were the strong candidates for active substances of gypsum. Furthermore, the research proved that gypsum and key elements (Mg, Ca, Zn, Mo) exhibits a notable antipyretic effect, while calcined gypsum does not. WB and qPCR analyses revealed a reduction in the expression of cyclooxygenase-2 (COX-2) in hypothalamic tissue in the gypsum-exposed group. Metabolomics profiling of serum suggests that the antipyretic effect of gypsum may involve primary bile acid biosynthesis. Association analysis involving gut microbiota indicated that gypsum may lead to the downregulation of five significant metabolites, including 15-Hydroxy-5,8,11,13-Eicosatetraenoic Acid, PC(16:1(9Z)/0:0), PC(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0) and PC(P-18:0/PGJ2), by downregulating Bacteroides, Ruminococcaceae and Roseburia to inhibit fever. Experiments involving fecal microbiota transplantation provide additional evidence for the involvement of gut bacteria in facilitating the antipyretic effects associated with gypsum.

CONCLUSIONS: This study pioneers in identifying the key elements (Mg, Ca, Zn, Mo) as the core antipyretic component of gypsum while establishing a multidimensional "mineral composition-gut microbiota-host metabolism" interaction network. Our findings provide mechanistic insights for optimizing quality standards of mineral-based TCM formulations.}, } @article {pmid40972730, year = {2025}, author = {Wang, X and Chen, M and Su, Y and Zhang, X and Chen, J and Huang, Z and Xie, J and Xie, Q and He, L and Su, L and Su, Z and Wang, H and Li, Y}, title = {A Novel Cholesterol-Reducing Mechanism of Polygonati Rhizoma: Dual Action via Bacteroides-Mediated Cholesterol Sulfonation and Feedback Inhibition of ACAT2 by Sulfated Metabolite.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {120619}, doi = {10.1016/j.jep.2025.120619}, pmid = {40972730}, issn = {1872-7573}, abstract = {Polygonati Rhizoma (PR) has the function of "invigorating spleen and tonifying kidney", and is historically applied as a homology of medicine and food to prevent and treat dyslipidemia in China. However, there is limited experimental evidence to buttress this application, and the underlying mechanism has not been fully deciphered.

AIM OF THE STUDY: To analyze the composition and illuminate the cholesterol-lowering potential and molecular mechanism of PR's aqueous extract (PRE) in high-fat emulsion (HFE)-induced hypercholesterolemia mouse model.

MATERIALS AND METHODS: Ion chromatograph was employed to determine the monosaccharide composition of PRE. HFE-induced Kunming mouse model was constructed to unravel the anti-hypercholesterolemia effect of PRE. Metagenomic sequences and liquid chromatography-mass spectrometry (LC-MS) analysis were performed to elucidate the mechanism through which PR regulated cholesterol metabolism. Antibiotic cocktail (ABX) intervention and fecal microbiota transplantation (FMT) were used to validate whether PRE regulated cholesterol metabolism through the intestinal microbiota. The cholesterol-reducing effect of cholesterol sulfate (CS) was explored in poloxamer 407 (P407)-induced mouse model of dyslipidemia. Molecular docking and molecular dynamics (MD) simulation were also employed to elucidate the underlying mechanisms. Furthermore, a combination of qRT-PCR, Western blot, and surface plasmon resonance (SPR) were employed to delineate its mechanism.

RESULTS: Our study indicated that the polysaccharides of PRE were mainly composed of fructose (92.33%) and glucose (5.25%). PRE treatment effectively blocked body weight gain, significantly decreased serum and hepatic levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), and increased high-density lipoprotein cholesterol (HDL-C) level. Additionally, PRE ameliorated hepatic lipid accumulation in mice with HFE-elicited hypercholesterolemia. Notably, metagenomic sequencing and LC-MS analysis indicated that PRE markedly increased the abundance of intestinal genera Bacteroides and significantly elevated the fecal CS concentration in HFE mice. Genome-based functional analysis further indicated that cofactors of sulfonation (ATP sulfurylase CysD and CysN, BT0414-BT0415) were significantly upregulated after treatment with PRE. The cholesterol-lowering effect of PRE was largely contingent upon microbial conversion of cholesterol-to-CS mediated by Bacteroides, as validated by antibiotics-induced intestinal microbiota depletion in pseudo-germ-free model and restoration of gut microbiota through FMT. In vitro study also showed that PRE promoted the growth of Bacteroides thetaiotaomicron. Furthermore, CS markedly alleviated serum, hepatic, bile, and fecal levels of TG, TC, LDL-C, HDL-C and TBA, indicative of appreciable lipid-lowering effect. MD simulation and SPR result indicated that CS directly bound to ACAT2. Consistent with this interaction, CS greatly downregulated the mRNA and protein expression of ACAT2 in small intestinal tissue.

CONCLUSION: These findings for the first time suggested that PR acted as a prebiotic agent to ameliorate hypercholesterolemia, at least in part, via dual mechanism involving modulation of Bacteroides-mediated sulfonation metabolic pathway and feedback inhibition of ACAT2 by CS, highlighting its therapeutic potential for cholesterol-related disorders. This work might also offer novel mechanistic insight and further buttressed the ethnopharmacological application of PR in the therapy of hypercholesterolemia.}, } @article {pmid40972191, year = {2025}, author = {Lévay, K and Kovács, S and Budai, A and Horváth, I and Kovács, N and Máthé, D and Szigeti, K and Dunai, Z and Makra, N and Juhász, J and Ostorházi, E and Bánky, B and Szijártó, A and Fülöp, A}, title = {Physical prehabilitation improves colonic anastomosis healing in a malnourished rat model only if attached to effective nutritional prehabilitation - Experimental study.}, journal = {Surgery}, volume = {188}, number = {}, pages = {109677}, doi = {10.1016/j.surg.2025.109677}, pmid = {40972191}, issn = {1532-7361}, abstract = {BACKGROUND: The importance of prehabilitation prior to colorectal surgery has recently gained attention. However, existing literature on its effectiveness is contradictory. Therefore, we investigated the impact of different prehabilitation protocols on intestinal anastomotic healing and the gut microbiome in a malnourished rat model.

METHODS: Rats were divided into 6 groups: ad libitum fed, ad libitum fed with exercise prehabilitation, malnourished, malnourished with exercise prehabilitation, malnourished with nutritional prehabilitation, and malnourished with combined nutritional and exercise prehabilitation. After 4 weeks of prehabilitation, body weight, body composition (measured by magnetic resonance imaging), gut circulation (assessed by short-wave infrared imaging), and microbiome diversity (evaluated by 16S rRNA sequencing) were determined. Colon resection and anastomosis were then performed. Anastomotic healing was assessed using the rat grimace scale, bursting pressure, adhesion score, bowel motility tests, and histopathologic examination. Correlations between microbiome composition and anastomotic healing parameters were also analyzed.

RESULTS: Malnutrition negatively affected all measured parameters related to body composition and postoperative outcomes. Physical prehabilitation alone did not improve these parameters in malnourished rats, whereas nutritional and bimodal prehabilitation successfully restored them. Specifically, these interventions led to improved body composition (P < .001), enhanced bowel perfusion (P < .05), and improved anastomotic healing (bursting pressure: P < .001; rat grimace scale: P < .0001; adhesion score: P < .0001) compared with untreated malnourished controls. Furthermore, nutritional and bimodal prehabilitation favorably modulated the fecal microbiome.

CONCLUSION: Our study demonstrates that nutritional and bimodal prehabilitation plays a primary role in improving colonic anastomotic healing under malnourished conditions. Moreover, we show for the first time that different prehabilitation protocols significantly influence the fecal microbiome, which may be fundamental to postoperative recovery.}, } @article {pmid40969847, year = {2025}, author = {Wu, H and Pang, MM and Li, YL and Hong, JH and Liu, PM and Bian, M and Yang, JJ}, title = {Allicin Aplealleviates Gouty Arthritis by Regulating the Gut-Joint Axis, Reducing XOD Activity, Inhibiting Oxidative Stress, and Suppressing NLRP3 Inflammasome Activation.}, journal = {Drug design, development and therapy}, volume = {19}, number = {}, pages = {7887-7907}, doi = {10.2147/DDDT.S540116}, pmid = {40969847}, issn = {1177-8881}, mesh = {Animals ; *Sulfinic Acids/pharmacology/administration & dosage ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/antagonists & inhibitors ; *Oxidative Stress/drug effects ; *Inflammasomes/metabolism/antagonists & inhibitors ; Rats ; Gastrointestinal Microbiome/drug effects ; Disulfides/pharmacology ; *Arthritis, Gouty/drug therapy/metabolism/pathology ; Male ; Rats, Sprague-Dawley ; *Superoxide Dismutase/metabolism/antagonists & inhibitors ; Disease Models, Animal ; Dose-Response Relationship, Drug ; }, abstract = {BACKGROUND: Gouty arthritis (GA) is a common joint inflammation closely related to hyperuricemia and urate crystal deposition, and its incidence is on the rise worldwide. Allicin, the primary biologically active component found in freshly crushed garlic extracts, has been reported to possess many beneficial biological functions.

METHODS: An animal model was used to evaluate the efficacy of allicin on GA rats, and 16S rRNA sequencing and metabolomics were used to explore changes in the gut microbiota and metabolites. Fecal microbiota transplantation (FMT) and fibroblast-like synoviocytes (FLS) used to explore the mechanism of allicin treating GA.

RESULTS: The results showed that allicin effectively improved the general state of GA rats, inhibited XOD activity, and significantly reduced ROS production and activation of the NLRP3 inflammasome, thereby exerting therapeutic efficacy to protect the kidneys and joints. Examination of the gut microbiota showed that the composition of the gut microbiota of GA rats improved after allicin treatment (increase in Lactobacillus). Metabolomic analysis revealed a significant increase in gut microbial short-chain fatty acid metabolites (butyric acid) following allicin treatment. Furthermore, FMT confirmed that allicin significantly alleviated GA and increased butyric acid content in a gut microbe-dependent manner. Finally, the role of butyric acid in inhibiting ROS generation and NLRP3 inflammasome activation in FLS was elucidated.

CONCLUSION: This study highlights allicin as a promising therapeutic candidate for GA, emphasizing its potential to inhibit oxidative stress and inflammatory responses by regulating the gut-joint axis.}, } @article {pmid40969441, year = {2025}, author = {Gong, J and Liu, Y and Huang, L}, title = {Laboratory preparation methods for human-derived fecal microbial suspensions for fecal microbiota transplantation: a review and standardization perspectives.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1637673}, doi = {10.3389/fmicb.2025.1637673}, pmid = {40969441}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) has advanced significantly as a therapeutic approach over the past few decades. Preparing fecal suspensions for FMT is one of the key steps. However, there is no unified standard or recognized procedure for preparing fecal suspensions in laboratories. This review evaluated the steps currently employed in laboratories to prepare fecal suspensions for FMT, including sample collection, suspension buffers, homogenization, purification, filtration, centrifugation, cryopreservation, dosage, the operating environment, and the transplantation form. This review focuses on the different operations of each preparation step, aiming to provide a reference for the laboratory preparation of fecal suspensions.}, } @article {pmid40967079, year = {2025}, author = {Jayaprakash, M and Vijaya Kumar, D and Chakraborty, G and Chakraborty, A and Kumar, V}, title = {Bacteria-mediated cancer therapy (BMCT): Therapeutic applications, clinical insights, and the microbiome as an emerging hallmark of cancer.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {192}, number = {}, pages = {118559}, doi = {10.1016/j.biopha.2025.118559}, pmid = {40967079}, issn = {1950-6007}, abstract = {The host microbiota has emerged as a critical modulator of immunity and cancer pathogenesis, influencing not only tumor initiation and progression but also therapeutic responses. This review explores the multifaceted roles of commensal and engineered bacteria in cancer therapy, highlighting the underlying mechanisms of bacterial tumor targeting, immunomodulation, and synergy with immune checkpoint inhibitors. We summarize the contributions of key bacterial genera-such as Clostridium, Bifidobacterium, Listeria, Salmonella, and Escherichia-focusing on their direct oncolytic properties, delivery systems, and interactions with the tumor microenvironment. Clinical trials employing live bacteria, bacterial metabolites, and fecal microbiota transplantation are also discussed, emphasizing their translational potential and current limitations. Additionally, we explore how the microbiome has been recognized as an enabling hallmark of cancer, capable of influencing inflammation, immune evasion, and therapeutic resistance. Despite significant progress, challenges such as safety, delivery specificity, and regulatory concerns remain. Advances in synthetic biology, precision microbiome engineering, and personalized medicine offer promising strategies to overcome these barriers. By integrating microbial biology with immuno-oncology, bacteria-mediated cancer therapy (BMCT) represents a novel frontier with transformative potential in cancer treatment.}, } @article {pmid40965701, year = {2025}, author = {Høyer, KL and Kornum, DS and Baunwall, SMD and Klinge, MW and Drewes, AM and Yderstræde, KB and Mikkelsen, S and Erikstrup, C and Krogh, K and Hvas, CL}, title = {Repeated faecal microbiota transplantation for individuals with type 1 diabetes and gastroenteropathy.}, journal = {Diabetologia}, volume = {}, number = {}, pages = {}, pmid = {40965701}, issn = {1432-0428}, abstract = {AIMS/HYPOTHESIS: Faecal microbiota transplantation (FMT) may alleviate gastrointestinal symptoms in individuals with diabetic gastroenteropathy, as demonstrated in a recent placebo-controlled trial. In most participants, symptom relief was transient, raising the need for repeated treatments. This study assessed the long-term efficacy, safety and feasibility of repeated, on-demand FMT as a maintenance treatment in this patient population.

METHODS: All 20 participants from the randomised clinical trial were offered extended open-label treatment with FMT. Symptom assessments were conducted by telephone every 2-3 months using the Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome (GSRS-IBS). Secondary measures included bowel movement frequency, stool consistency assessed using the Bristol Stool Scale, perceived treatment benefit on a seven-point Likert scale, and adverse events (AEs). FMT was primarily given as oral capsules, and colonoscopy was used for participants who could not swallow capsules.

RESULTS: Of the original 20 participants, 17 were included in the present study and followed from September 2021 to December 2024, with a median Duration of follow-up of 33.2 months (range 14.7-39.1 months). Participants received a total of 95 FMT treatments, with a median of five per participant and a median interval of 5.3 months between treatments. FMT induced consistent symptom relief, with reduced GSRS-IBS scores across multiple treatments. At the last FMT treatment provided, the mean GSRS-IBS score had decreased from 60 (95% CI 54, 66) at baseline to 35 (95% CI 29, 40), with a mean difference of -25 (95% CI -18, -33). The occurrence of frequent bowel movements 2 weeks after treatment (> 7 per day) decreased from 19% (95% CI 10%, 28%) to 3% (95% CI 0%, 7%). Stool consistency improved after treatment, and the frequency of normal stool types (Bristol Stool Scale score 3-5) increased from 28% (95% CI 18%, 39%) to 76% (95% CI 66%, 86%). Participant satisfaction was high, with 86% reporting considerable benefits (Likert scores 5-7). Repeated FMT was generally well tolerated, with most AEs being mild and self-limiting. Fifteen serious AEs were documented, of which only one was deemed to be possibly related to FMT.

CONCLUSIONS/INTERPRETATION: Repeated, on-demand FMT is effective and safe for long-term treatment of individuals with type 1 diabetes and severe diabetic gastroenteropathy.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04749030 FUNDING: The study was funded by a Steno Collaborative Grant (no. 0058906).}, } @article {pmid40965029, year = {2025}, author = {Pavithra, R and Kanimozhi, NV and Sonali, L and Suneetha, C and Sukumar, M}, title = {Unveiling Role of Gut Microbiota in Alzheimer's Disease: Mechanisms, Challenges and Future Perspectives.}, journal = {Current Alzheimer research}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115672050403066250904112611}, pmid = {40965029}, issn = {1875-5828}, abstract = {Alzheimer's disease (AD) is a neurodegenerative condition characterized by neuroinflammation, tau hyperphosphorylation, Aβ (Amyloid beta) accumulation, and synaptic dysfunction. New research indicates that the gut-brain axis, a network of two-way communication that involves immunological signals, neural pathways, and microbial metabolites, makes dysbiosis of the gut microbiota essential to the pathogenesis of AD. Alterations in the gut microbiota's composition hinder the production of crucial metabolites, such as short-chain fatty acids, trimethylamine- N-oxide, and secondary bile acids, which affect neuroinflammatory cascades, mitochondrial bioenergetics, and synaptic plasticity. Furthermore, Toll-like receptor 4 -4-mediated microglial responses are triggered by Gram-negative bacterial lipopolysaccharides. This cascade promotes oxidative stress, chronic neuroinflammation, and disruption of the (BBB) blood-brain barrier, all of which encourage the accumulation of neurotoxic proteins. Microbiome-modulating therapies, such as probiotics, prebiotics, and synbiotics, have been shown to have neuroprotective properties. They work by restoring microbial diversity, increasing (Short-chain fatty acids) SCFA-mediated anti-inflammatory pathways, and reducing glial activation. In addition to promoting gut microbiota equilibrium, dietary approaches like the Mediterranean and ketogenic diets, which are enhanced with polyphenols and omega-3 fatty acids, also lower systemic inflammation and increase neural resilience. Furthermore, the potential of postbiotics and fecal microbiota transplantation to attenuate AD-related neurodegeneration and restore gut-derived metabolic balance is being investigated. Translating these methods into standardized clinical applications is difficult, though, because individual microbiome composition varies. It will be essential to address these complications through mechanistic research and extensive clinical trials to establish gut microbiota as a promising therapeutic target in AD.}, } @article {pmid40964192, year = {2025}, author = {Dong, J and Xie, T and Shi, C and Feng, G and Zhang, H and Xu, Z and Dong, L}, title = {Gut-Spinal Cord Axis in Spinal Cord Injury: Bidirectional Inflammatory Mechanisms and Microbiota-Targeted Therapeutic Strategies.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {12549-12573}, pmid = {40964192}, issn = {1178-7031}, abstract = {Spinal cord injury (SCI) is a complex neurological disorder characterized not only by localized neuroinflammation but also by systemic immune dysregulation and multiorgan dysfunction. Emerging evidence has identified the gut microbiota as a critical extrinsic regulator of neural homeostasis, giving rise to the concept of the "gut-spinal cord axis". This review systematically examines the dynamic and bidirectional alterations in the gut microbial composition following SCI, with a particular emphasis on the role of microbiota-derived metabolites in the gut-spinal cord axis. These metabolites are recognized as key mediators that shape the spinal inflammatory milieu by modulating specific signaling pathways. In addition, the mechanistic basis of the gut-spinal cord axis is further dissected through neural, immune, and metabolic regulatory frameworks, highlighting how gut dysbiosis following SCI contributes to spinal inflammation via the modulation of vagal nerve signaling, immune cell polarization, and metabolic homeostasis. Moreover, the translational potential of microbiota-targeted interventions-such as probiotics and fecal microbiota transplantation (FMT)-is evaluated in terms of their ability to suppress inflammatory amplification and restore the disrupted bidirectional gut-spinal cord feedback loop. By integrating multiomics approaches and adopting a spatiotemporal perspective, this review underscores the importance of cross-system therapeutic strategies in SCI, aiming to provide a theoretical foundation and practical guidance for future precision interventions and translational research.}, } @article {pmid40963960, year = {2025}, author = {Wu, R and Teng, X and Guo, Y and Cai, Y and Lv, Y and Gao, H and Zhang, W and Shen, H and Fan, J}, title = {Gut microbiota characteristics and therapeutic effects of fecal microbiota transplantation in children with autism spectrum disorder in central China: a combined cross-sectional and prospective study.}, journal = {Frontiers in pediatrics}, volume = {13}, number = {}, pages = {1648471}, pmid = {40963960}, issn = {2296-2360}, abstract = {INTRODUCTION: Gut microbiota dysbiosis is implicated in autism spectrum disorder (ASD), yet scalable therapeutic interventions remain limited. This study investigated gut dysbiosis profiles in children with ASD and evaluated the clinical efficacy of a simplified fecal microbiota transplantation (FMT) protocol using pediatric donors.

METHODS: In a cross-sectional phase, 48 children with ASD and 51 age-/sex-matched healthy controls underwent gut microbiota analysis. Subsequently, 25 ASD participants received FMT via a streamlined protocol: 3-day bowel preparation followed by 6-day transcolonoscopic microbiota infusion from pediatric donors. Clinical outcomes and microbiota shifts were assessed at 3-month follow-up.

RESULTS: (1) Baseline Dysbiosis: ASD subjects exhibited reduced microbial diversity, with decreased Faecalibacterium and Bifidobacterium but elevated Megamonas and Akkermansia vs. controls. (2) Clinical Efficacy: Post-FMT, significant improvements occurred in core ASD symptoms and gastrointestinal comorbidities. (3) Microbiota Shifts: FMT recipients showed increased beneficial genera (Prevotella, Faecalibacterium, Agathobacter, Dorea) and reduced Escherichia-Shigella.

DISCUSSION: A simplified pediatric donor FMT protocol effectively modulates gut microbiota composition and alleviates both behavioral and gastrointestinal symptoms in children with ASD. This strategy demonstrates feasibility for clinical translation, highlighting microbiota-targeted therapy as a promising intervention for ASD.}, } @article {pmid40962064, year = {2025}, author = {Wu, ZN and Zhao, HL and Wang, Q and Chen, JL and Ren, Y and Qin, XM and Tian, JS}, title = {Analysis of a new anti-depression mechanism of Chaigui granules based on multi-omics integration: In-depth mining of intestinal microbiota-metabolite interaction network.}, journal = {Journal of affective disorders}, volume = {}, number = {}, pages = {120319}, doi = {10.1016/j.jad.2025.120319}, pmid = {40962064}, issn = {1573-2517}, abstract = {BACKGROUND: Depression is a common mental disorder that severely affects physical and psychological health of patients. Despite the proven clinical and experimental efficacy of Chaigui granules (CGG), a novel traditional Chinese medicine formulation for depression, its mechanism remains unclear owing to its multi-component nature.

METHODS: To establish an optimal depression model, the gut microbiota of humanized and murine donors under healthy and depressed conditions was compared, and subsequent behavioral effects via fecal microbiota transplantation in mice was assessed. Based on this, the mechanism of CCG in treating depression was characterized through combining 16S rRNA sequencing, LC-MS metabolomics and integration analysis.

RESULTS: The gut microbiota was markedly disrupted in depressed patients and mice. Through fecal microbiota transplantation (FMT), microbiota from depressed donors successfully colonized recipient mice and induced depression-like behaviors. Comparative results demonstrated the superiority of the murine FMT-induced depression model in terms of stability and translational relevance. CGG produced significant improvements in behavioral phenotypes, metabolic profiles, and microbial composition in depressed mice. Specifically, the treatment regulated 17 key metabolites and 7 bacterial strains, primarily involved in two major metabolic pathways. Integrated correlation analysis revealed five bacterial strains and seven metabolites that were strongly associated with depression-like behaviors.

CONCLUSION: Through integrated approaches, we hypothesize that Chaigui granules alleviate depressive-like behavior in murine FMT-induced depressed mice by modulating Aminoacyl-tRNA biosynthesis and Lysine degradation, inhibiting Bacteroides caccae, Clostridium cocleatum, and Muribaculum intestinale, while promoting Akkermansia muciniphila and Mucispirillum schaedleri, and regulating key metabolites including Glutaric acid, Threonine, Leucine, and Glutamic acid.}, } @article {pmid40961935, year = {2025}, author = {Brandow, AM and Atkinson, SN and Manjarres, Z and Ehlers, VL and Pratt, ML and Mehta, I and Mudunuri, S and Kappagantu, A and Shiers, SI and Mazhar, K and Simms, MA and Alhendi, S and Sheshadri, A and Cervantes, AM and Reese, JC and Tavares-Ferreira, D and Sankaranarayanan, I and Schaub, MK and Waltz, TB and Hayward, M and Rodríguez García, DM and Dussor, G and Salzman, NH and Palmer, KL and Stucky, CL and Price, TJ and Sadler, KE}, title = {Gut microbiota and metabolites drive chronic sickle cell disease pain in mice.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2025.08.012}, pmid = {40961935}, issn = {1934-6069}, abstract = {Individuals with sickle cell disease (SCD) suffer from debilitating chronic pain that does not have a clear etiology. Recent 16S ribosomal RNA gene sequencing studies revealed gut dysbiosis in individuals with SCD. It is unclear, however, whether these intestinal microbial changes contribute to chronic SCD pain. Using transgenic SCD mice, we determined that chronic SCD pain is alleviated following fecal microbiota transplantation from healthy controls, specifically by increasing the relative abundance of probiotic Akkermansia muciniphila. Reciprocally, transplantation of the SCD gut microbiome induced persistent pain in wild-type recipients via bilirubin-vagus nerve TRPM2 signaling. Biospecimens from individuals with SCD and spatial transcriptomic analysis of human nodose ganglia tissue identified additional bacterial species and neuronally expressed transcripts that should be explored as novel SCD analgesic targets.}, } @article {pmid40961414, year = {2025}, author = {Davis Iv, BT and Han, H and Islam, MBAR and Ford, K and Chen, Z and Abdala-Valencia, H and Greene, S and Weiss, C and Procissi, D and Schwulst, SJ}, title = {Short Chain Fatty Acid Supplementation After Traumatic Brain Injury Attenuates Neurologic Injury Via the Gut-Brain-Microglia Axis.}, journal = {Shock (Augusta, Ga.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/SHK.0000000000002706}, pmid = {40961414}, issn = {1540-0514}, abstract = {BACKGROUND: Traumatic brain injury (TBI) is an underrecognized public health threat. There are limited therapeutic options for TBI, and supportive care remains the mainstay of treatment. Our previously published data demonstrate that post-TBI fecal microbiome transplantation (FMT) can reverse TBI-induced depletion of commensal bacteria, preserve white matter connectivity and neurocognition, and decrease cortical volume loss in mice after TBI.

HYPOTHESIS: We hypothesized that post-TBI supplementation with Short Chain Fatty Acids (SCFAs), metabolites of commensal gut bacteria, would attenuate neurologic injury after TBI in mice.

METHODS: 14-week-old male C57BL/6 mice (n=52) underwent TBI via a controlled cortical impact vs. sham injury. Post-TBI, each group was treated with the SCFAs acetate, butyrate, and propionate vs. molar equivalent sodium chloride vehicle via free access to drinking water for four weeks post-TBI. The stool was collected three days pre-and sixty days post-TBI to assess the gut microbial community structure via 16s ribosomal RNA gene amplicon sequencing. Neurocognitive testing was performed with open-field and zero-maze testing. Ventricular volume and white matter connectivity were measured with 3D, contrast-enhanced MRI. Lastly, the transcriptional response of microglia was assessed with single-cell RNA sequencing (scRNAseq).

RESULTS: SCFA supplementation decreased TBI-induced microbial loss, attenuated ventricular volume loss, preserved white matter connectivity, and altered the transcriptional profile of microglia after TBI. Post-TBI SCFA supplementation preserved the abundance of the butyrate-producing taxa Firmicutes, Clostridia, Ruminoccacaceae, and Peptoccacaceae (p=0.01). SCFA also reduced the TBI-induced increase in Clostridiales and Bacteroidales compared to the salt vehicle group (p=0.05). We also observed the preservation of non-TBI murine anxiety-like behavior in SCFA-treated TBI mice compared to vehicle-treated TBI mice in zero-maze (152.3 ± 101.8 cm vs. 147.5 ± 60.0 cm, p=0.006). These results were recapitulated with open field testing (11.7 ± 3%-time in the center in SCFA-treated TBI mice vs. 15.0 ± 6% %-time in the center of the field in vehicle-treated mice; p=0.002). Lastly, we observed upregulation of transcripts for the neuroprotective heat shock family of proteins and downregulation of neurodegeneration-associated transcripts, indicating an overall neuroprotective phenotype in microglia after SCFA supplementation post-TBI.

CONCLUSIONS: We hypothesized that SCFA supplementation would attenuate neurologic injury after TBI in mice. SCFA supplementation attenuated neurocognitive deficits, reduced cortical volume loss, preserved white matter connectivity, and decreased neuroinflammation. These benefits may result from the direct replacement of SCFAs. However, there may also be secondary mechanisms related to commensal refeeding of butyrate-producing bacteria within the gut microbial community, a neuroprotective heat shock response, and a decrease in the expression of genes associated with neurodegeneration. The current study highlights the role of SCFAs in microbiome homeostasis and the potential of dietary intervention as a novel therapy in TBI.}, } @article {pmid40961234, year = {2025}, author = {Xie, X and Zou, A and Zhang, L and Ma, X and He, Y and Liu, H and Lu, Y and Yang, Y and Ouyang, J and Liu, K and Zhong, P and Li, J and Xu, S and Zhou, L and Han, B and Chen, M and Lv, K and Zhang, D and Liu, L and Mei, Y}, title = {Rbm38 Deficiency Impairs Erythroid Heme Biosynthesis and Induces Porphyria via Reduced Ferrochelatase Expression.}, journal = {Blood}, volume = {}, number = {}, pages = {}, doi = {10.1182/blood.2025028783}, pmid = {40961234}, issn = {1528-0020}, abstract = {RNA splicing and processing are critical for erythropoiesis, as dysregulation of RNA splicing ultimately disrupts protein synthesis. The RNA-binding protein Rbm38 is highly expressed during terminal erythropoiesis. While in vitro studies have implicated Rbm38 as a key regulator of erythroid differentiation, the landscape of RNA splicing regulated by Rbm38 and its role in terminal erythropoiesis in vivo have not been fully elucidated. Here, we generated whole-body and conditional knockout mouse models for Rbm38 and found that mature red blood cell production was impaired in the bone marrow of Rbm38-deficient mice. Rbm38-/- red blood cells exhibited reduced hemoglobin content and increased susceptibility to oxidative stress-induced hemolysis. These mutant mice also developed microcytic hypochromic anemia, along with dysregulated iron homeostasis. Additionally, they exhibited decreased mitochondrial heme biosynthesis and accumulation of free protoporphyrin (PPIX) in erythrocytes and feces, resembling human erythropoietic protoporphyria (EPP). Mechanistically, Rbm38 regulates the incorporation of ferrous iron (Fe2+) into PPIX to form heme by modulating alternative splicing, mRNA decay, and translation of the porphyrin metabolic enzyme gene Ferrochelatase (Fech). Importantly, enforced expression of Fech largely restored erythroid differentiation defects and ameliorated anemia in Rbm38-/- transplants. We further demonstrated that genetic variants in the human RBM38 gene locus influence PPIX levels in erythrocytes from healthy cohorts. Our findings demonstrate that Rbm38 governs terminal erythropoiesis by orchestrating RNA splicing, stability, and translation during heme biosynthesis.}, } @article {pmid40960982, year = {2025}, author = {Weninger, SN and Manley, A and Duca, FA}, title = {Managing Glucose Homeostasis Through the Gut Microbiome.}, journal = {Annual review of physiology}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-physiol-051524-094728}, pmid = {40960982}, issn = {1545-1585}, abstract = {The gut microbiota is a salient contributor to the development of type 2 diabetes mellitus (T2D) as a vast and complex metabolic cross talk that exists between the bacteria residing in the gastrointestinal tract and the host. This cross talk is largely influenced by external factors including diet, highlighting a potential avenue to effectively manipulate the gut microbiota to treat metabolic diseases such as diabetes. In this review, we discuss the influence of the gut microbiota on T2D development and targeting gut microbiota in both current and novel treatments for T2D, highlighting potential alternative therapies including fecal microbiota transplant, prebiotics, probiotics, synbiotics, or xenobiotics. A better understanding of both the impact of the gut microbiota in the etiology of diabetes and the therapeutic potential for manipulating the gut microbiota in metabolic disease could usher in a new approach to targeted treatment options to ameliorate T2D.}, } @article {pmid40960868, year = {2025}, author = {Su, Z and Lin, J and Zeng, X and Li, X and Hou, Q and Wang, Q and Liu, C and Qin, J and Li, Y and Zhang, J and Wang, X and Qian, S and Liao, L}, title = {Ozone water enema activates SIRT1-Nrf2/HO-1 pathway to ameliorate gut dysbiosis in mice receiving COVID-19 patient-derived faecal microbiota.}, journal = {Journal of medical microbiology}, volume = {74}, number = {9}, pages = {}, doi = {10.1099/jmm.0.002038}, pmid = {40960868}, issn = {1473-5644}, mesh = {Animals ; *Ozone/administration & dosage/pharmacology ; Mice ; *Dysbiosis/therapy/microbiology ; *COVID-19/microbiology ; *Gastrointestinal Microbiome/drug effects ; *NF-E2-Related Factor 2/metabolism/genetics ; *Heme Oxygenase-1/metabolism/genetics ; *Sirtuin 1/metabolism/genetics ; Humans ; Fecal Microbiota Transplantation ; *Enema/methods ; Male ; SARS-CoV-2 ; Mice, Inbred C57BL ; Disease Models, Animal ; Signal Transduction ; Feces/microbiology ; Water ; Female ; Membrane Proteins ; }, abstract = {Introduction. This study centres on how coronavirus disease 2019 (COVID-19) disrupts the intestinal microbiota and amplifies systemic inflammation and evaluates ozone water enemas as a strategy to restore gut microbial balance and activate the SIRT1 (silent information regulator of transcription 1)-Nrf2 (nuclear factor erythroid 2-related factor 2)/HO-1 (heme oxygenase-1) pathway for alleviating post-viral sequelae. Our findings demonstrate that ozone water intervention markedly improves the intestinal microenvironment in mice receiving COVID-19 patient-derived microbiota and attenuates systemic inflammation, offering a viable adjunctive approach for COVID-19 management.Hypothesis. Despite significant progress in reducing the incidence of COVID-19, its long-term consequences, including hepatic dysfunction, pulmonary injury and gut microbiota dysbiosis, remain challenging. While ozonated water enema therapy has shown efficacy in alleviating inflammation and neutralizing oxidative stress, the precise mechanisms by which ozonated water attenuates COVID-19 progression are not fully understood. We hypothesized that ozonated water enemas could enrich gut microbiota composition in COVID-19 patients, thereby optimizing the gut environment following faecal transplantation in a murine model.Aim. The overarching aim of this investigation was to ascertain whether ozonated water enemas could exert a salutogenic effect on the gut microbiota in a mouse model, as well as on the holistic gut and systemic health of critically ill COVID-19 patients subsequent to faecal transplantation.Methodology. The entire experiment was conducted over a 14-day period. WT mice were randomly allocated into three groups: Sham, FMT (faecal microbiota transplantation) and FMT+O3 (FMT with ozonewater enema treatment). Mid-stage faecal specimens were collected from 21 severe COVID-19 patients and randomly divided into seven subgroups (three specimens per subgroup). These specimens were transplanted into the WT mice of the FMT and FMT+O3 groups via faecal gavage on days 1 through 7. The healthy control group (Sham) received oral administration of ddH2O instead. Starting on day 8 post-transplantation, the FMT+O3 group underwent ozone water enema treatment for seven consecutive days. During this treatment period, assessments were performed to evaluate intestinal barrier function, inflammatory changes and alterations in gut microbiota. Additionally, improvements in intestinal, hepatic, pulmonary and systemic lesions were examined.Results. Our findings indicate that ozonated water enemas modulate the SIRT1-Nrf2/HO-1 pathway, significantly enhancing the intestinal environment in mice that received FMT from COVID-19 patients. This intervention increased microbiota populations, strengthened intestinal barrier integrity and reduced intestinal and systemic inflammatory responses.Conclusion. The results highlight the potential of ozonated water enemas as a therapeutic option for COVID-19 patients, particularly in optimizing intestinal microbiota and mitigating inflammatory responses through SIRT1-Nrf2/HO-1 pathway modulation. This approach offers a novel strategy for addressing residual effects of COVID-19.}, } @article {pmid40959063, year = {2025}, author = {Xie, X and Liu, H and Wan, K and Li, J and Qi, P}, title = {The gut microbiota in osteoporosis: dual roles and therapeutic prospects.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1617459}, pmid = {40959063}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Osteoporosis/therapy/microbiology/metabolism/etiology ; Animals ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Bone Remodeling ; Prebiotics/administration & dosage ; Bone and Bones/metabolism ; }, abstract = {Recent advances in bone biology have underscored the essential role of the gut microbiota in maintaining skeletal homeostasis. Gut-derived metabolites, particularly short chain fatty acids and tryptophan derivatives, influence bone metabolism through modulation of immune signaling, inflammation, and endocrine networks. Emerging evidence indicates that these effects are context dependent and dose dependent, rather than uniformly beneficial or detrimental. For instance, butyrate and lipopolysaccharide exhibit biphasic effects on both osteogenesis and osteoclastogenesis, contingent on concentration, immune status, and the local microenvironment. Microbiota-targeted strategies such as probiotics, prebiotics, and fecal microbiota transplantation are under active investigation as innovative interventions for osteoporosis in both preclinical and clinical contexts. However, substantial knowledge gaps persist, including inconsistent therapeutic outcomes, limited mechanistic insight into host-microbiota interactions, and the absence of standardized microbial intervention protocols. In addition, safety concerns related to FMT, particularly in immunocompromised elderly populations, emphasize the need for rigorous donor screening, extended follow-up periods, and personalized risk and benefit assessment models. To advance the field, future studies should incorporate multi-omics platforms and precision medicine tools to identify key microbial targets and enhance therapeutic efficacy. This review consolidates current evidence and proposes a conceptual framework to clarify the context-specific roles of the gut microbiota in bone remodeling. A deeper mechanistic understanding will be crucial for translating microbiota-based strategies into safe and effective treatments for metabolic bone disorders.}, } @article {pmid40957793, year = {2025}, author = {Castrillón-Lozano, JA and Lozano-Arce, JA and Arroyave-Zuluaga, RL}, title = {Fecal microbiota transplantation in recurrent Clostridioides difficile: Is greater methodological rigor and the analysis of other populations relevant?.}, journal = {Revista de gastroenterologia de Mexico (English)}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.rgmxen.2025.09.022}, pmid = {40957793}, issn = {2255-534X}, } @article {pmid40957789, year = {2025}, author = {Núñez, P and Quera, R and von Muhlenbrock, C}, title = {Response to "Fecal microbiota transplantation in recurrent Clostridioides difficile: Is greater methodological rigor and the analysis of other populations relevant?".}, journal = {Revista de gastroenterologia de Mexico (English)}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.rgmxen.2025.09.023}, pmid = {40957789}, issn = {2255-534X}, } @article {pmid40957477, year = {2025}, author = {Sala, L and Carlini, V and Macas-Granizo, MB and Trabucchi, E and Pontiroli, AE and Berra, C and Naselli, A and D'Anzeo, M and Porta, A and Delgado, JM and Vianello, E and Dozio, E and Romanelli, MC and Drago, L}, title = {The eternal struggle between titans: Fecal microbiota transplant (FMT) versus metformin in type 2 diabetes (T2D) gut dysmotility.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.09.021}, pmid = {40957477}, issn = {2090-1224}, abstract = {BACKGROUND: The prevalence of dysbiosis in type 2 diabetes (T2D) is increasing globally as a consequence of an imbalance in the distribution of gut microbial populations. Dysmotility of the gastrointestinal tract has emerged as a contributor to pathophysiology of T2D, where impaired motility may exacerbate dysbiosis and metabolic dysfunction. Current management of T2D, such as Metformin (Metf), demonstrate efficacy in improving metabolic parameters but are linked to gastrointestinal side effects, the mechanisms of which remain poorly understood. Novel promising therapeutic agents, based on the modulation of the gut microbiota has emerged for the treatment of metabolic disorders, particularly for T2D, in which Fecal microbiota transplant (FMT) assumes the major weight as strategy to improves insulin sensitivity and glucose tolerance, and potentially ameliorating gut motility. Although FMT represents a potential therapeutic alternative, its comparative effectiveness and safety profile relative to Metf in this specific setting remain to be established.

AIM OF THE REVIEW: This review aims to evaluate and compare these two potent modulators of microbial landscape, Metf and FMT, in addressing insulin resistance (IR) and gastrointestinal dysmotility in T2D. The study seeks to systematically delineate the mechanisms underlying their effects and assess their therapeutic potential, safety, and clinical efficacy.

The physiological roles of the gut microbiota and their metabolites are explored, highlighting their contribution to the onset and progression of metabolic disorders, particularly T2D. We examined the mechanisms through which Metf and FMT influence gut microbiota, insulin sensitivity, and glucose tolerance. Novel therapeutic approaches, including the combined use of Metf and FMT, are discussed in terms of molecular mechanisms, clinical outcomes, and safety profiles. Finally, the potential integration of these strategies into T2D management and their impact on gastrointestinal dysfunction are considered as areas for further research.}, } @article {pmid40752380, year = {2025}, author = {Sendo, S and Vela, AJ and Ro, M and Thiruppathy, D and Wilkinson, EL and Zhao, Z and Hsieh, WC and Yang, S and Coras, R and Bergot, AS and Guma, M and Nguyen, A and McBride, DA and Devkota, S and Thomas, R and Shah, NJ and Svensson, MND and Zengler, K and Stanford, SM and Bottini, N}, title = {Interaction between haploinsufficiency of PTPN2 and patient microbiome promotes autoimmune arthritis in mice.}, journal = {Journal of autoimmunity}, volume = {156}, number = {}, pages = {103452}, doi = {10.1016/j.jaut.2025.103452}, pmid = {40752380}, issn = {1095-9157}, mesh = {Animals ; *Haploinsufficiency ; Mice ; *Protein Tyrosine Phosphatase, Non-Receptor Type 2/genetics ; *Gastrointestinal Microbiome/immunology ; Humans ; *Arthritis, Rheumatoid/immunology/genetics/microbiology ; *Dysbiosis/immunology ; Disease Models, Animal ; *Arthritis, Juvenile/immunology/genetics/microbiology ; *Arthritis, Experimental/immunology ; Female ; Male ; Fecal Microbiota Transplantation ; }, abstract = {Gut dysbiosis is observed in patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), however, how it promotes disease in interaction with other environmental and genetic risk factors remains unclear. Here we assessed interactions between gut dysbiosis and RA/JIA-associated loss of function haplotypes of the RA/JIA-associated PTPN2 gene by inducing mannan-induced arthritis in germ-free PTPN2[+/+] and PTPN2 haploinsufficient (PTPN2[+/-]) SKG mice reconstituted with fecal microbiota from six patients with seropositive RA. Mannan-induced arthritis and lymph node T cell immunophenotypes were identical in germ free PTPN2[+/+] vs PTPN2[+/-] SKG mice. While no difference in arthritis severity was seen among PTPN2[+/+] mice recipient of RA gut microbiota, two microbiomes (RA#02 and RA#86) enhanced arthritis in PTPN2[+/-] mice. The microbiome of RA patient microbiota recipient mice exclusively clustered by patient of origin and the RA#86 microbiome was found to carry a significant expansion of Prevotella genera, which is associated with RA dysbiosis. RA#86 microbiota-recipient PTPN2[+/-] mice selectively displayed increased joint GM-CSF expression and an expansion of CD4[+]RORγt[+]FoxP3[-] T cells in the joints, without evidence of increased intestinal inflammation, gut barrier leakage or expansion of P. copri in post-mannan fecal samples. Monocolonization with P. copri caused enhanced arthritis and CD4[+]RORγt[+]FoxP3[-] T cells expansion in PTPN2[+/-] vs PTPN2[+/+] mice. Our data support current views about P. copri promotion of autoimmune arthritis and suggest that its pathogenicity can be amplified via interaction with a dysbiotic context and risk factors that enhance gut mucosa immune responses.}, } @article {pmid40952592, year = {2025}, author = {Chen, C and Wang, GQ and Li, DD and Zhang, F}, title = {Microbiota-gut-brain axis in neurodegenerative diseases: molecular mechanisms and therapeutic targets.}, journal = {Molecular biomedicine}, volume = {6}, number = {1}, pages = {64}, pmid = {40952592}, issn = {2662-8651}, support = {No. 82160690//National Natural Science Foundation of China/ ; No. ZK [2021]-014//Science and Technology Foundation of Guizhou Province/ ; No. 2020-39//Collaborative Innovation Center of Chinese Ministry of Education/ ; }, abstract = {The microbiota-gut-brain axis (MGBA) is an intricate bidirectional communication network that links intestinal microbiota with the central nervous system (CNS) through immune, neural, endocrine, and metabolic pathways. Emerging evidence suggests that dysregulation of the MGBA plays pivotal roles in the onset and progression of neurodegenerative diseases. This review outlines the key molecular mechanisms by which gut microbes modulate neuroinflammation, blood-brain barrier integrity, protein misfolding, and neuronal homeostasis. We discuss how microbial metabolites, such as short-chain fatty acids, tryptophan derivatives, and bile acids, interact with host to influence CNS functions. Disease-specific features are described across Alzheimer's disease, Parkinson's disease, Multiple sclerosis, and Amyotrophic lateral sclerosis, emphasizing the distinct and overlapping pathways through which gut dysbiosis may contribute to pathogenesis. We further explore the translational potential of microbiota-targeted therapies, including probiotics, fecal microbiota transplantation, dietary interventions, and small-molecule modulators. While preclinical results are promising, clinical trials reveal considerable variability, highlighting the need for personalized approaches and robust biomarkers. Challenges remain in deciphering causal relationships, accounting for inter-individual variability, and ensuring reproducibility in therapeutic outcomes. Future research should integrate multi-omics strategies, longitudinal human cohorts, and mechanistic models to clarify the role of the MGBA in neurodegeneration. Collectively, understanding the MGBA provides a transformative perspective on neurodegenerative disease mechanisms and offers innovative therapeutic avenues that bridge neurology, microbiology, and precision medicine.}, } @article {pmid40952509, year = {2025}, author = {Bretthauer, M}, title = {[What is confirmed in colorectal cancer screening?].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {}, number = {}, pages = {}, pmid = {40952509}, issn = {2731-7099}, abstract = {BACKGROUND: The incidence and mortality of colorectal cancer in Germany has declined in recent years. Nevertheless, colorectal cancer is still the second most common cancer in women (after breast cancer) and the third most common in men in Germany (after prostate cancer and lung cancer). Screening for colorectal cancer is well-established in many countries. The two most recommended screening strategies are colonoscopy and fecal immunochemical testing (FIT, stool test for occult blood).

OBJECTIVE: This article explains important conceptual and practical differences between the two strategies offered in Germany and summarizes the latest high-quality evidence for the benefits of the most frequently used screening tests. The aim is to provide physicians with decision aids for patients who show interest in colorectal cancer screening.

MATERIAL AND METHODS: Confirmed high-quality evidence from randomized trials on the benefits of screening for colorectal cancer with respect to incidence and mortality.

RESULTS: The lifetime risk to develop colorectal cancer in Germany is 5% for women and 6.5% for men. According to a large randomized trial, a screening colonoscopy reduces the risk of colorectal cancer from 1.2% to 0.8-0.9% after 10 years. New high-quality evidence from a recent Spanish randomized trial also showed that the benefits of FIT screening every other year are comparable to those of 1 colonoscopy over 10 years. The risks of perforation and bleeding during colonoscopy are 0.01% and 0.1%, respectively.

CONCLUSION: During the medical patient clarification on screening, it is recommended that the abovenamed facts on benefits and risks should be included and explained.}, } @article {pmid40952001, year = {2025}, author = {Raich, SS and Majzoub, ME and Haifer, C and Paramsothy, S and Shamim, MMI and Borody, TJ and Leong, RW and Kaakoush, NO}, title = {Bacterial taxonomic and functional changes following oral lyophilized donor fecal microbiota transplantation in patients with ulcerative colitis.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0099125}, doi = {10.1128/msystems.00991-25}, pmid = {40952001}, issn = {2379-5077}, abstract = {UNLABELLED: Oral lyophilized fecal microbiota transplantation (FMT) can induce remission in patients with active ulcerative colitis (UC); however, our understanding of how this form of FMT alters the patient microbiome remains limited. Here, we analyzed data from a recent randomized, double-blind, placebo-controlled clinical trial of FMT in UC to assess donor species colonization and factors responsible for efficacy using this form of therapy. The gut microbiome of donors and patients was profiled longitudinally using deep shotgun metagenomic sequencing, and microbiome diversity, species-genome bin presence, functional profiles, and the resistome were studied. The gut microbiome of patients treated with oral lyophilized FMT significantly increased in species-genome bin richness and shifted in composition toward the donor profiles; this was not observed in patients receiving placebo. While species-genome bin richness was not associated with clinical response in this trial, we identified donor- and patient-specific features associated with the induction of remission and maintenance of response. However, the presence of a Clostridium species-genome bin, as well as L-citrulline biosynthesis contributed by Alistipes spp., was seen in responders treated by either donor. Several of the above outcomes were found to be consistent when data were analyzed at the level of metagenome-assembled genomes. FMT was also found to deplete the resistome within patients treated with antibiotics to levels lower than the UC baseline. Single donor oral lyophilized FMT substantially modifies taxonomic diversity and composition as well as microbiome function and the resistome in patients with UC, with several features identified as strongly linked to response regardless of the donor used.

IMPORTANCE: There is a limited amount of work examining the effects of oral lyophilized fecal microbiota transplantation (FMT) on the microbiome of patients with ulcerative colitis (UC), and less so studies examining species-level dynamics and functional changes using this form of FMT. We performed deep shotgun metagenomic sequencing to provide an in-depth species-genome bin-level analysis of the microbiome of patients with UC receiving oral lyophilized FMT from a single donor. We identified key taxonomic and functional features that transferred into patients and were associated with clinical response. We also determined how FMT impacts the resistome of patients with UC. We believe these findings will be important in ongoing efforts to not only improve the efficacy of FMT in UC but also allow for the transition to defined microbial therapeutics, foregoing the need for FMT donors.}, } @article {pmid40951341, year = {2025}, author = {Liao, L and Zeng, M and Liu, D and He, Y and Du, W and Cao, Y}, title = {Focus on gut microbes: new direction in cancer treatment.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1505656}, pmid = {40951341}, issn = {2234-943X}, abstract = {Gut microbes are emerging as critical regulators in cancer therapy, influencing the efficacy and toxicity of radiotherapy, chemotherapy, immunotherapy, targeted therapy, Traditional Chinese Medicine, and rehabilitation interventions. Acting through metabolic reprogramming, immune modulation, DNA damage, and tumor microenvironment remodeling, specific microbial taxa and their metabolites can either enhance or hinder treatment outcomes. However, these interactions are highly context-dependent and shaped by individual factors such as diet, geography, and host immunity. While microbial interventions such as probiotics, fecal microbiota transplantation, and engineered bacteria show promise, their translation into precise and safe clinical applications remains limited by interindividual variability, regulatory hurdles, and incomplete mechanistic understanding. Future efforts should focus on defining high-evidence microbial signatures, clarifying causal mechanisms, and developing personalized microbiome-based therapeutic strategies, potentially integrated with nanotechnology. This review underscores the need for interdisciplinary approaches to harness gut microbiota as co-targets in cancer treatment.}, } @article {pmid40951313, year = {2025}, author = {Dai, X and Chen, H and Zhang, M and Yang, Q and Huang, Z and Tang, L}, title = {Exercise improves endothelial progenitor cell's function in mice with Type 2 diabetes via gut microbiota modulation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1606652}, pmid = {40951313}, issn = {2235-2988}, abstract = {INTRODUCTION: Evidence has proved that exercise increases migration and tube formation of rat EPCs. But the mechanism behind the improved function of EPCs by exercise remains unclear.

METHODS: This study conducted 8-week exercise interventions (aerobic, resistance, or combined) in 6-week-old type 2 diabetic mice, assessing post-exercise glucose, weight, GLP-1, and gut microbiota. Mice with optimal outcomes were selected as fecal donors for microbiota transplantation via gavage. Recipient mice were evaluated for GLP-1, microbiota changes, and endothelial progenitor cell (EPC) proliferation/migration.

RESULTS: Exercise altered microbial composition (e.g., increased Prevotellaceae and Ligilactobacillus), while fecal microbiota transplantation(FMT) enriched Akkermansia. Notably, FMT elevated plasma Glucagon-like peptide-1 (GLP-1) levels by 0.92 pmmol/L (P < 0.001) compared to controls, surpassing the modest, non-significant effects of exercise alone. Critically, FMT enhanced EPC's proliferation (P < 0.007 vs. controls) and migration (P < 0.05), mirroring exercise-induced improvements. While exercise reduced body weight (e.g., 10.58 g in aerobic training (AT), P < 0.001) and blood glucose, FMT amplified these metabolic benefits, lowering glucose by 9.22 mmol/L (P < 0.001).

DISCUSSION: Our findings suggest that exercise improves EPC's function in diabetic mice via gut microbiota modulation, with FMT synergistically enhancing GLP-1 secretion. The identified microbiota (Prevotellaceae, Ligilactobacillus, Akkermansia) may serve as therapeutic targets for T2DM(T2DM) and its cardiovascular complications.}, } @article {pmid40951310, year = {2025}, author = {Cui, X and Li, J and Yang, T}, title = {Editorial: Gut microbiota-derived metabolites and cardiovascular diseases.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1661489}, pmid = {40951310}, issn = {2235-2988}, } @article {pmid40950584, year = {2025}, author = {Cui, Y and An, P and Li, F and Duan, F and Mei, Z and Ye, Q and Wang, G and Zhang, H and Luo, Y}, title = {Strategies to reduce uric acid through gut microbiota intervention.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1654152}, pmid = {40950584}, issn = {1664-302X}, abstract = {Hyperuricaemia (HUA) is a metabolic disorder resulting from the dysregulation of purine metabolism. It is closely associated with gout and various metabolic syndromes, representing an increasing global public health challenge. Current treatment approaches for HUA and gout generally involve the lifelong administration of urate-lowering agents to maintain optimal serum urate concentrations. However, poor patient adherence, often due to potential hepatorenal toxicity, frequently leads to disease relapse. Recent evidence indicates that the gut microbiota plays a significant role in maintaining urate homeostasis through multiple mechanisms, including the modulation of purine metabolism, urate catabolism and excretion, regulation of inflammatory responses, and preservation of intestinal barrier integrity. These findings highlight the gut microbiota as a promising novel therapeutic target. This review synthesizes recent progress in three key areas: (1) the relationship between the gut microbiota and HUA; (2) microbial mechanisms underlying urate-lowering effects, such as microbial purine and urate metabolism, regulation of urate transporters like ABCG2, and production of anti-inflammatory metabolites; and (3) microbiota-based therapeutic interventions, including probiotics, engineered bacterial strains, fecal microbiota transplantation, and pharmabiotic strategies. Additionally, we explore the translational potential of microbiota modulation in clinical settings and outline directions for future research. By integrating mechanistic understanding with therapeutic innovation, this review offers researchers and clinicians a comprehensive framework for advancing microbiota-targeted approaches in the management of hyperuricaemia.}, } @article {pmid40948871, year = {2025}, author = {Thomas-Valdés, S and Jorquera, G}, title = {Editorial: Food-derived phytochemicals as regulators of gut microbiota.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1681732}, pmid = {40948871}, issn = {2296-861X}, } @article {pmid40948444, year = {2025}, author = {Bryson, S and Sisson, Z and Nelson, B and Grove, J and Reister, E and Liachko, I and Auch, B and Graiziger, C and Khoruts, A}, title = {Use of proximity ligation shotgun metagenomics to investigate the dynamics of plasmids and bacteriophages in the gut microbiome following fecal microbiota transplantation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2559019}, doi = {10.1080/19490976.2025.2559019}, pmid = {40948444}, issn = {1949-0984}, abstract = {Proximity ligation shotgun metagenomics facilitate the analysis of the relationships between mobile genetic elements, such as plasmids and bacteriophages, and their specific bacterial hosts. We applied this technique to investigate the changes in the fecal microbiome of patients receiving fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infections (rCDI). FMT was associated with successful engraftment of donor bacteria along with their associated bacteriophages. While fecal microbial diversity increased in all patients, the extent of specific bacterial taxa engraftment varied among individual patients. Interestingly, some donor bacteriophages remained closely linked to their original bacterial hosts, while others expanded their associations across different bacterial taxa. Notably, FMT partially reduced the content of vancomycin resistance and extended-spectrum beta-lactamase genes in the fecal microbiome of rCDI patients.}, } @article {pmid40948097, year = {2025}, author = {Gao, BY and Chen, SC}, title = {Gut Microbiota Typing and Donor Factors Shape Fecal Microbiota Transplantation Response in Psoriatic Arthritis.}, journal = {Arthritis & rheumatology (Hoboken, N.J.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/art.43392}, pmid = {40948097}, issn = {2326-5205}, } @article {pmid40948087, year = {2025}, author = {Kragsnaes, MS and Qin, P and Kjeldsen, J and Kristiansen, K and Ellingsen, T}, title = {Response to: "Gut Microbiota Typing and Donor Factors Shape Fecal Microbiota Transplantation Response in Psoriatic Arthritis".}, journal = {Arthritis & rheumatology (Hoboken, N.J.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/art.43394}, pmid = {40948087}, issn = {2326-5205}, } @article {pmid40947138, year = {2025}, author = {Wang, W and Yu, Y and Wang, R and Wang, Y and Ding, X and Lu, G and Lu, C and Liang, C and Zhang, S and Yi, B and Bai, J and Zhang, L and Li, P and Wen, Q and Cui, B and Zhang, F}, title = {Holdemanella biformis augments washed microbiota transplantation for the treatment of radiation enteritis.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-335230}, pmid = {40947138}, issn = {1468-3288}, abstract = {BACKGROUND: Current microbiome-based therapeutics face two prominent issues: the limited clinical efficacy of probiotics and the significant variability in the efficacy of microbiota transplantation across different diseases. Although washed microbiota transplantation (WMT) is a new faecal microbiota transplantation, a single therapeutic agent cannot be universally effective for multiple dysbiosis-related diseases.

OBJECTIVE: We introduced a new therapeutic concept, X-augmented WMT (X-auWMT), which combines a disease-specific beneficial microbe, 'X', with WMT to enhance its effectiveness. Our goal was to identify a candidate 'X' bacterium to augment WMT efficacy and examine the efficacy of X-auWMT in animal models of radiation enteritis (RE).

DESIGN: We conducted a prospective, non-randomised cohort study on a cohort of abdominal or pelvic cancer patients who developed RE after radiotherapy to identify a potential beneficial microbe. We used RE mouse models to evaluate the efficacy of X-auWMT compared with WMT. Multiomics analyses and experiments were undertaken to elucidate the underlying mechanisms.

RESULTS: WMT significantly alleviated multiple clinical symptoms in RE patients compared with routine treatments. We identified Holdemanella biformis as a candidate 'X' bacterium within the RE cohort and developed Hb-auWMT. Hb-auWMT significantly mitigated radiation-induced injury compared with WMT, exhibiting enhanced anti-apoptotic effects, improved maintenance of epithelial hypoxia, increased Treg cell levels and elevated butyrate and valerate levels in the RE mouse model. PPAR-γ is an essential pathway for the therapeutic efficacy of Hb-auWMT.

CONCLUSIONS: This study overcomes the aforementioned recognised limitations with probiotics and microbiota transplantation and provides a new research paradigm in the concept of microbiome-based therapeutics.}, } @article {pmid40947025, year = {2025}, author = {Yang, X and Liu, Z and You, T and Feng, H and Sun, F and Yao, J and Gao, Y and Yang, Y and Chen, C and Qiu, J}, title = {High-temperature exposure induces neurobehavioral abnormalities in mice through disruption of the gut microbiota.}, journal = {Journal of affective disorders}, volume = {}, number = {}, pages = {120318}, doi = {10.1016/j.jad.2025.120318}, pmid = {40947025}, issn = {1573-2517}, abstract = {Rising global temperatures pose significant health risks. However, the neurobehavioral consequences of high-temperature exposure remain understudied. In this study, C57BL/6J mice were exposed to three temperature levels (26 °C, 38 °C, and 40 °C) for 3, 7, and 14 days. Fecal microbiota transplantation (FMT) was performed to further investigate the role of the gut microbiota. Two-sample MR was employed to estimate the causal impact of gut microbiota composition on inflammation and neurobehavioral abnormalities. We found that mice exposed to 40 °C for 14 days exhibited impaired motor coordination and spatial memory, reduced exploratory behavior, and increased anxiety. Neuronal damage was observed in the cerebral cortex and hippocampus, along with structural damage and barrier dysfunction in the ileum and colon. Moreover, high-temperature exposure elicited a significant rise in circulating lipopolysaccharide (LPS), a concomitant dysregulation of inflammatory cytokine, and pronounced activation of the NF-κB signaling pathway. FMT from healthy mice ameliorated these adverse effects. Although high temperature reshaped both fungal and bacterial communities, only bacterial dysbiosis correlated with neurobehavioral abnormalities. MR further indicated that gut microbiota perturbations may causally drive inflammatory responses and neurobehavioral abnormalities. In summary, high-temperature exposure evokes inflammatory responses and neurobehavioral abnormalities via gut bacterial dysbiosis.}, } @article {pmid40946868, year = {2025}, author = {Deutschbein, F and Ianiro, G}, title = {Fecal microbiota transplantation for primary Clostridioides difficile infection. Ready for prime time?.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2025.09.017}, pmid = {40946868}, issn = {1528-0012}, } @article {pmid40946450, year = {2025}, author = {Zharova, NV and Mikhailidi, FD and Kabanova, DA and Tatarintseva, AY and Polyakova, OL and Zharikov, YO and Zharov, NA and Ryagin, SN and Pontes-Silva, A and Zharikova, TS}, title = {Influence of microbiota composition on the pathogenesis of type 2 diabetes: Physiological aspects.}, journal = {Molecular aspects of medicine}, volume = {106}, number = {}, pages = {101410}, doi = {10.1016/j.mam.2025.101410}, pmid = {40946450}, issn = {1872-9452}, abstract = {The development of type 2 diabetes may be influenced by enterotypes and bacterial metabolites. The most important of these are short-chain fatty acids (SCFAs), which play a role in forming the gut-brain axis and in the process of lipogenesis. An increase in lipogenesis can lead to obesity. High levels of adipose tissue in the body trigger chronic inflammation and insulin resistance. This review examines how microbiota composition influences the pathogenesis of type 2 diabetes and the possibility of regulating microbiota through proper nutrition, fecal microbiota transplantation, and prebiotics and probiotics. Additionally, the review notes that an imbalance in the gut microbiota can contribute to diabetes progression and increase cancer risk through inflammatory and immune mechanisms.}, } @article {pmid40945503, year = {2025}, author = {Bartu, L and Faith, JJ}, title = {Searching for the perfect match: MINDFUL trial pairs FMT and fiber for ulcerative colitis.}, journal = {Med (New York, N.Y.)}, volume = {6}, number = {9}, pages = {100842}, doi = {10.1016/j.medj.2025.100842}, pmid = {40945503}, issn = {2666-6340}, abstract = {Every trial of fecal microbiota transplantation for ulcerative colitis inspires the same question at seminars and journal clubs: can you combine FMT with a diet or fiber to improve strain engraftment and outcomes? The MINDFUL clinical trial explores this question by testing the impact of FMT with or without psyllium fiber supplementation in 27 ulcerative colitis patients.}, } @article {pmid40945252, year = {2025}, author = {Zhao, Y and Wang, Q and Wu, Z and Zhou, Y and Gao, X and Gong, W and Qin, X and Ren, Y and Tian, J}, title = {Modified Xiaoyaosan rescues depression-like behavior via remodeling gut microbiota and leucine metabolism.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {147}, number = {}, pages = {157241}, doi = {10.1016/j.phymed.2025.157241}, pmid = {40945252}, issn = {1618-095X}, abstract = {BACKGROUND: Social avoidance is a hallmark symptom of depression. Although Modified Xiaoyaosan (MXYS) has been reported to attenuate this behavior, the underlying mechanisms remain poorly understood.

PURPOSE: This study aimed to investigate the mechanisms by which MXYS alleviates social avoidance, with particular emphasis on gut microbiota composition and leucine metabolism.

METHODS: A chronic social defeat stress (CSDS) mouse model was established to evaluate the antidepressant effects of MXYS. Fecal samples were subjected to LC-MS-based untargeted metabolomics and 16S rRNA sequencing to characterize alterations in gut microbiota and metabolites. Fecal microbiota transplantation (FMT) was conducted to verify the contribution of gut microbes to MXYS's antidepressant effects. Furthermore, targeted GC-MS, LC-MS/MS, and Western blotting analyses were employed to elucidate the mechanisms underlying leucine reduction. Finally, exogenous leucine supplementation was administered to determine its potential antidepressant efficacy.

RESULTS: MXYS treatment significantly ameliorated CSDS-induced social avoidance and other depression-like behaviors. Integrated metabolomic and 16S rRNA analyses identified leucine metabolism as a potential therapeutic target. MXYS modulated gut microbial composition and functional pathways, particularly those involved in leucine metabolism. FMT experiments confirmed the essential role of gut microbiota in mediating the antidepressant effects of MXYS. Targeted metabolic profiling and protein expression analyses revealed that enhanced microbial degradation of leucine contributed to its systemic reduction. Moreover, leucine supplementation robustly reversed depressive-like behaviors and attenuated hippocampal oxidative stress.

CONCLUSION: MXYS alleviates social avoidance in CSDS mice by modulating gut microbiota-mediated leucine degradation, thereby restoring systemic leucine levels and improving hippocampal oxidative stress.}, } @article {pmid40944286, year = {2025}, author = {Tini, S and Baima, J and Pigni, S and Antoniotti, V and Caputo, M and De Palma, E and Cerbone, L and Grosso, F and La Vecchia, M and Bona, E and Prodam, F}, title = {The Microbiota-Diet-Immunity Axis in Cancer Care: From Prevention to Treatment Modulation and Survivorship.}, journal = {Nutrients}, volume = {17}, number = {17}, pages = {}, doi = {10.3390/nu17172898}, pmid = {40944286}, issn = {2072-6643}, support = {2020NCKXBR_004; P2022Z4EB5; 2022ALX9ZM//Ministero dell'Università e della Ricerca/ ; Micromeso project//LILT/ ; }, abstract = {Growing evidence highlights the pivotal role of the gut microbiota in cancer development, progression, response to therapy, and survivorship. Diet plays a central role in shaping gut microbiota composition, influencing the immune system and overall host health. Plant-based diets and the Mediterranean diet promote health-associated microbial communities that increase the production of several metabolic-end products, including short-chain fatty acids that support mucosal barrier integrity, anti-inflammatory effects, and modulation of the immunity of the host. Conversely, Western dietary patterns promote cancer progression and negatively impact the response to standard treatments. Furthermore, gut microbiota influences the effectiveness of cancer therapies, including chemotherapy, radiotherapy and, mainly, immunotherapy. Modulating microbial species, their metabolites, or their activities in the cancer microenvironment through dietary interventions, common or engineered probiotics, prebiotics, postbiotics, antibiotics or fecal microbial transplant are emerging as promising strategies for cancer prevention and tailored management in survivorship. In this review, we explore the intricate interplay between diet, gut microbiota, and cancer, focusing on how specific microbial communities' impact therapeutic outcomes, and the challenges in the modulation of the microbiota environment through several interventions, including diet. This emerging paradigm paves the way for integrating nutrition and microbiota-targeted strategies as innovative tools in the context of precision medicine.}, } @article {pmid40943741, year = {2025}, author = {Ichim, C and Boicean, A and Todor, SB and Anderco, P and Bîrluțiu, V}, title = {Fecal Microbiota Transplantation in Patients with Alcohol-Associated Cirrhosis: A Clinical Trial.}, journal = {Journal of clinical medicine}, volume = {14}, number = {17}, pages = {}, doi = {10.3390/jcm14175981}, pmid = {40943741}, issn = {2077-0383}, abstract = {Background: Gut microbiota dysregulation is increasingly recognized as a key contributor to the progression of liver cirrhosis and its complications, particularly hepatic encephalopathy. Fecal microbiota transplantation (FMT) has emerged as a novel therapeutic strategy aimed at restoring intestinal microbial homeostasis and modulating systemic inflammation. Methods: This prospective, single-center clinical trial evaluated the short-term safety and efficacy of FMT in patients with alcohol-related liver cirrhosis. Clinical assessment, liver stiffness (via elastography), steatosis (controlled attenuation parameter), inflammatory biomarkers, and extended biochemical panels were analyzed at baseline, one week and one month post-FMT. A control group receiving standard medical therapy was used for comparison. Results: FMT was associated with a significant reduction in hepatic encephalopathy severity (p = 0.014), sustained improvements in liver stiffness (p = 0.027) and decreased steatosis (p = 0.025). At one month, C-reactive protein and neutrophil-to-lymphocyte ratio both declined significantly (p = 0.043), indicating a measurable anti-inflammatory effect. No serious adverse events were recorded. In comparison with controls, FMT recipients showed lower systemic inflammation and improved neuropsychiatric status. Conclusions: FMT demonstrated a favorable safety profile and yielded early clinical and biochemical benefits in patients with cirrhosis. These preliminary findings support the potential utility of microbiota-based interventions in chronic liver disease and warrant validation in larger, multicenter trials.}, } @article {pmid40943575, year = {2025}, author = {Rubas, NC and Torres, A and Maunakea, AK}, title = {The Gut Microbiome and Epigenomic Reprogramming: Mechanisms, Interactions, and Implications for Human Health and Disease.}, journal = {International journal of molecular sciences}, volume = {26}, number = {17}, pages = {}, doi = {10.3390/ijms26178658}, pmid = {40943575}, issn = {1422-0067}, support = {R01MD016593//National Institute on Minority Health and 510 Health Disparities/ ; R56MD014630//National Institute on Minority Health and 510 Health Disparities/ ; }, abstract = {The human gut microbiome is a metabolically active and ecologically dynamic consortium that profoundly influences host physiology, in part by modulating epigenetic mechanisms such as DNA and RNA methylation. These modifications regulate gene expression and phenotypic plasticity and are shaped by a combination of environmental factors, such as diet, stress, xenobiotics, and bioactive microbial metabolites. Despite growing evidence linking microbial signals to host epigenetic reprogramming, the underlying molecular pathways remain incompletely understood. This review highlights recent mechanistic discoveries and conceptual advances in understanding microbiome-host epigenome interactions. We discuss evolutionarily conserved pathways through which gut microbiota regulate host methylation patterns, including one-carbon metabolism, polyamine biosynthesis, short-chain fatty acid signaling, and extracellular vesicle-mediated communication. We also examine how host factors such as aging, diet, immune activity, and sociocultural context reciprocally influence microbial composition and function. Beyond basic mechanisms, we outline translational frontiers-including biomarker discovery, live biotherapeutic interventions, fecal microbiota transplantation, and adaptive clinical trial designs-that may enable microbiome-informed approaches to disease prevention and treatment. Advances in high-throughput methylation mapping, artificial intelligence, and single-cell multi-omics are accelerating our ability to model these complex interactions at high resolution. Finally, we emphasize the importance of rigorous standardization and ethical data governance through frameworks such as the FAIR and CARE principles. Deepening our understanding of how the gut microbiome modulates host epigenetic programs offers novel opportunities for precision health strategies and equitable clinical translation.}, } @article {pmid40943409, year = {2025}, author = {Tonch-Cerbu, AK and Boicean, AG and Stoia, OM and Teodoru, M}, title = {Gut Microbiota-Derived Metabolites in Atherosclerosis: Pathways, Biomarkers, and Targets.}, journal = {International journal of molecular sciences}, volume = {26}, number = {17}, pages = {}, doi = {10.3390/ijms26178488}, pmid = {40943409}, issn = {1422-0067}, abstract = {The human gut microbiota is a complex ecosystem that influences host metabolism, immune function, and cardiovascular health. Dysbiosis, defined as an imbalance in microbial composition or function, has been linked to the development and progression of atherosclerosis. This connection is mediated by microbial metabolites that enter the systemic circulation and interact with vascular and immune pathways. Among these, trimethylamine N-oxide (TMAO) has been most extensively studied and is consistently associated with cardiovascular events. Other metabolites, including lipopolysaccharides (LPS), short-chain fatty acids (SCFAs), and secondary bile acids, also contribute by modulating inflammation, endothelial function, and lipid metabolism. Recent research has expanded to emerging metabolites such as indoxyl sulfate, indole-3-propionic acid, and polyamines, which may provide additional mechanistic insights. These microbial products are increasingly explored as biomarkers of cardiovascular risk. TMAO has shown predictive value in large human cohorts, while microbiota composition and diversity measures remain less consistent across studies. However, interpretation of these biomarkers is limited by methodological variability, interindividual differences, and lack of standardization. Therapeutic interventions targeting the gut-heart axis are under investigation. Dietary strategies such as the Mediterranean diet and fiber-rich nutrition, probiotics and prebiotics, and fecal microbiota transplantation (FMT) show promise, while pharmacological approaches targeting TMAO or bile acid pathways are in early stages. This review summarizes current knowledge on the mechanistic, diagnostic, and therapeutic links between the gut microbiota and atherosclerosis, highlighting both established findings and emerging directions for future research.}, } @article {pmid40941154, year = {2025}, author = {Zhang, J and Wei, ZJ and Fan, G}, title = {Emerging Understanding of Gut Microbiome in Colorectal Cancer and Food-Related Intervention Strategies.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {17}, pages = {}, doi = {10.3390/foods14173040}, pmid = {40941154}, issn = {2304-8158}, support = {2022YFF1100306//National Key Research & Development Program of China/ ; 2023AAC03272//the Natural Science Foundation of Ningxia Hui Autonomous Region/ ; }, abstract = {Colorectal cancer (CRC) is one of the most common cancers, accounting for approximately 10% of all new cancer cases globally. An increasing number of studies have revealed that the gut microbiome is strongly associated with the pathogenesis and progression of CRC. Based on these advances, this review delineates the mechanistic links between specific microbes and CRC, as well as emerging food-related nutritional intervention strategies. In vivo and in vitro studies have pinpointed the implications of key microbes such as Fusobacterium nucleatum, certain strains of Escherichia coli, enterotoxigenic Bacteroides fragilis, and Enterococcus faecalis, among others, and metabolite involvement and immune responses. Particular attention is paid to the roles of intratumoral microbiota in the development and treatment of CRC, given their direct interaction with tumor cells. Various food-related nutritional intervention strategies have been developed to mitigate CRC risk, including probiotics, antibiotics, or the administration of bioactive compounds such as luteoloside. Finally, we outline critical research directions regarding the influence of animal lineage, carcinoma location, population demographics, the application of advanced in vitro models, and the mediatory roles of gut-associated epithelial cells. In summary, this review might consolidate our current knowledge on the contribution of gut microbiota to CRC and highlights the microbe-based strategies to enhance nutritional interventions for this disease.}, } @article {pmid40940892, year = {2025}, author = {Mohamed, AS and Bhuju, R and Martinez, E and Basta, M and Deyab, A and Mansour, C and Tejada, D and Deshpande, V and Elias, S and Nagesh, VK}, title = {The Gut Microbiome's Impact on the Pathogenesis and Treatment of Gastric Cancer-An Updated Literature Review.}, journal = {Cancers}, volume = {17}, number = {17}, pages = {}, doi = {10.3390/cancers17172795}, pmid = {40940892}, issn = {2072-6694}, abstract = {The gut microbiota plays a critical role in maintaining gastrointestinal homeostasis, immune regulation, and metabolic processes. Recent evidence has highlighted its significant influence on gastric carcinogenesis. Helicobacter pylori, a well-established class I carcinogen, remains the most prominent microbial risk factor for gastric cancer. However, emerging studies indicate that alterations in the broader gastric and intestinal microbial communities, referred to as dysbiosis, may also contribute to tumor initiation, progression, and immune evasion. These microbial shifts can lead to chronic inflammation, genotoxic metabolite production, and modulation of signaling pathways such as NF-κB and Wnt/β-catenin. This review explores the current understanding of the gut microbiome's contribution to gastric cancer pathogenesis, including microbial signatures associated with precancerous lesions and the tumor microenvironment. Furthermore, the potential of microbiota-based biomarkers and therapeutic interventions, including probiotics, prebiotics, and fecal microbiota transplantation, is discussed as part of emerging precision medicine strategies.}, } @article {pmid40937436, year = {2025}, author = {Huang, X and Yu, Y and Tian, N and Huang, J and Zhang, X and Yu, R}, title = {Human microbiota-associated animal models: a review.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1644187}, pmid = {40937436}, issn = {2235-2988}, abstract = {Human microbiota-associated (HMA) animal models have become indispensable tools for investigating microbe-host interactions and disease pathogenesis. However, standardization challenges persist across different research groups when such models are used in fecal microbiota transplantation (FMT) protocols. Establishing a successful HMA model involves multiple stages, including donor screening, fecal suspension preparation, recipient preparation, and FMT. The outcomes of these stages are influenced by donor characteristics, recipient type, microbial viability, and dietary factors. This review examined the critical components of HMA model production, including the inclusion and exclusion criteria for human donors, collection time and processing methodology for fecal samples, recipient animal preparation strategies, and FMT regimens with engraftment validation. The key findings revealed that short-term antibiotic, probiotic, or laxative use constitutes an essential donor exclusion criterion. The time and method of fecal collection should be standardized as much as possible. Fecal samples should be processed as soon as possible, in anaerobic environments, with the addition of suitable protectants if they must be preserved at low temperatures. Microbial community profiling via 16S rRNA gene sequencing represents the primary method for analyzing microbiome composition and verifying microbiota engraftment efficacy throughout FMT procedures. The most commonly used recipients for HMA modeling included germ-free and pseudo-germ-free animals generated through antibiotic-mediated microbiota depletion. Although FMT with a single gavage of fecal suspension proved sufficient for model establishment, multiple frequencies and longer FMT durations significantly improved the efficiency of donor microbiota colonization. Overall, these findings are expected to aid the establishment of a standardized and reproducible protocol for preparing HMA models.}, } @article {pmid40937422, year = {2025}, author = {Bu, S and Cheng, X and Chen, M and Yu, Y}, title = {Ulcerative Colitis: Advances in Pathogenesis, Biomarkers, and Therapeutic Strategies.}, journal = {Pharmacogenomics and personalized medicine}, volume = {18}, number = {}, pages = {219-238}, pmid = {40937422}, issn = {1178-7066}, abstract = {Ulcerative colitis represents an inflammatory bowel disease with multiple contributing factors, marked by persistent inflammation of the colonic mucosa, which can lead to a reduced life expectancy and an elevated likelihood of requiring colectomy as well as developing colorectal cancer. Despite impacting roughly 5 million individuals worldwide, the intricate mechanisms underlying ulcerative colitis are still inadequately defined, hindering the development of effective treatments. Extra-intestinal complications, including enteropathic arthritis, are also addressed in the context of disease burden and management. This review explores the multifaceted pathogenesis of ulcerative colitis, emphasizing critical factors such as abnormalities in the epithelial barrier, irregular immune responses, the release of inflammatory mediators, and alterations in gut microbiota composition. We also underscore recent advancements in diagnostic biomarkers that improve the accuracy of disease detection and monitoring. Conventional medicinal strategies are reviewed alongside the emergence of biological therapies, notably those that target tumor necrosis factor (TNF), interleukins, and integrins, which have significantly altered management approaches. Established therapies (eg, 5-aminosalicylic acid, corticosteroids) and emerging agents (eg, JAK inhibitors, S1P modulators) are clearly delineated. Combination strategies-such as dual biologic regimens or JAK inhibitors combined with anti-integrin agents-are also discussed in dedicated subsections. We discuss novel therapies that utilize small molecule targeting, particularly those that inhibit Janus kinase (JAK) and modulate sphingosine-1-phosphate (S1P) receptors, presenting promising avenues for treatment. Additionally, fecal microbiota transplantation (FMT) is evaluated as a therapeutic option, as it shows promise in restoring microbial balance. Collectively, these advances underscore the pivotal roles of immune dysregulation, biologic therapies, and microbiota modulation in reshaping precision management of ulcerative colitis. This synthesis of current knowledge underscores the necessity for continued research to refine therapeutic strategies and improve patient outcomes in ulcerative colitis.}, } @article {pmid40937050, year = {2025}, author = {Peña, JA and Mazhuvanchery, CB and Santos, MJMN and Naz, S and Cruz, CC and Wali, S and Varatharajalu, K and Okhuysen, PC and Vuong, NN and Wang, Y}, title = {Bezlotoxumab for the prevention of recurrent Clostridioides difficile infection for patients with cancer.}, journal = {Annals of gastroenterology}, volume = {38}, number = {5}, pages = {519-525}, pmid = {40937050}, issn = {1108-7471}, abstract = {BACKGROUND: Several clinical factors increase the susceptibility of cancer patients to Clostridioides difficile infection (CDI), often resulting in lower CDI treatment response rates and higher rates of recurrent CDI (rCDI). Bezlotoxumab, a monoclonal antibody targeting and neutralizing C. difficile toxin B, demonstrates a significant reduction in rCDI rates compared to standard of care alone in the general population. However, the effectiveness of bezlotoxumab in the cancer patient population requires further investigation. We assessed the incidence of rCDI within 90 days of bezlotoxumab treatment in patients with cancer.

METHODS: This was a single-center retrospective cohort study conducted at a tertiary care cancer center, including patients who received bezlotoxumab with standard-of-care antibiotics for CDI or rCDI between March 2016 and January 2023. Descriptive analyses were conducted.

RESULTS: A total of 177 patients with cancer who received bezlotoxumab were included. Most (76.8%) experienced <2 CDI episodes, whereas 23.2% experienced ≥2 episodes. Bezlotoxumab was administered a median of 10 days (interquartile range [IQR] 5-12.5) after symptom onset, and fidaxomicin was the most frequently used concurrent antibiotic (41.2%). Eleven patients (6.2%) underwent fecal microbiota transplantation before or after bezlotoxumab treatment. The overall 90-day rCDI recurrence rate was 6.2% (11 patients), with a median time to recurrence of 50 days (IQR 25-58).

CONCLUSIONS: Bezlotoxumab demonstrated high efficacy in reducing rCDI within a 90-day period after administration, compared to rates in the non-cancer population. The findings suggest that administration of bezlotoxumab for rCDI prevention should be considered, given the improvement in the outcome of this high-risk group.}, } @article {pmid40936935, year = {2025}, author = {Wang, Y and Zhuang, K and Yi, Q and Wu, Y and Luo, Y and Ouyang, Y and Li, L and Li, C and Luo, H}, title = {High humidity environment increases FBG by impairing the intestinal barrier.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1625609}, pmid = {40936935}, issn = {1664-3224}, abstract = {INTRODUCTION: Climate and environmental changes pose significant threats to human metabolic health; however, the specific effects of individual environmental factors on metabolic diseases remain poorly understood. This study aimed to investigate the impact of a high humidity environment (HH) on fasting blood glucose (FBG), intestinal barrier integrity, and gut microbiota composition.

METHODS: We analyzed clinical samples collected during HH exposure and performed a controlled male mouse experiment. FBG and hormone levels were assessed, and intestinal barrier integrity was evaluated using western blot and immunofluorescence staining. Gut microbiota composition was profiled via 16S rDNA sequencing. Mechanistic insights were obtained through fecal microbiota transplantation (FMT), Mendelian randomization (MR) analysis, and metabolomic profiling. An antibiotic cocktail (ABX) intervention was applied to determine the reversibility of HH-induced effects.

RESULTS: Clinical samples collected under HH conditions showed elevated FBG, increased glucagon (GC) levels, impaired intestinal barrier function, and decreased serum gamma-aminobutyric acid (GABA) concentrations. 16S rDNA sequencing revealed increased abundances of Alistipes, Parabacteroides, and Akkermansia. Metabolomic analysis demonstrated reduced serum GABA levels, which correlated with intestinal barrier disruption and activation of the MDP-NOD2 pathway in pancreatic β-cells. HH exposure also downregulated GAD67 expression, reducing GABA synthesis and leading to enhanced GC secretion from islet α-cells. FMT suggested that gut microbiota alterations mediated HH-induced FBG elevation. ABX treatment effectively reversed these metabolic and microbial changes.

DISCUSSION: Our findings demonstrate that a high humidity environment disrupts gut microbiota homeostasis, impairs the intestinal barrier, and reduces GABA synthesis in pancreatic β-cells, thereby promoting the development of type 2 diabetes mellitus (T2DM).}, } @article {pmid40935212, year = {2025}, author = {Wang, Z and Zhu, Y and Wang, G and Sun, M and Yao, W and Ba, Q}, title = {Eucommia alleviates high fat diet-induced MASLD via the F. prausnitzii/butyrate/GPR43/GLP-1 signaling.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {120587}, doi = {10.1016/j.jep.2025.120587}, pmid = {40935212}, issn = {1872-7573}, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disorder worldwide, and remains without truly effective therapies. Eucommia ulmoides Oliver (Eucommia), a traditional Chinese medicinal herb, is widely known for its hepatoprotective actions, but its therapeutic potential in MASLD and underlying mechanisms remain largely unexplored.

AIM OF THE STUDY: In vitro and in vivo studies, the protective effect of Eucommia bark extract (EBE) on MASLD was elucidated, and investigate its hepatoprotective mechanism.

MATERIALS AND METHODS: A high-fat diet (HFD)-induced MASLD mouse model was used to evaluate the therapeutic efficacy of EBE. Mice were orally administered EBE throughout HFD feeding, and metabolic parameters, liver histology, and key signaling pathways were systematically assessed. To investigate the underlying mechanisms, gut microbiota composition was analyzed by 16S rRNA sequencing, and fecal microbiota transplantation from EBE-treated donors was performed to determine the microbiota-mediated effects.

RESULTS: EBE dramatically attenuated HFD-induced weight gain, oxidative stress, inflammation, lipid accumulation, and fibrosis in MASLD mice. Mechanistically, EBE raised circulating glucagon-like peptide-1 (GLP-1) levels, enhanced adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation downstream of GLP-1 receptor (GLP-1R), thereby suppressing lipogenesis and promoting lipophagy. Although EBE did not directly trigger GLP-1 release in STC-1 cells, microbiome profiling revealed a selective bloom of Faecalibacterium prausnitzii (F. prausnitzii) - a major butyric acid producer-leading to elevated colonic butyric acid. Butyrate activated G protein-coupled receptor 43 (GPR43) on enteroendocrine cells to drive GLP-1 synthesis, a response abolished by GPR43 knockdown. Crucially, fecal microbiota transplantation from EBE-treated donors recapitulated these metabolic improvements in recipient mice.

CONCLUSION: EBE ameliorates MASLD by reshaping the gut microbiota to enrich F. prausnitzii-derived butyrate, which in turn stimulates endogenous GLP-1 secretion and activates the hepatic GLP-1R/AMPK axis to preserves lipid metabolism disorders.}, } @article {pmid40933575, year = {2025}, author = {Ye, F and Li, H and Li, H and Mu, X}, title = {Identification of novel gut microbiota-related biomarkers in cerebral hemorrhagic stroke.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1636860}, doi = {10.3389/fmed.2025.1636860}, pmid = {40933575}, issn = {2296-858X}, abstract = {INTRODUCTION: Hemorrhagic stroke, especially intracerebral hemorrhage (ICH), is the most fatal type of stroke and a major cause of mortality and disability. Due to ambiguous symptoms and limited biomarkers, early diagnosis and prognosis remain challenging. Recent evidence suggests that gut microbiota dysregulation influences neuroinflammation and outcomes in ICH, but the underlying molecular mechanisms remain unclear.

METHODS: Transcriptome data from the GSE24265 dataset were analyzed to identify differentially expressed genes (DEGs) in ICH. Gut microbiota-related genes (GMRGs) were obtained from GeneCards and literature, and overlapping genes were defined as gut microbiota-related DEGs (GMRDEGs). Functional enrichment, gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) analyses were performed. Hub genes were screened using LASSO, RandomForest, and SVM-RFE algorithms. Validation was conducted in plasma samples from ICH patients (n=20) and controls (n < 20) by qRT-PCR, and in a collagenase-induced ICH mouse model. The therapeutic effect of fecal microbiota transplantation (FMT) was evaluated through neurological scoring, hematoma volume, brain edema, intestinal barrier protein expression, inflammatory cytokines, and hub gene expression.

RESULTS: We identified 806 DEGs in ICH, among which 65 overlapped with GMRGs. These GMRDEGs were enriched in immune processes and pathways such as TNF and IL-17 signaling. PPI network analysis highlighted IL1B, IL6, and CCL2 as central nodes. Machine learning identified four hub genes-LEF1, ITGAX, BLVRB, and ATF4. All were significantly upregulated in ICH tissues and plasma, correlating with immune cell infiltration. In vivo, FMT reduced hematoma volume and brain edema, improved neurological function, restored intestinal barrier proteins, decreased inflammatory cytokines, and downregulated hub gene expression.

DISCUSSION: LEF1, ITGAX, BLVRB, and ATF4 were identified as gut microbiota-related biomarkers of ICH. Their modulation by FMT highlights the role of the brain-gut axis in ICH and suggests potential diagnostic biomarkers and therapeutic targets.}, } @article {pmid40933007, year = {2025}, author = {Le, J and Hakimjavadi, H and Parsana, R and Chamala, S and Michail, S}, title = {Fecal Microbiota Transplantation Induces Sustained Gut Microbiome Changes in Pediatric Ulcerative Colitis: A Combined Randomized and Open-Label Study.}, journal = {Gastro hep advances}, volume = {4}, number = {10}, pages = {100741}, doi = {10.1016/j.gastha.2025.100741}, pmid = {40933007}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) is a promising tool to modulate the gut microbiome in pediatric ulcerative colitis (UC). We investigated the long-term impact of FMT on the gut microbiome and identified microbial signatures associated with disease severity and clinical outcomes.

METHODS: This study combined a randomized, double-blind trial comparing FMT to autologous placebo with an open-label extension to assess FMT's effects on the gut microbiome in pediatric UC patients over 48 weeks. Stool samples were collected at baseline and postintervention, and clinical response was evaluated using the Pediatric Ulcerative Colitis Activity Index. Shotgun metagenomic sequencing characterized the fecal microbiome's composition and functional potential. Taxon set enrichment analysis identified microbial taxon sets associated with UC and FMT.

RESULTS: FMT induced significant, sustained increases in gut microbial diversity over 48 weeks. Key changes included decreases in Klebsiella oxytoca and increases in Coprobacter fastidiosus post-FMT. Microbial signatures were associated with disease severity, including increased indole producers and decreased mucin degraders in mild UC compared to remission. Patients with clinical improvement post-FMT showed decreased Fusobacterium nucleatum and Veillonella parvula. Klebsiella pneumoniae and Klebsiella variicola decreased after open-label FMT.

CONCLUSION: FMT induces sustained changes in the pediatric UC gut microbiome, with distinct microbial signatures associated with disease severity and clinical outcomes. However, the high autologous placebo response rate underscores the need for further research to elucidate the mechanisms underlying FMT and placebo responses. Our study provides insights into the gut microbiome's role in pediatric UC, laying the foundation for developing personalized microbiome-targeted therapies. ClinicalTrials.gov number, NCT02291523.}, } @article {pmid40930564, year = {2025}, author = {Rauber, C and Roberti, MP and Vehreschild, MJ and Tsakmaklis, A and Springfeld, C and Teufel, A and Ettrich, T and Jochheim, L and Kandulski, A and Missios, P and Mohr, R and Reichart, A and Waldschmidt, DT and Sauer, LD and Sander, A and Schirmacher, P and Jäger, D and Michl, P and Dill, MT}, title = {Protocol: Faecal microbiota transfer in liver cancer to overcome resistance to atezolizumab/bevacizumab - a multicentre, randomised, placebo-controlled, double-blind phase II trial (the FLORA trial).}, journal = {BMJ open}, volume = {15}, number = {9}, pages = {e097802}, doi = {10.1136/bmjopen-2024-097802}, pmid = {40930564}, issn = {2044-6055}, mesh = {Humans ; *Liver Neoplasms/therapy/drug therapy ; *Bevacizumab/therapeutic use ; Double-Blind Method ; *Fecal Microbiota Transplantation/methods ; *Antibodies, Monoclonal, Humanized/therapeutic use ; *Carcinoma, Hepatocellular/therapy/drug therapy ; Drug Resistance, Neoplasm ; Clinical Trials, Phase II as Topic ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; Immune Checkpoint Inhibitors/therapeutic use ; Gastrointestinal Microbiome ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; }, abstract = {INTRODUCTION: Combined vascular endothelial growth factor/programmed death-ligand 1 blockade through atezolizumab/bevacizumab (A/B) is the current standard of care in advanced hepatocellular carcinoma (HCC). A/B substantially improved objective response rates compared with tyrosine kinase inhibitor sorafenib; however, a majority of patients will still not respond to A/B. Strong scientific rationale and emerging clinical data suggest that faecal microbiota transfer (FMT) may improve antitumour immune response on PD-(L)1 blockade. Early trials in melanoma with FMT and reinduction of immune checkpoint blockade (ICI) therapy in patients with anti-PD-1-refractory metastatic melanoma were reported in 2021 and demonstrated reinstatement of response to ICI therapy in many patients. Due to anatomical vicinity and the physiological relevance of the gut-liver axis, we hypothesise HCC to be a particularly attractive cancer entity to further assess a potential benefit of FMT in combination with ICI towards increased antitumour immunity. Additionally, HCC often occurs in patients with liver cirrhosis, where liver function is prognostically relevant. There is evidence that FMT may increase hepatic function and therefore could positively affect outcome in this patient population.

METHODS AND ANALYSIS: This prospective, multicentre, randomised, placebo-controlled, double-blind phase II clinical trial has been designed to assess immunogenicity and safety of FMT via INTESTIFIX 001 combined with A/B in advanced HCC in comparison to A/B with placebo. Primary endpoints are measured as tumour CD8+ T cell infiltration after 2 cycles of treatment with vancomycin, A/B+INTESTIFIX 001 in comparison to vancomycin-placebo, A/B+INTESTIFIX 001-placebo and safety of the therapeutic combination in advanced HCC. INTESTIFIX 001 is an encapsulated FMT preparation by healthy donors with a high alpha-diversity in their gut microbiome for oral administration, manufactured by the Cologne Microbiota Bank (CMB). Sample size was calculated to achieve a specific expected accuracy for the primary immunological endpoint. 48 subjects will be randomised to reach a goal of 42 usable measurements in the modified intention-to-treat set. Subjects will be randomised in a 2:1 ratio to A/B or placebo (28 A/B, 14 placebo).

ETHICS AND DISSEMINATION: The study was approved by ethics committee review and the German Federal Ministry of Drugs and Medical Devices. The trial is registered under EU CT no. 2023-506887-15-00. The outcome of the study will be disseminated via peer-reviewed publications and at international conferences.

TRIAL REGISTRATION NUMBER: NCT05690048.}, } @article {pmid40930304, year = {2025}, author = {Nguyen, L and Feuerstadt, P and Allegretti, JR and Axelrad, J}, title = {Fecal Microbiota-based therapies compared to Fecal Microbiota Transplantation for Preventing recurrent C. difficile Infection.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2025.08.029}, pmid = {40930304}, issn = {1542-7714}, } @article {pmid40930289, year = {2025}, author = {Ou, G and Liu, T and Wu, S and Wang, H and Wang, S and Wu, J and Chen, Y and Deng, L and Xu, L and Xu, H and Chen, X}, title = {Huopu Xialing Decoction Mitigates Influenza A-Induced Pulmonary Injury by inhibiting METTL3-Nlrp3(m6A) Mediated NLRP3 Inflammasome Activation.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {120577}, doi = {10.1016/j.jep.2025.120577}, pmid = {40930289}, issn = {1872-7573}, abstract = {Huopu Xialing Decoction (HXD) is a traditional Chinese medicine (TCM) formula widely used in the clinical treatment of respiratory viral infections. Despite its established application, the pharmacological mechanisms underlying its therapeutic effects against influenza remain to be fully elucidated.

AIM OF THE STUDY: This study aimed to investigate the protective effects of HXD against influenza A virus-induced lung inflammation and to explore the role of gut microbiota and epigenetic regulation in mediating these effects.

MATERIALS AND METHODS: An intranasal FM1 influenza virus infection model was established in mice. Lung histopathology was assessed by HE staining, and interleukin-1β (IL-1β) levels were measured using ELISA. Global N6-methyladenosine (m[6]A) methylation in lung tissues was detected by dot blot. RNA sequencing and SELECT™-m[6]A-qPCR were employed to identify and validate METTL3-mediated m[6]A modifications. 16S rRNA sequencing was used to profile gut microbiota alterations, and fecal microbiota transplantation (FMT) experiments were conducted to evaluate the role of microbiota in HXD-mediated effects.

RESULTS: HXD treatment significantly alleviated influenza-induced lung injury, suppressed IL-1β expression, and reduced METTL3-dependent m[6]A methylation of Nlrp3 mRNA. This was associated with decreased expression of NLRP3 inflammasome components, including ASC, pro-Caspase-1, cleaved-Caspase-1, GSDMD-N, and IL-1β. Furthermore, HXD modulated gut microbiota composition, marked by increased abundance of Lactobacillus and reduced Staphylococcus, which contributed to the downregulation of the pulmonary METTL3-Nlrp3 (m[6]A) axis.

CONCLUSION: HXD attenuates influenza-induced pulmonary inflammation by modulating the gut-lung axis and inhibiting METTL3-mediated m6A modification of Nlrp3, leading to suppression of NLRP3 inflammasome activation. These findings provide pharmacological evidence supporting the traditional use of HXD in respiratory infections and highlight the interplay between gut microbiota and epitranscriptomic regulation in the action of TCM.}, } @article {pmid40930236, year = {2025}, author = {Zhang, F and Ding, K and Zhang, LM and Liu, DY and Dong, X and Wang, MN and Zhou, FL and Sun, YW and Zhang, WK and Yan, Y and He, J and Xu, JK}, title = {The role of the gut microbiota in neuropsychiatric disorders and therapy.}, journal = {Ageing research reviews}, volume = {}, number = {}, pages = {102894}, doi = {10.1016/j.arr.2025.102894}, pmid = {40930236}, issn = {1872-9649}, abstract = {The vast microbial community residing in the gut is known as the gut microbiota (GM). Alterations in the compositional equilibrium of the GM, a phenomenon termed GM dysbiosis, have been increasingly associated with the pathogenesis of various diseases, particularly neuropsychiatric disorders. The microbiota-gut-brain axis (MGBA) serves as a bidirectional communication system that connects the gut to the brain. Notably, several prevalent neuropsychiatric disorders, including depression, Alzheimer's disease (AD), and Parkinson's disease (PD), collectively affect over one billion individuals globally. Emerging scientific evidence has consistently demonstrated the presence of GM dysbiosis in various neuropsychiatric disorders, suggesting a potential etiological role of GM in these conditions through MGBA-mediated mechanisms. In this comprehensive review, we systematically discussed the GM and MGBA, and presented evidence from both animal and human studies that highlighted the significance of GM in the occurrence and development of neuropsychiatric disorders. Subsequently, we emphasized the potential impact of GM and its metabolites on neuropsychiatric disorders. Next, we summarized the drugs used to treat diseases by regulating the GM. Finally, we proposed strategies to ameliorate the malignant progression of neuropsychiatric disorders by manipulating the composition of the GM. These strategies encompass the application of probiotics, prebiotics and synbiotics, postbiotics, fecal microbiota transplantation (FMT), dietary interventions. Collectively, targeted GM therapy has the potential to be an effective treatment for neuropsychiatric disorders.}, } @article {pmid40929883, year = {2025}, author = {Song, TY and Yang, XF and Wang, JY and Yin, LH and Zhao, XR and Wang, N and Xu, YW and Qi, Y and Xiong, CQ and Xu, LN}, title = {Gut microbiota-based metabolism contributes to the protection of pseudolaric acid B against MAFLD.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {147}, number = {}, pages = {157235}, doi = {10.1016/j.phymed.2025.157235}, pmid = {40929883}, issn = {1618-095X}, abstract = {BACKGROUND: The pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD) involves gut microbiota dysbiosis. This study investigated pseudolaric acid B (PAB), a diterpenoid from Pseudolarix kaempferi, for its potential to ameliorate MAFLD via microbiota-metabolite-host signaling pathways.

METHOD: We evaluated the effects of PAB on MAFLD in high-fat diet (HFD)-fed mice. 16S rRNA sequencing and metabolomics analyzed the regulations of PAB on gut microbiota and metabolites. The fecal microbiota transplantation (FMT) experiment was conducted to validate the causal role of the gut microbiota in the efficacy of PAB. Mechanistic studies employed molecular docking, microscale thermal migration (MST), western blot, immunofluorescence, and PCR to elucidate how PAB alleviates hepatic lipid metabolism dysregulation in MAFLD via microbial metabolites. In vivo intervention with candidate metabolites assessed improvement of disease phenotypes.

RESULTS: PAB effectively alleviatd the symptoms of HFD-induced MAFLD in mice, and repaired dysbiosis of intestinal microbiota, especially g_Faecalibaculum, g_Allobaculum, g_Ileibacterium, and g_Dubosiella, which were markedly down-regulated by PAB and showed a positive correlation with liver injury. FMT confirmed the relevance of PAB efficacy to the microbial community structure. Moreover, PAB intervention led to a dramatically enrichment of the tryptophan metabolism pathway, with cinnabarinic acid (CA), a microbial tryptophan metabolite, exhibiting a significat negative correlation with the abundance of the down-regulated bacteria. CA supplementation alleviated HFD-induced MAFLD in mice, indicating the hepatoprotective effect of CA. Molecular docking and MST revealed CA binds stablly to aryl hydrocarbon receptor (AhR) with higher affinity/stability, indicating a direct interaction between them. Mechanistically, PAB increased CA level and then activited AhR, downregulated hepatic lipogenesis genes by AhR-mediated IL-22/JAK1/STAT3 pathway.

CONCLUSION: PAB exerts a protective effect against MAFLD via restructuring the gut microbiota ecosystem, and activating CA/AhR/IL-22 signaling axis to reduce lipogenesis. These findings reveal a novel microbiota-metabolite-host mechanism and highlight PAB as a promising prebiotic-based therapeutic candidate for MAFLD.}, } @article {pmid40928298, year = {2025}, author = {Ge, J and Ye, Y and Yang, J and Di, Y and Jia, J and Bai, J and Jia, X and Wu, Z and Liu, X and Duan, X}, title = {Phosvitin Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice via Gut Microbiota Modulation.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c09135}, pmid = {40928298}, issn = {1520-5118}, abstract = {Dietary proteins have been demonstrated to alleviate ulcerative colitis. Phosvitin (PSV), a highly phosphorylated protein, possesses biological functions such as anti-inflammatory and antioxidant activities. This study aimed to investigate the preventive effects of PSV on dextran sulfate sodium (DSS)-induced colitis in mice and its underlying mechanisms. Following 4 weeks of PSV intervention (50 mg/kg b.w.), a colitis model was established by administering 2.5% DSS for 1 week. Results showed that PSV intervention significantly attenuated intestinal inflammation, reduced proinflammatory cytokine levels (e.g., TNF-α), and preserved intestinal barrier integrity. Furthermore, PSV modulated the gut microbiota by enhancing microbial diversity, decreasing the abundance of Escherichia-Shigella and Akkermansia, while increasing the abundance of Lachnospiraceae and Clostridium. Fecal microbiota transplantation (FMT) experiments further demonstrated the pivotal role of gut microbiota in PSV-mediated colitis prevention, as FMT from PSV-treated donor mice markedly alleviated colitis symptoms, achieving efficacy comparable to that of direct PSV intervention. These findings suggest that PSV alleviates colitis primarily through gut microbiota modulation.}, } @article {pmid40927726, year = {2025}, author = {Eiman, L and Moazzam, K and Anjum, S and Kausar, H and Sharif, EAM and Ibrahim, WN}, title = {Gut dysbiosis in cancer immunotherapy: microbiota-mediated resistance and emerging treatments.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1575452}, pmid = {40927726}, issn = {1664-3224}, mesh = {Humans ; *Dysbiosis/immunology/therapy ; *Gastrointestinal Microbiome/immunology ; *Neoplasms/therapy/immunology/microbiology ; *Immunotherapy/methods ; Animals ; *Drug Resistance, Neoplasm ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Tumor Microenvironment/immunology ; }, abstract = {Cancer is a multifaceted disease driven by a complex interplay of genetic predisposition, environmental factors and lifestyle habits. With the accelerating pace of cancer research, the gut microbiome has emerged as a critical modulator of human health and immunity. Disruption in the gut microbial populations and diversity, known as dysbiosis, has been linked with the development of chronic inflammation, oncogenesis, angiogenesis and metastasis. This review discusses the microbial species associated with various types of cancer and the pathways involved in their tumorigenic effect including mechanisms like inflammatory cytokine response, immune modulation, genotoxicity and modification of the tumor microenvironment. Diagnostic tools such as metagenomics, metabolomics, and the use of dysbiosis indexes help in the detection of gut bacterial imbalances, enabling early detection of cancer and potential intervention. Gut dysbiosis diminishes the efficacy of cancer treatments including immunotherapies, and creates immunotherapy resistance by altering drug metabolism and driving immunometabolic reprogramming, allowing tumor cells to evade immune attack. Immunometabolic reprogramming through gut microbiota modulation provides a new avenue to be explored that can restore anti-tumor immunity and reverse resistance to cancer treatments. This review also highlights the use of fecal microbiota transplantation and probiotics to mitigate chances of dysbiosis-related cancer progression. Through a comprehensive assessment of the role of gut microbiota in cancer, this review underscores the need for the use of gut microbial biomarkers for cancer detection and microbiome-targeting strategies to individualize cancer treatment.}, } @article {pmid40927374, year = {2025}, author = {Tan, S and Peng, C and Lin, X and Peng, C and Yang, Y and Liu, S and Huang, L and Bian, Y and Li, Y and Xu, C}, title = {Correction: Clinical efficacy of non-pharmacological treatment of functional constipation: a systematic review and network meta-analysis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1680092}, doi = {10.3389/fcimb.2025.1680092}, pmid = {40927374}, issn = {2235-2988}, abstract = {[This corrects the article DOI: 10.3389/fcimb.2025.1565801.].}, } @article {pmid40926100, year = {2025}, author = {Gibson, TE and Kim, Y and Acharya, S and Kaplan, DE and DiBenedetto, N and Lavin, R and Berger, B and Allegretti, JR and Bry, L and Gerber, GK}, title = {Learning ecosystem-scale dynamics from microbiome data with MDSINE2.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {40926100}, issn = {2058-5276}, support = {BRICS HR0011-15-C-0094//United States Department of Defense | Defense Advanced Research Projects Agency (DARPA)/ ; R01GM130777//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R35GM149270//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R35GM143056//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R21AI154075//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R35GM141861//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P30DK056338//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; MTM2 2025512//National Science Foundation (NSF)/ ; }, abstract = {Although dynamical systems models are a powerful tool for analysing microbial ecosystems, challenges in learning these models from complex microbiome datasets and interpreting their outputs limit use. We introduce the Microbial Dynamical Systems Inference Engine 2 (MDSINE2), a Bayesian method that learns compact and interpretable ecosystems-scale dynamical systems models from microbiome timeseries data. Microbial dynamics are modelled as stochastic processes driven by interaction modules, or groups of microbes with similar interaction structure and responses to perturbations, and additionally, noise characteristics of data are modelled. Our open-source software package provides multiple tools for interpreting learned models, including phylogeny/taxonomy of modules, and stability, interaction topology and keystoneness. To benchmark MDSINE2, we generated microbiome timeseries data from two murine cohorts that received faecal transplants from human donors and were then subjected to dietary and antibiotic perturbations. MDSINE2 outperforms state-of-the-art methods and identifies interaction modules that provide insights into ecosystems-scale interactions in the gut microbiome.}, } @article {pmid40925203, year = {2025}, author = {Kapoor, B and Gulati, M}, title = {Gut microbiome and rheumatoid arthritis: Revisiting the gut-joint axis.}, journal = {International immunopharmacology}, volume = {165}, number = {}, pages = {115503}, doi = {10.1016/j.intimp.2025.115503}, pmid = {40925203}, issn = {1878-1705}, abstract = {Over the past few decades, the scientific perspective on gut microbiota has undergone a profound transformation, particularly with the emergence and advancement of microbiome research. Next-generation sequencing technologies have emerged as a foundational tool in microbiome research, facilitating comprehensive characterization of microbial communities across diverse sample types and ecological niches. Significant alterations in gut microbiota composition have been observed in disease states compared to healthy individuals, suggesting a direct association between gut dysbiosis and host health status. Initially, alterations in gut microbiota were primarily thought to be associated with gastrointestinal disorders. With advancing research, however, it has become evident that gut dysbiosis is also implicated in a broad spectrum of extra-intestinal conditions, including neurological, dermatological, metabolic, and musculoskeletal diseases. The present review provides a comprehensive analysis of preclinical and clinical studies elucidating the role of gut dysbiosis in the pathogenesis and progression of rheumatoid arthritis. Advancements in the understanding of the gut-joint axis have facilitated the development of novel therapeutic modalities, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, that have been comprehensively discussed in present review.}, } @article {pmid40925130, year = {2025}, author = {Sahu, KK and Yadav, K and Pradhan, M and Sharma, M and Dubey, A and Sucheta, and Kirubakaran, JJ}, title = {Pharmacological insights into gut microbiota modulation in systemic lupus erythematosus: Mechanisms, treatment strategies, and clinical implications.}, journal = {The Journal of pharmacology and experimental therapeutics}, volume = {392}, number = {9}, pages = {103659}, doi = {10.1016/j.jpet.2025.103659}, pmid = {40925130}, issn = {1521-0103}, abstract = {Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by widespread inflammation and immune system dysregulation. Recent research suggests that the gut microbiota may play a role in the development of SLE by modulating immune system responses, affecting cytokine production, and altering the activity of T and B cells lymphocytes. As a result, there is a growing interest in microbiota-targeted therapies, including probiotics, dietary changes, and fecal microbiota transplantation. These methods may help restore the balance of microbes and reduce disease activity, but there are still a number of problems to solve. For example, microbiota composition varies greatly from person to person, and it is not clear how dysbiosis causes disease onset. There are also safety concerns about fecal microbiota transplantation. Experimental and clinical studies have started to shed light on the complicated ways in which microbial communities and immune function affect each other in SLE. These studies provide useful information, but their results are often inconsistent. As research continues, integrative methods like metagenomics and metabolomics may help find microbial signatures linked to disease, helping create more accurate and personalized treatments. The gut microbiome is a promising yet still developing area of research that could help us learn more about autoimmune diseases and their treatment, such as SLE. SIGNIFICANCE STATEMENT: Grasping the complex interplay between gut microbiota and systemic lupus erythematosus (SLE) has provided an avenue for therapeutic intervention. This study emphasizes the importance of gut dysbiosis in immune dysregulation, with connections between microbial translocation, molecular mimicry, and inflammatory pathways as contributing factors to the progression of SLE. This work sets the stage for novel and targeted approaches to treating SLE and improving patient outcomes by investigating microbiota-centric treatment options, such as probiotics, dietary interventions, and fecal microbiota transplantation.}, } @article {pmid40923448, year = {2025}, author = {He, MC and Ferrini, A and Parvizi, J}, title = {Periprosthetic joint infection: Time to think outside the box.}, journal = {Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA}, volume = {}, number = {}, pages = {}, doi = {10.1002/ksa.70056}, pmid = {40923448}, issn = {1433-7347}, abstract = {Despite undisputed success of orthopaedic procedures, surgical site infections (SSI) such as periprosthetic joint infection (PJI) continues to compromise the outcome and result in major clinical and economic burden. The overall rate of infection is expected to rise in the future resulting in significant associated mortality and morbidity. Traditional concepts have largely attributed the source of PJI to exogenous pathogens. However, recent studies indicate that pathogens from the patient's own microbiome, colonizing the skin, nasal passages, gut microbiota, and even the surgical site play a major role in causing SSIs. Immune cell-mediated 'Trojan Horse' pathways have been posited as the mechanism of how bacteria reach and persist at the surgical site. In light of these developing insights, novel therapeutic strategies are under investigation. Some exciting developments include the use of membrane-permeable antibiotics, bacteriophage therapy targeting intracellular pathogens as well as probiotics, prebiotics, or faecal microbiota transplantation. Overall, targeting the endogenous microbiome represents a promising frontier for improving the prevention and management of PJI in the era of rapidly increasing total joint arthroplasty procedures.}, } @article {pmid40920777, year = {2025}, author = {Nendl, A and Raju, SC and Braadland, PR and Nordborg, A and Bratseth, V and Broch, K and Jørgensen, SF and Aukrust, P and Kristiansen, K and Hov, JR and Trøseid, M and Awoyemi, A}, title = {Circulating metabolites in patients with chronic heart failure are not related to gut leakage or gut dysbiosis.}, journal = {PloS one}, volume = {20}, number = {9}, pages = {e0331692}, doi = {10.1371/journal.pone.0331692}, pmid = {40920777}, issn = {1932-6203}, mesh = {Humans ; *Dysbiosis/blood/microbiology/metabolism ; *Heart Failure/blood/microbiology/metabolism/physiopathology ; Male ; Female ; *Gastrointestinal Microbiome ; Middle Aged ; Aged ; Feces/microbiology ; Chronic Disease ; Case-Control Studies ; Metabolomics ; Metabolome ; }, abstract = {BACKGROUND: The gut microbiota produces numerous metabolites that can enter the circulation and exert effects outside the gut. Several studies have reported altered gut microbiota composition and circulating metabolites in patients with chronic heart failure (HF) compared to healthy controls. Limited data is available on the interplay between dysbiotic features of the gut microbiota and altered circulating metabolites in HF patients. We aimed to examine differences in circulating metabolites between people with and without chronic HF, and their association with gut microbiota dysbiosis and cardiac function.

METHODS: We collected plasma, serum, and stool samples from 123 adult patients with stable chronic HF and left ventricular ejection fraction (LVEF) ≤40%, and healthy controls (plasma: n = 51, stool samples: n = 69). Metabolomic and lipidomic profiling of plasma was performed using liquid chromatography with tandem mass spectrometry. Principal component analysis was used to explore differences in circulating profiles. Over-representation analysis was performed to identify pathways in which relevant metabolites were involved. Stool samples were sequenced using shotgun metagenomics. We calculated a dysbiosis index based on differential abundances of microbial taxa in patients vs. controls.

RESULTS: After adjusting for age, sex, and sampling location, we identified 67 enriched metabolites and 24 enriched lipids, and 115 depleted metabolites and 6 depleted lipids in HF patients compared to healthy controls. LVEF, N-terminal pro B-type natriuretic peptide, gut leakage markers, dysbiosis index, and fiber intake were not significantly related to any of the differentially abundant metabolites or lipids. Pathways related to energy metabolism differed most between HF patients and controls, however medication adjustment abolished all differences in circulating profiles.

CONCLUSIONS: Patients with chronic HF had distinct metabolomic and lipidomic profiles and energy metabolism differed significantly compared to healthy controls before adjusting for medication use. However, the alterations were not related to gut dysbiosis, gut leakage markers, cardiac function, or fiber intake.}, } @article {pmid40919202, year = {2025}, author = {Liu, W and Cheng, Y and Han, X and Xia, J and Wei, Q and Chang, B and Li, Q}, title = {Rivaroxaban alleviates hepatic sinusoidal obstruction syndrome in mice by modulating the gut microbiota and inhibiting the PI3K/Akt signaling pathway.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1607131}, pmid = {40919202}, issn = {1664-302X}, abstract = {INTRODUCTION: Hepatic sinusoidal obstruction syndrome (HSOS) is a vascular liver disease with a high mortality rate, and treatment methods are limited. Rivaroxaban is an oral anticoagulant. This study aimed to investigate the pharmacological effect and potential mechanism of rivaroxaban on HSOS.

METHODS: In this study, we induced an HSOS mouse model in male C57BL/6J mice by administering monocrotaline orally. The mice were randomly divided into four groups: the control group, the rivaroxaban (RIV) group, the monocrotaline (MCT) group, and the monocrotaline + rivaroxaban (MCT + RIV) group. Liver function and histopathology were evaluated. 16S rDNA sequencing of the small intestinal contents, transcriptomic sequencing of small intestine tissues, real-time qPCR, Western blot analysis of liver tissues, and correlation analysis were conducted. Antibiotic (ABX) treatment and fecal microbiota transplantation (FMT) experiments were also performed to explore the role of the gut microbiota.

RESULTS: Compared with the MCT group, rivaroxaban alleviated serum biochemical liver function analysis and liver histopathology in the MCT + RIV group. Additionally, 16S rDNA sequencing of the small intestinal contents revealed that, compared with the MCT group, the MCT + RIV group presented increased relative abundances of Allobaculum and Pediococcus but decreased relative abundances of Streptococcus, Staphylococcus, and Candidatus Arthromitus. Mechanistically, integrated analyses, including transcriptomic sequencing of small intestin e tissues, real-time qPCR, Western blot analysis of liver tissues, and correlation analysis, demonstrated that rivaroxaban protected against MCT-HSOS by inhibiting the PI3K/Akt signaling pathway. In addition, antimicrobial cocktail (ABX) treatment eliminated the beneficial effects of rivaroxaban on liver function and histopathological injury, whereas fecal microbiota transplantation (FMT) from rivaroxaban-treated donors significantly ameliorated liver dysfunction and histological damage in MCT-HSOS mice.

DISCUSSION: These findings suggest that rivaroxaban alleviates hepatic sinusoidal obstruction syndrome in mice by modulating the gut microbiota and inhibiting the PI3K/Akt signaling pathway. Rivaroxaban may be a promising therapeutic option for treating HSOS.}, } @article {pmid40917756, year = {2025}, author = {Vescovo, T and Bontempi, G and Bayat, M and Piredda, L and Fidaleo, M and Strippoli, R and Antonioli, M}, title = {Gut microbiota interplay with autophagy-EMT dynamics in colorectal cancer.}, journal = {Frontiers in cell and developmental biology}, volume = {13}, number = {}, pages = {1608248}, pmid = {40917756}, issn = {2296-634X}, abstract = {The human microbiota is composed of a complex community of microorganisms essential for maintaining host homeostasis, especially in the gastrointestinal tract. Emerging evidence suggests that dysbiosis is linked to various cancers, including colorectal cancer (CRC). The microbiota contributes to CRC development and progression by influencing inflammation, genotoxic stress, and key cell growth, proliferation, and differentiation pathways. Certain bacterial species, including Fusobacterium nucleatum and Escherichia coli, play a role in tumorigenesis by facilitating epithelial-mesenchymal transition (EMT), perturbing autophagy, and supporting immune evasion. In contrast, beneficial microorganisms such as Bifidobacterium and Lactobacillus provide protective effects by boosting immune surveillance and supporting the integrity of the intestinal barrier. This review examines the complex connection between gut microbiota and CRC, emphasizing how changes in microbial composition facilitate tumor development and influence treatment outcomes. We cover recent progress in microbiota-based biomarkers for CRC diagnosis and prognosis, showcasing their promise for early detection and improved patient stratification. Furthermore, we explore microbiota-focused therapeutic methods such as probiotics, prebiotics, faecal microbiota transplantation (FMT), and precision antibiotics, which show potential to complement standard CRC treatments. By highlighting the latest advancements in this area, we emphasise how microbiome research is transforming our comprehension of CRC and leading to new diagnostic and treatment approaches.}, } @article {pmid40916806, year = {2025}, author = {Javan, N and Ghotaslou, R and Samadi Kafil, H and Memar, MY and Sadeghi, J and Ghotaslou, P}, title = {Overcoming Multi-Drug-Resistant Klebsiella pneumoniae Infections.}, journal = {Microbial drug resistance (Larchmont, N.Y.)}, volume = {}, number = {}, pages = {}, doi = {10.1177/10766294251375937}, pmid = {40916806}, issn = {1931-8448}, abstract = {Antimicrobial resistance (AMR) is one of the most important concerns in the world, occurring for both Gram-positive and Gram-negative bacteria. Klebsiella pneumoniae (K. pneumoniae) is a Gram-negative bacterium belonging to the family of Enterobacteriaceae and also plays an important role in development of nosocomial infections. Three forms have emerged as a result of AMR including multi-drug resistant (MDR), extensively drug-resistant, and pan-drug-resistant. Nowadays, physicians cannot save most of the patients that suffer from MDR K. pneumoniae infections by typical antibiotics, so they should try other useful alternative treatments. Our aim in this review study was to search about the latest useful alternative methods against MDR K. pneumoniae infections. We collected some articles from PubMed, MEDLINE, and Google Scholar by the keywords of multi-drug-resistant K. pneumoniae, AMR, and alternative treatments, where finally 183 articles were selected. Also, inclusion criteria and exclusion criteria were identified separately. It was understood that there are novel therapeutic options against MDR K. pneumoniae infections, which include odilorhabdins, drug delivery systems, antibody drug conjugation treatments, nano-antibiotics, bacteriocins, probiotics, fecal transplant therapy, predatory bacteria, combined antibiotics, double-carbapenem therapy, synthetic lipopeptides, and phage therapy.}, } @article {pmid40916606, year = {2025}, author = {Piwchan, S and Aumpan, N and Chonprasertsuk, S and Pornthisarn, B and Siramolpiwat, S and Bhanthumkomol, P and Nunanan, P and Issariyakulkarn, N and Wongcha-Um, A and Miftahussurur, M and Mahachai, V and Yamaoka, Y and Vilaichone, RK}, title = {Fecal Microbiota Transplantation by Rectal Enema Improves Short-Term Insulin Resistance in Metabolic Syndrome: A Pilot Randomized Controlled Trial.}, journal = {Journal of obesity & metabolic syndrome}, volume = {}, number = {}, pages = {}, doi = {10.7570/jomes25014}, pmid = {40916606}, issn = {2508-7576}, abstract = {BACKGROUND: The gut microbiota plays a vital role in various physiological processes, including metabolism. Fecal microbiota transplantation (FMT) involves transferring fecal matter from a healthy donor to rebalance a patient's intestinal dysbiosis. The impact of FMT on metabolic syndrome (MetS) is subject to debate. This study assesses the effects of FMT on MetS when administered by rectal enema.

METHODS: In a double-blind, randomized controlled trial, subjects with MetS were assigned to receive either FMT (n=8) or a sham intervention (n=10) via rectal enema. Participants were followed at 6 and 12 weeks. The primary outcome was changes in the homeostatic model assessment of insulin resistance (HOMA-IR). Secondary outcomes included fasting blood glucose (FBG), body mass index (BMI), inflammatory markers, and hepatic steatosis. The mean adjusted difference (MAD) and 95% confidence interval (CI) between groups were reported as treatment effects using a linear marginal model for repeated measures.

RESULTS: The study included patients with a mean age of 50.4±10.7 years. Baseline BMI and HOMA-IR were similar between groups. Over 6 weeks, FMT significantly improved HOMA-IR (MAD, -1.63; 95% CI, -2.63 to -0.64; P=0.001). The FMT group also showed improvements in serum FBG and high-sensitivity C-reactive protein compared with levels in the sham group (P=0.044 and P=0.025, respectively). However, no significant changes in MetS-associated variables or liver steatosis were evident at 12 weeks. Stool microbiota analysis revealed a reduced relative abundance of Desulfovibrio, Bacteroides, and Parabacteroides after FMT.

CONCLUSION: FMT by rectal enema produced favorable changes in IR in patients with MetS. FMT may be an effective treatment for patients with metabolism-related diseases. Further research into the long-term benefits of the procedure is warranted.}, } @article {pmid40914633, year = {2025}, author = {Coman, T and Andreozzi, F and Bay, JO and Cornillon, J and Guillaume, T and Hamzy, F and Souchet, L and Turlure, P and Marçais, A and Dachy, F and Beguin, Y and Bulabois, CE and Daghri, S and Huynh, A and Magro, L and Chalandon, Y}, title = {[Acute graft-versus-host disease therapy: Which third line treatment after steroids and ruxolitinib? (SFGM-TC)].}, journal = {Bulletin du cancer}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bulcan.2025.05.014}, pmid = {40914633}, issn = {1769-6917}, abstract = {Acute graft-versus-host disease (GVHDa) is one of the leading causes of morbidity and mortality after allogeneic hematopoietic stem cell transplant (HSCT) patients. While the first-line consensus treatment has been based on systemic corticosteroid therapy for many years, ruxolitinib has recently been approved and has become the standard second-line treatment. Nevertheless, the effectiveness of ruxolitinib remains limited to 40 % of cortico-resistant patients, raising the crucial question of selecting a third-line treatment. Among the therapeutic modalities described, this workshop selected fecal microbiota transplantation (FMT), mesenchymal stromal cells (MSC) injection, and extracorporeal photopheresis (ECP) as the most promising or with a benefit/risk balance that favors their prescription at this stage. The workshop also highlighted the importance of research aimed at identifying markers or score calculations that guide toward a risk-adapted approach as early as possible. To date, aside from calprotectin, no marker or score is routinely used, but all are the subject of intense research. Finally, measures associated with specific treatment remain crucial, and new developments in dietary contributions, infection prophylaxis, and tissue regeneration are also addressed.}, } @article {pmid40913864, year = {2025}, author = {Xiang, X and Zhu, Y and Wang, T and Zhu, J and Ding, P and Cheng, K and Ming, Y}, title = {Gut microbiota and metabolites related intra-patient variability of tacrolimus pharmacokinetics predicted adverse one-year outcomes following kidney transplantation.}, journal = {International immunopharmacology}, volume = {165}, number = {}, pages = {115506}, doi = {10.1016/j.intimp.2025.115506}, pmid = {40913864}, issn = {1878-1705}, abstract = {Kidney transplantation (KT) is an effective treatment for end-stage renal disease, with over 90 % of recipients requiring lifelong tacrolimus (Tac). However, The Tac pharmacokinetics exhibit high intra-patient variability (IPV), posing significant challenges. This study included 102 KT recipients at our center from October 2022 to December 2023. Patients were stratified into high- and low-IPV groups based on the median coefficient of variation of the the Tac trough concentration-to-dose ratio during the first post-transplant month. Fecal samples were collected for 16S rRNA sequencing and untargeted metabolomics analysis, while clinical outcomes within the first year were assessed for associations with the Tac IPV. Microbiome analysis revealed significant beta diversity differences (p = 0.0451) and 19 differential taxa, including g__Clostridia_vadinBB60_group enriched in high-IPV patients and g__Clostridia_UCG_014 in the low-IPV group. Metabolomics identified 1298 differential metabolites, with 729 enriched in high-IPV patients. Network analysis highlighted cholesterol and unsaturated fatty acid biosynthesis as central pathways, while both microbial functional predictions and metabolic enrichment analyses emphasized bile secretion. A random forest model validated the classification potential of these biomarkers, and associations between differential taxa and metabolites were observed. Clinical correlation analysis indicated the high Tac IPV as an independent protective factor against post-transplant hyperuricemia but a positive predictor of new-onset diabetes. This study is the first to link the Tac IPV, gut microbiota, metabolism, and one-year outcomes, offering novel insights into personalized care and the mechanisms underlying the Tac IPV.}, } @article {pmid40913709, year = {2025}, author = {Jamal, A and Kamal, MA and Alqurashi, YE and Al-Malki, ES and Naiyer, MM and Hussain, SA and Hattiwale, HM}, title = {The microbiome-cancer axis as a hidden contributor to early-onset tumorigenesis.}, journal = {Medical oncology (Northwood, London, England)}, volume = {42}, number = {10}, pages = {464}, pmid = {40913709}, issn = {1559-131X}, mesh = {Humans ; *Neoplasms/microbiology ; *Carcinogenesis/pathology ; *Gastrointestinal Microbiome ; *Microbiota ; Dysbiosis/microbiology ; Age of Onset ; }, abstract = {The global incidence of early-onset cancer has surged by nearly 80% over the past three decades, yet the underlying causes remain poorly understood. While genetics and lifestyle are among the traditional risk factors, emerging evidence implicates the human microbiome as a potent and overlooked contributor to early tumorigenesis. Increases in the studies that are exploring the tissue-specific microbiome signatures such as the enrichment of Actinomyces and Bacteroidia in early-onset colorectal cancer, or Enterobacter and Neisseria in pancreatic tumors offer compelling evidence for age-stratified microbial contributions. Additionally, the recent works on the establishment of gut-testis, oral-gut, and gut-liver microbial axes are being explored to understand the modulation of systemic immune and endocrine landscapes in younger individuals that might unravel their unique predisposition to malignancy. Further, the microbiome-cancer axis has been regarded as a hidden driver in the initiation and progression of early-onset malignancies across diverse tissue types. Understanding this link will provide the missing mechanistic insights showcasing how microbial dysbiosis, biofilm formation, and microbially derived metabolites promote oncogenic inflammation, DNA damage, and immune evasion contributing to early-onset cancers. Considering the potential of these studies, microbial biomarkers with diagnostic promises that include probiotics, fecal microbiota transplantation, and diet have also been explored as emerging tools for prevention and therapy. Through this study, we aim to understand early-onset cancer through a patient microbiota and underscore an urgent need to integrate microbial dynamics into cancer surveillance and intervention strategies, especially for young and largely asymptomatic populations.}, } @article {pmid40913635, year = {2025}, author = {Ali, AQ and Mersal, EA and Samer, R and Alhjmohammad, SA and Alabdrabalridha, ZH and Alseeni, FY and Dawood, AF and Abdel All, MO and Abdelmoneim, AM and Shawky, TM}, title = {Berberine contributes to protecting against the cadmium-induced pancreatic damage: role of intestinal microbiome modulation and barrier function.}, journal = {Journal of molecular histology}, volume = {56}, number = {5}, pages = {296}, pmid = {40913635}, issn = {1567-2387}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Berberine/pharmacology ; *Cadmium/toxicity ; Rats ; Rats, Wistar ; Male ; *Pancreas/drug effects/pathology ; Intestinal Mucosa/drug effects/metabolism/microbiology ; *Protective Agents/pharmacology ; Disease Models, Animal ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Cadmium (Cad) is a worldwide heavy metal pollutant associated with global health challenges. Alteration of the intestinal microbiome, due to chemicals' exposure, plays a vital role in the pathogenesis of gastrointestinal diseases such as pancreatic disorders. Hence, modulation of the gut microbiota might be a targeted approach to manage pancreatic diseases. Using murine modeling, this study consisted of two dependent experiments to investigate the curative potential of berberine (BBR) in a Wistar rat model of Cad-provoked pancreatic toxicity and the possible contribution of gut microbiota to BBR protection. In experiment 1, Cad-induced pancreatic injury was established in rats via 8-week oral gavage of Cad at 4 mg/kg. The treatment group was exposed to BBR at 200 mg/kg body weight, oral gavage for 8 weeks. In experiment 2, transplantation of the fecal microbiome was done, in which the fecal microbiota in each group of experiment 1 was orally gavaged to the healthy rats of each corresponding group in experiment 2, once weekly for 8 weeks. The serum amylase and lipase levels, pancreatic inflammatory and oxidative markers, histological, and immunohistochemical analyses were evaluated. The markers of gut mucosal barrier, and mRNA expression of cell junction proteins were investigated for possible intestinal injury. 16S rRNA sequencing was applied to identify the gut bacterial changes and possible pancreatic bacterial translocation. Cad induced intestinal barrier disruption and elicited a state of pancreatic inflammation and apoptosis as indicated by TGF-β and BAX immunohistochemistry, which were relieved by BBR. A decreased firmicutes/bacteroidetes ratio and microbial migration due to interrupted intestinal mucosal barrier were reported. Furthermore, BBR restored the bacterial richness and proportions in the gut, thereby maintaining the intestinal microbial community, fixing the intestinal mucosal barrier structure, and inhibiting the pathway of bacterial migration. BBR protected against Cad-induced pancreatic damage, mostly through safeguarding the intestinal barrier function. Modulation of the intestinal bacterial community, repairing the gut barrier structure, and interference with the pancreatic bacterial migration and colonization were suggested BBR effects, potentially alleviating Cad-related pancreatic injury.}, } @article {pmid40912813, year = {2025}, author = {Yang, X and Li, S and Feng, Y and Guo, Y and Guo, Z and Hu, Y}, title = {A novel extracellular mannan from Bacillus velezensis ameliorates metabolic-associated fatty liver disease by modulating gut microbiota in mice model.}, journal = {Carbohydrate polymers}, volume = {368}, number = {Pt 1}, pages = {124150}, doi = {10.1016/j.carbpol.2025.124150}, pmid = {40912813}, issn = {1879-1344}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Bacillus/chemistry ; *Mannans/pharmacology/chemistry/isolation & purification/therapeutic use ; Mice ; Male ; Mice, Inbred C57BL ; Disease Models, Animal ; *Fatty Liver/drug therapy/metabolism ; Lipid Metabolism/drug effects ; Liver/drug effects/metabolism/pathology ; }, abstract = {Metabolic associated fatty liver disease (MAFLD) is a globally recognized chronic metabolic disorder characterized by lipid metabolism abnormalities. Accumulating evidence indicates that exopolysaccharides (EPS) could modulate the gut microbiota structure and function to prevent and treat MAFLD. Herein, a novel EPS designated BVP1 was isolated from Bacillus velezensis CGMCC 24752. Structural analysis revealed that BVP1 is a neutral α-mannan consisting of a backbone of 1,2,6-linked α-D-Manp, with branches composed of T-linked α-D-Manp, 1,2-linked α-D-Manp, and 1,3-linked α-D-Manp. Animal experiments showed that BVP1 significantly alleviated hepatic steatosis, liver injury and inflammation, and enhanced antioxidant activity in MAFLD mice. Single-nucleus RNA sequencing analysis revealed that BVP1 could restore HFD-induced imbalances in liver sinusoidal endothelial cells, hepatic stellate cells, macrophages and Kupffer cells by upregulating the expression of the lipid degradation gene Cps1 and downregulating the expression of the lipid synthesis gene Acsl1 in these cell subpopulations. Interestingly, BVP1 reshaped the gut microbiota and fecal metabolite profile by enriching beneficial bacteria and associated metabolites including salicylic acid, spermidine, and 4-hydroxyphenyl acetate. Fecal microbiota transplantation experiments verified that the anti-MAFLD effects are mediated by the BVP1-modified gut microbiota. Our findings highlight the potential of BVP1 as a promising therapeutic agent for MAFLD treatment.}, } @article {pmid40912415, year = {2025}, author = {Liu, X and He, J and Cui, L and Ye, Y and Luo, M and Xu, H and Zhai, Y and Zhao, Z and Huang, T and Li, Y and Wu, JL and Wen, J and Wang, Y and Zhou, T}, title = {Limosilactobacillus reuteri-Butyrate Axis in Depression Therapy: A Key Pathway Discovered Through a Novel Preclinical Human Flora-Associated Animal Model.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {107941}, doi = {10.1016/j.phrs.2025.107941}, pmid = {40912415}, issn = {1096-1186}, abstract = {The transition from preclinical to clinical drug development is critically impeded by interspecies disparities, which limit the predictive validity of preclinical efficacy for human outcomes. To address this limitation, we established a human flora-associated depression rat (HFADR) model through fecal microbiota transplantation (FMT). The HFADR model bridges the preclinical-clinical translation by recapitulating conserved microbial-host interactions identified through multi-omics analysis in a chronic unpredictable mild stress (CUMS) rat model and in patients with major depressive disorder. The HFADR model simulated the pathophysiological characteristics of clinical depression validated by gut-brain axis indices, including microbial composition, inflammatory biomarkers, brain-derived neurotrophic factor (BDNF), and monoamine neurotransmitters. Employing geniposide, a bioactive iridoid compound derived from medicinal plants, as a therapeutic prototype, the HFADR model revealed the novel Limosilactobacillus reuteri-butyrate axis as a conserved regulatory hub for the treatment of depression. Geniposide administration restored L. reuteri abundance in the HFADR model, which significantly correlated with improved gut-brain axis homeostasis. Metabolomics confirmed that L. reuteri exerts antidepressant effects via butyrate restoration in CUMS mice, with parallel butyrate level alterations observed in geniposide-treated HFADR model. Both L. reuteri supplementation and exogenous butyrate administration reversed depression-like behavior, mechanistically confirming the axis by reduced hippocampal astrocyte activation and elevated Nrf2 expression. This study established the HFADR model as a translational tool for evaluating microbiota-targeted therapies and identified the L. reuteri-butyrate axis as a novel therapeutic target. Our findings provide a theoretical and practical framework for refining preclinical models and advancing antidepressant development using microbiome-based strategies.}, } @article {pmid40912148, year = {2025}, author = {Gibril, BAA and Tu, X and Chai, X and Xu, J}, title = {Gut microbiota composition and dietary interventions modulate abdominal fat deposition in poultry: Mechanisms and applications.}, journal = {Poultry science}, volume = {104}, number = {11}, pages = {105754}, doi = {10.1016/j.psj.2025.105754}, pmid = {40912148}, issn = {1525-3171}, abstract = {Excessive abdominal fat deposition (AFD) in poultry reduces meat yield and efficiency. The gut microbiota regulates AFD through shifts in microbial composition and the production of metabolites. Reduced microbial diversity and fat-promoting taxa (e.g., Methanobrevibacter, Escherichia-Shigella) elevate AFD, while lean-linked bacteria (e.g., Bacteroides, Oscillospira) promote leanness. Dietary interventions, including botanical ingredients (e.g., honeycomb flavonoids elevating short-chain fatty acid producers), fermented feeds (e.g., cottonseed meal enriching butyrogenic taxa), probiotics (e.g., Lactobacillus johnsonii downregulating PPARγ/FAS), and additives (bile acids activating FXR/PPARα), modulate gut microbiota to reduce AFD by enhancing barrier function, suppressing pathogens, and regulating lipid metabolism. Fecal microbiota transplantation confirms microbiota-driven AFD reduction but faces donor-matching challenges. Breed-specific microbial signatures and context-dependent outcomes inform precision strategies to improve feed efficiency and lean yield.}, } @article {pmid40911227, year = {2025}, author = {Omar, TM and Alfarttoosi, KH and Sanghvi, G and Roopashree, R and Kashyap, A and Krithiga, T and Taher, WM and Alwan, M and Jawad, MJ and Al-Nuaimi, AMA}, title = {Engineering the Microbiome: a Novel Approach to Managing Autoimmune Diseases.}, journal = {Neuromolecular medicine}, volume = {27}, number = {1}, pages = {63}, pmid = {40911227}, issn = {1559-1174}, mesh = {Humans ; *Autoimmune Diseases/therapy/microbiology/immunology ; *Gastrointestinal Microbiome/immunology/genetics ; Animals ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Inflammatory Bowel Diseases/therapy/microbiology ; Immune Tolerance ; Multiple Sclerosis/therapy/microbiology ; }, abstract = {Autoimmune diseases occur when the immune system mistakenly attacks the body's own tissues, affecting millions of people and often requiring long-term treatment. Current therapies, such as immunosuppressants and biologics, help manage symptoms but can cause serious side effects. A promising new approach involves engineered microbiota-a method that modifies gut bacteria to influence immune function and potentially ease autoimmune conditions. The gut microbiome is crucial in regulating immunity, and imbalances in its composition have been linked to diseases, such as rheumatoid arthritis (RA), multiple sclerosis (MS), and inflammatory bowel disease (IBD). Engineered microbiota works by altering microbial communities, either by adding new strains, genetically modifying existing bacteria, or using carefully selected groups of microbes to control inflammation and immune responses. Recent studies in both animal models and human trials suggest this approach could help restore immune tolerance, reduce inflammation, and repair the gut barrier. However, challenges remain, including ensuring safety, long-term effectiveness, and meeting regulatory standards. Despite being in its early stages, engineered microbiota holds great promise as a future treatment for autoimmune diseases, paving the way for more precise and personalized therapies that leverage the power of the microbiome to improve health.}, } @article {pmid40911047, year = {2025}, author = {Che, Z and Xue, W and Zhao, X and Hu, C and Tian, Y}, title = {Regulatory Role and Biomarker Potential of Gut Microbiota Metabolites in the Progression of Metabolic dysfunction-associated steatotic liver disease (MASLD) to Hepatocellular Carcinoma (HCC).}, journal = {Clinical and translational gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ctg.0000000000000914}, pmid = {40911047}, issn = {2155-384X}, abstract = {Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. It is now updated as metabolic dysfunction-associated steatotic liver disease (MASLD). The progression of MASLD to hepatocellular carcinoma (HCC) involves complex mechanisms, with the gut microbiota and its metabolites playing a pivotal role in this transformation through the "gut-liver axis." This review systematically summarizes the characteristics of gut microbiota dysbiosis in NAFLD patients and the regulatory mechanisms of its metabolites (e.g., short-chain fatty acids [SCFAs], secondary bile acids, trimethylamine N-oxide [TMAO], and lipopolysaccharides [LPS]) in the progression from MASLD to HCC. SCFAs exert protective effects in the early stages by enhancing the intestinal barrier and modulating immune and metabolic responses. However, metabolic disturbances, such as the "paradoxical effect" of butyrate and the lipogenic effect of acetate, may promote the formation of a tumor microenvironment in the later stages. Secondary bile acids (e.g., deoxycholic acid) exacerbate liver fibrosis and carcinogenesis by activating inflammatory pathways (NF-κB, MAPK), inducing oxidative stress, and inhibiting foresaid X receptor (FXR) signaling. TMAO directly drives HCC progression by activating the MAPK/NF-κB pathway, promoting epithelial-mesenchymal transition (EMT), and creating an immunosuppressive microenvironment. LPS accelerates fibrosis and metabolic reprogramming through TLR4-mediated chronic inflammation and hepatic stellate cell activation. This review highlights that the dynamic changes in gut microbiota metabolites are closely associated with MASLD -HCC progression. Specific monitoring of these metabolites may serve as potential biomarkers for early detection. Furthermore, gut-targeted therapies (e.g., fecal microbiota transplantation) have shown translational potential. Future studies are needed to further validate their clinical value and develop precise prevention and treatment strategies.}, } @article {pmid40910235, year = {2025}, author = {Kaabi, YA}, title = {The Role of Gut Microbiota in Modulating Inflammation and Insulin Resistance in Type 2 Diabetes Mellitus: Implications for Complication Management.}, journal = {Current molecular medicine}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115665240393897250826074023}, pmid = {40910235}, issn = {1875-5666}, abstract = {Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and severe complications, including cardiovascular diseases, neuropathy, retinopathy, and nephropathy. This article examines the role of gut microbiota in modulating inflammation and insulin resistance in type 2 diabetes mellitus (T2DM), as well as its implications for managing complications associated with the disease. We analyzed published literature to elucidate mechanisms linking microbial dysbiosis, impaired gut barrier function, and chronic inflammation to glycemic control and T2DM complications. Key findings suggest that gut microbiota dysbiosis contributes to systemic inflammation and insulin resistance, thereby exacerbating the complications of type 2 diabetes mellitus (T2DM). Therapeutic strategies, such as probiotics, prebiotics, and fecal microbiota transplantation, promise to improve glycemic control and mitigate complications by restoring microbial balance. This review provides a comprehensive framework for understanding the role of the gut microbiota in type 2 diabetes mellitus (T2DM) and highlights potential therapeutic interventions to enhance the management of complications.}, } @article {pmid40909921, year = {2025}, author = {Shi, M and Wang, LF and Hu, WT and Liang, ZG}, title = {The gut microbiome in lung cancer: from pathogenesis to precision therapy.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1606684}, pmid = {40909921}, issn = {1664-302X}, abstract = {The gut microbiome has emerged as a key modulator of immune responses and treatment efficacy in oncology. Growing evidence links gut dysbiosis to resistance against immune checkpoint inhibitors (ICIs) in advanced cancers, prompting exploration of the gut-lung axis-a bidirectional network connecting intestinal microbiota with pulmonary health. Given lung cancer's status as the leading cause of cancer mortality worldwide, understanding this axis holds significant therapeutic potential. This review synthesizes current knowledge on gut microbiota's role in lung cancer development, diagnosis, and treatment. We highlight microbial signatures predictive of disease and therapy response, discuss microbiota-targeted interventions (e.g., probiotics, Fecal Microbiota Transplantation), and elucidate mechanistic insights into microbial-immune crosstalk. Finally, we outline future directions for leveraging the gut microbiome in personalized lung cancer management.}, } @article {pmid40909294, year = {2025}, author = {Zhou, L and Wu, Q and Jiang, L and Rao, J and Gao, J and Zhao, F and Wang, X}, title = {Role of the microbiota in inflammation-related related psychiatric disorders.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1613027}, pmid = {40909294}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Mental Disorders/microbiology/etiology/immunology/metabolism/therapy ; Animals ; *Inflammation/microbiology/immunology/metabolism ; Neuroimmunomodulation ; }, abstract = {The immune interactions within the gut-brain axis represent a critical etiological factor in psychiatric disorders. The gut microbiota and their metabolites serve as biological mediators that regulate neuroimmune activation and suppression in the central nervous system (CNS). During intestinal immune activation, pro-inflammatory cytokines (e.g., IL-6, TNF-α) propagate to the CNS via compromised blood-brain barrier (BBB) integrity or vagal afferent fibers, disrupting neurotransmitter metabolism and inducing microglial hyperactivation, thereby exacerbating neuroinflammation. Microglia, the principal immune sentinels of the CNS, adopt a pro-inflammatory phenotype upon peripheral inflammatory signaling characterized by morphological transformations, excessive chemokine/cytokine production (e.g., IL-1β, IL-6), and dysregulated neurotransmitter dynamics. These mechanisms are strongly implicated in neuropsychiatric conditions such as major depressive disorder, anxiety disorders, autism spectrum disorder, and schizophrenia. Emerging microbiota-targeted therapies, including probiotic interventions and fecal microbiota transplantation, demonstrate therapeutic potential by restoring tryptophan homeostasis and modulating systemic inflammation. This review synthesizes current evidence on the regulatory role of the gut microbiota in inflammation-related psychiatric disorders, specifically emphasizing the microbial modulation of neuroimmune crosstalk and neurotransmitter synthesis (e.g., serotonin, dopamine). Mechanistic insights into microbial metabolites, such as short-chain fatty acids and tryptophan derivatives, are critically evaluated for their dual roles in psychiatric disorders. These findings advance a unified framework for managing psychiatric comorbidities through precision modulation of the gut-brain axis.}, } @article {pmid40909137, year = {2025}, author = {Chen, K and Sun, L and Liu, Y and Chen, R}, title = {Safety and efficacy of fecal microbiota transplantation in the treatment of Parkinson's disease: a systematic review of clinical trials.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1639911}, pmid = {40909137}, issn = {1662-4548}, abstract = {INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disease with limited treatment options and increasing incidence. The Microbiota-Gut-Brain Axis (MGBA) offers new insights for PD treatment, as gut microbiota imbalances are linked to PD. Fecal microbiota transplantation (FMT) shows potential to improve gut dysbiosis and has gained attention for PD treatment.

METHODS: We conducted a review following PRISMA 2009 guidelines, searching PubMed, EMBASE, Web of Science, and Scopus up to December 1, 2024. We included clinical trials of FMT for PD patients, regardless of stage or type, with outcomes related to efficacy or safety. Non-clinical trials were excluded. Two investigators independently assessed studies, extracted data, and evaluated risk of bias and quality.

RESULTS: A total of 1,147 articles were retrieved, and six studies involving 104 patients were included. Four were randomized controlled trials, one was a cohort study, and one was a case series. Patients had a mean age of 63.2 years and disease duration of 5.6 years. After FMT, some patients showed improvements in UPDRS scores, H-Y grades, NMSS scores, and constipation symptoms, but results varied across studies. No serious FMT-related adverse events occurred. Most were mild gastrointestinal issues. Gut microbiota diversity and beneficial bacterial abundance changed after FMT, correlating with clinical outcomes. FMT materials were mostly from unrelated donors with diverse preparation and delivery methods.

DISCUSSION: FMT shows efficacy and safety in PD treatment but is insufficient as a standard due to study heterogeneity and small sample sizes. Future research needs larger samples, unified tools, and standardized FMT procedures. Combining FMT with other therapies may improve efficacy.}, } @article {pmid40909091, year = {2025}, author = {Vineesh, A and Shah, S and Shah, K and Zaigham Hassan, M and Sapkota, A and Khadka, SR and Rizwanullah, F and Dare Ibrahim, A and Kanduri Hanumantharayudu, S and Kumar Makam Surendraiah, P and Ahmed, B and Gyullu, N}, title = {Exploring the Relationship Between Gut Health and Autoimmune Diseases: A Systematic Review and Meta-Analysis.}, journal = {Cureus}, volume = {17}, number = {8}, pages = {e89300}, pmid = {40909091}, issn = {2168-8184}, abstract = {Autoimmune diseases (AIDs) are multifaceted, chronic illnesses characterized by immune dysregulation and systemic inflammation. Newer evidence has pointed a finger at the human gut microbiota, a trillion-fold population of microorganisms that inhabits the human GI tract, as a major influential modulator of immune reactivity and a significant contributor to autoimmune pathogenesis. This systematic review will seek to address how the literature correlates with systematic changes in the gut microbiota in AIDs as well as explore mechanistic associations with biological processes like intestinal permeability and modulation of the immune system, coupled with determining the effectiveness of microbiota-directed interventions. An extensive literature search was conducted in PubMed, Embase, Cochrane Central, and Web of Science, involving the availability of studies until May 2025. The eligible studies included observational studies, randomized controlled trials, and relevant mechanistic research regarding autoimmune diseases and alterations of the gut microbiome or administered interventions. Data extraction and risk of bias (ROB) assessments were performed by two independent reviewers, and a narrative synthesis with an illustrative meta-analysis was applied. Inclusion criteria were met by 10 studies, encompassing various autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), autoimmune thyroid diseases (AITDs), and psoriasis. Familiar patterns of microbiome dysbiosis were identified, such as a reduction in microbial diversity, increased intestinal permeability, and the expansion of pro-inflammatory species like Ruminococcus gnavus. Dietary interventions, fecal microbiota transplantation, and probiotics demonstrated positive effects on clinical outcomes and immune measures across multiple studies. The meta-analysis revealed that microbiota-directed interventions significantly improved disease activity and immune response markers in AIDs, indicating a robust link between gut microbiota composition and autoimmune pathology. In autoimmune disorders, gut microbiota is a key factor in immunopathology. Gut biology as an adjunct interventional strategy provides potential in managing these diseases. Additional studies are required to help standardize methods and identify microbial targets specific to diseases that can then be addressed through therapeutic interventions.}, } @article {pmid40908772, year = {2025}, author = {Faysal, M and Zehravi, M and Sutradhar, B and Al Amin, M and Shanmugarajan, TS and Arjun, UVNV and Ethiraj, S and Durairaj, A and Dayalan, G and Ahamad, SK and Rab, SO and Raman, K and Emran, TB}, title = {The Microbiota-Gut-Brain Connection: A New Horizon in Neurological and Neuropsychiatric Disorders.}, journal = {CNS neuroscience & therapeutics}, volume = {31}, number = {9}, pages = {e70593}, doi = {10.1111/cns.70593}, pmid = {40908772}, issn = {1755-5949}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Mental Disorders/microbiology/metabolism/therapy ; *Nervous System Diseases/microbiology/metabolism/therapy ; *Brain/metabolism ; Animals ; Dysbiosis ; *Brain-Gut Axis/physiology ; Probiotics ; }, abstract = {INTRODUCTION: The microbiota-gut-brain axis (MGBA), a complex two-way connection between the gut microbiota and the brain, has become a key regulator of neurological and neuropsychiatric disorders. Neurological disorders and gut microbiota dysbiosis are linked to these diseases. Changes in gut microbiota can lead to neurotransmitter imbalances, oxidative stress, and neuroinflammation. Gut dysbiosis may contribute to the development of diseases such as depression, autism, schizophrenia, bipolar disorder, Parkinson's disease, Alzheimer's disease, dementia, multiple sclerosis, epilepsy, anxiety, and autism spectrum disorders through immunological regulation, neuroinflammation, and neurotransmitter metabolism changes.

METHOD: This review systematically sourced articles related to microbiota gut brain axis, neurological disorders, neuropsychiatric disorders and clinical studies from major medical databases, including Scopus, PubMed, and Web of Science.

RESULTS: This review explores the molecular processes underlying MGBA interactions, including vagus nerve signaling, systemic immunological responses, and metabolites produced by microorganisms. The discussion explores the potential of microbiome-targeted treatments like fecal microbiota transplantation, probiotics, and prebiotics as effective treatment methods. The comprehension of the MGBA can revolutionize neurology and psychiatry, introducing innovative diagnostic and therapeutic approaches. Multiple elements, including diet, metabolism, age, stress, and medications, shape the human gut microbiota, and intestinal imbalances can lead to CNS diseases. The MGBA interacts with gut bacteria, and gut dysbiosis is associated with neurological disorders.

CONCLUSIONS: The review demonstrates the correlation between gut microbiota and neurologically associated diseases, highlighting its importance in neurogenesis, mental development, emotions, and behaviors. MGBA, mediated by microbial metabolites, affects brain function and neuroinflammation. Interventions like fetal microbiota transplantation, probiotics, and prebiotics can improve microbial balance, but more clinical research is needed.}, } @article {pmid40907403, year = {2025}, author = {Zhang, D and Wu, J and Feng, H and Tang, P and Zhou, Y and Zhao, C and Liu, J and Feng, W and Peng, C}, title = {Gastrodin ameliorates ulcerative colitis via modulating gut microbial tryptophan metabolism and AhR/NLRP3 pathway.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {147}, number = {}, pages = {157217}, doi = {10.1016/j.phymed.2025.157217}, pmid = {40907403}, issn = {1618-095X}, abstract = {BACKGROUND: Ulcerative colitis (UC), a chronic idiopathic inflammatory bowel disorder, presents persistent therapeutic challenges in clinical management. Gastrodin (GAS) is an active compound isolated from traditional Chinese medicine Gastrodia elata (Tianma), exhibits robust anti-inflammatory bioactivity. However, the role of GAS in UC has not been thoroughly studied.

PURPOSE: The study aimed to investigate the protective effect of GAS against UC induced by DSS and its underlying mechanisms, with a particular emphasis on gut microbiota-metabolite interactions.

METHODS: The ameliorative effect of GAS on UC was examined, followed by 16S rRNA sequencing, targeted metabolomics, MALDI-MSI analysis, and western blotting analysis, fecal microbiota transplantation (FMT) to investigate the underlying mechanism of GAS on UC.

RESULTS: Evaluation of symptoms showed that GAS exhibited dose-dependent beneficial effects on UC. Targeted metabolites showed that GAS increased the production of tryptophan-derived metabolites, including kynurenic acid (Kyna), indole-3-acetic acid (IAA), indole-3-carboxaldehyde (IAld), and indole-3-lactic acid (ILA), etc. MALDI-MSI confirmed that GAS increased the levels of aryl hydrocarbon receptor (AhR) ligands IAld and IAA in the colon tissue. Western blotting showed that GAS mitigated colon inflammation through the activation of the AhR/NOD-like receptor protein 3 (NLRP3) pathway. Finally, FMT confirmed that GAS ameliorates UC in a microbiota-dependent manner and the involvement of gut microbiota derived AhR ligands and AhR/NLRP3 pathway.

CONCLUSION: GAS alleviates UC via modulating gut microbiota-derived tryptophan metabolites (Kyna, IAA, IAld, ILA) in a microbiota-dependent manner and suppressing AhR/NLRP3 pathway. Our study has important practical implications for the application of traditional Chinese medicine-derived active ingredients in the treatment of UC.}, } @article {pmid40906320, year = {2025}, author = {Ilozumba, MN and Gomez, MF and Lin, T and Himbert, C and Round, JL and Zac Stephens, W and Warby, CA and Hardikar, S and Li, CI and Figueiredo, JC and Damerell, V and Fillmore, GC and Pickron, B and Toriola, AT and Shibata, D and Holowatyj, AN and Kahlert, C and Sankar, K and Siegel, EM and Jedrzkiewicz, J and Gigic, B and Byrd, DA and Ose, J and Ulrich, CM}, title = {Pre-surgery gut microbial diversity and abundance are associated with post-surgery onset of cachexia in colorectal cancer patients: the ColoCare Study.}, journal = {Cancer causes & control : CCC}, volume = {}, number = {}, pages = {}, pmid = {40906320}, issn = {1573-7225}, support = {U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; U01 CA206110, R01 CA189184, R01 CA207371, R01 CA211705, R01 CA254108//National Institutes of Health/ National Cancer Institute/ ; 01KD2101D//the German Ministry of Education and Research project PerMiCCion/ ; 01KD2101D//the German Ministry of Education and Research project PerMiCCion/ ; }, abstract = {BACKGROUND: Cachexia accounts for about 20% of all cancer-related deaths and it is indicative of poor prognosis and progressive functional impairment. The role of the gut microbiome in the development of cachexia in colorectal cancer (CRC) patients has not been established.

METHODS: Pre-surgical stool samples from n = 103 stage I-III CRC patients in the ColoCare Study were analyzed using 16S rRNA gene sequencing (Illumina) to characterize fecal bacteria. We calculated estimates of alpha- and beta-diversity and a priori- and exploratory-selected bacterial relative abundance. Using Fearon criteria, cachexia onset at 6 months post-surgery was defined as > 5% weight loss over the past 6 months and/or body mass index (BMI) of < 20 kg/m[2] and weight loss of > 2%. Associations of microbial metrics with cachexia onset were estimated using multivariable logistic regression models.

RESULTS: Higher alpha-diversity was positively associated with cachexia onset, with stronger associations in females, patients < 65 years, those receiving adjuvant treatment, consuming high fiber, or with energy intake outside USDA recommendations (p < 0.05). Porphyromonas (OR = 0.51, 95% CI 0.26-0.89, p = 0.03) and Actinomyces (OR = 0.72, 95% CI 0.48-1.03, p = 0.08) were inversely associated with cachexia, although the association for Actinomyces did not reach statistical significance. Stratified analyses revealed a stronger inverse association between Porphyromonas and cachexia onset in males, patients with rectal or stage III tumors, those receiving neoadjuvant treatment, physically inactive individuals, and those consuming low fiber. However, these associations did not reach statistical significance (0.05 ≤ p < 0.10).

CONCLUSION: Higher gut microbial alpha-diversity and lower relative abundances of the genera Porphyromonas and Actinomyces in pre-surgery stool samples were associated with onset of cachexia in CRC patients six months post-surgery. This is the first study to explore a link between the gut microbiome and cachexia in CRC patients, providing novel insights into the biology of cachexia and potential clinical interventions.}, } @article {pmid40906312, year = {2025}, author = {Arjmand, B and Badamchizadeh, S and Mehran, P and Sarvari, M and Alavi-Moghadam, S and Arjmand, R and Rezaei-Tavirani, M and Janbabaei, G and Vaezi, M and Larijani, B}, title = {Gut Microbiome and its Impact on Outcomes following Hematopoietic Stem Cell Transplantation: a Comprehensive Review.}, journal = {Stem cell reviews and reports}, volume = {}, number = {}, pages = {}, pmid = {40906312}, issn = {2629-3277}, abstract = {Hematopoietic stem cell transplantation is an important treatment for hematological malignancy and disorders, but is fraught with high risks, including graft-versus-host disease, infection, and relapse. Recent evidence now identifies that the microbiome plays a significant role in influencing transplant outcomes, in which microbial dysbiosis-defined by reduced diversity and pathogen overgrowth-is linked to greater complications and death. Microbiome manipulation with approaches including beneficial microbial species, fiber, fecal transplants, and diet has the potential to mitigate these risks. Experiments show that the restoration of beneficial microbes can restore immunity, reduce graft-versus-host disease severity, and reduce infection. Some challenges remain, including standardization of protocols, long-term efficacy, and safety in immunocompromised recipients. Future research will be focused on mechanisms, trials, and new technology for microbiome-based therapy, with the ultimate goal of improving survival and quality of life for transplant recipients. Hereupon, this review addresses how microbiome engineering can revolutionize cancer treatment by optimizing gut microbial communities for better outcomes in hematopoietic stem cell transplantation (HSCT).}, } @article {pmid40905977, year = {2025}, author = {Liu, Y and Gao, J and Chen, L and Chen, Y and Jiang, J and Chen, H and Ma, L}, title = {Lithocholic acid ameliorates ulcerative colitis via the PXR/TLR4/NF-κB/NLRP3 signaling pathway and gut microbiota modulation.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {82}, number = {1}, pages = {336}, pmid = {40905977}, issn = {1420-9071}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Colitis, Ulcerative/drug therapy/pathology/metabolism/microbiology/chemically induced ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Toll-Like Receptor 4/metabolism ; *Pregnane X Receptor/metabolism ; *Signal Transduction/drug effects ; *Lithocholic Acid/pharmacology/therapeutic use ; *NF-kappa B/metabolism ; Male ; Mice, Inbred C57BL ; Mice ; Dextran Sulfate ; Disease Models, Animal ; Humans ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory condition of the colon, closely linked to dysbiosis of gut microbiota and imbalances in bile acids. Lithocholic acid (LCA), a secondary bile acid, plays a crucial role in maintaining gut health; however, its specific therapeutic potential in UC remains to be fully elucidated. This study investigates the efficacy of LCA in alleviating UC and explores the underlying mechanisms, particularly focusing on the PXR/TLR4/NF-κB/NLRP3 signaling pathway and gut microbiota modulation. Using a dextran sulfate sodium (DSS)-induced colitis model, our findings demonstrate that LCA administration significantly alleviates colitis symptoms, evidenced by reduced disease activity index (DAI), increased colon length, improved intestinal barrier function, and decreased colonic inflammation. Mechanistically, LCA activates the pregnane X receptor (PXR), which inhibits TLR4-mediated NF-κB/NLRP3 inflammasome activation, leading to reduced colonic inflammation and lower levels of pro-inflammatory cytokines. Furthermore, LCA remodels gut microbiota by promoting beneficial bacterial growth, such as Akkermansiaceae, Lactobacillaceae and Muribaculaceae, while suppressing pathogenic and opportunistic pathogens, including Enterobacteriaceae and Bacteroidaceae. The gut microbiota-dependent effects of LCA were corroborated through antibiotic treatment and fecal microbiota transplantation (FMT) experiments. Notably, the absence of intestinal flora affected PXR expression and activity, modifying the aforementioned effects. Overall, our findings reveal that LCA ameliorates experimental colitis by regulating the PXR/TLR4/NF-κB/NLRP3 signaling cascade and modulating gut microbiota composition. This study underscores LCA's potential as a targeted therapeutic strategy and a promising microbiota-focused approach for managing UC, offering new insights into the role of bile acids in intestinal health and disease management.}, } @article {pmid40904889, year = {2025}, author = {Lv, J and Zhao, HP and Yu, Y and Wang, JH and Zhang, XJ and Guo, ZQ and Jiang, WY and Wang, K and Guo, L}, title = {From gut microbial ecology to lipid homeostasis: Decoding the role of gut microbiota in dyslipidemia pathogenesis and intervention.}, journal = {World journal of gastroenterology}, volume = {31}, number = {30}, pages = {108680}, pmid = {40904889}, issn = {2219-2840}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Dyslipidemias/microbiology/therapy/metabolism/etiology ; Homeostasis ; *Lipid Metabolism ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Prebiotics/administration & dosage ; Dysbiosis/microbiology/therapy ; }, abstract = {Dyslipidemia, a complex disorder characterized by systemic lipid profile abnormalities, affects more than half of adults globally and constitutes a major modifiable risk factor for atherosclerotic cardiovascular disease. Mounting evidence has established the gut microbiota (GM) as a pivotal metabolic modulator that is correlated with atherogenic lipid profiles through dietary biotransformation, immunometabolic regulation, and bioactive metabolite signaling. However, the host-microbe interactions that drive dyslipidemia pathogenesis involve complex gene-environment crosstalk spanning epigenetic modifications to circadian entrainment. Mechanistically, GM perturbations disrupt lipid homeostasis via lipopolysaccharide-triggered hepatic very low-density lipoprotein overproduction, short-chain fatty acid-G protein-coupled receptor 43/41-mediated adipocyte lipolysis, bile acid-farnesoid X receptor/Takeda G protein-coupled receptor 5 axis dysfunction altering cholesterol flux, microbial β-oxidation intermediates impairing mitochondrial energetics, and host-microbiota non-coding RNA crosstalk regulating lipogenic genes. This comprehensive review systematically examines three critical dimensions, including bidirectional GM-lipid axis interactions, molecular cascades bridging microbial ecology to metabolic dysfunction, and translational applications of GM modulation through precision probiotics, structure-specific prebiotics, and a metabolically optimized fecal microbiota transplantation protocol. Notwithstanding these advances, critical gaps persist in establishing causal microbial taxa-pathway relationships and optimal intervention timing. Future directions require longitudinal multi-omic studies, gnotobiotic models for mechanistic validation, and machine learning-driven personalized microbiota profiling. This synthesis provides a framework for developing microbiota-centric strategies targeting dyslipidemia pathophysiology, with implications for precision dyslipidemia management and next-generation cardiovascular disease prevention.}, } @article {pmid40904642, year = {2025}, author = {Sun, Q and Jiang, Z and Yang, L and Liu, H and Song, P and Yuan, L}, title = {Towards an Asian paradigm of inflammatory bowel disease management: A comparative review of China and Japan.}, journal = {Intractable & rare diseases research}, volume = {14}, number = {3}, pages = {192-202}, pmid = {40904642}, issn = {2186-3644}, abstract = {This systematic review compares inflammatory bowel disease (IBD) management between China and Japan across epidemiology, clinical strategies, health insurance, and social security policies. Epidemiologically, the incidence of IBD is rapidly increasing in China, contributing to a growing disease burden. In contrast, Japan has a stabilized incidence but a rising prevalence, driven by an aging patient population. Clinically, step-up therapy remains the mainstream approach in China, limited by regional and financial disparities in biologic access. In contrast, Japan, benefiting from the "Designated Intractable Diseases" program, favors early intensive therapy with a focus on mucosal healing. In the area of precision medicine, China is advancing rapidly in therapeutic drug monitoring (TDM) for anti-TNF agents. In contrast, Japan leads in AI-assisted endoscopic assessment, despite slower adoption of TDM. Japan's comprehensive insurance covers most costs of IBD; China has significantly reduced drug prices via national negotiations, and yet reimbursement rates vary regionally. China has made progress in telemedicine and standardized fecal microbiota transplantation (FMT); Japan excels in AI endoscopy and use of an elemental diet. To optimize IBD care in the Asia-Pacific, China should enhance access to advanced therapies, implement hierarchical diagnosis/ treatment, and develop multi-tiered insurance. Japan must address aging-related challenges and insurance sustainability while expanding use of TDM. Sino-Japanese collaboration in genetics, microbiome research, and AI-driven diagnostics, supported by sustained policy dialogue, is key to advancing precision IBD care and shaping a scalable "Asian model" for chronic disease management.}, } @article {pmid40904056, year = {2025}, author = {Dassanayake, P and Diksha, D and Varela-Mattatall, G and Sun, Q and Donnelly, SC and Suchy, M and Bartolome, D and Furlong, S and Deans, L and Biernaski, H and Huston, Y and Thompson, RT and Burton, JP and Moran, G and Gelman, N and Prato, FS and Kovacs, MS and Thiessen, JD and Goldhawk, DE and Schellenberg, J and Fox, MS}, title = {Biodistribution and dosimetry of [89]Zirconium-labeled microbiota transplants in the pig gut.}, journal = {Medical physics}, volume = {52}, number = {9}, pages = {e18087}, doi = {10.1002/mp.18087}, pmid = {40904056}, issn = {2473-4209}, mesh = {Animals ; *Zirconium/chemistry ; *Radioisotopes/chemistry ; Swine ; Tissue Distribution ; Radiometry ; Female ; Escherichia coli ; *Gastrointestinal Microbiome ; Positron-Emission Tomography ; Magnetic Resonance Imaging ; Isotope Labeling ; }, abstract = {BACKGROUND: The gastrointestinal (GI) microbiota, composed of diverse microbial communities, is essential for physiological processes, including immune modulation. Strains such as Escherichia coli Nissle 1917 support gut health by reducing inflammation and resisting pathogens. Microbial therapies using such strains may restore GI balance and offer alternatives to antibiotics, whose overuse contributes to antibiotic resistance. However, effective treatment will require optimizing delivery and understanding microbial dissemination and engraftment.

PURPOSE: We developed a method to monitor microbial migration and GI permeability post-ingestion using hybrid PET/MRI. To simulate probiotic therapy, bacteria were radiolabeled with [89]Zr, encapsulated, and administered to pigs. Organ level and whole-body dosimetry was determined from the time activity curves recorded over 7 days post ingestion.

METHODS: We administered [89]Zr-labeled Lactobacillus crispatus ATCC33820 (Gram-positive) to six female Duroc pigs (weight = 33.3 ± 4.6 kg) and E. coli Nissle 1917 (Gram-negative). Scans were performed between 6 h and 7 days post-ingestion using a hybrid PET/MRI system. The mean administered dose was 74.7 ± 12.9 MBq. Whole-body PET scans were acquired simultaneously with MRI using a T2-weighted HASTE sequence. Images were processed using 3D-Slicer co-registering PET with MRI and semi-automated organ segmentation was performed. Gender-averaged human equivalent organ-level effective doses (ED) and whole body ED were calculated using OLINDA.

RESULTS: PET imaging showed [89]Zr-labeled L. crispatus and E. coli post-ingestion localized primarily within the GI tract before excretion within feces. The highest mean ED for [89]Zr-labeled L. crispatus and E. coli were in the distal colon (26.8 ± 4.9 µSv/MBq and 28.4 ± 7.9 µSv/MBq, respectively) and proximal colon (17.9 ± 3.7 µSv/MBq and 18.4 ± 5.1 µSv/MBq, respectively). EDs in other organs were low. Whole body ED were 60.5 ± 9.5 µSv/MBq (L. crispatus) and 66.7 ± 14.9 µSv/MBq (E. coli).

CONCLUSIONS: The whole-body ED for L. crispatus and E. coli is lower than reported values for ingested tracers, such as that from [89]Zr labelled antibodies and [111]In labelled "meals" used to determine gut transit times. Hence ingestion of [89]Zr labelled bacteria shows promise for becoming a human nuclear-medicine procedure to determine the effectiveness of probiotic therapies.}, } @article {pmid40903950, year = {2025}, author = {Liu, Y and Tang, T and Cai, H and Liu, Z}, title = {Bidirectional communication between the gut microbiota and the central nervous system.}, journal = {Neural regeneration research}, volume = {}, number = {}, pages = {}, doi = {10.4103/NRR.NRR-D-25-00434}, pmid = {40903950}, issn = {1673-5374}, abstract = {In recent years, an increasing number of researchers have become interested in the bidirectional communication between the gut microbiota and the central nervous system. This communication occurs through the microbiota-gut-brain axis. As people age, the composition of the gut microbiota undergoes considerable changes, which are now known to play an important role in the development of many neurodegenerative diseases. This review aims to investigate the complex bidirectional signaling pathways between the gut and the brain. It summarizes the latest research findings on how the gut microbiota and its metabolites play critical roles in regulating inflammation, maintaining gut health, and influencing the development of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The review also analyzes the current clinical applications of gut microbiota-based treatments for neurological disorders, including fecal microbiota transplantation, probiotics, and prebiotics. Many studies show that the gut microbiota affects the brain in several ways. For example, it can produce substances such as short-chain fatty acids and activate inflammatory pathways. Studies involving animals and laboratory models have demonstrated that adjusting the gut microbiota can help improve behavior and reduce neurological problems. Recent metagenomic and metabolomics studies have shown that the microbiota plays a crucial role in maintaining the organism's health. Microorganisms primarily colonize the gut and are involved in host nutrient metabolism, maintaining the structural integrity of the intestine, preserving the intestinal mucosal barrier, and modulating the immune system. The gut microbiota communicates with the brain through a bidirectional microbiota-gut-brain axis. The composition of the gut flora changes considerably with age, and ecological dysregulation has been recognized as one of the twelve most recent hallmarks of aging. Recent studies have linked these changes to a variety of age-related neurological disorders, including Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, multiple sclerosis, and Huntington's disease. Specifically, the gut microbiota influences the brain through the production of key metabolites such as short-chain fatty acids and the activation of inflammatory and other relevant signaling pathways. In preclinical studies, targeted modulation of the gut microbiota, through methods such as fecal microbiota transplantation, probiotics, and prebiotics, has demonstrated potential in improving host behavioral outcomes. Therefore, gut microbiotabased treatments offer new hope for the treatment of nervous system diseases. However, due to the complexity of the gut microbiota and the potential adverse reactions associated with these therapies, researchers need to carefully assess their safety and efficacy before widespread clinical application.}, } @article {pmid40903035, year = {2025}, author = {Hou, Y and Wu, H and Zhang, Z and Wang, J and Chen, Q and Lian, C and He, D and Li, Z and Wei, W and Lin, X and Sun, D and Cao, B and Xu, T and Cai, M and Wang, G and Zhang, X and Duan, L and Hao, H and Zheng, X}, title = {Bacteroides intestinalis mediates the sensitivity to irinotecan toxicity via tryptophan catabolites.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2024-334699}, pmid = {40903035}, issn = {1468-3288}, abstract = {BACKGROUND: Late-onset diarrhoea remains a poorly managed concern for clinical irinotecan therapy. Although bacterial β-glucuronidases (β-GUS) mediated SN-38 production is prevailingly thought to mediate intestinal toxicity, β-GUS inhibitors confer limited benefits in the clinic.

OBJECTIVE: This study aimed to explore the role and mechanism of endogenous bacterial metabolites in susceptibility to irinotecan toxicity.

DESIGN: Gut microbiota profiles and metabolites in patients with colorectal cancer (CRC) with or without diarrhoea were investigated via 16S rRNA sequencing, shotgun metagenomics and metabolomics. The role of microbial metabolites was investigated in mice by metabolic bioengineering and intestinal organoid culture. The mechanism of microbial metabolites on intestinal stem cells was investigated by transcriptional profiling and chemical intervention.

RESULTS: Gut microbial configuration was differentially remodelled in diarrhoea and non-diarrhoea patients with irinotecan therapy, and the susceptibility was transmissible to recipient mice via transplantation of baseline faecal microbiome. Bacteroides intestinalis (B. intestinalis) was notably expanded in the diarrhoea-prone cohorts as well as in irinotecan-treated mice. B. intestinalis colonisation sensitised intestinal epithelia to irinotecan-induced chemical injury, partially via tryptophan metabolite indole-3-acetate (IAA). Both B. intestinalis and bioengineered bacteria that produce IAA exacerbated irinotecan-induced intestinal epithelial injury in mice. Mechanistically, IAA suppressed PI3K-Akt signalling, thereby impairing the renewal of intestinal epithelia under the insult of irinotecan. In clinical patients receiving irinotecan therapy, faecal IAA level was closely associated with the diarrhoea severity.

CONCLUSION: Our study uncovers the mechanism of endogenous bacterial metabolite in shaping the individual susceptibility to irinotecan toxicity and suggests IAA as a potential predictive biomarker.}, } @article {pmid40902967, year = {2025}, author = {Lu, Y and Liu, Y and Bai, X and Jiang, T and Chen, X and Wang, Y and Du, P and Sun, Y and Liu, C and Duan, J}, title = {Mechanisms of Podophyllotoxin-induced Enterotoxicity: A Multi-omics Integration of Gut Microbiota, Short-chain Fatty Acids, and Inflammatory Mediators.}, journal = {Toxicology}, volume = {}, number = {}, pages = {154274}, doi = {10.1016/j.tox.2025.154274}, pmid = {40902967}, issn = {1879-3185}, abstract = {Podophyllotoxin (PPT), a lignan extracted from the roots and stems of Podophyllum species, exhibits significant enterotoxicity that limits its clinical application. However, its underlying mechanisms remain unclear. This study aimed to elucidate the mechanisms underlying PPT-induced enterotoxicity. Changes in body weight, fecal morphology, toxic phenotypes, and histopathological features were evaluated. 3D reconstruction, 16S rRNA sequencing, targeted short-chain fatty acids (SCFAs) analysis, and inflammatory cytokine assays were performed. The findings demonstrated that PPT induced pathological changes in rats, including weight loss, diarrhea, and colonic damage. PPT administration significantly reduced beneficial bacteria such as Lactobacillus, while increasing harmful bacteria such as Escherichia-Shigella. The predicted pathways of bacterial invasion of epithelial cells and lipopolysaccharide biosynthesis were significantly upregulated. Levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were also increased. Additionally, the expression of undecaprenyl-diphosphate synthase (UPPS) and SCFAs production was reduced. These findings indicate that PPT may alter gut microbial composition, increase Escherichia-Shigella invasion in the intestinal epithelial cells, promote lipopolysaccharide production, enhance the release of pro-inflammatory cytokines, including TNF-α and IL-6, and inhibit UPPS expression and SCFAs generation, collectively contributing to enterotoxicity. This study provides novel insights into the mechanisms behind PPT-induced enterotoxicity, which is essential for preventing and treating PPT toxicity.}, } @article {pmid40902672, year = {2025}, author = {Sharma, S and Bashir, B and Kolekar, KA and Acharya, A and Gupta, M and Jena, R and Vishwas, S and Kaur, J and Gupta, G and Kumbhar, PS and Patle, D and Chaitanya, M and Gulati, M and Singh, SK}, title = {Tailoring the biomarkers of Alzheimer's disease using a gut microbiome-centric approach: Preclinical, clinical, and regulatory perspectives.}, journal = {Ageing research reviews}, volume = {}, number = {}, pages = {102888}, doi = {10.1016/j.arr.2025.102888}, pmid = {40902672}, issn = {1872-9649}, abstract = {Alzheimer's disease (AD), a progressive neurodegenerative disorder, poses significant therapeutic challenges due to its complex etiology and limited treatment options. Traditional pharmacotherapies targeting amyloid-β (Aβ) and cholinergic pathways offer modest benefits and are often associated with adverse effects. Emerging evidence implicates gut dysbiosis and the gut-brain axis in the pathogenesis and progression of AD. This review explores the multifactorial pathophysiology of AD and evaluates the therapeutic potential of gut-based interventions such as probiotics, prebiotics, synbiotics, metabiotics, postbiotics, and fecal microbiota transplantation (FMT) in mitigating disease pathology. Emphasis has also been given on role of miRNA released from FMT in management of AD. Preclinical and clinical studies demonstrate that these strategies can restore microbial homeostasis, reduce neuroinflammation, enhance gut barrier integrity, and improve cognitive outcomes. The regulatory aspects with use of probiotics based products and FMT is also highlighted. The modulation of neuroimmune, neuroendocrine, and neural pathways through microbiota-derived metabolites offers a promising avenue for AD management. Despite encouraging findings, further research is needed to address interindividual microbiome variability, delivery challenges, and the requirement for large-scale, randomized trials. Personalized gut-targeted approaches may open new horizons for the prevention and treatment of AD.}, } @article {pmid40901606, year = {2025}, author = {Al-Busafi, SA and Alwassief, A and Madian, A and Atalla, H and Alboraie, M and Elbahrawy, A and Eslam, M}, title = {Exploring the interplay between metabolic dysfunction-associated fatty liver disease and gut dysbiosis: Pathophysiology, clinical implications, and emerging therapies.}, journal = {World journal of hepatology}, volume = {17}, number = {8}, pages = {108730}, doi = {10.4254/wjh.v17.i8.108730}, pmid = {40901606}, issn = {1948-5182}, abstract = {Metabolic dysfunction-associated fatty liver disease (MAFLD) now affects roughly one-quarter of the world's population, reflecting the global spread of obesity and insulin resistance. Reframing non-alcoholic fatty liver disease as MAFLD emphasizes its metabolic roots and spotlights the gut-liver axis, where intestinal dysbiosis acts as a key driver of hepatic injury. Altered microbial communities disrupt epithelial integrity, promote bacterial translocation, and trigger endotoxin-mediated inflammation that accelerates steatosis, lipotoxicity, and fibrogenesis. Concurrent shifts in bile acid signaling and short-chain fatty acid profiles further impair glucose and lipid homeostasis, amplifying cardiometabolic risk. Epidemiological studies reveal pervasive dysbiosis in MAFLD cohorts, linked to diet quality, sedentary behavior, adiposity, and host genetics. Newly developed microbiome-derived biomarkers, advanced elastography, and integrated multi-omics panels hold promise for non-invasive diagnosis and stratification, although external validation remains limited. In early trials, interventions that re-engineer the microbiota including tailored pre-/pro-/synbiotics, rational diet patterns, next-generation fecal microbiota transplantation, and bile-acid-modulating drugs show encouraging histological and metabolic gains. Optimal care will likely couple these tools with weight-centered lifestyle programmes in a precision-medicine framework. Key challenges include inter-ethnic variability in microbiome signatures, the absence of consensus treatment algorithms, and regulatory barriers to live biotherapeutics. Rigorous longitudinal studies are required to translate mechanistic insight into durable clinical benefit and improve patient-centered outcome measures.}, } @article {pmid40901203, year = {2025}, author = {Elendu, C and Omeludike, EK and Aregbesola, ET and Mordi, P and Blewusi, GS and Ogidan, AO and Okeke, NG and Obidigbo, BT and Asini, AO and Ubi, ES and Etakewen, PO and Amahalu, CA and Foncham, RF and Gana, LT and Onwe, CJ and Ojeabuo, OF and Ojo, AO and Ikeaba, CS and Opara, NC}, title = {Fecal microbiota transplantation as a therapeutic modality for recurrent Clostridioides difficile infection: reviewing efficacy, safety, mechanisms of action, and outcomes.}, journal = {Annals of medicine and surgery (2012)}, volume = {87}, number = {9}, pages = {5829-5850}, doi = {10.1097/MS9.0000000000003649}, pmid = {40901203}, issn = {2049-0801}, abstract = {Recurrent Clostridioides difficile infection (rCDI) remains a significant global health challenge, characterized by high morbidity, substantial healthcare costs, and an increased risk of severe complications. C. difficile, a gram-positive, spore-forming bacterium, is the primary cause of healthcare-associated diarrhea. The pathogenesis of rCDI is closely tied to gut microbiota disruptions, often triggered by antibiotic use, immunosuppression, and prolonged hospital stays. While effective for initial episodes, standard antibiotic therapies paradoxically exacerbate microbiota dysbiosis, increasing the risk of recurrence. Approximately 20%-30% of patients experience a recurrence after the initial episode, with rates rising to 45%-65% in those with multiple episodes. Fecal microbiota transplantation (FMT) has arrived as a transformative therapy for rCDI, leveraging donor microbiota to restore gut homeostasis and suppress C. difficile colonization. Clinical trials consistently report success rates exceeding 80%, markedly surpassing outcomes with antibiotics. Innovations in delivery methods, including oral capsules, have enhanced FMT's accessibility and patient acceptability. However, concerns surrounding safety and standardization persist. Adverse events, such as gastrointestinal discomfort and rare cases of multidrug-resistant organism transmission, underscore the need for stringent donor screening protocols. Emerging evidence reveals complex mechanisms underpinning FMT's efficacy, including restoring microbial diversity, bile acid metabolism, and short-chain fatty acid production. Long-term benefits, such as sustained microbiota stability, and potential applications in other conditions, including inflammatory bowel disease and metabolic disorders, are promising but require further validation. Addressing challenges in donor selection, regulatory oversight, and personalized approaches will be critical to optimizing FMT as a safe and effective therapeutic strategy for rCDI.}, } @article {pmid40901024, year = {2025}, author = {Chen, N and Li, L and Han, Y and Chen, Z}, title = {The Role of Gut Microbiota in the Modulation of Pulmonary Immune Response to Viral Infection Through the Gut-Lung Axis.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {11755-11781}, doi = {10.2147/JIR.S525880}, pmid = {40901024}, issn = {1178-7031}, abstract = {Viral respiratory infections, including influenza, respiratory syncytial virus (RSV), and SARS-CoV-2, remain major global health challenges due to their high morbidity and mortality. Emerging evidence highlights the pivotal role of the gut-lung axis in regulating pulmonary immunity. The gut microbiota communicates with the lungs via endocrine, immune, and neuroimmune pathways-particularly through metabolites such as short-chain fatty acids (SCFAs) and vagus nerve-mediated signaling-which modulate immune cells including alveolar macrophages and dendritic cells. Disruption of gut microbial balance has been linked to impaired pulmonary immune responses and increased susceptibility to infection. This review synthesizes findings from animal models and clinical studies, demonstrating that interventions such as probiotics (eg, Lactobacillus gasseri), prebiotics (eg, galacto-oligosaccharides), fecal microbiota transplantation (FMT), and Traditional Chinese Medicine (eg, Astragalus, curcumin) can enhance antiviral cytokine production, restore gut-lung homeostasis, and reduce lung inflammation. For example, FMT from H7N9-survivor mice improved influenza resistance in recipients, and oral probiotics reduced respiratory failure risk in COVID-19 patients. These findings suggest that gut-lung axis modulation is a promising adjunctive approach for treating viral respiratory infections. Future research should prioritize personalized microbiome-based therapies and large-scale clinical trials to validate efficacy and safety.}, } @article {pmid40900873, year = {2025}, author = {Hafez, MM and Bahcecioglu, IH and Yalniz, M and Kouta, KA and Tawheed, A}, title = {Future of inflammatory bowel disease treatment: A review of novel treatments beyond guidelines.}, journal = {World journal of methodology}, volume = {15}, number = {4}, pages = {107643}, doi = {10.5662/wjm.v15.i4.107643}, pmid = {40900873}, issn = {2222-0682}, abstract = {Inflammatory bowel disease (IBD) is a chronic condition consisting of two main types: Crohn's disease and ulcerative colitis. Conventional treatments for these diseases include aminosalicylates, corticosteroids, immunomodulators, and biologics. However, these treatments have several drawbacks, including high costs for patients and numerous side effects. Recently, advanced treatments have been developed, such as small-molecule therapies, targeted biologics, innovative drug delivery systems, and microbiome-based interventions. Emerging therapies like anti-interleukin-23 monoclonal antibody inhibitors, sphingosine-1-phosphate receptor modulators, and Janus kinase inhibitors are more specialized in reducing immune activity. They enhance bioavailability, reduce side effects, and specifically target the gastrointestinal tract without affecting other systems. Innovative drug delivery systems for IBD, such as nanoparticles, hydrogels, and microgrippers, improve bioavailability and prolong drug release. The combination of conventional and advanced therapies may benefit from the synergistic effects of both. Furthermore, fecal microbiota transplantation and probiotics can help restore the balance of gastrointestinal microbiota, reducing disease flare-ups. Advances in artificial intelligence, endoscopic techniques, and stem cell therapies have shown great potential in treating IBD, although several significant challenges remain. Treating this disease requires multidisciplinary integration and the application of technology and telemedicine.}, } @article {pmid40900872, year = {2025}, author = {Singh, JP and Aleissa, M and Chitragari, G and Drelichman, ER and Mittal, VK and Bhullar, JS}, title = {Uncovering the role of microbiota and fecal microbiota transplantation in Crohn's disease: Current advances and future hurdles.}, journal = {World journal of methodology}, volume = {15}, number = {4}, pages = {106148}, doi = {10.5662/wjm.v15.i4.106148}, pmid = {40900872}, issn = {2222-0682}, abstract = {Crohn's disease (CD) is an idiopathic, chronic, and recurrent inflammatory condition of the gastrointestinal tract. Recent studies suggest a potential role of gut microbiota in CD, particularly dysbiosis-an imbalance in gut bacteria. While dysbiosis is consistently observed in CD, it remains uncertain whether it is a cause or a consequence of the disease. Given its association with CD, the therapeutic potential of fecal microbiota transplantation (FMT) has been explored. This review examines the role of gut microbiota in CD, evaluates the therapeutic potential of probiotics and FMT, and highlights current research findings and limitations. Key studies on the relationship between gut dysbiosis, probiotics, and FMT in CD were analyzed, with a focus on randomized trials, meta-analyses, and clinical observations. Dysbiosis is a consistent feature of CD, but its causative role remains unclear. Probiotics, prebiotics, and synbiotics have shown no efficacy in inducing or maintaining remission in CD. FMT shows potential as a therapeutic option for CD, but its efficacy remains inconsistent and inconclusive. The variability in outcomes, including diminished effects over time despite repeated FMT, underscores the need for larger, well-controlled trials. Only one randomized controlled trial (RCT) has compared FMT with sham transplantation, but the sample size was very small. Other studies are limited by factors such as small sample sizes, lack of control groups, short follow-up periods, and inconsistent methodologies, making it challenging to draw definitive conclusions. While gut dysbiosis likely plays a role in CD pathogenesis, its causative role remains uncertain. Current evidence does not support FMT as a reliable treatment for inducing or maintaining remission in CD, though it appears generally safe. Larger, standardized, RCTs are necessary to clarify the therapeutic role of FMT in CD management.}, } @article {pmid40900041, year = {2025}, author = {Xue, M and Zhang, X and Zhou, Y and Yan, J and Gao, H and Bai, Y and Shi, J and Liu, Y and Xu, Y and Zhang, N and Li, L and Shi, S and Liang, H}, title = {Sulfated Fucooligosaccharides Ameliorated Neuroinflammation in D-Galactose-Induced Aging Model Mice via the Gut-Brain Axis.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c08350}, pmid = {40900041}, issn = {1520-5118}, abstract = {This study was aimed to reveal the neuroprotective effect of sulfated fucooligosaccharides (FOS) in an aging mouse model induced by d-galactose. The results showed that FOS treatment ameliorated inflammation, improved behavioral decline in memory and cognition, and exerted neuroprotective effects. FOS reduced microglia activation by decreasing the expression of P38 mitogen-activated protein kinase (P38 MAPK), cyclic-AMP response binding protein (CREB), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). In addition, FOS improved intestinal mucosal barrier damage and reduced the release of lipopolysaccharide. FOS increased the diversity of the gut flora and promoted a significant enrichment of the Akkermansia genus. FOS also increased the butyric acid level and reduced the expression of histone deacetylase 3 (HDAC3), Toll-like receptor 4 (TLR4), and nuclear factor kappa-B (NF-κB). Fecal microbiota transplantation from the FOS-treated mice showed a similar effect to FOS treatment in inhibiting neuroinflammation and reduced d-galactose-induced cognitive dysfunction. The results suggested that FOS supplementation ameliorated d-galactose-induced neuron damage and exerted neuroprotective effects through the gut-brain axis.}, } @article {pmid40899744, year = {2025}, author = {Jin, JY and Yang, XY and Feng, R and Ye, ML and Xu, H and Wang, JY and Hu, JC and Zuo, HT and Lu, JY and Song, JY and Zhao, Y and Wang, Y and Tong, Q}, title = {Gut Microbiota-Derived Metabolites Orchestrate Metabolic Reprogramming in Diabetic Cardiomyopathy: Mechanisms and Therapeutic Frontiers.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {39}, number = {17}, pages = {e71004}, pmid = {40899744}, issn = {1530-6860}, support = {2022YFA0806400//the National Key R&D Program of China/ ; 2022YFC3601305//the National Key R&D Program of China/ ; 2021-I2M-1-028//the CAMS Innovation Fund for Medical Sciences/ ; 2021-I2M-1-027//the CAMS Innovation Fund for Medical Sciences/ ; 2023-I2M-2-006//the CAMS Innovation Fund for Medical Sciences/ ; 82173888//the National Natural Science Foundation of China/ ; 81973290//the National Natural Science Foundation of China/ ; Z141102004414062//the Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; *Diabetic Cardiomyopathies/metabolism/microbiology/therapy ; Energy Metabolism ; Oxidative Stress ; Metabolic Reprogramming ; }, abstract = {Diabetic cardiomyopathy (DCM) is a major cardiovascular complication of diabetes mellitus, characterized by myocardial structural and functional abnormalities in the absence of overt coronary artery disease or hypertension. A growing body of evidence implicates the gut microbiota and its metabolites as key modulators of systemic metabolic homeostasis, influencing energy metabolism, inflammation, and oxidative stress. The gut microbiota emerges as a novel regulator of cardiac remodeling and metabolic reprogramming in DCM through the gut-heart axis. This review aims to synthesize current mechanistic insights into how gut microbiota and its bioactive metabolites contribute to metabolic reprogramming in DCM. It further evaluates the potential of microbiota-targeted interventions as emerging therapeutic strategies to mitigate disease progression and restore cardiac homeostasis. A narrative, mechanistically focused literature review was conducted using PubMed and Web of Science databases. It covered experimental, preclinical, and translational studies up to April 2025. Articles were selected based on relevance to gut microbial metabolism, host cardiac metabolic pathways, and therapeutic interventions linked to DCM. Gut microbiota-derived metabolites-including short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), bile acids, lipopolysaccharides (LPS), tryptophan catabolites, and hydrogen sulfide-modulate cardiometabolic pathways via epigenetic regulation, altered energy substrate utilization, inflammatory signaling, and mitochondrial oxidative stress. These metabolites influence insulin resistance, lipid accumulation, mitochondrial dynamics, and cardiac fibrosis. Therapeutic strategies such as dietary modulation, probiotics, prebiotics, fecal microbiota transplantation, and drugs like SGLT2 inhibitors and GLP-1 receptor agonists have shown promising effects in modulating gut microbiota composition and alleviating DCM phenotypes in animal models. However, clinical evidence remains limited. The gut microbiota plays a pivotal role in the pathogenesis and potential treatment of DCM through its ability to reprogram host metabolism and inflammation. While preclinical data are compelling, further translational research-including humanized models and multi-omics integration-is required to validate microbiota-targeted therapies for cardiovascular applications. Targeting the microbiota-metabolite axis offers an innovative therapeutic avenue for personalized intervention in diabetic heart disease.}, } @article {pmid40899722, year = {2025}, author = {Shi, X and Wan, L and Ni, S and Wu, X and Mu, J and Pei, W and Chen, Z and Xia, Y and Li, L and Zhang, Z}, title = {Chronic Exposure to Sunset Yellow Promotes Susceptibility to Experimental Colitis in Mice through Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c06410}, pmid = {40899722}, issn = {1520-5118}, abstract = {Sunset yellow (SY) is a widely used food additive. However, its impacts on ulcerative colitis (UC) development remain unclear. Here, SY exposure exacerbated dextran sulfate sodium (DSS)-induced UC symptoms in mice, including body weight loss, elevated disease activity index, histological damage, inflammation, gut barrier impairment, disruption of gut microbiota composition, and sulfur metabolism. Moreover, fecal microbiota transplantation from SY-exposed mice also exacerbated colitis in the recipient mice. Notably, SY exposure both in vivo and in vitro inhibited the growth of Akkermansia muciniphila (AKK). Nontargeted metabolomics revealed that SY exposure impaired glutathione (GSH) metabolism, as evidenced by reduced GSH and glutathione disulfide levels in both normal and colitis mice. In AKK, SY exposure significantly decreased GSH content, suppressed glutathione S-transferase activity, and disrupted sulfur metabolism. Importantly, GSH supplementation markedly reversed the SY-induced AKK growth inhibition. Collectively, these findings suggest that long-term SY exposure promotes experimental colitis in mice through gut microbiota-dependent GSH metabolic dysregulation.}, } @article {pmid40899693, year = {2025}, author = {Bo, T and Xu, X and Liu, H and Tang, L and Xu, H and Zhao, S and Lv, J and Wang, D}, title = {Convergent gut microbial functional strategies drive energy metabolism adaptation across Ursidae species and challenge the uniqueness of giant panda.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ismejo/wraf201}, pmid = {40899693}, issn = {1751-7370}, abstract = {The gut microbiota is a key regulator of host energy metabolism, but its role in seasonal adaptation and evolution of bears is still unclear. Although giant pandas are considered an extraordinary member of the Ursidae family due to their specialized herbivory and low metabolic rate, there is still controversy over whether the metabolic regulation mechanism of their gut microbiota is unique. This study analyzed the seasonal dynamics of gut microbiota in giant pandas (Ailuropoda melanoleuca), Asian black bears (Ursus thibetanus), brown bears (Ursus arctos), and polar bears (Ursus maritimus), and combined with fecal microbiota transplantation (FMT) experiments, revealed the following findings. The microbial composition of the four bear species is similar, with both Firmicutes and Proteobacteria dominating. The enrichment of Firmicutes in winter enhances lipid metabolism, and adapts to dietary differences, indicating the existence of convergent microbial functional strategies in the Ursidae family. Our results demonstrate that bear gut microbiota promoted seasonal adaptation. In FMT experiments, bear gut microbiota in winter may had stronger functional capabilities on regulating host energy metabolism in mice, and regulate host appetite to increase energy intake. Finally, despite feeding on bamboo, giant pandas microbiota driven energy metabolism pathways (such as SCFAs) are highly conserved compared to other bears, suggesting a deep commonality in the adaptability of bear microbiota in evolution. Therefore, this study challenges the traditional view of microbial uniqueness of giant pandas, and emphasizes the co-evolutionary mechanism of energy metabolism adaptation in bear animals through microbial plasticity. In the future, it is necessary to integrate wild samples to eliminate the interference of captive diet and further analyze the genetic basis of host gut microbiota interactions.}, } @article {pmid40541100, year = {2025}, author = {Tang, X and Mao, M and Zhang, X and Gao, H and Wang, Z and Fang, R and Cheng, HW and Jiang, S}, title = {Cecal microbiota transplantation enhances calcium retention through modulation of gut microbiota and intestinal calcium transporter gene expression in chicks.}, journal = {Poultry science}, volume = {104}, number = {9}, pages = {105437}, pmid = {40541100}, issn = {1525-3171}, mesh = {Animals ; *Chickens/microbiology/genetics/metabolism/growth & development/physiology ; *Gastrointestinal Microbiome/physiology ; Cecum/microbiology ; Female ; *Fecal Microbiota Transplantation/veterinary ; *Avian Proteins/metabolism/genetics ; Random Allocation ; *Gene Expression ; *Calcium/metabolism ; }, abstract = {Bone development during early life is crucial for maintaining skeletal health and productivity in laying hens. The aim of this study was to investigate the effects of transferring cecal bacterial material of healthy adult hens on growth performance, gut integrity, microbial development, and bone metabolism of recipient chicks. Cecal contents were collected from 12 healthy Lohmann Pink-shell laying hens aged 47 weeks (donors). A total of 120 1-day-old Lohmann Pink chicks (recipients) were randomly assigned to 2 treatments for a 34-day trial: CONT (0.1 mL saline, Control) and CMT (0.1 mL cecal microbial solution). Each group had 10 replicates and 6 chicks per replicate. The pooled cecal sample as well as saline was administered via oral gavage once daily from day 1 to day 10, and then boosted on days 16, 23, and 30. One bird from each replicate was randomly taken for sample collection at day 34 (n=10). The results showed that CMT chicks had significantly higher Ca and P retention rates than CONT chicks. The mRNA expressions of intestinal Ca transporters, CaBP-D28K and VDR in the ileum and NCX1 in the jejunum, were also upregulated in CMT chicks. Additionally, the mRNA expression of a tight junction protein, ZO-1, was upregulated in the duodenum of CMT chicks. CMT chicks also had higher mRNA expressions of pro-inflammatory cytokines, IL-6, IL-1β, and TNF-α, in the intestinal tract. Furthermore, CMT chicks had a more diverse and mature gut microbial community compared to CONT chicks. The relative abundances of SCFA-produced bacteria (e.g., Bacteroides, Rikenellaceae_RC9_gut_group, and Prevotellaceae_UCG-001) were increased, while the relative abundances of Alistipes, Lactobacillus, and Barnesiella were reduced in CMT chicks. However, there were no CMT effects on body weight, organ indexes, bone morphology, and gene expression-associated with bone metabolism. This study demonstrates that transferring cecal bacteria from adult laying hens enhances calcium absorption and retention in newly hatched chicks by upregulating key calcium transporters and enhancing intestinal barrier integrity via modulating the gut microbiome.}, } @article {pmid40898211, year = {2025}, author = {Ma, X and Shi, W and Wang, Z and Li, S and Ma, R and Zhu, W and Wu, L and Feng, X and Cong, B and Li, Y}, title = {Butyric acid and valeric acid attenuate stress-induced ferroptosis and depressive-like behaviors by suppressing hippocampal neuroinflammation.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {974}, pmid = {40898211}, issn = {1479-5876}, support = {82130055//Key Projects of the National Natural Science Foundation of China/ ; 82293651//Major Projects of the National Natural Science Foundation of China/ ; 82072109//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Depression is closely associated with stress-induced hippocampal damage and dysfunction. Emerging evidence demonstrates that the gut microbiota and its metabolites, acting as probiotics or prebiotics, can modulate brain structure and function via the gut-brain axis, thereby offering therapeutic potential for ameliorating related neurological and psychiatric disorders. This study delves into the contribution of the gut microbiota and its metabolites to stress-induced ferroptosis of hippocampal neurons and the associated molecular pathways.

METHODS: This study used time-course stress paradigms combined with ferroptosis inhibitors to identify hippocampal neuronal ferroptosis. Fecal microbiota transplantation were conducted to analyze the role of gut microbiota in this process. Subsequently, 16 S rDNA sequencing and metabolomics techniques were applied to identify key gut microbiota and metabolites. Metabolites intervention were performed to examine their causal relationship with neuronal ferroptosis. Finally, we used histochemical and molecular assays to assess both intestinal and blood-brain barrier integrity as well as inflammation in peripheral blood and hippocampal tissue, along with GPR41/RhoA/Rock1 pathway changes, to preliminarily investigate the molecular mechanisms underlying stress-induced hippocampal neuronal ferroptosis.

RESULTS: We demonstrated that stress triggered hippocampal neuronal ferroptosis and subsequent depressive-like behaviors in mice. Fecal microbiota transplantation successfully replicated the ferroptosis phenotype. Butyric acid and valeric acid were identified as key metabolites significantly reduced in the serum of acutely and chronically stressed mice, respectively. Intervention with these metabolites markedly alleviated ferroptosis. Furthermore, valerate intervention increased hippocampal GPR41 expression and significantly suppressed the pro-inflammatory RhoA/Rock1 pathway in chronically stressed mice, thereby reducing neuroinflammation and ameliorating neuronal ferroptosis. However, butyrate intervention showed no significant effect on the GPR41/RhoA/Rock1 pathway.

CONCLUSION: Stress induces ferroptosis in hippocampal neurons, where reduced abundance of short-chain fatty acid-producing bacteria plays a key role. Key metabolites butyric acid and valeric acid alleviate neuroinflammation to improve ferroptosis via the gut-brain axis in acute and chronic stress, respectively. Specifically, valeric acid exerts neuroprotective effect through the GPR41/RhoA/Rock1 pathway, whereas butyric acid-mediated protection likely operates through alternative mechanisms.}, } @article {pmid40895486, year = {2025}, author = {Ge, S and Zhang, S and She, L and Gu, T and Wang, S and Huang, X and Wang, L and Miao, M}, title = {Synergistic therapy of Chinese herbal medicine and gut microbiota modulation for post-stroke cognitive recovery: focus on microbial metabolite and immunoinflammation.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1623843}, doi = {10.3389/fmicb.2025.1623843}, pmid = {40895486}, issn = {1664-302X}, abstract = {Post-stroke cognitive impairment (PSCI), a common complication following stroke, significantly impacts patients' quality of life and rehabilitation. Recent studies have highlighted the role of gut microbiota and their metabolites in modulating immunoinflammation and cognitive function via the gut-brain axis. Traditional Chinese medicine (TCM) and microbiota interventions including probiotics and fecal microbiota transplantation, have shown potential in reshaping gut microbial communities and metabolite profiles. Some studies suggest that combining these approaches via identical or related therapeutic mechanisms may yield enhanced efficacy in treating Post-Stroke Cognitive Impairment (PSCI). These findings establish a theoretical foundation for future research and clinical practice. This review systematically examines the mechanistic role of gut microbial metabolites in neuroimmune modulation and comprehensively evaluates the therapeutic potential of combined TCM and microbiota-targeted therapies for PSCI, adopting a multifactorial approach that addresses neuroinflammation, microbial dysbiosis, and metabolic dysregulation.}, } @article {pmid40895468, year = {2025}, author = {Yang, J and Chen, J and Li, D and Wu, Q and Zhang, Y and Li, Y and Deng, Y}, title = {Hyperuricemia and the gut microbiota: current research hotspots and future trends.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1620561}, doi = {10.3389/fmicb.2025.1620561}, pmid = {40895468}, issn = {1664-302X}, abstract = {BACKGROUND: Hyperuricemia (HUA), found widely in humans and birds, is a key physiological factor responsible for the development of gout. In recent years, the relationship between the gut microbiota and HUA has garnered significant attention from researchers. This study aims to explore the current research hotspots, knowledge gaps, and future research trends regarding the gut microbiota and HUA.

METHODS: We performed a thorough search of the literature on gut flora and HUA published between 2005 and 2024 using the Web of Science and PubMed databases. The resulting data were analyzed using VOSviewer, CiteSpace, and Bibliometrix.

RESULTS: Including 735 papers in total, the study found that the number of publications in the subject increased significantly between 2020 and 2024, with 2024 being the year with the highest number of publications. The primary research countries are highlighted as China and the United States, with institutions such as the University of California, San Diego, and Qingdao University making significant contributions. Sanjay K. Nigam and Chenyang Lu have made the most important contributions as authors. Keywords analysis highlighted high-frequency terms including "gastrointestinal microbiome," "uric acid," "hyperuricemia," "inflammation," "gout," and "probiotics." In the visualization map of the keyword timeline, emerging research hotspots include "diets," "dietary fiber," "fecal microbiota transplantation," and "gut-kidney axis."

CONCLUSION: This study is the first to conduct a quantitative literature analysis in the field of gut microbiota in HUA, revealing that the core research hotspots include disease-related microbiota characteristics, probiotic therapy, microecological intervention, and the gut-distal target organ axis. The emerging hotspots focus on dietary supplementation, fecal microbiota transplantation (FMT) treatment strategies, and in-depth research on the above organ axes. Provide valuable guidance for future research directions.}, } @article {pmid40895097, year = {2025}, author = {Jin, Y and Wang, H and Song, J}, title = {Gut-brain axis modulation in remote rehabilitation of Parkinson's disease: reconstructing the fecal metabolome and nigral network connectivity.}, journal = {Frontiers in neurology}, volume = {16}, number = {}, pages = {1644490}, doi = {10.3389/fneur.2025.1644490}, pmid = {40895097}, issn = {1664-2295}, abstract = {The pathogenesis of Parkinson's disease (PD) is gradually evolving from a central neurodegeneration-centered concept to a multi-pathway pathological model at the gut-brain system level. Studies have shown that PD patients commonly exhibit dysbiosis, reduced short-chain fatty acids (SCFAs; microbial fermentation products of dietary fiber that play key roles in host metabolism and immune regulation), abnormal tryptophan metabolism, and impaired gut barrier function. These alterations may contribute to dopaminergic neuronal damage through mechanisms including neuroinflammation, oxidative stress, and α-synuclein (α-syn) aggregation. The vagus nerve plays a critical role in bidirectional gut-brain signaling, and its dysfunction may represent a key route for pathological protein transmission from the periphery to the brain. In response, remote rehabilitation and gut-targeted interventions-including probiotics, prebiotics, dietary modulation, fecal microbiota transplantation (FMT), and transcutaneous vagus nerve stimulation (tVNS)-have shown potential in improving neurological function and inflammation in both animal and clinical studies. Multimodal data analyses have revealed significant associations between SCFA levels in fecal metabolomics and brain imaging features. Despite ongoing challenges in mechanistic extrapolation, biomarker sensitivity, and translational implementation, the integration of metagenomics, metabolomics, neuroimaging, and digital therapeutics-collectively referred to as multi-omics and digital profiling techniques-represents an emerging research direction with the potential to inform future clinical paradigms for precision remote management of PD.}, } @article {pmid40894980, year = {2025}, author = {Wang, YM}, title = {How to Approach Immune Checkpoint Inhibitor Enterocolitis.}, journal = {Gastroenterology & hepatology}, volume = {21}, number = {8}, pages = {501-503}, pmid = {40894980}, issn = {1554-7914}, } @article {pmid40894608, year = {2025}, author = {Lopez, ML and Kang, T and Espeleta, A and Rubtsova, VI and Baek, J and Songcuan, J and Moyer, EM and Kim, J and Song, WS and Jung, S and D'Sa, N and Anica, A and Tran, E and Chun, Y and Choi, W and Jang, KH and Kelly, ME and Tamburini, IJ and Alam, YH and Le, J and Ramirez, CB and Kataru, RP and Hong, SP and Nicholas, DA and Xue, KS and Lee, G and Bae, H and Jang, C}, title = {Intestinal catabolism of dietary fructose promotes obesity and insulin resistance via ileal lacteal remodeling.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.08.18.670963}, pmid = {40894608}, issn = {2692-8205}, abstract = {UNLABELLED: High-fructose corn syrup (HFCS) consumption is a risk factor for obesity and metabolic syndrome, yet the underlying mechanisms are incompletely understood. Catabolism of dietary fructose primarily occurs in the small intestine and liver, with fructose breakdown in the liver being pathological, while small intestinal fructose clearance protects the liver. Here, we unexpectedly found that inhibition of fructose catabolism specifically in the small intestine mitigates fructose-induced obesity and insulin resistance. Mechanistically, blocking intestinal fructose catabolism reduces dietary fat absorption, which is associated with a decrease in the surface area of the ileal lacteals and alterations in gut microbiome. Fecal transplantation experiments revealed that such a microbiome stimulates the intestine-resident macrophages, promoting lacteal growth and boosting dietary fat absorption. Given the preclinical and clinical studies reporting the effect of fructose catabolism suppression on mitigating diet-induced obesity, our data suggest that such effects are partly mediated by intestinal lacteal remodeling.

SIGNIFICANCE STATEMENT: Here, we uncover a previously unappreciated link between intestinal fructose catabolism and ileal lacteal remodeling, suggesting the mechanisms by which fructose intake promotes obesity. Using mice lacking the fructose-processing enzyme specifically in the intestine, we show that blocking intestinal fructose metabolism protects against diet-induced obesity by reducing fat absorption. Changes in gut microbiome and immune cell interactions drive this effect.}, } @article {pmid40894444, year = {2025}, author = {Xu, P}, title = {Gut Microbiota Metabolites Targeting the Immune Response in Sepsis: Mechanisms and Therapies.}, journal = {International journal of general medicine}, volume = {18}, number = {}, pages = {4709-4734}, doi = {10.2147/IJGM.S539237}, pmid = {40894444}, issn = {1178-7074}, abstract = {Sepsis is a global health challenge, affecting millions annually and remaining a leading cause of mortality in intensive care units. Gut microbiota plays a complex role in the onset and progression of sepsis, with its alterations reflecting disease severity. Recently, modulating gut microbiota and its metabolites has emerged as a promising therapeutic strategy for sepsis. This review highlights the role of gut microbiota in sepsis and systematically identifies key immune response targets directly influenced by gut microbiota metabolites, such as short-chain fatty acids (SCFAs), bile acids, and indoleacetic acid, among other important metabolites. Additionally, it offers a full overview of current research on gut microbiota-regulated therapeutic approaches, including fecal microbiota transplantation (FMT) and artificial intelligence (AI) applications. These insights offer a novel perspective for advancing the understanding of sepsis pathogenesis and its treatment.}, } @article {pmid40893829, year = {2025}, author = {Allegretti, JR}, title = {Current Status of Fecal Microbiota Transplantation for Inflammatory Bowel Disease Management.}, journal = {Gastroenterology & hepatology}, volume = {21}, number = {7}, pages = {451-453}, pmid = {40893829}, issn = {1554-7914}, } @article {pmid40891897, year = {2025}, author = {Bertin, L and Bonazzi, E and Facchin, S and Lorenzon, G and Maniero, D and DE Barba, C and Tomasulo, A and Fortuna, A and Zingone, F and Barberio, B and Savarino, EV}, title = {The microbiota-brain connection in neurological diseases: the ubiquitous short-chain fatty acids.}, journal = {Minerva gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.23736/S2724-5985.25.03866-5}, pmid = {40891897}, issn = {2724-5365}, abstract = {The connection between the gut and brain forms a sophisticated two-way communication system where compounds produced by intestinal bacteria, especially short-chain fatty acids, play essential roles in brain-related disease processes. Evidence across multiple neurological disorders reveals convergent pathophysiological pathways involving SCFAs, which modulate neurological function via histone deacetylase inhibition, G-protein coupled receptor activation, and blood-brain barrier regulation. Clinical investigations demonstrate disorder-specific signatures: reduced butyrate-producing bacteria correlate with Parkinson's disease progression; Alzheimer's disease exhibits significant reductions in key SCFAs; and diminished butyrate production disrupts immunoregulatory homeostasis in multiple sclerosis. Additionally, neurodevelopmental disorders like autism show distinctive microbiome alterations affecting both gut and brain function. Beyond SCFAs, microbiota influence neural communication through immune modulation, neurotransmitter production, and vagus nerve signaling. Interventional studies targeting the microbiome through precision probiotics, prebiotics, and fecal microbiota transplantation demonstrate preliminary efficacy, particularly in Parkinson's disease and autism. Methodological heterogeneity and challenges establishing causality remain significant limitations. Future priorities include longitudinal characterization of microbiome dynamics preceding symptom onset, development of personalized therapeutics, and implementation of predictive computational models. Progress in these domains could transform microbiome-based approaches from experimental interventions to precision medicine applications in neurological disease management.}, } @article {pmid40890737, year = {2025}, author = {Lu, G and Zhang, S and Wang, R and Wu, X and Chen, Y and Wen, Q and Cui, B and Zhang, F and Li, P}, title = {Fecal microbiota transplantation improves bile acid malabsorption in patients with inflammatory bowel disease: results of microbiota and metabolites from two cohort studies.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {511}, pmid = {40890737}, issn = {1741-7015}, support = {81873548//National Natural Science Foundation of China/ ; 82100583//National Natural Science Foundation of China/ ; 2020-3//Nanjing Medical University Fan Daiming Research Funds for Holistic Integrative Medicine/ ; }, abstract = {BACKGROUND: Bile acid malabsorption (BAM) or bile acid diarrhea (BAD) complicates more than 30% of Crohn's disease (CD), yet no non-invasive biomarker reliably identifies patients who will benefit from fecal microbiota transplantation (FMT). We investigated whether serum 7α-hydroxy-4-cholesten-3-one (C4), a hepatic bile-acid synthesis precursor, can predict BAM and FMT response in inflammatory bowel disease (IBD).

METHODS: We included 106 pairs of IBD patients treated with FMT from two longitudinal cohorts of prospective trials and 24 matched healthy individuals to identify a multi-omics analysis of microbiota-metabolism and evaluate real-world effectiveness of FMT. Fecal and serum samples before and after FMT along with medical information were collected and detected through 16S rRNA amplicon sequencing and untargeted liquid chromatography mass spectrometry. Mice models were used to preliminarily verify the exacerbation of colitis through administration of primary BAs and treated by FMT.

RESULTS: Patients in BAM group tended to achieve sustained higher and stable clinical response (66.67% vs. 49.41%) and remission (52.38% vs. 40.00%) than non-BAM group at 3 months after FMT, along with a significantly decrease of C4 (P < 0.001), improvement of obvious abdominal pain and diarrhea, which was especially obvious in CD patients with ileal resection and ileal /ileocolonic type. Random forest classifiers predicted BAM in IBD patients with 18 or top 4 differential OTUs, showing an area under the curve of 0.92 and 0.83, respectively. Furthermore, results from primary bile acid-induced colitis mice models reinforced these findings.

CONCLUSIONS: Serum C4 and a minimal gut microbiota may identify IBD patients with BAM who are most likely to achieve durable remission after FMT. These translatable biomarkers can guide precision use of microbiota-directed therapy.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT01790061 and NCT01793831.}, } @article {pmid40889045, year = {2025}, author = {Wang, H and Wang, Y and Wu, H and Shen, C and Li, Y and Bai, B and Sun, X and Liu, Y and Zhang, Q and Shi, L}, title = {High-fat diet-induced obesity-related hypertension via altered gut microbiota-mediated histone butyrylation.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, pmid = {40889045}, issn = {1869-1889}, abstract = {Hypertension is a chronic cardiovascular disease that significantly impacts human quality of life. Gut microbiota and its metabolites have been reported to be involved in lipid metabolism and blood pressure regulation, but the specific alterations and pathogenic mechanisms of gut microbiota in obesity-related hypertension (OrHTN) remain unclear. In this study, we observed a significant proliferation of Desulfobacterota and Proteobacteria, while a decrease in the abundance of several butyrate-producing bacterial genera, accompanied by decreased fecal and plasma butyrate levels in high-fat diet (HFD)-induced OrHTN rats. Histone 3 lysine 9 butyrylation (H3K9bu) modification in the kidney of OrHTN rats was reduced and downregulated the expression of the hypertension-related gene MAS1. Subsequent transplantation of cecal contents from OrHTN rats on HFD into recipient rats on a normal chow diet resulted in hypertension but without obesity. Furthermore, in vitro experiments suggested that sodium butyrate increased H3K9bu modification and the expression of MAS1 in a concentration-dependent manner. In conclusion, our findings suggest that gut microbiota may contribute to the development of OrHTN by altering the expression of hypertension-related genes through butyrate-mediated histone butyrylation. This work may provide new insights into the prevention and treatment of hypertension by targeting the regulation of gut microbiota and metabolites.}, } @article {pmid40886868, year = {2025}, author = {Wang, Z and Ren, X and Peng, Z and Zeng, M and Wang, Z and Chen, Q and Chen, J and Dai, X and Christian, M and Qie, X and He, Z}, title = {Flavonoid-rich extracts of Nelumbo nucifera leaves alleviate obesity in HFD-fed mice via microbiota-dependent modulation of brown fat thermogenesis.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {120513}, doi = {10.1016/j.jep.2025.120513}, pmid = {40886868}, issn = {1872-7573}, abstract = {Nelumbo nucifera Gaertn (lotus) leaf is a commonly used traditional Chinese herbal medicine with a wide range of pharmacological properties, especially lipid-lowering and weight-loss effects. Accumulating evidence highlights activation of the thermogenic program of brown adipose tissue (BAT) as a promising anti-obesity strategy. However, it remains unclear whether such beneficial metabolic effects induced by the lotus leaf are related to its regulatory role in BAT function.

AIM OF THE STUDY: This work aims to investigate whether the lotus leaf reduces obesity by activating BAT and to elucidate whether the mechanism behind it is related to the regulation of gut microbiota.

MATERIAL AND METHODS: A mouse model of obesity was established using a high-fat diet (HFD), and the anti-obesity effect of flavonoid-rich lotus leaf extract (LLE) was determined in vivo. An animal energy metabolism monitoring system confirmed that LLE promoted energy expenditure. Then, RT-qPCR, immunohistochemistry, and Western blotting were conducted to detect the expression of genes and proteins involved in BAT thermogenesis. Subsequently, the underlying mechanisms were demonstrated by 16S rRNA gene sequencing and non-targeted metabolism analysis. Finally, fecal microbiota transplantation (FMT) was performed to investigate the LLE-dependent alleviation of obesity via the gut microbiota-BAT axis.

RESULTS: Our study demonstrated that LLE effectively reduced weight gain, ameliorated glucolipid disorders, and enhanced energy expenditure in HFD-fed mice. Notably, LLE augmented BAT activity by increasing thermogenic markers (e.g., SIRT1, PGC-1α, UCP1) and repressing inflammatory responses, potentially through activation of β3-AR/AMPK/p38 signaling pathways. Importantly, LLE could mitigate HFD-induced microbial dysbiosis (decrease in Proteobacteria, Verrucomicbiota, Acidobacteriota, Bacteroides, Dubosiella, and increase in Bilophila, Tyzzerella, Oscillibacter, Akkermansia, and Alistipes) and significantly altered 5 metabolite pathways, especially primary bile acid biosynthesis and linoleic acid metabolism. The FMT experiment confirmed that the microbial changes induced by LLE were associated with reduced body weight, enhanced energy expenditure, increased BAT activity, and thermogenesis.

CONCLUSIONS: Collectively, our findings reveal that lotus leaf promotes brown fat thermogenesis by modulating gut microbiota, identifying it as a promising new treatment target for obesity.}, } @article {pmid40886596, year = {2025}, author = {Li, W and Wang, N and Lyu, D and Yu, X and He, X and Yu, K and Qiu, Y and Jiao, X}, title = {Gut dysbiosis mediates neurotoxic effects of environmentally relevant tylosin exposure in adult zebrafish.}, journal = {Ecotoxicology and environmental safety}, volume = {303}, number = {}, pages = {118960}, doi = {10.1016/j.ecoenv.2025.118960}, pmid = {40886596}, issn = {1090-2414}, abstract = {Tylosin, a widely used veterinary macrolide antibiotic, raises environmental concerns due to its persistence and potential health risks. However, the neurotoxic effects of chronic low-dose tylosin exposure remain unclear. This study assessed the neurotoxicity of chronic exposure to environmentally relevant tylosin concentrations (5000 ng/L) in adult zebrafish. Behavioral tests indicated anxiety- and depression-like behaviors, including reduced exploration and increased freezing. Histopathology revealed neuronal degeneration, evidenced by decreased Nissl staining in key brain areas. Transcriptomic analysis identified significant changes in genes related to neuroinflammation, synaptic dysfunction, immune response, and steroid metabolism. Multi-omics approaches further showed substantial alterations in gut microbiota composition and metabolic profiles, particularly involving tryptophan metabolism and steroid hormone synthesis. These gut changes correlated with impaired intestinal barrier function, including fewer goblet cells and reduced tight junction and mucin-2 protein expression. Fecal microbiota transplantation confirmed the role of altered gut microbiota in inducing anxiety- and depression-like behaviors, highlighting microbiota-gut-brain axis involvement. Molecular docking identified microbial metabolites (MG 20:4, 2E-dodecenedioic acid, Ononin) interacting with critical neurodevelopmental and stress-response proteins (LRAT, BHLHE40, HSPA5), potentially linking microbiota shifts to brain dysfunction. Our results demonstrate that chronic environmental tylosin exposure induces neurotoxicity through gut dysbiosis and compromised intestinal barriers, disrupting essential neuroactive pathways. These findings emphasize the importance of considering microbiota-gut-brain axis disruption in environmental antibiotic risk assessments.}, } @article {pmid40885910, year = {2025}, author = {Huang, W and Chai, Y and Li, X and Zhang, Q and Yan, Z and Wang, Y and Tao, X and Zhang, J and Qiu, F}, title = {Metagenomics and metabolomics to evaluate the potential role of gut microbiota and blood metabolites in patients with cerebral infarction.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {567}, pmid = {40885910}, issn = {1471-2180}, support = {2018YFA0108601//Clinical research on intracerebral precision transplantation of neural stem cells for stroke treatment/ ; L255012//The Huairou Innovation Joint Fund Project of Beijing Natural Science Foundation/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Cerebral Infarction/microbiology/blood/metabolism ; *Metabolomics/methods ; *Metagenomics/methods ; Male ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; Middle Aged ; Female ; Aged ; *Bacteria/classification/genetics/isolation & purification/metabolism ; Tandem Mass Spectrometry ; Adult ; Chromatography, High Pressure Liquid ; }, abstract = {Cerebral infarction, a cerebrovascular disorder, is characterized by the sudden onset of neurological deficits and clinical symptoms. It ranks among the leading causes of death and severe disability worldwide. The etiology of cerebral infarction is multifaceted, with common risk factors including dietary patterns, smoking, hypertension, and diabetes mellitus. In recent years, the role of the gut microbiota in systemic immunity and tumorigenesis has been intensively explored, thrusting the research on the gut-brain axis into the spotlight. However, there is a lack of literature investigating the relationship between the gut microbiota and blood metabolites in cerebral infarction. In this study, we employed 16S rRNA analysis and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for a comprehensive metagenomic and metabolomic analysis of fecal samples from cerebral infarction patients and the general population. Our results revealed a significant correlation between the gut microbiome and serum metabolites, highlighting the impact of the microbiome on metabolic pathways. Specifically, we found that 35 gut microbiome taxa, such as Actinobacteriota and Peptostreptococcales-Tissierellales, were significantly enriched in the control group (N group). Through Linear Discriminant Analysis Effect Size (LEfSe) analysis, 72 taxa showed significant differences between cerebral infarction patients and healthy individuals. Among them, 22 key taxa were identified as microbial biomarkers for differentiating patients from healthy controls. These findings suggest that variations in the microbiome and metabolites could potentially serve as biomarkers for future diagnostic and therapeutic strategies in cerebral infarction.}, } @article {pmid40884832, year = {2025}, author = {Chen, S and Liu, F and Han, X and Jia, D and Chen, J and Wei, Y and Yu, Z and He, L and Liao, C and Ding, K}, title = {Exposure to Bovine Viral Diarrhea Virus Disrupts Intestinal Barrier Function via NLRP3/Caspase-1-Mediated Pyroptosis and Gut Microbiota Dysbiosis.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c04854}, pmid = {40884832}, issn = {1520-5118}, abstract = {Bovine viral diarrhea virus (BVDV) is a major global pathogen that causes severe economic losses in dairy herds due to diarrhea, reproductive disorders, and reduced milk yield. Despite its well-documented systemic effects, the mechanism of BVDV-induced intestinal damage remains unclear. In our study, BVDV triggered cytopathic effects in intestinal epithelial cells, including cell death, goblet cell depletion, and disruption of barrier proteins. Although BVDV alters gut microbiota by activating the NLRP3/caspase-1 inflammasome pathway and thereby causing pyroptosis and intestinal injury, fecal microbiota transplantation mitigated those effects by suppressing NLRP3/caspase-1's activation. Those findings reveal key pathways in BVDV's pathogenesis and suggest novel therapeutic strategies to combat livestock infections.}, } @article {pmid40882395, year = {2025}, author = {Chen, X and Zou, J and Hong, T and Zhang, H and Yang, J and Mai, H and Shi, H and Li, X and Feng, D}, title = {Bisphenol A increases fat mass in adipose tissue by disturbing gut microbiota-dependent bile acid metabolism and TGR5/UCP1 signaling pathways in CD-1 mice.}, journal = {Ecotoxicology and environmental safety}, volume = {303}, number = {}, pages = {118922}, doi = {10.1016/j.ecoenv.2025.118922}, pmid = {40882395}, issn = {1090-2414}, abstract = {Disorder of gut microbiota-mediated bile acid (BA) metabolism plays a pivotal role in the pathogenesis of obesity. Our previous research showed that bisphenol A (BPA) exposure induced hepatic fat accumulation and gut microbiota dysbiosis. However, whether the gut microbiota-dependent BA metabolism alteration is involved in BPA-induced fat accumulation and obesity remains elusive. This study aimed to investigate the gut microbiota-dependent metabolic mechanism of obesity induced by BPA. Male CD-1 mice were exposed to a low dose of BPA (50 μg/kg/day) for six months. Our findings demonstrated that BPA exposure significantly augmented the fat mass of both brown and white adipose tissue, along with the proportion of adipose tissue weight relative to body weight. Furthermore, BPA reduced the relative abundance of Bacteroides, Parabacteroides, and Akkermansia, which are associated with BA metabolism. Additionally, serum levels of lithocholic acid, the most potent activator of Takeda G protein-coupled receptor 5 (TGR5), and TGR5 expression in adipose tissue were substantially diminished following BPA exposure. Inhibition of TGR5 reduced cyclic adenosine monophosphate levels, subsequently decreasing the expression of iodothyronine deiodinase 2 and fibroblast growth factor 21. These changes down-regulated the expression of uncoupling protein 1 (UCP1), ultimately leading to reduced energy expenditure and increased fat mass. Moreover, further fecal microbiota transplantation and microbiota elimination confirmed the role of gut microbiota in BPA-induced adverse effects. Collectively, our study demonstrated that the suppression of gut microbiota-BA-TGR5/UCP1 signaling pathways may constitute a potential mechanism underlying BPA-induced fat mass gain, providing a novel target for the prevention of BPA-induced obesity.}, } @article {pmid40881288, year = {2025}, author = {Pourrat, A and Baillieu, V and Ansel, S and Leonardi, M and Poiron, P and Bellais, S and Paul, M and Nebbad, B}, title = {Standardized freeze-dried FMT: is the ideal protectant out there?.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1618067}, doi = {10.3389/fmicb.2025.1618067}, pmid = {40881288}, issn = {1664-302X}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infections. Freeze-drying offers a next-generation, more practical, and aesthetically acceptable FMT formulation that could facilitate standardized preparation methods. Viable preservation is a critical step in freeze-drying, yet no universal medium effectively protects both anaerobes and aerobes.

OBJECTIVE: This study aimed to evaluate different protectants compared to trehalose 5% (T5) after confirming its efficacy.

METHODS: A mix of inulin and glucosamine (IG5) and a High-antioxidant Matrix with trehalose (HM) were tested. Viability was assessed using colony-forming unit (CFU) enumeration and flow cytometry with a LIVE/DEAD™ staining method.

RESULTS: T5 demonstrated satisfactory bacterial recovery after freeze-drying, with viability of 84 ± 28% for anaerobes and 59 ± 39% for Bifidobacterium (BIF), confirming its efficiency in our preparation facilities. While HM showed highest results (91 ± 7% for anaerobes, 121 ± 33% for BIF), it did not significantly outperform T5. IG5, however, resulted in a significant loss of bacteria, with only 16 ± 12% viability for anaerobes (p = 0.016) and 19 ± 9% for BIF (p = 0.031).

CONCLUSION: HM and T5 both proved effective for freeze-dried FMT, with HM yielding the highest recovery but not significantly outperforming T5. Given its simplicity and consistent results, T5 may serve as a reliable standalone protectant or as a base for improved formulations. IG5 showed significant bacterial loss and is unsuitable. Further biological validation and stability data will guide the development of optimized freeze-dried oral FMT capsules.}, } @article {pmid40880458, year = {2025}, author = {Dinis, L and Pinheiro, H and Póvoa, P and Calhau, C and Pestana, D and Marques, C}, title = {Advancing Access to Intestinal Microbiota Transplant: Bridging the Gap Between National Practices and the European Strategy.}, journal = {Acta medica portuguesa}, volume = {}, number = {}, pages = {}, doi = {10.20344/amp.22750}, pmid = {40880458}, issn = {1646-0758}, abstract = {Clostridioides difficile is an opportunistic pathogen that can cause a range of conditions, from asymptomatic carriage to severe illness, posing a significant public health threat due to its high mortality rates and substantial healthcare costs. Traditional treatment options, including antibiotics, often fail to eradicate the infection, leading to recurrent cases that severely impact patients' lives. Intestinal microbiota transplant (IMT) has emerged as an effective strategy for decolonizing pathogenic agents, demonstrating safety and efficacy, particularly in treating recurrent Clostridioides difficile infection (rCDI). Despite its potential, access to IMT is limited due to safety concerns, logistical challenges, and a lack of proper guidance, underscoring the urgent need for structured intestinal microbiota banks (IMBs). These organized facilities are crucial for the collection, screening, processing, and distribution of intestinal microbiota preparations, thereby facilitating the clinical application of IMT. In this narrative review, we discuss the relevance of applying IMT for the treatment of rCDI in Europe, with a focus on Portugal. We highlight the existence and distribution of IMBs across Europe and their importance in improving access to IMT. This review also addresses the challenges in creating an IMB and the development of such a structure in Portugal as a centralized repository for high-quality, standardized microbiota preparations, making IMT accessible for national hospitals. Additionally, it emphasizes the need to raise awareness among healthcare providers and the public to support the broader adoption of IMT.}, } @article {pmid40878918, year = {2025}, author = {Liu, X and Xie, Y and Yang, S and Jiang, C and Shang, K and Luo, J and Zhang, L and Hu, G and Liu, Q and Yue, B and Fan, Z and He, Z and Li, J}, title = {Multi-omics investigation of spontaneous T2DM macaque emphasizes gut microbiota could up-regulate the absorption of excess palmitic acid in the T2DM progression.}, journal = {eLife}, volume = {14}, number = {}, pages = {}, pmid = {40878918}, issn = {2050-084X}, support = {2021YJ0136//Science and Technology Foundation of Sichuan Province/ ; 32171607//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Diabetes Mellitus, Type 2/microbiology/pathology/metabolism ; *Palmitic Acid/metabolism ; Macaca mulatta ; Mice ; Disease Models, Animal ; Male ; Gene Expression Profiling ; Metabolome ; RNA, Ribosomal, 16S/genetics ; Disease Progression ; Multiomics ; }, abstract = {Although gut microbiota and lipid metabolites have been suggested to be closely associated with type 2 diabetes mellitus (T2DM), the interactions between gut microbiota, lipid metabolites, and the host in T2DM development remains unclear. Rhesus macaques may be the best animal model to investigate these relationships given their spontaneous development of T2DM. We identified eight spontaneous T2DM macaques and conducted a comprehensive study investigating the relationships using multi-omics sequencing technology. Our results from 16 S rRNA, metagenome, metabolome, and transcriptome analyses identified that gut microbiota imbalance, tryptophan metabolism and fatty acid β oxidation disorders, long-chain fatty acid (LCFA) accumulation, and inflammation occurred in T2DM macaques. We verified the accumulation of palmitic acid (PA) and activation of inflammation in T2DM macaques. Importantly, mice transplanted with spontaneous T2DM macaque fecal microbiota and fed a high PA diet developed prediabetes within 120 days. We determined that gut microbiota mediated the absorption of excess PA in the ileum, resulting in the accumulation of PA in the serum, consequently leading to T2DM in mice. In particular, we demonstrated that the specific microbiota composition was probably involved in the process. This study provides new insight into interactions between microbiota and metabolites and confirms causative effect of gut microbiota on T2DM development.}, } @article {pmid40877311, year = {2025}, author = {Wilson, BC and Zuppi, M and Derraik, JGB and Albert, BB and Tweedie-Cullen, RY and Leong, KSW and Beck, KL and Vatanen, T and O'Sullivan, JM and Cutfield, WS and , }, title = {Long-term health outcomes in adolescents with obesity treated with faecal microbiota transplantation: 4-year follow-up.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {7786}, pmid = {40877311}, issn = {2041-1723}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Adolescent ; Male ; Female ; Follow-Up Studies ; Double-Blind Method ; *Pediatric Obesity/therapy ; Treatment Outcome ; Body Composition ; Body Mass Index ; Gastrointestinal Microbiome ; *Obesity/therapy ; Metabolic Syndrome/therapy ; Feces/microbiology ; }, abstract = {Faecal microbiota transplantation (FMT) has been explored as a potential treatment for obesity, but its long-term effects on metabolic health remain unclear. Here, we report 4-year follow-up findings from a double-blind, randomised, placebo-controlled trial assessing FMT in adolescents with obesity (ACTRN12615001351505, Australian New Zealand Clinical Trials Registry). This unblinded follow-up study evaluated 63% (55/87) of the original participants (27 FMT, 28 placebo). There was no difference in BMI between the two groups, after adjusting for sex, age, diet, and physical activity (-3.6 kg/m[2], p = 0.095). However, FMT recipients showed clinical improvements in body composition and metabolic health compared to the placebo group. Specifically, FMT recipients had smaller waist circumference (-10.0 cm, p = 0.026), total body fat (-4.8%, p = 0.024), metabolic syndrome severity score (-0.58, p = 0.003), and systemic inflammation (-68% hs-CRP, p = 0.002) and higher levels of HDL cholesterol (0.16 mmol/L, p = 0.037). No group differences were observed in glucose markers, or other lipid parameters. Shotgun metagenomic sequencing revealed sustained long-term alterations in gut microbiome richness, composition and functional capacity, with persistence of donor-derived bacterial and bacteriophage strains. These findings highlight the potential relevance of FMT as a microbiome-augmenting intervention for obesity management and metabolic health, warranting further investigation.}, } @article {pmid40876612, year = {2025}, author = {Xie, X and Ge, W and Luo, Y and Xing, X and Sun, X}, title = {Ginsenoside Rb3 Modulates Gut Microbiota to Alleviate Cerebral Inflammation and Ferroptosis via the NLRP3/NF-κB/GPX4 Pathway in Rats with Cerebral Ischemia/Reperfusion Injury.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {178091}, doi = {10.1016/j.ejphar.2025.178091}, pmid = {40876612}, issn = {1879-0712}, abstract = {Cerebral ischemia/reperfusion injury (CIRI) poses a significant threat to human life and health. Ginsenoside Rb3 (Rb3) is known to exhibit protective effects against myocardial ischemia, its impact on CIRI remains unclear. Therefore, we investigated the protective effects of Rb3 on CIRI and its underlying mechanisms. Our results showed that Rb3 reduced cerebral infarct volume, decreased blood-brain barrier (BBB) permeability, and improved neurological deficits in CIRI rats. Rb3 also mitigated cerebral ferroptosis and alleviated neuroinflammation, as evidenced by decreased iron levels, reduced MDA content, an improved GSH/GSSG ratio, and lower levels of TNF-α, IL-1β, and IL-6, through modulation of the NLRP3/NF-κB/GPX4 pathway. Additionally, Rb3 alleviated intestinal inflammation, improved the intestinal barrier, and corrected gut microbiota dysbiosis and reduced the microbial metabolites TMAO and LPS in CIRI rats. It is noteworthy that in pseudo germ-free rats with CIRI, fecal microbiota transplants (FMT) from Rb3-treated rats conferred similar protective effects as Rb3. Summarily, this study reveals that Rb3 reduces neuroinflammation and ferroptosis in the brains of middle cerebral artery occlusion/reperfusion (MCAO/R) rats via the NLRP3/NF-κB/GPX4 pathway in a gut microbiota-dependent manner.}, } @article {pmid40876561, year = {2025}, author = {de Oliveira, DG and Machado, A and Lacerda, PC and Karakikla-Mitsakou, Z and Vasconcelos, C}, title = {Systemic lupus erythematosus and the gut microbiome: To look forward is to look within - A systematic review and narrative synthesis.}, journal = {Autoimmunity reviews}, volume = {}, number = {}, pages = {103921}, doi = {10.1016/j.autrev.2025.103921}, pmid = {40876561}, issn = {1873-0183}, abstract = {BACKGROUND: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease shaped by complex interactions involving genetic and environmental factors. Among these, the gut microbiome is emerging as potentially modulating immune responses and influencing disease susceptibility, progression, and activity.

OBJECTIVES: To synthesize current evidence on gut microbiome changes in adult SLE patients, framed along the clinical pathway - from diagnosis to treatment - to help bridge bench and bedside for microbiome-informed SLE care and research.

METHODS: A systematic search identified primary research studies examining gut microbiota in adult SLE patients. Studies were reviewed in a stepwise manner by independent investigators. Findings were synthesized narratively, emphasizing human data.

RESULTS: SLE patients exhibit gut microbiome dysbiosis, with reduced microbial richness and altered bacterial taxa. A lower Firmicutes/Bacteroidetes ratio is frequently observed. Enrichment of specific taxa, such as Enterococcus, Lactobacillus, and Ruminococcus gnavus, is reported. Dysbiosis correlates with increased gut permeability, immune activation, and autoreactivity. Clinical associations include disease activity, flares, nephritis, and other manifestations. SLE treatments, such as hydroxychloroquine and corticosteroids, influence the microbiome. Emerging interventions such as dietary modulation and fecal microbiota transplantation show promise in early studies. However, considerable heterogeneity exists across studies in terms of patient characteristics, methodology, and taxa-level findings.

CONCLUSIONS: The gut microbiome has multifaceted associations with SLE pathogenesis, disease activity, and therapeutic response. Translation will require standardized methods, functional validation, longitudinal follow-up, and clinical integration. While uncertainties remain, the gut microbiome is increasingly relevant, and clinicians caring for patients with SLE should be aware of its emerging implications.}, } @article {pmid40876127, year = {2025}, author = {Cao, S and Guo, X and Xin, M and Wang, X and Huo, J and Yue, Y and Li, X and Xu, D and Liu, L}, title = {Sesamin ameliorates ulcerative colitis by modulating the DUSP1/ERK feedback loop and restoring gut microbiota homeostasis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {147}, number = {}, pages = {157188}, doi = {10.1016/j.phymed.2025.157188}, pmid = {40876127}, issn = {1618-095X}, abstract = {BACKGROUND: Sesamin (SSM), a plant-derived lignan, possesses anti-inflammatory and immunomodulatory effects. The pathogenesis of ulcerative colitis (UC) is complex and involves intestinal mucosal damage, inflammation, and dysbiosis of the gut microbiota. However, to date, the protective effects and therapeutic mechanisms of SSM in UC have hardly been investigated.

PURPOSE: The purpose of the study was to investigate the protective effects and therapeutic mechanisms of SSM in UC.

METHODS: This study utilized a dextran sulfate sodium-induced mouse model of UC to investigate the therapeutic effects of SSM and its impact on gut microbiota using molecular biology techniques, including histological staining, western blotting, proteomics, molecular docking, 16S rRNA sequencing, and fecal microbiota transplantation.

RESULTS: SM significantly alleviated inflammation, repaired intestinal mucosal barrier, and improved gut microbiota structure in mice with UC (p < 0.05). Further studies revealed that SSM upregulated dual-specificity phosphatase 1 (DUSP1) by suppressing extracellular signal-regulated protein kinase (ERK) phosphorylation, whereas DUSP1 knockdown increased p-ERK levels (p < 0.05). Additionally, SSM regulated the distribution of gut microbiota by increasing the abundance of beneficial bacteria (such as Lactobacillus), reducing the abundance of opportunistic pathogens (such as Staphylococcus), and restoring gut microbiota homeostasis (p < 0.05).

CONCLUSION: In summary, this is the first study to demonstrate that SSM exerts anti-inflammatory and intestinal barrier-restoring effects through modulating the DUSP1/ERK feedback loop and restoring gut microbiota homeostasis, thereby offering a novel therapeutic strategy for UC.}, } @article {pmid40875477, year = {2025}, author = {Guo, YF and Wang, Y and Wu, H and Wang, L and Miao, X}, title = {Rauvolfia Verticillata Pectic Polysaccharides Alleviate Inflammation-Associated Colorectal Cancer and Correlate with Modulation of Gut Microbiota, Short-Chain Fatty Acid Metabolism, and NF-κB/IL-6/STAT3 Signaling Pathways.}, journal = {Nutrition and cancer}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/01635581.2025.2551294}, pmid = {40875477}, issn = {1532-7914}, abstract = {Background: Colorectal cancer (CRC) is increasingly common in younger individuals and strongly linked to chronic inflammation. Gut microbiota and pathways like NF-κB/STAT3 play key roles, which highlights the therapeutic potential of natural compounds that target intestinal immunity and microbial balance. Objective: To investigate the therapeutic effects of pectic polysaccharides (PPs) from Rauvolfia verticillata in inflammation-associated CRC via the modulation of of gut microbiota and NF-κB/IL-6/STAT3 signaling pathways. Methods: C57BL/6 mice were subjected to azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CRC and treated with PP (100 mg/kg/day), the STAT3 inhibitor W2014-S (10 mg/kg), or fecal microbiota transplantation (FMT) from PP-treated donors. Histopathology, immunohistochemistry (IHC), Western blot, immunofluorescence (IF), 16S rRNA sequencing, and SCFA analysis were performed to assess inflammation, signaling pathways, gut microbiota composition, and metabolic changes. Results: PP intervention significantly mitigated AOM/DSS-induced weight loss, intestinal lesions, and disease activity index (DAI) scores while suppressing NF-κB and STAT3 activation. PP restored gut microbiota diversity, reduced pro-inflammatory genera, and regulated SCFA levels, particularly hexanoic those of and isohexanoic acids. FMT from PP-treated donors similarly attenuated colitis and inhibited NF-κB/STAT3 pathways. Conclusions: PP alleviates CRC and is associated with modulation of gut microbiota, SCFA metabolism, and NF-κB/IL-6/STAT3 signaling, offering a potential therapeutic strategy for inflammation-driven CRC.}, } @article {pmid40873786, year = {2025}, author = {Pinto, S and Benincà, E and Nooij, S and Terveer, EM and Keller, JJ and van der Meulen-de Jong, AE and Steyerberg, EW and Bogaards, JA}, title = {Ecological resilience in ulcerative colitis: microbial dynamics of donor and resident species in a longitudinal fecal microbiota transplantation study.}, journal = {ISME communications}, volume = {5}, number = {1}, pages = {ycaf119}, pmid = {40873786}, issn = {2730-6151}, abstract = {Fecal microbiota transplantation (FMT) is a promising treatment for the chronic immune-mediated disease ulcerative colitis (UC). However, the microbial dynamics underlying clinical remission remain poorly understood. To investigate these dynamics, we analysed data from 22 UC patients treated with four rounds of FMT donated by two healthy donors. Microbiota samples from patients were collected at nine timepoints before, during, and after treatment, covering a period of 14 weeks. Additionally, 27 donor samples were analysed. Species in the recipients' gut microbiota were categorised into ecological categories based on their origin and temporal dynamics: species already present in the recipient pre-FMT, species derived from the donor, or novel species, i.e. absent before FMT in both recipient and donor but detected during or after treatment. Overdispersed Poisson regression models were employed to model the number of species within each category over time. Furthermore, we investigated the change in relative abundance for recipient, colonising, and novel species. The results revealed that recipient species with higher relative abundances prior to FMT were more likely to persist following FMT. Notably, patients who achieved combined clinical and endoscopic remission at week 14 retained a higher number of recipient species compared to non-responders. In contrast, non-responders initially exhibited colonisation of more donor species than responders, but colonisation rate decreased over time in non-responders whereas colonisation rate remained stable in responders. These findings suggest that clinical remission following FMT is associated with controlled incorporation of donor species without replacement of resident species, which may reflect a resilient recipient gut community.}, } @article {pmid40873717, year = {2025}, author = {Li, D and Tao, H and Tan, X and Ling, H and Lu, Y and Zhang, H and Theany, S and Xu, H}, title = {Gut microbiota and their metabolites ameliorate acute and chronic colitis in mice via modulating Th17/Treg balance.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1643209}, pmid = {40873717}, issn = {1664-302X}, abstract = {INTRODUCTION: Ulcerative colitis (UC) is a recurrent inflammatory bowel disease affecting the colorectum, which remains a prominent research focus due to significant individual variations in clinical therapeutic outcomes. Fecal microbiota transplantation (FMT), as a therapeutic approach to restore intestinal homeostasis, has demonstrated favorable efficacy in UC management. However, given the characteristic alternating cycles of active and remission phases in UC, there remains a paucity of in-depth research regarding the optimal timing for FMT intervention. Concurrently, butyrate - a crucial microbial metabolite - ameliorates murine colitis through both direct and indirect mechanisms, while the therapeutic effectiveness of FMT in UC correlates closely with intestinal butyrate concentration.

METHODS: This study established acute and chronic UC murine models and employed FMT and butyrate interventions to monitor dynamic alterations in gut microbiota and lymphocyte subsets. Through comprehensive analyses, we aimed to elucidate the interplay between gut microbiota and host immune mechanisms, identify the optimal therapeutic timing for UC interventions, and evaluate the mechanistic role of butyrate. These findings provide theoretical foundations for personalized microbiota-targeted therapies in UC.

RESULTS: Our findings demonstrate that gut microbiota and their metabolites exert therapeutic effects on murine acute/chronic colitis through modulation of the T helper cell 17 (Th17)/T regulatory cell (Treg) ratio. Specifically, the remission phase represents a more favorable window for intestinal homeostasis modulation, with combination therapy involving microbial metabolites exhibiting superior anti-inflammatory efficacy.

DISCUSSION: The maintenance of an appropriate Th17/Treg equilibrium during microbiota restoration demonstrates therapeutic advantages. Notably, butyrate synergistically enhances microbial therapeutic effects, providing experimental evidence for personalized modulation of gut ecosystems in inflammatory bowel disease management.}, } @article {pmid40873657, year = {2025}, author = {Chapon, J and Scanzi, J and Sokol, H and Pereira, B and Buisson, A}, title = {Efficacy of different modalities of faecal microbiota transplantation in ulcerative colitis: systematic review and network meta-analysis.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848251369624}, pmid = {40873657}, issn = {1756-283X}, abstract = {BACKGROUND: While several small sample size randomized controlled trials suggested the superiority of faecal microbiota transplantation (FMT) over placebo in ulcerative colitis (UC), the most effective modality to perform FMT remains unknown.

OBJECTIVES: To compare the efficacy of different modalities of FMT to induce clinical remission in patients with UC.

DATA SOURCES AND METHODS: We performed a systematic review and network analysis (sources: MEDLINE, Embase, Cochrane CENTRAL; random effects model) of randomized controlled trials including at least one arm of FMT in adult patients with active UC. The primary endpoint, that is, clinical remission (total Mayo score ⩽2 with Mayo endoscopic score ⩽1), was assessed between weeks 6 and 12. Results are expressed as relative risks with 95% confidence intervals, adjusted for bowel cleansing and pre-FMT antibiotics. Ranking of FMT modalities was calculated as their surface under the cumulative ranking (SUCRA).

RESULTS: Among the 12 selected studies, patients were exclusively bio-naïve in 4 studies (4/12), while between 9% and 32% had prior biologics exposure in the other trials. The risk of bias was low across all domains in seven studies. Contrary to upper gastrointestinal tract (GI) FMT (Relative risk (RR) = 1.1 (0.2-7.7)), oral capsule (RR = 7.1 (1.8-33.3)), lower GI FMT (RR = 4.5 (1.7-12.5) and combination of both (RR = 12.5 (2.1-100)) are more effective than placebo to induce clinical remission. The combination of lower GI FMT and oral capsule was significantly more effective than upper GI FMT to induce clinical remission (RR = 10.7 (1.1-104.2)). Combination of lower GI FMT and oral capsule ranked the highest for the induction of clinical remission (SUCRA = 0.93). Multidonor FMT did not perform better than single donor FMT. Autologous FMT ranked lower than placebo (SUCRA = 0.12 vs 0.22).

CONCLUSION: The combination of lower GI and oral capsule FMT seems to be the best modality of FMT for patients with UC. In clinical trials, autologous FMT should be avoided due to a potential detrimental effect.

TRIAL REGISTRATION: PROSPERO registration number: CRD42023385511.}, } @article {pmid40873417, year = {2025}, author = {You, Y and Xiang, T and Yang, C and Xiao, S and Tang, Y and Luo, G and Ling, Z and Luo, F and Chen, Y}, title = {Interactions between the gut microbiota and immune cell dynamics: novel insights into the gut-bone axis.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2545417}, doi = {10.1080/19490976.2025.2545417}, pmid = {40873417}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Bone and Bones/immunology ; Dysbiosis/immunology/microbiology ; Animals ; Osteoarthritis/immunology/microbiology ; Arthritis, Rheumatoid/immunology/microbiology ; Probiotics ; Osteoporosis/immunology/microbiology ; *Bone Diseases/immunology/microbiology ; Immune System ; Gastrointestinal Tract/immunology/microbiology ; Prebiotics ; }, abstract = {Over the past few decades, accumulating evidence has demonstrated that gut microbiota engages in a sustained dialog with the immune system, leading to microbiota-driven immune responses that mediate the regulation of bone-related diseases. Despite the complexity of the dynamic interactions within the gut-immune-bone axis, advancements in high-throughput multi-omics sequencing have significantly facilitated the detailed exploration of this intricate network, thereby providing the potential to develop novel therapeutic strategies for bone-related diseases. In this review, we first summarize the variations in gut microbiota composition observed in patients with bone-related diseases, such as rheumatoid arthritis (RA), osteoarthritis (OA), and osteoporosis (OP), in comparison to healthy controls, along with the factors influencing these changes. The review that follows synthesize evidences highlighting the profound effects of gut microbial dysbiosis on immune homeostasis and bone microenvironment, respectively. We further elaborate that the gut-immune axis and gut-bone axis are not independent but three-dimensional networks, emphasizing gut microbial dysbiosis as a pivotal driver of immune dysregulation and subsequent bone homeostasis imbalance. Therapeutic strategies to manipulate the gut-immune-bone axis based on the use of probiotics as well as prebiotics, fecal microbiota transplantation, dietary modifications, and pharmacological interventions are also discussed. Finally, we discuss the challenges of current research on the gut-immune-bone axis and propose future directions for identifying novel therapeutic targets based on this axis to treat these diseases.}, } @article {pmid40873073, year = {2025}, author = {, }, title = {[Expert consensus on the clinical application of gut microbiota transplant therapy in chronic liver disease (version 2025)].}, journal = {Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology}, volume = {33}, number = {8}, pages = {738-746}, doi = {10.3760/cma.j.cn501113-20250429-00163}, pmid = {40873073}, issn = {1007-3418}, support = {82470598//National Natural Science Foundation of China/ ; 2023A0505010007//Science and Technology Planning Project of Guangdong Province/ ; K-202401210//Guangdong Weiji Medical Development Foundation Specialized Research Fund for Gastroenterology/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Liver Diseases/therapy ; Chronic Disease ; Consensus ; Liver Cirrhosis/therapy ; Liver Neoplasms/therapy ; }, abstract = {The gut microbiota plays an important role in maintaining host health and liver function, and gut microbiota transplant (also known as fecal microbiota transplantation) has shown potential clinical benefits in the treatment of chronic liver disease. To help clinical professionals to quickly master and standardize the clinical application of gut microbiota transplant in chronic liver disease, the Group of the Liver Disease-related Gastroenterology Branch of the Chinese Medical Association organized experts in related fields to formulate the "Expert Consensus on the Clinical Application of Gut Microbiota Transplant in the Treatment of Chronic Liver Disease" such as chronic hepatitis, cirrhosis and liver cancer, including indications, contraindications, effectiveness, safety, donor selection, transplant routes, transplant precautions, prevention and treatment of adverse reactions, and other aspects to provide reference and guidance for clinicians to implement gut microbiota transplant.}, } @article {pmid40872257, year = {2025}, author = {Cianci, G and Maini, G and Ferraresi, M and Pezzi, G and Bortolotti, D and Rizzo, S and Beltrami, S and Schiuma, G}, title = {Immune Modulation by Microbiota and Its Possible Impact on Polyomavirus Infection.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {8}, pages = {}, doi = {10.3390/pathogens14080747}, pmid = {40872257}, issn = {2076-0817}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Polyomavirus Infections/immunology/microbiology/virology/therapy ; *Polyomavirus/immunology ; Dysbiosis/immunology ; Fecal Microbiota Transplantation ; Animals ; Immunocompromised Host ; }, abstract = {Polyomaviruses are a family of small DNA viruses capable of establishing persistent infections, and they can pose significant pathogenic risks in immunocompromised hosts. While traditionally studied in the context of viral reactivation and immune suppression, recent evidence has highlighted the gut microbiota as a critical regulator of host immunity and viral pathogenesis. This review examines the complex interactions between polyomaviruses, the immune system, and intestinal microbiota, emphasizing the role of short-chain fatty acids (SCFAs) in modulating antiviral responses. We explore how dysbiosis may facilitate viral replication, reactivation, and immune escape and also consider how polyomavirus infection can, in turn, alter microbial composition. Particular attention is given to the Firmicutes/Bacteroidetes ratio as a potential biomarker of infection risk and immune status. Therapeutic strategies targeting the microbiota, including prebiotics, probiotics, and fecal microbiota transplantation (FMT), are discussed as innovative adjuncts to immune-based therapies. Understanding these tri-directional interactions may offer new avenues for mitigating disease severity and improving patient outcomes during viral reactivation.}, } @article {pmid40871460, year = {2025}, author = {Ren, J and Wang, Q and Hong, H and Tang, C}, title = {Fecal Microbiota Transplantation in Alzheimer's Disease: Mechanistic Insights Through the Microbiota-Gut-Brain Axis and Therapeutic Prospects.}, journal = {Microorganisms}, volume = {13}, number = {8}, pages = {}, doi = {10.3390/microorganisms13081956}, pmid = {40871460}, issn = {2076-2607}, support = {HY202411//One health Interdisciplinary Research Project, Ningbo University/ ; D16013//National 111 Project of China/ ; the Health Fund of Translational Biomedicine//the Health Fund of Translational Biomedicine/ ; }, abstract = {Alzheimer's disease (AD), a prevalent neurodegenerative disorder in the aging population, remains without definitive therapeutic solutions. Emerging insights into the gut microbiota (GM) and its bidirectional communication with the central nervous system(CNS) through the microbiota-gut-brain axis (MGBA) have unveiled potential correlative mechanisms that may contribute to AD pathogenesis, though causal evidence remains limited. Dysregulation of GM composition (dysbiosis) exacerbates AD progression via neuroinflammation, amyloid-β (Aβ) deposition, and tau hyperphosphorylation (p-tau), while restoring microbial homeostasis presents a promising therapeutic strategy. Fecal microbiota transplantation (FMT), a technique to reconstitute gut ecology by transferring processed fecal matter from healthy donors, has demonstrated efficacy in ameliorating cognitive deficits and neuropathology in AD animal models. Preclinical studies reveal that FMT reduces Aβ plaques, normalizes tau phosphorylation, suppresses inflammasome activation, and restores microglial homeostasis through modulation of microbial metabolites and immune pathways. Although clinical evidence remains limited to case reports and small-scale trials showing potential therapeutic effect, safety concerns regarding long-term effects and protocol standardization necessitate further investigation. This review synthesizes current knowledge on GM-AD interactions, evaluates FMT's mechanistic potential, and discusses challenges in translating this ancient practice into a cutting-edge AD therapy. Rigorous randomized controlled trials and personalized microbiota-based interventions are imperative to advance FMT from bench to bedside.}, } @article {pmid40871301, year = {2025}, author = {Chen, S and Liu, T and Chen, J and Shen, H and Wang, J}, title = {Fecal Virome Transplantation Confirms Non-Bacterial Components (Virome and Metabolites) Participate in Fecal Microbiota Transplantation-Mediated Growth Performance Enhancement and Intestinal Development in Broilers with Spatial Heterogeneity.}, journal = {Microorganisms}, volume = {13}, number = {8}, pages = {}, doi = {10.3390/microorganisms13081795}, pmid = {40871301}, issn = {2076-2607}, support = {Project No. CZ004306//"Tianshan Talent" Program/ ; Project No. XJLG-CYJSTX-10//Xinjiang Modern Agriculture Industry Technology System/ ; }, abstract = {Fecal microbiota transplantation (FMT) promotes growth performance and intestinal development in yellow-feathered broilers, but whether the virome and metabolites contribute to its growth-promoting effect remains unclear. This study removed the microbiota from FMT filtrate using a 0.45 μm filter membrane, retaining the virome and metabolites to perform fecal virome transplantation (FVT), aiming to investigate its regulatory role in broiler growth. Healthy yellow-feathered broilers with high body weights (top 10% of the population) were used as FVT donors. Ninety-six 8-day-old healthy male yellow-feathered broilers (95.67 ± 3.31 g) served as FVT recipients. Recipient chickens were randomly assigned to a control group and an FVT group. The control group was gavaged with 0.5 mL of normal saline daily, while the FVT group was gavaged with 0.5 mL of FVT solution daily. Growth performance, immune and antioxidant capacity, intestinal development and related gene expression, and microbial diversity were measured. The results showed that FVT improved the feed utilization rate of broilers (the feed conversion ratio decreased by 3%; p < 0.05), significantly increased jejunal length (21%), villus height (69%), and crypt depth (84%) (p < 0.05), and regulated the jejunal barrier: insulin-like growth factor-1 (IGF-1) (2.5 times) and Mucin 2 (MUC2) (63 times) were significantly upregulated (p < 0.05). FVT increased the abundance of beneficial bacteria Lactobacillales. However, negative effects were also observed: Immunoglobulin A (IgA), Immunoglobulin G (IgG), Immunoglobulin M (IgM), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), and Interferon-gamma (IFN-γ) in broilers were significantly upregulated (p < 0.05), indicating immune system overactivation. Duodenal barrier-related genes Mucin 2 (MUC2), Occludin (OCLN), Claudin (CLDN1), and metabolism-related genes solute carrier family 5 member 1 (SLC5A1) and solute carrier family 7 member 9 (SLC7A9) were significantly downregulated (p < 0.05). The results of this trial demonstrate that, besides the microbiota, the gut virome and metabolites are also functional components contributing to the growth-promoting effect of FMT. The differential responses in the duodenum and jejunum reveal spatial heterogeneity and dual effects of FVT on the intestine. The negative effects limit the application of FMT/FVT. Identifying the primary functional components of FMT/FVT to develop safe and targeted microbial preparations is one potential solution.}, } @article {pmid40870405, year = {2025}, author = {Bibolar, AC and Nechita, VI and Lung, FC and Crecan-Suciu, BD and Păunescu, RL}, title = {Gut Feelings: Linking Dysbiosis to Depression-A Narrative Literature Review.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {8}, pages = {}, doi = {10.3390/medicina61081360}, pmid = {40870405}, issn = {1648-9144}, mesh = {Humans ; *Dysbiosis/complications/psychology/physiopathology/microbiology ; *Depression/microbiology/etiology/psychology/physiopathology ; *Gastrointestinal Microbiome/physiology ; Animals ; Probiotics/therapeutic use ; }, abstract = {The balance between physiological, psychological, and environmental factors often shapes human experience. In recent years, research has drawn attention to the gut microbiota as a significant contributor to brain function and emotional regulation. This narrative review examines how changes in gut microbiota may relate to depression. We selected studies that explore the link between intestinal dysbiosis and mood, focusing on mechanisms such as inflammation, vagus nerve signaling, HPA axis activation, gut permeability, and neurotransmitter balance. Most of the available data come from animal models, but findings from human studies suggest similar patterns. Findings are somewhat difficult to compare due to differences in measurement procedures and patient groups. However, several microbial shifts have been observed in people with depressive symptoms, and trials with probiotics or fecal microbiota transplant show potential. These results remain limited. We argue that these interventions deserve more attention, especially in cases of treatment-resistant or inflammation-driven depression. Understanding how the gut and brain interact could help define clearer subtypes of depression and guide new treatment approaches.}, } @article {pmid40869967, year = {2025}, author = {Fu, Y and Bonifacio-Mundaca, J and Desterke, C and Casafont, Í and Mata-Garrido, J}, title = {Genomic Alterations and Microbiota Crosstalk in Hepatic Cancers: The Gut-Liver Axis in Tumorigenesis and Therapy.}, journal = {Genes}, volume = {16}, number = {8}, pages = {}, doi = {10.3390/genes16080920}, pmid = {40869967}, issn = {2073-4425}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Liver Neoplasms/genetics/microbiology/therapy/pathology ; *Carcinoma, Hepatocellular/genetics/microbiology/therapy/pathology ; *Carcinogenesis/genetics ; Liver/pathology/metabolism/microbiology ; *Cholangiocarcinoma/genetics/microbiology/therapy ; Mutation ; Epigenesis, Genetic ; Animals ; }, abstract = {Background/Objectives: Hepatic cancers, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are major global health concerns due to rising incidence and limited therapeutic success. While traditional risk factors include chronic liver disease and environmental exposures, recent evidence underscores the significance of genetic alterations and gut microbiota in liver cancer development and progression. This review aims to integrate emerging knowledge on the interplay between host genomic changes and gut microbial dynamics in the pathogenesis and treatment of hepatic cancers. Methods: We conducted a comprehensive review of current literature on genetic and epigenetic drivers of HCC and CCA, focusing on commonly mutated genes such as TP53, CTNNB1, TERT, IDH1/2, and FGFR2. In parallel, we evaluated studies addressing the gut-liver axis, including the roles of dysbiosis, microbial metabolites, and immune modulation. Key clinical and preclinical findings were synthesized to explore how host-microbe interactions influence tumorigenesis and therapeutic response. Results: HCC and CCA exhibit distinct but overlapping genomic landscapes marked by recurrent mutations and epigenetic reprogramming. Alterations in the gut microbiota contribute to hepatic inflammation, genomic instability, and immune evasion, potentially enhancing oncogenic signaling pathways. Furthermore, microbiota composition appears to affect responses to immune checkpoint inhibitors. Emerging therapeutic strategies such as probiotics, fecal microbiota transplantation, and precision oncology based on mutational profiling demonstrate potential for personalized interventions. Conclusions: The integration of host genomics with microbial ecology provides a promising paradigm for advancing diagnostics and therapies in liver cancer. Targeting the gut-liver axis may complement genome-informed strategies to improve outcomes for patients with HCC and CCA.}, } @article {pmid40868265, year = {2025}, author = {Haidar, L and Bănărescu, CF and Uța, C and Zimbru, EL and Zimbru, RI and Tîrziu, A and Pătrașcu, R and Șerb, AF and Georgescu, M and Nistor, D and Panaitescu, C}, title = {Beyond the Skin: Exploring the Gut-Skin Axis in Chronic Spontaneous Urticaria and Other Inflammatory Skin Diseases.}, journal = {Biomedicines}, volume = {13}, number = {8}, pages = {}, doi = {10.3390/biomedicines13082014}, pmid = {40868265}, issn = {2227-9059}, abstract = {Emerging evidence suggests a critical role of the gut microbiome in modulating systemic immune responses, with increasing relevance in dermatological diseases. Chronic spontaneous urticaria (CSU), traditionally viewed as an isolated cutaneous disorder, is now recognized as a systemic immune condition involving complex interactions between innate and adaptive immunity, mast cell dysregulation, and non-IgE-mediated pathways. This review explores the gut-skin axis as a unifying concept linking intestinal dysbiosis to inflammatory skin diseases, including atopic dermatitis, psoriasis, rosacea, and acne. Special emphasis is placed on CSU, where altered gut microbial composition, characterized by reduced diversity, depletion of short-chain fatty acid-producing bacteria, and expansion of Proteobacteria, may contribute to increased intestinal permeability, systemic immune activation via toll-like receptors, and heightened mast cell sensitivity. We discuss findings from animal models demonstrating that gut microbiota modulation can attenuate mast cell hyperreactivity and reduce urticarial symptoms. In parallel, we examine clinical evidence supporting the potential role of probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation as adjunctive strategies in CSU management. Despite promising findings, challenges remain in translating microbiome research into effective therapies due to interindividual variability, the complexity of host-microbiome interactions, and a lack of standardized protocols. Future research should focus on identifying predictive microbial patterns and developing personalized microbiome-targeted interventions. Understanding the bidirectional gut-skin relationship may open new therapeutic avenues beyond symptomatic treatment, positioning the microbiome as a novel target in CSU and related inflammatory dermatoses.}, } @article {pmid40868053, year = {2025}, author = {Maruyama, T and Ishikawa, D and Kurokawa, R and Masuoka, H and Nomura, K and Haraikawa, M and Orikasa, M and Odakura, R and Koma, M and Omori, M and Ishino, H and Ito, K and Shibuya, T and Suda, W and Nagahara, A}, title = {Hydrogen Gas Inhalation Improved Intestinal Microbiota in Ulcerative Colitis: A Randomised Double-Blind Placebo-Controlled Trial.}, journal = {Biomedicines}, volume = {13}, number = {8}, pages = {}, doi = {10.3390/biomedicines13081799}, pmid = {40868053}, issn = {2227-9059}, support = {None//MiZ Co., Ltd/ ; }, abstract = {Background/Objective: Dysbiosis is implicated in the pathogenesis of ulcerative colitis. Hydrogen has been reported to promote intestinal microbiota diversity and suppress ulcerative colitis progression in mice models. In this study, we investigated changes in the intestinal microbiota, therapeutic effects, and safety of hydrogen inhalation in patients with ulcerative colitis. Methods: In this randomised, double-blind, placebo-controlled trial, 10 active patients with ulcerative colitis (aged ≥20 years; Lichtiger's clinical activity index, 3-10; and Mayo endoscopic subscores ≥1) participated, and they were assigned to either a hydrogen or air inhalation group (hydrogen and placebo groups, respectively). All patients inhaled gas for 4 h every day for 8 weeks. Subsequently, we performed clinical indices and microbiota analyses using the metagenomic sequencing of stool samples before and after inhalation. Results: There was significant difference in the sum of the Mayo endoscopic subscores before and after inhalation in the clinical assessment indices. The hydrogen group showed higher α-diversity (p = 0.19), and the variation in β-diversity was markedly different, compared to the placebo group, in intestinal microbiota analysis (p = 0.02). Functional gene analysis revealed 115 significant genetic changes in the hydrogen group following treatment. No inhalation-related adverse events were observed. Conclusions: Hydrogen inhalation appeared to improve intestinal microbiota diversity; however, no clear therapeutic effect on ulcerative colitis was observed. Further studies are needed, and hydrogen inhalation may possibly lead to a logical solution combined with microbiome therapy, such as faecal microbiota transplantation, with fewer adverse events.}, } @article {pmid40868023, year = {2025}, author = {Kullar, R and Johnson, S and Goldstein, EJC}, title = {Clostridioides difficile in Peripartum Women: Review of Outcomes and Treatment.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {8}, pages = {}, doi = {10.3390/antibiotics14080829}, pmid = {40868023}, issn = {2079-6382}, abstract = {Background:Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections in the United States with increasing rates in younger patients and those in the community. CDI incidence may also be on the rise in peripartum women. Methods: We conducted a literature review to assess the incidence and outcomes of CDI in the peripartum population and review treatment options. Results: Peripartum patients have a high risk of complications and adverse events associated with CDI. Most patients have been treated with vancomycin or metronidazole; however, cases of patients recurring on standard treatment have been described, with patients having successful outcomes with fidaxomicin or fecal microbiota transplantation (FMT). Probiotics have been shown to be safe in peripartum women; however, the role in preventing primary and secondary CDI has not been studied. Conclusions: Peripartum women that develop CDI are at increased risk for complications. Treatment includes vancomycin, metronidazole, or fidaxomicin or FMT for recurrent cases.}, } @article {pmid40867077, year = {2025}, author = {Ebadi, M and Reddi, S and Senyshyn, L and Minot, SS and Gooley, T and Kabage, AJ and Lee, SJ and Hill, GR and Khoruts, A and Rashidi, A}, title = {Effect of fecal microbiota transplantation on gut microbiota functional profile in recipients of allogeneic hematopoietic cell transplantation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2551882}, doi = {10.1080/19490976.2025.2551882}, pmid = {40867077}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Male ; Middle Aged ; Female ; Adult ; Bacteria/classification/genetics/isolation & purification/metabolism ; *Dysbiosis/therapy/microbiology ; Transplantation, Homologous ; Feces/microbiology ; Aged ; }, abstract = {Intestinal dysbiosis has been associated with both the effectiveness and toxicity of immunotherapy in cancer patients, inspiring multiple trials investigating fecal microbiota transplantation (FMT) in these patients. FMT restores microbial community structures damaged by antibiotics and enriches the microbiota with beneficial bacteria. However, the precise mechanism through which FMT exerts its effects and provides clinical benefits remains incompletely understood. Efforts to date have primarily focused on characterizing taxonomic changes following FMT. We hypothesized that FMT may also modify the functional pathways and metabolic capabilities of the gut microbiota, with possible clinical impact. To investigate this, we conducted a study involving 17 patients with blood disorders who received prophylactic FMT from one of the three healthy donors shortly after hematopoietic cell transplantation (HCT). By analyzing shotgun metagenomic profiles of the baseline, pre-FMT, and post-FMT gut microbiota, we demonstrate that FMT effectively restored pathways that had been depleted following HCT. However, it did not significantly reduce pathways that had expanded, indicating that FMT operates primarily through a restorative mechanism, reestablishing lost functional capabilities in the microbiota rather than suppressing overactive pathways. These findings highlight the potential for optimizing FMT protocols and identifying patient populations where FMT may be particularly beneficial.}, } @article {pmid40866789, year = {2025}, author = {Kusakabe, S and Kurashige, R and Fukushima, K and Shimizu, K and Yoshihara, T and Motooka, D and Nakamura, S and Kurashige, M and Nakata, K and Hino, A and Kasahara, H and Ueda, T and Fujita, J and Hosen, N and Takehara, T and Oda, J}, title = {Fecal microbiota transplantation for Crohn's disease-like intestinal lesions arising after allogeneic stem cell transplantation.}, journal = {International journal of hematology}, volume = {}, number = {}, pages = {}, pmid = {40866789}, issn = {1865-3774}, abstract = {Several cases of inflammatory bowel disease (or similar gastrointestinal lesions) arising after allogeneic hematopoietic stem cell transplantation have been reported, but the effect of intestinal dysbiosis on development of these lesions remains unclear. We performed fecal microbiota transplantation (FMT) and 16S rRNA microbiome analysis in a patient who developed Crohn's disease-like lesions after allogeneic transplantation. A 62-year-old woman underwent haploidentical stem cell transplantation from her daughter to treat double-hit lymphoma relapsed after chimeric antigen receptor T-cell therapy, and achieved remission without developing acute graft-versus-host disease. Eight months later, she developed Crohn's disease-like intestinal lesions after cytomegalovirus enteritis. Her condition did not improve with the conventional treatment, so she underwent FMT from her daughter as part of a clinical trial. Diarrhea gradually improved, and follow-up endoscopy 4 months after the FMT showed ulcer healing and scarring. The 16S rRNA analysis revealed a reduction in the relative abundance of the Enterococcus genus after FMT, suggesting that dysbiosis may have contributed to lesion development. The patient is currently on a regular diet, with no symptom recurrence, and the primary disease remains in remission. Although this outcome suggests that FMT is effective, careful patient selection is required to reduce the risk of FMT-associated sepsis.}, } @article {pmid40865967, year = {2025}, author = {Jee, JJ and Park, S and Kim, J and Lee, H and Koh, H and Koo, BN}, title = {Bacterial extracellular vesicle as a predictive biomarker for postoperative delirium status after spinal surgery: a prospective cohort study.}, journal = {International journal of surgery (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1097/JS9.0000000000003024}, pmid = {40865967}, issn = {1743-9159}, abstract = {BACKGROUND: Prognostic factors significantly associated with postoperative delirium (POD) have been reported discordantly, possibly due to heterogeneous cohorts. Here, bacteria extracellular vesicles (BEVs) were introduced to predict the POD status of a unique patient cohort.

METHODS: One hundred twenty-eight patients who underwent spinal surgery participated in this prospective cohort study. Significant preoperative factors (i.e., baseline characteristics, and sequences of 16s rRNA genes from bloods and stools) between patients with and without delirium were subjected to random forest classifiers for prediction model, and potential metabolites that regulate the POD were inferred in silico.

RESULTS: No significant differences were found between patients with and without delirium in terms of demographics, anthropometrics, intervention history or preoperative cognitive function scores, except for circulating BEVs; delirium group had less diverse BEVs dominated with EVs from Gammaproteobacteria, whereas more diverse BEVs enriched with EVs from Bacilli and Alphaproteobacteria were significantly associated with non-delirium. Compared to that with baseline characteristics or gut microbiome, prediction model using random forest classifier with the significant BEVs yielded the lowest error rate of 21.59%, and was validated with an independent data set, resulting in 80% accuracy. Moreover, EVs from Moraxellaceae and Acinetobacter showed the highest probabilities of prediction of the POD despite their low relative abundance, indicating the most significant prognostic markers for the POD. As the inference of a potential metabolites that regulate the POD, succinate and enterobacterial common antigens delivered from BEV cargo were expected to participate in pathogenic events, whereas S-methyl-5'-thioadenosine, 2-oxoglutarate, pyruvate, acetate and butyrate may play a neuroprotective role in the POD.

CONCLUSIONS: The profile of circulating preoperative BEVs is the key prognostic factor for distinguishing POD in elderly surgical patients with controlled baseline conditions. Metabolites of defensive and offensive mechanisms inferred from BEVs will be essential for developing next-generation POD prevention strategies.}, } @article {pmid40865561, year = {2025}, author = {Wei, S and Lu, J}, title = {Microbial Modulation of the Gut-Liver Axis in Autoimmune Liver Diseases.}, journal = {Seminars in liver disease}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2679-3641}, pmid = {40865561}, issn = {1098-8971}, abstract = {Autoimmune liver diseases (AILDs), including autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, are chronic inflammatory conditions influenced by complex interactions among genetic, environmental, and immunological factors. Recent studies have highlighted the critical role of the gut microbiota in regulating immune responses beyond the gastrointestinal tract via the gut-liver axis. This review examines the interactions between intestinal microecology and AILDs, with a focus on mechanisms such as bacterial translocation, disruption of the intestinal barrier, and modulation of microbial metabolites. Dysbiosis, involving alterations in both bacterial and fungal communities, has been associated with immune dysregulation and hepatic inflammation. Evidence indicates that short-chain fatty acids, bile acids, and microbial products such as lipopolysaccharides influence hepatic immune tolerance and inflammatory signaling pathways. Several diagnostic and therapeutic approaches, including probiotics, fecal microbiota transplantation, and bile acid regulation, have shown potential to slow or alter disease progression. However, the clinical translation of these findings remains limited due to interindividual variability and the complex nature of the gut-liver axis. Continued research is needed to develop precision medicine strategies that can harness intestinal microecology for improved management of AILDs.}, } @article {pmid40865528, year = {2025}, author = {Shi, Y and Li, Y and Li, H and Haerheng, A and Marcelino, VR and Lu, M and Lemey, P and Tang, J and Bi, Y and Pettersson, JH and Bohlin, J and Klaps, J and Wu, Z and Wan, W and Sun, B and Kang, M and Holmes, EC and He, N and Su, S}, title = {Extensive cross-species transmission of pathogens and antibiotic resistance genes in mammals neglected by public health surveillance.}, journal = {Cell}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cell.2025.08.016}, pmid = {40865528}, issn = {1097-4172}, abstract = {Non-traditional farmed and wild mammals are often neglected in pathogen surveillance. Through metagenomic and metatranscriptomic sequencing of fecal and tissue samples from 973 asymptomatic mammals, we identified 128 viruses (30 novel), including a new coronavirus genus, 10,255 bacterial species (over 7,000 undescribed), 201 fungi, and 7 parasites. Farmed and wild mammals shared 13.3% of virus species, including canine coronavirus in Asiatic black bears and Getah virus in rabbits, while the 2.3.4.4b clade of H5N1 avian influenza virus was found in a wild leopard cat. We identified potential bacterial pathogen transmission between farmed and wild mammals and bacterial strains with high genetic similarity to those found in humans. We observed 157 clinically prioritized antibiotic resistance genes (ARGs) in mammalian microbiomes with greater than 99% identity to ARGs from human microbiomes, often co-occurring with mobile genetic elements. Overall, this work highlights cross-species risks at the human-animal interface.}, } @article {pmid40865242, year = {2025}, author = {Zhang, Y and Chen, Q and Xu, Y and Lv, Y and Wang, Y and Shi, XY and Liu, J and Wen, J and Li, X and Li, B}, title = {Soy isoflavones mitigate atrazine-induced dopaminergic neuron damage via reshaping short-chain fatty acid-producing bacteria in gut microbiota and modulating the GPR43/GLP-1/GLP-1R axis.}, journal = {Ecotoxicology and environmental safety}, volume = {303}, number = {}, pages = {118938}, doi = {10.1016/j.ecoenv.2025.118938}, pmid = {40865242}, issn = {1090-2414}, abstract = {Atrazine (ATR), a widely used herbicide, is linked to dopaminergic neurotoxicity and persistent gut microbiota dysbiosis after early life exposure. However, whether the gut microbiota mediates ATR-induced loss of dopaminergic neurons remains unclear. Mice were exposed to ATR from juvenility (4th week) until adulthood (12th week), after which exposure ceased until the 20th week. The role of gut microbiota was confirmed through fecal microbiota transplantation (FMT), which was classified into different groups based on the donor's ATR treatment status. 16S rRNA sequencing revealed that Akkermansia, which exhibited significant differences across FMT groups, is a classic short-chain fatty acid (SCFA)-producing bacteria. FMT recipients receiving ATR-donor microbiota exhibited reduced colonic G Protein-Coupled Receptor 43 (GPR43), serum Glucagon-like Peptide-1 (GLP-1), and substantia nigra Glucagon-like Peptide-1 receptor (GLP-1R)/Tyrosine hydroxylase (TH) levels. Soy isoflavones (SIF), selected for their dual prebiotic and neuroprotective effects, attenuated ATR-induced dopaminergic neurotoxicity by enriching SCFA-producing gut microbiota and the level of SCFAs, thereby activating the GPR43/GLP-1/GLP-1R axis and reducing neuronal loss. These findings demonstrate the critical role of gut microbiota in ATR-induced dopaminergic neurodegeneration, positioning SIF-mediated microbiota modulation as a promising therapeutic approach within the "food-medicine homology" framework.}, } @article {pmid40863733, year = {2025}, author = {Alaeddin, S and Ko, Y and Steiner-Lim, GZ and Jensen, SO and Roberts, TL and Ho, V}, title = {The Effect of Faecal Microbiota Transplantation on Cognitive Function in Cognitively Healthy Adults with Irritable Bowel Syndrome: Protocol for a Randomised, Placebo-Controlled, Double-Blinded Pilot Study.}, journal = {Methods and protocols}, volume = {8}, number = {4}, pages = {}, pmid = {40863733}, issn = {2409-9279}, abstract = {Faecal microbiota transplantation (FMT) is an emerging therapy for gastrointestinal and neurological disorders, acting via the microbiota-gut-brain axis. Altering gut microbial composition may influence cognitive function, but this has not been tested in cognitively healthy adults. This randomised, double-blinded, placebo-controlled pilot trial investigates whether FMT is feasible and improves cognition in adults with irritable bowel syndrome (IBS). Participants receive a single dose of FMT or placebo via rectal retention enema. Cognitive performance is the primary outcome, assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Secondary outcomes include IBS symptom severity and mood. Tertiary outcomes include microbiome composition and plasma biomarkers related to inflammation, short-chain fatty acids, and tryptophan metabolism. Outcomes are assessed at baseline and at one, three, six, and twelve months following treatment. We hypothesise that FMT will lead to greater improvements in cognitive performance than placebo, with benefits extending beyond practice effects, emerging at one month and persisting in the long term. The findings will contribute to evaluating the safety and efficacy of FMT and enhance our understanding of gut-brain interactions.}, } @article {pmid40861872, year = {2025}, author = {Baydoun, H and Hussain, N and Wu, KO and Kelly, CR and Fischer, M}, title = {What's New and What's Next in Fecal Microbiota Transplantation?.}, journal = {Biologics : targets & therapy}, volume = {19}, number = {}, pages = {481-496}, pmid = {40861872}, issn = {1177-5475}, abstract = {Fecal microbiota transplantation (FMT) has evolved from a niche therapy to a cornerstone in the treatment of recurrent Clostridioides difficile infection (rCDI). Initially introduced in the 1950s, its relevance has surged with the emergence of virulent and antibiotic-resistant C. difficile strains. In recent years, the FDA approved two standardized microbiota-based therapeutics-Rebyota™ (fecal microbiota, live-jslm) and Vowst™ (fecal microbiota spores, live-brpk)-for rCDI prevention. Multiple pivotal trials support the efficacy and safety of both traditional FMT and the FDA-approved prescription FMTs, with sustained response rates surpassing 80% in select populations. In parallel, live biotherapeutic products (LBPs)-donor independent, well-defined microbial consortia produced in laboratory setting are under development. Examples include VE303 and NTCD-M3, a single non-toxigenic C. difficile strain (M3). Beyond the FDA approved therapeutics, conventional FMT is gaining traction as a potential treatment for severe or fulminant CDI, especially in patients not responding to antibiotics and ineligible for surgery. Investigational indications include decolonizing multidrug-resistant organisms and treatment of noninfectious conditions such as inflammatory bowel disease, irritable bowel syndrome, liver disease, and metabolic syndrome. Given the differing pathophysiology of these conditions, a tailored approach supported by rigorous clinical trials is essential. Although there is a growing shift, particularly in the United States, toward the use of FDA-approved FMTs, global practices remain heterogeneous, with conventional FMT still widely employed. Meanwhile, regulatory pathways and clinical guidelines for microbiota-derived biologics and live biotherapeutic products continue to evolve. In this manuscript, we provide an update on the emerging use of FDA-approved prescription microbiota-derived therapeutics for the prevention of rCDI, review data on investigational agents including both donor dependent and donor independent microbial products, and summarize current evidence on the use of conventional FMT for indications beyond prevention of rCDI.}, } @article {pmid40861794, year = {2025}, author = {Wang, B and Stephen, SJ and Cyphert, EL and Liu, C and Hernandez, CJ and Vashishth, D}, title = {Fecal microbiota transplantation in mice improves bone material properties through altered mineral quality.}, journal = {JBMR plus}, volume = {9}, number = {9}, pages = {ziaf115}, pmid = {40861794}, issn = {2473-4039}, abstract = {Disruptions of the composition of the gut microbiome are linked to impaired bone tissue strength. Fecal microbiota transplantation (FMT) is an established clinical therapy that can restore a healthy gut microbiome and reduce systemic inflammation. However, whether FMT from a healthy donor could rescue bone fragility is unknown. As induced inflammation causes mineralization defects, we hypothesize that manipulations of the gut microbiota alter bone fracture resilience through changes in mineral quality. Here, we altered the compositions of the gut microbiome in mice via antibiotics (ampicillin and neomycin) and FMT. Mice were allocated to 5 groups (M/F, N = 13-18/group): Unaltered, Continuous (dosed 4-24 wk), Initial (dosed 4-16 wk), Reconstituted (dosed 4-16 wk with subsequent FMT from age- and sex-matched mice with unaltered gut microbiota), and Delayed (dosed 16-24 wk). Fracture toughness testing and Raman spectroscopy were conducted on the femora. The maximum toughness was greater in the Reconstituted group (for females, p < .05 compared to Continuous, Unaltered, and Delayed groups; for males, p < .05 compared to groups with antibiotic dosing). The Reconstituted group showed lower type-B carbonate substitution in the bone mineral (all p < .01 for both sexes), and lower mineral-to-matrix ratio (all p < .01 for males, for females, p < .01 compared to Unaltered, Initial, and Delayed groups). In females, mineral crystallinity was higher in the Reconstituted group than those dosed with antibiotics (all p < .05). Serum inflammation marker TNF-α was positively correlated with type-B carbonate substitutions (ρ = 0.66), mineral-to-matrix ratio (ρ = 0.71), and carboxymethyl-lysine (CML) in bone matrix (ρ = 0.43). Enhanced bone maximum fracture toughness was associated with reduced type-B carbonate substitution (r = -0.45), decreased mineral-to-matrix ratio (r = -0.40), increased mineral crystallinity (r = 0.33), and lower levels of bone CML (r = -0.49, all p < .01). These results suggest that the introduction of more beneficial gut microbiota can increase fracture resistance by modifying mineral composition and quality, likely through the reduction of systemic inflammation.}, } @article {pmid40861764, year = {2025}, author = {Mishra, AP and Marrelli, LM and Bonner-Reid, FT and Shekhawat, P and Toney, R and Benipal, IK and Dias, HA and Kandi, A and Siddiqui, HF}, title = {Gut-Brain Axis: Understanding the Interlink Between Alterations in the Gut Microbiota and Autism Spectrum Disorder.}, journal = {Cureus}, volume = {17}, number = {7}, pages = {e88579}, pmid = {40861764}, issn = {2168-8184}, abstract = {Autism spectrum disorder (ASD) is an umbrella term used for a complex neurobehavioral disorder. ASD is a multifactorial condition, with significant roles played by environmental, immunological, and genetic factors. The microbiota-gut-brain axis has been implicated in the pathophysiology of ASD in recent years. This review article aims to explore the correlation between gut dysbiosis and autism, and its potential impact on management strategies. Gastrointestinal (GI) symptoms, including diarrhea, constipation, and bloating, are prevalent among children with ASD. These disorders are commonly linked to increased behavioral symptoms, such as social disengagement, anxiety, and irritability. Increased gut permeability, attributable to gut dysbiosis, plays a significant role in disrupting the gut-brain axis, which is coordinated by neurological, immunological, and endocrinological routes. Elevated levels of inflammatory cytokines, changes in the generation of neurotransmitters, and disturbances in gut-derived metabolites are all considered direct consequences of dysbiosis. Treatment options, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary changes, have shown promising results. However, the effectiveness and long-term safety of these therapies are still being studied. It is imperative to explore this perplexing interaction through further research to encourage clinicians to adopt therapeutic approaches targeting the gut microbiota in patients with ASD.}, } @article {pmid40861492, year = {2025}, author = {Yu, X and Yu, X and Wang, Y and Guo, X and Wang, C and Wang, F}, title = {Respiratory diseases and the gut microbiota: an updated review.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1629005}, pmid = {40861492}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/microbiology ; COVID-19/microbiology ; Lung/microbiology/immunology ; *Respiratory Tract Diseases/microbiology ; SARS-CoV-2 ; Probiotics ; Animals ; Pulmonary Disease, Chronic Obstructive/microbiology ; }, abstract = {The gut microbiota constitutes a vital ecosystem within the human body playing a pivotal role in immune regulation and metabolic homeostasis. Emerging research underscores a sophisticated interplay between the gut and lungs, termed the "gut-lung axis." Gut microbes exert influence over pulmonary immunity and metabolism via immune mediators (e.g., cytokines and interleukins), metabolites (e.g., short-chain fatty acids) and direct microbial translocation. Dysbiosis of the gut microbiota has been implicated in a spectrum of respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), Coronavirus Disease 2019 (COVID-19), lung cancer, idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), acute lower respiratory infection (ALRI) and tuberculosis (TB). Although multi-omics technologies have elucidated certain mechanisms underlying the gut-lung axis, numerous pathways remain to be fully delineated. This review synthesizes current knowledge on the role of gut microbiota and their metabolites in respiratory diseases and assesses their therapeutic potential. Future investigations should prioritize strategies to restore and maintain microbial homeostasis, such as dietary modifications, probiotic supplementation and fecal microbiota transplantation to pioneer novel preventive and therapeutic approaches. These summaries of advances in gut microbiology research promise better management and exploration of therapeutic strategies for respiratory diseases.}, } @article {pmid40861487, year = {2025}, author = {Tao, W and Yu, Y and Tan, D and Huang, X and Huang, J and Lin, C and Yu, R}, title = {Microbiota and enteric nervous system crosstalk in diabetic gastroenteropathy: bridging mechanistic insights to microbiome-based therapies.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1603442}, pmid = {40861487}, issn = {2235-2988}, mesh = {Humans ; *Enteric Nervous System/physiopathology ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/microbiology ; Animals ; *Gastrointestinal Diseases/microbiology/therapy ; *Diabetes Complications/microbiology/therapy ; }, abstract = {Diabetes mellitus has emerged as a global public health crisis, with over half of patients experiencing gastrointestinal (GI) symptoms that exacerbate glucose fluctuations and impair quality of life. While prior research on the pathophysiology of diabetic gastroenteropathy (DGE) focused primarily on autonomic neuropathy, particularly involving the vagus nerve, recent studies have shifted toward the impairment of the enteric nervous system (ENS). As the largest autonomous neural network governing GI motility independent of central control, structural and functional abnormalities of the ENS constitute the fundamental pathological basis for DGE. This review first delineates gut microbial alterations in diabetes and mechanisms by which dysbiosis compromises the integrity of the ENS. Second, we analyze how microbiota-derived metabolites (short-chain fatty acids, bile acids, tryptophan), gut hormones (glucagon-like peptide-1, ghrelin), and neurotransmitters (acetylcholine, vasoactive intestinal peptide, nitric oxide) multitarget the ENS-collectively establishing the "microbiota-ENS axis" as the central hub for GI sensorimotor control. Finally, we provide an overview of preclinical and clinical evidence for microbiome-targeted therapies (probiotics, prebiotics, fecal microbiota transplantation) in alleviating DGE symptoms and repairing ENS while outlining translational challenges and future research priorities.}, } @article {pmid40860437, year = {2025}, author = {Ma, C and He, H and Wang, K and Guo, J and Liu, L and Chen, Y and Li, B and Xiao, H and Li, X and Lu, X and Wang, T and Wen, Y and Wang, H and Chen, L}, title = {Maternal gut microbiota-derived daidzein prevents osteoporosis in female offspring following prenatal prednisone exposure.}, journal = {iMeta}, volume = {4}, number = {4}, pages = {e70037}, pmid = {40860437}, issn = {2770-596X}, abstract = {Prenatal exposure to glucocorticoids is linked to long-term health risks in offspring, but the role of maternal gut microbiota in mediating these effects remains unclear. Here, we demonstrate that prenatal prednisone therapy (PPT) in humans and prenatal prednisone exposure (PPE) in rats result in sex-specific long bone dysplasia in offspring, including reduced peak bone mass (PBM) and heightened osteoporosis risk in female offspring. Multi-omics profiling and fecal microbiota transplantation show that PPE alters maternal gut microbiota composition and depletes the microbial metabolite daidzein (DAI). DAI deficiency suppresses Hoxd12 expression, impairs osteogenesis, and leads to PBM decline in female offspring. In bone marrow-derived mesenchymal stem cells from PPE female offspring, DAI promoted Hoxd12 expression and osteogenic differentiation. Notably, DAI supplementation restored H3K9ac levels, enhanced Hoxd12 expression, and promoted osteogenic differentiation through the ERβ/KAT6A pathway. Furthermore, maternal DAI supplementation during pregnancy prevented osteoporosis susceptibility in PPE female offspring and alleviated functional abnormalities in multiple organs, including the liver, hippocampus, ovary, and adrenal gland. In conclusion, PPE induces multiorgan dysplasia and increases disease predisposition (e.g., osteoporosis) in female offspring by disrupting maternal gut microbiota and depleting DAI. Maternal DAI supplementation provides a promising preventive strategy to counteract these adverse outcomes.}, } @article {pmid40860435, year = {2025}, author = {Wang, C and Liu, Z and Zhou, T and Wu, J and Feng, F and Wang, S and Chi, Q and Sha, Y and Zha, S and Shu, S and Qu, L and Du, Q and Yu, H and Yang, L and Malashicheva, A and Dong, N and Xie, F and Wang, G and Xu, K}, title = {Gut microbiota-derived butyric acid regulates calcific aortic valve disease pathogenesis by modulating GAPDH lactylation and butyrylation.}, journal = {iMeta}, volume = {4}, number = {4}, pages = {e70048}, pmid = {40860435}, issn = {2770-596X}, abstract = {The involvement of gut microbiota in calcific aortic valve disease (CAVD) pathogenesis remains underexplored. Here, we provide evidence for a strong association between the gut microbiota and CAVD development. ApoE[-/-] mice were stratified into easy- and difficult- to calcify groups using neural network and cluster analyses, and subsequent faecal transplantation and dirty cage sharing experiments demonstrated that the microbiota from difficult-to-calcify mice significantly ameliorated CAVD. 16S rRNA sequencing revealed that reduced abundance of Faecalibacterium prausnitzii (F. prausnitzii) was significantly associated with increased calcification severity. Association analysis identified F. prausnitzii-derived butyric acid as a key anti-calcific metabolite. These findings were validated in a clinical cohort (25 CAVD patients vs. 25 controls), where serum butyric acid levels inversely correlated with disease severity. Functional experiments showed that butyric acid effectively hindered osteogenic differentiation in human aortic valve interstitial cells (hVICs) and attenuated CAVD progression in mice. Isotope labeling and [13]C flux analyses confirmed that butyric acid produced in the intestine can reach heart tissue, where it reshapes glycolysis by specifically modifying GAPDH. Mechanistically, butyric acid-induced butyrylation (Kbu) at lysine 263 of GAPDH competitively inhibited lactylation (Kla) at the same site, thereby counteracting glycolysis-driven calcification. These findings uncover a novel mechanism through which F. prausnitzii and its metabolite butyric acid contribute to the preservation of valve function in CAVD, highlighting the gut microbiota-metabolite-glycolysis axis as a promising therapeutic target.}, } @article {pmid40860180, year = {2025}, author = {Pan, Z and Jin, X and Li, Q and Zhou, Y and Zeng, Y and Wang, X and Jin, Y and Chen, Y and Li, D and Ling, W}, title = {Citrus Pectin Supplementation Alleviated Hepatic Lipid Accumulation through Gut Microbiota Indole Lactic Acid Promoting Hepatic Bile Acid Synthesis and Excretion.}, journal = {International journal of biological sciences}, volume = {21}, number = {11}, pages = {5015-5033}, pmid = {40860180}, issn = {1449-2288}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Pectins/pharmacology ; Mice ; *Bile Acids and Salts/metabolism/biosynthesis ; Male ; *Liver/metabolism/drug effects ; Mice, Inbred C57BL ; *Lipid Metabolism/drug effects ; *Indoles/metabolism ; Diet, High-Fat ; Dietary Supplements ; }, abstract = {Metabolic-associated fatty liver disease (MAFLD) represents a critical global health challenge. A few studies have suggested that citrus pectin may confer protective effects against MAFLD; however, the underlying mechanism remains unclear. The gut microbiota and its metabolites strongly contribute to MAFLD regulation by the gut‒liver axis. The present study explored the influence of pectin intervention on liver lipid accumulation in high-fat and high-sugar diet-fed mouse models. Pectin supplementation alleviated hepatic lipid accumulation and substantially restructured the gut microbial communities, particularly enhancing the proliferation of Akkermansia muciniphila (A. muciniphila) and Escherichia coli (E. coli), which subsequently increased indole-3-lactic acid (ILA) production. Mechanistic investigations revealed that ILA upregulated hepatic CYP7A1 and FXR-BSEP expression, stimulating hepatic bile acid biosynthesis and biliary excretion to alleviate liver steatosis. Results of previous fecal microbiota transplantation (FMT) and antibiotic-mediated microbial dysbiosis studies have confirmed the microbiota-dependent nature of the therapeutic effects of pectin. Furthermore, the administration of exogenous ILA has been demonstrated to be an effective intervention for the rescue of metabolic dysregulation in dysbacteriosis mouse models. This work delineated an unrecognized dietary pectin-microbiota-ILA-hepatic bile acid synthesis and excretion regulatory axis for the improvement of MAFLD.}, } @article {pmid40859356, year = {2025}, author = {Yang, K and Du, J and Huang, F and Si, Y and Gu, Y and Xu, N and Fan, Z and Xue, R and Wang, P and Yao, X and Liu, H and Li, X and Xu, J and Wang, Z and Sun, J and Chen, Y and Xuan, L and Liu, Q}, title = {Fecal microbiota transplantation for refractory chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation: a pilot open-label, non-placebo-controlled study.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {498}, pmid = {40859356}, issn = {1741-7015}, support = {2023M741581, 2024T170387, GZC20231061//China Postdoctoral Science Foundation/ ; 2023KF04//Open Research Funds of the State Key Laboratory of Ophthalmology/ ; 2025A1515010737//GuangDong Basic and Applied Basic Research Foundation/ ; 82293634, 82170213, 82370216//Major Program of National Natural Science Foundation of China/ ; 2022YFA1105003, 2022YFC2502600-5//National Key Research and the Development Program of China/ ; }, mesh = {Humans ; *Graft vs Host Disease/therapy/etiology/microbiology ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; Middle Aged ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Pilot Projects ; Adult ; Gastrointestinal Microbiome ; Chronic Disease ; Transplantation, Homologous ; Young Adult ; Treatment Outcome ; Feces/microbiology ; }, abstract = {BACKGROUND: Dysbiosis of the intestinal microbiota plays a crucial role in the initiation and development of graft-versus-host disease (GVHD). Fecal microbiota transplantation (FMT) has been reported to be effective for refractory acute GVHD; however, whether FMT is effective for refractory chronic GVHD (cGVHD) remains unknown.

METHODS: To investigate the efficacy and safety of FMT for refractory cGVHD and the underlying mechanism, 12 patients with refractory cGVHD received FMT via colonoscopy, and the response was evaluated at 12 weeks after FMT.

RESULTS: Among the 12 patients who underwent FMT, 1 patient achieved a complete response, and 5 patients achieved a partial response. Patients with refractory cGVHD presented lower α diversity and higher abundance of Escherichia-Shigella and Enterobacteriaceae. FMT increased gut microbial diversity, increased the abundance of short-chain fatty acid (SCFA)-producing bacteria, and decreased the abundance of Escherichia-Shigella and Enterobacteriaceae in responder patients. Moreover, it increased SCFA levels in fecal samples from the responder group and promoted the expansion of peripheral CD4[+]CD127[-] regulatory T (Treg) cells. Colon pathological examination revealed that CD4[+] T and CD19[+] B cell infiltration decreased and that CD4[+] Treg infiltration increased after FMT.

CONCLUSIONS: The results of the present study suggest that FMT is feasible and deserves further investigation for use in patients with refractory cGVHD.

TRIAL REGISTRATION: ClinicalTrials.gov (NCT06938165).}, } @article {pmid40858171, year = {2025}, author = {Lin, W and Wang, X and Zhuang, T and Wang, Z and Yang, L and Wang, X and Ding, L and Tao, F}, title = {Lithospermum erythrorhizon polysaccharide alleviates obesity via gut microbiota-mediated reprogramming of bile acid and short-chain fatty acid metabolism.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {147082}, doi = {10.1016/j.ijbiomac.2025.147082}, pmid = {40858171}, issn = {1879-0003}, abstract = {Lithospermum erythrorhizon, a traditional Chinese medicinal herb and functional food ingredient, contains bioactive soluble polysaccharide with documented anti-obesity and metabolic regulatory properties. However, the precise mechanisms underlying the anti-obesity effects of Lithospermum erythrorhizon polysaccharide (LEP) fraction remain poorly characterized. In this study, diet-induced obese (DIO) mice treated with LEP exhibited significant suppression of body weight gain and hepatic lipid deposition, accompanied by improved liver function and elevated systemic energy expenditure. Mechanistic investigations revealed that LEP administration selectively suppressed the intestinal colonization of bile salt hydrolase (BSH)-producing bacterial taxa, leading to increased circulating levels of taurine-conjugated bile acids and enhanced cecal short-chain fatty acids (SCFAs) production. Concurrently, LEP activated adipose tissue thermogenesis, as evidenced by upregulated expression of thermogenic markers. Antibiotic-induced gut microbiota ablation abolished these metabolic benefits, whereas fecal microbiota transplantation from LEP-treated mice recapitulated the anti-obesity phenotype in recipient animals. These results establish that LEP ameliorates obesity through a gut microbiota-dependent mechanism involving BSH inhibition, taurine-conjugated bile acid accumulation, SCFAs elevation, and subsequent activation of adipose thermogenic pathways. These findings highlight the potential of LEP as a dietary supplement or microbiota-targeted intervention for obesity management.}, } @article {pmid40856929, year = {2025}, author = {Yan, C and Chen, Y and Tian, Y and Hu, S and Wang, H and Zhang, X and Chu, Q and Huang, S and Sun, W}, title = {The emerging role of microbiota in lung cancer: a new perspective on lung cancer development and treatment.}, journal = {Cellular oncology (Dordrecht, Netherlands)}, volume = {}, number = {}, pages = {}, pmid = {40856929}, issn = {2211-3436}, support = {Y-2023AZMETQN-0066//Beijing Xisike Clinical Oncology Research Foundation/ ; 62131009//National Natural Science Foundation of China/ ; }, abstract = {Lung cancer remains the leading cause of cancer-related mortality worldwide, with limited treatment efficacy and frequent resistance to conventional therapies. Recent advances have uncovered the critical influence of the human microbiota-complex communities of bacteria, viruses, fungi, and other microorganisms-on lung cancer pathogenesis and therapeutic responses. This review synthesizes current knowledge on the compositional and functional roles of microbiota across multiple body sites, including the gut, lung, tumor microenvironment, circulation, and oral cavity, highlighting their contributions to tumor initiation, progression, metastasis, and immune regulation. We emphasize the bidirectional communication between microbial metabolites and host immune pathways, particularly the gut-lung axis, which modulates systemic and local antitumor immunity. Importantly, microbiota composition has been linked to differential responses and toxicities in chemotherapy, radiotherapy, targeted therapy, and immune checkpoint blockade. Microbiota-targeted interventions, such as probiotics, fecal microbiota transplantation, and selective antibiotics, show promising potential to enhance treatment efficacy and mitigate adverse effects. However, challenges remain in clinical translation due to interindividual microbiome variability, mechanistic complexities, and limited longitudinal data. Future research integrating multi-omics, microbial functional profiling, and controlled clinical trials is essential to harness the microbiome as a precision medicine tool in lung cancer management. This review provides a comprehensive overview of the emerging role of microbiota in lung cancer development and therapy, offering new perspectives for innovative therapeutic strategies.}, } @article {pmid40852996, year = {2025}, author = {Zhou, Y and Lei, M and Cai, W and Chang, Z and An, L and Zhang, S and Wei, D and Jiao, R and Gao, J and Xu, Y and Yang, H and Zhu, M and Cao, J and Li, S and Duan, X and Wu, W}, title = {Human fecal microbiota transplantation attenuates high dietary oxalate-induced renal calcium oxalate crystal depositions in rats via repairing Allobaculum-related gut barrier damage.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0081025}, doi = {10.1128/msystems.00810-25}, pmid = {40852996}, issn = {2379-5077}, abstract = {UNLABELLED: High dietary oxalate (HDOx) diet is a key factor in kidney stone formation, with gut microbiota playing a significant role. Although several studies have indicated that fecal microbiota transplantation from healthy animals can effectively reduce renal calcium oxalate (CaOx) depositions in rats, the gut microbiota composition between human and animal still remains different. This study aims to explore the effect and underlying mechanisms of healthy human-source fecal microbiota transplantation (hFMT) on CaOx crystal depositions, providing new evidence for its potential clinical application in hyperoxaluria and kidney stone treatment. First, fecal microbiota were screened and collected from healthy individuals and transplanted into rats fed with hydroxyproline. We found that hFMT effectively inhibited crystal depositions and kidney injury induced by HDOx diet, regardless of antibiotic pretreatment. Additionally, 16S rDNA sequencing of gut microbiota identified that hFMT treatment reversed HDOx-induced gut microbiota composition change, particularly restoring the abundance and ecological network of Allobaculum, which was a key indicator genus associated with CaOx crystal depositions. Compared to controls, the abundance of Allobaculum was increased in fecal samples from kidney stone patients and another rat model fed with potassium oxalate. Mechanistically, hFMT markedly attenuated HDOx-induced intestinal barrier disruption to reverse the formation of CaOx crystallization. These findings suggest that HDOx diets could significantly influence the rat gut microbiota. hFMT effectively reduces HDOx-induced renal CaOx crystal depositions and kidney injury via repairing Allobaculum-related gut barrier damage in rats. These findings underscore the potential of hFMT as a therapeutic strategy for hyperoxaluria and kidney stone treatment.

IMPORTANCE: This study investigated that healthy hFMT could serve as a novel strategy to inhibit kidney CaOx deposition induced by HDOx diet. By transplanting healthy human gut microbiota into HDOx rats, we found that hFMT significantly reduced CaOx crystal depositions and kidney damage. The treatment also restored the gut microbiota composition, particularly the abundance of Allobaculum, a genus closely associated with CaOx crystal depositions. Importantly, hFMT restored intestinal barrier function, providing a new mechanistic insight into the gut-kidney axis in kidney stone formation. These findings highlight hFMT's potential as a therapeutic strategy for managing hyperoxaluria and kidney stone, offering a promising alternative to traditional treatment.}, } @article {pmid40852937, year = {2025}, author = {Ullern, A and Holm, K and Andresen, NK and Røssevold, AH and Bang, C and Naume, B and Hov, JR and Kyte, JA}, title = {Gut microbiota diversity is prognostic in metastatic hormone receptor-positive breast cancer patients receiving chemotherapy and immunotherapy.}, journal = {Molecular oncology}, volume = {}, number = {}, pages = {}, doi = {10.1002/1878-0261.70117}, pmid = {40852937}, issn = {1878-0261}, support = {802544/ERC_/European Research Council/International ; CA209-9FN//Bristol Myers Squibb Foundation/ ; 214972/WT_/Wellcome Trust/United Kingdom ; 272910//Norwegian Cancer Society/Norwegian Breast Cancer Society/ ; 2018090//Norwegian Health Region South-East/ ; 2017100//Norwegian Health Region South-East/ ; }, abstract = {Immune checkpoint blockade (ICB) is standard treatment in several cancer types, despite not being proven efficacious in metastatic hormone receptor-positive breast cancer (HR+ mBC). The gut microbiota is associated with patient outcome and toxicity from cancer therapy, although limited data are available for breast cancer. In the randomized phase 2b trial ICON, immunomodulating chemotherapy was investigated in combination with dual ICB in HR+ mBC. To determine whether gut microbiota could inform prognosis, we performed 16S (V3-V4) rRNA sequencing on fecal samples collected at baseline and after 8 weeks of study treatment. We showed that high alpha diversity before treatment was associated with prolonged progression-free survival (PFS; primary trial endpoint) and overall survival. Alpha diversity was lower in patients with prior chemotherapy in the metastatic setting. However, alpha diversity remained significantly associated with PFS after correcting for prior chemotherapy and other factors in bivariate analyses. High-grade immune-related toxicity was also associated with high alpha diversity. These findings suggest that high alpha diversity should be further investigated as a positive prognostic factor in HR+ mBC and approaches to increase alpha diversity could potentially improve clinical outcome.}, } @article {pmid40851996, year = {2025}, author = {Nebieridze, A and Abu-Bakr, A and Nazir, A and Ghosson, A and Minova, A and Uwishema, O}, title = {Microbiome and cardiovascular health unexplored frontiers in precision cardiology: a narrative review.}, journal = {Annals of medicine and surgery (2012)}, volume = {87}, number = {7}, pages = {4255-4261}, pmid = {40851996}, issn = {2049-0801}, abstract = {BACKGROUND AND PURPOSE: Gut microbiota has a symbiotic relationship with their host. It is known that the gut microbiome has the potential to affect the host and vice versa. Cardiovascular disease and its comorbidities are the leading cause of death worldwide. Patients with various heart conditions have been observed to have a different composition of the gut microbiome. It has been postulated that the gut microbiome and its derivatives exert various effects on the cardiovascular system, termed the gut-heart axis. In this study, we aim to explore how the gut microbiome and the active metabolites produced by these microorganisms affect patient cardiovascular health. Additionally, we will discuss how gut microbiota can become a target for the new era of precision cardiology.

METHODS: Data were collected through the online databases PubMed, Google Scholar, Ovid MEDLINE, and ScienceDirect. Articles regarding cardiovascular health and pathology as well as its overlap with gut microbiome and health were used.

RESULTS: Emerging evidence suggests that gut microbiome has a significant influence on cardiovascular disease through its metabolites, such as trimethylamine N-oxide and short-chain fatty acids, which impact cholesterol metabolism, systemic inflammation, and plaque stability. Targeting said derivatives has proven to provide beneficial results for patients suffering from cardiovascular disease.

CONCLUSIONS: Finding reported here highlights the importance of microbiome in cardiovascular disease and health and suggest that microbiome-based interventions hold promise for prevention and treatment of cardiovascular disease. More research needs to be conducted to study more concrete effects of specific microorganisms on cardiovascular health. Multicenter, longitudinal studies with a large sample size will provide the best evidence for clinically significant findings. Using precision cardiology, to target the gut microbiome and its derivatives, with medications like antibiotics, and nonpharmacologic interventions like lifestyle modification and fecal transplantation can positively influence cardiovascular health and help with the effective management of ongoing diseases.}, } @article {pmid40851483, year = {2025}, author = {Kurhaluk, N and Kamiński, P and Tkaczenko, H}, title = {Role of Gut Microbiota in Modulating Oxidative Stress Induced by Environmental Factors.}, journal = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology}, volume = {59}, number = {S2}, pages = {2-52}, doi = {10.33594/000000799}, pmid = {40851483}, issn = {1421-9778}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Oxidative Stress/drug effects ; Animals ; Dysbiosis ; Signal Transduction/drug effects ; *Environmental Pollutants/toxicity ; Probiotics/therapeutic use ; Reactive Oxygen Species/metabolism ; }, abstract = {The widespread presence of environmental pollutants, including toxic metals, microplastics, and antibiotics, has significantly altered gut microbiota composition and functionality, leading to dysbiosis and oxidative stress. These changes contribute to various adverse physiological effects, including systemic inflammation, mitochondrial dysfunction, and intestinal barrier dysfunction. This review provides a comprehensive analysis of the molecular mechanisms by which these environmental factors induce oxidative damage, emphasising the importance of redox imbalance, the overproduction of reactive oxygen species, and inflammatory signalling pathways. Key pathways involved include NF-κB, Nrf2/Keap1, PI3K/AKT, p38-MAPK, JAK/STAT and TLR4/MyD88. These pathways collectively contribute to the progression of chronic inflammatory conditions. Furthermore, this article synthesises findings from 354 studies published between 2016 and 2024, integrating human and animal research evidence. Existing literature suggests that gut dysbiosis exacerbates oxidative stress through impaired short-chain fatty acid production, downregulation of peroxisome proliferator-activated receptor gamma, and disruption of antioxidant enzyme activity. This review explores these mechanisms in more detail. Additionally, the review evaluates studies investigating microbiota-targeted therapeutic interventions to mitigate oxidative stress. These interventions include probiotics, prebiotics, polyphenols, and postbiotics, focusing on their reported modulation of Nrf2 and AMPK signalling pathways. The potential of faecal microbiota transplantation as an innovative approach to restoring a healthy gut ecosystem and counteracting pollutant-induced oxidative damage is also discussed. In light of the growing global exposure to environmental pollutants and their associated long-term health implications, it is imperative to gain a deeper understanding of their impact on gut microbiota and oxidative stress. This topic remains at the forefront of biomedical research due to its implications for public health, disease prevention, and developing novel therapeutic strategies.}, } @article {pmid39862395, year = {2025}, author = {Allegretti, JR and Feuerstadt, P and Knapple, WL and Orenstein, R and Pinton, P and Sheh, A and Khanna, S}, title = {Safety and Efficacy of Fecal Microbiota, Live-jslm (REBYOTA®), for the Prevention of Recurrent Clostridioides difficile Infection in Participants With Inflammatory Bowel Disease in PUNCH CD3-OLS.}, journal = {Inflammatory bowel diseases}, volume = {31}, number = {8}, pages = {2112-2122}, pmid = {39862395}, issn = {1536-4844}, support = {//Ferring Pharmaceuticals/ ; }, mesh = {Humans ; Female ; Male ; Adult ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Clostridium Infections/prevention & control/microbiology ; *Inflammatory Bowel Diseases/microbiology/complications ; Middle Aged ; *Feces/microbiology ; *Clostridioides difficile ; Treatment Outcome ; Secondary Prevention/methods ; Young Adult ; Prospective Studies ; Gastrointestinal Microbiome ; Recurrence ; }, abstract = {BACKGROUND: Fecal microbiota, live-jslm (RBL; REBYOTA®), is the first single-dose, broad consortia, microbiota-based live biotherapeutic approved by the US Food and Drug Administration to prevent recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care antimicrobials. Inflammatory bowel disease (IBD) is a common risk factor for rCDI, yet patients with IBD are often excluded from prospective trials. This subgroup analysis of PUNCH CD3-OLS (NCT03931941) evaluated the safety and efficacy of RBL in participants with rCDI and IBD.

METHODS: Participants with IBD (ulcerative colitis [UC], Crohn's disease [CD], or unspecified) who had rCDI were included. Treatment-emergent adverse event (TEAE) data were collected for up to 6 months following RBL administration. Efficacy outcomes included treatment success at 8 weeks and sustained clinical response at 6 months.

RESULTS: Overall, 793 participants were enrolled, and 697 received RBL; 74 had IBD (UC: n = 45; CD: n = 25; unspecified IBD: n = 4). TEAEs within 8 weeks of administration were reported by 45.9% and 47.5% of participants with and without IBD, respectively; most were mild or moderate gastrointestinal symptoms. Serious TEAEs within 8 weeks of administration were reported by 1.4% and 4.2% of participants with and without IBD, respectively. The treatment success rate at 8 weeks was 78.9%, and the sustained clinical response rate at 6 months was 91.1% in participants with IBD, similar to rates in participants without IBD (73.2% and 91.0%, respectively).

CONCLUSIONS: The results of this subgroup analysis of PUNCH CD3-OLS suggest RBL is safe and efficacious in patients with IBD.}, } @article {pmid40851072, year = {2025}, author = {Zhang, L and Wang, S and Wong, MCS and Mok, CKP and Ching, JYL and Mak, JWY and Chen, C and Huo, B and Yan, S and Cheung, CP and Chiu, EOL and Fung, EYT and Cheong, PK and Chan, FKL and Ng, SC}, title = {The resident gut microbiome modulates the effect of synbiotics on the immunogenicity after SARS-COV-2 vaccination in elderly and diabetes patients.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {171}, pmid = {40851072}, issn = {2055-5008}, support = {COVID19F07//Health Bureau, The Government of the Hong Kong Special Administrative Region/ ; COVID19F07//Health Bureau, The Government of the Hong Kong Special Administrative Region/ ; COVID19F07//Health Bureau, The Government of the Hong Kong Special Administrative Region/ ; COVID19F07//Health Bureau, The Government of the Hong Kong Special Administrative Region/ ; NCI202346//New Cornerstone Science Foundation/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; Aged ; *Synbiotics/administration & dosage ; SARS-CoV-2/immunology ; Female ; Male ; *COVID-19/prevention & control/immunology ; *COVID-19 Vaccines/immunology/administration & dosage ; Feces/microbiology ; Bifidobacterium ; *Immunogenicity, Vaccine ; *Diabetes Mellitus/immunology/microbiology ; Vaccination ; BNT162 Vaccine/immunology ; Middle Aged ; Antibodies, Viral/blood ; }, abstract = {The study aims to tackle the seed and soil microbiome and mechanisms that contribute to the effect of synbiotics in enhancing immunogenicity after SARS-CoV-2 vaccination in elderly and diabetic patients. Among 369 subjects who received 3 months of SIM01, a gut microbiota-derived synbiotic formula of three Bifidobacterium strains (B. adolescentis, B. bididum, and B. longum) or a placebo after the SARS-CoV-2 vaccines (mRNA vaccine BNT162b2 (Pfizer-BioNTech) or the inactivated vaccine Sinovac-CoronaVac), we performed metagenomic sequencing in stool samples of 280 vaccinees collected at baseline and 3-month postvaccination and metabonomic sequencing in 276 vaccinees collected at baseline and 1-month postvaccination. The open niche of autochthonous gut microbiota (lower levels of Bifidobacterium and decreased functional potential for carbohydrate metabolism) was associated with enhancing SIM01-contained species. The enrichment of three bifidobacterial species after 3 months of SIM01 intervention (BABBBL_fc) was positively correlated with the level of neutralizing antibodies to the BNT162b2 vaccine at 6-month postvaccination. The fold change of benzoic acid was positively correlated with BABBBL_fc in the BNT162b2 vaccinees, which was also implicated with SARS-CoV-2 surrogate virus neutralization test (sVNT)% levels at 1-month postvaccination. Importantly, SIM01 strain engraftment assessed by StrainPhlAn (A metagenomic strain-level population genomics tool) was associated with a higher fold change of three bifidobacterial species and could be predicted based on the baseline gut microbiome. Therefore, the resident gut microbiome affected the SIM01 engraftment, which was associated with the immunogenicity of SARS-CoV-2 BNT162b2 vaccines.}, } @article {pmid40850941, year = {2025}, author = {Zhang, X and Yang, Y}, title = {Gut: The gate and key to brain.}, journal = {Chinese medical journal}, volume = {}, number = {}, pages = {}, pmid = {40850941}, issn = {2542-5641}, abstract = {Brain science is the frontier of modern science, and new advances have been made in brain-like designs and brain-computer interfaces to simulate or develop brain functions. However, given that the brain is hermetically sealed within the skull, exploration and deciphering of the brain structure and functions are limited. Growing evidence suggests that the gut is not just a digestive organ. It not only provides essential nutrients and electrolytes for brain neurodevelopment and the maintenance of brain function, but it also transmits external environmental and intestinal wall signals from the intestinal lumen to the central nervous system through multiple pathways to regulate brain activity, function, and structure. A variety of gut-brain interaction pathways have been identified, including neural pathways, neuroimmune signaling, endocrine pathways, and biochemical messengers produced by gut microbes. Gut microbes interact with food and the gut to modulate gut-brain communication. The gut's important role and potential in neurodevelopment, maintenance of normal function, and disease development make it an increasingly important area of research in brain science and neuropsychiatric disorders. The gut's unique role in brain functions and its accessibility for research (compared to direct brain studies) establish it as a critical gate to understanding the mysteries of brain science. Crucially, intestinal nutrients and microbes provide two unique keys to unlock this gate-enabling neural regulation and novel treatments for neuropsychiatric diseases.}, } @article {pmid40850681, year = {2025}, author = {Wei, Z and Gao, G and He, Q and Kwok, LY and Sun, Z}, title = {The gut-tumor connection: the role of microbiota in cancer progression and treatment strategies.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.08.038}, pmid = {40850681}, issn = {2090-1224}, abstract = {BACKGROUND: The tumor microenvironment (TME) has become a critical focus in the diagnosis and treatment of cancer. The involvement of the microbiome in tumor initiation and progression underscores its potential as a promising biomarker and therapeutic target. Furthermore, microorganisms in the gut and other ecological niches play pivotal roles in shaping cancer immune surveillance and modulating responses to immunotherapy, acting as key mediators connecting gut health to cancer progression. Thus, investigating the intricate interplay between the TME and gut microbiota could offer valuable insights to advance personalized cancer therapies.

AIM OF REVIEW: This comprehensive review explores the complex interactions between the gut microbiota, tumor-associated microbiota, and TME, examining their origins, diversity, connections, and therapeutic implications. We investigate the potential for gut microbiota to translocate to tumors, where they may directly impact the TME and influence cancer progression. We compile the current knowledge on the diversity of intratumoral microbiota across various cancer types and its effects on cellular, immune, and spatial heterogeneity within the TME. Furthermore, we assess the efficacy of various methods for characterizing and identifying intratumoral microbiome, emphasizing their importance in understanding their composition and function in the TME. We also explore the therapeutic potential of modulating the gut microbiota, highlighting strategies such as dietary interventions, fecal microbiota transplantation, probiotics, prebiotics, and synthetic biology approaches. We then address the challenges and future directions in this emerging field, emphasizing the need for standardized protocols, advanced sequencing technologies, and refined animal models to enhance our understanding of microbiota-cancer interactions. In conclusion, the gut microbiota represents a promising therapeutic target for cancer treatment. Harnessing the power of gut microbial modulation could lead to novel combinatorial strategies that improve clinical outcomes for cancer patients. Nevertheless, further research is essential to surmount existing challenges and translate these insights into impactful, personalized cancer therapies.}, } @article {pmid40849919, year = {2025}, author = {Li, S and Wu, W and Zhou, Y and Zhang, S and Wei, D and Zhu, M and Ying, X and Sun, X and Liu, H and Zhu, W and Tang, D and Jiao, R and Zeng, G and Duan, X and Liu, J and Wu, W}, title = {Gut microbiota-regulated unconjugated bilirubin metabolism drives renal calcium oxalate crystal deposition.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2546158}, doi = {10.1080/19490976.2025.2546158}, pmid = {40849919}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Calcium Oxalate/metabolism/chemistry ; *Bilirubin/metabolism ; Rats ; Humans ; Dysbiosis/metabolism/microbiology ; Male ; *Kidney/metabolism/pathology ; *Kidney Calculi/metabolism ; Rats, Sprague-Dawley ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Drosophila ; Bacteria/classification/metabolism/genetics/isolation & purification ; }, abstract = {Gut microbial dysbiosis and the resultant metabolic disorder are intimately associated with calcium oxalate (CaOx) stone formation. Renal CaOx crystal deposition is one of the primary initiating factors of CaOx formation; however, the critical signaling metabolites communicating along the gut-kidney axis, and their regulation on renal CaOx crystal deposition remain unclear. Here, we investigate the role of gut microbiota-associated unconjugated bilirubin (UCB) metabolism in renal CaOx crystalline pathogenesis. The UCB was first distinguished as a significant risk factor of renal CaOx crystal deposition, by transplantation of fecal microbiota derived from healthy rat (healthy-FMT) to alleviate the renal CaOx crystal deposition in rat models, which was also testified in CaOx stone patients. Further experiments showed that UCB could increase renal CaOx crystal deposition significantly in both rat and Drosophila models. Mechanistically, UCB can promote apoptosis in renal tubular epithelial cells, enhance oxalate secretion by upregulating Slc26a6 expression, and facilitate CaOx crystal nucleation and aggregation, all of which contribute to renal CaOx crystalline pathogenesis. Furthermore, we identified significant gut microbiota dysbiosis in renal CaOx crystal deposition rats, particularly in β-glucuronidase (β-GD) and bilirubin reductase (BilR)-related dysbiosis, which modulate UCB levels and its enterohepatic circulation. These findings suggest that UCB is a novel regulator of renal CaOx crystal deposition, and targeting its metabolism via modulation of the gut microbiota may offer a promising therapeutic strategy for preventing renal CaOx crystal deposition-related nephropathy.}, } @article {pmid40849632, year = {2025}, author = {Jang, S and Lee, EJ and Park, S and Lim, H and Ahn, B and Huh, Y and Koh, H and Park, YR}, title = {Spatial host-microbiome profiling demonstrates bacterial-associated host transcriptional alterations in pediatric ileal Crohn's disease.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {189}, pmid = {40849632}, issn = {2049-2618}, abstract = {BACKGROUND: Crohn's disease (CD) is a chronic inflammatory bowel disease involving complex relationships between the gut microbiome and host immune system. However, the spatial relationships between tissue-resident bacteria and host cells in CD pathogenesis remain poorly understood. We developed a spatial host-microbiome profiling approach to simultaneously detect host transcriptomics and bacterial species at high taxonomic resolution in pediatric ileal CD tissues.

RESULTS: In this prospective case-control study, we analyzed 14 terminal ileal tissue samples from six pediatric patients with ileal CD and two controls. Spatial host-microbiome sequencing, combined spatial transcriptomics and in-situ polyadenylation, and bulk shotgun metagenome sequencing were performed. We developed a comprehensive bioinformatics pipeline to identify bacterial species and analyze host-microbiome interactions at cellular resolution, resulting in 13,876 analyzed cells. Our approach revealed increased bacterial abundance in CD tissues compared with controls. The extent of bacterial infiltration at diagnosis correlated with disease prognosis and severity of endoscopic findings. We identified 16 potentially beneficial and nine pathogenic microbiome members in ileal CD, including several newly discovered risk-modulating bacterial species. Cell-type-specific host gene expression analysis revealed transcriptome alterations related to bacterial defense mechanisms in the presence of various bacterial species.

CONCLUSIONS: Our spatial host-microbiome profiling approach enables simultaneous species-level identification of bacteria and host transcriptomics. It reveals the intricate interactions between host cells and bacteria, providing cellular-level insights into CD pathogenesis. Our approach offers a powerful tool for investigating host-microbiome interactions in various microbiome-associated diseases to direct new strategies for microbiome-based therapeutics and prognostic markers. Video Abstract.}, } @article {pmid40848995, year = {2025}, author = {Wang, J and Xue, L and Zhang, M and Shen, P and Zhao, W and Tong, Q and Wu, S and Dai, W and Yang, X and Wang, H}, title = {Colonoscopic fecal microbiota transplantation for Mild-to-Moderate Parkinson's Disease: A randomized controlled trial.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {106086}, doi = {10.1016/j.bbi.2025.106086}, pmid = {40848995}, issn = {1090-2139}, abstract = {OBJECTIVE: Growing evidence supports the efficacy and safety of fecal microbiota transplantation (FMT) in treating Parkinson's disease (PD). Fecal microbiota are commonly transplanted via oral capsules, a nasojejunal tube, or colonoscopy, but freezing often decreases the diversity and viability of transplanted microbiota. This single-center, double-blind, randomized, placebo-controlled trial aims to explore the efficacy and safety of fresh FMT via colonoscopy in dealing with PD.

METHODS: Thirty patients with mild-to-moderate PD (Hoehn-Yahr stage I-III) were randomly assigned into the FMT group (fresh FMT via colonoscopy) and placebo group (saline injection via colonoscopy) in a 1:1 ratio. Motor and non-motor symptoms, constipation, quality of life, cognitive function, emotional state and sleep quality were assessed using relevant scales. Fecal samples were harvested before and at 4, 8 and 12 weeks after treatment for metagenomic and metabolomics analyses.

RESULTS: A total of 30 patients with mild-to-moderate PD were enrolled in the present study, involving 18 males and 12 females with a median age of 68 years, a median age of onset of 63.5 years, and a median disease duration of 3 years. At 12 weeks, scores of the UPDRS Ⅲ (group × time effect, B =  - 8.80 [-13.79, -3.81]), PAC-QOL (group × time effect, B =  - 29.67 [-45.35, -13.98]), UPDRS Ⅱ (group × time effect, B =  - 5.07 [-8.85, -1.28]), NMSS (group × time effect, B =  - 35.60 [-53.59, -17.61]), PDQ-39 (group × time effect, B =  - 17.80 [-28.21, -7.39]), HAMA (group × time effect, B =  - 1.66 [-2.92, -0.40]), and HAMD (group × time effect, B =  - 1.33 [-2.49, -0.16]) were significantly reduced in the FMT group, while CSBM per week (group × time effect, B = 3.03 [1.42, 4.63]) and the Bristol Stool Scale score (group × time effect, B = 1.95 [0.12, 3.79]) significantly increased (all P < 0.05). Significant alterations were seen in the gut microbiota and fecal metabolites in the FMT group. No adverse events were observed during the follow-up period.

CONCLUSION: Fresh FMT via colonoscopy is a safe and well-tolerated procedure for treating mild-to-moderate PD. It effectively alleviates motor and non-motor symptoms, thus facilitating defecation and improving the quality of life. These effects can be maintained for a minimum of 12 weeks and may be attributed to the optimization of gut microbiota and fecal metabolites.}, } @article {pmid40847330, year = {2025}, author = {Stefansson, M and Bladh, O and Nowak, P and Rombo, L and Hedenstierna, M and Ursing, J}, title = {Risk factors for further recurrences of Clostridioides difficile infection at the first and second recurrence: a retrospective cohort.}, journal = {BMC infectious diseases}, volume = {25}, number = {1}, pages = {1057}, pmid = {40847330}, issn = {1471-2334}, mesh = {Humans ; *Clostridium Infections/epidemiology/microbiology/therapy ; Female ; Male ; Retrospective Studies ; Risk Factors ; Aged ; Recurrence ; Aged, 80 and over ; *Clostridioides difficile ; Fecal Microbiota Transplantation ; Sweden/epidemiology ; }, abstract = {BACKGROUND: Recurrent Clostridioides difficile infection is most effectively treated with faecal microbiota transplantation. Swedish and European guidelines suggest faecal microbiota transplantation after a first or second recurrence, respectively. The aims of this study were to evaluate risk factors for further relapses at the first and second recurrence, related to treatment recommendations.

METHODS: Patients aged ≥ 18 years with two positive tests for C. difficile within eight weeks and treated at the study hospitals during 2014-2022 were eligible for inclusion. Retrospectively collected data included age, sex, treatment, and clinical characteristics for each episode. Risk factors for further recurrences at the first and second recurrence were identified using multivariable logistic regression analysis.

RESULTS: The median age in the total cohort (n = 231) was 76 (IQR 67-84) years, 52% were females and 15% were healthy without comorbidities. One recurrence only occurred in 110 patients (48%), however, no clinically significant risk factors predicting more than one recurrence were identified. Two or more recurrences occurred in 110 patients, of whom, 44 (40%) had further recurrences. Frailty (Clinical Frailty Scale ≥ 4) was significantly associated with more than two recurrences (p = 0.03). The respective median times between the first and the second recurrences were 12 and 17 days in patients with more than two recurrences compared to two recurrences only (p = 0.02).

CONCLUSIONS: Patients experiencing a second recurrence of C. difficile infection who were frail and relapsed in a shorter time span after the first recurrence had a significantly increased risk of further recurrences.}, } @article {pmid40846688, year = {2025}, author = {Ding, SQ and Lei, Y and Zhao, ZM and Li, XY and Lang, JX and Zhang, JK and Li, YS and Zhang, CD and Dai, DQ}, title = {Crosstalk Between Microbiome and Ferroptosis in Diseases: From Mechanism to Therapy.}, journal = {Comprehensive Physiology}, volume = {15}, number = {4}, pages = {e70042}, doi = {10.1002/cph4.70042}, pmid = {40846688}, issn = {2040-4603}, support = {81972322//National Natural Science Foundation of China/ ; JYTMS20230108//Scientific Study Project for Institutes of Higher Learning, Ministry of Education, Liaoning Province/ ; RXXM202302//Young Backbone Talents of China Medical University/ ; 2023-MS-163//Liaoning Provincial Natural Science Foundation/ ; }, mesh = {*Ferroptosis/physiology ; Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; Iron/metabolism ; Dysbiosis/metabolism ; Reactive Oxygen Species/metabolism ; *Microbiota/physiology ; Lipid Peroxidation ; }, abstract = {The human microbiome is a unique organ and maintains host immunomodulation and nutrient metabolism. Structural and functional microbiome alterations are commonly known as dysbiosis, which is strongly associated with disease progression. Ferroptosis is a novel iron-dependent cell death mode characterized by intracellular iron accumulation, increased reactive oxygen species (ROS), and lipid peroxidation (LPO). Importantly, the complex crosstalk between the microbiome and ferroptosis in disease has attracted considerable research attention. The microbiome influences ferroptosis by regulating host iron homeostasis, mitochondrial metabolism, and LPO, among many other pathways. Thus, the in-depth analysis of microbiome-ferroptosis crosstalk and associated mechanisms could provide new strategies to treat human diseases. Therefore, understanding this crosstalk is critical. Here, we systematically explore the associations between gut microbiome and ferroptosis across multiple diseases. We show that the oral microbiome also influences disease progression by regulating ferroptosis. Furthermore, we provide a potential for certain disease therapies by targeting the crosstalk between the microbiome and ferroptosis.}, } @article {pmid40842975, year = {2025}, author = {Tu, J and Yu, L and Zou, R and He, J and Qu, C}, title = {Influence of the gut microbiome on lymphoma treatment: current evidence and future therapeutic directions.}, journal = {Therapeutic advances in medical oncology}, volume = {17}, number = {}, pages = {17588359251363207}, pmid = {40842975}, issn = {1758-8340}, abstract = {The heterogeneity of lymphoma responses to various treatments remains a significant challenge in clinical practice. Emerging evidence implicates the potential role of the gut microbiome in lymphoma pathogenesis and progression. Advances in high-throughput sequencing and metabolomics have significantly enhanced our understanding of the complex interaction between the gut microbiome and lymphoma. Although causality requires further elucidation, the gut microbiome critically shapes host responses to traditional combined chemotherapy, hematopoietic stem cell transplantation, and targeted therapies, including chimeric antigen receptor T-cell therapy. Notably, the use of antibiotics, particularly broad-spectrum antibiotics, can alter the gut microbiome, thereby impacting treatment efficacy. Prudent antibiotic management should balance infection control with microbiome-dependent immune homeostasis. Strategies to restore gut microbial balance through a high-fiber diet, probiotics, prebiotics, fecal microbiota transplantation, and butyrate supplementation are critically important. Integrating microbiome-based therapies into lymphoma treatment could establish low-toxicity therapeutic paradigms for lymphoma patients.}, } @article {pmid40842134, year = {2025}, author = {Korten, NM and Thelen, AC and Voelz, C and Beyer, C and Seitz, J and Trinh, S and Blischke, L}, title = {Exploring the Link Between the Gut Microbiota and Epigenetic Factors in Anorexia Nervosa.}, journal = {Brain and behavior}, volume = {15}, number = {8}, pages = {e70733}, doi = {10.1002/brb3.70733}, pmid = {40842134}, issn = {2162-3279}, mesh = {*Anorexia Nervosa/microbiology/genetics/metabolism ; Humans ; *Gastrointestinal Microbiome/physiology ; *Epigenesis, Genetic/physiology ; Brain/metabolism ; Dysbiosis ; }, abstract = {OBJECTIVE: Anorexia nervosa (AN) is an often chronic eating disorder that involves genetic, neurohormonal, and epigenetic factors along with key contributions from the microbiota-gut-brain axis. However, interactions between these factors are poorly understood. Recent studies have emphasized the microbiota-gut-brain axis and epigenetic changes as potentially important contributors to AN. Exploring these interactions may improve understanding of the etiology and persistence of AN.

METHODS: Studies specifically addressing microbial-epigenetic interactions in AN remain limited. However, similar associations have been documented in related disorders such as obesity and depression, providing potential models for AN research.

RESULTS: Research in obesity has shown that dietary factors influence the composition of the gut microbiota and subsequent epigenetic modifications, affecting metabolic parameters and disease progression. Similarly, in depression, microbially produced metabolites influence brain function and epigenetic processes, contributing to neuropsychiatric symptoms. In AN, altered microbial composition may affect weight regulation and epigenetic patterns. Therapies targeting the microbiome, such as fecal microbiota transplantation, are under investigation for AN, highlighting the potential therapeutic utility of ameliorating microbial dysbiosis.

DISCUSSION: This article highlights the importance of investigating microbial-epigenetic interactions in AN. By drawing parallels with obesity and depression, we aim to deepen our understanding of AN mechanisms and ultimately improve patient outcomes.}, } @article {pmid40744276, year = {2025}, author = {Cassir, N and Ghani, R and Biehl, LM and Graells, T and Kuijper, EJ and Mullish, BH and Marchesi, JR and Benech, N and , }, title = {Nonantimicrobial therapies for recurrent urinary tract infection in women: is there a place for faecal microbiota transfer?.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2025.07.022}, pmid = {40744276}, issn = {1469-0691}, abstract = {BACKGROUND: Recurrent urinary tract infection (rUTI) is a common condition, affecting approximately one-third of women after an initial UTI. It significantly impacts health care costs and patients' quality of life. The relationship between the pathophysiology of UTI and the gut and vaginal microbiota is recognized as a contributing factor to rUTI in women. As antibiotic resistance among uropathogens continues to increase, there is a clear need to develop novel therapeutic interventions. Faecal microbiota transfer (FMT) is a potent nonantimicrobial strategy for modulating the gut microbiota; however, its clinical relevance in the context of rUTI is unclear.

OBJECTIVES: This narrative review aimed to summarize the current evidence on the use of FMT for the treatment of rUTI, focusing on women, excluding those with mechanical dysfunctions such as urinary incontinence, neurogenic bladder, and bladder cancer, compared with other nonantimicrobial interventions. We also discussed the pathophysiology and epidemiology of rUTI to identify patients for whom microbiota-targeting therapies may be the most effective.

CONTENT: Periurethral colonization and migration to the bladder of uropathogens that inhabit the gut and vagina have been linked to the aetiology of UTI in women, particularly in patients with multidrug-resistant organisms. FMT appears to be a promising approach for preventing the clinical development of rUTI, although prospective data remain limited. In contrast, other reported nonantimicrobial strategies targeting the gut and urogenital microbiota have shown variable significant clinical efficacy. Prospective randomized controlled clinical trials are then needed to further confirm a potential therapeutic benefit, optimize the FMT procedure, and better assess its cost-effectiveness.}, } @article {pmid40695592, year = {2025}, author = {Welsch, EC and Barron, MR and Storage, KM and Kazen, AB and Aboulalazm, FA and Kirby, JR and Kindel, TL}, title = {Gut microbiome and bile acid changes after male rodent sleeve gastrectomy: what comes first?.}, journal = {American journal of physiology. Regulatory, integrative and comparative physiology}, volume = {329}, number = {3}, pages = {R410-R421}, doi = {10.1152/ajpregu.00297.2024}, pmid = {40695592}, issn = {1522-1490}, support = {R01HL158900//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; HL072483//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; Clowes Career Development Award//American College of Surgeons (ACS)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Bile Acids and Salts/metabolism ; *Gastrectomy/methods ; Male ; Mice, Inbred C57BL ; *Liver/metabolism ; Mice ; Fecal Microbiota Transplantation ; }, abstract = {Understanding how a sleeve gastrectomy (SG) achieves metabolic improvement is challenging due to the complex relationship between the liver, bile acid (BA) pool, and gut microbiome. We hypothesized that SG alters the gut microbiome, which then increases the BA pool, leading to metabolic efficacy. We performed fecal material transfer (FMT) from SG or sham mice to surgically naïve mice with an intact microbiome. We evaluated the effect of surgery and FMT on BA-related liver enzymes, BA concentrations, and gut microbiome composition via 16S and metagenomic analysis. SG significantly deflected weight gain compared with sham surgery, 5 ± 2 g versus 10 ± 3 g, respectively (P = 0.004). SG significantly increased the BA pool and decreased liver transcription of slc10a1 (P = 0.04) and cyp8b1 (P = 0.03). Random forest analysis identified several features with significantly increased relative abundance in SG compared with sham mice, including Lactobacillus. Examination of metabolic profiles with metagenomic analysis revealed a BA salt hydrolase produced by the Ligilactobacillus species. FMT of SG stool to surgically naïve mice significantly decreased the BA pool compared with sham FMT (P = 0.034). Unlike SG surgery, we found no effect of SG or sham FMT on bile acid-related enzymes in the liver after 14 wk of treatment. Overall, we propose that the metabolic benefits of SG surgery are related to decreased liver transcription of cyp8b1 and slc10a1 with subsequent increases in the systemic and enterohepatic BA pool, including lithocholic acid. The gut microbiome adapts to the altered BA pool with associated increases in Ligilactobacillus and bile salt hydrolase production.NEW & NOTEWORTHY We propose that the metabolic benefits of sleeve gastrectomy are initiated by decreased liver transcription of cyp8b1 and slc10a1. A notable downstream effect includes changes in systemic bile acid composition and circulation, including increased LCA. An altered gut microbiome after surgery includes increases in Ligilactobacillus that was shown to express a bile salt hydrolase, which could be a contributor to the post-sleeve gastrectomy gut microbiome changes.}, } @article {pmid40838552, year = {2025}, author = {Szegedi, I and Bomberák, D and Éles, Z and Lóczi, L and Bagoly, Z}, title = {Cardiovascular disease and microbiome: focus on ischemic stroke.}, journal = {Polish archives of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.20452/pamw.17088}, pmid = {40838552}, issn = {1897-9483}, abstract = {Cardiovascular and cerebrovascular diseases, encompassing conditions such as ischemic heart disease and ischemic stroke (IS), remain the leading global cause of death and disability. While traditional cardiovascular risk factors (eg, hypertension, diabetes, and atherosclerosis) are well established, emerging research underscores the critical role of gut microbiota in the development and progression of both cardiac and cerebrovascular events. The microbiota-gut-brain axis is a bidirectional communication system involving neural, immune, and metabolic pathways that link gut microbial activity to vascular and brain function. Dysbiosis, marked by reduced microbial diversity and an imbalance between beneficial and pathogenic taxa, has been associated with systemic inflammation, endothelial dysfunction, increased intestinal permeability, and thrombosis. Microbial metabolites, such as trimethylamine N‑oxide (TMAO), short‑chain fatty acids, and bile acid derivatives modulate blood-brain barrier integrity, vascular tone, and neuroinflammatory responses. Both cardiovascular and cerebrovascular diseases share key microbiota‑related mechanisms, including TMAO‑mediated platelet activation and low‑grade endotoxemia, although IS is more acutely affected by gut barrier disruption and neuroinflammation. In IS, gut dysbiosis also contributes to poststroke complications, such as hemorrhagic transformation, neuropsychiatric issues, and epilepsy. Advances in sequencing and metabolomics enabled identification of microbial signatures associated with the risk for an acute ischemic event and patient prognosis. Therapeutic strategies targeting the gut microbiota-including dietary interventions, probiotics, prebiotics, and synbiotics, fecal microbiota transplantation, and intestinal epithelial stem cell therapy-show promise in mitigating vascular injury and improving recovery. This narrative review highlights current insights into microbiota‑related cardiovascular and cerebrovascular events, with a focus on IS.}, } @article {pmid40838009, year = {2025}, author = {Yuan, S and Jia, W and Liu, X and Liu, R and Cao, M and Wu, Y and Li, Y and Xu, W and Xiao, C and Hong, Z and Zhang, B}, title = {Therapeutic effect of fecal microbiota transplantation on hyperuricemia mice by improving gut microbiota.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1599107}, pmid = {40838009}, issn = {1664-302X}, abstract = {OBJECTIVE: The primary objective of this study was to assess the impact of fecal microbiota transplantation (FMT) on serum biochemical parameters, renal injury, and gut microbiota in hyperuricemia (HUA) mice.

METHODS: Six-week-old male C57BL/6 J mice were given a high-purine diet and potassium oxonate injections to induce HUA, followed by a two-week FMT treatment. Regular body weight checks, serum biochemical analyses, and fecal sampling for 16S rRNA gene sequencing were conducted to evaluate the treatment's impact on gut microbiota.

RESULTS: The model group showed significant increases in uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN) levels, and increased xanthine oxidase (XOD) activity compared to controls (p < 0.05). FMT treatment effectively reduced these levels and XOD activity (p < 0.05). At the genus level, specific taxa like Muribaculaceae and Prevotellaceae_UCG-001 were less abundant, while Blautia and Ruminiclostridium_9 were more abundant in the model group. Following FMT, gut microbiota composition returned to near-normal levels, with significant differences from the model group (p < 0.05).

CONCLUSION: This study demonstrates that FMT holds therapeutic potential for HUA mice by reducing UA levels, alleviating renal damage, and restoring gut microbiota balance.}, } @article {pmid40836410, year = {2025}, author = {Quan, J and Liu, X and Liang, S and Nie, L and Zhang, L and Hong, X and He, M and Lei, S and Duan, L and Zhang, Y and Zhuang, L}, title = {Electroacupuncture suppresses motor impairments via microbiota-metabolized LPS/NLRP3 signaling in 6-OHDA induced Parkinson's disease rats.}, journal = {International immunopharmacology}, volume = {162}, number = {}, pages = {115089}, doi = {10.1016/j.intimp.2025.115089}, pmid = {40836410}, issn = {1878-1705}, mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Electroacupuncture ; *Gastrointestinal Microbiome ; Lipopolysaccharides/metabolism ; Male ; Rats ; Oxidopamine ; Signal Transduction ; Rats, Sprague-Dawley ; Dopaminergic Neurons ; *Parkinson Disease/therapy ; Disease Models, Animal ; Fecal Microbiota Transplantation ; }, abstract = {Emerging evidence indicates that electroacupuncture (EA) exerts significant therapeutic effects on Parkinson's disease (PD)-related symptoms, with the immune mechanisms of the gut-brain axis playing a pivotal role in PD pathophysiology. This study aimed to explore whether EA mitigated PD-related symptoms and conferred neuroprotection to dopaminergic neurons in a 6-hydroxydopamine (6-OHDA) rat model by modulating the microbiota-metabolized lipopolysaccharide (LPS)/NLRP3 pathway. EA treatment ameliorated motor and anxiety symptoms in 6-OHDA rats and elevated the levels of TH. Metabolomic analysis indicated that the therapeutic effects of EA are associated with the gut microbiota and the NOD-like receptor signaling pathway. 16S rRNA sequencing demonstrated that EA significantly modified the composition of the gut microbiota, evidenced by alterations in the relative abundance of 16 genera, and led to the downregulation of the LPS and NOD-like receptor signaling pathways. Additionally, EA was found to attenuate intestinal inflammation, decrease serum inflammatory markers, reduce neuroinflammation, and suppress the overexpression of microglia and astrocytes, while concurrently preserving the integrity of the intestinal and blood-brain barriers. Fecal microbiota transplantation experiments further substantiated the pivotal role of gut microbiota in mediating the anti-PD effects of EA. In summary, EA has the potential to alleviate PD-related symptoms and safeguard dopaminergic neurons by rectifying gut microbiota dysbiosis and downregulating the LPS/NLRP3 immune pathway along the gut-brain axis in PD rat models.}, } @article {pmid40836368, year = {2025}, author = {Guo, P and Zeng, M and Liu, M and Zhang, Y and Jia, J and Zhang, Z and Liang, S and Zheng, X and Feng, W}, title = {Zingibroside R1 Isolated From Achyranthes bidentata Blume Ameliorates LPS/D-GalN-Induced Liver Injury by Regulating Succinic Acid Metabolism via the Gut Microbiota.}, journal = {Phytotherapy research : PTR}, volume = {}, number = {}, pages = {}, doi = {10.1002/ptr.70067}, pmid = {40836368}, issn = {1099-1573}, support = {22A360004//Key scientific research plan of colleges in Henan Province/ ; 2019YFC1708802//National Key Research and Development Project/ ; 2017YFC1702800//National Key Research and Development Project/ ; ZYQR201810080//Henan province high-level personnel special support "Zhong Yuan One Thousand People Plan," Zhong Yuan Leading Talent/ ; 171100310500//The Major Science and Technology Projects in Henan Province: Study on the key technology for quality control and the key characteristics of Rehmannia glutinosa, Dioscorea opposita Thunb and Achyranthes bidentata Blume from Henan Province/ ; 2023KYCX059//Henan University of Traditional Chinese Medicine 2023 Graduate Student Research and Innovation Ability Enhancement Program/ ; }, abstract = {Achyranthes bidentata Blume is a traditional Chinese medicine used to treat liver and kidney protection and improve liver injury; however, its active components and mechanism of action remain unclear. This study focused on the monomer compound zingibroside R1 (R1) from Achyranthes bidentata Blume, specifically studying its effects on liver injury through the modulation of succinic acid-mediated immunity and inflammation via the gut microbiota. We isolated R1 and investigated its therapeutic effects in a lipopolysaccharide (LPS)- and D-galactosamine-induced acute liver injury mouse model. Liver tissue pathology, serum biomarkers, oxidative stress parameters, immune inflammation, and the gut microbiota composition were assessed. Metabolic profiling was performed via UPLC-Q-TOF-MS, and faecal microbiota transplantation experiments were conducted to validate the role of the gut microbiota in the hepatoprotective effects of R1. R1 treatment significantly alleviated LPS/GalN-induced liver injury, reducing liver haemorrhaging, hepatocyte necrosis, nuclear shrinkage, and inflammatory infiltration. R1 treatment also decreased the serum ALT and AST levels and mitigated oxidative stress. The levels of inflammation and immunity were markedly reduced following R1 treatment. Gut microbiota analysis revealed that R1 treatment restored Lactobacillus levels. Metabolomic analysis indicated that R1 influenced key metabolic pathways, including purine metabolism and glycerophospholipid metabolism pathways, and succinic acid was identified as a critical metabolite in the gut-liver interaction. Faecal microbiota transplantation (FMT) results confirmed that the therapeutic effect of R1 on liver injury is exerted by the gut microbiota, which affects the inflammation mediated by succinic acid metabolism. R1 from Achyranthes bidentata Blume provides hepatoprotective protection against LPS/GalN-induced liver injury by modulating the gut microbiota and succinic acid metabolism. These findings underscore the potential of R1 as a therapeutic agent for treating liver diseases, highlighting the importance of the gut microbiota in mediating liver health.}, } @article {pmid40832881, year = {2025}, author = {Cai, J and He, Y and Qu, L and Liu, J and Xie, X and Cao, Y}, title = {Liberation of galactose from lactose by gut microbial β-galactosidase prevents uterine bacterial infection.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ismejo/wraf185}, pmid = {40832881}, issn = {1751-7370}, abstract = {Reproductive infection is closely associated with adverse reproductive outcomes, contributing to a reduced live birth rate per pregnancy and an elevated infertility rate. Nutrition is widely acknowledged as a fundamental determinant of human and animal health, as well as the etiopathogenesis of various diseases, with the gut microbiota playing an integral part in this process. Lactose, a disaccharide present in mammalian milk, has been identified as a potential prebiotic. Here, we found that lactose was able to mitigate the inflammatory response elicited by uterine bacterial infection, preserve the integrity of the endometrial epithelial barrier, and reduce the bacterial load in the uterus. The protective effects of lactose were found to be gut microbiota-dependent and fecal microbiota transplantation from lactose-treated mice to recipient mice also ameliorated E. coli-induced metritis. 16S rRNA gene amplicon sequencing revealed that lactose supplementation changed the gut microbiota, specifically increasing the abundance of Lactobacillus intestinalis (L. intestinalis). Whole-genome sequencing identified that L. intestinalis expressed β-galactosidase, a lactose-metabolizing enzyme. Inhibition or exogenous supplementation of β-galactosidase confirmed its essential role in mediating lactose's protective effects against E. coli uterine infection. Furthermore, intragastric administration of [1-13Cgal]-lactose confirmed that galactose, a lactose metabolite, could translocate from the gut to the uterus. Mechanistically, galactose upregulated the CEBPB-dependent S100a8 expression after E. coli infection, and the protective effect could be blunted by S100a8 inhibition. Collectively, these findings highlight a nutrition-microbiota-host interaction that is stimulated by lactose supplementation, providing potential benefits for reproductive infection.}, } @article {pmid40832481, year = {2025}, author = {Kim, J and Kim, Y and Lee, YJ and Lee, HJ and Sim, I and Koh, S and Suh, DH and Jung, ES and Jo, JC}, title = {Gut Microbiome and Metabolome Dynamics as Predictors of Clinical Outcomes in Hematopoietic Stem Cell Transplantation.}, journal = {MedComm}, volume = {6}, number = {9}, pages = {e70334}, pmid = {40832481}, issn = {2688-2663}, abstract = {Hematopoietic stem cell transplantation (HSCT) profoundly disrupts the gut microbiome and metabolome, which in turn influence immune-related complications and patient outcomes. To systematically characterize these perturbations, we performed a longitudinal analysis of fecal microbiota composition and metabolite profiles in HSCT recipients at three critical timepoints: pre-transplant (T1), peri-transplant (T2), and post-transplant (T3). We observed that reduced microbial diversity at T1 and T3 was strongly associated with increased incidence of graft-versus-host disease (GVHD), progressive disease (PD), and decreased overall survival (OS). Metabolomic profiling revealed a significant decline in short-chain fatty acids (SCFAs), particularly acetate, from T1 to T2, which correlated with adverse clinical outcomes including GVHD, diarrhea, PD, and lower OS. Elevated levels of uric acid at T2 were predictive of GVHD onset, while decreased 1-phenylethylamine was linked to transplant-associated diarrhea. Furthermore, enrichment of beneficial bacterial taxa such as Lachnospiraceae and Ruminococcaceae was associated with improved survival. Together, these findings highlight the gut microbiome-metabolome axis as a dynamic biomarker for HSCT prognosis. This integrated insight offers potential avenues for microbiota-targeted diagnostics and interventions aimed at mitigating transplant-related complications and improving patient survival.}, } @article {pmid40832205, year = {2025}, author = {Fan, Y and Ni, M and Aggarwala, V and Mead, EA and Ksiezarek, M and Cao, L and Kamm, MA and Borody, T and Paramsothy, S and Kaakoush, NO and Grinspan, A and Faith, JJ and Fang, G}, title = {Long read metagenomics-based precise tracking of bacterial strains and genomic changes after fecal microbiota transplantation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.09.30.615906}, pmid = {40832205}, issn = {2692-8205}, abstract = {Fecal microbiota transplantation (FMT) has revolutionized the treatment of recurrent Clostridioides difficile infection (rCDI) and is being evaluated across other diseases. Accurate tracking of bacterial strains that stably engraft in recipients is critical for understanding the determinants of strain engraftment, evaluating their correlation with clinical outcomes, and guiding the development of therapeutic bacterial consortia. While short-read sequencing has advanced FMT research, it faces challenges in strain-level de novo metagenomic assembly. In this study, we described a novel framework, LongTrack, which uses long-read metagenomic assemblies and rigorous informatics tailored for FMT strain tracking. We highlighted LongTrack advantage over short-read approaches especially when multiple strains co-exist in the same sample. We showed LongTrack uncovered hundreds of engrafted strains across six FMT cases of rCDI and inflammatory bowel disease patients. Furthermore, long reads also allowed us to assess the genomic and epigenomic stability of engrafted strains during the 5-year follow-ups, revealing structural variations that may be associated with strain adaptation in a new host environment. Combined, our study advocates the use of long-read metagenomics and LongTrack to enhance strain tracking in future FMT studies, paving the way for the development of more effective defined biotherapeutic as an alternative to FMT.}, } @article {pmid40832058, year = {2025}, author = {Zhao, Y and Wang, B and Wei, X and Liu, D and Wang, R and Ma, H and Qiao, Z and Kong, N and Feng, J and Cui, D and Hou, S and Zhang, H}, title = {Gut Microbiota Dysbiosis in Preeclampsia: Mechanisms, Biomarkers, and Probiotic-Based Interventions.}, journal = {Mediators of inflammation}, volume = {2025}, number = {}, pages = {3010379}, pmid = {40832058}, issn = {1466-1861}, mesh = {Female ; Animals ; *Pre-Eclampsia/microbiology/blood/metabolism ; Pregnancy ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology ; Mice ; Mice, Inbred C57BL ; *Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Humans ; Tumor Necrosis Factor-alpha/blood ; Biomarkers/blood/metabolism ; Feces/microbiology ; Interleukin-6/blood ; RNA, Ribosomal, 16S/genetics ; Anti-Bacterial Agents/therapeutic use ; Lipopolysaccharides/blood ; }, abstract = {Background: This study aimed to investigate the impact of fecal microbiota transplantation (FMT) on gut microbiota composition and serum inflammatory factors in a murine model. Methods: Female C57BL/6J mice (n = 60) were divided into four groups: control (Con), negative (Neg), normal transplantation (NT), and preeclampsia transplantation (PET). The Con group received no treatment, while the Neg, NT, and PET groups were administered a triple antibiotic regimen (ampicillin, neomycin sulfate, and metronidazole) for 14 days to deplete gut microbiota. Following antibiotic treatment, FMT was performed: the NT group received fecal microbiota from healthy pregnant women and the PET group received microbiota from severe preeclampsia patients. Fecal samples and serum were collected for 16S rRNA sequencing and inflammatory factor analysis, respectively. Results: Significant differences in gut microbial composition were observed between the PET group and other groups, with enriched taxa such as Coprococcus, Bacillales, and Staphylococcus in the PET group. Conversely, taxa such as Helicobacter and Klebsiella were more abundant in the fecal microbiota of mice in the NT group. Furthermore, serum levels of lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) were markedly elevated in the PET group compared to the control, negative, and NT groups. Transplantation with fecal bacteria from preeclampsia patients leads to significant alterations in gut microbiota composition and increased serum inflammatory factors levels in mice. Conclusion: These findings provide insights into the relationship between gut microbiota and inflammatory processes in preeclampsia and underscore the potential therapeutic implications of FMT in modulating gut microbiota dysbiosis and inflammatory responses.}, } @article {pmid40831851, year = {2025}, author = {Hamad, S and Mubarak Jan, B and Al-Mohammed, A}, title = {Recurrent Clostridioides difficile Infection in a Patient With Chronic Colitis: A Successful Response to Fecal Microbiota Transplantation.}, journal = {Cureus}, volume = {17}, number = {7}, pages = {e88285}, pmid = {40831851}, issn = {2168-8184}, abstract = {Recurrent Clostridioides difficile infection (rCDI) remains a significant treatment challenge, particularly in patients with underlying gastrointestinal conditions. We present the case of a 72-year-old woman with multiple sclerosis and sarcoidosis, who experienced four separate episodes of rCDI despite treatment with vancomycin, fidaxomicin, and intravenous metronidazole. Colonoscopy revealed patchy inflammation with aphthous ulcerations, and histology confirmed chronic colitis without dysplasia or cytomegalovirus infection. Following a structured vancomycin taper, the patient underwent fecal microbiota transplantation (FMT), with complete resolution of symptoms. This case supports the early use of FMT in rCDI and highlights the need for individualized treatment strategies in patients with co-existing colonic inflammation.}, } @article {pmid40831218, year = {2025}, author = {Zhou, L and Wang, C and Gao, J and Wu, X and Li, G and Jiang, X and Xia, Y and Zhang, J and Lv, B and Zhao, F and Zhang, H and Pi, H and Qiu, J and Xu, S and Zou, Z and Chen, C}, title = {Novel Role of Gut-Derived Roseburia Intestinalis in Safeguarding Intestinal Barrier Integrity and Microenvironment Homeostasis During Arsenic Exposure.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e11895}, doi = {10.1002/advs.202511895}, pmid = {40831218}, issn = {2198-3844}, support = {82473594//National Natural Science Foundation of China/ ; KJQN 202200448//Science and Technology Research Program of Chongqing Municipal Education Commission/ ; W0043//Future Medical Youth Innovation Team of Chongqing Medical University/ ; 2023DBXM006//Chongqing Medical Scientific Research Project, Joint project of Chongqing Health Commission and Science and Technology Bureau/ ; CSTB2023NSCQ-LZX0059//Natural Science Foundation of Chongqing/ ; }, abstract = {As a well-known metalloid, arsenic usually causes human intestinal disorders via contaminated drinking water. However, the mechanisms underlying how arsenic induces intestinal injury remain unresolved, and the effective means of intervention are very limited. By establishing an acute arsenic exposure animal model, this work shows that arsenic disrupts the mechanical, chemical, immunological, and biological barriers of the intestine, and thereby changes the microenvironment in the gut. We further verify that the administration of fecal microbiota transplantation with a healthy gut microbiome alleviates the intestinal damage induced by arsenic. Intriguingly, by using 16S rRNA sequencing and anaerobic culture, we identify a novel role of gut-derived strain, Roseburia intestinalis, which exhibits significant protection against arsenic-induced intestinal toxicity in mice. By applying non-targeted metabolomics after arsenic exposure, this work further establishes the beneficial effects and the potential metabolites associated with Roseburia intestinalis, including cacodylic acid, carindone, 3-hydroxymelatonin and L-galacto-2-heptulose, etc. Transcriptomic analysis reveals that the protective effects of Roseburia intestinalis against arsenic-induced intestinal injury include mainly immune-related pathways. Taken together, these findings highlight that supplementation with gut-derived Roseburia intestinalis is an alternative strategy that could be used in the prevention and treatment of arsenic-related intestinal disorders.}, } @article {pmid37338497, year = {2025}, author = {Wong, EYT and Lee, JWJ and Lim, JFY and Toh, HC}, title = {The East Asian gut microbiome and its role in oncology: a narrative review.}, journal = {Singapore medical journal}, volume = {66}, number = {8}, pages = {426-430}, pmid = {37338497}, issn = {2737-5935}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Neoplasms/therapy/microbiology ; Immunotherapy/methods ; Asia, Eastern ; *Medical Oncology ; Fecal Microbiota Transplantation ; Immune Checkpoint Inhibitors/therapeutic use ; East Asian People ; }, abstract = {The field of onco-microbiome is rapidly expanding. Multiple studies have shown the crucial role of gut microbiota in the regulation of nutrient metabolism, immunomodulation and protection against pathogens. Tools for manipulating the gut microbiota include dietary modification and faecal microbiota transfer. Accumulating evidence has also documented the application of specific intestinal microbiome in cancer immunotherapy, notably in enhancing the efficacy of immune checkpoint inhibitors. The aim of this review is to focus on the East Asian microbiome and to provide a current overview of microbiome science and its clinical application in cancer biology and immunotherapy.}, } @article {pmid40818717, year = {2025}, author = {Yang, S and Yang, M and Lu, X and Tan, Y and Chang, W and Yang, H and Xu, D and Li, D}, title = {Stimulator of interferon genes-targeted positron emission tomography tracks early microbiota-induced tumor immune remodeling and guides immunotherapy.}, journal = {Journal of controlled release : official journal of the Controlled Release Society}, volume = {}, number = {}, pages = {114132}, doi = {10.1016/j.jconrel.2025.114132}, pmid = {40818717}, issn = {1873-4995}, abstract = {Immune checkpoint inhibitors (ICIs) have made dramatic evolution in cancer management, yet their curative effect remains limited in most tumors characterized by "cold" immunophenotype. Immune remodeling by transforming "cold" tumor to "hot" one is essential to improve ICIs response, and gut microbiota modulation has emerged as a promising approach. Nevertheless, a significant challenge lies in the absence of reliable tools for early assessment of immune remodeling. To address this, we focused on the stimulator of interferon genes (STING), an essential molecule for launching anti-tumor immunity, and developed the STING-targeted PET tracer [[18]F]FBTA. [[18]F]FBTA-PET detected a significant increase in tumor uptake with a more homogeneous spatial distribution following Lactobacillus rhamnosus GG (LGG) treatment. This increased [[18]F]FBTA uptake was prior to changes in tumor volume, T cell infiltration, and [[18]F]FDG-PET signals, and showed a strong correlation with STING expression in tumor tissues. The immune remodeling mediated by LGG administration, as captured by [[18]F]FBTA-PET, was also successfully replicated in recipient mice through fecal microbiota transplantation. Guided by [[18]F]FBTA-PET, the combination of LGG with αPD-L1 achieved superior anti-tumor efficacy. Furthermore, [[18]F]FBTA binding radioactivity positively correlated with STING expression in patients' tumor tissues. Our results established [[18]F]FBTA-PET as a robust indicator for early assessment of immune remodeling and guiding ICI-based combination therapies, highlighting its potential for clinical translation.}, } @article {pmid40816223, year = {2025}, author = {Merrick, B and Prossomariti, D and Allen, E and Bisnauthsing, K and Kertanegara, M and Sergaki, C and Le Guennec, AD and Delord, M and Bell, JT and Conte, MR and Moyes, DL and Shankar-Hari, M and Douiri, A and Goodman, AL and Shawcross, DL and Goldenberg, SD}, title = {Erratum to "Faecal microbiota transplant to ERadicate gastrointestinal carriage of Antibiotic-Resistant Organisms (FERARO): A feasibility randomised controlled trial" [J Infect 91 (2025) 106504].}, journal = {The Journal of infection}, volume = {91}, number = {3}, pages = {106583}, doi = {10.1016/j.jinf.2025.106583}, pmid = {40816223}, issn = {1532-2742}, } @article {pmid40785733, year = {2025}, author = {Pachhain, S and Halverstadt, B and Anekwe, EC and Phuntumart, V and Sprague, JE and Ward, CS and Cromwell, HC}, title = {Data on ethanol drinking and microbiome in alcohol preferring and non-preferring rats after a fecal microbiota transplant.}, journal = {Data in brief}, volume = {62}, number = {}, pages = {111901}, pmid = {40785733}, issn = {2352-3409}, abstract = {Alcohol Use Disorders (AUDs) constitute a global health crisis with limited effective treatments. Alterations in gut microbiome have been shown to be major contributors to substance use disorder and mental illness. Fecal Microbial Transfer (FMT) is emerging as a promising method for manipulating the Brain-Gut-Microbiome Axis in diverse health and disease states including AUD and has potential as a clinical treatment. The well characterized behavioral genetics of Alcohol Preferring (P) and Non-Preferring (NP) rat model offer valuable insights into the underlying mechanisms of AUD. This data article describes the quantitative results from an experiment on ethanol drinking behaviors and gut microbiome composition in P and NP rats that were administered fecal transfer of the microbiota. The results include data on ethanol consumption and preference of the two groups of animals prior to and following the FMT. Microbiome analysis showed that P rat ethanol-induced dysbiosis involved increased relative abundance of Akkermansia muciniphila and reduced Bacteroidetes and Lactobacillus while the FMT treatment partially restored levels. Gene abundance analysis showed an increase in alcohol metabolizing genes in P rats following three weeks ethanol access, indicating that the gut favors alcohol metabolizers after ethanol intake, which significantly decreased after FMT. These data provide details of the distinct microbial communities found in P and NP rats and the first to report data on detailed composition of the microbiome prior to and following FMT.}, } @article {pmid40770861, year = {2025}, author = {Drobnik, J and Pobrotyn, P and Grata-Borkowska, U and Madziarska, K and Baran, M}, title = {Trends and Efficacy in Clostridioides difficile Infection Management at a Polish Clinical Hospital.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {31}, number = {}, pages = {e948254}, pmid = {40770861}, issn = {1643-3750}, mesh = {Humans ; *Clostridium Infections/drug therapy/epidemiology ; Poland/epidemiology ; Male ; Female ; Vancomycin/therapeutic use ; *Clostridioides difficile/drug effects/pathogenicity ; Middle Aged ; Fidaxomicin/therapeutic use ; Aged ; Anti-Bacterial Agents/therapeutic use ; Metronidazole/therapeutic use ; Treatment Outcome ; Adult ; Hospitalization ; Aged, 80 and over ; Retrospective Studies ; Drug Therapy, Combination ; }, abstract = {BACKGROUND Clostridioides difficile infection (CDI) is a significant clinical problem. Treatment includes fidaxomicin and vancomycin, with second and subsequent recurrences treated with decreasing doses or sequential therapy with rifaximin, as well as considering treatment with a fecal transplant. This study aimed to analyze the method of treatment of CDI among patients hospitalized at the University Clinical Hospital in Wrocław (Poland). MATERIAL AND METHODS The study was conducted by analyzing medical records from 316 patients treated between 2016 and 2018. Due to the limited number of patients treated with fidaxomicin and rifaximin per year, these cases were combined for analysis when exploring the relationship between the year of hospitalization and CDI treatment. Patients spanning the turn of the year were assigned to the year with a longer hospitalization duration for a more robust analysis. RESULTS The predominant treatments for CDI were metronidazole and vancomycin in combination (40.5%), metronidazole alone (26.9%), and vancomycin alone (20.6%). Fidaxomicin was rarely used (1.6%) despite its 100% effectiveness. Although administered to only 5 patients, fidaxomicin achieved a 100% cure rate, highlighting its therapeutic promise. Treatment patterns shifted over the study period, but no significant difference in mortality was observed between years (P=0.904). Overall mortality among CDI patients was 24.7%, compared to 1.52% in the general inpatient population. Patients who died were more likely to have received metronidazole + vancomycin (P=0.009). CONCLUSIONS The mortality rate among CDI patients was notably high. Use of metronidazole alone decreased while alternative therapies (rifaximin, fidaxomicin) increased, but without impacting year-to-year mortality differences. Given its 100% cure rate in our cohort, broader use of fidaxomicin could meaningfully improve patient outcomes.}, } @article {pmid40770084, year = {2025}, author = {Xie, M and Li, X and Lau, HC and Yu, J}, title = {The gut microbiota in cancer immunity and immunotherapy.}, journal = {Cellular & molecular immunology}, volume = {}, number = {}, pages = {}, pmid = {40770084}, issn = {2042-0226}, abstract = {The human gastrointestinal tract harbors trillions of microorganisms, including bacteria, fungi, and viruses, to form the gut microbiota. Cumulative evidence has demonstrated the critical impact of gut microbes on cancer immunity. In cancer, an altered gut microbiota enriched with pathogenic bacteria can actively promote immune evasion and disrupt antitumor immunity, thereby supporting tumor growth and survival. Conversely, beneficial commensal bacteria (e.g., Lactobacillus and Bifidobacterium) have emerged as therapeutic probiotics for cancer prevention and as adjuvants for cancer therapy. The gut microbiota is also closely linked to the efficacy of immunotherapy. This review summarizes the effects of pathogenic bacteria and beneficial commensals, including T cells, B cells, natural killer cells, innate lymphoid cells, and myeloid-derived suppress cells, on various innate and adaptive immune cell populations in cancer. It also explores the mechanisms by which the gut microbiota influences immunotherapy efficacy, such as the modulation of innate immune cells and CD8[+] T cells. Given its importance, an increasing number of studies have developed approaches to target the gut microbiota to improve immunotherapy outcomes and reduce immune-related adverse events. These strategies include antimicrobial intervention, probiotics, prebiotics/dietary modifications, microbial metabolites, phage therapy, and fecal microbiota transplantation. This review also evaluates clinical applications that use the gut microbiota to predict immunotherapy outcomes. Overall, the current understanding of host‒microbe interactions within the tumor microenvironment has laid a critical foundation for the translation of microbiota research into clinical practice, ultimately benefiting patients.}, } @article {pmid38109364, year = {2024}, author = {Pun, CK and Huang, HC and Chang, CC and Hsu, SJ and Huang, YH and Hou, MC and Lee, FY}, title = {Hepatic encephalopathy: From novel pathogenesis mechanism to emerging treatments.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {87}, number = {3}, pages = {245-251}, doi = {10.1097/JCMA.0000000000001041}, pmid = {38109364}, issn = {1728-7731}, mesh = {Humans ; *Hepatic Encephalopathy/therapy/drug therapy ; Quality of Life ; Gastrointestinal Agents ; Lactulose/therapeutic use ; Rifaximin/therapeutic use ; }, abstract = {Hepatic encephalopathy (HE) is one of the major complications of liver disease and significantly affects the quality of life (QOL) of patients. HE is common and frequently relapses in cirrhotic patients. The management of HE is supportive, and precipitating conditions should be eliminated. Most drugs used to treat HE are conventional and include nonabsorbable disaccharides such as lactulose, and antibiotics such as rifaximin. However, their therapeutic efficacy is still suboptimal, and novel therapeutic agents are urgently needed. In addition, the optimal management and diagnosis of minimal HE/covert HE are under debate. In this review, we focus on novel pathogenetic mechanisms such as central nervous system clearance, and emerging therapeutic targets of HE, such as fecal material transplantation. We also discuss different classifications and etiologies of HE.}, } @article {pmid35068600, year = {2022}, author = {Zhu, J and Su, J}, title = {Alterations of the Gut Microbiome in Recurrent Malignant Gliomas Patients Received Bevacizumab and Temozolomide Combination Treatment and Temozolomide Monotherapy.}, journal = {Indian journal of microbiology}, volume = {62}, number = {1}, pages = {23-31}, pmid = {35068600}, issn = {0046-8991}, abstract = {UNLABELLED: This case-control study explored compositions of gut microbiome in recurrent malignant gliomas patients who had received bevacizumab and Temozolomide combination treatment and Temozolomide monotherapy. We investigated gut microbiota communities in feces of 29 recurrent malignant gliomas patients received combination treatment with bevacizumab and Temozolomide (Group 1) and monotherapy with Temozolomide alone (Group 2). We took advantage of the high-throughput Illumina Miseq sequencing technology by targeting the third and fourth hypervariable (V3-V4) regions of the 16S ribosomal RNA (rRNA) gene. We found that the structures and richness of the fecal microbiota in Group 1 were different from Group 2 with LEfSe analysis. The fecal microbiota in both Group 1 and Group 2 were mainly composed by Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria. However, Group 1 patients had higher relative abundance of Firmicutes, Bacteroidetes, Actinobacteria and lower relative abundance of Bacteroidetes and Cyanobacteria in their fecal microbiota than that in Group 2 patients. To evaluate bevacizumab involved post-treatment state of the fecal microbiota profile, we used random forest predictive model and ensembled decision trees with an AUC of 0.54. This study confirmed that the gut microbiota was different in recurrent malignant gliomas patients received the combination therapy of bevacizumab and Temozolomide compared with Temozolomide monotherapy. Our discover can help better understand the influence of bevacizumab related treatment on recurrent malignant gliomas patients. Therefore, this finding may also support the potentially therapeutic options for recurrent malignant gliomas patients such as fecal microbiota transplant.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-021-00962-2.}, } @article {pmid40825820, year = {2025}, author = {Ahn, JS and Kim, HM and Han, EJ and Hong, ST and Chung, HJ}, title = {Discovery of intestinal microorganisms that affect the improvement of muscle strength.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {30179}, pmid = {40825820}, issn = {2045-2322}, support = {RS-2023-00224099//the National Research Foundation (NRF)/ ; }, abstract = {This study provides the first evidence related to the identification of microbial strains closely associated with muscle strength enhancement, independent of the host's genetic background. Fecal transplants from humans into mice revealed a significant impact of gut bacteria on muscle strength, with some mice experiencing increases, while others showed no change or decreases. Interestingly, analysis of the fecal and gastrointestinal tract bacteria from each mouse classified by the degree of muscle strength revealed significant differences based on muscle strength. Furthermore, a more diverse microbial community was observed in the gastrointestinal tract compared to the feces. Further investigation identified two bacterial species, Lactobacillus johnsonii (L. johnsonii) and Limosilactobacillus reuteri (L. reuteri), that are related to improved muscle strength. Indeed, we confirmed that the supplementation with these bacteria in aged mice significantly enhanced their muscle strength by increasing the mRNA expression levels of follistatin (FST) and insulin-like growth factor-1 (IGF1) in muscle tissue. Overall, this study provides the first evidence that specific gut bacteria can directly improve muscle strength and introduces a novel approach to studying the gut microbiome's influence on complex traits.}, } @article {pmid40825448, year = {2025}, author = {Qi, XY and Liu, MX and Jiang, XJ and Gao, T and Xu, GQ and Zhang, HY and Su, QY and Du, Y and Luo, J and Zhang, SX}, title = {Gut microbiota in rheumatoid arthritis: Mechanistic insights, clinical biomarkers, and translational perspectives.}, journal = {Autoimmunity reviews}, volume = {}, number = {}, pages = {103912}, doi = {10.1016/j.autrev.2025.103912}, pmid = {40825448}, issn = {1873-0183}, abstract = {Rheumatoid arthritis (RA) is a systemic autoimmune disease shaped by complex interactions between genetics and environmental factors, among which gut microbiota has emerged as a critical modulator. Recent advances have implicated gut microbiota dysbiosis in RA pathophysiology, with evidence spanning mechanistic, diagnostic, and therapeutic dimensions. This review summarizes current knowledge of the gut-joint axis and outlines microbiota-based strategies for RA management. Numerous studies have demonstrated consistent alterations in gut microbial communities in patients with RA, with enrichment of Prevotella copri observed in 75% of patients with new-onset RA compared to 21.4% of healthy controls, suggesting a potential association with disease initiation. Mechanistically, we detail how microbial dysbiosis, including that of bacteria, fungi, and viruses, disrupts intestinal barrier integrity, skews T helper 17/T regulatory and T follicular helper/T follicular regulatory immune axes, induces molecular mimicry, and alters the profiles of microbial metabolites such as short-chain fatty acids. Diagnostically, microbial taxa and metabolites serve as promising biomarkers. Machine learning models based on microbiota profiles have achieved area under the curve (AUC) values exceeding 0.88, with discriminatory taxa such as Ruminococcus gnavus and Fusicatenibacter. Therapeutically, we reviewed microbiota-targeted interventions, such as probiotics, prebiotics, antibiotics, fecal microbiota transplantation, diet, and herbal medicines, highlighting the emerging field of pharmacomicrobiomics. Gut microbial signatures have shown promise in predicting treatment responses, including methotrexate efficacy via the enterotype-based gut microbial human index model (AUC = 0.945). This review proposes an integrated framework linking microbial alterations with RA onset and progression and presents gut microbiota as a promising frontier for biomarker discovery, personalized intervention, and precision medicine.}, } @article {pmid40825385, year = {2025}, author = {Du, Y and He, C and An, Y and Zhao, Y and Zhang, H and Shan, Z and Yang, Y and Wang, M and Xie, J and Huang, Y and Fu, W and Yuan, Y and Zhao, B}, title = {Gut microbiota modified by mulberry leaf water extract improves T2DM through browning of WAT/BAT activation mediated by SCFAs-AMPK/SIRT1/PGC-1α signaling pathway.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {120408}, doi = {10.1016/j.jep.2025.120408}, pmid = {40825385}, issn = {1872-7573}, abstract = {Mulberry leaf (Morus alba L.), traditionally recorded in "Compendium of Materia Medica" for diabetes treatment. Mulberry leaf water extract (MLE) has also been shown in modern studies to improve blood glucose levels while restoring gut microbiota homeostasis and increasing short-chain fatty acids (SCFAs) levels. However, the causal relationship between MLE-promoted SCFAs elevation and improvements in glucose/lipid metabolism as well as the exact mechanism, remain unclear.

AIM OF THE STUDY: This study aimed to clarify the causal relationship between MLE-promoted SCFAs elevation and improvements in glucose/lipid metabolism as well as the exact mechanism.

MATERIALS AND METHODS: db/db mice received antibiotic-induced microbiota depletion to generate pseudo-germ-free model, followed by parallel interventions: fecal microbiota transplantation (FMT) from MLE (4 g crude drug/kg)-treated or untreated donors, and direct SCFAs supplementation. Glucose and lipid metabolism in brown adipose tissue (BAT) and inguinal white adipose tissue (IWAT), and hepatic steatosis/inflammation were evaluated through biochemical assays, qRT-PCR and histology. Protein expressions in adipose tissues were assessed by Western blotting and immunohistochemistry. Gut microbiota composition was analyzed by 16S rRNA sequencing and fecal SCFAs levels were detected by targeted metabolomics.

RESULTS: Both FMT-MLE and SCFAs treatments demonstrated marked metabolic benefits, including enhanced glucose/lipid homeostasis, improved lipid metabolism, alleviated hepatic steatosis and inflammation, restored microbial balance, and elevated SCFAs concentrations. Mechanistically, mice treated with FMT-MLE and SCFAs showed increased BAT activity and exhibited increased energy expenditure, and browning of WAT. Additionally, FMT-MLE and SCFAs upregulated the protein expression of phosphorylated-AMP-activated protein kinase (p-AMPK), p-AMPK/adenosine monophosphate-activated protein kinase (AMPK), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) in BAT and IWAT.

CONCLUSION: MLE-modulated gut microbiota ameliorates T2DM via SCFAs-activated AMPK/SIRT1/PGC-1α signaling, promoting WAT browning and BAT activation.}, } @article {pmid40823499, year = {2025}, author = {Mikulska, M and Robin, C and Neofytos, D and Oltolini, C and Piekarska, A and Reigadas, E and Gil, L and Chemaly, RF and Groll, AH and Muñoz, P and Teh, BW}, title = {Management of Clostridioides difficile infection in patients with haematological malignancies and after cellular therapy: guidelines from 10th European Conference on Infections in Leukaemia (ECIL-10).}, journal = {EClinicalMedicine}, volume = {87}, number = {}, pages = {103371}, doi = {10.1016/j.eclinm.2025.103371}, pmid = {40823499}, issn = {2589-5370}, abstract = {Clostridioides difficile infection (CDI) poses a significant challenge in patients with haematological malignancies (HM) and those undergoing cellular therapy such as haematopoietic cell transplantation (HCT) or CAR T-cell therapy. These patients have high rates of both colonization with Clostridioides difficile and diarrhoea due to non-infectious causes, leading to challenges with establishing diagnosis and optimal management of CDI, especially in the setting of molecular detection of toxin genes alone. Current severity criteria are of limited usefulness since underlying haematological disease and its treatment impact white blood count and inflammatory manifestations of severe CDI. Extensive exposure to antibiotics, profound microbiota damage and bidirectional relationship with gastro-intestinal graft-versus-host disease after transplant further complicate clinical management. Therefore, the 10th European Conference on Infections in Leukemia (ECIL-10) group comprehensively reviewed the literature (published 01/01/2010-15/09/2024) on the epidemiology, treatment and prevention of CDI, and formulated consensus recommendations for the management of CDI specific to this population. New definitions of proven, probable and possible CDI in this population were developed and proposed for use in clinical research to standardise reporting.}, } @article {pmid40822487, year = {2025}, author = {Han, M and Zhou, Y and Gao, X and Cheng, X and Deng, L and Ji, S and Li, Z and Cai, Y and Yan, C and Chen, Y}, title = {Modulation of gut microbiota by Gardeniae Fructus oil exerts TLR4/NF-κB/NLRP3 pathway-mediated antidepressant effects based on transcriptomics and fecal transplantation.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1635897}, doi = {10.3389/fphar.2025.1635897}, pmid = {40822487}, issn = {1663-9812}, abstract = {BACKGROUND: Although our team has demonstrated the antidepressant effect of Gardeniae Fructus oil (OGF) in the early stages, the mechanism of whether OGF works by regulating the gut microbiota is not clear. This study aims to elucidate OGF's gut-brain axis mechanism in depression.

METHODS: Chronic unpredictable mild stress (CUMS) was used to establish a depressed mouse model, and the depression-like behavior of mice was observed by behavioral tests after antibiotic pretreatment and fecal microbiota transplantation (FMT). HE staining was used to observe the pathological changes in the hippocampus and colon; ELISA was used to detect the content of neurotransmitters and pro-inflammatory factors; Western blot was used to detect the expression of colonic tight junction proteins. The signaling pathways regulating the antidepressant properties of OGF were obtained by transcriptome sequencing analysis and validated at the protein level.

RESULTS: Compared with the CON group, mice in the CUMS group showed significant depressive-like behavior, pathological damage to the hippocampus and colon tissues, significant decrease in levels of 5-HT, DA, and BDNF in the hippocampus, significant increase in levels of IL-1β, IL-6, TNF-α, DAO, and LPS in serum, significant decrease in colonic tight junction protein expression, and significant increase in protein expression of TLR4, p-NF-κB, NLRP3, ASC, and IL-1β in the hippocampus (P < 0.01); Compared with the CUMS group, the FMT group could effectively improve the above situation (P < 0.05, P < 0.01), whose therapeutic effect was second only to the OGF group (P < 0.01), while ABX + OGF group did not show obvious therapeutic effect.

CONCLUSION: OGF might exert antidepressant effects by modulating gut microbiota and mediating the hippocampal TLR4/NF-κB/NLRP3 pathway.}, } @article {pmid40822485, year = {2025}, author = {Hu, P and Zhang, L and Hu, H and Wang, D and Chen, J and Xiao, J and Wu, H and Qi, L and Qin, K and Zuo, X and Li, J}, title = {Red yeast rice extract improves lipid metabolism by modulating gut microbiota in high-fat diet mice.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1608582}, doi = {10.3389/fphar.2025.1608582}, pmid = {40822485}, issn = {1663-9812}, abstract = {As a traditional food-medicine dual-purpose substance, red yeast rice (RYR) has gained wide attention for its lipid-lowering activity. However, existing studies mainly focus on the liver-targeted effects of statin-like components, with limited systematic insights into its lipid metabolism regulation via gut microbiota. This study combines high-fat diet (HFD)-induced hyperlipidemia mouse models, 16S rRNA gene sequencing, untargeted metabolomics, and fecal microbiota transplantation (FMT) to investigate the potential of RYR extract in improving lipid metabolism through gut microbiota modulation. The results showed that RYR extract significantly improved body weight, serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) levels, and hepatic lipid deposition in HFD-fed mice. Additionally, RYR extract effectively restored the intestinal structural damage and enhanced intestinal barrier function. 16S rRNA revealed that RYR extract significantly modulated the gut microbiota, increasing the abundance of beneficial bacteria such as Bifidobacterium and restoring the ratio of Firmicutes to Bacteroidota. Metabolomics analysis revealed that RYR extract significantly modulated the gut microbiota-derived metabolites, particularly in the tryptophan metabolism and phenylalanine metabolism. FMT experiments showed that the fecal microbiota from RYR-treated group obviously improved the blood lipid levels, liver pathology, and intestinal function in HFD-fed mice. These results suggest that RYR extract improves lipid metabolism through the modulation of gut microbiota and related metabolic pathways, which provides new insights into the mechanism research of RYR's lipid-lowering effect.}, } @article {pmid40822387, year = {2025}, author = {Wang, K and Gao, C and Zhu, L and Chen, M and Tong, YX and Zhang, S}, title = {Fecal microbiota transplantation for chronic constipation: a systematic review and meta-analysis of clinical efficacy, safety, and microbial dynamics.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1604571}, doi = {10.3389/fmicb.2025.1604571}, pmid = {40822387}, issn = {1664-302X}, abstract = {BACKGROUND: Chronic constipation, a prevalent gastrointestinal disorder with limited treatment efficacy in refractory cases, has prompted exploration of fecal microbiota transplantation (FMT) as a novel therapeutic strategy. This systematic review and meta-analysis evaluate the efficacy, safety, and gut microbial dynamics of FMT in adults with chronic constipation.

METHODS: We systematically searched PubMed, Embase, Web of Science, and Cochrane Library up to January 2025, identifying 1,072 records. Nine studies (n = 245 patients) met inclusion criteria for qualitative synthesis, with eight contributing to meta-analysis. Outcomes included constipation remission and improvement, stool metrics, quality of life, and microbiota changes. Random-effects models analyzed pooled remission rates, mean differences (MDs), and heterogeneity (I[2] statistics).

RESULTS: Fecal microbiota transplantation achieved a 50.7% pooled remission rate (95% CI: 38.7%-62.7%) and 64.8% improvement rate (95% CI: 51.4%-76.3%). Significant improvements were observed in stool consistency (MD = 1.32, 95% CI: 1.05-1.35), quality of life (GIQLI MD = 32.19, 95% CI: 17.15-47.23), and symptom severity (Wexner MD = -4.83, 95% CI: -7.15-2.51). Post-FMT microbiota analyses revealed enrichment of beneficial taxa (Bifidobacterium, Prevotella; Firmicutesacteroidetes) and suppression of pro-inflammatory Enterobacteriaceae. Transient gastrointestinal adverse events (e.g., bloating: 17.3%) resolved spontaneously, with no severe complications reported.

CONCLUSION: Fecal microbiota transplantation demonstrates clinically meaningful symptom relief and gut microbiota remodeling in chronic constipation, supported by favorable short-term safety. While heterogeneity in protocols and limited RCT data warrant caution, these findings advocate standardized FMT frameworks and confirmatory trials to optimize therapeutics for refractory constipation.

https://www.crd.york.ac.uk/prospero/, identifier CRD42025643634.}, } @article {pmid40821820, year = {2025}, author = {Dai, Z and Cheng, W and Peng, H and Qiu, X and Sun, J and Liu, X and Sun, X and Cai, J and Wang, J and Li, G and Lv, Y and Chen, S and Zhong, Z}, title = {Microbiota composition-based donor selection affects FMT efficacy in a murine colitis model.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1635244}, doi = {10.3389/fimmu.2025.1635244}, pmid = {40821820}, issn = {1664-3224}, abstract = {BACKGROUND: Growing evidence links gut microbial dysbiosis to inflammatory bowel disease (IBD) pathogenesis, establishing fecal microbiota transplantation (FMT) as a microbiota-targeted therapy; however, variable outcomes in randomized trials highlight the need to identify compositional features of donor microbiota associated with FMT efficacy.

OBJECTIVE: This study aimed to investigate how the composition of the donor gut microbiota influences the therapeutic efficacy of FMT in IBD.

METHOD: Fecal DNA from 39 IBD patients and 42 healthy donors was analyzed via 16S rRNA sequencing. Donor-enriched genera (identified through differential analysis and median abundance thresholds) guided FMT selection. Dextran sulfate sodium (DSS)-induced colitis mice received donor microbiota transplants; disease activity and microbiota dynamics were evaluated through longitudinal sequencing.

RESULTS: IBD patients showed reduced microbial diversity and increased Proteobacteria phylum versus healthy donors, as well as the genera Escherichia-Shigella, Megamonas, and Klebsiella. Linear discriminant analysis effect size (LEfSe) analysis identified 50 differentially abundant genera, with 36 beneficial taxa enriched in donors. Based on median abundance of these health-associated genera, four high- and low-abundance donors were selected. FMT from high-abundance donors outperformed low-abundance donors and 5-ASA in colitis mice, restoring microbial diversity to healthy levels. Recipient mice showed increased Firmicutes and Bacteroidota and decreased Verrucomicrobiota, with Lactobacillus and Dubosiella enrichment and normalization of Lachnospiraceae NK4A136 group, Akkermansia, Turicibacter, and Parabacteroides. LEfSe identified 24 genera distinguishing IBD and control mice; post-FMT microbiota of high-abundance donor recipients more closely resembled controls, correlating with therapeutic success.

CONCLUSION: FMT ameliorated IBD symptoms in murine models, with therapeutic efficacy associated with the relative abundance of health-associated microbial genera in donor microbiota.}, } @article {pmid40821112, year = {2025}, author = {Zhao, S and Dan, L and Huang, R and Shen, Z and Huang, D and Wu, P and Ma, Z}, title = {Decoding the impact of gut microbiota on heart failure.}, journal = {Genes & diseases}, volume = {12}, number = {6}, pages = {101592}, doi = {10.1016/j.gendis.2025.101592}, pmid = {40821112}, issn = {2352-3042}, abstract = {Decreased cardiac output in heart failure leads to intestinal ischemia and increased permeability. Substantial changes occur in the gut microbiota, characterized by a decline in beneficial bacteria and an overgrowth of potentially harmful bacteria. The gut microbiota is intricately linked to prevalent risk factors for heart failure, including hypertension, diabetes, obesity, and renal insufficiency. Furthermore, imbalanced microbiota-derived metabolites enter the bloodstream and may contribute to the progression of heart failure. Ongoing research explores gut microbiota manipulation to alleviate heart failure with probiotics, targeted antibiotics, fecal microbiota transplantation, and dietary adjustments. This review summarizes how gut microbiota participates in heart failure and highlights the emerging promise of modulating gut dysbiosis as a therapeutic approach for managing heart failure.}, } @article {pmid40819131, year = {2025}, author = {Tang, B and Li, S and Li, X and He, J and Zhou, A and Wu, L and Xiao, X and Wang, S and Jiang, H and Jian, J and Hou, Z and Ge, Y and Lei, Y and Zhou, J and Tu, D and Lu, C and Yang, M and Yang, S}, title = {Cholecystectomy-related gut microbiota dysbiosis exacerbates colorectal tumorigenesis.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {7638}, pmid = {40819131}, issn = {2041-1723}, support = {82030020//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82172958//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Cholecystectomy represents the most prevalent biliary surgical procedure for gallbladder abnormalities. Growing evidence suggests that cholecystectomy is associated with an elevated risk of colorectal cancer. However, the underlying mechanism remains elusive. Here we show that cholecystectomy exacerbates colorectal tumorigenesis in both AOM/DSS and APC[min/+] mice models. Metagenomic sequencing and targeted metabolomics show that cholecystectomy leads to a decrease of Bifidobacterium breve (B. breve) and an increase of Ruminococcus gnavus (R. gnavus), along with increased levels of glycoursodeoxycholic acid (GUDCA) in human and tauroursodeoxycholic acid (TUDCA) in mice. Fecal microbiota transplantation, single bacterial colonization and bile acid supplementation demonstrate that cholecystectomy-related gut microbiota perturbations promote the production of TUDCA and facilitate colorectal tumorigenesis. RNA-sequencing and co-immunoprecipitation reveal that the compromised bile acid metabolism inhibits farnesoid X receptor (FXR) signaling, disrupts the FXR/β-catenin interaction, and ultimately exacerbates colorectal tumorigenesis. Significantly, FXR agonist obeticholic acid (OCA) averts cholecystectomy-related colorectal tumorigenesis. The gut microbiota holds a crucial position in cholecystectomy-induced colorectal tumorigenesis, and modulation of the gut microbiota-bile acid-FXR axis represents a promising preventive strategy.}, } @article {pmid40818981, year = {2025}, author = {Tao, M and Wu, T and Zhou, X and Li, F and Chen, Y and Ling, K and Liang, Z}, title = {Butyrate enhances gut dysbiosis by activating the cAMP/PKA/CREB signaling pathway to inhibit the progression of endometrial carcinoma.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {516}, pmid = {40818981}, issn = {1471-2180}, support = {2019YFC1005202//National Key Technology R&D Program of China/ ; }, } @article {pmid40818371, year = {2025}, author = {Zhang, H and Yan, S and Du, R and Ma, Z and Xue, Y and Zhao, Y and Yao, W and Chen, C and Li, X and Bao, S and Song, Y}, title = {Epiberberine alleviates cadmium-induced duodenal inflammation in Hu sheep by inhibiting HIF-1 signaling pathway.}, journal = {Ecotoxicology and environmental safety}, volume = {303}, number = {}, pages = {118861}, doi = {10.1016/j.ecoenv.2025.118861}, pmid = {40818371}, issn = {1090-2414}, abstract = {Environmental cadmium (Cd) exposure not only poses a significant threat to livestock health but also induces intestinal disorders in sheep. As a critical region for digestion and absorption, damage to the duodenum directly impairs systemic health. To elucidate the key mechanisms underlying Cd-induced duodenal injury and identify preventive and therapeutic strategies, this study utilized Cd-exposed Hu sheep as experimental models and applied multi-omics technologies, including non-targeted metabolomics, proteomics, and transcriptomics. The results showed that Cd exposure caused severe damage to the duodenum of Hu sheep, characterized by inflammatory cell infiltration and disruption of the intestinal barrier. Multi-omics analysis revealed that Cd exposure reduced levels of beneficial metabolites (such as vitamin K and riboflavin) while activating the HIF-1 signaling pathway. Through network pharmacology screening and molecular docking validation, epiberberine (EPI) was identified as a promising therapeutic candidate targeting the HIF-1α. Mouse fecal microbiota transplantation (FMT) experiments further confirmed that EPI can restore the intestinal barrier integrity, mitigate inflammatory responses, and effectively alleviate Cd-induced duodenal damage by inhibiting the HIF-1 signaling pathway, providing a novel approach for preventing and treating intestinal diseases under cadmium exposure.}, } @article {pmid40816629, year = {2025}, author = {Xu, J and Lao, Y and Zhang, W and Chen, L and Zhang, H and Liu, H and Yan, T and Huang, R and Xu, Y and Ye, L and Zhi, F and Yang, H}, title = {Berberine alleviates metabolic dysfunction-associated steatohepatitis by enhancing the abundance of Akkermansia muciniphila.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {110069}, doi = {10.1016/j.jnutbio.2025.110069}, pmid = {40816629}, issn = {1873-4847}, abstract = {Metabolic dysfunction-associated steatohepatitis (MASH) is associated with intestinal barrier defects and gut microbiota dysbiosis. The gut commensal bacterium Akkermansia muciniphila (Akk) maintains intestinal barrier integrity and improves MASH-related metabolic syndromes. Berberine (BBR), a traditional Chinese medicine, shows promise in treating MASH. However, research on drugs that target Akk regulation and its underlying mechanisms remains limited. This study investigates the mechanisms by which BBR regulates Akk in MASH. We fed C57BL/6J male mice a methionine-choline-deficient (MCD) diet for 6 weeks to establish the MASH mouse models. The gut microbiota was analyzed using 16S rRNA sequencing and bacterial quantification measured by qPCR analysis. An antibiotic cocktail (Abx) and fecal microbiota transplantation (FMT) were applied to modulate gut microbiota. Results showed that BBR reduced hepatic and colonic inflammation, preserved intestinal barrier integrity and prevented microbiota translocation into the liver. The 16S rRNA sequencing and qPCR analysis revealed a significant increase in Akk abundance in fecal samples following BBR treatment. Mechanistically, BBR did not promote Akk growth directly, but it reduced the bacterial load and enhanced MUC2 expression, thereby facilitating Akk colonization indirectly. While disruption of the gut microbiota by antibiotics treatment weakened the therapeutic effect of berberine on MASH, transplanting of the fecal microbiota from BBR-treated mice could mitigate MASH in antibiotic-treated mice. Finally, BBR and Akk exhibited synergistic therapeutic effects against MASH. Our study illustrated that BBR alleviates MASH mice by enhancing Akk abundance and restoring intestinal barrier integrity. BBR and Akk combination therapy would be a promising strategy for MASH prevention.}, } @article {pmid40816342, year = {2025}, author = {Wellens, J and Vanderstappen, J and Hoekx, S and Vissers, E and Luppens, M and Van Elst, L and Lenfant, M and Raes, J and Derrien, M and Verstockt, B and Ferrante, M and Verbeke, K and Matthys, C and Vermeire, S and Sabino, J}, title = {Effect of five dietary emulsifiers on inflammation, permeability, and the gut microbiome: a placebo-controlled randomized trial.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2025.08.005}, pmid = {40816342}, issn = {1542-7714}, abstract = {BACKGROUND AND AIMS: Dietary emulsifier consumption might promote intestinal inflammation, eventually leading to inflammatory bowel diseases. However human data are scarce and involve a limited number of emulsifiers. We studied the effects of an emulsifier-free diet (EFD) and specific emulsifier supplementation.

METHODS: Sixty healthy participants followed an EFD for two weeks. Then, using a randomized placebo-controlled trial design, participants continued an EFD for four weeks with the addition of either carboxymethyl cellulose (CMC), polysorbate-80, carrageenan, soy lecithin, native rice starch (NRS), or no additives administered through brownies. Effects on cardiometabolic markers, gut microbiota, intestinal inflammation and permeability were explored.

RESULTS: After two weeks of EFD, cholesterol levels decreased (p=0.00006). Under emulsifier-supplementation, alpha diversity remained stable, yet microbial composition was affected by treatment and visit. Compared to placebo, concentrations of all short chain fatty acids (SCFAs) were lower in those consuming CMC, which was mirrored by other emulsifiers although not all reaching significance. No differences in faecal calprotectin, CRP, LBP, cholesterol levels or other metabolic markers were observed between placebo and emulsifiers at the end of the intervention. Serum inflammatory and cardiometabolic proteins remained unchanged. In individuals consuming carrageenan, transcellular intestinal permeability increased (p=0.04) compared to baseline.

CONCLUSION: In this double-blind placebo-controlled exploratory trial, emulsifier supplementation lowered SCFA concentration compared to placebo. Emulsifier supplementation did not impact intestinal or systemic inflammation, or metabolic endpoints. Cholesterol levels decreased after two weeks of EFD. These results point towards potential intestinal benefits of limiting dietary emulsifiers in the diet, requiring further investigation.}, } @article {pmid40816329, year = {2025}, author = {Smith, B}, title = {The heroes within: utilizing the gut microbiome, microbiome therapeutics, and fecal microbiota transplant in managing companion animal health and disease.}, journal = {Journal of the American Veterinary Medical Association}, volume = {}, number = {}, pages = {1-8}, doi = {10.2460/javma.25.03.0218}, pmid = {40816329}, issn = {1943-569X}, abstract = {Microbiome therapeutics are gaining recognition for their role in the management of companion animal health and disease. This narrative review provides the current definition of the gut microbiome, the organisms comprising the theater, and their contributions to host homeostasis. Several testing modalities to determine the composition and distribution of bacterial groups within the gut microbiome are available. Sensitivity, specificity, and depth of analysis differ among these testing platforms and, while further research is needed to build on their interpretation, provides the veterinary practitioner a way to identify dysbiosis occurrence in their patients. Integrating microbiome therapeutics into clinical practice can be achieved through a multimodal approach that utilizes diet, prebiotics, probiotics, postbiotics, bacteriophages, and fecal microbiota transplant to modulate the microbiome balance and restore eubiosis to patients in dysbiotic states. Available literature is revealing the potential broad applications of microbiome modulation, but further study is needed to determine more precise mechanisms of action of these therapies in order to fully explore their potential.}, } @article {pmid40815946, year = {2025}, author = {Li, ZX and Kang, KW and Zheng, H and Li, DL and Xu, JC and Lv, HQ and Wu, RH and Gan, LS}, title = {Puerarin-rich compound Puerariae lobatae formulas alleviate hyperuricemia in mice by enhancing renal and intestinal function through regulating gut microbiota.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {146}, number = {}, pages = {157115}, doi = {10.1016/j.phymed.2025.157115}, pmid = {40815946}, issn = {1618-095X}, abstract = {BACKGROUND: Hyperuricemia, a metabolic disorder strongly associated with gout and cardiorenal diseases, has become a global health threat affecting over 15% of the worldwide population. Current pharmacotherapies face limitations due to adverse effects during prolonged use. Natural medicines like Radix Puerariae Lobatae have demonstrated therapeutic potential with superior safety profiles.

PURPOSE: This study investigated the anti-hyperuricemic efficacy of compound Puerariae lobatae formulas (PLF1 and PLF2) and their bioactive component puerarin, focusing on their mechanisms for enhancing renal/intestinal uric acid excretion, alleviating pathological damage, and modulating gut microbiota composition.

METHODS: A hyperuricemic mouse model was established using an adenine/potassium oxonate diet. Mice were treated with PLF1 (250/500 mg/kg), PLF2 (300/600 mg/kg), puerarin (100 mg/kg), or benzbromarone (40 mg/kg, positive control). Plasma and tissue uric acid levels, XOD and ADA activities, and renal/intestinal transporter expression (ABCG2, OAT1) were analyzed. Histopathological examinations were performed using HE staining to assess kidney, liver, and intestinal integrity. Gut microbiota composition was evaluated via PacBio Sequel II 16S rRNA sequencing. Antibiotic-induced microbiota depletion and fecal microbiota transplantation (FMT) approaches were employed to validate microbiota-dependent effects.

RESULTS: PLF1, PLF2, and puerarin significantly reduced plasma uric acid levels and suppressed XOD/ADA activities. Histopathological analysis demonstrated marked improvements in renal tubular injury, hepatic steatosis, and intestinal structural integrity, including restoration of villus architecture and crypt morphology. The expression of renal ABCG2 and OAT1, as well as intestinal ABCG2, was significantly upregulated, accompanied by enhanced expression of colonic tight junction proteins (ZO-1 and occludin). Antibiotic-induced microbiota depletion abolished the hypouricemic effect of puerarin, while FMT from puerarin-treated donors significantly alleviated hyperuricemia in recipient mice. Gut microbiota analysis revealed that both PLF2 and puerarin selectively enriched the beneficial bacterium Akkermansia muciniphila while simultaneously reducing pathogenic taxa.

CONCLUSION: This study establishes Puerariae lobatae formulas and puerarin as multi-target therapeutics for hyperuricemia, offering dual advantages over conventional drugs by enhancing renal/intestinal uric acid excretion while also repairing organ damage, and remodeling gut microbiota to enrich probiotics like A. muciniphila. The microbiota-dependent efficacy of puerarin not only underscores its potential as a novel natural therapeutic agent but also provides critical pharmacological evidence for advancing puerarin and Radix Puerariae Lobatae-based formulas in hyperuricemia treatment, bridging traditional herbal medicine with modern microbiota-targeting strategies.}, } @article {pmid40815137, year = {2025}, author = {Skryabin, V}, title = {Gut microbiota and alcohol use disorder: a new frontier in treatment and recovery.}, journal = {BJPsych bulletin}, volume = {}, number = {}, pages = {1-8}, doi = {10.1192/bjb.2025.10129}, pmid = {40815137}, issn = {2056-4694}, abstract = {AIMS AND METHOD: Alcohol use disorder (AUD) is a major global health concern associated with limited treatment efficacy and high relapse rates. Recent research highlights the gut microbiota as a critical modulator of AUD pathophysiology through its influence on the gut-brain axis. Chronic alcohol consumption induces gut dysbiosis, characterised by reduced microbial diversity, impaired gut barrier function and systemic inflammation, which perpetuate neuroinflammation, stress dysregulation and neurotransmitter imbalances. These disruptions exacerbate addiction-related behaviours, contributing to the cycle of dependence and relapse. This critical review synthesises current evidence on the role of gut microbiota in AUD, examining the mechanisms linking dysbiosis to addiction and evaluating therapeutic interventions such as probiotics, prebiotics, faecal microbiota transplantation (FMT), psychobiotics and dietary modifications.

RESULTS: The strategies evaluated show significant potential in restoring microbial homeostasis and improving AUD outcomes, but challenges remain, including gaps in mechanistic understanding, variability in methodologies, and barriers to clinical translation.

CLINICAL IMPLICATIONS: There is a need for multi-omics research, personalised medicine approaches and integrated treatment models to advance microbiota-based therapies. Gut microbiota-targeted strategies might then transform AUD management, offering innovative and personalised solutions for addiction recovery.}, } @article {pmid40814761, year = {2025}, author = {Qin, P and Kragsnaes, MS and Holm, DK and Horn, HC and Nilsson, AC and Kjeldsen, J and Kristiansen, K and Ellingsen, T}, title = {Clinical Significance of Gut Microbiota Community Types for Long-term Response to Fecal Microbiota Transplantation in Patients with Psoriatic Arthritis.}, journal = {Arthritis & rheumatology (Hoboken, N.J.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/art.43359}, pmid = {40814761}, issn = {2326-5205}, abstract = {OBJECTIVE: Fecal microbiota transplantation (FMT) holds promises as a beneficial supplement to methotrexate in patients with psoriatic arthritis (PsA). We therefore investigated how gut bacterial signatures in patients and donor strain engraftment associated with long-term response to FMT.

METHODS: This exploratory study is based on the FLORA trial cohort encompassing 31 patients with moderate-to-high PsA disease activity and four FMT donors. Out of fifteen patients receiving one single-donor FMT, thirteen were included in the per-protocol (PP) population. Stool samples were collected before and after FMT (week 4, 12, and 26). We performed shotgun metagenomics to characterize gut microbiota features.

RESULTS: At baseline, 17 patients (55%) had a gut microbiota community type dominated by the Bacteroides genus (B-type) while 14 (45%) had a Prevotella-driven community type (P-type). The B- and P-type patients did not differ in disease activity nor demographics, but the B-type had a significantly higher species diversity compared to the P-type (P=0.005). In the PP population, five out of seven B-type patients vs none out of six P-type patients (P=0.021) achieved a long-term clinical beneficial response at week 26. Bacterial strain richness increased significantly from baseline to week 4 and 26 in B-type (P=0.016), but not in P-type, patients. Eighteen engrafted strains persisted only in B-type recipients by week 26, including a Bacteroides clarus strain, which demonstrated a negative effect size regarding arthritis pain and the patients' global assessment of disease.

CONCLUSION: Recipients with a Bacteroides-dominated community structure were more likely to achieve long-term beneficial response following one FMT.}, } @article {pmid40812693, year = {2025}, author = {Pan, Y and Deng, Y and Yang, H and Yu, M}, title = {The aryl hydrocarbon receptor: A promising target for intestinal fibrosis therapy.}, journal = {Pharmacological research}, volume = {219}, number = {}, pages = {107909}, doi = {10.1016/j.phrs.2025.107909}, pmid = {40812693}, issn = {1096-1186}, abstract = {Intestinal fibrosis, a severe complication of inflammatory bowel disease, leads to intestinal stenosis. Effective therapies for this condition are lacking. The aryl hydrocarbon receptor (AhR), a highly conserved nuclear transcription factor activated by diverse ligands, plays dual roles in fibrogenesis, but its relationship to intestinal fibrosis has not been comprehensively reviewed. This review explores the pathogenesis of intestinal fibrosis, and places particular focus on the mechanistic role of AhR signaling pathways, which may be mediated by dietary, microbial, and environmental ligands. We propose a new strategy for the targeting of AhR-related dietary ligands to prevent intestinal fibrosis. Dietary AhR ligands, such as glucobrassicin, flavonoids, and curcumin, exert anti-fibrotic effects by modulating the gut microbiota, suppressing collagen deposition, and inhibiting transforming growth factor-β pathways. Conversely, environmental pollutants (e.g., polycyclic aromatic hydrocarbons, microplastics, and propiconazole) exacerbate fibrosis via AhR activation. In multiple disease models, 16S rRNA sequencing has revealed positive and negative linear relationships between the gut microbiota and fibrosis. Intestinal microbiota-derived metabolites also affect fibrosis, including via immune cell regulation to indirectly reduce collagen deposition and direct action on extracellular matrix-related proteins to relieve intestinal fibrosis. The interaction among the AhR, microbiota, and diet suggests new therapeutic strategies, such as dietary interventions and fecal microbiota transplantation, to restore the microbial balance and inhibit fibrosis. The promotion of intestinal fibrosis by AhR agonists in environmental pollutants further emphasizes the need to reduce exposure to environmental toxins while following a plant-based diet rich in AhR agonists.}, } @article {pmid40812589, year = {2025}, author = {Liu, L and Liang, L and Liang, H and Wang, M and Zhou, W and Mai, G and Yang, C and Chen, Y}, title = {Microbiome-metabolome generated bile acids gatekeep infliximab efficacy in Crohn's disease by licensing M1 suppression and Treg dominance.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.08.017}, pmid = {40812589}, issn = {2090-1224}, abstract = {INTRODUCTION: Despite the effectiveness of infliximab in treating Crohn's disease (CD), up to 40 % of patients fail to respond adequately.

OBJECTIVES: This study aimed to identify predictive biomarkers of primary non-response to infliximab in treatment-naïve CD patients by characterizing baseline gut microbiome-metabolome interactions and to validate their mechanistic role in driving therapeutic resistance.

METHODS: In a prospective cohort of 100CD patients initiating infliximab therapy and 49 healthy controls, we performed longitudinal 16S rRNA sequencing and untargeted metabolomics on pre-/post-treatment fecal samples. Machine learning (twelve algorithms including K-Nearest Neighbors, Linear Discriminant Analysis, Naive Bayes, and LightGBM) identified predictive microbial and metabolic features, with findings experimentally validated through fecal microbiota transplantation (FMT) in a murine TNBS-induced colitis model.

RESULTS: Non-responders demonstrated significant microbial dysbiosis marked by reduced α-diversity, depletion of Bifidobacterium, Blautia, and Lachnospiraceae, and enrichment of Escherichia/Shigella. Metabolomic profiling identified 179 differentially abundant metabolites, including deficiencies in taurochenodeoxycholic acid (TCDCA) and perturbations in glycerophospholipid metabolism and primary bile acid biosynthesis pathways. Among single-omics models, the microbiome-based Linear Discriminant Analysis achieved optimal performance (test AUC = 0.805), surpassing metabolomics-only (best AUC = 0.634) and integrated multi-omics approaches (best AUC = 0.779). SHAP analysis revealed Bifidobacterium as the dominant protective predictor, with its depletion strongly associated with non-response. Mechanistically, MIMOSA2 analysis linked Bifidobacterium catenulatum to TCDCA production, while FMT from non-responders exacerbated murine colitis through Treg depletion and M1 macrophage polarization, confirming microbiome-driven immune dysregulation.

CONCLUSIONS: These findings establish gut microbiome composition, particularly Bifidobacterium abundance, as a critical determinant of anti-TNF response in CD, mediated through bile acid-dependent regulation of Treg/M1 macrophage homeostasis. While multi-omics integration did not enhance predictive performance, microbiome-based machine learning models offer clinically actionable biomarkers for treatment stratification, providing a roadmap for precision therapy to overcome biological resistance in inflammatory bowel disease.}, } @article {pmid40812483, year = {2025}, author = {Han, Q and Xia, S and Huang, X and He, J and Yin, Y and Yin, J}, title = {Age-related differences in the gut microbiota of pigs influence fat deposition in the mouse.}, journal = {The Journal of nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tjnut.2025.07.022}, pmid = {40812483}, issn = {1541-6100}, abstract = {BACKGROUND: The gut microbiota significantly influences lipid metabolism, but the impact of its developmental patterns at different growth stages on fat deposition remains unclear.

OBJECTIVES: This study aimed to explore the dynamic changes in microbial diversity and composition during the growth of pig models and assess their involvement in fat deposition.

METHODS: Forty-five Duroc-Landrace-Yorkshire (DLY) crossbred pigs were euthanized at five ages: 90, 120, 150, 180, and 210 days of age (n=9). Fecal samples were collected 1 day and 15 days before each euthanasia, and the fecal microbiota were detected by 16S rRNA sequencing. The backfat thickness, serum lipid levels, intramuscular fat, and fatty acid content in the longissimus dorsi muscle of pigs were measured to assess lipid metabolism. Fecal microbiota transplantation (FMT) from DLY pigs of different ages to antibiotics-challenged mice (n=8) was used to confirm the effects of microbial development on fat deposition. Metagenomic sequencing was conducted on feces from pigs aged 150 and 180 days and their corresponding transplanted mice to identify key strains involved in fat deposition.

RESULTS: We observed marked alterations and an increase in intestinal microbial α-diversity with age, peaking at 150 days of age in DLY pigs (P<0.05). Spearman correlation analyses indicated that 20 genera significantly correlated with the muscle fatty acid contents (P<0.05). FMT further confirmed that the developmental patterns of the gut microbiota affected host fat deposition, with notable differences observed between the fecal microbiota at day 150 and 180 of age in pigs. Schaalia canis was identified as a potential key microbial strain involved in the developmental patterns of the gut microbiota-governed fat deposition, and its colonization in mice reduced fat deposition by downregulating of LXRα/β gene expressions (P<0.05).

CONCLUSIONS: This study indicated that gut microbiota development impacted fat deposition in pigs, with Schaalia canis capable of inhibiting fat deposition.}, } @article {pmid40811474, year = {2025}, author = {Hosari, S and Ramser, M and Turina, M}, title = {Faecal incontinence in the era of sacral neuromodulation.}, journal = {Swiss medical weekly}, volume = {155}, number = {}, pages = {4298}, doi = {10.57187/s.4298}, pmid = {40811474}, issn = {1424-3997}, abstract = {Faecal incontinence is a debilitating condition that significantly affects an individual's quality of life. Accurate assessment and a thorough understanding of the underlying aetiology are crucial in determining the appropriate management approach. Conservative management strategies, including dietary modifications, pelvic floor exercises and biofeedback therapy are the first therapeutic steps. If these measures are not effective, patients should be referred to a specialised pelvic floor centre for further treatment evaluations. With the latest updates on national and international guidelines, this review aims to provide a comprehensive overview of current best practices in the management of faecal incontinence, with a particular focus on the role of sacral neuromodulation.}, } @article {pmid40810777, year = {2025}, author = {Li, S and Lian, S and Chen, Z and Luo, Y and Xia, P}, title = {The Application and Limitations of Promising Biological Therapies in Livestock Production under the Context of Antibiotic Restrictions.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {40810777}, issn = {1867-1314}, support = {No. 32072820//The Chinese National Science Foundation/ ; 2021YFD1800404//the National Key Research and Development Program of China/ ; }, abstract = {The inappropriate use of antibiotics in livestock production has raised significant public health concerns, including the emergence of bacterial resistance and the presence of drug residues. In an era characterized by "antibiotic reduction and restriction", scientific inquiry has increasingly focused on developing alternatives to antibiotics, particularly through biocontrol strategies that utilize beneficial microorganisms to counteract pathogenic ones. Common biological therapies include probiotic therapy, phage therapy, and fecal microbiota transplantation (FMT). These innovative approaches can effectively eliminate or suppress pathogenic microorganisms with fewer side effects, thereby enhancing the safety of food animals and their products. This review systematically examines these three biological interventions, elucidating their molecular mechanisms, veterinary applications, and current limitations. This paper aims to critically evaluate the translational potential and practical implementation of these novel therapies while providing evidence-based perspectives on their future optimization and advancement.}, } @article {pmid40810221, year = {2025}, author = {Raoqiong, W and Linyao, H and Ye, LU and Lingxue, W and Jianrong, LI and Yan, P and Hongmei, T and Shuangyang, LI and Xue, B}, title = {Mechanism analysis of Tongqiao Yizhi decoction in treating vascular dementia rats by brain tissue untargeted metabonomics and fecal 16S rRNA gene sequencing.}, journal = {Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan}, volume = {45}, number = {4}, pages = {759-769}, pmid = {40810221}, issn = {2589-451X}, support = {southwest Medical University [2021] No. 1//Southwest Medical University Project: Exploring the Neuroprotective Mechanism of Tongqiao Yizhi Decoction on Vascular Dementia Rats Based on the Brain Gut Axis/ ; }, abstract = {OBJECTIVE: To analyze the mechanism of Tongqiao Yizhi decoction (TQYZD,) in treating vascular dementia (VaD) rats using brain tissue untargeted metabonomics and fecal 16S rRNA gene sequencing.

METHODS: The chemical composition of TQYZD was analyzed by ultra-high performance liquid chromatography-high resolution mass spectrometry. The effects of TQYZD on VaD rats were evaluated by water maze test, hematoxylin-eosin staining, enzyme-linked immunosorbent assay and Western blot. Untargeted metabolomics and 16S rRNA sequencing were utilized to explore the relationship between metabolic profiles and the structure and function of intestinal flora. Fecal microbiota transplantation (FMT) was used to validate the role of gut microbiota in VaD. Spearman correlation analysis of differential metabolites and gut microbiota was performed.

RESULTS: The results showed that TQYZD improved cognitive function and neuronal damage in VaD rats, and reduced inflammatory response and repaired the intestinal barrier. In addition, TQYZD had the effect of modulating gut microbes in VaD rats, and FMT further confirmed that gut flora plays an important role in TQYZD treatment of VaD. Untargeted metabolomics revealed that VaD could lead to metabolic disorders in brain tissues, and TQYZD significantly altered the metabolites of brain tissues in Middle Cerebral Artery Occlusion rats. The results of spearman correlation analysis showed that there was a significant correlation between intestinal flora and the metabolites of brain tissues.

CONCLUSION: In this study, we demonstrated that TQYZD can improve metabolic disorders in vascular dementia rats by acting on intestinal flora.}, } @article {pmid40809053, year = {2025}, author = {Huo, S and Lv, K and Han, L and Zhao, Y and Jiang, J}, title = {Gut microbiota in gastric cancer: from pathogenesis to precision medicine.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1606924}, pmid = {40809053}, issn = {1664-302X}, abstract = {Gastric cancer (GC) remains a significant global health burden, driven by a complex interplay of genetic, environmental, and microbial factors. Emerging evidence highlights the critical role of gut microbiota in gastric carcinogenesis, as microbial dysbiosis disrupts gastrointestinal homeostasis, fuels chronic inflammation, and promotes immunomodulation and metabolic reprogramming. Helicobacter pylori, a key microbial player, initiates tumorigenic pathways through reactive oxygen species production and the manipulation of dietary and microbial metabolites, leading to epigenetic and genetic alterations. Targeting gut microbiota has emerged as a promising therapeutic strategy, with interventions such as probiotics, prebiotics, dietary modifications, antibiotics, and fecal microbiota transplantation (FMT) showing potential in restoring microbial balance and attenuating tumor progression. Furthermore, advances in microbiota research have identified microbial biomarkers as valuable tools for early diagnosis, prognosis, and personalized treatment of GC. This review evaluates therapeutic strategies for microbiota modulation, assesses its diagnostic and prognostic potential, and highlights current gaps in the field. It also advocates for the integration of microbiota-targeted therapies into clinical practice, emphasizing their transformative potential in the prevention and management of GC. By addressing these aspects, this review aims to provide a comprehensive understanding of the role of gut microbiota in GC and to guide future research and clinical applications.}, } @article {pmid40809043, year = {2025}, author = {Yan, J and Pan, Y and Liu, H and Yuan, J and Chen, J and Gao, Y and Lin, C and Lin, F and Wang, R and He, Y and Wang, C and Xu, C and Li, T and Zhang, P and Lan, Y and Shao, W and Pang, X and Yin, D and Sun, X and Luo, W}, title = {Bisphenol F exposure induced vascular toxicity through intestinal microbiota imbalance.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1622488}, pmid = {40809043}, issn = {1664-302X}, abstract = {INTRODUCTION: Bisphenol F (BPF), a common substitute for bisphenol A (BPA), has documented toxicity in multiple organs, but its vascular effects remain unclear. This study investigated BPF's role in vascular calcification (VC) and underlying mechanisms.

METHODS: Differences in the intestinal microbiota were analyzed by 16S ribosomal RNA gene sequencing. Metabolites were analyzed using liquid chromatography-mass spectrometry. Faecal microbiota transplantation and antibiotic treatment experiments were performed to evaluate the functions of the intestinal microbiota in VC.

RESULTS: We enrolled consecutively 57 patients. Patients were assigned to a calcification group (30 patients) and a non-calcification group (27 patients) based on the presence or absence of calcification in the thoracic aorta wall. The results showed that patients with vascular calcification (VC) had higher levels of bisphenol F (BPF), bisphenol S (BPS) and bisphenol A (BPA) in the fecal samples than patients without VC. The thoracic aortic calcification score was significantly positively correlated with the BPF (Spearman r = 0.4935, p < 0.001), BPA (Spearman r = 0.2860, p < 0.05) and BPS (Spearman r = 0.2650, p < 0.05). We then explored the effects of BPF exposure on normal and vitamin D3 + nicotine (VDN)-treated rats. BPF exposure induced mild VC in normal rats and aggravated VC in VDN-treated rats. BPF exposure disturbed the gut microbiota and promoted inflammatory responses.

CONCLUSION: The results here elucidate the mechanism underlying BPF-triggered or BPF-aggravated VC through the gut-vascular axis and provide a theoretical basis for cardiovascular disease risk assessment in humans.}, } @article {pmid40808958, year = {2025}, author = {Wang, Y and Li, X and Gao, F}, title = {Chronic obstructive pulmonary disease: in-depth analysis of microbiota association and innovative prevention and treatment approaches from the gut-lung axis perspective.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1549865}, pmid = {40808958}, issn = {1664-3224}, abstract = {The pathogenesis of chronic obstructive pulmonary disease (COPD) is complex and affects multiple systems. This article focuses on COPD and elaborates on the roles of the lung and gut microbiota as well as preventive and therapeutic strategies. Innovatively, this article reveals the impact of the connection between the lung and gut microbiota via the gut-lung axis on COPD, clarifies the association between changes in the lung microbiota and clinical features, enriches the understanding of the correlation between gut dysbiosis and COPD, breaks through the limitations of single-organ research, and opens up a completely new path for uncovering the underlying pathogenesis of COPD. In terms of prevention and treatment, gut microbiota-targeted therapies (fecal microbiota transplantation, probiotics and prebiotics) provide new ideas and evidence. Research on dietary factors (vitamins, dietary fiber) helps with precise nutritional interventions and highlights the significance of dietary adjustments. The multi-target actions of natural compounds integrate traditional and modern medicine and lay the foundation for the development of new approaches, which is of great significance and value for COPD research, clinical translation, and the improvement of patient health.}, } @article {pmid40808658, year = {2025}, author = {Emile, SH and Oslin, RL and Wignakumar, A and Horesh, N and Garoufalia, Z and Wexner, SD and Boutros, M}, title = {Association between anastomotic leak after rectal resection and bowel dysfunction, a systematic review, meta-analysis and meta-regression.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {27}, number = {8}, pages = {e70186}, pmid = {40808658}, issn = {1463-1318}, abstract = {BACKGROUND: Anastomotic leak (AL) after colorectal anastomosis can be a risk factor for bowel dysfunction, namely low anterior resection syndrome (LARS). The present study aimed to assess bowel dysfunction in patients who developed AL after anterior resection compared to patients without AL.

METHODS: We conducted a PRISMA-compliant systematic review of PubMed, Scopus and Cochrane Library for randomized and observational studies investigating the association between AL after anterior resection and bowel dysfunction. The main outcomes were LARS, faecal incontinence and urgency. Pairwise meta-analyses were conducted to calculate the relative risk (RR) of the study outcomes and their 95% confidence intervals (CI).

RESULTS: This review included 20 retrospective studies comprising 4764 patients (61.6% male, median age 63 years). AL was detected in 14% of patients and those who experienced AL had a higher risk of LARS (six studies; 1329 patients, RR: 1.27 95%CI: 1.02, 1.58, p = 0.035), major LARS (seven studies; 1395 patients, RR: 1.38, 95%CI: 1.07, 1.79, p = 0.012), urgency (five studies; 955 patients, RR: 1.15, 95%CI: 1.04, 1.27, p = 0.005) and had higher LARS scores (seven studies; 1450 patients, WMD: 6.64, 95%CI: 3.76, 9.52, p < 0.001) and Wexner incontinence scores (seven studies; 1045 patients, WMD: 1.72, 95%CI: 0.16, 3.28, p = 0.031).

CONCLUSION: Based on low to moderate certainty evidence, AL after colorectal and coloanal anastomoses was significantly associated with an increased risk of LARS, particularly major LARS, urgency and higher LARS and Wexner/Cleveland Clinic Florida-Fecal Incontinence Scores.}, } @article {pmid40806882, year = {2025}, author = {Lahoud, C and Habib, T and Kalta, D and Dimachkie, R and El Sayegh, S and Deeb, L}, title = {Intestinal Microbiota and Fecal Transplantation in Patients with Inflammatory Bowel Disease and Clostridioides difficile: An Updated Literature Review.}, journal = {Journal of clinical medicine}, volume = {14}, number = {15}, pages = {}, pmid = {40806882}, issn = {2077-0383}, abstract = {Background/Objectives: Inflammatory bowel disease (IBD) is characterized by chronic relapsing and remitting inflammation of the gastrointestinal tract. Fecal microbiota transplantation (FMT) has emerged as an FDA-approved treatment for recurrent Clostridioides difficile infections (CDIs), with promising potential in patients with IBD. This manuscript aimed to provide a comprehensive and updated review of the available literature on fecal microbiota transplantation, its clinical use in IBD in general, as well as in patients with IBD and CDI. Methods: An extensive literature search was performed from October 2024 to March 2025. All publications available within PubMed, Medline, Embase, Google Scholar, and Cochrane databases were reviewed. All original articles, case reports, review articles, systematic reviews, and meta-analyses were included. Qualitative and quantitative data were both extracted. Discussion: Intestinal microbiota is an integral part of the human body, and dysbiosis (an imbalance in the gut's microbial community) has been linked with several pathologies. Dysbiosis in IBD is marked by reduced beneficial bacteria and increased pro-inflammatory pathogens, contributing to mucosal damage and immune dysregulation. FMT has emerged as a solution to dysbiosis, with the first case recorded in 1917. FMT has been successful in treating patients with CDI. The diagnostic value of the gut microbiome is currently being explored as a possible therapeutic approach to IBD. Several studies have assessed FMT in patients with IBD and CDI with promising results in both ulcerative colitis (UC) and Crohn's disease (CD) but varying efficacy based on administration routes, donor selection, and processing methods. In the context of recurrent CDI in patients with IBD, FMT demonstrates a high cure rate and potential benefit in concurrently improving IBD activity. However, risks such as IBD flare-ups post-FMT remain a concern. Conclusions: FMT holds promising potential in the management of CDI in patients with IBD. By restoring microbial diversity and correcting dysbiosis, FMT offers a novel, microbiota-targeted alternative to conventional therapies. While data support its efficacy in improving disease remission, variability in outcomes underscores the need for standardized protocols and additional large-scale, controlled studies. Continued research efforts into donor selection, treatment regimens, and long-term safety will be critical to optimizing FMT's role in IBD and CDI care as well as improving patient outcomes.}, } @article {pmid40806022, year = {2025}, author = {Yang, H and Er, D and Wang, YH and Zhai, BT and Ge, R}, title = {Camel Milk-Derived Extracellular Vesicles as a Functional Food Component Ameliorate Hypobaric Hypoxia-Induced Colonic Injury Through Microbiota-Metabolite Crosstalk.}, journal = {Nutrients}, volume = {17}, number = {15}, pages = {}, pmid = {40806022}, issn = {2072-6643}, support = {2024-QYY-1//2024 Qinghai University Youth Research Fund Project (Natural Sciences)/ ; Grant No. 2025-ZJ-911Q//2025 Youth Project of Qinghai Provincial Basic Research Program/ ; Grant No. 2025-ZJ-748//2025 Basic Research Program/ ; }, abstract = {Background/Objectives: This study investigates the therapeutic potential of camel milk-derived extracellular vesicles (CM-EVs) for treating colonic damage caused by high-altitude hypoxia, supporting the WHO's "Food as Medicine" initiative. Methods: Using a 5500 m mouse model, researchers induced colonic injury and treated it with oral CM-EVs for 15 days, comparing results to whole camel milk. Results: CM-EVs outperformed whole milk, significantly improving colon health by restoring barrier integrity and reducing disease activity index (DAI) (p < 0.01). They boosted beneficial bacteria like Lactobacillus and Bifidobacterium and decreased Enterobacteriaceae (p < 0.01). Metabolic analysis showed restored bile acid balance and amino acid modulation via the FXR/NF-κB pathway, reducing TLR4/MyD88-mediated inflammation and oxidative stress (p < 0.01). Fecal microbiota transplantation in the CM-EVs group notably decreased DAI and increased colon length (p < 0.05). Conclusions: CM-EVs repair mucosal damage, balance microbiota, and regulate metabolism to combat hypoxia-induced colonic damage, suggesting their potential as nutraceuticals and altitude-adaptive foods. This showcases nanotechnology's role in enhancing traditional dietary benefits via precision nutrition.}, } @article {pmid40803572, year = {2025}, author = {Mahajan, S and Navya, M and Banerjee, SK}, title = {Future potential therapeutics to treat MASH.}, journal = {Drug discovery today}, volume = {}, number = {}, pages = {104451}, doi = {10.1016/j.drudis.2025.104451}, pmid = {40803572}, issn = {1878-5832}, abstract = {Metabolic dysfunction-associated steatohepatitis (MASH), a progressive form of Metabolic-associated steatotic liver disease (MASLD), poses a significant global health challenge due to its association with obesity, type 2 diabetes, and cardiovascular complications. Despite its rising prevalence, effective therapies remain limited. This review highlights emerging therapeutic strategies that target key pathways involved in MASH pathogenesis, including THR-β, FXR, PPAR, GLP-1RA, FGF21, and SGLT2. In addition, novel approaches such as gene therapy (siRNA), probiotics, fecal microbiota transplantation, and stem cell therapy show promise for the treatment of MASH. Ongoing clinical trials and mechanistic insights into fibrosis, inflammation, and lipid metabolism provide hope for tailored, multi-targeted treatments. Future efforts must address safety, long-term efficacy, and non-invasive diagnostics to advance the management of MASH.}, } @article {pmid40803054, year = {2025}, author = {Moutsoglou, D and Blake, M and Belhasan, DC and Peichel, G and Vang, BM and Weir, EK and Lopez, S and Prins, KW and Kabage, AJ and Prisco, SZ and Kremer, BP and Khoruts, A and Thenappan, T}, title = {Microbiota Transplant Therapy Is Safe and Feasible in Pulmonary Arterial Hypertension.}, journal = {JACC. Basic to translational science}, volume = {10}, number = {9}, pages = {101347}, doi = {10.1016/j.jacbts.2025.101347}, pmid = {40803054}, issn = {2452-302X}, support = {R01 HL158795/HL/NHLBI NIH HHS/United States ; R01 HL162927/HL/NHLBI NIH HHS/United States ; }, abstract = {Pulmonary arterial hypertension (PAH) is a complex inflammatory disease that the gut microbiome likely contributes to and may be a potential therapeutic avenue for nontoxically improving outcomes. Here, we show that microbiota transplant therapy (MTT) is safe and feasible. The MTT regimen achieves only modest levels of donor microbiota engraftment but is accompanied by a transient reduction in circulating pro-inflammatory cytokines. These findings of decreased systemic inflammation with only modest donor engraftment support the potential of MTT as a novel treatment for PAH. (Microbiota Transplant Therapy for Pulmonary Arterial Hypertension: Early Safety and Feasibility Study; NCT04884971).}, } @article {pmid40801260, year = {2025}, author = {Yan, B and Zheng, X and Lu, D and Li, T and Chen, X and Shao, Z and Fu, T}, title = {Silibinin-drived microbiota enrich (R)-2,3-dihydroxy-isovalerate and ameliorate colitis via the GAT-3/RARβ/RORγt axis.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ismejo/wraf175}, pmid = {40801260}, issn = {1751-7370}, abstract = {Microbiota-associated factors are increasingly recognized as significant contributors to the progression of ulcerative colitis, and microbial modulation has emerged as an effective therapy for this condition. The herbal compound silibinin has demonstrated properties that modulate gut microbiota. Herein, we investigated the response of gut microbiota to silibinin in ameliorating colitis, using a mouse model of colitis coupled with antibiotic exposure. Results indicated that antibiotic pretreatment negated the benefits of silibinin in mice with colitis. Furthermore, fecal microbiota transplantation involving silibinin-modulated gut microbiota further substantiated the gut microbiota-dependent effects of silibinin. Within the metabolic profiles of silibinin-regulated microbiota, we identified that Alistipes-associated (R)-2,3-dihydroxy-isovalerate exhibited the most pronounced anti-inflammatory effects in vitro and demonstrated protective effects against colitis. Moreover, (R)-2,3-dihydroxy-isovalerate reinstated the protective effects of silibinin in mice with colitis under antibiotic exposure. These effects were primarily mediated via the targeting of the colonic GABA transporter 3 by (R)-2,3-dihydroxy-isovalerate. We further revealed that the retinoic acid receptor β and the retinoid-related orphan nuclear receptor γt may mediate the impact of silibinin-derived microbiota and (R)-2,3-dihydroxy-isovalerate on colitis. Additionally, the knockdown of colonic GABA transporter 3 diminished the impact of silibinin on the GABA transporter 3/retinoic acid receptor β/retinoid-related orphan nuclear receptor γt axis and colitis. Our findings highlight that (R)-2,3-dihydroxy-isovalerate, enriched from microbiota derived from silibinin, can target the GABA transporter 3/retinoic acid receptor β/retinoid-related orphan nuclear receptor γt axis, which is essential for anti-colitis properties of silibinin-regulated microbiota.}, } @article {pmid40799652, year = {2025}, author = {Liu, M and Geng, J and Liu, T and Liu, X}, title = {Gut microbiome dysregulation in noninfectious uveitis.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1614304}, pmid = {40799652}, issn = {1664-3224}, abstract = {Noninfectious uveitis (NIU) is a vision-threatening autoimmune disease of the eye, but its pathogenesis is still not fully understood. Recently, accumulating evidence suggests that gut microbiome dysbiosis may affect the development and progression of NIU through potential mechanisms, including translocation, molecular mimicry, and bystander activation. Understanding the mechanisms of gut microbiome-host interactions, especially the gut-eye axis regulation, can offer a theoretical foundation for developing novel therapeutic strategies. We summarized current evidence on the dysregulation of gut microbiome and metabolites in NIU, and explored potential mechanisms involved. Furthermore, possible therapeutic measures are discussed, including probiotics, prebiotics, dietary modifications, antibiotic interventions, as well as fecal microbial transplantation, aiming to exert beneficial effects on NIU progression by reshaping the gut microbial composition.}, } @article {pmid40797316, year = {2025}, author = {Tang, A and Jiang, H and Li, J and Chen, Y and Zhang, J and Wang, D and Hu, S and Lai, J}, title = {Gut microbiota links to cognitive impairment in bipolar disorder via modulating synaptic plasticity.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {470}, pmid = {40797316}, issn = {1741-7015}, support = {82201676//National Natural Science Foundation of China/ ; 82471542//National Natural Science Foundation of China/ ; No. JNL-2023001B//Research Project of Jinan Microecological Biomedicine Shandong Laboratory/ ; 2023YFC2506200//National Key Research and Development Program of China/ ; 2021C03107//Zhejiang Provincial Key Research and Development Program/ ; 2023ZFJH01-01//Fundamental Research Funds for the Central Universities/ ; 2024ZFJH01-01//Fundamental Research Funds for the Central Universities/ ; No. 2021R52016//Leading Talent of Scientific and Technological Innovation - "Ten Thousand Talents Program" of Zhejiang Province/ ; 2022KTZ004//Chinese Medical Education Association/ ; }, abstract = {BACKGROUND: Cognitive impairment is an intractable clinical manifestation of bipolar disorder (BD), but its underlying mechanisms remain largely unexplored. Preliminary evidence suggests that gut microbiota can potentially influence cognitive function by modulating synaptic plasticity. Herein, we characterized the gut microbial structure in BD patients with and without cognitive impairment and explored its influence on neuroplasticity in mice.

METHODS: The gut structure of microbiota in BD without cognitive impairment (BD-nCI) patients, BD with cognitive impairment (BD-CI) patients, and healthy controls (HCs) were characterized, and the correlation between specific bacterial genera and clinical parameters was determined. ABX-treated C57 BL/J male mice were transplanted with fecal microbiota from BD-nCI, BD-CI patients or HCs and subjected to behavioral testing. The change of gut microbiota in recipient mice and its influence on the dendritic complexity and synaptic plasticity of prefrontal neurons were examined. Finally, microbiota supplementation from healthy individuals in the BD-CI mice was performed to further determine the role of gut microbiota.

RESULTS: 16S-ribosomal RNA gene sequencing reveals that gut microbial diversity and composition are significantly different among BD-nCI patients, BD-CI patients, and HCs. The Spearman correlation analysis suggested that glucose metabolism-related bacteria, such as Prevotella, Faecalibacterium, and Roseburia, were correlated with cognitive impairment test scores, and inflammation-related bacteria, such as Lachnoclostridium and Bacteroides, were correlated with depressive severity. Fecal microbiota transplantation resulted in depression-like behavior, impaired working memory and object recognition memory in BD-CI recipient mice. Compared with BD-nCI mice, BD-CI mice exhibited more severely impaired object recognition memory, along with greater reductions in dendritic complexity and synaptic plasticity. Supplementation of gut microbiota from healthy individuals partially reversed emotional and cognitive phenotypes and neuronal plasticity in BD-CI mice.

CONCLUSIONS: This study first characterized the gut microbiota in BD-CI patients and highlighted the potential role of gut microbiota in BD-related cognitive deficits by modulating neuronal plasticity in mice model.}, } @article {pmid40796882, year = {2025}, author = {He, Y and Li, Q and Sun, Q and Li, H and Yu, T and Chen, M and Zhang, G and Zhang, B and Wang, W and Ju, S}, title = {Gut microbiota contributes to polystyrene nanoplastics-induced fetal growth restriction by disturbing placental nicotinamide metabolism.}, journal = {Journal of nanobiotechnology}, volume = {23}, number = {1}, pages = {561}, pmid = {40796882}, issn = {1477-3155}, support = {PAPD//Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; KYCX24_0999//Graduate Research and Innovation Projects of Jiangsu Province/ ; }, abstract = {Polystyrene nanoplastics (PS-NPs) are ubiquitous in the environment, eliciting significant concerns about their possible risks to human health, especially reproductive health. Various reproductive toxicities of PS-NPs have been reported, however, information regarding the effects of PS-NPs exposure during pregnancy on offspring development and the underlying mechanisms remains limited. In this study, pregnant mice were orally administered PS-NPs (approximately 100 nm in diameter) at different concentrations (1, 10, and 100 mg/kg/day) for 17.5 consecutive days, from gestational day (GD) 0.5 to GD 17.5. The relevant samples were collected on GD 18.5 to investigate the intergenerational effects. The results indicated that PS-NPs induced placental injury and metabolic abnormalities, leading to adverse pregnancy outcomes. Specifically, PS-NPs exposure observably reduced the levels of nicotinamide (NAM) and nicotinamide adenine dinucleotide (NAD[+]) in the placenta, resulting in decreased ATP production, increased oxidative stress and ferroptosis. Meanwhile, PS-NPs disrupted the maternal gut microbiome, specifically manifested as a reduction in Lactobacillus levels and abundances of norank_f_Muribaculaceae, Turicibacter, Alloprevotella, Parabacteroides and Ruminococcus. Fecal microbial transplant (FMT) experiments demonstrated that the microbiota from PS-NPs-administered pregnant mice could similarly induce intestinal barrier damages and placental injury. Treatment with NAM effectively mitigated disruptions in placental metabolism and reversed the adverse pregnancy outcomes caused by PS-NPs. These findings highlight the novel role of the gut microbiota in PS-NPs-induced placental injury and adverse pregnancy outcomes, and suggest that NAM could serve as a promising preventative strategy against this intergenerational damage caused by PS-NPs.}, } @article {pmid40796472, year = {2025}, author = {Lucky, CW and Kelly, BJ and Kwon, JH and Woodworth, MH and Medernach, RL}, title = {Microbiome Therapeutics for Clostridioides difficile Infection.}, journal = {Infectious disease clinics of North America}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.idc.2025.07.007}, pmid = {40796472}, issn = {1557-9824}, abstract = {Microbiota-based therapies are used increasingly for the treatment and prevention of Clostridioides difficile infection (CDI), particularly in cases of recurrent CDI (rCDI). This review discusses the different types of microbiota-based therapies, including fecal microbiota transplant, fecal microbiota products, and live biotherapeutic products. The authors present efficacy data regarding clinical use in rCDI and highlight the unique aspects of each product.}, } @article {pmid40796471, year = {2025}, author = {Sehgal, K and Feuerstadt, P and Wilcox, MH}, title = {Making Sense of Differing Guidelines for Clostridioides difficile Infection.}, journal = {Infectious disease clinics of North America}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.idc.2025.07.010}, pmid = {40796471}, issn = {1557-9824}, abstract = {The Clostridioides difficile infection (CDI) epidemic has been impacting the world for years. Understanding accurate diagnostics is imperative to allow the appropriate patients to be treated and improve outcomes. This article leverages multiple global societal guidelines to focus on the evolving diagnostic tests available summarizing best diagnostic practices including 2-step diagnostic testing. Therapeutically, guideline recommendations more recently have favored fidaxomicin and incorporated immune-based therapies and microbial restoration therapies. As treatment options and guideline recommendations change, it is imperative to understand why these recommendations have evolved and understand current best diagnostic and therapeutic practices in managing CDI.}, } @article {pmid40796226, year = {2025}, author = {Skawratananond, S and McCrea, G and Lie, P and Buxton, MB and Daly, SP and Vojtkofsky, NA and Smith, SC and Zhang, C and Hernandez, M and Hindle, A and Logsdon, AF and Lawrence, JJ}, title = {The Synergistic Interplay between Vitamin A, Dietary Fiber, and the Microbiota-Gut-Brain Axis: A Potential Mechanism for Preventing Alzheimer's Disease.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpgi.00097.2025}, pmid = {40796226}, issn = {1522-1547}, support = {AG071859//HHS | NIH | National Institute on Aging (NIA)/ ; MSSRP//Texas Tech University Health Sciences Center (TTUHSC)/ ; MSSRP//Texas Tech University Health Sciences Center (TTUHSC)/ ; AG073826//HHS | NIH | National Institute on Aging (NIA)/ ; }, abstract = {The human gastrointestinal tract harbors a vast and diverse microbial community, with the gut microbiome playing a fundamental role in numerous biological processes that influence overall health and disease progression. Emerging evidence has identified bacterial lipopolysaccharides in the hippocampus of Alzheimer's disease (AD) patients, highlighting the intricate relationship between the gastrointestinal tract, gut microbiome, and the central and enteric nervous systems-commonly referred to as the "microbiota-gut-brain axis." In this review, we explore the mechanisms by which the microbiota-gut-brain axis contributes to AD pathogenesis. We propose that sufficient levels of all-trans retinoic acid (ATRA), the bioactive form of vitamin A, enhance intestinal barrier integrity by upregulating tight junction proteins and modulating immune function through the induction of regulatory T-cell differentiation, thereby mitigating inflammation. Furthermore, dietary fiber complements this process by promoting the production of short-chain fatty acids, such as butyrate, via bacterial fermentation. Butyrate, in turn, acts as a histone deacetylase inhibitor, upregulating ATRA bioavailability by elevating aldehyde dehydrogenase gene expression. Our mechanistic framework is supported by the endotoxin hypothesis of AD, which purports that the movement of infectious pathogens across the blood-brain barrier causes a vicious cycle of neuroinflammation, a key factor of AD pathogenesis, leading to amyloid-beta deposition, microglial activation, and CYP26A1-mediated ATRA degradation. Finally, we discuss microbiome-based therapeutic strategies and dietary interventions, including prebiotic compounds, probiotic bacteria, fecal microbiota transplantation, the MIND diet, and a combined approach consisting of vitamins A/D, and dietary fiber, as potential approaches to mitigate AD progression via the microbiota-gut-brain axis.}, } @article {pmid40796104, year = {2025}, author = {Fan, Z and Huang, L and Zheng, M and Lin, Z and Li, Z and Liu, Y and Liu, B and Xiao, L and Chen, Y and Mai, X and Xu, Y and Xie, L}, title = {Fecal Microbiota Transplantation Reveals the Impact of Gut Microbiota Dysbiosis on Osteoporosis Development in Ovariectomized Mice.}, journal = {FEMS microbiology letters}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsle/fnaf081}, pmid = {40796104}, issn = {1574-6968}, abstract = {Osteoporosis is characterized by low bone mineral density and deteriorated bone microarchitecture. The gut microbiota has emerged as a potential regulator of bone metabolism through the gut-bone axis. This study investigates the role of gut microbiota dysbiosis in osteoporosis. Fecal microbiota transplantation (FMT) was employed to assess the transferability of osteoporosis-associated gut microbiota dysbiosis to healthy mice and to explore whether restoration of gut microbial composition could reverse bone loss in OVX mice. It was demonstrated that gut microbiota from OVX mice induced osteoporosis in healthy recipient mice, establishing a causal link between gut microbiota dysbiosis and bone health. Short-term FMT from healthy donors restored microbial diversity; however, a significant improvement in trabecular bone density was not observed in OVX mice. This suggest that longer colonization periods or additional interventions may be required. Correlation analysis revealed significant associations between specific bacterial taxa and bone health parameters. These findings highlight the complexity of the gut-bone axis and underscore the need for further research investigating targeted microbial interventions for the management of osteoporosis. Future therapeutic strategies should be considered for modulation of the gut microbiota, enhancement of gut barrier integrity, and mitigation of systemic inflammation as novel approaches to osteoporosis treatment.}, } @article {pmid40794475, year = {2025}, author = {Lin, J and Qi, Z and Wang, G and Wu, C and Mumby, W and Huang, Y and Peng, Y and Sun, Q}, title = {Permethrin Stimulates Fat Accumulation via Regulating Gut Microbiota and Its Metabolites in Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c05013}, pmid = {40794475}, issn = {1520-5118}, abstract = {Permethrin, a commonly used type I pyrethroid insecticide, has been shown to induce insulin resistance and adipogenesis, however the molecular mechanisms driving these effects remain unclear. This research demonstrated that permethrin disrupts the balance of gut microbiota, particularly altering Firmicutes and Bacteroidetes ratios, leading to increased adipogenesis and metabolic disorders. Antibiotic treatment significantly alleviated the effects of permethrin, highlighting the potential role of gut microbiota in obesity and insulin resistance. Fecal microbiota transplantation further confirmed the causal role of microbiota in fat accumulation. Additionally, microbial metabolites such as butyrate and indole were found to mitigate the fat accumulation induced by permethrin. Overall, our findings reveal that permethrin promotes obesity through the regulation of gut microbiota and their metabolites, providing important new insights into the health risks associated with permethrin exposure.}, } @article {pmid40791287, year = {2025}, author = {Jha, M and Waheed, A and Hooti, JA and Nair, S and Najam, A and Mal, M and Tummala, N and Shariq, AS and Hurairah, A and Daniel, M}, title = {Advancements in Immunomodulatory Therapies for IBD and Their Interplay With the Gut-Brain Axis: An Updated Review of Current Literature and Beyond.}, journal = {Health science reports}, volume = {8}, number = {8}, pages = {e71157}, pmid = {40791287}, issn = {2398-8835}, abstract = {BACKGROUND AND AIMS: The incidence of inflammatory bowel disease (IBD), characterized by chronic gastrointestinal inflammation, has significantly increased over the last two decades. Concurrently, advancements in treatment strategies have accelerated, aiming not only to induce but also to maintain remission. Emerging evidence highlights the intricate bidirectional relationship between the gut and brain, forming the gut-brain axis, which is now a major therapeutic target.

METHODS AND RESULTS: This narrative review synthesizes findings from a wide range of research studies to summarize IBD incidence trends, underlying pathophysiological mechanisms, and recent therapeutic advancements. A major focus is placed on dysregulated immunomodulation and its role in disease progression. The review examines conventional treatments such as aminosalicylates and corticosteroids, surgical interventions, and newer therapies targeting the gut-brain microbiota axis, including biological agents, stem cell therapy, probiotics, and fecal microbiota transplantation (FMT).

CONCLUSION: Recent advancements in immunomodulatory therapies have significantly improved patient outcomes. Biological agents such as infliximab and vedolizumab have demonstrated remission rates of 40%-69% in IBD patients, with infliximab reducing colectomy. Rates to 10% at 54 weeks. Meanwhile, fecal microbiota transplantation (FMT) has emerged as a promising therapy for ulcerative colitis, with trials reporting 87.1% clinical remission at 48 weeks compared to 66.7% in the placebo group, along with higher endoscopic and histological remission rates. A trial on multidonor-intensive FMT found a 27% clinical remission rate at week 8, significantly higher than 8% in the placebo group, reinforcing its potential as an adjunct therapy in IBD. By examining their interplay with the gut-brain axis, this review provides insights into the mechanisms and clinical relevance of these therapies, paving the way for more targeted and effective IBD management strategies.}, } @article {pmid40791147, year = {2025}, author = {Ji, X and Wang, J and Lan, T and Zhao, D and Xu, P}, title = {Gut microbial metabolites and the brain-gut axis in Alzheimer's disease: A review.}, journal = {Biomolecules & biomedicine}, volume = {}, number = {}, pages = {}, doi = {10.17305/bb.2025.12921}, pmid = {40791147}, issn = {2831-090X}, abstract = {Alzheimer's disease (AD) is increasingly recognised as a disorder that extends beyond the brain, with accumulating evidence implicating gut microbiota-derived metabolites in its onset and progression. This narrative review synthesises 92 peer-reviewed animal, human and meta-analytic studies published between 2010 and 2025 that investigated short-chain fatty acids (SCFAs), tryptophan-derived indoles and kynurenines, trimethylamine N-oxide (TMAO) and secondary bile acids in the context of AD. Collectively, the literature shows that SCFAs support blood-brain-barrier integrity, dampen microglial reactivity and enhance synaptic plasticity, yet can paradoxically amplify β-amyloid (Aβ) deposition under germ-free or supraphysiological conditions, highlighting the importance of host status and dosing. Beneficial indole metabolites such as indole-3-propionic acid counter oxidative stress, strengthen intestinal and cerebral barriers and suppress pro-inflammatory cascades, whereas a shift toward neurotoxic kynurenines correlates with cognitive decline. TMAO emerges as a consistently deleterious metabolite that aggravates endothelial dysfunction, neuroinflammation and Aβ aggregation; dietary precursor restriction and microbial enzyme inhibitors are therefore being explored as mitigation strategies. Secondary bile acids and polyphenol derivatives further modulate mitochondrial bioenergetics and NF-κB signalling, broadening the therapeutic landscape. Multi-omics profiling reveals that AD patients typically exhibit reduced SCFAs and indoles but elevated TMAO, changes that scale with Mini-Mental State Examination scores, brain atrophy and cerebrospinal Aβ42 levels. Early probiotic and faecal-microbiota-transplant trials have begun to normalise these metabolite profiles and yield modest cognitive benefits, underscoring translational potential. Altogether, gut-derived metabolites are not passive by-products but active modulators of neural, immune and metabolic circuits along the microbiota-gut-brain axis; their targeted manipulation and standardised metabolomic assessment could enable earlier diagnosis and precision microbiome-based interventions for AD, a promise that now warrants validation in large, longitudinal and mechanistically informed clinical studies.}, } @article {pmid40789505, year = {2025}, author = {Zhou, Y and Yang, T and Zheng, S and Gan, T and Yu, F and Liu, G and Zhou, T}, title = {Genetical TRPV4 deletion-associated gut microbiota alleviates cardiac dysfunction in mice with diabetic cardiomyopathy.}, journal = {Journal of molecular and cellular cardiology}, volume = {207}, number = {}, pages = {37-50}, doi = {10.1016/j.yjmcc.2025.08.001}, pmid = {40789505}, issn = {1095-8584}, abstract = {Diabetic cardiomyopathy (DCM) is a serious complication associated with diabetes that characterized by the cardiac dysfunction and myocardial fibrosis. Recent studies emphasize the significance of the gut-heart axis in the development of DCM. This current study investigates the effect of systematic-genetical TRPV4 knockout on DCM progression and explores the underlying mechanisms involving gut microbiota modulation and intestinal barrier integrity. The removal of TRPV4 in mice with DCM markedly enhances cardiac performance, decreases myocardial fibrosis, and modifies the composition of gut microbiota, resulting in a significant rise in Bacteroides acidifaciens (BA). TRPV4 deletion also upregulates tight junction proteins (Zonula occludens-1 (ZO-1), Occludin, and Claudin-1) and reduces serum lipopolysaccharide levels. Furthermore, fecal microbiota transplantation from the DCM donors with TRPV4 knockout to the DCM receptors replicates these cardioprotective effects in mice, and administration of BA improves cardiac function and relieves the fibrosis. Our study suggests that the cardioprotective effects of the genetic deletion of TRPV4 are related to changes in the gut microbiome, highlighting the importance of the connection between TRPV4, the gut, and the heart in the disease mechanism and potential therapeutic strategies for DCM.}, } @article {pmid40789485, year = {2025}, author = {Mullish, BH and Javed, A and Ghani, R and Davies, F and Ghazy, A and Ranganathan, N and Alexander, JL and Roberts, LA and Chrysostomou, D and Thursz, MR and Marchesi, JR and Gilchrist, M and Williams, HRT}, title = {Operational considerations for the running of an NHS faecal microbiota transplant (FMT) service.}, journal = {The Journal of hospital infection}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhin.2025.07.022}, pmid = {40789485}, issn = {1532-2939}, } @article {pmid40789381, year = {2025}, author = {Fan, XQ and Fan, SM and Dong, BY and Zhang, CM and Zuo, J and Zhang, DW and Xiong, X and Luo, D and Fan, XM}, title = {Recent advances in the interaction between acute respiratory distress syndrome and gut microbiota: A narrative review.}, journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases}, volume = {134}, number = {}, pages = {105810}, doi = {10.1016/j.meegid.2025.105810}, pmid = {40789381}, issn = {1567-7257}, abstract = {Acute respiratory distress syndrome (ARDS) is a sudden, widespread inflammatory damage to the lungs resulting from multiple etiologies. ARDS is characterized by high sickness rates, mortality, and costly treatments and is a significant global health issue that lacks an effective treatment strategy. The microbiota of the gut is an intricate ecology indispensable for the host's health, immunology, and metabolism. Human immunity and intestinal barrier function depend on gut microbes. Several disorders are linked to gut microbiota dysbiosis. Scientists have been concentrating on the role that gut microbes play in the onset of ARDS. This study examines the relationship between ARDS and intestinal microbiota, specifically addressing two facets: how ARDS affects the composition of the gut microbiota and the integrity of the intestinal barrier, alongside the effects of mechanisms such as bacterial translocation and inflammatory activation resulting from gut microbiota dysregulation on ARDS. Additionally, various therapeutic strategies involving gut microbiota and its metabolites, such as selective digestive decontamination (SDD), fecal microbiota transplantation (FMT), microbiological preparations, and metabolites produced from the microbiota, are explored. It is anticipated that this exploration will make a substantial contribution to the prevention and therapy of ARDS.}, } @article {pmid40784117, year = {2025}, author = {Zhang, J and Hu, H and Zhu, Y and Xin, X and Jin, Y and Zhao, Q and Zhang, H and Heng, D and Ma, Z and Chai, X and Lin, R and Zhao, Y and Ye, Y and Li, D}, title = {Polystyrene/polylactic acid microplastics impair transzonal projections and oocyte maturation via gut microbiota-mediated lipoprotein lipase inhibition.}, journal = {Journal of hazardous materials}, volume = {496}, number = {}, pages = {139475}, doi = {10.1016/j.jhazmat.2025.139475}, pmid = {40784117}, issn = {1873-3336}, abstract = {This study focuses on the impacts of polystyrene/polylactic acid microplastics (PS/PLA-MPs) on ovarian reserve and oocyte maturation in female mice, along with the underlying mechanisms. 1 μm PS-MPs and PLA-MPs were prepared, with PLA-MPs having a rougher surface and broader size distribution. In vitro, PLA-MPs showed higher cytotoxicity to granulosa cells compared to PS-MPs. In vivo, MPs exposure disrupted the estrous cycle, and damaged ovarian reserve. Granulosa cell apoptosis and cytokine activation led to transzonal projection retraction, oocyte oxidative stress, meiotic abnormalities, and reduced oocyte retrieval and polar body extrusion rate, thus reducing litter size. PS-MPs induced more severe intestinal and ovarian impairment. Analysis of feces 16S rRNA, serum metabolomics, and ovarian RNA sequencing revealed that lipoprotein lipase (LPL) was suppressed by both MPs, linking gut microbiota, lipid metabolism, and ovarian injury. Fecal microbiota transplantation as a rescue strategy in MPs exposed mice upregulated LPL, alleviating ovarian reserve decline. In PLA-MPs exposed mice, ovarian reserve related indicators partially recovered after a two-week exposure cessation. These results clarify the similarities and differences in how PS-MPs and PLA-MPs impair ovarian function via gut-ovary axis and lipid metabolism dysregulation.}, } @article {pmid40783567, year = {2025}, author = {Yang, J and Zhou, Y and Du, A and Zhang, Z and Wang, B and Tian, Y and Liu, H and Cai, L and Pang, F and Li, Y and Du, C and Wu, X and Yan, C and Wu, W and Jiang, M and Shen, K and Zhang, C and Feng, Y and Kang, Y and Shen, B and Zong, Z}, title = {Microbiome-mediated colonization resistance to carbapenem-resistant Klebsiella pneumoniae in ICU patients.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {157}, pmid = {40783567}, issn = {2055-5008}, support = {2019HXBH088//post-doctoral fund by West China Hospital of Sichuan University/ ; 2023YFC2308800//National Key Research and Development Program of China/ ; ZYYC08006 and no. ZYGD22001//1.3.5 project for disciplines of excellence grants by the West China Hospital of Sichuan University/ ; }, mesh = {Humans ; *Klebsiella Infections/microbiology/therapy ; *Klebsiella pneumoniae/drug effects/growth & development ; Intensive Care Units ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Mice ; *Carbapenems/pharmacology ; Animals ; Male ; *Carbapenem-Resistant Enterobacteriaceae/drug effects ; Anti-Bacterial Agents/pharmacology ; Female ; Middle Aged ; Feces/microbiology ; Probiotics/administration & dosage ; Aged ; }, abstract = {Carbapenem-resistant Klebsiella pneumoniae (CRKP) causes serious intensive care unit (ICU)-acquired infections, yet the mechanisms of microbiota-mediated colonization resistance remain unclear. We analyzed the gut microbiome and metabolic profiles of healthy individuals and ICU patients, distinguishing those with and without CRKP colonization. ICU patients showed distinct microbial communities compared to healthy controls, and CRKP-positive patients exhibited unique microbial and metabolic signatures. We demonstrated that a healthy gut microbiome is essential for providing resistance against CRKP colonization in antibiotic-perturbed mouse with fecal microbiota transplantation (FMT). Both in vitro and in vivo experiments revealed that Lactiplantibacillus plantarum and Bifidobacterium longum as significant contributors to the decolonization of CRKP. Furthermore, we showed that probiotic supplementation or FMT significantly improved CRKP colonization resistance. The findings highlight that a specific gut microbiome is essential for resisting CRKP colonization, and that targeted microbiome restoration may serve as a viable strategy to prevent CRKP colonization in ICU patients.}, } @article {pmid40783052, year = {2025}, author = {Formelli, MG and Palloni, A and Tavolari, S and Deiana, C and Andrini, E and Di Marco, M and Campana, D and Lamberti, G and Brandi, G}, title = {Classic versus innovative strategies for immuno-therapy in pancreatic cancer.}, journal = {Advanced drug delivery reviews}, volume = {225}, number = {}, pages = {115671}, doi = {10.1016/j.addr.2025.115671}, pmid = {40783052}, issn = {1872-8294}, abstract = {Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a dismal prognosis. Immunotherapy with immune checkpoint inhibitors (ICIs), either as monotherapy, in combination with other ICIs, or alongside chemotherapy, has significantly improved outcomes in several solid tumors. However, its efficacy in PDAC remains limited due to multiple resistance mechanisms. Key determinants of immunotherapy resistance in PDAC include physical barriers that hinder immune cells infiltration, such as aberrant vasculature, cancer-associated fibroblasts (CAFs), and excessive hyaluronic acid deposition in the tumor microenvironment (TME). Additionally, PDAC is characterized by an immunosuppressive TME enriched with regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), and by low immunogenicity of tumor cells due to KRAS mutations, MYC overexpression, and a low tumor mutational burden, further impairing antitumor immunity. This review discusses advanced drug delivery systems to overcome determinants of immunotherapy resistance and to improve outcomes, explores emerging immunotherapy strategies, including adoptive cell therapies, cancer vaccines, and the potential role of microbiota as modulator of TME through fecal microbiota transplantation or intratumoral bacterial inoculation. Given the ambivalent role of microbiota in PDAC, the need for a clear definition of favorable strains and their selection is highlighted. Emerging approaches involving engineered bacteria and artificial intelligence applications are also explored. Finally, we propose a hypothetical conceptual framework for an innovative multimodal immunotherapy approach to overcome resistance and improve clinical outcomes in PDAC.}, } @article {pmid40782764, year = {2025}, author = {Wang, FY and Yi, J and Zhou, LL and Tan, JL and Cao, XY and Zhang, C and Wan, JJ and Song, L and Dai, AG}, title = {Unlocking the gut-lung axis: Feixin decoction as a novel modulator in hypoxic pulmonary hypertension.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {146}, number = {}, pages = {157118}, doi = {10.1016/j.phymed.2025.157118}, pmid = {40782764}, issn = {1618-095X}, abstract = {BACKGROUND: Feixin decoction (FXD) is an effective traditional Chinese medicine prescription for treating chronic pulmonary heart disease and hypoxic pulmonary hypertension (HPH), However, the pharmacological mechanism of FXD in preventing HPH remains unclear.

PURPOSE: This study aimed to evaluate the preventive and therapeutic effect of FXD on HPH and confirm the association between HPH, gut microbiota, and FXD.

METHODS: Multiple in vivo animal models were used, including HPH rat models, microbiota depletion models, and fecal microbiota transplantation (FMT) models. The HPH phenotype was evaluated through: right heart catheterization for hemodynamic parameters, doppler echocardiography for cardiac function assessment, hematoxylin-eosin staining for histopathological examination, and immunofluorescence labeling for specific protein expression analysis. Concurrently, transmission electron microscopy was utilized to observe the ultrastructure of the intestinal barrier, combined with immunofluorescence to examine the distribution characteristics of tight junction proteins. To elucidate the mechanism by which HPH ameliorates gut microbiota dysbiosis and associated metabolites, the study integrated 16S rRNA sequencing for microbiota composition analysis, dual-platform untargeted metabolomics for differential metabolite screening, and targeted metabolomics for quantitative validation.

RESULTS: FXD exhibited significant therapeutic effects in HPH rats, ameliorating pulmonary vascular remodeling, attenuating right ventricular hypertrophy, reducing systemic inflammation, and restoring intestinal barrier function. Additionally, FXD partially restored intestinal ecological balance by enriching beneficial species (Lactobacillus and Lactobacillus johnsonii) while reducing pathogenic genera (Escherichia-Shigella and Helicobacter rodentium). Concurrently, FXD treatment induced favorable metabolic alterations, characterized by elevated levels of beneficial metabolites including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), along with reduced concentrations of pro-inflammatory 5-hydroxytryptamine (5-HT). Gut microbiota depletion and fecal microbiota transplantation (FMT) studies established that FXD's therapeutic effects on HPH are mediated through gut microbiota modulation. Mechanistic investigations revealed that this protection likely involves inhibition of the TLR4/MyD88/NF-κB signaling pathway. In vitro studies further corroborated these findings, showing that FXD-enriched metabolites potently suppressed abnormal proliferation, migration and apoptosis in human pulmonary arterial smooth muscle cells (HPASMCs). Notably, EPA, the most significantly increased metabolite, specifically attenuates hypoxia-induced HPASMCs proliferation by interfering with the TLR4/MyD88/NF-κB signaling axis.

CONCLUSIONS: Our study confirms that FXD alleviates HPH by regulating gut microbiota and its associated metabolites and validates the potential of FXD as a gut microbiota modulator and an HPH treatment, thereby providing a new therapeutic strategy to improve treatment efficacy.}, } @article {pmid40781053, year = {2025}, author = {Kociolek, LK and Sandora, TJ and Mehrotra, P}, title = {Clostridioides difficile in Children.}, journal = {Infectious disease clinics of North America}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.idc.2025.07.011}, pmid = {40781053}, issn = {1557-9824}, abstract = {After a significant increase in pediatric Clostridioides difficile infection (CDI) in the United States over the past 2 decades, incidence has declined over the past 5 y. Community-associated CDI incidence is 3 times higher than healthcare facility-associated CDI in children, but sources of community acquisition are poorly defined. Diagnosis of CDI is challenging because of high frequency of colonization in infants and some groups of older children. Recent data suggest that vancomycin should be considered a first-line treatment for CDI in children and that fidaxomicin and fecal microbiota transplantation are safe and effective therapies for recurrent CDI.}, } @article {pmid40781016, year = {2025}, author = {Rubin, J and Roman, M}, title = {Veterinary Medical Ozone Therapy: An Integrative Approach.}, journal = {The Veterinary clinics of North America. Small animal practice}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cvsm.2025.06.009}, pmid = {40781016}, issn = {1878-1306}, abstract = {Veterinary medical ozone therapy, a key component of integrative veterinary medicine, leverages advanced oxygenation techniques and natural immune-modulating effects to treat a broad range of clinical conditions in small, large and exotic animals. This article explores the mechanisms of action, clinical applications, safety considerations, and integration of medical ozone therapy with conventional and complementary treatments, providing veterinary professionals with a practical and comprehensive resource. With the growing challenge of antimicrobial resistance posing significant public health concerns, the role of medical ozone therapy has become increasingly vital.}, } @article {pmid40780339, year = {2025}, author = {Gao, Y and Lin, J and Liu, D and Zhao, W and Pei, J and Abd El-Aty, AM}, title = {A selenium-enriched glycosaminoglycan from sturgeon cartilage: characterization and anti-metabolic syndrome potential.}, journal = {International journal of biological macromolecules}, volume = {322}, number = {Pt 1}, pages = {146637}, doi = {10.1016/j.ijbiomac.2025.146637}, pmid = {40780339}, issn = {1879-0003}, abstract = {This study develops a novel selenium-enriched chondroitin sulfate (CSSE) from selenium-rich sturgeon cartilage that has potent multitarget activity against high-carbohydrate/high-fat diet-induced metabolic syndrome. Structural analyses (NMR/MALDI-TOF MS) confirmed Se-O-SO3 covalent bonds (δ 78.5 ppm in [13]C NMR) and a molecular weight of 16.8 kDa, indicating hepatic targeting with lower renal toxicity. Compared with sodium selenite, CSSE showed superior antioxidant capacity (65-80 % vs. 30-45 % DPPH scavenging) and biocompatibility (89.5 % vs. 66.4 % cell viability) (p = 0.009). In high-carbohydrate/high-fat diet (HCHF)-fed mice, CSSE markedly decreased body weight gain (-35 %), fasting glucose (-55 %), and triglyceride levels (-44 %), outperforming inorganic selenium by 2.1-3.5-fold. Mechanistically, CSSE inhibited mammalian target of rapamycin complex 1 (mTORC1) activation (32.7 % phosphorylated mammalian target of rapamycin (p-mTOR)/mammalian target of rapamycin (mTOR)), restored insulin signaling via the phosphoinositide 3-kinase-protein kinase B (PI3K-Akt)/insulin receptor substrate 1 (IRS-1) (↑103 % phosphorylated Akt (p-Akt)/protein kinase B (Akt), and upregulated the fibroblast growth factor 21 (FGF21)/fibroblast growth factor 19 (FGF19) gut-liver axis (p = 0.028). CSSE enriched beneficial gut bacteria (e.g., Ligilactobacillus) while suppressing Allobaculum, increasing short-chain fatty acid (SCFA) production by 58.1 % and enhancing gut barrier function (↓49 % fluorescein isothiocyanate (FITC)-dextran leakage, p = 0.007). Fecal microbiota transplantation (FMT) has validated microbiota-mediated benefits. The dual antioxidant and lipid-lowering actions of CSSE, combined with its targeted delivery and safety, position it as a pioneering marine organoselenium therapy. This study also establishes a sustainable approach to transform aquaculture byproducts into precision nutraceuticals, advancing metabolic health through circular bioeconomic solutions.}, } @article {pmid40780229, year = {2025}, author = {Rhode, P and Mehdorn, M and Lange, UG and Rabe, SM and Quart, J and Nowotny, R and Plum, PS and Niebisch, S and Stelzner, S}, title = {[Functional Outcome of Radiotherapy, Chemotherapy and Surgery in the Treatment of Rectal Cancer].}, journal = {Zentralblatt fur Chirurgie}, volume = {150}, number = {4}, pages = {353-361}, doi = {10.1055/a-2646-2695}, pmid = {40780229}, issn = {1438-9592}, mesh = {Humans ; *Rectal Neoplasms/therapy/pathology/surgery/drug therapy/radiotherapy ; Combined Modality Therapy ; Neoadjuvant Therapy ; Treatment Outcome ; Fecal Incontinence/etiology ; Neoplasm Staging ; Postoperative Complications/etiology ; }, abstract = {Treatment of rectal cancer is multimodal and based on tumour stage and location, as well as morphological and biological risk factors - using surgery, radiotherapy, and chemotherapy. In a large number of cases, there are several treatment options, some of which can cause similar and some of which can cause different functional limitations. Comparisons of functional outcomes between different treatment modalities are currently limited.This narrative review presents the functional outcomes of different treatment strategies for middle and lower third rectal cancer, as based on a literature search.This paper analyses the evidence on the functional outcomes of different treatment strategies, especially regarding fecal continence, urinary and sexual function. The functional outcome after organ-preserving strategies appears to be slightly better in terms of stool frequency compared to surgical therapy alone, but this has to be weighed up against chemotherapy-induced polyneuropathy and radiogenic toxicities such as cystitis, radionecrosis or fistula formation. In addition, the functional side effects of perioperative and surgical therapy accumulate in the event of incomplete remission. A few days of treatment during surgical therapy contrast with the significantly more protracted treatment of total neoadjuvant therapy. A conclusive evaluation based on the current evidence is only possible to a limited extent.This study emphasises the importance of providing patients with detailed information about the functional consequences, duration of treatment and possible complications and offers a decision-making aid for planning individual treatment, taking quality of life into account.}, } @article {pmid40778357, year = {2025}, author = {Ren, J and Lian, XY and Ye, WQ and Wen, YL and Lu, CL and Cao, X}, title = {Gut microbiota regulates innate anxiety through neural activity of medial prefrontal cortex in male mice.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1599818}, pmid = {40778357}, issn = {1662-4548}, abstract = {INTRODUCTION: Innate anxiety, a stable personality trait conceptualized as trait anxiety, represents a fundamental dimension of individual differences in emotional regulation. Clinical evidence and animal studies indicate that elevated innate anxiety significantly increases susceptibility to psychiatric disorders. While the gut microbiota has been increasingly recognized as a critical modulator of neuropsychiatric health, its specific contribution to innate anxiety has yet to be fully elucidated.

METHODS: We investigated gut microbiota contributions to innate anxiety in mice using stratified behavioral phenotyping in the elevated plus maze (EPM), antibiotic (ABX)-mediated microbiota depletion, fecal microbiota transplantation (FMT), c-FOS staining, transcriptomic profiling, and vivo fiber photometry.

RESULTS: We found that innate high-anxiety (HA) and low-anxiety (LA) mice exhibited distinct gut microbial compositions. Microbiota depletion induced significant anxiolytic effects, while FMT from HA donors recapitulated anxiety-like behaviors. Neural activation mapping revealed elevated c-FOS expression in the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and central amygdala (CeA) of HA-FMT recipients. Transcriptomic analysis of mPFC tissue in HA- and LA-FMT recipients demonstrated microbiota driven regulation of transcriptional reprogramming, protein modification, and synapse modulation, indicating mechanistic connections along the microbiota gut-brain axis. Fiber photometry confirmed heightened mPFC neuronal activity during innate anxiety states in HA-FMT mice.

DISCUSSION: Our findings establish that gut microbiota modulates innate anxiety through mPFC neural activity, providing novel insights into microbiome-based interventions for anxiety.}, } @article {pmid40776644, year = {2025}, author = {Lin, Y and Wang, P and Hu, X and Wang, Q and Shi, Q and Zhou, Y and Liu, R and Cai, X}, title = {Recent Advancement of Fecal Microbiota Transplantation in the Treatment of Ulcerative Colitis- A Review.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0109298673404225250730100935}, pmid = {40776644}, issn = {1875-533X}, abstract = {Fecal Microbiota Transplantation (FMT) involves the transfer of gut microbiota from healthy donors to recipients, aiming to reestablish microbial equilibrium within the gastrointestinal tract. The human gut harbors a complex and diverse microbial ecosystem, comprising bacteria, viruses, and fungi, that is essential for maintaining intestinal homeostasis. Emerging evidence indicates a strong association between gut microbial dysbiosis and the pathogenesis of Ulcerative Colitis (UC). FMT has been shown to modulate microbial composition, alter immune signaling pathways, enhance intestinal barrier function, and influence the production of proinflammatory mediators, thereby affecting disease progression. This review critically examines the efficacy, safety, modulatory factors, combination therapies, and predictive strategies associated with FMT in the context of UC. The findings suggest that FMT represents a highly promising therapeutic modality for UC. Overall, this review aims to provide a comprehensive and impartial synthesis of current knowledge regarding FMT, offering deeper insights into its therapeutic potential and clinical applicability in UC management.}, } @article {pmid40776414, year = {2025}, author = {Kong, X and Wu, SY and Jiang, JZ and Luo, S and Zhang, J and Yang, GF and Lu, GM and Zhang, LJ}, title = {Efficacies of Bifidobacterium and Fecal Microbiota Transplantation in Rats With Chronic Hepatic Encephalopathy Assessed by [[18]F]PBR146 Imaging of Neuroinflammation.}, journal = {The European journal of neuroscience}, volume = {62}, number = {3}, pages = {e70227}, doi = {10.1111/ejn.70227}, pmid = {40776414}, issn = {1460-9568}, support = {81401468//National Natural Science Foundation of China/ ; 81601486//National Natural Science Foundation of China/ ; 82127806//National Natural Science Foundation of China/ ; 82230068//National Natural Science Foundation of China/ ; 81830057//National Natural Science Foundation of China/ ; 81322020//National Natural Science Foundation of China/ ; 81230032//National Natural Science Foundation of China/ ; 81171313//National Natural Science Foundation of China/ ; 2020AAA0109500//Science and Technology Innovation 2030-Major Projects/ ; 021414380531//Fundamental Research Funds for the Central Universities of China/ ; 201801B055//Program B for Outstanding PhD Candidate of Nanjing University/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Hepatic Encephalopathy/therapy/diagnostic imaging ; Rats ; Male ; Positron Emission Tomography Computed Tomography ; *Bifidobacterium ; Rats, Sprague-Dawley ; Brain/diagnostic imaging ; *Neuroinflammatory Diseases/diagnostic imaging/therapy ; Pyrimidines ; }, abstract = {Neuroinflammation significantly contributes to hepatic encephalopathy (HE). The radiotracer [[18]F]PBR146 is used for in vivo imaging of neuroinflammation. Promising treatments like Bifidobacterium (BIF) and fecal microbiota transplantation (FMT) are being explored for HE. This study evaluated and compared the efficacies of BIF and FMT in reducing neuroinflammation in chronic HE rats induced by bile duct ligation (BDL) using [[18]F]PBR146 micro-PET/CT imaging. Thirty rats were divided into four groups: (1) Sham-operated rats received normal saline (Sham + NS group), (2) BDL rats treated with NS (BDL + NS group), (3) BDL rats administered with BIF (BDL + BIF group), and (4) BDL rats administered with FMT (BDL + FMT group). Following the establishment of the chronic HE model, we conducted sequential behavioral assessments, collected fecal samples, and performed micro-PET/CT scans. Data analysis included average %ID/g values across the whole brain and specific regions, alongside biochemical and pathological evaluations. No significant differences in behavioral results or levels of IL-1β, IL-6, IL-10, and TNF-α were found among the groups. While there was no significant difference in global brain uptake values of [[18]F]PBR146 among the four groups (p = 0.053), regional analyses showed significant discrepancies in areas such as the bilateral accumbens and retrosplenial cortex. The Sham + NS group was enriched with Parasutterella, Streptococcus, and Anaeroplasma, the BDL + FMT group had Enterococcus, Aestuariispira, Lactobacillus, Pseudomonas, and Globicatella, while the BDL + BIF group contained Enterorhabdus. Results indicated that BIF inhibited neuroinflammation in BDL rats, whereas FMT showed no positive effects, possibly due to dysbiosis. Notably, [[18]F]PBR146 could effectively and noninvasively monitor the efficacies of gut-targeted treatments in chronic HE models.}, } @article {pmid40774824, year = {2025}, author = {Lee, I and Kim, BS and Suk, KT and Lee, SS}, title = {Gut Microbiome-Based Strategies for the Control of Carbapenem-Resistant Enterobacteriaceae.}, journal = {Journal of microbiology and biotechnology}, volume = {35}, number = {}, pages = {e2406017}, pmid = {40774824}, issn = {1738-8872}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Carbapenem-Resistant Enterobacteriaceae/drug effects/physiology ; Humans ; Fecal Microbiota Transplantation ; *Enterobacteriaceae Infections/prevention & control/microbiology/therapy ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Animals ; Carbapenems/pharmacology ; Antimicrobial Stewardship ; }, abstract = {Carbapenem-resistant Enterobacteriaceae (CRE) represent a critical antimicrobial resistance threat due to their resistance to last-resort antibiotics and high transmission potential. While conventional strategies-such as infection control, antimicrobial stewardship, and novel antibiotic development-remain essential, growing attention has shifted toward the gut microbiome, which plays a central role in mediating colonization resistance against CRE. Disruption of the intestinal microbiota-primarily driven by antibiotic exposure and further exacerbated by non-antibiotic drugs such as proton pump inhibitors-reduces microbial diversity and impairs functional integrity, facilitating CRE acquisition, prolonged carriage, and horizontal transmission. In response, microbiome-based strategies-including microbiome disruption indices (MDIs), fecal microbiota transplantation (FMT), and rationally designed symbiotic microbial consortia-are being explored as novel approaches for CRE prevention and decolonization. Mechanistic studies have shown that colonization resistance is mediated by both direct mechanisms (e.g., nutrient competition, short-chain fatty acid production) and indirect mechanisms (e.g., immune modulation via IL-36 signaling). Advances in metagenomics, metabolomics, and culturomics have enabled high-resolution profiling of gut microbial communities and their functional roles. Emerging preclinical and clinical evidence supports the potential of microbiome-informed interventions to predict infection risk, enhance antimicrobial stewardship, and guide the development of next-generation probiotics targeting CRE. Longitudinal studies continue to evaluate the efficacy of FMT and synthetic microbial consortia in eradicating intestinal CRE colonization. Collectively, these insights underscore the promise of gut microbiome science as a complementary and innovative strategy for CRE control in the post-antibiotic era.}, } @article {pmid40774378, year = {2025}, author = {Chatonidi, G and Rosseel, R and Dalile, B and Satriawan, D and Vandermeulen, G and Van Holm, B and Comer, L and Maes, P and Everaert, N and Courtin, CM and Verbeke, K}, title = {Effect of whole meal yeast-leavened, sourdough-leavened and yeast-sourdough-leavened bread consumption on appetite, energy intake, and postprandial metabolic responses: A randomized, blinded, cross-over study.}, journal = {Appetite}, volume = {216}, number = {}, pages = {108256}, doi = {10.1016/j.appet.2025.108256}, pmid = {40774378}, issn = {1095-8304}, abstract = {Bread is a major source of carbohydrates in Europe, and whole meal varieties may offer better metabolic responses and increased satiety than white bread. We compared the effects of three types of whole meal bread: whole meal yeast bread (WYB), whole meal sourdough bread (WSB), and whole meal sourdough and yeast bread (WSYB), on appetite regulation and metabolic outcomes in healthy subjects. The sourdough contained Fructilactobacillus sanfranciscensis and Maudiozyma humilis, and the process time depended on the leavening agent. In this double-blind, randomized crossover trial, 44 participants (25 ± 4 years, BMI: 22 ± 2 kg/m[2]) consumed 180g/day of each bread type for two weeks, separated by a 2-week washout period. Habitual food intake was reported and a fecal sample was collected for microbiota analysis. During a study visit on the final day of each intervention period, participants consumed 100 g of the test bread for breakfast. Oral processing, gastric emptying, and postprandial glucose, C-peptide, appetite and hormonal responses were measured. The primary outcome was ad-libitum energy intake at the subsequent lunch. Ad-libitum energy intake at lunch did not differ after consumption of the test breads. WYB and WSYB were consumed more slowly than WSB and led to slightly higher satiety (p < 0.05). Compared to the other breads, WSYB led to higher C-peptide levels, WYB resulted in greater PYY responses, and both WSB and WYB stimulated higher GLP-1 release (p < 0.05). In contrast, gastric emptying, glucose responses, ad-libitum energy intake, habitual energy intake, cholesterol, or gut microbiota composition did not differ between breads (p > 0.05). Despite the small metabolic differences, our findings suggest that whole meal bread with baker's yeast and/or sourdough had similar effects on appetite regulation.}, } @article {pmid40774255, year = {2025}, author = {Carr, AV and Baliga, NS and Diener, C and Gibbons, SM}, title = {Personalized Clostridioides difficile colonization risk prediction and probiotic therapy assessment in the human gut.}, journal = {Cell systems}, volume = {}, number = {}, pages = {101367}, doi = {10.1016/j.cels.2025.101367}, pmid = {40774255}, issn = {2405-4720}, abstract = {Clostridioides difficile (C. difficile) colonizes up to 40% of community-dwelling adults without causing disease but can eventually lead to infection (C. difficile infection [CDI]). There has been a lack of focus on how to prevent colonization and facilitate the successful clearance of C. difficile prior to the emergence of CDI. We show that microbial community-scale metabolic models (MCMMs) accurately predict C. difficile colonization susceptibility in vitro and in vivo, offering mechanistic insights into microbiota-specific interactions involving metabolites like succinate, trehalose, and ornithine. MCMMs reveal distinct C. difficile metabolic niches-two growth-associated and one non-growth-associated-observed across 15,204 individuals from five cohorts. We further demonstrate that MCMMs can predict personalized C. difficile growth suppression by a probiotic cocktail designed to replace fecal microbiota transplants (FMTs) for the treatment of recurrent CDI, and we identify new probiotic targets for future validation. MCMMs represent a powerful framework for predicting pathogen colonization and assessing probiotic efficacy across diverse microbiota contexts. A record of this paper's transparent peer review process is included in the supplemental information.}, } @article {pmid40772940, year = {2025}, author = {Ryan, K and Cunningham, A and Runde, J}, title = {Reaching for Remission: Integrating Complementary and Alternative Strategies into Inflammatory Bowel Disease Management.}, journal = {Pediatric annals}, volume = {54}, number = {8}, pages = {e274-e279}, doi = {10.3928/19382359-20250612-07}, pmid = {40772940}, issn = {1938-2359}, mesh = {Humans ; *Complementary Therapies/methods ; *Inflammatory Bowel Diseases/therapy ; Child ; Gastrointestinal Microbiome ; Probiotics/therapeutic use ; Remission Induction ; Fecal Microbiota Transplantation ; Mind-Body Therapies ; }, abstract = {Pediatric inflammatory bowel disease (IBD) is increasing in prevalence in the United States. While medical therapy options continue to expand, patients and their families often inquire about applications of complementary and alternative medicine (CAM). In this article, we review the existing literature for a wide variety of CAMs, including mind-body practices, modulation of the gut microbiome, and herbal supplements, which can be integrated into traditional medical treatments. Mind-body practices, particularly cognitive behavioral therapy, yoga, and acupuncture, have promising data for improved quality of life and potential for disease modification. Methods for gut microbiome modulation, such as probiotics and fecal microbiota transplant, have potential for modifying disease in IBD but need more studies evaluating safety and efficacy. Plant-based traditional remedies with anti-inflammatory properties, including curcumin and Indigo naturalis (Qing dai), have shown promising results in clinical trials demonstrating improvements in ulcerative colitis disease activity, although more pediatric trials are needed.}, } @article {pmid40772261, year = {2025}, author = {Pan, Z and Gao, Z and Chen, J and Quan, Y and Xu, J and Liang, X and Xie, W and He, X and Wu, L}, title = {Does constipation affect the effectiveness of washed microbiota transplantation in treating autism spectrum disorders?.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1602681}, pmid = {40772261}, issn = {1662-4548}, abstract = {PURPOSE: Washed microbiota transplantation (WMT) has been shown to improve the symptoms of Autism Spectrum Disorder (ASD). It's currently unclear whether the presence of constipation affects the efficacy of WMT in children with ASD. This study aims to investigate whether constipation affects the efficacy of WMT in children with ASD.

PATIENTS AND METHODS: To investigate the efficacy of WMT for ASD, we conducted a retrospective analysis of changes in ASD-related symptoms, sleep disturbances, gastrointestinal manifestations, intestinal barrier integrity, and gut microbiota composition in 103 ASD patients undergoing WMT. They were divided into two groups according to whether constipation was present or not before treatment.

RESULTS: 1. Aberrant Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Sleep Disturbance Scale for Children (SDSC) scores in the non-constipation and constipation groups decreased with an increase in the number of WMT treatments. 2. Comparison of two groups: ABC scores in the non-constipation group decreased more after the first WMT course, whereas ABC scores in the constipation group decreased more after two WMT courses. 3. Intestinal Barrier Function: D-lactate levels decreased more in the constipation group after the first two courses. In general, WMT treatment had no significant effect on intestinal barrier function in patients with ASD. 4. Effect of WMT on constipation: As the number of WMT courses increased, Bristol Stool Form Scale (BSFS) scores in constipation group gradually approached 4. 5. Constipation group had lower microbial diversity than non-constipation group at baseline. After one course of WMT, constipation group showed an obvious increase in microbial diversity and a significant increase in the relative abundance of Bifidobacteria compared to non-constipation group.

CONCLUSION: Post WMT, core symptoms and sleep disorders were significantly improved in both groups. Feces returned to normal shape in the constipation group. A difference in efficacy between the two groups was observed in early stages, but after multiple courses of WMT no difference in efficacy was noted. Although in the short-term, children with ASD and comorbid constipation showed a significant increase in microbial diversity after receiving WMT, mid-term outcomes indicate that constipation does not affect the efficacy of WMT in treating ASD.}, } @article {pmid40771816, year = {2025}, author = {Ma, J and Fang, Y and Hu, J and Li, S and Zeng, L and Chen, S and Li, Z and Meng, R and Yang, X and Zhang, F and Ji, G and Liao, P and Chen, L and Wu, W}, title = {Innovative microbial strategies in atopic dermatitis.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1605434}, pmid = {40771816}, issn = {1664-3224}, mesh = {Humans ; *Dermatitis, Atopic/therapy/microbiology/immunology ; Fecal Microbiota Transplantation/methods ; Probiotics/therapeutic use ; Animals ; *Gastrointestinal Microbiome/immunology ; Prebiotics/administration & dosage ; Dysbiosis/therapy ; *Microbiota ; }, abstract = {Atopic dermatitis (AD) is characterized by chronic and recurrent itching with a high burden of disability-adjusted life years (DALYs, a measure of overall disease burden). Traditional treatments mainly include corticosteroids, which have a good effect on controlling inflammation but adverse side effects. Recently, advancements in understanding the pathogenesis of AD have led to the emergence of a variety of novel therapeutic approaches, such as microbiome manipulation, offering renewed hope for more effective management of this condition. These strategies are particularly promising for mild-to-moderate AD, where dysbiosis and immune imbalance (e.g., Th2 skewing) are key drivers, though some approaches (e.g., fecal microbiota transplantation) are being explored for refractory cases. It has been shown that microbiome manipulation has the potential to improve disease states and regulates the balance of the inflammatory system in a variety of ways. Various approaches have been preclinically and clinically tested, including probiotics (and multiple co-applications), prebiotics, postbiotics, unmethylated CpG motifs, fecal microbiota transplantation, herbal fermentation technology with microorganisms and phage. In this review, we discuss these microbiome manipulation methods and emphasizes the potential of microbiome-based interventions to modulate Th1/Th2 balance with fewer side effects, ultimately leading to control of inflammation in AD. Further translational research in this field is needed to integrate when we apply this therapy and the capability for disease treatment and prevention.}, } @article {pmid40771692, year = {2025}, author = {Cao, Q and Yang, M and Chen, M}, title = {Metabolic interactions: how gut microbial metabolites influence colorectal cancer.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1611698}, pmid = {40771692}, issn = {1664-302X}, abstract = {Colorectal cancer (CRC) is a growing public health concern due to its rising incidence and high rate of cancer-associated deaths. Emerging evidence suggests that gut microbiota and their metabolites are critically involved in the initiation and advancement of CRC. These metabolites, which originate from the breakdown of nutrients from food and host-related substances through microbial activity in the gut, can profoundly influence tumor formation. In addition to well-studied compounds such as short-chain fatty acids (SCFAs), bile acids (BAs), tryptophan metabolites, and polyamines, this review highlights emerging metabolites-including hydrogen sulfide (H2S) and formate-that have recently drawn attention for their roles in colorectal carcinogenesis. We also incorporate recent mechanistic insights, such as butyrate-induced ferroptosis and H2S-mediated protein persulfidation, to illustrate how microbial metabolites influence cancer cell metabolism. Moreover, the potential of microbial metabolites as biomarkers for early diagnosis and prognosis of CRC is discussed. Therapeutic strategies targeting microbial metabolites-such as dietary modulation, combination therapies, fecal microbiota transplantation (FMT), and phage therapy-are also reviewed. By providing a comprehensive and up-to-date overview of microbial metabolic networks associated with CRC, this review underscores the critical functions of gut microbial metabolites in tumorigenesis, offering novel insights into their utility as diagnostic and prognostic biomarkers, as well as promising therapeutic targets.}, } @article {pmid40771615, year = {2025}, author = {Safdar, N}, title = {PREVENTION OF HEALTH CARE-ASSOCIATED INFECTIONS IN U.S. HEALTH SYSTEMS: HARNESSING THE GUT MICROBIOME TO COMBAT INFECTION.}, journal = {Transactions of the American Clinical and Climatological Association}, volume = {135}, number = {}, pages = {260-268}, pmid = {40771615}, issn = {0065-7778}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Fecal Microbiota Transplantation ; United States/epidemiology ; *Clostridium Infections/prevention & control/microbiology/therapy ; *Clostridioides difficile/pathogenicity ; *Cross Infection/prevention & control/microbiology/epidemiology ; Anti-Bacterial Agents/adverse effects/therapeutic use ; }, abstract = {Health care-associated infections (HAIs) remain a major challenge in the U.S. health care system, with Clostridioides difficile (C. difficile or C. diff) being the most prevalent. The use of antibiotics disrupts the gut microbiota, predisposing individuals to infection. Recent research has highlighted the role of the gut microbiome in preventing and treating C. difficile infections (CDI). Strategies such as fecal microbiota transplantation (FMT) and live biotherapeutic products (LBPs) offer promising alternatives to conventional antibiotic treatments. This paper explores the mechanisms underlying CDI, the role of the gut microbiome in infection prevention, and innovative therapeutic approaches.}, } @article {pmid40768832, year = {2025}, author = {Cintado, E and Muela, P and Martín-Rodríguez, L and Alcaide, I and Tezanos, P and Vlckova, K and Valderrama, B and Bastiaanssen, TFS and Rodríguez-Muñoz, M and de Ceballos, ML and Aburto, MR and Cryan, JF and Trejo, JL}, title = {Gut microbiota regulates exercise-induced hormetic modulation of cognitive function.}, journal = {EBioMedicine}, volume = {119}, number = {}, pages = {105876}, doi = {10.1016/j.ebiom.2025.105876}, pmid = {40768832}, issn = {2352-3964}, abstract = {BACKGROUND: Lifestyle factors, particularly physical exercise, significantly influence brain structure and cognitive function through a hormetic effect -a phenomenon where low to moderate doses of a stimulus (in this case, exercise) induce beneficial adaptations, while excessive doses could lead to detrimental effects. This effect depends on exercise intensity and duration, though the underlying mechanisms remain largely unexplored. Recently, the gut microbiota has emerged as potent modulator of lifestyle-induced changes in brain and behaviour.

METHODS: We used a 40-min, 1200 cm/min exercise protocol. We measured cognition through several tests and analysed microbiota composition comparing adult exercised animals to sedentary controls. Finally, we performed fecal microbiota transplantation from exercised to sedentary mice.

FINDINGS: Exercise enhances cognitive abilities related to object recognition and object location memory, as well as increases hippocampal neurogenesis. However, these cognitive and neurogenic benefits vanish when the exercise intensity or duration is increased. Furthermore, we identified significant changes in alpha and beta diversity and distinct bacteria composition profiles in the gut microbiota associated with different exercise regimens. Specific bacterial families showed altered relative abundances depending on exercise intensity and duration, with certain families' quantities significantly correlating with cognitive performance (Angelakisella, Acetatifactor, Erysipelatoclostridium, and Coriobacteriaceae UCG-002.). To explore causal mechanisms, we performed fecal microbiota transplantation from exercised to sedentary mice, which replicated the cognitive and neurogenic changes observed in the donor animals.

INTERPRETATION: These findings suggest that the hormetic effects of physical exercise on cognitive function and neurogenesis are mediated by corresponding changes in the gut microbiota, highlighting a novel mechanistic link between exercise, brain function, and gut microbiota composition.

FUNDING: E.C. and P.M. were funded by predoctoral fellowship (FPI) grants from the Spanish Ministry of Economy and Competitiveness (BES-2017/080415 E.C.) and the Spanish Ministry of Science and Innovation (PRE2020/093032 P.M.), and P.T. by a predoctoral fellowship (FPU) from the Spanish Ministry of Universities (18/00069). Work was supported by project grants PID2019-110292RB-100 and PID2022-136891NB-I00 (from Spanish Ministry of Science and Innovation), (to J.L.T.).}, } @article {pmid40768805, year = {2025}, author = {Chen, J and Zhang, L and Chen, Y and Yan, Y and Lu, C}, title = {Alpha-tocopheryl quinone attenuates liver fibrosis through enriching Christensenella minuta and modulating bile acids metabolism via gut-liver axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {146}, number = {}, pages = {157108}, doi = {10.1016/j.phymed.2025.157108}, pmid = {40768805}, issn = {1618-095X}, abstract = {BACKGROUND: Liver fibrosis, characterized by the progressive accumulation of excessive extracellular matrix (ECM), remains a major global health issue with limited treatment options. The gut-liver axis, particularly the dynamics of gut microbiota and bile acids (BAs), plays a pivotal role in modulating hepatic fibrogenesis. Alpha-tocopheryl quinone (TQ), a vitamin E metabolite, exhibits antioxidative and anti-inflammatory properties; however, its impact on liver fibrosis remains unexplored.

METHODS: A murine fibrosis model was induced using carbon tetrachloride (CCl4), coupled with gut microbiota depletion via antibiotic cocktail (Abx) and fecal microbiota transplantation (FMT) from cirrhotic donors, to evaluate TQ's therapeutic effects. Biochemical and histological analyses assessed liver injury and fibrosis, while 16S rRNA sequencing determined gut microbiota composition. BAs profiles were quantified using LC-MS/MS. Glycine-β-muricholic acid (Gly-MCA), a gut-restricted farnesoid X receptor (FXR) antagonist, was employed for investigating mechanistic pathways.

RESULTS: TQ treatment significantly alleviated liver damage and fibrosis in CCl4-treated mice, with a notable reshaping of the gut microbiota, particularly an increased abundance of Christensenella minuta (C. minuta). Mechanistically, TQ activated the intestinal FXR/FGF15 pathway, resulted in reduced hepatic BAs synthesis and enhanced fecal excretion. Abx and FMT experiments confirmed the microbiota-dependent antifibrotic effects of TQ, with C. minuta identified as a key mediator. Co-treatment with Gly-MCA abrogated the protective effects of C. minuta, highlighting the critical role of intestinal FXR signaling.

CONCLUSIONS: TQ attenuates liver fibrosis via modulation of gut microbiota, particularly enriching C. minuta abundance, and regulating BAs metabolism via activation of the intestinal FXR/FGF15 axis. These results establish TQ as a promising therapeutic targeting the gut-liver axis, with C. minuta identified as a pivotal mediator in BAs metabolism and fibrotic resolution. This study lays the groundwork for microbiota-centered therapeutic strategies against hepatic fibrosis.}, } @article {pmid40767874, year = {2025}, author = {Sadhu, S and Paul, T and Yadav, N}, title = {Therapeutic engineering of the gut microbiome using synthetic biology and metabolic tools: a comprehensive review with E. coli Nissle 1917 as a model case study.}, journal = {Archives of microbiology}, volume = {207}, number = {9}, pages = {213}, pmid = {40767874}, issn = {1432-072X}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Escherichia coli/genetics/metabolism/enzymology ; *Metabolic Engineering/methods ; *Synthetic Biology/methods ; Probiotics/therapeutic use ; Phenylalanine Ammonia-Lyase/genetics/metabolism ; Phenylketonurias/therapy ; }, abstract = {The human gut microbiome significantly influences host physiology, metabolism, and immune function. The engineering of microbial communities represents a significant advancement in contemporary biotechnology. Conventional methods, including Fecal Microbiota Transplantation (FMT) and probiotic administration, exhibit limitations in efficacy and raise safety and reproducibility concerns; however, they have shown potential therapeutic benefits. Recent progress in biocatalysis and metabolic engineering has led to the development of genetically tractable gut bacteria for targeted therapeutic purposes, particularly in the last five years. This chapter offers an overview of the development of microbiota-based interventions, from early recombinant probiotics to advanced synthetic biology platforms that can detect and respond to host and environmental signals. This analysis examines the mechanistic aspects of enzyme engineering, including improvements in metabolic pathways for the production of short-chain fatty acids, the breakdown of harmful metabolites, and the biosynthesis of immunomodulatory compounds. This review also examines conditions including inflammatory bowel disease, metabolic dysfunction, and colorectal cancer, highlighting microbial production systems pertinent to gut health. The engineering of Escherichia coli Nissle 1917 to produce phenylalanine ammonia-lyase (PAL) and L-amino acid deaminase (LAAD) represents a significant advancement in gut-based metabolic intervention for patients with phenylketonuria (PKU) by degrading excess phenylalanine. Recent studies offer peer-reviewed evidence supporting the translational potential of these inventions, as demonstrated through figures and tables highlighting engineered metabolic circuits, therapeutic outputs, and strain performance metrics. This combination of developments demonstrates the potential of synthetic microbiome engineering to provide precision biotherapeutics for various gut-related conditions.}, } @article {pmid40766454, year = {2025}, author = {Liow, YJ and Eshima, S and Talay, M and Yeliseyev, V and Bry, L and Carmody, RN}, title = {Polyunsaturated fatty acids promote appetite via the microbiome-gut-brain axis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40766454}, issn = {2692-8205}, support = {P30 DK034854/DK/NIDDK NIH HHS/United States ; R01 AI179807/AI/NIAID NIH HHS/United States ; }, abstract = {Appetite is regulated by nutrient-sensing systems that integrate long-term signals from energy stores and short-term cues from dietary intake, yet this regulation is increasingly disrupted by industrialized diets. Although the physiological effects of industrialized diets are well documented, the continued rise in metabolic and eating disorders underscores a critical gap in our understanding of how these diets shape neural regulation of eating behavior. Here, we tested how distinct properties of industrialized diets alter brain neurochemistry and change appetite. We probed the properties of an industrialized diet through contrasts targeting the overall diet pattern (Western vs. control), enriched macronutrients (fat vs. sugar), and isocaloric trade-offs of macronutrient variants (saturated fatty acids vs. polyunsaturated fatty acids [PUFA]). The most salient effects emerged from the finest-grained contrast: PUFA conditioning increased appetite through a mechanism involving elevated brain 5-hydroxyindoleacetic acid (5-HIAA), a primary serotonin catabolite associated with the gut microbiome. Fecal microbiota transplants into germ-free mice confirmed that the PUFA-conditioned gut microbiota carries an appetite-enhancing signature. Together, our findings delineate a diet-microbiome-gut-brain axis through which dietary components of industrialized diets can modulate appetite and contribute to altered eating behavior.}, } @article {pmid40762371, year = {2025}, author = {Li, X and Chen, Y and Gao, Z and Liu, X and Song, Z and Gao, F and Wang, S and Yu, C and Sun, L and Huang, Y and Zheng, L and Wang, G and Sun, Y and Li, J and Yang, X and Bao, Y}, title = {TSP50 in Neural Stem Cells Regulates Aging-Related Cognitive Decline and Neuroinflammation by Altering the Gut Microbiota.}, journal = {Aging cell}, volume = {}, number = {}, pages = {e70188}, doi = {10.1111/acel.70188}, pmid = {40762371}, issn = {1474-9726}, support = {GZC20240236//Postdoctoral Fellowship Program of CPSF/ ; 20230204067YY//the Science and Technology Development Program of Jilin Province/ ; 135131002//Fundamental Research Funds for the Central Universities/ ; }, abstract = {Aging is a process of gradual decline in physical and cognitive function and is a major risk factor for mortality. Despite the increasing number of relevant studies, the mechanisms regulating the aging process have not been fully elucidated. Genetic factors have long been recognized as key factors in controlling the rate of aging. Testes-specific protease 50 (TSP50) has been shown to be involved in the regulation of embryonic development and intestinal homeostasis, but its role in the regulation of aging remains unclear. Here, we showed that TSP50 expression was reduced in the hippocampus of both aged humans and mice. TSP50 deficiency in neural stem cells (NSCs) drove accelerated aging in mice, characterized by exacerbated age-related cognitive impairments and significantly elevated neuroinflammation. Notably, aged mice with NSCs-specific knockout of TSP50 exhibited impaired intestinal mucosal barriers, dysbiosis of gut microbiota, and a marked reduction in the production of short-chain fatty acids (SCFAs). Restoring gut microbial ecology using fecal microbiota transplantation (FMT) and overexpressing TSP50 successfully alleviated aging-associated cognitive decline and neuroinflammation. Taken together, our study suggests that TSP50 plays a critical role in the aging process and identifies gut microbiota as a pivotal mediator of TSP50's influence on age-related cognitive decline and neuroinflammation. These findings highlight the potential therapeutic value of targeting TSP50 and gut microbiota for aging, offering insights into aging mechanisms and interventions for aging-related neurodegenerative diseases.}, } @article {pmid40760849, year = {2025}, author = {Gong, H and Zhang, L and Liu, Y and Yuan, X and Liu, Y and Tang, J and Zhou, M and Song, J and Zhang, T}, title = {Oxidative Stress and Gut Microbiota Interplay Exacerbates Periodontitis in Diabetic Mice.}, journal = {Journal of clinical periodontology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jcpe.70003}, pmid = {40760849}, issn = {1600-051X}, support = {82170968//National Natural Science Foundation of China/ ; U22A20314//National Natural Science Foundation of China/ ; 2022YFC2504200//National Key Research and Development Program of China/ ; YXQN202401//Chongqing Municipal Youth Science and Technology Talent Training Project/ ; }, abstract = {AIM: To investigate the interplay between oxidative stress and gut microbiota in the pathogenesis of increased periodontitis in diabetic mice and explore potential therapeutic strategies.

MATERIALS AND METHODS: Diabetic periodontitis (DP) mouse models were established and subjected to interventions including antioxidant treatment, co-housing experiments and faecal microbiota transplantation (FMT). Alveolar bone loss, periodontal inflammation, oxidative stress markers, gut microbiota composition and intestinal barrier function were evaluated.

RESULTS: Diabetes exacerbated alveolar bone loss and inflammation markers in mice with periodontitis. DP mice exhibited significantly elevated systemic oxidative stress and gut dysbiosis compared to controls. Curcumin treatment effectively improved these parameters. Co-housing experiments between curcumin-treated and untreated DP mice showed that beneficial gut microbiota could be transferred between cage mates, leading to improved periodontal outcomes in untreated mice. Additionally, FMT from healthy donors reduced alveolar bone loss and periodontal inflammatory markers while improving oxidative stress parameters and restoring gut microbiota balance and barrier function.

CONCLUSIONS: This study demonstrates that the interaction between oxidative stress and gut dysbiosis may form a pathogenic loop associated with the exacerbation of periodontitis in diabetic conditions. The successful outcomes of antioxidant treatment and FMT suggest multiple adjunctive therapeutic approaches for managing DP.}, } @article {pmid40759593, year = {2025}, author = {Kwon, WA and Kim, H and Song, YS}, title = {Prostate Cancer at the Microbial Crossroads: Illuminating a New Frontier in Precision Medicine.}, journal = {The world journal of men's health}, volume = {}, number = {}, pages = {}, doi = {10.5534/wjmh.250045}, pmid = {40759593}, issn = {2287-4208}, abstract = {The human body harbors a complex, dynamic community of trillions of microbes, collectively termed the microbiota, which profoundly affects homeostasis and disease processes, including cancer. Prostate cancer remains a major cause of morbidity and mortality among men worldwide; however, critical questions remain regarding its etiology, progression, and resistance to therapy. Multiple epidemiological studies have found associations between certain urinary and intestinal microorganisms and an increased prostate cancer risk, although the causal mechanisms remain incompletely understood. Recent studies suggest that dysregulated microbial communities, or dysbiosis, are hypothesized to drive chronic inflammation, induce genotoxic insults, and modulate steroid metabolism, thereby influencing tumor initiation and progression. Conflicting findings across different investigations often stem from heterogeneous sampling methods, population differences, and disparate bioinformat ics pipelines, underscoring the critical need for standardized protocols and reproducible data analytics. For example, diet induced alterations in the gut microbiota can shift systemic inflammatory and hormonal pathways in ways that predispose individuals to malignant transformation. Simultaneously, prostatic and urinary microbes are hypothesized to fuel local inflam mation and promote precursor lesions, although whether this microbial activity is causative or merely reflective of the exist ing tumor biology remains a key unresolved question. Microbiota-driven mechanisms also shape responses to radiotherapy, chemotherapy, and emerging immunotherapies, highlighting the potential of interventions such as probiotics, prebiotics, and fecal microbiota transplantation to enhance treatment efficacy and mitigate side effects. Innovative approaches, including ar tificial intelligence-assisted predictive modeling, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based microbial gene editing, and immunomodulatory strategies (e.g., chimeric antigen receptor-T cells), offer new avenues for exploiting microbiota for therapeutic benefits. Nevertheless, unresolved questions regarding the long-term safety, ecological balance, and individual patient factors require caution. By integrating rigorous methodologies with these novel technologies, prostate cancer research may ultimately harness microbial insights to refine diagnostic tools, personalize therapies, and im prove patient outcomes.}, } @article {pmid40759441, year = {2025}, author = {Hadi, DK and Baines, KJ and Jabbarizadeh, B and Miller, WH and Jamal, R and Ernst, S and Logan, D and Belanger, K and Esfahani, K and Elkrief, A and Parvathy, SN and Silverman, MS and Routy, B and Maleki Vareki, S and Lenehan, JG}, title = {Improved survival in advanced melanoma patients treated with fecal microbiota transplantation using healthy donor stool in combination with anti-PD1: final results of the MIMic phase 1 trial.}, journal = {Journal for immunotherapy of cancer}, volume = {13}, number = {8}, pages = {}, doi = {10.1136/jitc-2025-012659}, pmid = {40759441}, issn = {2051-1426}, mesh = {Humans ; *Melanoma/therapy/mortality/pathology ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; Middle Aged ; Aged ; Adult ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Combined Modality Therapy ; }, abstract = {BackgroundMicrobiome manipulation research is focused on developing techniques to modify the gut microbiome and augment responses to immune checkpoint inhibitors (ICI). Fecal microbiota transplantation (FMT) represents a potential strategy to overcome primary or acquired resistance to ICI. 20 patients with advanced melanoma were enrolled in a phase I multicenter trial to evaluate the safety and response to anti-PD1 combined with FMT using healthy donor stool as first-line treatment (MIMic, NCT03772899). Combination therapy was safe, and the objective response rate (ORR) was 65%. We now report survival data based on over 3 years of follow-up. Patients with advanced melanoma and treatment-naïve for advanced disease received a single FMT with healthy donor stool followed by standard anti-PD1 therapy. Progression-free survival (PFS) and overall survival (OS) were measured from the date of FMT to event. Radiographic response was measured using RECIST 1.1 criteria. Both median PFS (mPFS) and median OS (mOS) were determined using the Kaplan-Meier method. Post hoc analyses assessed the impact of specific factors on survival outcomes. Minimum follow-up was 40 months from the date of FMT of the last patient, with the longest surviving patient in complete response at 62.2 months. At the time of data analysis, eight patients were alive and seven patients were without progression. No patients remain on anti-PD1 therapy. Only two patients received additional lines of therapy. The mPFS was 29.6 months and mOS 52.8 months. The 1, 2, and 3 years estimated survival rates were 95%, 74% and 53%, respectively. Post hoc analysis demonstrated significantly improved mPFS in responders and patients with FMT-specific toxicity. Combining first-line anti-PD1 therapy and oral FMT with healthy donor stool in this small cohort was safe and demonstrated an improvement in ORR, mPFS, and mOS, compared with randomized trials. Our sample size was small, and results were only hypothesis generating. The potential benefit of microbiome manipulation using oral FMT from healthy donors prior to ICI in patients with advanced melanoma will be evaluated in the ME.17 randomized phase 2 Canadian study (NCT06623461).}, } @article {pmid40759431, year = {2025}, author = {Yao, Y and Cai, X and He, D and Zheng, Y and Liu, M and Zhang, M and Li, Z and Fei, W and Zheng, C}, title = {Short-chain fatty acids regulate T cell heterogeneity to alleviate recurrent spontaneous abortion.}, journal = {British journal of pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bph.70155}, pmid = {40759431}, issn = {1476-5381}, support = {LHDMZ23H190002//Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China/ ; }, abstract = {BACKGROUND AND PURPOSE: The aetiology of recurrent spontaneous abortion (RSA) is multifactorial, with immune factors playing a critical role. Gut microbiota and its metabolites have been found to participate in host immune regulation. This study explores the role of gut microbiota-derived short-chain fatty acids (SCFAs) in immune tolerance in RSA.

EXPERIMENTAL APPROACH: Single-cell sequencing was used to analyse the cell profile of RSA patients. 16S rDNA sequencing was used to analyse the gut microbiota structure. Faecal microbiota transplantation (FMT) was used to explore the role of the gut microbiota in immune-related RSA in mice. SCFAs supplementation was used to explore the role of SCFAs in immune-related RSA mice. Conventional molecular biology methods were used to explore molecular mechanisms.

KEY RESULTS: The peripheral immune cell profile of RSA patients was altered. The gut microbiota structure of RSA patients was also altered, with a decrease in their SCFA levels. FMT significantly improved pregnancy outcomes in immune-related RSA in mice. SCFAs affected the differentiation of peripheral CD4[+] T cells and the expression of marker genes. SCFA supplementation altered the gut microbiota structure in immune-related RSA mice and improved colonic barrier function. SCFAs regulate CD4[+] T cell differentiation by targeting GPR43. Finally, the colon-targeted SCFA delivery nanoparticle system that we designed optimised the therapeutic effects of SCFAs.

CONCLUSION AND IMPLICATIONS: Gut microbiota-derived SCFAs regulate T cell heterogeneity to alleviate RSA. The findings of this study increase the understanding of maternal-fetal immune tolerance mechanisms and provide new insights for future therapeutic strategies for RSA.}, } @article {pmid40759389, year = {2025}, author = {Berry, P and Tariq, R and Pardi, D and Khanna, S}, title = {Effectiveness and Safety of Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection in Immunocompromised Patients.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2025.06.043}, pmid = {40759389}, issn = {1542-7714}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) poses a significant health risk to immunocompromised hosts due to the increased risk of severe infection and recurrence. Microbiota-based therapies have emerged as a promising strategy for CDI, but safety and efficacy in immunocompromised populations remain underexplored.

METHODS: A comprehensive literature search across Ovid MEDLINE(R), Ovid EMBASE, Clinicaltrials.gov, and Scopus from inception until December 16, 2024, identified studies meeting inclusion criteria, covering fecal microbiota transplantation (FMT) for recurrent CDI (rCDI) in immunocompromised individuals, including those on immunosuppressants, transplant recipients, undergoing chemotherapy, and with advanced HIV. Case reports and studies not separately reporting outcomes in immunocompromised patients were excluded. Statistical analysis was performed using random-effects models to account for heterogeneity among studies.

RESULTS: A total of 44 studies (31 full-text articles, 13 abstracts) were included, comprising 3,476 participants, of whom 1,208 were immunocompromised. The population included solid organ transplant recipients (n=219), cancer patients on chemotherapy (n=101), hematopoietic stem cell transplant recipients (n=29), and advanced HIV patients (n=11). The most common FMT route was colonoscopy (n=12 studies), followed by upper gastrointestinal routes, capsules, and rectal retention enemas. The clinical resolution rate after a single FMT was 75.3% (95% CI 71.7%-78.6%), increasing to 87.4% (95% CI 84.8%-89.6%) with consecutive treatments. The recurrence rate was 23.9% (95% CI 19.2%-29.4%), and the serious adverse event rate was 10.1% (95% CI 6.7%-14.8%).

CONCLUSIONS: The safety and effectiveness outcomes of FMT in mild to moderately immunocompromised populations for recurrent CDI are comparable to those in immunocompetent cohorts.}, } @article {pmid40755720, year = {2025}, author = {Bi, Y and Cheng, B and Zou, B and Liu, S and Cui, Z}, title = {The current landscape of fecal microbiota transplantation in treating inflammatory bowel disease.}, journal = {Translational gastroenterology and hepatology}, volume = {10}, number = {}, pages = {55}, pmid = {40755720}, issn = {2415-1289}, abstract = {Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is a chronic, immune-mediated disorder that impacts the intestinal tract. The gut microbiota, a diverse community of microorganisms, plays a pivotal role in the initiation, development, and progression of IBD by modulating inflammation, and immune responses, and maintaining gut homeostasis. Dysbiosis, or an imbalance in the gut microbiota, is frequently observed in IBD patients and is believed to contribute to the pathogenesis of the disease by disrupting the mucosal immune system. Fecal microbiota transplantation (FMT) involves transferring feces from a healthy donor (HD) into a recipient and has emerged as a promising therapeutic approach for IBD. The primary goal of FMT is to restore microbial balance in the recipient's gut, improving both microbiota composition and immune function. Numerous preclinical and clinical studies have demonstrated varying degrees of success in alleviating IBD symptoms through FMT. The benefits of FMT include modulation of gut bacteria abundance, restoration of microbial diversity, and enhancement of immune system regulation, all of which contribute to reducing IBD-related inflammation. This review presents a comprehensive analysis of animal studies and clinical trials exploring using FMT as a treatment for IBD. Understanding the underlying mechanisms of FMT in IBD is crucial for designing effective therapeutic strategies and optimizing its clinical impact.}, } @article {pmid40755230, year = {2025}, author = {Groenewegen, B and Ruissen, MM and Crossette, E and Menon, R and Prince, AL and Norman, JM and Ballieux, BEPB and Lamb, HJ and Terveer, EM and Keller, JJ and Tushuizen, ME}, title = {Consecutive fecal microbiota transplantation for metabolic dysfunction-associated steatotic liver disease: a randomized controlled trial.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2541035}, pmid = {40755230}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation ; Male ; Middle Aged ; Female ; Gastrointestinal Microbiome ; *Fatty Liver/therapy/microbiology ; Adult ; Double-Blind Method ; Aged ; Feces/microbiology ; Liver/metabolism ; Bacteria/classification/isolation & purification/genetics ; Treatment Outcome ; }, abstract = {The gut microbiota is increasingly considered a contributory factor in metabolic dysfunction-associated steatotic liver disease (MASLD). This double-blind RCT evaluated the effect of three consecutive fecal microbiota transplantations (FMT) on hepatic steatosis in MASLD. Twenty patients with MASLD were randomized (1:1) to receive allogeneic or autologous FMTs at weeks 0, 3, and 6, with follow-up through week 12. FMT material was derived from two donors. We assessed changes in hepatic steatosis (magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF)), glucose tolerance (oral glucose tolerance test), liver biochemistry, and gut microbiota composition/engraftment. Change in MRI-PDFF from baseline to week 12 was notsignificantly different between groups (p = 0.50). Liver biochemistry and glucose tolerance also showed no significant overall changes. Patients' stool microbiota exhibited high baseline alpha diversity and similar composition across treatment groups, diverging by week 12 (p = 0.02). Two microbial taxa belonging to the families Gastranaerophilaceae and Rikenellaceae were associated with triglyceride levels after FMT. No further microbiota signatures were associated with FMT-treatment or response. Donor microbiota engraftment appeared donor-specific, but not treatment- or response-specific. In conclusion, FMT did not significantly affect hepatic steatosis, glucose tolerance, liver biochemistry, or gut microbiota signatures. Future studies should consider including patients with low microbiota diversity. Dutch Trial Register: NL-OMON48776; Central Committee on Research Involving Human Subjects: NL66705.058.18; Clinicaltrials.gov: NCT04465032.}, } @article {pmid40754032, year = {2025}, author = {Liu, X and Zhao, J and Liu, J and Deng, W and Yan, L and Huang, Y and Zhang, L and Liu, Z and Cui, M and Xiao, H and Liu, X}, title = {Ganoderma lucidum sporoderm-broken spore powder alleviates kidney aging by modulating gut microbiota.}, journal = {Journal of ethnopharmacology}, volume = {353}, number = {Pt A}, pages = {120344}, doi = {10.1016/j.jep.2025.120344}, pmid = {40754032}, issn = {1872-7573}, abstract = {Ganoderma lucidum (G. lucidum), a revered medicinal mushroom in traditional Chinese medicine (TCM), has been historically documented for its anti-aging properties and nephroprotective effects. Nevertheless, its mechanism of action through gut microbiota modulation to attenuate renal and systemic aging remains incompletely understood.

AIM OF THE STUDY: To elucidate the gut microbiota-dependent anti-aging mechanisms of G. lucidum on renal and systemic senescence using integrative multi-omics approaches.

MATERIALS AND METHODS: We systematically evaluated the anti-aging efficacy of G. lucidum sporoderm-broken spore powder (Gl-SBSP) via the gut-kidney axis in naturally aged and radiation-induced premature senescence mouse models. Renal aging phenotypes were assessed using histopathological analyses (hematoxylin-eosin and Masson staining), immunofluorescence (IF), complete blood counts, enzyme-linked immunosorbent assay (ELISA), and quantitative real-time PCR (RT-qPCR). Gut microbiota involvement was confirmed via antibiotic-treated mice and fecal microbiota transplantation (FMT). Multi-omics integration of 16S rRNA sequencing and metabolomic profiling identified microbiota-derived metabolites, functionally validated in HK-2 cells and aged mice. Mechanistic pathways were elucidated via transcriptomic analysis.

RESULTS: Gl-SBSP attenuated kidney aging phenotypes in both natural aging and irradiation models. It selectively enriched Lachnospiraceae, whose metabolite nicotinamide riboside (NR) elevated renal NAD[+] levels (in vitro and in vivo), rejuvenated senescent kidneys, and improved renal function through steroid metabolism regulation.

CONCLUSION: Gl-SBSP counters renal aging through Lachnospiraceae-driven gut microbiota remodeling, where NR serves as the core rejuvenating metabolite. By activating NAD[+] biosynthesis and modulating steroid metabolism via the gut-kidney axis, this mechanism offers a novel therapeutic strategy against age-related renal decline and validates Ganoderma lucidum's ethnopharmacological relevance.}, } @article {pmid40754005, year = {2025}, author = {Hegazy, RA}, title = {Unraveling Liver Cirrhosis: Bridging Pathophysiology to Innovative Therapeutics.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.70037}, pmid = {40754005}, issn = {1440-1746}, abstract = {Liver cirrhosis is a complex and progressive condition resulting from sustained liver injury and chronic inflammation. Characterized by extensive fibrosis, disrupted liver architecture, and impaired function, cirrhosis represents the end stage of many chronic liver diseases. While traditionally considered irreversible, emerging evidence suggests that targeted interventions may modify disease progression, offering new hope for patients. This review explores the evolving understanding of liver cirrhosis, integrating insights into pathophysiology, systemic implications and innovative therapeutic approaches. At the core of cirrhosis development lies the activation of hepatic stellate cells (HSCs), driven by a cascade of pro-fibrotic signals, including transforming growth factor-beta (TGF-β) and Wnt/β-catenin pathways. Recent studies highlight the pivotal role of epigenetic regulation, mechanotransduction and cellular crosstalk in perpetuating fibrogenesis. Advances in single-cell transcriptomics and spatial biology are revealing unprecedented details of the cellular and molecular heterogeneity within cirrhotic tissue. Beyond the liver, cirrhosis exerts systemic effects, involving the gut-liver axis, vascular remodeling, and multi-organ dysfunction. The gut microbiome has emerged as a critical modulator, with dysbiosis and microbial translocation contributing to inflammation and disease progression. Therapeutic strategies targeting microbiome restoration, such as probiotics and fecal microbiota transplantation (FMT), are showing promise. Diagnostics are undergoing a paradigm shift with the advent of noninvasive tools, including elastography and liquid biopsy technologies. Circulating biomarkers, such as extracellular vesicles and noncoding RNAs, offer real-time insights into disease dynamics. On the therapeutic front, anti-fibrotic agents, senolytics, and regenerative approaches, such as stem cell therapy and liver organoids, are being explored. As artificial intelligence and computational modeling enhance predictive capabilities, a precision medicine approach to cirrhosis management is becoming feasible. This review highlights the need for interdisciplinary research to translate these advances into effective clinical solutions, bridging the gap between pathophysiology and innovative therapeutics.}, } @article {pmid40753182, year = {2025}, author = {Lan, Q and Liufu, S and Chen, B and Wang, K and Chen, W and Xiao, L and Liu, X and Yi, L and Liu, J and Xu, X and Liu, C and Liu, M and Yin, Y and Ma, H}, title = {Gut-resident Phascolarctobacterium succinatutens decreases fat accumulation via MYC-driven epigenetic regulation of arginine biosynthesis.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {150}, pmid = {40753182}, issn = {2055-5008}, support = {2023ZD04046//Biological Breeding-National Science and Technology Major Project/ ; U23A20229//National Natural Science Foundation of China/ ; U23A20229//National Natural Science Foundation of China/ ; 202305AF150211//Program of talent of science & technology and platforms of Yunnan Province/ ; 202305AF150211//Program of talent of science & technology and platforms of Yunnan Province/ ; 202202AE090032//Major Science and Technology Special Plan of Yunnan Province/ ; 202202AE090032//Major Science and Technology Special Plan of Yunnan Province/ ; 2021kjc-js072//Breeding of Lancang Black Pigs and its application/ ; 2021kjc-js072//Breeding of Lancang Black Pigs and its application/ ; SNQYKJXT-01//Key technologies for the exploration of excellent genetic resources and their efficient farming and its application in Tibetan pigs/ ; SNQYKJXT-01//Key technologies for the exploration of excellent genetic resources and their efficient farming and its application in Tibetan pigs/ ; }, mesh = {Animals ; *Arginine/biosynthesis/blood ; Swine ; *Epigenesis, Genetic ; Mice ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; *Proto-Oncogene Proteins c-myc/genetics/metabolism ; *Clostridiales ; }, abstract = {Uncovering the mechanisms of excessive fat accumulation in livestock can not only protect animal health but also maintain the revenue of the intensive feeding industry. In this study, a bacteria-wide association study was conducted in a cohort of 129 commercial Yorkshire pigs. We found that Phascolarctobacterium succinatutens (P. succinatutens) was a key bacterium with greater abundance in low backfat thickness (LBF) pigs and was positively correlated with serum arginine concentrations. Fecal microbiota transplantation (FMT) experiment verified the beneficial roles of P. succinatutens in intestinal and lipid homeostasis. Administration of P. succinatutens in mice curbed weight gain, reduced adipocyte size, attenuated gut inflammation aggravation, and elevated circulating arginine levels. Propionate, a main metabolite produced by P. succinatutens, played a significant role in the above effects. Mechanistically, we indicated that P. succinatutens-generated propionate alleviated colonic inflammation by inhibiting the TLR4 signaling cascade. Importantly, propionate was found to stimulate the de novo synthesis of arginine by inhibiting the chromatin accessibility of MYC near the intron region. Finally, we found that the increase of arginine induced by P. succinatutens reduced fat deposition by suppressing the PI3K/Akt/FOXO3a signaling pathway. Our work provides novel insights into the epigenetic regulation of probiotic-mediated anti-obesity effects and highlights the potential of P. succinatutens in combating excessive obesity in commercial pigs.}, } @article {pmid40752199, year = {2025}, author = {Zhou, X and You, Y and Ren, L and Akhtar, M and Ji, H and Wang, T and Meng, N and Fan, X and Yang, S and Zhou, Z and Xiao, Y and Shi, D}, title = {Lactobacillus gallinarum improves broiler performance by enhancing antioxidant capacity and regulating intestinal microbiota.}, journal = {Poultry science}, volume = {104}, number = {10}, pages = {105537}, pmid = {40752199}, issn = {1525-3171}, abstract = {The predominant objective in large-scale poultry farming has consistently been to enhance broiler. In this context, the supplementing of probiotics, specifically Lactobacilli, has emerged as a promising strategy to improve production efficiency. Numerous studies have demonstrated that Lactobacilli could modulate intestinal microbiota. To identify effective growth-promoting Lactobacilli, the present study replicated the "high body weight" phenotype of broiler chickens through fecal microbiota transplantation (FMT) and subsequently isolated target strains from FMT recipients exhibiting high body weight. The results demonstrated that Lactobacillus gallinarum CD-13 (CD-13) produced protease and exhibited inhibitory (P < 0.05) effects against pathogenic Gram-positive and Gram-negative bacteria. In vivo experimentation revealed that an average daily gain of broilers in the CD-13 group was increased by 17.72 %, along with enhanced (P < 0.05) duodenal villus height in the CD-13 group compared to the control group (Ctrl). Furthermore, the antioxidant capacity of broilers was improved, as evidenced by elevated levels of catalase (CAT) (P < 0.05) and glutathione peroxidase (GSH-Px) (P < 0.05) in the serum, while the level of malondialdehyde (MDA) was reduced (P < 0.05). 16S rRNA analysis revealed, the CD-13 group exhibited an increase (P < 0.05) in the diversity index of the intestinal microbiota, an elevated Bacteroidota/Firmicutes ratio, and the relative abundance of Bacteroides, whereas a decrease in the relative (P < 0.05) abundance of Alistipes compared with the Ctrl group. In conclusion, CD-13 demonstrated the capacity to enhance broiler growth performance through modulation of the intestinal microbiota and improvement of antioxidant capacity, thereby reducing of intestinal inflammation. The findings of this investigation substantiated the probiotic properties of CD-13 and provided a theoretical foundation for its potential application as a probiotic additive in the poultry industry.}, } @article {pmid40751371, year = {2025}, author = {El-Salhy, M and Valeur, J and Brønstad, I and Gilja, OH and Hatlebakk, JG}, title = {Possible Role of Butyric Acid in Long-Term Symptom Relief in Irritable Bowel Syndrome Patients Following Fecal Microbiota Transplantation.}, journal = {Neurogastroenterology and motility}, volume = {}, number = {}, pages = {e70115}, doi = {10.1111/nmo.70115}, pmid = {40751371}, issn = {1365-2982}, support = {//Helse Vest/ ; }, abstract = {BACKGROUND: We previously found that the fecal levels of short-chain fatty acids (SCFAs) changed in irritable bowel syndrome (IBS) patients at 1 month and 1 year after fecal microbiota transplantation (FMT). This study analyzed SCFAs at 2 and 3 years after FMT in the same IBS patients included in those previous studies.

METHODS: This study randomized 113 IBS patients into placebo, 30-g, and 60-g groups, who received FMT with 30 g of their own feces and with 30 g and 60 g of the donor's feces, respectively. The patients completed four questionnaires to assess IBS symptoms, fatigue, and quality of life, and supplied fecal samples at the baseline and at 2 and 3 years after FMT. The fecal SCFA levels were measured using gas chromatography.

RESULTS: The butyric acid level was significantly increased at 2 and 3 years after FMT in the 30-g and 60-g groups, and was significantly higher than that in the placebo group. The total SCFA and acetic acid levels decreased significantly in the 30-g and 60-g groups at 2 and 3 years after FMT, while the propionic acid level decreased in the 60-g group at both time points. The butyric acid level was inversely correlated with IBS symptoms and fatigue.

CONCLUSION AND INFERENCES: The increased butyric acid levels in IBS patients at 2 and 3 years after FMT and their inverse correlation with both IBS symptoms and fatigue suggest that butyric acid contributes to the long-term improvement seen after FMT (www.

CLINICALTRIALS: gov: NCT03822299).}, } @article {pmid40750814, year = {2025}, author = {Wan, M and Li, Q and Xiao, Y and Zhou, D and Lei, Q and Wang, S}, title = {Gut microbiota from Mori fructus (Morus alba L.) polyphenols and polysaccharides-dosed mice activates the PPARα/PGC-1α signaling pathway to mitigate HFD-induced metabolic syndrome in mice.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {28137}, pmid = {40750814}, issn = {2045-2322}, support = {2020YFS0031//the Sichuan Province Science and Technology Support Program/ ; 21JR11RM044//the Science and Technology Planning Project of Gansu Province/ ; 2024QB-120//the Gansu Provincial University Young Doctoral Support Project/ ; XYBYZK2310//the Ph.D. Foundation Program of Long Dong University/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Metabolic Syndrome/metabolism/etiology ; *Polyphenols/pharmacology ; *Morus/chemistry ; Mice ; Signal Transduction/drug effects ; *Polysaccharides/pharmacology/administration & dosage ; *Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism ; Diet, High-Fat/adverse effects ; *PPAR alpha/metabolism ; Male ; Fecal Microbiota Transplantation ; Plant Extracts/pharmacology ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {Mori Fructus, rich in polysaccharides and polyphenols, has long been used in East Asia as a functional food and medicinal agent. In traditional Chinese medicine, it is used to treat various ailments like wasting-thirst syndrome and constipation. Studies suggest its extract fractions may alleviate metabolic syndrome symptoms by affecting gut microbiota. To explore this, fecal microbiota transplantation (FMT) was used in an experiment. Pseudo-germ-free mice were created with antibiotics and given a high-fat, high-sugar diet (HFD) to induce metabolic syndrome. Then, fecal bacterial infusions were transplanted. Results showed significant improvement in metabolic syndrome parameters in the FMT-MFPS(fecal microbiota transplantation-Mori Fructus polyphenols plus polysaccharides) group. Dyslipidemia, liver, and kidney injuries were modulated in treated mice. The PPARα/PGC-1α signaling pathway was activated. These findings indicate Mori Fructus extract fractions prevent metabolic syndrome via gut microbiota modulation, with effects sustained through FMT, providing a reference for prevention.}, } @article {pmid40750041, year = {2025}, author = {Kenneth, MJ and Chen, JS and Fang, CY and Tsai, HC and Wu, CC and Hsu, TK and Chen, CC and Hsu, BM}, title = {Exploring the therapeutic potential of Bacteriophage-mediated modulation of Gut microbiota towards Colorectal Cancer.}, journal = {International journal of antimicrobial agents}, volume = {}, number = {}, pages = {107585}, doi = {10.1016/j.ijantimicag.2025.107585}, pmid = {40750041}, issn = {1872-7913}, abstract = {The rising incidence of colorectal cancer (CRC), particularly among young individuals, necessitates urgent preventive and therapeutic strategies to reduce mortality and financial burdens associated with CRC treatment. According to studies, gut dysbiosis is associated with CRC, indicating that restoration to a healthy gut microbiota can improve CRC outcomes. Conventional antibiotics can rapidly eliminate CRC-associated gut microbiota, however, their lack of taxonomic precision results in non-selective elimination of both pro-tumoral and antineoplastic bacteria. In this review, we explore the potential of phage therapy to specifically target and eliminate CRC-associated bacteria, thereby mitigating their role in CRC pathogenesis. Tailored phage therapy, including phage cocktails and Fecal Microbial Transplantation (FMT), has shown promise in treating various diseases. As the efficacy of FMT is met with safety concerns, we highlight in this review how fecal viral transplantation (FVT) offers a safer alternative by using filtered fecal samples devoid of intact bacteria that would cause adverse effects. As a relatively new field with complex host-phage interactions, FVT requires further research to fully understand its potential and safety profile. Despite its potential for modulating the gut microbiota and improving CRC treatment, phage therapy still requires more clinical studies and experimental evidence to further establish its efficacy and safety in CRC patients.}, } @article {pmid40749821, year = {2025}, author = {Tian, Y and Jin, W and Jin, X and Wang, Y and Wu, R and Yu, R and Jiang, J and Zhu, M}, title = {Fecal microbiota transplantation promotes hair growth through gut microbiome and metabolic regulation.}, journal = {Life sciences}, volume = {379}, number = {}, pages = {123887}, doi = {10.1016/j.lfs.2025.123887}, pmid = {40749821}, issn = {1879-0631}, abstract = {BACKGROUND: Gut microbiota plays a role in the etiology of a number of skin illnesses. In this study, we aimed to determine the relationship between intestinal flora (and related metabolites) and Androgenetic Alopecia (AGA).

METHODS: Mendelian randomization (MR) analysis was used to explore the causal relationship between gut microbiota and AGA. Gut microbiota was detected by fecal 16S rRNA sequencing, and fecal metabolites were analyzed by non-targeted metabolomics. Senescence and inflammation levels in the colon and hair follicles of mice were detected by β-galactosidase assay kits and other staining methods. Hair growth was assessed by dermoscopy and hair growth scoring.

RESULTS: Mendelian randomization analysis revealed a significant correlation between Lactobacillaceae (OR = 0.981, 95 % CI: 0.969-0.992, p = 0.001) and Lactobacillus (OR = 0.985, 95 % CI: 0.973-0.997, p = 0.018) with AGA. A similar reduction in Lactobacillaceae and Lactobacillus was observed in the feces of AGA mice (p < 0.05). Fecal microbiota transplantation (FMT) increased Lactobacillaceae and Lactobacillus levels (p < 0.05), and Lactobacillus rhamnosus GG (LGG) reversed aging and inflammation in the gut and hair follicles, promoting hair growth.

CONCLUSION: There is an intestinal-skin axis regulation pattern in the pathological process of AGA, and the aging of intestinal tissues and the alteration of bacterial flora and related metabolites can affect hair follicle aging and inflammation.}, } @article {pmid40747461, year = {2025}, author = {Zhu, Z and Zhu, Y and Sun, Q and Xue, J and Xie, M and Yu, Y and Wang, B and Shangguan, W and Feng, Z and Wu, P}, title = {Pentosan polysulfate alleviates interstitial cystitis/bladder pain syndrome by modulating bile acid metabolism and activating the TGR5 receptor through gut microbiota regulation.}, journal = {Bladder (San Francisco, Calif.)}, volume = {12}, number = {2}, pages = {e21200036}, pmid = {40747461}, issn = {2327-2120}, abstract = {BACKGROUND: The disrupted gut microbiome has been found to be implicated in the development of interstitial cystitis/bladder pain syndrome (IC/BPS). Pentosan polysulfate (PPS) is an oral medication used for treating IC/BPS, acting as both an anti-inflammatory agent and a bladder barrier protector. However, the precise mechanisms by which the PPS-mediated modulation of the gut microbiome alleviates IC/BPS are not fully understood.

OBJECTIVE: This study aimed to identify the key gut microbiota species and metabolites involved in PPS's protective effects against IC/BPS.

METHODS: We employed a multifaceted approach, including 16S rDNA gene sequencing, antibiotic treatment, and fecal microbiota transplantation, to validate the dependency of PPS's protective effects on the gut microbiome. Furthermore, we performed a comprehensive metabolomic profiling using non-targeted metabolomics and liquid chromatography-tandem mass spectrometry.

RESULTS: PPS significantly elevated the abundance of the xylan-degrading bacteria, Eubacterium xylanophilum group, which, through its interaction with the gut microbiome, markedly reduced inflammation and barrier damage induced by cyclophosphamide in IC/BPS. In addition, PPS significantly increased the level of ursodeoxycholic acid (UDCA), a secondary bile acid, demonstrating a strong correlation with the abundance of the E. xylanophilum group. Ex vivo supplementation with UDCA mitigated lipopolysaccharide-induced inflammation and barrier disruption in SV-HUC-1 cells by activating the TGR5 receptor.

CONCLUSION: PPS exerts its protective effects against IC/BPS by modulating the gut microbiome and its metabolites.}, } @article {pmid40747222, year = {2025}, author = {Pamungkas, KMN and Lesmana Dewi, PIS and Alamsyah, AZ and Dewi, NLPY and Dewi, NNGK and Mariadi, IK and Sindhughosa, DA}, title = {Microbiome dysbiosis and immune checkpoint inhibitors: Dual targets in Hepatocellular carcinoma management.}, journal = {World journal of hepatology}, volume = {17}, number = {7}, pages = {106810}, pmid = {40747222}, issn = {1948-5182}, abstract = {Hepatocellular carcinoma (HCC), a primary malignancy of the liver and leading cause of cancer-related mortality worldwide, poses substantial therapeutic challenges, particularly in advanced and unresectable stages. Immune checkpoint inhibitors (ICIs) have emerged as critical therapeutic agents, targeting immune checkpoint pathways to restore antitumor immune responses. Combinations such as atezolizumab (anti-programmed cell death ligand 1 with bevacizumab (anti-vascular endothelial growth factor), as well as antibodies directed against cytotoxic T-lymphocyte associated protein 4 and programmed cell death protein 1 (e.g., ipilimumab and nivolumab), have demonstrated improved clinical outcome in selected patients. However, the overall efficacy of ICIs remains hindered by variable response rate and primary or acquired resistance. Recent evidence suggests that the gut microbiome plays a pivotal role in modulating host immune responses and may significantly influence the therapeutic efficacy of ICIs. Dysbiosis within the gut-liver axis has been implicated not only in pathogenesis and progression of HCC but also diminishing immunotherapy effectiveness. Emerging studies highlight the potential of microbiome-targeted interventions including dietary modulation, prebiotics, probiotics, and fecal microbiota transplantation to enhance ICIs responsiveness. This review explores the evolving interplay between the gut microbiota and immunotherapy in HCC, with a focus on microbiome-based strategies aimed at optimizing clinical outcomes.}, } @article {pmid40745657, year = {2025}, author = {Hu, J and Chen, H and Zhu, L and Tong, Y and Cheng, C and Yan, G and Shen, H}, title = {Baitouweng decoction modulates gut microbial production of indole-3-propionic acid and epithelial necroptosis to alleviate DSS-induced colitis in mice.}, journal = {Chinese medicine}, volume = {20}, number = {1}, pages = {119}, pmid = {40745657}, issn = {1749-8546}, support = {82205023//The National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Ulcerative colitis (UC) is a kind of inflammatory disorder structuring in the colon. Baitouweng decoction (BD) derived from Treatise on Cold Damage (Shang-Han-Lun in Chinese) has been used for the treatment of UC in clinical practice for more than 2000 years. However, the clear mechanism of BD is still unknown. Our previous study revealed the regulation of BD on gut microbiota in colitis mice. This study aimed to investigate the crosstalk between intestinal flora and host immunity in the therapeutic effect of BD on colitis.

METHODS: The model of colitis in mice was established using dextran sulfate sodium in drinking water, and the treatment group received BD, 5-ASA, or indole-3-propionic acid (IPA). The disease symptoms were documented, and assessments were conducted on both local and systemic inflammation as well as intestinal barrier function. The gut microbiota structure was analyzed using 16S ribosomal RNA sequencing. The metabolomic assay was performed using ultra-high performance liquid chromatography and quadrupole time-of-flight mass spectrometry, and RNA-sequencing was used to explore the mechanism of IPA on colitis treatment.

RESULTS: BD could improve colitis mice's colonic injury and rebalance the gut microbiota dysbiosis. Fecal microbiota transplantation experiments confirmed that the therapeutic effects of BD depend on the intestinal flora, while antibiotic treatment abrogated the effect of BD. The concentration of IPA, a microbial tryptophan metabolite, was upregulated after BD-treated. IPA was further evaluated for its effect on the development of colitis and it was identified as an inhibitor of necroptosis of intestinal epithelial cells.

CONCLUSIONS: Our findings suggest that BD could alleviate colitis by regulating the gut microbiota-metabolism homeostasis to inhibit the necroptosis of intestinal epithelial cells.}, } @article {pmid40743285, year = {2025}, author = {Herman, C and Bolyen, E and Simard, A and Gehret, L and Caporaso, JG}, title = {Assessing microbiome engraftment extent following fecal microbiota transplant with q2-fmt.}, journal = {PLoS computational biology}, volume = {21}, number = {7}, pages = {e1013299}, pmid = {40743285}, issn = {1553-7358}, support = {U24 CA248454/CA/NCI NIH HHS/United States ; }, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; Computational Biology/methods ; *Gastrointestinal Microbiome ; Feces/microbiology ; *Microbiota ; Software ; }, abstract = {We present q2-fmt, a QIIME 2 plugin that provides diverse methods for assessing the extent of microbiome engraftment following fecal microbiota transplant. The methods implemented here were informed by a recent literature review on approaches for assessing FMT engraftment, and cover aspects of engraftment including Community Coalescence, Indicator Features, and Resilience. q2-fmt is free for all use, and detailed documentation illustrating worked examples on a real-world data set are provided in the project's documentation.}, } @article {pmid40742160, year = {2025}, author = {Bo, T and Song, G and Zhang, M and Xu, X and Duan, J and She, H and Fang, Y and Li, W and Wen, J and Liu, J and Wang, D and Lei, F}, title = {Gut microbiota contribute to high-altitude adaptation in tree sparrows.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0063025}, doi = {10.1128/msystems.00630-25}, pmid = {40742160}, issn = {2379-5077}, abstract = {UNLABELLED: The intricate relationship between gut microbiota and various physiological functions in animals has emerged as a focal point in understanding host adaptability. Unlike the native birds of the Qinghai-Tibet Plateau (QTP), the tree sparrow (Passer montanus) is believed to have colonized the plateau within the last few thousand years. Given the vast expanse and harsh conditions of the plateau, the role of gut microbiota in facilitating the tree sparrow's adaptation to this high-altitude habitat remains largely unexplored and holds significant scientific interest. Therefore, we employed a multidisciplinary approach combining amplicon sequencing, transcriptome analysis, and fecal microbiota transplantation (FMT) to investigate the functional role of gut microbiota in high-altitude tree sparrows across different seasons. Results indicate that the gut microbiota of tree sparrows exhibits seasonal and altitude-dependent changes, with an increase in Lactobacillus in winter, which may promote heat production to cope with the cold. FMT experiments confirmed that "high-altitude gut microbiota" enhances the expression of heat-related proteins (avUCP) and upregulates heat-related genes syt1 and chodl. These findings suggest an adaptive strategy whereby tree sparrows utilize their gut microbiota to modulate energy metabolism, ultimately conserving energy in the resource-limited high-altitude environment.

IMPORTANCE: This study provides one evidence that gut microbiota mediates high-altitude adaptation in tree sparrow. By integrating multi-omics and fecal transplantation in tree sparrows (Passer montanus)-a species invading the Qinghai-Tibet Plateau within millennia-we reveal seasonally dynamic microbial strategies critical for survival in extreme environments. These findings establish gut microbiota as a key driver of rapid altitudinal adaptation, offering new insights into how microbial functions enable vertebrate range expansion into challenging ecosystems. The mechanistic framework also informs conservation strategies for wildlife facing climate-driven habitat shifts.}, } @article {pmid40741477, year = {2025}, author = {Ma, L and Zhang, MH and Xu, YF and Hao, YX and Niu, XX and Li, Y and Xing, HC}, title = {Fecal microbiota transplantation: A promising treatment strategy for chronic liver disease.}, journal = {World journal of gastroenterology}, volume = {31}, number = {28}, pages = {105089}, pmid = {40741477}, issn = {2219-2840}, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects/methods ; *Gastrointestinal Microbiome ; Treatment Outcome ; Animals ; *Dysbiosis/therapy/microbiology ; *Liver Diseases/therapy/microbiology ; Liver/pathology/microbiology ; Chronic Disease ; Clinical Trials as Topic ; }, abstract = {Chronic liver disease has become a global health crisis, with increasing incidence and mortality rates placing a substantial burden on healthcare systems worldwide. A key factor in the progression of chronic liver disease is intestinal microbiota dysbiosis, which influences liver function via the intricate liver-gut axis. This axis plays a central role in various physiological processes, and disruptions in microbial composition can exacerbate liver pathology. Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic strategy, with the potential to restore the composition and metabolic functions of the intestinal microbiota. Supported by encouraging findings from clinical trials and animal studies, FMT has demonstrated therapeutic benefits, including improvements in clinical symptoms, objective indicators, and long-term prognosis. These benefits encompass reductions in hepatic lipid deposition and inflammation, mitigation of complications in advanced liver disease, promotion of hepatitis B e antigen seroconversion, and enhancement of cognitive function. Although clinical evidence remains preliminary, current data underscore the transformative potential of FMT in managing chronic liver diseases. Nonetheless, challenges persist, including the need for standardized procedures, variability among donors, potential risks, and concerns regarding long-term safety. This review provides a comprehensive evaluation of the current literature on the efficacy and safety of FMT, while exploring future research directions to expand its application in liver disease management.}, } @article {pmid40741168, year = {2025}, author = {Gu, C and Du, H and Li, N and Zhou, Y and Li, S and Sun, Y and Han, Y and Xu, X and Li, X}, title = {The gut-bone axis in osteoporosis: a multifaceted interaction with implications for bone health.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1569152}, pmid = {40741168}, issn = {1664-2392}, mesh = {Humans ; *Osteoporosis/metabolism/microbiology ; *Gastrointestinal Microbiome/physiology ; *Bone and Bones/metabolism ; Animals ; }, abstract = {With the accelerated aging of the population, degenerative orthopedic diseases, particularly osteoporosis, have become a major public health challenge, threatening bone health and affecting the quality of life. Existing anti-osteoporosis regimens remain rather unitary or poorly adhered, which also limits the maintenance of bone health to some extent. Given the increasingly elucidated prominence of gut-related factors in osteoblasts/osteoclasts and bone formation/metabolism/maintenance, focusing on intestinal microecology and then targeting the distal bone tissue via the gut-bone axis have been recognized as a feasible intervention strategy. This review systematically summarized the interaction of the gut-bone axis while highlighting the physicochemical barriers formed by intestinal intrinsic structures, the gut microbiota, and related molecules for bone health maintenance through the immune and endocrine pathways. Meanwhile, we emphasized the ideal anti-osteoporotic property and individual achievability of methods like fecal microbiota transplantation, probiotic and prebiotic supplementation, and dietary pattern modification. The conceptual framework of the gut-bone axis plus X was innovatively proposed, given the potential synergy among different organs in disease characterization and pathogenesis, which may help better explain the etiology and manage other co-morbidities concurrent with or secondary to osteoporosis. Since the intersection of orthopedics with other subjects, we also supported the application of nano-biomaterials, bacterial synthetic biology, and novel small molecules in anti-osteoporosis, which is expected to unlock broader prospects for the multidisciplinary integration of the gut-bone axis.}, } @article {pmid40739711, year = {2025}, author = {Xu, Y and Zhu, Y and Wu, X and Peng, W and Zhong, Y and Cai, Y and Chen, W and Liu, L and Tan, B and Chen, T}, title = {Gut Microbiota-Derived Acetate Ameliorates Endometriosis via JAK1/STAT3-Mediated M1 Macrophage Polarisation.}, journal = {Microbial biotechnology}, volume = {18}, number = {8}, pages = {e70202}, pmid = {40739711}, issn = {1751-7915}, support = {8216140922//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Female ; *Endometriosis/therapy/microbiology/metabolism ; Mice ; Humans ; Fecal Microbiota Transplantation ; *STAT3 Transcription Factor/metabolism ; *Janus Kinase 1/metabolism ; *Macrophages/metabolism/immunology ; Disease Models, Animal ; *Acetates/metabolism ; Signal Transduction ; Feces/microbiology/chemistry ; }, abstract = {Endometriosis (EMs) is a common inflammatory disorder in women of reproductive age, severely impacting patients' quality of life and fertility. Current hormonal therapies offer limited efficacy, and surgical interventions often fail to prevent recurrence. Recent studies suggest a close association between gut microbiota and the pathophysiology of EMs, though the precise mechanisms remain unclear. To investigate the influence of gut microbiota on EMs, this study established an EMs mouse model and performed faecal microbiota transplantation (FMT) using samples from healthy donors (AH group) and EMs patients (AE group) into the model mice. Results demonstrated that compared to the model group (M group), FMT from healthy donors (AH group) significantly reduced ectopic lesion volume (658.3 ± 116.1 vs. 167.2 ± 112.8 mm[3], p < 0.01) and weight (0.7420 ± 0.1233 vs. 0.1885 ± 0.1239 mg, p < 0.01). Conversely, FMT from EMs patients exacerbated disease progression. Mechanistic studies revealed that healthy donor FMT attenuated EMs by remodelling the gut microbial composition (enhancing α-diversity and Lactobacillus abundance while suppressing Bacteroidetes), significantly elevating acetate levels in faeces and ectopic lesions, activating the JAK1/STAT3 signalling pathway within lesions, and thereby driving macrophage polarisation toward the M1 phenotype (by increased iNOS/CD86 expression and decreased Arg1/CD206 expression). Simultaneously, healthy donor FMT enhanced intestinal barrier integrity by upregulating tight junction proteins (ZO-1, Occludin, Claudin-1/5) and reducing levels of intestinal permeability markers (DAO, IFABP). In contrast, AE group FMT disrupted gut microbial ecology, reduced acetate production, failed to activate the JAK1/STAT3 pathway, promoted M2 macrophage polarisation and impaired intestinal barrier function. Collectively, this study elucidates for the first time that acetate, as a key gut microbiota metabolite, exerts anti-EMs effects by activating the JAK1/STAT3 signalling pathway to drive macrophage reprogramming toward the M1 phenotype, thereby positioning gut microbiota reconstruction as a novel therapeutic strategy for endometriosis.}, } @article {pmid40739580, year = {2025}, author = {Song, J and Zhang, W and Wang, D}, title = {Gut microbiome in gastrointestinal neoplasms: from mechanisms to precision therapeutic strategies.}, journal = {Gut pathogens}, volume = {17}, number = {1}, pages = {57}, pmid = {40739580}, issn = {1757-4749}, abstract = {BACKGROUND: The incidence of Gastrointestinal Neoplasms (GI neoplasms) continues to increase globally. Colorectal cancer (CRC), in particular, has emerged as the second leading cause of cancer-related mortality worldwide. Now, Specific pathogenic bacteria, such as Fusobacterium nucleatum (F. nucleatum) and Helicobacter pylori (H. pylori), critically promote tumorigenesis through multiple mechanisms, including the induction of genotoxic damage, host metabolic reprogramming, and remodeling of the tumor immune microenvironment. Notably, a dysbiotic Gut Microbiome (GM) state significantly compromises patient response rates to cancer therapeutics. This review aims to systematically analyze the core molecular mechanism of GM affecting tumor development and explore the precise intervention strategies guided by clinical translation.

METHODS: This systematic review adhered to the PRISMA-2020 guidelines. We conducted a comprehensive literature search in PubMed (2008-2025) using key terms including "Gut Microbiome", "Gastrointestinal Neoplasms", "Fecal Microbiota Transplantation (FMT)", "immunotherapy resistance", "precision-based interventions", and "emerging research frontiers". Preclinical and clinical studies investigating the mechanisms, diagnostic applications, and therapeutic interventions of the GM in GI neoplasms were included.

RESULTS: This review systematically elucidates the tripartite mechanisms by which the GM influences the initiation and progression of GI neoplasms. And we innovatively proposed the "Proinflammation-metabolism-Immune framework (Dysbiosis of the GM jointly leads to the occurrence, development and metastasis of GI neoplasms by driving three interrelated processes: chronic inflammation (Proinflammation), reshaping the Metabolism of the host and TME(Metabolism), and inhibiting or altering the host Immune surveillance (Immune))" To deepen the understanding of host-microbe interactions. Based on this framework, we focused on discussing the therapeutic strategy targeting GM and confirmed its significant impact on the efficacy of anti-cancer treatment. Although these strategies have demonstrated clinical potential, current research is still mainly confined to preclinical models and the early clinical trial stage. To address this, we outline future directions: Integrating emerging technologies like multi-omics and artificial intelligence will enable dynamic monitoring and real-time modulation of microbial activity. This integration aims to establish a novel paradigm for microbiome-based personalized precision medicine.

DISCUSSION: This review systematically clarifies that GM is a key target for optimizing the treatment of GI neoplasms. Future research should integrate multi-omics and AI technologies for dynamic microbial monitoring and modulation, paving the way for microbiome-based precision medicine. Overcoming challenges in standardization and clinical translation is essential.}, } @article {pmid40737908, year = {2025}, author = {An, K and Yan, D and Lv, X and Liu, Y and Xia, Z}, title = {T-2 toxin induces gut and liver injury through triggering gut microbiota dysbiosis.}, journal = {Poultry science}, volume = {104}, number = {10}, pages = {105577}, pmid = {40737908}, issn = {1525-3171}, abstract = {T-2 toxin (T-2), a foodborne mycotoxin, causes gut and liver injury in organisms. However, its effects on intestine in ducks and the mediating role of gut microbiota in pathogenesis remain unclear. This study investigated the involvement of gut microbiota in T-2-induced enterotoxicity and hepatotoxicity in ducks. Thirty 1-day-old ducklings were divided into control (CON) and T-2-exposed (400 μg/kg BW/day via oral gavage) groups for two weeks. Alterations in gut microbiota composition and barrier function were assessed. To further elucidate the role of microbiota, antibiotics mixture (ABX) treatment and fecal microbiota transplantation (FMT) were employed. Results revealed that T-2 exposure induced ileal dysbiosis characterized by increased relative abundance of Firmicutes, Candidatus Arthromitus, and Lactococcus, decreased Corynebacterium abundance with diminished α-diversity. For gut physical barrier function, ileal villi heights and mRNA levels of mucin2, Occludin, zonula occludens-1 were significantly downregulated by T-2, and serum concentration of lipopolysaccharide was increased. Notably, ABX treatment prevented T-2-induced gut barrier disruption, completely suppressed hepatic inflammation via toll-like receptor 4 (TLR4) pathway inhibition. Hepatic lipid accumulation induced by T-2 was significantly attenuated by ABX treatment. Furthermore, FMT confirmed the essential role of T-2-altered microbiota in recapitulating pathological features including intestinal leakage, hepatic inflammation and steatosis, and upregulated TLR4 pathway and lipid metabolism genes (angiopoietin-like 4, carnitine palmitoyltransferase 1B, perilipin 1) expression. These findings establish gut microbiota as a critical mediator in T-2-induced multiorgan toxicity, providing new insights into the potential therapeutic strategies.}, } @article {pmid40736248, year = {2025}, author = {Huang, X and Wu, R and Liang, X and Yu, Z and Qin, P and Wang, Z and Guo, P and Zeng, Y and Yan, Z and Xiao, W and Ma, Y}, title = {Streptococcus salivarius-derived ilexgenin A alleviates pneumonia through the gut-lung axis.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0073125}, doi = {10.1128/msystems.00731-25}, pmid = {40736248}, issn = {2379-5077}, abstract = {The alteration of gut microbiota during critical illness is associated with adverse clinical outcomes. This connection between intestinal dysbiosis and poor outcomes has prompted the idea that restoring healthy microbial communities could offer a novel approach to life-support treatment for patients with severe pneumonia. In this study, using 16S rRNA sequencing and fecal microbiota transplantation (FMT), we demonstrated that alterations in intestinal microbiota structure during pneumonia exacerbate disease outcomes. A notable feature of these alterations is the reduction in the relative levels of Streptococcus salivarius (S. salivarius). In combination with metabolomics analysis, we found that the administration of S. salivarius increased the level of ilexgenin A (IA) in mice, which enhances the resistance of mice to Pseudomonas aeruginosa (P. aeruginosa)-induced pneumonia. Mechanistically, IA regulates lipopolysaccharide-induced overexpression of macrophage inflammation through Toll-like receptor 4 (TLR4)-mediated NF-κB and MAPK signaling pathways. Our findings reveal the role of the microbial-immune axis in pneumonia, highlighting the potential of S. salivarius and IA in providing promising treatment strategies for pneumonia.IMPORTANCEOne of the major challenges faced by the clinical microbiome research community is to convert the connections between dysbiosis and negative clinical outcomes into rationalized and targeted therapeutic interventions. In the present work, 30 fecal samples from pneumonia and non-pneumonia patients were subjected to FMT and 16S rRNA analysis. The results revealed that a characteristic feature of gut microbiota dysbiosis in pneumonia hosts is the reduction of S. salivarius. Supplementation with S. salivarius can effectively enhance the resistance of mice to P. aeruginosa pneumonia. Moreover, we confirmed the anti-inflammatory effects of IA derived from S. salivarius both in vivo and in vitro. Thus, these findings enhance our understanding of how gut microbiota influences the outcomes of pneumonia and underscore the potential of S. salivarius as a precision microbial therapeutic for combating pneumonia.}, } @article {pmid40735439, year = {2025}, author = {Wang, Q and Han, Y and Pang, L and Zhou, Z and Dai, L}, title = {Gut microbiome remodeling in chronic kidney disease: implications of kidney replacement therapies and therapeutic interventions.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1620247}, pmid = {40735439}, issn = {2296-858X}, abstract = {The escalating global burden of end-stage renal disease (ESRD), driven by aging populations and rising metabolic comorbidities, underscores the urgent need for innovative therapeutic strategies. Emerging evidence highlights the gut microbiome as a pivotal modulator of renal pathophysiology through the gut-kidney axis, with microbial dysbiosis exacerbating gut microbial metabolites (e.g., uremic toxins), systemic inflammation, and multi-organ damage. This narrative review explores the divergent impacts of kidney replacement therapies (KRT)-hemodialysis (HD) and peritoneal dialysis (PD)-on gut microbiota dynamics: HD is associated with Firmicutes and Proteobacteria enrichment, reduced butyrate-producing taxa (e.g., Faecalibacterium, Roseburia), and systemic microbial translocation; whereas PD-driven glucose absorption and iron supplementation foster pathogenic proliferation (e.g., Enterobacteriaceae) and impair short-chain fatty acid (SCFA) metabolism. Current interventions, including probiotics, prebiotics, plant-based diets (PBDs), and fecal microbiota transplantation (FMT), demonstrate potential in mitigating dysbiosis and uremic toxin accumulation. PBDs reduce inflammatory markers (IL-6, CRP) and lower all-cause mortality risk by 24% in PD patients; synbiotics (e.g., Lactobacillus casei + galactooligosaccharides) reduce serum p-cresyl sulfate by 20% in HD patients; and FMT increases levels of short-chain fatty acids (propionate, butyrate) and lowers trimethylamine N-oxide (TMAO) concentrations in streptozotocin-induced diabetic nephropathy mouse models. However, clinical translation remains challenged by small sample sizes, heterogeneous outcomes, and a lack of hard endpoints. Future research must prioritize standardized protocols, personalized microbial profiling, and synergistic integration of dietary and microbiome-targeted therapies. Bridging mechanistic insights with clinical validation will advance precision medicine in ESRD management, offering transformative potential for patients burdened by this therapeutic impasse.}, } @article {pmid40735351, year = {2025}, author = {Dean, EA and Roy, A and Lin, RY and Gharaibeh, RZ and Li, DM and Gauthier, J and Jobin, C and Wingard, JR}, title = {Gut Faecalibacterium abundance in patients with plasma cell disorders is associated with survival after autologous HSCT.}, journal = {Blood neoplasia}, volume = {2}, number = {3}, pages = {100114}, pmid = {40735351}, issn = {2950-3280}, abstract = {The gut microbiota (GM) has been linked to the development, progression, and response to therapy in plasma cell neoplasms (PCNs). The primary goal of this study was to investigate the relationship between the composition of the GM before and during autologous hematopoietic stem cell transplant (HSCT) with clinical outcomes of patients with PCNs. We focused on the genus Faecalibacterium, which includes the most abundant anaerobic commensal bacterium in the GM. Fecal samples were collected prospectively before, mid (at 1 week from the start of intervention), and end (at engraftment) of intervention (liberalized vs neutropenic diet) and subjected to 16S ribosomal DNA sequencing. Eighty-three patients were enrolled. Their median age was 64 (range, 31-79) years. Fifty-four patients received HSCT as part of frontline therapy and 29 for relapsed/refractory disease. With median follow-up time for survivors (n = 82) of 32 (range, 0.7-61) months, the median progression-free survival (PFS) was 40 months. Higher preintervention Faecalibacterium abundance was associated with improved PFS (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.86-0.99; P = .02). Faecalibacterium abundance was found to decrease early after transplant (P < .01). Although the administration of high-dose melphalan (200 mg/m[2]) was significantly associated with PFS in both univariable (HR, 0.38, 95% CI, 0.19-0.75; P = .006) and multivariable (HR, 0.42; 95% CI, 0.20-0.87; P = .02) analyses, preintervention Faecalibacterium abundance remained independently associated with PFS (HR, 0.93; 95% CI, 0.86-0.99; P = .04) on multivariable analysis. In conclusion, lower preintervention Faecalibacterium abundance was associated with inferior PFS.}, } @article {pmid40733607, year = {2025}, author = {Shrivastav, K and Nasser, H and Ikeda, T and Nema, V}, title = {Possible Crosstalk and Alterations in Gut Bacteriome and Virome in HIV-1 Infection and the Associated Comorbidities Related to Metabolic Disorder.}, journal = {Viruses}, volume = {17}, number = {7}, pages = {}, pmid = {40733607}, issn = {1999-4915}, mesh = {Humans ; *Gastrointestinal Microbiome ; *HIV Infections/virology/complications/microbiology ; *Virome ; *Metabolic Diseases/virology/microbiology ; Dysbiosis ; HIV-1 ; Comorbidity ; }, abstract = {Improved antiretroviral therapy (ART) has significantly increased the life expectancy of people living with HIV (PLWH). At the same time, other complications like metabolic syndrome (MetS) are coming up as new challenges to handle. This review aims to explore the emerging evidence of gut microbiome and virome alterations in human immunodeficiency virus-1 (HIV-1) infection and associated metabolic disorders, such as type-2 diabetes (T2DM) and cardiovascular disease (CVD), with a focus on their interplay, contribution to immune dysfunction, and potential as therapeutic targets. We conducted a comprehensive review of the current literature on gut bacteriome and virome changes in HIV-1-infected individuals and those with metabolic comorbidities emphasizing their complex interplay and potential as biomarkers or therapeutic targets. HIV-1 infection disrupts gut microbial homeostasis, promoting bacterial translocation, systemic inflammation, and metabolic dysregulation. Similarly, metabolic disorders are marked by reduced beneficial short-chain fatty acid-producing bacteria and an increase in pro-inflammatory taxa. Alterations in the gut virome, particularly involving bacteriophages, may exacerbate bacterial dysbiosis and immune dysfunction. Conversely, some viral populations have been associated with immune restoration post-ART. These findings point toward a dynamic and bidirectional relationship between the gut virome, bacteriome, and host immunity. Targeted interventions such as microbiome modulation and fecal virome transplantation (FVT) offer promising avenues for restoring gut homeostasis and improving long-term outcomes in PLWH.}, } @article {pmid40732941, year = {2025}, author = {Marano, G and Rossi, S and Sfratta, G and Acanfora, M and Anesini, MB and Traversi, G and Lisci, FM and Rinaldi, L and Pola, R and Gasbarrini, A and Sani, G and Gaetani, E and Mazza, M}, title = {Gut Microbiota in Women with Eating Disorders: A New Frontier in Pathophysiology and Treatment.}, journal = {Nutrients}, volume = {17}, number = {14}, pages = {}, pmid = {40732941}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Female ; *Feeding and Eating Disorders/microbiology/physiopathology/therapy ; Dysbiosis/microbiology/physiopathology/therapy ; Probiotics/therapeutic use ; Prebiotics/administration & dosage ; Fecal Microbiota Transplantation ; }, abstract = {Emerging evidence highlights the critical role of the gut microbiota in the development and progression of eating disorders (EDs), particularly in women, who are more frequently affected by these conditions. Women with anorexia nervosa, bulimia nervosa, and binge eating disorder exhibit distinct alterations in gut microbiota composition compared to healthy controls. These alterations, collectively termed dysbiosis, involve reduced microbial diversity and shifts in key bacterial populations responsible for regulating metabolism, inflammation, and gut-brain signaling. The gut microbiota is known to influence appetite regulation, mood, and stress responses-factors closely implicated in the pathogenesis of EDs. In women, hormonal fluctuations related to menstruation, pregnancy, and menopause may further modulate gut microbial profiles, potentially compounding vulnerabilities to disordered eating. Moreover, the restrictive eating patterns, purging behaviors, and altered dietary intake often observed in women with EDs exacerbate microbial imbalances, contributing to intestinal permeability, low-grade inflammation, and disturbances in neurotransmitter production. This evolving understanding suggests that microbiota-targeted therapies, such as probiotics, prebiotics, dietary modulation, and fecal microbiota transplantation (FMT), could complement conventional psychological and pharmacological treatments in women with EDs. Furthermore, precision nutrition and personalized microbiome-based interventions tailored to an individual's microbial and metabolic profile offer promising avenues for improving treatment efficacy, even though these approaches remain exploratory and their clinical applicability has yet to be fully validated. Future research should focus on sex-specific microbial signatures, causal mechanisms, and microbiota-based interventions to enhance personalized treatment for women struggling with eating disorders.}, } @article {pmid40732937, year = {2025}, author = {Zhang, G and Dou, Y and Xie, H and Pu, D and Wang, L and Wang, R and Han, X}, title = {Sea Cucumber Egg Oligopeptides Ameliorate Cognitive Impairments and Pathology of Alzheimer's Disease Through Regulating HDAC3 and BDNF/NT3 via the Microbiota-Gut-Brain Axis.}, journal = {Nutrients}, volume = {17}, number = {14}, pages = {}, pmid = {40732937}, issn = {2072-6643}, support = {DLUXK-2024-YB-006//Dalian University/ ; }, mesh = {Animals ; *Alzheimer Disease/pathology/metabolism ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Brain-Derived Neurotrophic Factor/metabolism ; *Cognitive Dysfunction/drug therapy ; *Histone Deacetylases/metabolism ; *Oligopeptides/pharmacology ; *Sea Cucumbers/chemistry ; Disease Models, Animal ; Brain/metabolism/pathology/drug effects ; Male ; Fecal Microbiota Transplantation ; Neuroprotective Agents/pharmacology ; Fatty Acids, Volatile/metabolism ; Mice, Inbred C57BL ; *Eggs ; *Brain-Gut Axis/drug effects ; Feces/microbiology ; }, abstract = {BACKGROUND: Oligopeptides from sea cucumber eggs (SCEPs) are rarely studied for their neuroprotective effects.

METHODS: Therefore, we prepared SCEPs via simulated gastrointestinal digestion and then administered them to an Alzheimer's disease (AD) mouse model via gavage. Behavior tests, gut-brain histopathology and fecal microbiota transplantation (FMT) experiments were conducted, and gut microbiota and metabolite short-chain fatty acids (SCFAs) were evaluated via 16sRNA gene sequencing and LC-MS.

RESULTS: The results showed that both the SCEP and FMT groups experienced improvements in the cognitive impairments of AD and showed reduced levels of Aβ, P-Tau, GFAP, and NFL in the brain, especially in the hippocampus. SCEP remodeled the gut microbiota, increasing the relative abundances of Turicibacter and Lactobacillus by 2.7- and 4.8-fold compared with the model at the genus level. In the SCEP and FMT treatments, four SCFA-producing bacteria obtained from gut microbiota profiling showed consistent trends, indicating that they may be involved in mediating the neuroprotective effects of SCEP. Mechanically, SCEP regulated the SCFA distribution in feces, blood, and the brain, greatly increased the content of SCFAs in the brain up to 2000 μg/mg, eased gut-brain barrier dysfunction, inhibited HDAC3 overexpression, and upregulated BDNF/NT3 levels.

CONCLUSIONS: This study provides a promising candidate for preventing AD and a reference for applying SCEP.}, } @article {pmid40732886, year = {2025}, author = {Dipalma, G and Marinelli, G and Ferrante, L and Di Noia, A and Carone, C and Colonna, V and Marotti, P and Inchingolo, F and Palermo, A and Tartaglia, GM and Del Fabbro, M and Inchingolo, AM and Inchingolo, AD}, title = {Modulating the Gut Microbiota to Target Neuroinflammation, Cognition and Mood: A Systematic Review of Human Studies with Relevance to Fibromyalgia.}, journal = {Nutrients}, volume = {17}, number = {14}, pages = {}, pmid = {40732886}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Fibromyalgia/therapy/microbiology/psychology ; Probiotics/administration & dosage/therapeutic use ; *Cognition ; Prebiotics/administration & dosage ; *Affect ; *Neuroinflammatory Diseases/therapy/microbiology ; Fecal Microbiota Transplantation ; }, abstract = {AIM: This systematic review aims to evaluate the effectiveness of microbiota-modulating interventions (such as probiotics, prebiotics, and fecal microbiota transplantation) in reducing cognitive symptoms, pain, and neuroinflammation in human studies relevant to fibromyalgia (FM). The review will investigate the role of gut-brain axis modulation through these interventions and explore the potential therapeutic benefits for FM management.

MATERIALS AND METHODS: A comprehensive search was conducted in electronic databases including PubMed, Scopus, and the Cochrane Library for studies published from 1 January 2015 to 30 April 2025. Studies were eligible if they were randomized controlled trials (RCTs), pilot studies, or observational studies assessing the impact of microbiota-targeted interventions (probiotics, prebiotics, fecal microbiota transplantation) on cognitive function, pain, or neuroinflammation in patients with FM. Studies were excluded if they involved animal models, lacked relevant outcome measures, or were not peer-reviewed. Although only a subset of the included studies directly involved FM patients, all were selected for their relevance to symptom domains (e.g., pain, cognition, mood) and mechanisms (e.g., neuroinflammation, gut-brain axis dysfunction) that are central to FM. A total of 11 human studies were included in the final qualitative synthesis.

RESULTS: Preliminary findings from the included studies suggest that microbiota-targeted interventions, particularly probiotics and prebiotics, show promise in reducing cognitive symptoms, pain, and neuroinflammation in FM patients. Improvements in mood and quality of life were also reported, indicating potential benefits for overall well-being. However, heterogeneity in study designs, sample sizes, and outcome measures limit the ability to draw definitive conclusions.

CONCLUSIONS: This systematic review highlights the potential of microbiota modulation as a therapeutic strategy for managing FM symptoms, particularly cognitive dysfunction and neuroinflammation.}, } @article {pmid40732657, year = {2025}, author = {Maisetta, G and Moneta, S and Tuvo, B and Giordano, C and Petrocelli, PA and Tincani, G and Campani, D and Ghinolfi, D and Falcone, M and Bruschi, F and Lupetti, A}, title = {Three Autochthonous Cases of Amoebic Liver Abscess Clustered in a Small Village of Tuscany (Central Italy), a Non-Endemic Area.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {7}, pages = {}, pmid = {40732657}, issn = {2076-0817}, mesh = {Humans ; *Liver Abscess, Amebic/diagnosis/parasitology/epidemiology/pathology ; Italy/epidemiology ; Male ; Middle Aged ; *Entamoeba histolytica/isolation & purification/genetics ; Female ; Adult ; Feces/parasitology ; Aged ; }, abstract = {Amebiasis is a rare condition in industrialised countries but is epidemiologically growing. Clinical manifestations may range from asymptomatic to invasive disease. An amebic abscess can be the result of extraintestinal amebiasis, and it is associated with relatively high morbidity and mortality. We present three indigenous cases of amoebic liver abscesses observed within a few weeks (October-November 2023) in patients living in a small area near Lucca in Tuscany, Central Italy. Fever accompanied by abdominal pain and liver abscess was observed in all three patients, and one of them presented necrotising colitis and pleural effusion, too. The parasitological diagnosis was performed by microscopy and confirmed with real-time PCR in liver abscess drainage fluid and stools.}, } @article {pmid40732223, year = {2025}, author = {Li, W and Huang, D and Luo, Z and Zhou, T and Jin, Z}, title = {Yinchenhao Decoction Mitigates Cholestatic Liver Injury in Mice via Gut Microbiota Regulation and Activation of FXR-FGF15 Pathway.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {7}, pages = {}, pmid = {40732223}, issn = {1424-8247}, support = {82004417//National Natural Science Foundation of China/ ; 2021M702214//China Postdoctoral Science Foundation/ ; 2024//the 2024 Shanghai Public Health Research Special Project/ ; }, abstract = {Objective: Yinchenhao decoction (YCHD), a classical herbal formula comprising Artemisia capillaris, Gardenia jasminoides, and Rheum palmatum, has been clinically used for over 1000 years to treat cholestasis. However, its mechanism of action remains undefined. This study aimed to elucidate YCHD's therapeutic mechanisms against cholestasis, with a focus on the gut microbiota-mediated regulation of the farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) pathway. Methods: An alpha-naphthyl isothiocyanate (ANIT)-induced cholestasis mouse model was established. Mice received YCHD (3/9 g/kg) for 7 days. 16S rRNA sequencing, targeted LC/MS (bile acid (BA) quantification), untargeted GC/MS (fecal metabolite detection), qPCR/Western blot (FXR pathway analysis), fecal microbiota transplantation (FMT), and antibiotic depletion were employed to dissect the gut-liver axis interactions. Results: YCHD alleviated cholestatic liver injury by reducing serum biomarkers, restoring BA homeostasis via FXR-FGF15 activation, and suppressing hepatic Cyp7a1-mediated BA synthesis. It remodeled gut microbiota, enriched FXR-activating secondary BAs (CDCA, DCA, CA), and restored the intestinal barrier integrity. Antibiotic cocktail abolished YCHD's efficacy, while FMT from YCHD-treated mice enhanced its therapeutic effects, confirming microbiota dependency. Conclusions: YCHD mitigates cholestasis through gut microbiota-driven FXR activation and direct hepatobiliary regulation. These findings bridge traditional medicine and modern pharmacology, highlighting microbiome modulation as a therapeutic strategy for cholestatic liver diseases.}, } @article {pmid40730543, year = {2025}, author = {Du, L and Ding, X and Zhang, W and Huang, L and Lü, H and Jian, T and Li, J and Gai, Y and Meng, X and Niu, G and Chen, J and Li, W}, title = {Anthocyanins from blueberry and blackberry ameliorate metabolic syndrome by Prevotella histicola and acetic acid.}, journal = {NPJ science of food}, volume = {9}, number = {1}, pages = {158}, pmid = {40730543}, issn = {2396-8370}, support = {KYCX24-1240//Postgraduate Research & Practice Innovation Program of Jiangsu Province/ ; 82004018//National Natural Science Foundation of China/ ; 81973463//National Natural Science Foundation of China/ ; 32170377//National Natural Science Foundation of China/ ; }, abstract = {Metabolic syndrome (MetS) is a globally prevalent disorder and poses a significant threat to human health and social harmony. Consumption of anthocyanins has been proven to improve disrupted gut microbiota and obesity in mice and humans. However, the potential specific gut microbiota and metabolites that might mediate these beneficial effects on MetS remain unknown. Here, the MetS-mice model, induced by a high-fat diet (HFD), was employed to investigate the specific effects of ACNs. Additionally, 16S rRNA sequencing and targeted metabolomics analysis of short-chain fatty acids (SCFAs) were utilized to evaluate the influence on gut microbiota composition and SCFAs levels. More importantly, we also utilized antibiotics to construct a pseudo-germ-free mouse model for fecal microbiota transplantation (FMT) to further confirm the regulation of gut microbiota by ACNs and demonstrating that the related effects on MetS could be transferable through FMT. Our data demonstrated that the amelioration of MetS by ACNs might be achieved through modulation of the gut microbiota, which was validated through FMT, and the related benefits could be transferable by FMT. Furthermore, acetic acid and Prevotella histicola might be key microbial metabolites and bacteria, respectively, in this process. These findings highlight the diet-gut-metabolites-diseases system crosstalk and provide new research perspectives for plant-derived ingredients with poor bioavailability.}, } @article {pmid40728956, year = {2025}, author = {Qiao, Y and Cheng, R and Li, X and Zheng, H and Guo, J and Wei, L and Gao, T and Bi, H}, title = {Plateau Environment, Gut Microbiota, and Depression: A Possible Concealed Connection?.}, journal = {Current issues in molecular biology}, volume = {47}, number = {7}, pages = {}, pmid = {40728956}, issn = {1467-3045}, support = {Grant No. 82171863//the Natural Science Foundation of China/ ; 2020-ZJ-T08//the Innovation Platform Program of Qinghai Province/ ; None//the Tianfu Emei Project of Sichuan Province/ ; }, abstract = {Plateau environments present unique mental health challenges owing to stressors including hypoxia, low temperatures, and intense ultraviolet (UV) radiation. These factors induce structural and functional alterations in the gut microbiota, disrupting gut-brain axis homeostasis and contributing to the higher prevalence of depression in plateau regions relative to flatland areas. For example, studies report that 28.6% of Tibetan adults and 29.2% of children/adolescents on the Qinghai-Tibet Plateau experience depression, with increasing evidence linking this trend to alterations in the gut microbiota. Dysbiosis contributes to depression through three interconnected mechanisms: (1) Neurotransmitter imbalance: Reduced bacterial diversity impairs serotonin synthesis, disrupting emotional regulation. (2) Immune dysregulation: Compromised gut barrier function allows bacterial metabolites to trigger systemic inflammation via toll-like receptor signaling pathways. (3) Metabolic dysfunction: Decreased short-chain fatty acid levels weaken neuroprotection and exacerbate hypothalamic-pituitary-adrenal axis stress responses. Current interventions-including dietary fiber, probiotics, and fecal microbiota transplantation-aim to restore microbiota balance and increase short-chain fatty acids, alleviating depressive symptoms. However, key knowledge gaps remain in understanding the underlying mechanisms and generating population-specific data. In conclusion, existing evidence indicates an association between plateau environments, the gut microbiota, and depression, but causal relationships and underlying mechanisms require further empirical investigation. Integrating multiomics technologies to systematically explore interactions among high-altitude environments, the microbiota and the brain will facilitate the development of precision therapies such as personalized nutrition and tailored probiotics to protect mental health in high-altitude populations.}, } @article {pmid40728532, year = {2025}, author = {Zhu, L and Song, B and Zhang, R and Wang, C and He, X and Cao, Y and Li, G}, title = {Gut microbiota in sexual function: exploring new avenues.}, journal = {Sexual medicine reviews}, volume = {}, number = {}, pages = {}, doi = {10.1093/sxmrev/qeaf039}, pmid = {40728532}, issn = {2050-0521}, support = {2022xkjT020//Basic and Clinical Collaborative Research Program of Anhui Medical University/ ; 82201777//The National Natural Science Foundation of China/ ; }, abstract = {INTRODUCTION: The gut microbiota, which is recognized for its crucial role in regulating numerous physiological processes, harbors a relationship with sexual function that has remained relatively understudied.

OBJECTIVES: This narrative review aims to integrate the existing evidence regarding the association between the gut microbiota and sexual function. Additionally, it endeavors to discuss the research challenges and delineate the future directions within this burgeoning field.

METHODS: A comprehensive analysis was carried out on both pre-clinical and clinical studies. The scope of the analysis encompassed: (1) the associations between the composition of the gut microbiota and various forms of sexual dysfunctions, (2) the risk factors for sexual dysfunction that are associated with alterations in the microbiota, and (3) the potential interventions that target the regulation of the gut microbiota.

RESULTS: In the context of erectile dysfunction and hypoactive sexual desire disorder, several investigations have identified specific changes in the gut microbiota. Additionally, risk factors for sexual dysfunction, such as mental health disorders, obesity, diabetes, hypertension, and thyroid dysfunction, are also influenced by the gut microbiota. Promising intervention strategies include dietary modification, supplementation with probiotics or prebiotics, fecal microbiota transplantation, and bioengineering approaches.

CONCLUSION: The current body of evidence has established a link between gut microbial dysbiosis and the pathophysiology of various sexual health issues. Despite the fact that our understanding and assessment of the impact of gut microbes on the sexual function of the host are still in their infancy, continued advancements may unveil novel potential targets for the management of sexual health.}, } @article {pmid40727459, year = {2025}, author = {Xue, J and Zhou, Q}, title = {Effects of Emodin on Lung Inflammation and Intestinal Microbes in Chronic Obstructive Pulmonary Disease.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {9795-9809}, pmid = {40727459}, issn = {1178-7031}, abstract = {INTRODUCTION: The impact of COPD on human health is enormous. Emodin, which has anti-inflammatory, anti-cancer, spasmolysis, and laxative effects, has not been systematically investigated within a study with regard to the treatment of COPD.

METHODS: In this study, we conducted Experiment 1 to evaluate the effects of emodin on COPD. Emodin was purchased from Shanghai Yuanye Biotechnology Co. Ltd. (batch number: T17A10F95418). Pathological changes in lung tissue and the average lung lining interval were used to evaluate the severity of emphysema. Inflammatory cell counts in alveolar lavage fluid and the ratio of neutrophils and lymphocytes were used to observe the level of inflammation. The level of HMGB1-RAGE expression was determined via PCR. Moreover, we compared changes in the metabolites of the intestinal microbial community following an intervention with emodin. In Experiment 2, we observed the effect of fecal on the inflammatory response in COPD mice. A mouse dual intervention model was established using flora depletion and COPD modeling. We evaluated the general health of the model mice, specific pathological changes in lung tissue, the average lung lining interval, inflammatory cell counts within the alveolar lavage fluid, and HMGB1-RAGE pathway expression.

RESULTS: Our results demonstrated that emodin statistically significantly improved lung tissue inflammation in COPD mice, and that butanoic acid was the main differential metabolite in intestinal bacteria. Transplanting the feces of the emodin group mice in Experiment 1 to the model mice evaluated in Experiment 2 reduced the infiltration of inflammatory cells and down-regulated the HMGB1-RAGE inflammation pathway.

CONCLUSION: Our findings provide important information for guiding future research directions.}, } @article {pmid40725913, year = {2025}, author = {Ugwu, OP and Okon, MB and Alum, EU and Ugwu, CN and Anyanwu, EG and Mariam, B and Ogenyi, FC and Eze, VHU and Anyanwu, CN and Ezeonwumelu, JOC and Egba, SI and Uti, DE and Onohuean, H and Aja, PM and Ugwu, MN}, title = {Unveiling the therapeutic potential of the gut microbiota-brain axis: Novel insights and clinical applications in neurological disorders.}, journal = {Medicine}, volume = {104}, number = {30}, pages = {e43542}, pmid = {40725913}, issn = {1536-5964}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Probiotics/therapeutic use ; *Nervous System Diseases/therapy/microbiology ; *Dysbiosis/therapy/complications ; *Brain ; Fecal Microbiota Transplantation/methods ; Prebiotics/administration & dosage ; *Brain-Gut Axis/physiology ; }, abstract = {Over the last several years, the gut microbiota-brain axis has been the focus of medical study, demonstrating the bidirectional nature of gut and brain communication and the resulting influence on neurological and mental health. Trillions of microorganisms, particularly those found in the gastrointestinal tract, contribute the most to the pathophysiology recovery of organs that are critical to human health, such as digestive processes and metabolism, immune responses, and even cognitive function. Dysbiosis (a disturbance in the microbiome balance) has been identified as one of the risk factors for neuropsychiatric illnesses such as depression, anxiety, autism spectrum disorder, Parkinson's disease, and Alzheimer's disease. Therapeutic strategies aimed at the gut microbiota, such as probiotics, dietary modifications, prebiotics, and fecal microbiota transplantation, will eventually offer ways to alleviate symptoms associated with these disorders by restoring microbial balance, modulating the immune response, and influencing the production of major neurotransmitters. Innovative drug carriers, such as microbially-derived nanoparticles and probiotics that target particular parts of the gut or microbial communities, may improve pharmaceutical treatment efficacy and specificity. The resolution of difficulties such as ethical concerns, unexpected repercussions, and peak performance optimization in a clinical setting is critical for the advancement of this subject.}, } @article {pmid40725626, year = {2025}, author = {Augustynowicz, G and Lasocka, M and Szyller, HP and Dziedziak, M and Mytych, A and Braksator, J and Pytrus, T}, title = {The Role of Gut Microbiota in the Development and Treatment of Obesity and Overweight: A Literature Review.}, journal = {Journal of clinical medicine}, volume = {14}, number = {14}, pages = {}, pmid = {40725626}, issn = {2077-0383}, abstract = {The gut microbiota, dominated by bacteria from the Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria phyla, plays an essential role in fermenting indigestible carbohydrates, regulating metabolism, synthesizing vitamins, and maintaining immune functions and intestinal barrier integrity. Dysbiosis is associated with obesity development. Shifts in the ratio of Firmicutes to Bacteroidetes, particularly an increase in Firmicutes, may promote enhanced energy storage, appetite dysregulation, and increased inflammatory processes linked to insulin resistance and other metabolic disorders. The purpose of this literature review is to summarize the current state of knowledge on the relationship between the development and treatment of obesity and overweight and the gut microbiota. Current evidence suggests that probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) can influence gut microbiota composition and metabolic parameters, including body weight and BMI. The most promising effects are observed with probiotic supplementation, particularly when combined with prebiotics, although efficacy depends on strain type, dose, and duration. Despite encouraging preclinical findings, FMT has shown limited and inconsistent results in human studies. Diet and physical activity are key modulators of the gut microbiota. Fiber, plant proteins, and omega-3 fatty acids support beneficial bacteria, while diets low in fiber and high in saturated fats promote dysbiosis. Aerobic exercise increases microbial diversity and supports growth of favorable bacterial strains. While microbiota changes do not always lead to immediate weight loss, modulating gut microbiota represents an important aspect of obesity prevention and treatment strategies. Further research is necessary to better understand the mechanisms and therapeutic potential of these interventions.}, } @article {pmid40724502, year = {2025}, author = {Lazăr, DC and Chiriac, SD and Drăghici, GA and Moacă, EA and Faur, AC and Avram, MF and Turi, VR and Nicolin, MR and Goldiș, A and Salehi, MA and Jipa, R}, title = {Gastric Cancer and Microbiota: Exploring the Microbiome's Role in Carcinogenesis and Treatment Strategies.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {7}, pages = {}, pmid = {40724502}, issn = {2075-1729}, abstract = {Gastric cancer (GC) remains a major global health burden, with high morbidity and mortality rates, particularly in regions with prevalent Helicobacter pylori (H. pylori) infection. While H. pylori has long been recognized as a primary carcinogenic agent, recent research has underscored the broader contribution of the gastric microbiota to gastric carcinogenesis. Alterations in the microbial community, or dysbiosis, contribute to chronic inflammation, immune modulation, and epithelial transformation through a range of mechanisms, including disruption of mucosal integrity, activation of oncogenic signaling pathways (e.g., PI3K/Akt, NF-κB, STAT3), and epigenetic alterations. Furthermore, microbial metabolites, such as short-chain fatty acids, secondary bile acids, and lactate, play dual roles in either promoting or suppressing tumorigenesis. Oral and gut-derived microbes, translocated to the gastric niche, have been implicated in reshaping the gastric microenvironment and exacerbating disease progression. The composition of the microbiota also influences responses to cancer immunotherapy, suggesting that microbial profiles can serve as both prognostic biomarkers and therapeutic targets. Emerging strategies, such as probiotics, dietary interventions, and fecal microbiota transplantation (FMT), offer new avenues for restoring microbial balance and enhancing therapy response. This review synthesizes current knowledge on the complex interplay between microbiota and gastric cancer development and emphasizes the potential of microbiome modulation in both preventive and therapeutic frameworks.}, } @article {pmid40723882, year = {2025}, author = {Neagu, AI and Bostan, M and Ionescu, VA and Gheorghe, G and Hotnog, CM and Roman, V and Mihaila, M and Stoica, SI and Diaconu, CC and Diaconu, CC and Ruta, SM and Bleotu, C}, title = {The Impact of the Microbiota on the Immune Response Modulation in Colorectal Cancer.}, journal = {Biomolecules}, volume = {15}, number = {7}, pages = {}, pmid = {40723882}, issn = {2218-273X}, mesh = {Humans ; *Colorectal Neoplasms/immunology/microbiology/therapy ; *Gastrointestinal Microbiome/immunology ; Animals ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Colorectal cancer (CRC) is a multifactorial disease increasingly recognized for its complex interplay with the gut microbiota. The disruption of microbial homeostasis-dysbiosis-has profound implications for intestinal barrier integrity and host immune function. Pathogenic bacterial species such as Fusobacterium nucleatum, Escherichia coli harboring polyketide synthase (pks) island, and enterotoxigenic Bacteroides fragilis are implicated in CRC through mechanisms involving mucosal inflammation, epithelial barrier disruption, and immune evasion. These pathogens promote pro-tumorigenic inflammation, enhance DNA damage, and suppress effective anti-tumor immunity. Conversely, commensal and probiotic bacteria, notably Lactobacillus and Bifidobacterium species, exert protective effects by preserving epithelial barrier function and priming host immune responses. These beneficial microbes can promote the maturation of dendritic cells, stimulate CD8[+] T cell cytotoxicity, and modulate regulatory T cell populations, thereby enhancing anti-tumor immunity. The dichotomous role of the microbiota underscores its potential as both a biomarker and a therapeutic target in CRC. Recent advances in studies have explored microbiota-modulating strategies-ranging from dietary interventions and prebiotics to fecal microbiota transplantation (FMT) and microbial consortia-as adjuncts to conventional therapies. Moreover, the composition of the gut microbiome has been shown to influence the responses to immunotherapy and chemotherapy, raising the possibility of microbiome-informed precision oncology therapy. This review synthesizes the current findings on the pathogenic and protective roles of bacteria in CRC and evaluates the translational potential of microbiome-based interventions in shaping future therapeutic paradigms.}, } @article {pmid40723792, year = {2025}, author = {Guo, H and Tang, X and He, X and Weng, Y and Zhang, Q and Fang, Q and Zhang, L}, title = {A Comprehensive Review of the Role of the Microbiota-Gut-Brain Axis via Neuroinflammation: Advances and Therapeutic Implications for Ischemic Stroke.}, journal = {Biomolecules}, volume = {15}, number = {7}, pages = {}, pmid = {40723792}, issn = {2218-273X}, support = {KJXW2023013//Xingwei Kejiao science and technology project of Suzhou/ ; SSD2024058//Suzhou Basic Research Pilot Project/ ; 82001125//National Natural Science Foundation of China/ ; BK20180201//Natural Science Foundation of Jiangsu Province/ ; 23KJB320016//The Natural Science Foundation of the Jiangsu Higher Education Institutions of China/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Ischemic Stroke/microbiology/therapy/metabolism ; Animals ; *Brain/metabolism ; *Neuroinflammatory Diseases/microbiology/metabolism/therapy ; Probiotics/therapeutic use ; *Brain-Gut Axis ; Fecal Microbiota Transplantation ; }, abstract = {The human gastrointestinal tract harbors a complex and diverse microbial community. Emerging evidence has revealed bidirectional communication between the gut microbiome and the central nervous system, termed the "microbiota-gut-brain axis". This axis serves as a critical regulator of glial cell function, positioning it as an essential target for ameliorating the onset and progression of ischemic stroke. In this review, we discuss the developments in the relationship between ischemic stroke and neuroinflammation via MGBA. The gut microbiome plays a critical role in signaling to microglia, astrocytes, and other immune components within this axis. We also summarize the interactions between the gut microbiota and glial cells under both healthy and ischemic stroke conditions. Additionally, we also focus on the role of microbiota-derived metabolites and neurotransmitters in ischemic stroke. Furthermore, we investigate the potential of targeting the intestinal and blood-brain barriers to improve MGBA. Finally, we evaluate the preclinical and clinical evidence for dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation in ischemic stroke. A comprehensive understanding of the MGBA is essential for developing MGBA-based treatment for ischemic stroke.}, } @article {pmid40723178, year = {2025}, author = {Tudorache, M and Treteanu, AR and Gradisteanu Pircalabioru, G and Lixandru-Petre, IO and Bolocan, A and Andronic, O}, title = {Gut Microbiome Alterations in Colorectal Cancer: Mechanisms, Therapeutic Strategies, and Precision Oncology Perspectives.}, journal = {Cancers}, volume = {17}, number = {14}, pages = {}, pmid = {40723178}, issn = {2072-6694}, abstract = {Colorectal cancer (CRC) is one of the most prevalent and lethal oncological diseases worldwide, with a concerning rise in incidence, particularly in developing countries. Recent advances in genetic sequencing have revealed that the gut microbiome plays a crucial role in CRC development. Mechanisms such as chronic inflammation, metabolic alterations, and oncogenic pathways have demonstrated that dysbiosis, a disruption of the gut microbiome, is linked to CRC. Associations have been found between tumor progression, treatment resistance, and pathogenic microbes such as Fusobacterium nucleatum and Escherichia coli. A promising approach for CRC prevention and treatment is microbiome manipulation through interventions such as probiotics, prebiotics, fecal microbiota transplantation, and selective antibiotics. This article explores how gut microbiome alterations influence CRC pathogenesis and examines microbiome modulation strategies currently used as adjuncts to traditional treatments. Advances in artificial intelligence, single-cell and spatial transcriptomics, and large-scale initiatives such as the ONCOBIOME Project are paving the way for the identification of microbiome-derived biomarkers for early CRC detection and personalized treatment. Despite promising progress, challenges such as interindividual variability, causal inference, and regulatory hurdles must be addressed. Future integration of microbiome analysis into multi-omics frameworks holds great potential to revolutionize precision oncology in CRC management.}, } @article {pmid40722867, year = {2025}, author = {Akinrimisi, OI and Maasen, K and Scheijen, JLJM and Nemet, I and Nieuwdorp, M and Schalkwijk, CG and Hanssen, NMJ}, title = {Does Gut Microbial Methylglyoxal Metabolism Impact Human Physiology?.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {7}, pages = {}, pmid = {40722867}, issn = {2076-3921}, support = {09150172210019/NWO_/Dutch Research Council/Netherlands ; 2021T055//Hartstichting/ ; }, abstract = {Methylglyoxal (MGO) is a highly reactive dicarbonyl associated with oxidative stress, inflammation, and chronic diseases, particularly diabetic vascular complications and atherosclerosis through the formation of advanced glycation end products (AGEs). In the setting of human/host diseases, the formation of MGO has mainly been considered as the byproduct of glycolysis. Gut microbes play an important role in the development of cardiometabolic diseases. Here, we discuss a possibility that gut microbes can modulate the MGO pool within the host through (i) the alternation of the host metabolism, and (ii) direct MGO synthesis and/or detoxification by human commensal microorganisms. We also explore how dietary MGO impacts the composition of the gut microbiota and their potential role in modulating host health. This paradigm is highly innovative, with the current literature providing observations supporting this concept. Targeting the gut microbiome is emerging as an approach for treating cardiometabolic diseases through dietary, pre-, pro-, and postbiotic interventions, faecal microbiota transplantations, and the use of small molecule inhibitors of microbial enzymes. This can be a novel strategy to reduce MGO stress in the setting of cardiometabolic diseases and lowering the burden of diabetic complications and cardiovascular disease.}, } @article {pmid40722839, year = {2025}, author = {Carrossa, G and Misenti, V and Faggin, S and Giron, MC and Antonini, A}, title = {The Small Intestinal Microbiota and the Gut-Brain Axis in Parkinson's Disease: A Narrative Review.}, journal = {Biomedicines}, volume = {13}, number = {7}, pages = {}, pmid = {40722839}, issn = {2227-9059}, abstract = {Researchers are increasingly focusing on understanding the microbiota's influence on disease susceptibility and overall health. The vast number of microorganisms in our gastrointestinal tract and their extensive surface area underscore their undeniable impact on well-being. Viewing the gut microbiome as a distinct pool of microbial genetic information that interacts with the human genome highlights its pivotal role in genetically predisposed diseases. Investigating this complex crosstalk may lead to the development of novel therapeutic strategies-such as targeting dysbiosis-to complement conventional treatments and improve patient care. Parkinson's disease (PD) is a multifactorial condition originating from a combination of genetic and environmental risk factors. Compelling evidence points to the enteric nervous system as an initial site of pathological processes that later extend to the brain-a pattern known as the 'body-first' model. Furthermore, most patients with PD exhibit both qualitative and quantitative alterations in the composition of the gut microbiota, including dysbiosis and small intestinal overgrowth. Nonetheless, the existing literature predominantly addresses fecal microbiota, while knowledge of upper intestinal sections, like the duodenum, remains scarce. Given the potential for microbiota modulation to impact both motor and gastrointestinal symptoms, further research exploring the therapeutic roles of balanced diets, probiotics, and fecal transplants in PD is warranted.}, } @article {pmid40722483, year = {2025}, author = {Dragasevic, S and Nikolic, A and Zgradic, S and Stojkovic Lalosevic, M and Stojkovic, S and Matovic Zaric, V and Lukic, S and Glisic, T and Kmezic, S and Saponjski, D and Popovic, D}, title = {Dysbiosis of Gut Microbiota in Microscopic Colitis: Diagnostic and Therapeutic Implications.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {14}, pages = {}, pmid = {40722483}, issn = {2075-4418}, abstract = {Microscopic colitis (MC) is an idiopathic inflammatory bowel disease characterized by watery, non-bloody diarrhea and histopathological changes but normal endoscopic findings. Increasing evidence now suggests that alterations in the gut microbiota contribute to the pathogenesis of MC. In this narrative review, we summarize evidence from nine case-control studies examining microbial composition using sequencing technology. The research presented here illustrates reduced alpha diversity, high dysbiosis, and pro-inflammatory oral-associated taxa enrichment, such as Veillonella dispar, and loss of protective microbes such as Akkermansia muciniphila and Bacteroides stercoris. These microbial changes have the potential to be non-invasive diagnostic biomarkers that can differentiate MC from other etiologies. In addition, the characterization of gut microbiota in MC can guide personalized therapeutic strategies, such as directed probiotic therapy or fecal microbiota transplantation, to help restore microbial balance. These microbial patterns can be applied to guide the creation of diagnostic biomarkers and personalized therapy. Despite differences in sample types and sequencing methods, general microbial trends highlight the need for further longitudinal and standardized investigations.}, } @article {pmid40721426, year = {2025}, author = {Yang, Y and Ye, M and Song, Y and Xing, W and Zhao, X and Li, Y and Shen, J and Zhou, J and Arikawa, K and Wu, S and Song, Y and Xu, N}, title = {Gut microbiota and SCFAs improve the treatment efficacy of chemotherapy and immunotherapy in NSCLC.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {146}, pmid = {40721426}, issn = {2055-5008}, support = {2020YFC2003700//National Key R&D Plan/ ; ZD2021CY001//Shanghai Municipal Science and Technology Major Project/ ; 20Z11901000, 20DZ2261200, 20XD1401200, 22Y11900800//Science and Technology Commission of Shanghai Municipality/ ; SHDC2020CR5010-002//Clinical Research Plan of SHDC/ ; shslczdzk02201//Shanghai Municipal Key Clinical Specialty/ ; ZY(2021-2023)-0207-01//Shanghai Municipal Health Commission and Shanghai Municipal Administrator of Traditional Chinese Medicine/ ; 81401877, 82130001, and 82272243//National Natural Science Foundation of China/ ; 81401877, 82130001, and 82272243//National Natural Science Foundation of China/ ; }, mesh = {*Gastrointestinal Microbiome ; Humans ; *Carcinoma, Non-Small-Cell Lung/therapy/microbiology/drug therapy ; *Immunotherapy/methods ; Animals ; *Lung Neoplasms/therapy/microbiology/drug therapy ; Mice ; *Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome ; *Bacteria/classification/genetics/isolation & purification/metabolism ; Female ; Male ; Metagenomics ; Middle Aged ; Aged ; Dysbiosis/microbiology ; Antineoplastic Agents/therapeutic use ; }, abstract = {The role of gut dysbiosis in shaping immunotherapy responses is well-recognized, yet its effect on the therapeutic efficacy of chemotherapy and immunotherapy combinations remains poorly understood. We analyzed gut microbiota in non-small cell lung cancer (NSCLC) patients treated with chemo-immunotherapy, comparing responders and non-responders using 16S rRNA sequencing. Responders showed higher microbial richness and abundance of specific genera like Faecalibacterium and Subdoligranulum, and the phylum Firmicutes. Support vector machine (SVM), a machine learning model based on microbial composition, predicted treatment efficacy with the area under the curve (AUC) values of 0.763 for genera and 0.855 for species. Metagenomic analysis revealed significant differences in metabolic pathways, with responders exhibiting higher short-chain fatty acids (SCFAs) production. Fecal microbiota transplantation (FMT) and SCFAs supplementation in mouse models enhanced treatment efficacy by promoting effector T cell activity in tumors. Our study suggests that gut microbiota, through SCFAs production, regulates chemo-immunotherapy efficacy, offering new strategies to improve NSCLC treatment outcomes.}, } @article {pmid40716617, year = {2025}, author = {Yi, D and Li, T and Xiao, Y and Li, X and Shao, B and Wu, Z and Hao, Q and Zhang, F and Zhang, X and Yang, G and Zhang, C and Deng, H and Sun, X and Wang, N}, title = {Hydroxytyrosol improved insulin resistance in male offspring born to high-fat diet dams by remodeling gut microbiota.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {110041}, doi = {10.1016/j.jnutbio.2025.110041}, pmid = {40716617}, issn = {1873-4847}, abstract = {Maternal obesity during pregnancy and lactation critically influences offspring metabolic programming, increasing insulin resistance (IR) risk through gut microbiome alterations. This study investigated whether hydroxytyrosol (HT), a polyphenol, could exert metabolic benefits through intergenerational regulation of gut microbiota. Through dietary intervention and fecal microbiota transplantation experiments in pregnant and lactating C57BL/6J dams, combined with 16S rRNA sequencing and interaction analysis, we found that maternal high-fat diet (60% fat for energy) during gestation and lactation caused obesity and IR associated phenotypes in male offspring at 4 weeks of age, but not in female young pups. Oral gavage of HT (50 mg/kg) during pregnancy and lactation alleviated abnormal adipocyte hypertrophy, hyperplasia, and excessive leptin secretion in male offspring born to obese dams. Additionally, HT reduced systemic insulin intolerance, hyperglycemia, and hyperinsulinemia, decreased liver index and liver injury, attenuated hepatocyte ballooning, hepatic oxidative stress, and systemic inflammation, and restored hepatic PI3K/AKT signaling in male offspring. Furthermore, HT recovered intestinal barrier function and gut microbiota homeostasis in male offspring, especially the community structure represented by β-diversity, microbial dysbiosis index and SCFAs content. Importantly, the beneficial effects of maternal HT ingestion on offspring IR were closely associated with gut microbiota remodeling and could be transmitted through intergenerational microbial inheritance between mothers and offspring. Together, our study indicated that the intergenerational transmission of microbiota may underlie maternal obesity-induced IR and that HT intake could be a promising intervention.}, } @article {pmid40716471, year = {2025}, author = {Mkilima, T}, title = {Synthetic biology approaches for restoring gut microbial balance and engineering disease-specific microbiome therapeutics.}, journal = {Microbial pathogenesis}, volume = {207}, number = {}, pages = {107931}, doi = {10.1016/j.micpath.2025.107931}, pmid = {40716471}, issn = {1096-1208}, mesh = {Humans ; *Synthetic Biology/methods ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/therapy/microbiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Metabolic Engineering/methods ; Inflammatory Bowel Diseases/therapy/microbiology ; Gene Editing ; *Microbial Consortia ; }, abstract = {The human gut microbiome plays a pivotal role in regulating digestion, immune function, and metabolic homeostasis. Disruption of this microbial equilibrium, known as dysbiosis, is increasingly linked to chronic conditions including inflammatory bowel disease (IBD), obesity, diabetes, and neurodegenerative disorders. Conventional interventions, such as probiotics and faecal microbiota transplantation (FMT), often yield inconsistent results due to individual microbiome variability and limited ecological stability. Engineered artificial microbial consortia (AMCs) have emerged as a next-generation strategy for precision modulation of the gut microbiome. This review critically examines cutting-edge advances in synthetic biology, CRISPR-based genome editing, metabolic engineering, and multi-omics integration that underpin the rational design of AMCs targeted to disease-specific microbial dysfunctions. Notably, this work presents an ecological precision engineering framework that integrates regional microbiome ecotypes, diet-responsive modular design, and adaptive metabolic modelling to ensure cross-population compatibility and stability. Enabling technologies, such as gut-on-a-chip platforms, high-throughput co-culture screening, and ecological modelling, are explored in the context of optimizing AMC performance across diverse host environments. Furthermore, the review highlights the potential for AMC-based therapeutics to be equitably scaled through regionally adapted templates, thereby extending microbiome-based healthcare to low-resource settings. By bridging ecological diversity and therapeutic specificity, this review presents a globally relevant roadmap for developing reproducible, adaptable, and inclusive microbiome interventions within the broader framework of precision medicine.}, } @article {pmid40720392, year = {2025}, author = {Solis, AJ and Zucchi, P and Romo, JA}, title = {Biofilm Assay for Clostridioides difficile with Applications for Drug Discovery.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {221}, pages = {}, doi = {10.3791/67913}, pmid = {40720392}, issn = {1940-087X}, mesh = {*Biofilms/drug effects/growth & development ; *Clostridioides difficile/drug effects/physiology ; *Drug Discovery/methods ; *Anti-Bacterial Agents/pharmacology ; Humans ; Clostridium Infections/microbiology/drug therapy ; }, abstract = {Clostridioides difficile is a gastrointestinal bacterial pathogen able to take advantage of a dysbiotic microbiota environment to proliferate, secrete toxins, and damage the intestinal epithelium. A subset of C. difficile infection (CDI) patients will experience antibiotic (15%-30%) or fecal microbiota transplant (FMT) (<10%) treatment failure. Therefore, the development of additional therapeutic interventions is of critical importance. The role of C. difficile biofilms in recurrence is unclear. However, biofilms in other organisms are responsible for chronic and relapsing disease, suggesting this could also be the case in recurrent CDI. We hypothesize that biofilms of C. difficile present a valuable therapeutic target. The goal of the protocol presented here is to adapt a biofilm formation assay for the identification of repositionable compounds with activity against established C. difficile biofilms. The protocol refines a robust and reproducible assay for forming biofilms, couples it to a metabolic assay, and applies it to drug discovery. This protocol outlines the biofilm formation assay, biomass and metabolic activity readouts, drug susceptibility testing, drug screening of a repositioning library, and representative results.}, } @article {pmid40719366, year = {2025}, author = {Wang, X and Wang, N and Gao, T and Zhang, Y and Fu, Z and Zhao, Y and Huang, Y and Zheng, X and Gao, X and Lu, L and Yang, L}, title = {Symptom-specific gut microbial and metabolic profiles in ADHD reveal SCFA deficiency as a Key pathogenic mechanism.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2537755}, pmid = {40719366}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; *Attention Deficit Disorder with Hyperactivity/microbiology/metabolism ; Animals ; Humans ; Mice ; Male ; Female ; *Fatty Acids, Volatile/metabolism ; Feces/microbiology/chemistry ; Fecal Microbiota Transplantation ; Child ; *Bacteria/classification/metabolism/genetics/isolation & purification ; Metabolome ; Adolescent ; Metabolomics ; }, abstract = {Previous evidence links gut microbiota to attention-deficit/hyperactivity disorder (ADHD) through the gut-brain axis. However, the specific microbiota contributing to symptoms remain unclear. To characterize the gut microbial profile related to different symptoms and explore the mediation mechanism between microbiota alterations and the core ADHD symptoms, we conducted shotgun metagenomic sequencing and fecal metabolomics analysis on 94 ADHD patients and 94 age- and gender-matched controls. Microbial characteristics of three subgroups exhibiting different ADHD core symptom presentations were analyzed. We developed a metabolic model and conducted causal mediation analyses to examine how metabolites connect the microbiota to the symptoms. Fecal microbiota transplantation in mice was employed to validate the findings. The redundancy analysis identified ADHD symptoms as environmental gradients and explained the changes in beta diversity (F = 1.345, pFDR = 0.015). Greater gut microbial alterations were observed in combined presentations (ADHD-C). Several beneficial bacteria involved in short-chain fatty acid synthesis were found to be downregulated, with Lactobacillus sanfranciscensis notably linked to all three core symptoms (p.adj = 1.04E-13; p.adj = 5.07E-07; p.adj = 2.61E-05). Various taxa, functional pathways, and metabolites associated with specific ADHD symptom domains were identified. Imidazoleacetic acid partially mediated the effects between Lactobacillus sanfranciscensis and inattention (p = 0.012). In mice subjected to feces from ADHD patients with a low abundance of Lactobacillus sanfranciscensis, treatment with this strain greatly improved both hyperactivity (t = 2.665, p = 0.0237) and inattention (t = 2.389, p = 0.0380), while acetate supplementation only alleviated inattention (t = 2.362, p = 0.0398). Our findings suggest that different ADHD symptoms were related to common and different gut microbiota and metabolites. Fecal microbiota transplantation in mice validated the hypothesis that gut microbial composition affects ADHD symptoms through metabolic alterations. This study provides more insight into the mechanisms underlying metabolic disturbances in ADHD and elucidates the role of gut microbiota in these processes.}, } @article {pmid40717663, year = {2025}, author = {Liu, Y and Wang, Z and Zhang, Y and Zhao, T and Zhang, Q and Huang, W and Lu, B}, title = {Dietary cholesterol impairs cognition via gut microbiota-derived deoxycholic acid in obese mice.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2537753}, pmid = {40717663}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Deoxycholic Acid/metabolism ; Mice ; Diet, High-Fat/adverse effects ; Male ; Hippocampus/metabolism ; Mice, Inbred C57BL ; *Cognitive Dysfunction/etiology/microbiology/metabolism ; *Cholesterol, Dietary/adverse effects/metabolism ; *Cognition/drug effects ; Mice, Obese ; *Obesity/microbiology/metabolism ; Bacteria/classification/genetics/metabolism/isolation & purification ; Fecal Microbiota Transplantation ; Bile Acids and Salts/metabolism ; }, abstract = {Dietary cholesterol is often found in a high-fat diet (HFD) and excessive intake is harmful to cognitive function. The gut microbiome constitutes an environmental factor influenced by diet, which regulates cognitive function via the gut-brain axis. The present study explored the role of dietary cholesterol in HFD-induced cognitive impairment and the participation of the gut microbiota and metabolites. Here, we found that dietary cholesterol promoted cognitive impairment in HFD-fed mice, which was associated with an increase in gut microbiota containing 7α-dehydroxylase, including Lachnospiraceae bacterium, Dorea sp. Clostridium sp. and elevated levels of deoxycholic acid (DCA) in the hippocampus. Upon dietary cholesterol intake, the activity of gut microbiota in mice to produce DCA is increased. Fecal microbiota transplantation confirmed that the cognitive impairment-promoting process was driven by gut microbiota. Reducing circulating bile acid levels with cholestyramine improved cognitive decline in mice, whereas hippocampal administration of DCA worsened cognitive function. Pharmacological inhibition of hippocampal apical sodium bile acid transporter reduces neuronal DCA accumulation and improves neuronal apoptosis as well as cognitive impairments in mice. Overall, this study revealed that dietary cholesterol promotes HFD-induced cognitive impairment by inducing the production of DCA through gut microbiota metabolism.}, } @article {pmid40715107, year = {2025}, author = {Lei, W and Zhou, K and Lei, Y and Li, Q and Zhu, H}, title = {Gut microbiota shapes cancer immunotherapy responses.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {143}, pmid = {40715107}, issn = {2055-5008}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Neoplasms/therapy/immunology/microbiology ; *Immunotherapy/methods ; Tumor Microenvironment/immunology ; Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {The gut microbiota significantly influences cancer immunotherapy efficacy by modulating immune responses, remodeling the tumor microenvironment (TME), and producing key metabolites. Strategies such as FMT, probiotics, and dietary interventions show promise in enhancing responses to ICIs and ACTs while reducing immune-related adverse events (irAEs). This review summarizes clinical and preclinical findings and discusses microbiota-based interventions and future directions for precision immunotherapy.}, } @article {pmid40714355, year = {2025}, author = {Nóbrega, R and Costa, CFFA and Cerqueira, Ó and Inês, A and Carrola, JS and Gonçalves, C}, title = {Association between gut microbiota and pediatric obesity: A systematic review.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {140}, number = {}, pages = {112875}, doi = {10.1016/j.nut.2025.112875}, pmid = {40714355}, issn = {1873-1244}, abstract = {OBJECTIVES: Pediatric obesity is a multifactorial public health problem with increasing prevalence. Among the many contributing factors, the intestinal microbiota has emerged as a key area of investigation due to its potential role in metabolism, immunity, and energy regulation. Understanding and modulating the gut microbiota may offer novel therapeutic strategies. This systematic review aims to explore the relationship between the intestinal microbiota composition and obesity in pediatric age.

METHODS: The review followed PRISMA recommendations. Two databases (PubMed and Scopus) were consulted in May 2024 for research and two independent reviewers screened abstracts, following extraction of relevant data. Risk of bias was assessed using the Cochrane Collaboration's RoB 2 and ROBIN-I tools.

RESULTS: This review included a set of 70 studies, of which 23 were clinical trials and 47 were cross-sectional studies. They all analyzed the intestinal microbiota using fecal DNA sequencing, comparing microbial and metabolomic profiles between normal-weight children and overweight children. The effects of current interventions, such as the use of probiotics, supplementation, physical activity, and fecal microbiota transplantation, are also explored. Despite variability in findings, certain genera-such as Akkermansia, Bifidobacterium, Blautia, and Faecalibacterium-emerged as frequently associated with obesity-related traits. The Firmicutes/Bacteroidetes ratio showed inconsistent associations.

CONCLUSIONS: Pediatric obesity is associated with distinct changes in gut microbiota composition and function. While promising, the current evidence is heterogeneous. Future research should focus on longitudinal designs and standardized methodologies to clarify the role of diet, physical activity, and microbiota-based therapies in obesity prevention and management.}, } @article {pmid40713811, year = {2025}, author = {Sun, B and Yuan, J and Zhang, X and Ma, X and Hao, Z and Wang, L and Li, Y and Zhang, L and Li, L}, title = {Metaproteomics Reveals Community Coalescence Outcomes in Co-Cultured Human Gut Microbiota.}, journal = {Proteomics}, volume = {}, number = {}, pages = {e70009}, doi = {10.1002/pmic.70009}, pmid = {40713811}, issn = {1615-9861}, support = {32370050//National Natural Science Foundation of China/ ; 82371559//National Natural Science Foundation of China/ ; }, abstract = {The human gut microbiome exhibits characteristics of complex ecosystems, including the ability to resist and compete with exogenous species or communities. Understanding the microbiome response that emerges from such competitive interactions is crucial, particularly for applications like fecal microbiota transplantation (FMT), where the success of treatment largely depends on the outcome of these microbial competitions. During these processes, microbial communities undergo coalescence, a phenomenon where distinct microbial communities combine and interact, leading to complex ecological outcomes that are still being uncovered. In this study, we examined the coalescent dynamics of 10 different pairs of human gut microbiota by co-culturing the plateau-phase communities of individual samples in vitro, and highlighted the critical role of metaproteomics in elucidating the competitive dynamics of co-cultured human fecal samples. Results showed that microbiome changes observed after coalescent co-culture were not straightforwardly an approximate average of the initial taxonomic or functional compositions of the two samples. Instead, both coalescent microbiotas behaved as cohesive structures, influencing the competitive outcome toward one of them. Although co-cultured communities usually exhibited high degrees of taxonomic similarities to one of its parental samples, we found that 23% of the observed proteins still showed differential expression or abundance at the metaproteomic level. Interestingly, and somewhat counterintuitively, no specific microbial ecological characteristic could linearly determine which of the two initial microbiotas would act as the driving microbiota. Instead, we observed that the outcomes of the microbial co-cultures resembled a "rock-paper-scissors"-like dynamic. Through an analysis of co-colonizing species in such "rock-paper-scissors"-like triangle, we discovered that co-colonizing species that contributed to winning each between-community competition differed from one community pair to another. This suggests that no single species or function consistently dominates across all situations; instead, this involves more complex mechanisms, which require further in-depth investigation in future studies. Our findings demonstrate that the complex competitive interactions between microbial communities make predicting success through a single parameter challenging, whereas pre-co-culturing shows promise as an effective method for predicting outcomes in ecological therapies such as FMT. SUMMARY: This study underscores the critical importance of integrating metaproteomics with microbial systems ecology to gain a functional understanding of microbial coalescence. By addressing the ecological question of how two communities compete when they are brought into contact, we investigated the metaproteomic responses of pairs of coalescent co-cultured human gut microbiotas. Our results revealed significant insights: post-co-culture microbiota changes were not merely a simple average of the initial compositions but instead exhibited distinct shifts toward one of the original samples. Notably, due to the observed rock-paper-scissors-like cycle of winning, we argue that no single microbial ecological characteristic could straightforwardly predict which of the two samples would dominate as the driving microbiota. Overall, our findings suggest that during coalescence, microbial communities behave as cohesive structures both taxonomically and functionally, influencing competitive dynamics and ecosystem complexity, indicating that an in vitro coalescence pretest may help predict the success of therapies like FMT.}, } @article {pmid40713799, year = {2025}, author = {Soleimani Samarkhazan, H and Nouri, S and Maleknia, M and Aghaei, M}, title = {"The microbiome in graft-versus-host disease: a tale of two ecosystems".}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {832}, pmid = {40713799}, issn = {1479-5876}, mesh = {*Graft vs Host Disease/microbiology/therapy ; Humans ; *Microbiota ; Hematopoietic Stem Cell Transplantation ; Animals ; *Ecosystem ; Fecal Microbiota Transplantation ; Dysbiosis ; }, abstract = {Graft-versus-host disease (GVHD), a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT), is shaped by a dynamic interplay between two microbial ecosystems: the recipient's disrupted microbiome and the donor's transplanted microbiota. This narrative review unravels the "tale of two ecosystems," exploring how pre-transplant chemotherapy, radiation, and antibiotics induce recipient dysbiosis-marked by loss of beneficial taxa (Clostridia, Faecalibacterium) and dominance of pathobionts (Enterococcus). These shifts impair barrier integrity, fuel systemic inflammation, and skew immune responses toward pro-inflammatory T-cell subsets, exacerbating GVHD. Conversely, emerging evidence implicates donor microbiota in modulating post-transplant immune reconstitution, though its role remains underexplored. Therapeutic strategies, including probiotics, prebiotics, and fecal microbiota transplantation (FMT), demonstrate promise in restoring microbial balance, enhancing short-chain fatty acid (SCFA)-driven immune regulation, and reducing GVHD severity. However, challenges such as strain-specific efficacy, safety in immunocompromised hosts, and protocol standardization persist. By bridging microbial ecology and immunology, this review underscores the microbiome's transformative potential in redefining GVHD management and advocates for personalized, microbiome-targeted interventions to improve HSCT outcomes.}, } @article {pmid40713743, year = {2025}, author = {Wang, L and Li, M and Dong, Y and Wang, J and Qin, S and Li, L and Li, B and Wang, B and Cao, H}, title = {Magnoflorine alleviates colitis-induced anxiety-like behaviors by regulating gut microbiota and microglia-mediated neuroinflammation.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {172}, pmid = {40713743}, issn = {2049-2618}, support = {82270574, 82070545 and 81970477//National Natural Science Foundation of China/ ; 82270574, 82070545 and 81970477//National Natural Science Foundation of China/ ; 22ZYYJQ02//Tianjin Medical University General Hospital Fund for Distinguished Young Scholars/ ; 21JCYBJC00810//Diversified Fund Project of the Natural Science Foundation of Tianjin, China/ ; TJYXZDXK-002A//Tianjin Key Medical Discipline (Specialty) Construction Project/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Anxiety/drug therapy/etiology/microbiology ; *Microglia/drug effects/metabolism ; *Aporphines/pharmacology/therapeutic use ; *Colitis, Ulcerative/drug therapy/microbiology/complications ; Ziziphus/chemistry ; Male ; *Colitis/complications/drug therapy/microbiology ; Disease Models, Animal ; Mice, Inbred C57BL ; *Neuroinflammatory Diseases/drug therapy ; Humans ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) and anxiety are often comorbid and are interconnected through the microbiota-gut-brain axis. Therapeutic medications for anxiety are often constrained by adverse effects that limit their long-term use. Therefore, recent research has focused on identifying natural, safe drugs for anxiety, and elucidating the precise mechanisms underlying the interplay between drugs and the gut-brain axis in modulating mood.

RESULTS: We revealed a significant association between active ulcerative colitis (UC) and anxiety. The results of Mendelian randomization analysis suggested that UC has a causal relationship with anxiety, but not depression. We identified Ziziphus jujuba, a natural plant, as a dual therapeutic agent for both UC and anxiety using the Batman database. Magnoflorine, the predominant compound found in Ziziphus jujuba, exhibits promising therapeutic properties for the treatment of UC and anxiety disorders. We found that magnoflorine not only alleviated colitis but also reduced colitis-induced anxiety behaviors through the gut microbiota. Mechanistically, magnoflorine increased the abundance of Odoribacteraceae and Ruminococcus and regulated bile acid metabolism, especially hyodeoxycholic acid (HDCA) in mice with colitis. HDCA supplementation alleviated both colitis and colitis-induced anxiety. HDCA inhibited the binding of lipopolysaccharide to the TLR4/MD2 complex, thereby inhibiting microglial activation and alleviating neuroinflammation.

CONCLUSION: Our study revealed that magnoflorine alleviated colitis-induced anxiety-like behaviors by regulating the gut microbiota and microglia-mediated neuroinflammation, which has the potential to treat patients with IBD and anxiety disorders. Video Abstract.}, } @article {pmid40713718, year = {2025}, author = {Pisani, A and Petito, V and Paciello, F and Emoli, V and Masi, L and Hizam, VM and Puca, P and Montuoro, R and Chierico, FD and Putignani, L and Grassi, C and Galli, J and Taglialatela, M and Caristo, ME and Ianiro, G and Lopetuso, LR and Cammarota, G and Gasbarrini, A and Fetoni, AR and Scaldaferri, F}, title = {Intestinal inflammation and microbiota modulation impact cochlear function: emerging insights in gut-ear axis.}, journal = {Cell communication and signaling : CCS}, volume = {23}, number = {1}, pages = {357}, pmid = {40713718}, issn = {1478-811X}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Cochlea/physiopathology/pathology ; Female ; Mice, Inbred C57BL ; Mice ; *Inflammation/pathology ; Humans ; Dysbiosis ; Fecal Microbiota Transplantation ; Colitis, Ulcerative/microbiology ; Myeloid Differentiation Factor 88/metabolism ; *Intestines/microbiology/pathology ; }, abstract = {BACKGROUND: Although several evidence demonstrates a "gut-microbiota-brain axis", suggesting a bidirectional communication between gut microbiota and the central nervous system, less is known about a possible link between the gut and the peripheral nervous system, including the inner ear.

METHODS: Here, we investigated the impact of intestinal inflammation and the modulation of gut microbiota through fecal microbiota transplantation on hearing sensitivity. Female C57BL/6 mice were assigned to four groups: control (Ctrl), DSS-induced colitis (DSS), FMT from patients with active ulcerative colitis (FMT aUC), and FMT from patients with ulcerative colitis in remission (FMT rUC). Auditory function was evaluated by auditory brainstem responses (ABR). Morphological and molecular analyses on cochlear tissues were performed using immunofluorescence, histological staining, and Western blot to assess inflammation, oxidative stress, and blood-labyrinth barrier integrity. Donor microbiota composition was characterized by 16S rRNA sequencing, and systemic inflammation was evaluated by measuring serum lipopolysaccharide (LPS) levels.

RESULTS: We found that intestinal dysbiosis is associated with functional, morphological, and molecular alterations in the cochlea, such as increased oxidative stress, inflammation, and altered blood-labyrinth barrier permeability. This leads to macrophage infiltration and immune response activation through the MyD88/NF-κB pathway. Notably, these effects were exacerbated by FMT from subjects with aUC, while FMT from patients with rUC provided a protective effect on cochlear functions.

CONCLUSIONS: Overall, our findings suggest that gut inflammation, microbiota alteration, or its therapeutic modulation can impact inner ear pathology: worsening gut inflammatory status negatively affects hearing sensitivity, while the restoration of gut microbiota positively impacts auditory function.}, } @article {pmid40712381, year = {2025}, author = {Li, Q and Wang, G and Zhao, J and Chen, W and Tian, P}, title = {Gut microbiota and myelination: Crosstalk across the lifespan and microbiota-based modulation strategies.}, journal = {Microbiological research}, volume = {300}, number = {}, pages = {128286}, doi = {10.1016/j.micres.2025.128286}, pmid = {40712381}, issn = {1618-0623}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Myelin Sheath/metabolism/physiology ; Animals ; Probiotics ; Fecal Microbiota Transplantation ; Multiple Sclerosis/microbiology ; Autism Spectrum Disorder/microbiology ; }, abstract = {Myelin, a lipid-rich sheath that insulates axons, is essential for efficient neural signal transmission and the modulation of neural circuits. Its formation, maintenance, and regeneration are tightly regulated processes that shape neurodevelopment, cognition, and emotional stability. Recent evidence positions the gut microbiota as a critical modulator of myelination, orchestrating metabolic signaling, immune homeostasis, and neuroinflammatory responses. Notably, the synchronized development and remodeling of gut microbiota and myelin across key life stages suggest a dynamic and bidirectional interplay essential for sustaining neurological health. Disruptions in this axis are increasingly recognized as contributing factors in dysmyelination-related disorders, including autism spectrum disorder, Alzheimer's disease, and multiple sclerosis. Harnessing microbiota-targeted interventions-such as fecal microbiota transplantation, dietary modulation, and probiotic therapies-holds promise for restoring myelin integrity and mitigating disease pathology. This review provides a comprehensive synthesis of the gut microbiota-myelin interface, delineating mechanistic insights and translational opportunities for microbiome-based therapeutic strategies in neuroprotection.}, } @article {pmid40711721, year = {2025}, author = {Shoukry, AEA and Rahhal, A and Constantinou, C}, title = {The role of the gut microbiota and metabolites in heart failure and possible implications for treatment.}, journal = {Heart failure reviews}, volume = {}, number = {}, pages = {}, pmid = {40711721}, issn = {1573-7322}, abstract = {The prevalence of heart failure has increased significantly in recent years, prompting investigations into novel contributory factors. Among these, alterations in the gut microbiota composition have garnered attention due to their potential association with heart failure. Disruption in the bacterial environment associated with heart failure is characterized by heightened levels of Proteobacteria and Firmicutes and decreased levels of Bifidobacteria and Bacteroides. Reduced blood supply weakens the gut barrier, facilitating the transportation of bacteria and metabolites into the bloodstream. This breach can trigger an immune response and inflammation, subsequently contributing to the pathogenesis of heart failure through the generation of harmful organic compounds in the gastrointestinal tract and bloodstream. Specific metabolites, including short-chain fatty acids, trimethylamine, and trimethylamine N-oxide also contribute to the development of heart failure. Management of heart failure includes pharmacological management, surgery, and lifestyle modifications including recommendations for the consumption of a diet high in fruits and low in animal products. Heart failure can be managed by modulating the gut microbiota. Clinical interventions include antibiotics, prebiotics, and dietary changes. However, other approaches including fecal microbial transplantation, probiotics, and natural phytochemicals are still under study in animal models. This review highlights the significant yet underexplored link between gut microbiota and heart failure, suggesting that further research could lead to new therapeutic strategies and dietary recommendations to mitigate heart failure progression.}, } @article {pmid40709504, year = {2025}, author = {Sheng, H and Xu, W and He, Y and Cai, Y and Wang, Z and Tao, X and Qiu, L and Wei, H}, title = {Amelioration of hypercholesterolemia by Lactiplantibacillus plantarum GLPL02 via regulating intestinal flora and cholesterol metabolism.}, journal = {Journal of the science of food and agriculture}, volume = {}, number = {}, pages = {}, doi = {10.1002/jsfa.70078}, pmid = {40709504}, issn = {1097-0010}, support = {82360114//National Natural Science Foundation of China/ ; 82160791//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: In recent years, hypercholesterolemia has become one of the important risk factors for death around the world. Lactic acid bacteria (LAB), especially Lactiplantibacillus plantarum, exhibit strain-specific property of cholesterol-lowering activity. However, the metabolic mechanism involved in lipid-lowering capacity and regulation of intestinal flora of L. plantarum has not been well elucidated comprehensively.

RESULTS: The present study aimed to screen out cholesterol-lowering lactic acid bacteria from healthy lean individuals, evaluate their cholesterol-lowering effect and disclose its mechanism of amelioration of hypercholesterolemia in mice fed a high-cholesterol diet (HCD). Upon probiotic properties evaluation, the cholesterol removal rate of Lactiplantibacillus plantarum GLPL02 was 53.58%, and cholesterol degradation rate was 39.39%. In the systematic exploration of a model of HCD-induced mice and fecal microbiota transplantation, L. plantarum GLPL02 was found to reduce plasma lipid profiles (total cholesterol, triglycerides and low-density lipoprotein-cholesterol) and glucose tolerance, alleviate liver damage and steatosis, positively regulate intestinal flora related to cholesterol metabolism, upregulate genes relevant to decomposition (CYP7A1) and transportation (LDLR, ABCG5/8 and NPC1L1) of cholesterol, and downregulate genes relevant to synthesis (SREBP-2 and HMGCR), thereby improving hypercholesterolemia. Meanwhile, acetate and butyrate affected cholesterol metabolism in HepG2 cell through regulating cholesterol metabolism. Therefore, L. plantarum GLPL02 ameliorated hypercholesterolemia by regulating intestinal flora and genes related to cholesterol metabolism.

CONCLUSION: The present study indicates that L. plantarum GLPL02 and short-chain fatty acids (propionate, butyrate) ameliorated hypercholesterolemia and offers new insights into the role of L. plantarum in systemic cholesterol reduction from the perspective of microbiota-short-chain fatty acid interactions. © 2025 Society of Chemical Industry.}, } @article {pmid40709417, year = {2025}, author = {Lee, SB}, title = {[Expanding Role of Gastroenterologists in Acute Gastrointestinal Graft-versus-Host Disease: From Diagnosis and Management to Microbiome-Based Strategies].}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {85}, number = {3}, pages = {268-273}, doi = {10.4166/kjg.2025.049}, pmid = {40709417}, issn = {2233-6869}, mesh = {Humans ; *Graft vs Host Disease/diagnosis/therapy/pathology/drug therapy ; Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Pyrimidines ; Acute Disease ; Antibodies, Monoclonal, Humanized/therapeutic use ; Pyrazoles/therapeutic use ; Nitriles ; }, abstract = {Acute graft-versus-host disease (GVHD) is a major complication following allogeneic hematopoietic stem cell transplantation. Steroid-refractory cases have poor outcomes, so an accurate diagnosis, particularly differentiation from cytomegalovirus colitis, is critical. Ruxolitinib is the standard second-line therapy, while Vedolizumab has shown potential in gut-specific modulation. Recent studies have reported that reduced microbiome diversity and the loss of short-chain fatty acid-producing bacteria are linked to acute GVHD severity and mortality. Fecal microbiota transplantation may offer benefit in selected steroid-refractory cases, but the evidence remains limited and variable. Gastroenterologists play an essential role in diagnosis and microbiome-guided care. A personalized approach incorporating microbial biomarkers may improve the future outcomes.}, } @article {pmid40708926, year = {2025}, author = {Zhang, Y and Dong, Y and Sun, C and Zhang, L and Zhang, Y and Wang, D and Chen, Q and Yao, J and Wu, Y and Wang, T}, title = {Shouhui Tongbian Capsule ameliorates 5-fluorouracil induced constipation in mice by modulating gut microbiota and activating PI3K/AKT/AQP3 signaling pathway.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1596881}, pmid = {40708926}, issn = {1664-302X}, abstract = {OBJECTIVE: Shouhui Tongbian Capsule (SHTC) has been clinically applied to treat various types of constipation, including chemotherapy-induced constipation. However, the pharmacological mechanism by which it regulates intestinal peristalsis and treats constipation is unclear. In this study, we aimed to investigate the underlying mechanism of SHTC on chemotherapy-induced constipation through regulating of gut microbiota and PI3K/AKT/AQP3 signaling pathway.

METHODS: Chemotherapy-induced constipation was induced with 5-Fluorouracil in C57BL/6 mice. SHTC was administrated with different dosages (100, 200, 400 mg/kg) for 12 days. The intestinal tissues were collected for the measurements of intestinal propulsion rate, time of first black stool, and expressions of colonic aquaporin. 16S rRNA sequencing, short-chain fatty acids (SCFAs) profiling, and fecal microbiota transplantation (FMT) were performed to confirm whether gut microbiota is a key target for SHTC. Finally, the expressions of proteins or genes related to PI3K/AKT/AQP3 pathway were detected.

RESULTS: SHTC markedly improved the pathological manifestations associated with constipation and restored the deregulated gut microbiota. The mice that were given fecal supernatant from SHTC-treated mice showed significant improvement in constipation symptoms. Additionally, SHTC increased the level of acetic acid and upregulated the expression of AQP3, with activation of PI3K/AKT. Furthermore, the blockade of PI3K reversed the beneficial effect of acetic acid on the expression of AQP3.

CONCLUSION: Our findings indicated that SHTC effectively relieved 5-FU-induced constipation in mice, mainly by regulating homeostasis of gut microbiota and activating PI3K/AKT/AQP3 pathway, making it a potential protective agent against chemotherapy-induced constipation.}, } @article {pmid40708753, year = {2025}, author = {Zheng, YM and Ye, MM and Zhang, HY and Luo, DP and Liu, T and He, XX and Chen, XY and Wu, LH}, title = {Retrospective review: single- and multidonor washed microbiota transplantation have equivalent efficacy in the treatment of autism.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1606417}, pmid = {40708753}, issn = {2235-2988}, mesh = {Humans ; Retrospective Studies ; Male ; *Fecal Microbiota Transplantation/methods ; Female ; Feces/microbiology ; Child ; Treatment Outcome ; *Autism Spectrum Disorder/therapy/microbiology ; Child, Preschool ; Gastrointestinal Microbiome ; Adolescent ; *Autistic Disorder/therapy ; }, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder with no effective treatment. This study explored the short-term clinical effects of washed microbiota transplantation (WMT) with different numbers of donors on autism.

METHODS: Consecutive ASD patients treated with two continuous WMT courses from March 2020 to March 2022 at the First Affiliated Hospital of Guangdong Pharmaceutical University were retrospectively assessed. Basic information, aberrant behavior checklist (ABC) scores, childhood autism rating scale (CARS) scores, sleep disturbance scale for children (SDSC) scores, adverse reactions, and feces were collected.

RESULTS: Forty-four patients were included (single-donor group: 17 patients; multidonor group: 27 patients). The CARS, ABC and SDSC scores didn't differ between the two groups before treatment. After two courses, the scores for the 44 patients were lower than those at baseline (P<0.05), with no severe adverse reactions observed. After the first course, the mean ABC (P=0.049) and SDSC (P=0.019) scores were significantly different between the single-donor and multidonor groups, but the difference disappeared after two courses. The alpha-diversity of the faecal flora in the effective-group was greater than that in the ineffective-group (Shannon index P=0.0018). Lactobacillus was the predominant genus in the effective group, whereas Faecalibacterium, Campylobacter, and Sphingomonas were predominant genera in the ineffective group.

CONCLUSION: After two WMT courses, the symptoms of ASD improved, with good short-term treatment efficacy. The ASD symptom improvement did not differ between the single-donor and multidonor groups. Changes in the alpha-diversity and abundance of the faecal microbiota after WMT may be related to treatment efficacy.}, } @article {pmid40707990, year = {2025}, author = {Drevland, OM and de Muinck, EJ and Trosvik, P and Hammerstad, M and Kvitne, KE and Midtvedt, K and Åsberg, A and Robertsen, I}, title = {Microbiome-derived reactivation of mycophenolate explains variations in enterohepatic recirculation in kidney transplant recipients.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {169}, pmid = {40707990}, issn = {2049-2618}, support = {315792//Norges Forskningsråd/ ; 315792//Norges Forskningsråd/ ; }, mesh = {*Mycophenolic Acid/pharmacokinetics/analogs & derivatives/metabolism ; *Kidney Transplantation ; Humans ; *Gastrointestinal Microbiome/drug effects ; Male ; Female ; *Immunosuppressive Agents/pharmacokinetics/therapeutic use ; Middle Aged ; Feces/microbiology ; Adult ; Transplant Recipients ; Glucuronidase/metabolism/genetics ; Glucuronides/metabolism ; Metagenomics/methods ; *Enterohepatic Circulation ; }, abstract = {BACKGROUND: The pivotal role of microbes in drug metabolism is increasingly recognized, as variation in the gut microbiome composition between individuals has been shown to impact systemic drug exposure, efficacy and toxicity. Mycophenolate mofetil (MMF) is a cornerstone in immunosuppressive therapy following solid organ transplantation. However, dosing and tolerance are challenged by significant pharmacokinetic variability among patients, largely due to variable degrees of enterohepatic recirculation of mycophenolic acid (MPA), the active moiety of MMF. It is hypothesized that the variability in MPA recirculation is driven by gut microbiome-derived β-glucuronidase (β-GUS) mediated cleavage of MPA-glucuronide (MPAG) excreted in the bile. Here, we investigated the bidirectional interaction between MPA and the gut microbiome in kidney transplant recipients, using a combination of in vivo and in vitro data.

RESULTS: We compared the fecal microbiomes of kidney transplant recipients (n = 21) both pre- and post-transplantation to healthy individuals (n = 15) using shotgun metagenomic sequencing. We also determined the individual microbiome-derived reactivation rate of MPAG to MPA and show a strong positive correlation between this reactivation rate and the degree of MPA enterohepatic recirculation in vivo. Through metagenomic analysis, the reactivation rate of MPA was linked to specific gut microbial species. In particular, specific β-GUS gene variants associated with Faecalibacterium prausnitzii showed a strong impact on the conversion of MPAG to MPA. Furthermore, our study confirmed a significant shift in microbial composition post-transplantation and revealed notable fluctuations in species such as F. prausnitzii and Akkermansia muciniphila across different time points after transplantation. Lastly, we provide evidence that the microbiome-derived reactivation rate of MPA is linked to specific beta-glucuronidase alleles.

CONCLUSIONS: We highlight for the first time that the ex vivo determined reactivation rate of MPA explains the variation of enterohepatic recirculation, emphasizing the important role of F. prausnitzii in this process. More broadly, our findings suggest that the gut microbiome significantly influences the degree of enterohepatic recirculation of MPA, providing valuable insights that could be relevant for optimizing individualized immunosuppressive drug dosing in transplant patients. Video Abstract.}, } @article {pmid40707965, year = {2025}, author = {Wang, X and Xiao, ZJ and Xue, CZ and Wu, WT and Yang, JH and Yan, C and Wang, Y and Kui, Y and Luo, WB and Du, X and Zan, RN and Shang, RJ and Li, S and Na, R and Han, S and Li, SZ}, title = {Clinical confirmation of an infection with Echinococcus multilocularis (Mongolian genotype): first case report of human alveolar echinococcosis in Inner Mongolia, China.}, journal = {Infectious diseases of poverty}, volume = {14}, number = {1}, pages = {74}, pmid = {40707965}, issn = {2049-9957}, support = {82404325//National Natural Science Foundation of China/ ; GWVI-11.1-12//Three-Year Initiative Plan for Strengthening Public Health System Construction in Shanghai (2023-2025) Key Discipline Project/ ; }, mesh = {*Echinococcus multilocularis/genetics/isolation & purification/classification ; Humans ; Female ; China ; Middle Aged ; Animals ; Genotype ; *Echinococcosis/parasitology/diagnosis ; Phylogeny ; *Echinococcosis, Hepatic/parasitology/diagnosis/surgery ; Fatal Outcome ; Dogs ; Liver Transplantation ; }, abstract = {BACKGROUND: Alveolar echinococcosis (AE), caused by the larval stage of Echinococcus multilocularis, poses a substantial global health challenge due to its high mortality profile. This study reports the inaugural human infection of echinococcosis caused by the Mongolian genotype of E. multilocularis in China, also the first reported indigenous AE case in Inner Mongolia.

CASE PRESENTATION: A 58-year-old female pastoralist from Inner Mongolia, who had no endemic region exposure history but prolonged occupational contact with dogs, presented with severe AE. Clinical examinations revealed a massive hepatic lesion exceeding 10 cm in diameter, accompanied by elevated eosinophils (0.90 × 10[9]/L) and basophils (0.08 × 10[9]/L). Despite undergoing liver transplantation, the patient succumbed postoperatively. Histopathological confirmation and molecular phylogenetics identified the Mongolian genotype of E. multilocularis infection, distinct from the predominant Asian genotype in China. Potential evidence of zoonotic transmission was discovered through genotype-matched E. multilocularis detection in corsac fox (Vulpes corsac) feces from the grasslands along the shores of Hulun Lake (Hulun Buir City, northeastern Inner Mongolia, China).

CONCLUSIONS: This report provides the primary evidence of a locally acquired human AE infection in China caused by the Mongolian genotype of Echinococcus multilocularis. The discovery of this case challenges historical classifications of echinococcosis endemic areas. The findings call for revised AE-endemic identification criteria, improved AE diagnostic protocols, and enhanced AE surveillance in the Inner Mongolia region to generate further epidemiological evidence and information on disease progression.}, } @article {pmid40706525, year = {2025}, author = {Gutting, T and Brobeil, A and Strach, L and Stricker, E and Boxberger, M and Trierweiler-Hauke, B and Heine, C and Michl, P and Luntz, S and Robert, B and Göbel, F and Weis, C and Pfützner, A}, title = {Sealing efficiency and safety of a polyurethane-based fecal management system in intensive care-Results from a real-world study.}, journal = {Australian critical care : official journal of the Confederation of Australian Critical Care Nurses}, volume = {38}, number = {5}, pages = {101296}, doi = {10.1016/j.aucc.2025.101296}, pmid = {40706525}, issn = {1036-7314}, abstract = {OBJECTIVE: Fecal management systems (FMSs) are critical for preventing skin irritations and anal dermatitis in intensive care. A polyurethane-based system (hygh-tec® [Advanced Medical Balloons]) has been introduced in the European Union and United States. This real-world observational study aimed to evaluate the sealing efficiency and safety of the system in routine care.

METHODS: Thirty-nine patients were included in the descriptive analysis (18 females and 21 males; mean age: 66.4 ± 10.5 years; body mass index: 28.8 ± 11.7 kg/m[2]). Intensive care nurses documented findings related to sealing efficiency, anal lesions, and adverse events during their shifts.

RESULTS: Sealing efficiency was assessed from 1110 shift reports. The mean device usage duration was 10.8 days (range: 3-31 days). No visible perianal contamination was noted in 76.0% of shift reports (n = 844). Relevant leakage was documented in 10.7% of cases and was independent of body mass index, anal sphincter muscle tone, and reason for admission. Stool consistency and patient vigilance had minimal influence. There were no device-related adverse events, and the incidence of anal lesions was 0.8% over 31 days of use.

CONCLUSION: The polyurethane-based FMS demonstrated excellent sealing efficiency, tolerability, and safety. Controlled studies are needed to confirm these findings and evaluate economic implications. FMSs can improve both work quality and patient safety.}, } @article {pmid40705333, year = {2025}, author = {Woodworth, MH and Babiker, A and Prakash-Asrani, R and Mehta, CC and Steed, DB and Ashley, A and Koundakjian, D and Acharya, A and Grooms, L and Bower, CW and Suchindran, DR and Trehan, T and Halpin, AL and Spalding Walters, M and Reddy, SC and Samore, MH and Roghmann, MC and Hayden, MK and Van Riel, J and Burd, EM and Lohsen, S and Satola, SW and Fridkin, SK}, title = {Microbiota Transplantation Among Patients Receiving Long-Term Care: The Sentinel REACT Nonrandomized Clinical Trial.}, journal = {JAMA network open}, volume = {8}, number = {7}, pages = {e2522740}, pmid = {40705333}, issn = {2574-3805}, support = {UM1 AI104681/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Female ; Male ; *Fecal Microbiota Transplantation/methods/adverse effects ; Aged ; Middle Aged ; *Long-Term Care/methods ; }, abstract = {IMPORTANCE: Intestinal multidrug-resistant organism (MDRO) colonization is highly prevalent in long-term acute care hospital (LTACH) patients and is associated with MDRO infection and transmission. However, there are no therapies approved by the US Food and Drug Administration to reduce intestinal MDRO colonization.

OBJECTIVE: To determine the safety and acceptability of fecal microbiota transplantation (FMT) in LTACH patients.

This single-center, open-label nonrandomized clinical trial was conducted from April to December 2023 at an LTACH in the Southeastern US with median 50-patient census and 28-day length of stay. Patients with MDRO colonization were identified by perirectal prevalence sampling. Patients colonized with at least 1 target MDRO were approached for informed consent for FMT. FMT recipients were compared with untreated controls with MDRO colonization. Data were analyzed from August 2024 to May 2025.

INTERVENTION: Healthy donor fecal microbiota (50-100 g stool and 250 mL normal saline with 9% glycerol) instilled via gastrostomy tube or enema without antibiotic or bowel preparation conditioning.

MAIN OUTCOMES AND MEASURES: The primary outcome was frequency and severity of adverse events. Solicited adverse events were recorded for 7 days. Unsolicited adverse events were recorded for 6 months. Four weekly perirectal MDRO cultures were performed after FMT.

RESULTS: A total of 42 patients, including 10 (mean [SD] age, 63.8 (14.5) years; 7 [70%] female) who received FMT and 32 contemporaneous controls (mean [SD] age, 64.0 [13.7] years; 13 [41%] female) were assessed. In 2 prevalence surveys, 23 of 32 (72%) and 26 of 34 (77%) perirectal cultures grew at least 1 MDRO. Among the FMT group, 5 patients received FMT via gastrostomy alone, 4 via enema alone, and 1 with both routes more than 30 days apart. No serious adverse events were attributed to FMT, and post-FMT solicited adverse events were mild. At final visit, all perirectal cultures from FMT recipients grew at least 1 MDRO. Post hoc analyses found numerically fewer FMT recipients had positive blood culture results (0 individuals vs 6 individuals [19%]; P = .31), pathogen intestinal dominance (2 of 8 individuals [25%] vs 4 of 8 individuals [50%]; P = .61), and 7 fewer days of antibiotic therapy per 1000 patient days (median [IQR], 12.6 [0-25.2] days vs 19.7 [6.5-36.1] days; P = .38) compared with controls in the 6 months after prevalence survey, although these differences were not statistically significant. Accounting for higher baseline FMT recipient antibiotic use, difference-in-differences analysis estimated 26 (95% CI, -64 to 12) fewer days of antibiotic therapy per 1000 patient-days after FMT, although this difference was also not statistically significant.

CONCLUSIONS AND RELEVANCE: In this nonrandomized pilot clinical trial, FMT was acceptable for LTACH patients without related serious adverse events. Although not powered to test these outcomes, this study found potential reductions in bacteremia, intestinal pathogen domination, and antibiotic use associated with FMT, suggesting FMT should be evaluated in larger, randomized trials.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05780801.}, } @article {pmid40703681, year = {2025}, author = {Hlavaty, M and Brezina, J and Osadcha, T and Fabian, O and Vajsova, A and Drastich, P and Cahova, M and Bajer, L}, title = {Serological Markers of Intestinal Barrier Function and Inflammation as Potential Predictors of Recurrent Primary Sclerosing Cholangitis.}, journal = {Clinical and experimental gastroenterology}, volume = {18}, number = {}, pages = {171-178}, pmid = {40703681}, issn = {1178-7023}, abstract = {The impairment of intestinal barrier function is implicated in primary sclerosing cholangitis, but the clinical evidence is scarce. Therefore, we performed a cross-sectional study to evaluate serological markers of inflammation and intestinal permeability (Reg3a, iFABP, Zonulin, Calprotectin) in patients after liver transplantation (LT) for PSC. The cohort included 26 subjects with PSC recurrence (rPSC), 87 subjects without PSC recurrence (non-rPSC), and a unique control group consisting of post-LT patients (n = 113) transplanted due to alcohol cirrhosis. Generalized Linear Models were calculated to assess the association between serological markers of intestinal barrier function or inflammation (IP_Models) and PSC diagnosis per se (IP_Model_1), non-rPSC (IP_Model_2) or rPSC incidence (IP_Model_3) and compared with models (ST_Models) based on validated PSC markers (ALP, GGT, bilirubin). The increased probability of PSC occurrence (IP_Model_1, p < 0.001, AIC = 182) was associated with higher serum Reg3a concentration, while a negative association was found for iFABP, BMI, and age. The probability of non-recurrence (IP_Model_2, p < 0.001, AIC = 167) was associated with lower Reg3a concentration, older age, and BMI. The performance of IP_Models_1,2 and ST_models_1,2 was comparable. rPSC prediction was less precise by both models (IP_Model_3 p = 0.063, AIC = 92; ST_Model_3 p < 0.001, AIC = 108). rPSC incidence was positively associated with fecal calprotectin and serum zonulin concentrations, while it was independent of Reg3a, iFABP, age or BMI. In conclusion, this pilot study suggests that impaired intestinal permeability is associated with the pathophysiology of rPSC. Our data could serve as a basis for testing in a larger independent validation cohort and, if confirmed, help to explain the mechanisms underlying the pathophysiology of PSC and the recurrence of this disease after transplantation.}, } @article {pmid40703302, year = {2025}, author = {Zhang, J and Ren, X and Li, B and Zhao, Z and Li, S and Zhai, W}, title = {Fecal microbiota transplantation is a promising therapy for kidney diseases.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1628722}, pmid = {40703302}, issn = {2296-858X}, abstract = {Kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD), pose growing global public health challenges. With the emergence and expanding understanding of the "microbiota-gut-kidney axis," increasing evidence indicates that intestinal barrier disruption, abnormal microbial metabolite production, and intestinal mucosal immune dysregulation play critical roles in the pathogenesis of various kidney diseases. Therapeutic modulation of the gut microbiota through probiotics, prebiotics, synbiotics, and natural products has shown potential for slowing kidney disease progression. Fecal microbiota transplantation (FMT), a direct method of reconstructing gut microbial communities, has demonstrated promise in CKD by targeting mechanisms such as inhibition of the renin-angiotensin system (RAS), attenuation of inflammation and immune activation, and restoration of intestinal barrier integrity. Although FMT has not yet been applied to AKI, its use in CKD subtypes, such as diabetic nephropathy, IgA nephropathy, membranous nephropathy, and focal segmental glomerulosclerosis, has shown encouraging preclinical and preliminary clinical results. This review systematically summarizes the current research on FMT in the context of kidney disease, evaluates its therapeutic mechanisms and feasibility, and highlights its limitations. Most studies remain in the preclinical stage, while available clinical trials are limited by small sample sizes, heterogeneous designs, and lack of standardization. To enhance the translational potential of FMT in nephrology, future studies should incorporate artificial intelligence for personalized intervention strategies and establish standardized protocols to ensure safety, efficacy, and reproducibility.}, } @article {pmid40703229, year = {2025}, author = {Yuan, C and Liu, L and Zeng, D and Yuan, J and Guo, L and Zhang, J}, title = {Exploring the influence of gut microbiota metabolites on vitiligo through the gut-skin axis.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1566267}, pmid = {40703229}, issn = {1664-302X}, abstract = {Vitiligo is an autoimmune skin disease with a complex pathogenesis closely linked to immune imbalance and oxidative stress. Currently, comprehensive curative treatments and effective relapse prevention strategies are lacking. Recently, the "gut-skin axis" hypothesis has offered new insights into the pathological mechanisms of vitiligo. Studies indicate that gut microbiota and their metabolic products significantly affect disease progression by regulating immune homeostasis and inflammatory responses in the host. This review systematically examines the effects of short-chain fatty acids, secondary bile acids, and tryptophan metabolites on the human immune system and the inflammatory milieu, and their direct impact on melanocytes. Furthermore, considering the reduced diversity of gut microbiota in individuals with vitiligo, this article also evaluates methods including probiotic intervention, the Mediterranean diet, and fecal microbiota transplantation, which may emerge as potential therapeutic strategies for vitiligo by restoring microbiota balance. Future multidimensional therapeutic strategies that target gut microbiota metabolites show promise for pioneering innovative approaches in vitiligo management.}, } @article {pmid40701508, year = {2025}, author = {Chen, WJ and Wang, JP and Zhou, JR and He, Y and An, DQ and Tian, TT and Liang, MT and Aikepa, D and Kahaer, M and Sun, YP}, title = {Efficacy and mechanisms of compound Bai Mao Yin in regulating uric acid transport and improving the intestinal microbiota to alleviate hyperuricemia via the enterorenal axis.}, journal = {Microbial pathogenesis}, volume = {207}, number = {}, pages = {107922}, doi = {10.1016/j.micpath.2025.107922}, pmid = {40701508}, issn = {1096-1208}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; Humans ; *Uric Acid/metabolism/blood ; Mice ; *Hyperuricemia/drug therapy/metabolism/microbiology ; Male ; Fecal Microbiota Transplantation ; Disease Models, Animal ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Middle Aged ; Feces/microbiology ; Female ; Metagenomics ; Kidney/metabolism/drug effects ; RNA, Ribosomal, 16S/genetics ; Signal Transduction/drug effects ; Biological Transport/drug effects ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: The compound Bai Mao Yin (BMY) has demonstrated therapeutic efficacy in reducing uric acid (UA) levels; however, its underlying mechanisms remain unclear.

METHODS: The UA-lowering effects of BMY were evaluated in a cohort of 40 patients with hyperuricemia (HUA) who received BMY treatment for 90 days. Fecal samples were collected at baseline (day 0), mid-treatment (day 30), and post-treatment (day 90) for metagenomic sequencing to analyze changes in gut microbiota and identify potential BMY targets in HUA. These clinical findings were validated in a hyperuricemic mouse model induced by xanthine and potassium oxonate. Mouse fecal samples were analyzed via 16S rDNA (V3-V4 region) sequencing to assess microbiota shifts. Additionally, fecal microbiota transplantation (FMT) from BMY-treated mice to HUA mice and in vitro cell experiments using HK2 cells were conducted to investigate the roles of BMY and the reconstructed microbiota in UA metabolism, renal UA transport, and inflammation through upstream signaling pathways.

RESULTS: Clinical cohort studies demonstrated that the BMY effectively lowers UA levels in patients with HUA without inducing hepatorenal toxicity. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of metagenomic data revealed that BMY modulates the gut microbiota and influences ATP-binding cassette transporters and UA metabolism-related pathways. In animal models, BMY increased the relative abundance of beneficial gut bacteria, reduced intestinal permeability, and regulated UA transporters in both intestinal and renal systems, contributing to UA reduction. In vitro assays showed that BMY directly decreased UA levels in the cell supernatant and suppressed interleukin-1β (IL-1β) and interleukin-6 (IL-6) expression by downregulating the TLR4/MYD88/NFκB signaling pathway, thereby alleviating inflammation.

CONCLUSIONS: Compound BMY was found to improve the intestinal microenvironment and modulate UA transport via the enterorenal axis, effectively reducing HUA.}, } @article {pmid40701347, year = {2025}, author = {Yun, F and Han, X and Wang, Z and Gao, Q and Xu, M and Liu, H and Fang, N and Zhang, Y and Li, Y and Gong, Y}, title = {Intermittent fasting ameliorates resistant hypertension through modulation of gut microbiota.}, journal = {Pharmacological research}, volume = {219}, number = {}, pages = {107864}, doi = {10.1016/j.phrs.2025.107864}, pmid = {40701347}, issn = {1096-1186}, abstract = {Resistant hypertension (RH) remains a major cardiovascular challenge despite optimal pharmacological treatment. Intermittent fasting (IF) has demonstrated beneficial effects in various diseases, but its impact on RH and the underlying mechanisms remain unclear. In this study, we explored the effects of a 2 week IF regimen (16 h fasting/8 h eating) on RH patients and spontaneously hypertensive rats (SHRs) resistant to antihypertensive drugs. We found that IF significantly reduced blood pressure in RH patients, accompanied by a shift in the gut microbiota, including increased abundance of Akkermansia muciniphila and Adlercreutzia equolifaciens. These microbiota alterations were correlated with a decrease in lipopolysaccharide (LPS) and trimethylamine-N-oxide (TMAO) levels, and an increase in short-chain fatty acids (SCFAs). Furthermore, fecal microbiota transplantation (FMT) from drug-resistant SHRs successfully transferred both hypertension and impaired drug efficacy to recipient rats. Supplementation with Akkermansia muciniphila and Adlercreutzia equolifaciens significantly lowered blood pressure in SHR rats resistant to antihypertensive drugs. In RH patients, oral supplementation with Akkermansia muciniphila reduced blood pressure and normalized LPS, TMAO, and SCFA levels. Our findings provide both clinical and mechanistic evidence supporting IF and A. muciniphila supplementation as promising non-pharmacological approaches for managing resistant hypertension.}, } @article {pmid40699664, year = {2025}, author = {Bonù, ML and Georgopulos, A and Ramera, M and Andreuccetti, J and Guerini, AE and Bozzola, AM and Morelli, V and Balduzzi, J and Katica, M and Cefaratti, M and Granello, L and Triggiani, L and Buglione, M and Magrini, SM and Marampon, F and Mondini, M and Parisi, S and Timon, G and Bellu, L and Rescigno, M and Arcangeli, S and Scorsetti, M}, title = {Microbiota Modulation of Radiosensitiveness and Toxicity in Gastrointestinal Cancers: What Radiation Oncologists Need to Know-A Review on Behalf of the Italian Association of Radiobiology (AIRB).}, journal = {Current issues in molecular biology}, volume = {47}, number = {4}, pages = {}, pmid = {40699664}, issn = {1467-3045}, abstract = {The impact of the microbiota on radiation (RT)-induced toxicity and cancer response to radiotherapy is an emerging area of interest. In this review, we summarize the available preclinical and clinical evidence concerning microbiota modulation of RT toxicity and efficacy in the main gastrointestinal (GI) districts. A huge amount of data supports the clinical application of microbiota modulation, particularly through prebiotics and probiotics, to prevent or mitigate radiotherapy-induced toxicity in rectal cancer. Preclinical and clinical studies also support the observation of microbiota modulation to impact the toxicity and efficacy of treatment in esophageal cancer, hepatocellular carcinoma (HCC), and anal squamous cell carcinoma (ASCC). However, insufficient evidence remains to endorse microbiota modulation as a strategy to enhance tumor radiosensitivity in clinical practice. Well-designed studies focusing on prebiotics, probiotics, and fecal microbiota transplantation are needed across all GI sites to evaluate their potential to improve treatment efficacy, as suggested by promising preclinical findings. The impact of pre-treatment microbiota analyses should be addressed in prospective studies to verify the efficacy of patient-level tailored strategies. Additionally, the repurposing of radioprotective agents with innovative delivery systems, such as encapsulated amifostine, holds significant promise for mitigating small bowel toxicity, thereby enabling more effective RT treatment.}, } @article {pmid40697274, year = {2025}, author = {Wei, N and Dai, S and Li, W and Zhou, J and Chen, Y}, title = {Gut microbiota and sepsis-associated encephalopathy: pathogenesis and precision therapies.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1596467}, pmid = {40697274}, issn = {1662-4548}, abstract = {Sepsis is defined as a condition of immune dysregulation in response to an infection, and sepsis-associated encephalopathy (SAE) is often the initial symptom that manifests in patients with sepsis. This condition is characterized by its high mortality rates and the potential to cause significant disability among survivors. Despite its severity, the underlying pathophysiologic mechanisms that contribute to the development of SAE are not yet fully understood. Additionally, there are no established strict diagnostic criteria or potent treatment options available for this condition. However, an increasing body of evidence suggests that an imbalance in the gut microbiota is associated with SAE, potentially through the gut-brain axis (GBA). The GBA axis refers to the bidirectional communication between the gut microbiota and the central nervous system. In this review, we discuss the changes in the gut microbiota in SAE and the mechanisms of the GBA axis, involving neural, immune, endocrine, and neurotransmitter pathways. Finally, we conclude by evaluating the preclinical and clinical evidence for fecal microbiota transplantation and probiotics in SAE. Targeting the GBA axis will be an actionable target to ameliorate the development and progression of SAE.}, } @article {pmid40697099, year = {2025}, author = {Zhang, Y and Tu, M and Long, P and Zheng, J and Du, G and Xiao, S and Gao, C}, title = {Efficacy of probiotics pretreatment in Helicobacter pylori eradication therapy: a systematic review and meta-analysis of clinical outcomes.}, journal = {Annals of medicine}, volume = {57}, number = {1}, pages = {2533431}, pmid = {40697099}, issn = {1365-2060}, mesh = {*Probiotics/therapeutic use/administration & dosage ; Humans ; *Helicobacter Infections/therapy/microbiology/drug therapy ; *Helicobacter pylori/drug effects ; Anti-Bacterial Agents/therapeutic use ; Treatment Outcome ; Gastrointestinal Microbiome/drug effects ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: Probiotics inhibit Helicobacter pylori (H. pylori) growth and alter gut microbiome, in addition to alleviating the side effects of H. pylori eradication. It has also been reported that H. pylori be eradicated after fecal microbiota transplantation in some cases. However, whether probiotics used before H. pylori eradication improves the eradication rate remains unclear. This study evaluates their role through a systematic review and meta-analysis.

METHODS: We searched PubMed, EMBASE, the Cochrane Library, and the Conference Proceedings Citation Index up to January 31, 2024, to identify randomized controlled studies (RCTs) assessing the efficacy of probiotics used before H. pylori eradication. Meta-analyses of eradication rates were performed.

RESULTS: Twelve eligible RCTs with 2,144 participants were included. The intention-to-treat analysis revealed that the overall eradication rate of H. pylori was higher in the probiotics pretreatment group compared to the control group (80.34% vs. 70.49%), with a risk ratio (RR) of 1.14 (95% CI: 1.08 to 1.19; I[2] = 36%) and side effects were less (16.0% vs. 28.3%, RR = 0.59, 95% CI 0.41 to 0.84). The per-protocol analysis yielded similar results (86.43% vs. 76.88%, RR = 1.12, 95% CI: 1.08 to 1.17; I[2] = 57%). Subgroup analyses, considering factors like geographic location, eradication regimens, and probiotic combinations, consistently confirmed the benefits. Finally, probiotics pretreatment durations of 14 days or more, as well as the study designs pre vs. free and pre and combine vs. free, demonstrated significant effects. Shorter durations and other study designs with fewer studies did not show significant effects.

CONCLUSION: There is moderate to high evidence to suggest that probiotics pretreatment improves H. pylori eradication rate and reduces side effects. These findings highlight the potential value of gut microbiome modulation in H. pylori treatment and offer a new direction for addressing the challenges of antibiotic resistance and treatment failure.}, } @article {pmid40696369, year = {2025}, author = {Song, S and Wen, X and Chen, F and Li, J and Shi, K and Lou, Y and Xu, A and Wen, C and Shao, T}, title = {Qu-zhuo-tong-bi decoction exerts gouty arthritis therapy by skewing macrophage polarization through butanoate metabolism.}, journal = {Chinese medicine}, volume = {20}, number = {1}, pages = {115}, pmid = {40696369}, issn = {1749-8546}, support = {82274302//National Natural Science Foundation of China/ ; 82074248//National Natural Science Foundation of China/ ; 2023C03040//Key Research and Development Program of Zhejiang Province/ ; }, abstract = {BACKGROUND: Qu-zhuo-tong-bi decoction (QZTBD), a traditional Chinese medicine (TCM), has demonstrated efficacy in the treatment of gouty arthritis. However, to date, the precise pharmacological mechanisms remain unclear.

PURPOSE: The study aims to ascertain the therapeutic effects and the underlying mechanisms of QZTBD in the treatment of gouty arthritis.

METHODS: The efficacy and safety of different doses of QZTBD were investigated in Uox-KO mice. Candidate active ingredients were identified using UHPLC-MS/MS. The potential therapeutic pathways of the active ingredients were predicted through network pharmacology. The mechanisms of QZTBD in alleviating gouty arthritis were explored via comprehensive analyses of gut microbiota, combined with RT-qPCR, western blot, immunofluorescence, ELISA, flow cytometry, and Seahorse assay. Fecal microbiota transplantation (FMT), bacterial culture experiment, butyrate-producing bacteria (BPB) and butyrate administration, and 2-DG intervention were conducted to explore the roles of BPB and butanoate metabolism in gout progression and therapeutic mechanisms of QZTBD. In vitro studies further validated the regulatory effects of butyrate and QZTBD on macrophage polarization through glycolysis modulation.

RESULTS: 18.0 g/kg/d of QZTBD effectively alleviated the symptoms of gouty arthritis with excellent hepatic and renal safety. UHPLC-MS/MS analysis and network pharmacology revealed that QZTBD exerts its effects on butanoate metabolism during gouty arthritis inflammation. QZTBD treatment increased the abundance of BPB, the levels of serum and colon butyrate, and the expression levels of Buk and But. The transplantation of QZTBD-treated microbiota reproduced the therapeutic effects of QZTBD. M1 macrophage polarization was suppressed after QZTBD intervention. The administration of BPB and butyrate attenuated gouty arthritis and orchestrated macrophage polarization. Inhibition of glycolysis regulated the phenotype of macrophage and attenuated inflammatory processes. In vitro analysis unveiled that QZTBD and butyrate modulated glycolysis to regulate macrophage polarization, thereby alleviating gouty arthritis.

CONCLUSION: QZTBD targeted butanoate metabolism to regulate macrophage polarization, thereby effectively alleviating intestinal inflammation and restoring immune homeostasis in gouty arthritis. These findings establish a mechanistic foundation for developing precision therapeutic strategies leveraging QZTBD to combat gouty arthritis.}, } @article {pmid40693962, year = {2025}, author = {Mutengo, M and Dashti, A and Liptáková, M and Mulunda, NR and Chabala, FW and Hayashida, K and Chinyanta, S and Chisanga, K and Mwansa, J and Köster, PC and Santín, M and Sotillo, J and Sánchez, S and Carmena, D}, title = {High prevalence of Enterocytozoon bieneusi (microsporidia) in asymptomatic schoolchildren, Zambia.}, journal = {Medical mycology}, volume = {63}, number = {7}, pages = {}, doi = {10.1093/mmy/myaf065}, pmid = {40693962}, issn = {1460-2709}, support = {//Health Institute Carlos III (ISCIII)/ ; PI19CIII/00029//Spanish Ministry of Economy and Competitiveness/ ; FI20CIII/00002//PFIS/ ; //Spanish Ministry of Science and Innovation and Universities/ ; //Women Program of the Women for Africa Foundation/ ; }, mesh = {Humans ; Zambia/epidemiology ; *Enterocytozoon/genetics/isolation & purification/classification ; Child ; Male ; *Microsporidiosis/epidemiology/microbiology ; Female ; Adolescent ; Prevalence ; Feces/microbiology ; Child, Preschool ; Genetic Variation ; DNA, Fungal/genetics ; *Asymptomatic Infections/epidemiology ; Genotype ; Sequence Analysis, DNA ; Polymerase Chain Reaction ; }, abstract = {Microsporidia are single-celled, fungi-related eukaryotic intracellular parasites able to infect a wide diversity of invertebrate and vertebrate hosts. Among them, Enterocytozoon bieneusi and Encephalitozoon spp. (including Enc. cuniculi, Enc. hellem, and Enc. intestinalis) are known causative agents of infectious diseases in immunocompromised individuals, including HIV/AIDS patients and organ transplant recipients. Additionally, asymptomatic microsporidial infections seem more frequent than initially anticipated and might represent an overlooked public health threat. Here, we provide novel data on the occurrence and genetic diversity of microsporidial infections in individual stool samples (n = 247) collected from apparently healthy schoolchildren (age range: 5-18 years; male/female ratio: 1.1) in Lusaka, Zambia. Stool DNA samples were analysed by PCR and Sanger sequencing methods. A basic epidemiological questionnaire was used to retrieve data on variables potentially linked with higher odds of harbouring E. bieneusi infections. A high prevalence rate was found for E. bieneusi (9.3%, 23/247; 95% CI: 6.0-13.6), whereas Enc. intestinalis was much less frequent (0.4%, 1/247; 95% CI: 0.01-2.2). Four known (D, S2, S6, and Type IV) and three novel (HhZbEb1, HhZbEb2, and HhZbEb3) genotypes were identified within E. bieneusi. Genotype D was the predominant genotype found (30.8%, 4/13), followed by genotypes Type IV, HhZbEb2, and HhZbEb3 (15.4%, 2/13 each), and genotypes S2, S6, and HhZbEb1 (7.7%, 1/13 each). The only Encephalitozoon-positive sample was identified as Enc. intestinalis. Subclinical infections by E. bieneusi were common in the investigated paediatric population. Infected children could act as disregarded spreaders of microsporidial pathogens at the community level, thus representing a potential public health concern.}, } @article {pmid40693424, year = {2025}, author = {Lu, HH and Nguyen, NTK and Panwar, R and Lin, CI and Cross, TL and Lin, SH}, title = {Ameliorating Gastrointestinal Symptoms in Children With Autism Spectrum Disorder by Modulating the Gut Microbiota: A Systematic Review and Meta-Analysis.}, journal = {Autism research : official journal of the International Society for Autism Research}, volume = {}, number = {}, pages = {}, doi = {10.1002/aur.70091}, pmid = {40693424}, issn = {1939-3806}, abstract = {Children with autism spectrum disorder (ASD) exhibit a high prevalence (55%) of gastrointestinal symptoms (GISs) and gut dysbiosis. Most studies involving children with ASD have focused on behavioral symptoms but not GISs. This systematic review and meta-analysis investigated the effects of gut microbiota-modulating interventions (GMMIs) on GISs and gut microbial composition in children with ASD. Five databases were searched for relevant domestic and international articles published from database inception until July 15, 2024. The meta-analysis included human trials wherein children with ASD received prebiotics, probiotics, synbiotics, or fecal microbiota transplantation. Intervention effects were measured on the basis of α-diversity, and genus- and phylum-level data were analyzed using a random-effects model and forest plots. This study included 19 trials (n = 1154). The results indicated that GMMIs significantly ameliorated GISs (p = 0.0017), reduced six-item Gastrointestinal Symptom Index scores by 1.86 points (p = 0.0187), and significantly increased the relative abundance of Bifidobacterium spp. (p = 0.0205). Longer interventions (≥ 8 weeks) were more effective in ameliorating GISs. Limitations in this investigation include the fact that the included studies neither incorporated any dietary control groups nor collected relevant dietary data, and the relatively small sample size (19 studies) may have hindered the identification of sources of heterogeneity in the pooled results. Overall, our findings suggest that GMMIs, especially probiotics, ameliorate GISs in children with ASD by modulating gut microbial composition, particularly by increasing the relative abundance of Bifidobacterium spp. These interventions may alleviate symptoms such as constipation, diarrhea, abnormal stool consistency and smell, flatulence, and abdominal pain. Our evidence supports that treatments involving GMMIs can be considered for children with ASD.}, } @article {pmid40692142, year = {2025}, author = {Chao, J and Tan, Z and Li, Z and Xu, C}, title = {The Role of the Microbiota-Gut-Brain Axis in Perinatal Depression: Novel Insights for Treatment.}, journal = {Current neuropharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/011570159X380460250710061340}, pmid = {40692142}, issn = {1875-6190}, abstract = {Perinatal depression, a prevalent mood disorder complicating pregnancy and childbirth, poses significant threats to maternal health and neonatal development. While psychotherapy and antidepressants constitute current standard treatments, their clinical application faces substantial limitations during pregnancy and lactation, including safety concerns, treatment resistance, and poor adherence rates. These therapeutic constraints have spurred growing interest in novel gut-brain axis (GBA)-targeted interventions. Emerging evidence suggests that the gut microbiota communicates with the brain through a complex network of neural, immune, and endocrine pathways, playing a critical role in regulating mood, behavior, and cognitive functions. Interventions such as probiotics and fecal microbiota transplantation (FMT) are increasingly explored for their potential to restore microbial balance and alleviate depressive symptoms. This review aims to systematically examine the role of the GBA in the context of perinatal depression, offering novel insights to inform clinical treatment strategies. Furthermore, it evaluates the promise and limitations of microbiota-targeted interventions while discussing future directions for personalized microbiome therapeutics.}, } @article {pmid40691891, year = {2025}, author = {Song, H and Zhang, H and Qin, X and Liu, Y and Lai, Y and Yang, W and Zhang, L and Hu, W and Wang, X and Zeng, J and Liu, R}, title = {Gut microbiota dysbiosis and disturbed tryptophan metabolism mediate cognitive impairment in mice with circadian rhythm disruption.}, journal = {Brain research bulletin}, volume = {229}, number = {}, pages = {111473}, doi = {10.1016/j.brainresbull.2025.111473}, pmid = {40691891}, issn = {1873-2747}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Tryptophan/metabolism ; Mice ; *Cognitive Dysfunction/metabolism/microbiology ; *Dysbiosis/metabolism/microbiology ; Male ; Mice, Inbred C57BL ; *Chronobiology Disorders/metabolism/microbiology/complications ; Circadian Rhythm/physiology ; Fecal Microbiota Transplantation ; Disease Models, Animal ; 5-Hydroxytryptophan/metabolism ; }, abstract = {Circadian rhythm disorder (CRD) is a risk factor for cognitive deficits, yet its mechanisms remain unclear. We previously found CRD model mice developed cognitive impairment mediated through gut microbiota disturbance, intestinal barrier damage, and microglia activation, but the signaling pathway was undefined. Here, we show CRD induces cognitive deficits and gut microbiota disturbance in mice. Fecal microbiota transplantation (FMT) from CRD mice to normal mice reproduced intestinal barrier damage, microglia activation, neuronal damage, and cognitive deficits. Notably, gut metabolite analysis revealed significant alterations, with tryptophan metabolism being particularly affected: tryptophan decreased by 26.9 % and 5-hydroxytryptophan (5-HTP) by 30.7 % (both P < 0.05). Dietary tryptophan supplementation restored serum tryptophan and 5-HTP levels, ameliorating the neuronal damage and cognitive deficits caused by CRD gut microbiota. Collectively, these findings indicate that disturbances in gut microbiota and metabolites play a key role in CRD-induced neurological damage in mice, suggesting targeting the gut microbiota or tryptophan metabolism may prevent CRD-induced cognitive dysfunction.}, } @article {pmid40691449, year = {2025}, author = {Vázquez-Castellanos, JF and Maciel, LF and Wauters, L and Gregory, A and Van Oudenhove, L and Geboers, K and Verbeke, K and Smokvina, T and Tack, J and Vanuytsel, T and Derrien, M and Raes, J}, title = {Probiotic-mediated modulation of gut microbiome in students exposed to academic stress: a randomized controlled trial.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {140}, pmid = {40691449}, issn = {2055-5008}, mesh = {Humans ; *Probiotics/administration & dosage ; *Gastrointestinal Microbiome/drug effects ; *Stress, Psychological/microbiology ; *Students/psychology ; Male ; Female ; *Lacticaseibacillus rhamnosus/physiology ; RNA, Ribosomal, 16S/genetics ; Young Adult ; Adult ; Feces/microbiology ; *Bacteria/classification/genetics/isolation & purification ; Anxiety ; Metagenomics ; }, abstract = {Probiotics have been widely tested for their effect on mental well-being, albeit with heterogeneous outcomes. Direct and indirect effects through the gut microbiome might lie at the basis of these observations. Here, in a post-hoc analysis, we assessed the effect of 4-week consumption of a probiotic candidate strain on the gut microbiome in students exposed to academic stress. Healthy students were randomized to consume a fermented milk product with Lacticaseibacillus rhamnosus CNCM I-3690 (N = 39) or an acidified non-fermented milk product (N = 40) twice daily for 4 weeks before academic exams. The gut microbiome was analysed by Quantitative Microbiome Profiling based on 16S rRNA gene amplicon and shotgun metagenomic sequencing. Stress and anxiety were assessed using both objective and self-reported markers. Changes of alpha-diversity markers and community shifts from baseline (beta diversity) were lower in L. rhamnosus treated individuals over controls, suggesting lower overall changes of gut microbiota during psychological stress in the Probiotic group. The intake of L. rhamnosus CNCM I-3690 induced differential abundance of some species, such as the maintenance of the quantitative abundance of Ruminococcus bicirculans, and co-varied with species, which differed according to visits (i.e., stress level), suggesting a potential beneficial effect of the strain before the highest increase of stress level. The higher quantitative abundance of F. prausnitzii induced by the probiotic intake was associated with lowered self-reported anxiety levels before the exam. Functional analysis revealed minor changes upon intake of the probiotic strain. Taken together, using a quantitative framework, we found that L. rhamnosus CNCM I-3690 has a potential effect on gut microbiome response to stress, although further studies are needed to better understand the precise interaction.}, } @article {pmid40690011, year = {2025}, author = {Nazir, MM and Ghaffar, W and Mustafa, G and Saeed, S and Ijaz, MU and Ashraf, A}, title = {Modulating depression through the gut-brain axis: the role of gut microbiota in therapeutic interventions.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {40690011}, issn = {1432-1912}, abstract = {Depression is a multifactorial mental disorder increasingly linked to gut microbiota through the microbiota-gut-brain axis (MGBA). This review aims to explore how alterations in gut microbial composition influence depressive symptoms via neurochemical, immunological, and neuroendocrine pathways. Key mechanisms include microbial modulation of serotonin, dopamine, and GABA levels; systemic inflammation; hypothalamic-pituitary-adrenal (HPA) axis dysregulation; and vagus nerve signaling. Emerging evidence suggests that gut microbiota may also influence the efficacy of selective serotonin reuptake inhibitors (SSRIs), potentially via vagal pathways. Additionally, a distinct microbial signature has been observed in individuals with depression, with therapeutic probiotics targeting this dysbiosis showing beneficial effects. This review further evaluates the therapeutic potential of probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary interventions in managing depression. We highlight the need for microbiota-based biomarkers and personalized interventions in future clinical applications. Overall, this review underscores the therapeutic relevance of targeting the gut-brain axis in depression treatment.}, } @article {pmid40686934, year = {2025}, author = {Alaeddin, S and Chatterjee, A and Roberts, TL and Steiner-Lim, GZ and Jensen, SO and Gyengesi, E and Muench, G and Ho, V}, title = {Exploring the effects of faecal microbiota transplantation on cognitive function: A review of clinical trials.}, journal = {Brain, behavior, & immunity - health}, volume = {48}, number = {}, pages = {101049}, pmid = {40686934}, issn = {2666-3546}, abstract = {Faecal Microbiota Transplantation (FMT) is a widely used microbiota-modulation technique to treat recurrent Clostridioides difficile infections (rCDI). Rodent studies and clinical trials on probiotic interventions indicate that alterations in microbiota composition may impact cognitive function. To explore whether FMT influences cognitive function in humans, we conducted a systematic search and narrative synthesis and identified 14 studies examining its effects on cognition. A variety of cohort studies, single-arm trials, case reports and randomised, placebo-controlled trials have been conducted on different neurological patient cohorts, including those with Hepatic Encephalopathy, Parkinson's Disease, dementia, and Mild Cognitive Impairment. FMT has been shown to have a significant impact on cognitive function in these populations, accompanied by alterations in microbial composition and blood markers. Interestingly, success was influenced by the route of FMT administration, indicating greater efficacy of rectal cf. oral administration on microbiome composition and cognitive improvements. However, no clinical trials have yet examined the effects of FMT on cognitively healthy individuals. FMT appears to have potential as a therapeutic strategy for cognitive impairment, though further research with larger sample sizes is needed to explore its effects in both impaired and cognitively healthy populations.}, } @article {pmid40686307, year = {2025}, author = {Li, W and Xu, M and Cheng, M and Wei, J and Zhu, L and Deng, Y and Guo, F and Bi, F and Liu, M}, title = {Current Advances and Future Directions for Sensitizing Gastric Cancer to Immune Checkpoint Inhibitors.}, journal = {Cancer medicine}, volume = {14}, number = {14}, pages = {e71065}, pmid = {40686307}, issn = {2045-7634}, support = {ZYJC21043//West China Hospital, Sichuan University/ ; 2023YFS0111//Sichuan Province Science and Technology Support Program/ ; }, mesh = {Humans ; *Stomach Neoplasms/therapy/immunology/drug therapy/mortality/pathology ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Tumor Microenvironment/drug effects/immunology ; *Immunotherapy/methods ; Combined Modality Therapy ; Drug Resistance, Neoplasm ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; }, abstract = {BACKGROUND: Immunotherapy combined with chemotherapy has become the standard treatment for HER2-negative gastric cancer (GC), but its clinical benefits remain limited, with a median progression-free survival (mPFS) of 6-8 months and median overall survival (mOS) of 15-18 months. These outcomes are particularly poor in patients with CPS < 1. The marked heterogeneity of GC, along with primary and secondary resistance, presents significant clinical challenges and underscores the urgent need for novel therapeutic strategies.

RECENT ADVANCES: To address these limitations, several combination therapies are being explored. Anti-VEGF therapy combined with immune checkpoint inhibitors (ICIs) has shown synergistic effects by enhancing immune cell infiltration and reducing tumor-mediated immunosuppression, thereby improving response rates and survival. Radiotherapy combined with ICIs also holds promise, with low-dose radiation remodeling the tumor microenvironment and high-dose radiation inducing immunogenic cell death. Other potential combinations include PD-1/PD-L1 inhibitors paired with targeted therapies against HER2, FGFR2, DKK1, PARP, LSD1, HDAC, and other emerging targets. Novel approaches such as hyperbaric oxygen therapy, oncolytic viruses, metabolic modulators, and fecal microbiota transplantation are also under investigation to further enhance immune responses.

CONCLUSION: These multimodal strategies represent a promising shift toward personalized, mechanism-driven immunotherapy sensitization. By targeting diverse pathways to overcome immune resistance, they aim to reshape the tumor microenvironment, restore immune responsiveness, and improve outcomes in GC. While many remain in early-stage development, accumulating evidence supports their potential. Future research should prioritize optimizing combination regimens, clarifying resistance mechanisms, and identifying predictive biomarkers through multi-omics and artificial intelligence to enable more precise, individualized immunotherapy.}, } @article {pmid40685369, year = {2025}, author = {Rahman, R and Marcolla, CS and Willing, BP}, title = {Fecal microbiota transplantation in pigs: current status and future perspective.}, journal = {Animal microbiome}, volume = {7}, number = {1}, pages = {76}, pmid = {40685369}, issn = {2524-4671}, support = {res0030386//Alberta Livestock and Meat Agency/ ; RGPIN-2019-06336//Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {Fecal microbiota transplantation (FMT) is gaining attention as a method to modulate the gut microbiome in pigs, with the goal of enhancing health and production outcomes. While some studies indicate that FMT can enhance growth performance and intestinal health in piglets, others report minimal or even negative effects. This variability highlights the need for standardized protocols and further research to optimize FMT for swine applications. Currently, the use of FMT in pigs is still in its early stages, with limited studies showing considerable methodological differences. Although some evidence supports the effectiveness of FMT, significant gaps remain in our understanding of its approach and underlying mechanisms. Therefore, this review summarizes the role and development of gut microbiota in pigs, analyzes existing FMT research in pigs, emphasizes the varying outcomes, illustrates the potential mechanisms of action based on human and animal studies and discusses the innovative potential of using co-evolved microbial communities as a transplant material. As our understanding of pig gut microbiome advances, FMT and related microbiome-based interventions could become valuable tools in pig production. However, ongoing research is essential to elucidate their mechanisms and develop reliable protocols.}, } @article {pmid40685095, year = {2025}, author = {Cheng, YY and Lin, CC and Tung, CS and Liu, CC and Liu, YP}, title = {The effects of autologous fecal microbiota transplantation on fear memory and anxiety abnormalities induced by single prolonged stress - Implication of gut-brain axis regulation.}, journal = {Brain research bulletin}, volume = {229}, number = {}, pages = {111472}, doi = {10.1016/j.brainresbull.2025.111472}, pmid = {40685095}, issn = {1873-2747}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Fear/physiology/psychology ; Male ; *Gastrointestinal Microbiome/physiology ; Rats ; *Anxiety/therapy ; Stress, Psychological ; Rats, Sprague-Dawley ; Extinction, Psychological/physiology ; Stress Disorders, Post-Traumatic/therapy ; *Memory/physiology ; Corticosterone/blood ; *Brain-Gut Axis/physiology ; Brain/metabolism ; Serotonin/metabolism ; Disease Models, Animal ; }, abstract = {Increasing evidence suggests that alterations in the gut microbiota play a crucial role in the pathophysiology of psychiatric disorders, including post-traumatic stress disorder (PTSD). This implies that restoring gut microbiota might serve as a therapeutic strategy, with autologous fecal microbiota transplantation (FMT) being the most promising treatment due to its effectiveness and fewer pharmacological side effects. However, the hypothesis that adjusting gut microbiota may help to restore the impairment of fear memory is still less examined. To evaluate this hypothesis, we employed single prolonged stress (SPS) rat model to examine the impact of autologous FMT on PTSD-related fear memory extinction retention deficits and increased anxiety, and to investigate changes in the levels of gut microbiota, central monoamines, and plasma corticosterone. The correlations between gut microbiota and central serotonin (5-HT) with fear extinction retention deficits and anxiety were analyzed. Note that littermates were used in the gut microbiota analysis to minimize individual differences. Our results demonstrated that autologous FMT significantly ameliorated SPS-induced deficits in fear extinction retention and conditioned anxiety but did not mitigate unconditioned anxiety. These improvements were significantly correlated with the restoration of 5-HT levels in the medial prefrontal cortex (mPFC), dorsal hippocampus (dHPC), and hypothalamus (HT). Autologous FMT also reversed SPS-induced reductions in plasma corticosterone level. Additionally, fecal microbiota analysis revealed significant changes at the genus level, with the relative abundance of the Prevotellaceae Ga6A1 group reduced after SPS, and Intestinimonas increased by FMT, as well as some taxa significantly correlated with fear extinction retention deficits. This study suggests that autologous FMT offers potential as a novel therapeutic strategy for PTSD.}, } @article {pmid40684867, year = {2025}, author = {Cao, J and Shi, D and Cui, Y and Zhu, H and Liang, H and Wei, Q and Huang, J}, title = {Genistein maintains intestinal homeostasis in colitis mice via activating GPR30-Nrf2 signaling pathway.}, journal = {The Journal of nutritional biochemistry}, volume = {145}, number = {}, pages = {110036}, doi = {10.1016/j.jnutbio.2025.110036}, pmid = {40684867}, issn = {1873-4847}, abstract = {Genistein (GEN) is a natural polyphenolic compound widely present in leguminous plants, which has many biological functions such as anti-inflammatory and antioxidant activities, and has attracted attention in the treatment of inflammatory bowel disease (IBD). However, the molecular mechanism underlying the beneficial effects of GEN in IBD remains unclear. Here, we demonstrated that GEN enhanced the relative abundance of beneficial bacteria (e.g., Akkermansia muciniphila) and increased microbiota-derived short-chain fatty acids (SCFAs) levels in colitis mice. Further, the antibiotic cocktails (ABX) and fecal microbiota transplantation (FMT) experiments confirmed that gut microbiota at least partially mediated the anti-colitis effect of GEN. Interestingly, we found that GEN could also activate G protein-coupled receptor 30 (GPR30) and its downstream transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in intestinal epithelial cells (IECs). The activation of the GPR30-Nrf2 signaling led to reduced reactive oxygen species (ROS) production, which consequently inhibited NLRP3 inflammasome activation and improved intestinal epithelial barrier dysfunction. In addition, studies using GPR30 knockout mice confirmed that GPR30 is crucial for inhibiting NLRP3 inflammasome activation and alleviating colitis. Collectively, our study unveils that GEN is an effective anti-inflammatory agent and suggests that both the gut microbiota and the GPR30-Nrf2 signaling pathway represent potential therapeutic targets for treating IBD.}, } @article {pmid40684508, year = {2025}, author = {Wu, B and Tian, XY and Ni, WS and Gao, HX and Wang, YW and Zhang, LH and Li, YB and Lv, YL and Song, YN and Yan, YC and Geng, XZ and Li, YM and Yang, HF and Zhao, J}, title = {Acetamiprid mediates cognitive dysfunction through the gut-brain axis: Synaptic damage and immune-mediated blood-brain barrier dysfunction.}, journal = {Journal of hazardous materials}, volume = {496}, number = {}, pages = {139287}, doi = {10.1016/j.jhazmat.2025.139287}, pmid = {40684508}, issn = {1873-3336}, abstract = {Acetamiprid is a widely used neonicotinoid pesticide that can increase the risk of inducing nervous system diseases. Considering the increased exposure to acetamiprid and its impact on cognitive function, further clarification is needed. Therefore, we used a mouse model of drinking water to evaluate the effects of acetamiprid on cognitive dysfunction and the possible underlying mechanisms. Our study revealed that acetamiprid can cause damage to hippocampal and synaptic structures, which in turn leads to a decline in spatial learning and memory abilities in mice. Importantly, acetamiprid exposure altered the composition and diversity of the intestinal flora and induced a systemic immune response in the gutbrain axis. Specifically, acetamiprid exposure damages the gutbrain axis, including structural disorders of the intestinal flora, related neurotransmitters and systemic immune factors. In addition, fecal microbiota transplantation restored the homeostasis of the gut microbiota and reduced the degree of damage to synaptic and spatial learning and memory. Moreover, intestinal barrier function is restored, effectively preventing the entry of harmful substances into intestinal tissue and thereby reducing damage to the bloodbrain barrier and the immune response in the gutbrain. This study provides new insights into potential new mechanisms of acetamidine exposure related to cognitive function.}, } @article {pmid40684494, year = {2025}, author = {Tao, Y and Wang, L and Xiong, S and Ding, Y and Nhamdriel, T and Zhang, Y and Zhang, J and Fan, G}, title = {Milk-processed Polygonatum cyrtonema Hua ameliorates cyclophosphamide-induced immunosuppression in mice by regulating gut microbiota and immune response.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {145}, number = {}, pages = {157076}, doi = {10.1016/j.phymed.2025.157076}, pmid = {40684494}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Cyclophosphamide/adverse effects ; Mice ; *Polygonatum/chemistry ; Cytokines/metabolism ; Male ; Fecal Microbiota Transplantation ; Fatty Acids, Volatile/metabolism ; Immunosuppression Therapy ; Immunosuppressive Agents ; Mice, Inbred BALB C ; Drugs, Chinese Herbal/pharmacology ; }, abstract = {BACKGROUND: Immune dysfunction is linked to the progression of various diseases. Milk-processed Polygonatum cyrtonema Hua (MPC) is a traditional medicine with nourishing effects in the Qinghai-Tibet Plateau region of China. However, the immune-enhancing effect of MPC and its underlying mechanism remain unclear.

PURPOSE: This study aims to investigate the therapeutic effect and underlying mechanism of MPC on immunosuppressed mice.

STUDY DESIGN: A cyclophosphamide (CY)-induced immunosuppressive mouse model was established to evaluate the effects of MPC on the gut microbiota, intestinal barrier and immune response.

METHODS: The chemical composition of MPC was identified by UPLC-Q-Exactive Orbitrap MS technology. Immune organ weight, body weight, colon length, biochemical parameters, and histopathology were examined. The levels of three short-chain fatty acids (SCFAs) were quantified via HPLC. 16S rRNA sequencing, fecal microbiota transplantation (FMT), antibiotic intervention, and Western blot were applied to explore the mechanism of MPC.

RESULTS: MPC significantly enhanced the production of some key cytokines (IL-2, IFN-γ, IL-4, IL-10, and TGF-β3), immunoglobulins (IgM and IgG), and transcription factors (T-bet, GATA-3, RORγt, and Foxp3). Additionally, MPC maintained intestinal mucosal integrity by upregulating tight junction proteins ZO-1, Claudin-1, E-cadherin, and Occludin. 16S rRNA sequencing of fecal samples revealed that MPC increased the relative abundance of beneficial SCFA-producing bacteria, specifically Lachnospiraceae_UCG-006, while decreasing the relative abundance of several pathogenic taxa, including Prevotellaceae, Alloprevotella, and Eubacterium_coprostanoligenes_group. Notably, antibiotic intervention and FMT experiments demonstrated that the immune-enhancing effect of MPC was dependent on the gut microbiota. MPC also increased the levels of three SCFAs including acetate, propionate, and butyrate. Besides, MPC was found to activate the SCFAs/GPR43/Blimp-1 pathway, leading to the production of IL-10, which enhanced the immune response.

CONCLUSION: This study demonstrates for the first time that MPC has a significant immune-enhancing effect. The mechanisms include restoring the balance of gut microbiota, promoting the production of SCFAs, repairing intestinal mucosal damage and enhancing immune function. These findings support the potential of MPC as a natural agent for improving gut health and systemic immunity.}, } @article {pmid40684490, year = {2025}, author = {Chen, YY and Lu, YT and Wang, YD and Ding, NN and Huang, ZX and Hu, JB and Tong, JX and Zhang, YR and Deng, LJ and Luo, X and Hao, WZ and Chen, JX}, title = {Xiaoyaosan improves depression-like behaviours in mice with post-stroke depression by modulating gut microbiota and microbial metabolism and regulating P2X7R/NLRP3 inflammasome.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {145}, number = {}, pages = {157078}, doi = {10.1016/j.phymed.2025.157078}, pmid = {40684490}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Receptors, Purinergic P2X7/metabolism ; *Depression/drug therapy/etiology/microbiology ; Inflammasomes/metabolism/drug effects ; Male ; Mice ; Fecal Microbiota Transplantation ; *Drugs, Chinese Herbal/pharmacology ; *Stroke/complications ; Mice, Inbred C57BL ; Disease Models, Animal ; Behavior, Animal/drug effects ; }, abstract = {BACKGROUND: Post-stroke depression (PSD) represents the most prevalent complication of stroke and has been reported to be associated with an imbalance in the gut microbiota. Clinically, Xiaoyaosan (XYS) alleviates depressive symptoms in patients with PSD. However, the existing literature does not provide sufficient evidence to ascertain whether XYS can alleviate these symptoms by modulating gut microbiota.

PURPOSE: This study aims to investigate the potential mechanism of XYS to improve depression-like behavior in mice with PSD by regulating intestinal flora and microbial metabolism.

STUDY DESIGN: The authors assessed the effect of XYS on the behaviour of PSD mice and evaluated the effects of XYS on structure and metabolism of gut microbiota, the protein expression levels of P2X7 and NLRP3, and associated inflammatory factors in PSD mice. In addition, by performing faecal microbiota transplantation (FMT) on PSD mice with faecal bacteria treated with XYS, the authors further clarified the relationship between intestinal flora disorder, the onset of PSD, and the intervention effect of XYS.

METHODS: To investigate the ameliorative effect of XYS on behavioural abnormalities and clarify the important role of intestinal flora regulation in the improvement of PSD by XYS in diseased mice, the authors employed various methodologies, including the PSD model, behavioural tests, haematoxylin and eosin staining, ultrastructural morphology, enzyme-linked immunosorbent assay, western blotting, 16S rRNA sequencing, metabolomic analyses, and FMT.

RESULTS: Oral administration of XYS effectively alleviated depression-like behaviours in PSD mice and repaired the damaged colonic mucosa. XYS inhibited inflammatory factors in serum and hippocampus and regulated the protein expression levels of P2X7 and NLRP3 in the colon and hippocampus of PSD mice. Moreover, XYS restored the gut microbiota and modulated intestinal metabolites in PSD mice. It effectively reduced the abundances of microbes including Ligullacoccus, Streptococcus, and Staphylococcus, while significantly increased the abundances of microbes including Faecalibaculum, Allobaculum, and Monolobus. Furthermore, XYS effectively regulated intestinal metabolites such as methylparaben, valproic acid (Depakene), and disulfiram. More importantly, faecal transplants from the PSD models reproduced depression-like behaviours in normal mice, while XYS-FMT effectively alleviated depression-like behaviours in PSD mice.

CONCLUSION: Our findings indicate that XYS improves depression-like behaviours in mice with PSD by modulating the gut microbiota and microbial metabolism, and regulating the P2X7R/NLRP3 inflammasome.}, } @article {pmid40683544, year = {2025}, author = {Ran, C and Xu, Y and Wang, Q and Cao, H and Li, D and Wang, Y and Yan, J and Yang, J and Sun, J and Liu, Y and Xia, Y and Zhang, L and Wang, X and Zhang, F}, title = {Gut microbiota from osteoarthritic patients without obesity aggravates osteoarthritis progression in rats by enriching acetic acid.}, journal = {Microbial pathogenesis}, volume = {207}, number = {}, pages = {107911}, doi = {10.1016/j.micpath.2025.107911}, pmid = {40683544}, issn = {1096-1208}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Osteoarthritis/microbiology/pathology ; Humans ; Rats ; Obesity/microbiology/complications ; *Acetic Acid/metabolism ; Rats, Sprague-Dawley ; Male ; Disease Progression ; Feces/microbiology/chemistry ; Fecal Microbiota Transplantation ; Fatty Acids, Volatile/analysis/metabolism ; Female ; Disease Models, Animal ; Middle Aged ; Cytokines/blood ; Aged ; Tumor Necrosis Factor-alpha/blood ; }, abstract = {OBJECTIVE: Although obesity is recognized as a mechanical driver of osteoarthritis (OA), emerging evidence suggests gut microbiota independently contributes to OA pathogenesis. OA develops even in individuals without obesity, yet the distinct mechanistic roles of gut microbiota in OA progression among hosts with and without obesity remain uncharacterized. OA can develop in individuals without obesity, yet the distinct roles of gut microbiota in OA progression among those with and without obesity remain unclear. This study directly compares how gut microbiota differentially modulates OA development in these two populations.

METHODS: Twenty-five SD rats underwent anterior cruciate ligament transection (ACLT), gut microbiota depletion and fecal microbiota transplantation (FMT) from four types of donors: healthy controls (C), OA patients without obesity (OA), non-OA patients with obesity (OB), and OA patients with obesity (OAB). Five rats in group SAB underwent sham surgery and received FMT from OA patients with obesity. After 8 weeks, joint histopathology, plasma cytokines, fecal Short-chain fatty acids (SCFAs), and microbiota composition were analyzed.

RESULTS: Rats receiving FMT from OA patients without obesity displayed the most severe cartilage degeneration and synovitis, with elevated levels of IL-6/TNF-α and acetic acid. Bacteroides acidifaciens was the dominant microbe in the OA group and correlated with both OA severity and acetic acid levels. In contrast, rats receiving FMT from patients with/without obesity (OB/OAB) exhibited enrichment of propionic acid producers, Lactobacillus and Oscillibacter, which were inversely associated with inflammation. Mechanical stress primarily drove OA in rats with obesity, whereas OA pathology in individuals without obesity was microbiota dependent.

CONCLUSION: Gut microbiota from OA patients without obesity exacerbates disease via B. acidifaciens mediated acetic acid overproduction, while the presence of obesity enriches beneficial taxa that attenuate inflammation. Mechanical load remains pivotal in OA with obesity. Targeting microbiota dysbiosis may offer novel therapeutic avenues, particularly for OA patients without obesity.}, } @article {pmid40682107, year = {2025}, author = {Pianka, ML and Werba, A and Zimmermann, S and Vey, JA and Kalkum, E and Tenckoff, S and Tony-Odigie, A and Michalski, CW and Pianka, F}, title = {The role of the MicroBiome in PANCreatic cancer and its precursors- the study protocol of the MiBiPanc systematic review and meta-analysis.}, journal = {Systematic reviews}, volume = {14}, number = {1}, pages = {150}, pmid = {40682107}, issn = {2046-4053}, support = {01KC2310//Bundesministerium für Bildung und Forschung/ ; }, mesh = {Humans ; *Pancreatic Neoplasms/microbiology ; Systematic Reviews as Topic ; *Microbiota ; Meta-Analysis as Topic ; Pancreas/microbiology ; *Gastrointestinal Microbiome ; Pancreatitis, Chronic/microbiology ; *Precancerous Conditions/microbiology ; }, abstract = {BACKGROUND: Pancreatic cancer is the third leading cause of cancer-related death in Northern America and fourth in Europe. Emerging evidence suggests that the pancreatic microbiome may play a significant role in the development and progression of this disease. Although the human microbiota contributes to health by supporting nutritional and hormonal homeostasis, modulating inflammation, detoxifying harmful compounds, and producing beneficial metabolites, several studies have implicated its crucial modulatory role in numerous diseases, including cancer. The main objective of this review is to investigate the specific relationship between the microbiome and pancreatic carcinogenesis.

METHODS: A comprehensive literature search will identify studies examining the microbiome in human samples of saliva, pancreatic fluid, bile, pancreatic tissue, and feces of patients with chronic pancreatitis, precancerous pancreatic lesions, and pancreatic cancer. Studies differentiating bacteria to at least the genus level will be prioritized. Eligible studies include randomized controlled trials and observational studies analyzing the human microbiome in patients with chronic pancreatitis, pancreatic precursor lesions, or pancreatic cancer compared to healthy controls. Studies analyzing nonhuman samples, single bacterial strains, or lacking comparator groups will be excluded. The following databases will be searched without any restrictions to the publication date up until December 2024: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via PubMed), Embase, and Web of Science. Animal studies, case reports, and studies not reporting analyses of human samples are excluded. Details regarding blinding, risk of bias, and funding sources will be extracted and assessed. The main outcomes include the bacterial diversity in each sample type (stool, saliva, bile, intratumoral, and tissue) itemized for each diagnosis, identifying differentially abundant or depleted taxa, and evaluating the correlation of specific bacteria with disease prevention or progression and clinical outcomes. Data extraction will be performed independently by two reviewers. Risk-of-bias assessment will be performed using Cochrane tools appropriate for each study design. Comparisons will be analyzed by descriptive statistics, and meta-analyses will be performed when applicable. The review will be conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.

DISCUSSION: In summary, this systematic review aims to synthesize studies analyzing microbiome profiles in patients with chronic pancreatitis, precursor lesions, and pancreatic cancer, focusing on identifying bacterial diversity and specific taxa related to disease progression and development of cancer in comparison to healthy controls and will include a thorough critical appraisal of the available literature. Anticipated limitations include heterogeneity in microbiome sampling methods and potential variability in taxonomic resolution across studies.

PROSPERO CRD42023487995.}, } @article {pmid40680146, year = {2025}, author = {Li, B and Sakaguchi, T and Tani, H and Ito, T and Murakami, M and Okumura, R and Kobayashi, M and Okuzaki, D and Motooka, D and Ikeuchi, H and Ogino, T and Mizushima, T and Hirota, S and Otake-Kasamoto, Y and Kishikawa, T and Nakamura, S and Kobiyama, K and Ishii, KJ and Hashiguchi, T and Kawai, T and Kuroda, E and Shinzaki, S and Ise, W and Kurosaki, T and Kikuchi, A and Tomofuji, Y and Okada, Y and Takeda, K and Kayama, H}, title = {OTUD3 prevents ulcerative colitis by inhibiting microbiota-mediated STING activation.}, journal = {Science immunology}, volume = {10}, number = {109}, pages = {eadm6843}, doi = {10.1126/sciimmunol.adm6843}, pmid = {40680146}, issn = {2470-9468}, mesh = {Animals ; *Colitis, Ulcerative/immunology/microbiology/prevention & control/genetics/pathology ; Mice ; Humans ; *Membrane Proteins/metabolism/immunology ; *Gastrointestinal Microbiome/immunology ; Mice, Inbred C57BL ; Fibroblasts/metabolism/immunology ; Male ; Female ; Nucleotides, Cyclic/metabolism ; Mice, Knockout ; }, abstract = {Ulcerative colitis (UC) develops through a complicated interaction between the host and microbiota. Intestinal fibroblasts are believed to play crucial roles in the pathogenesis of UC, but the influence of the host-microbiota interaction on the pathophysiology of intestinal fibroblasts remains poorly understood. Here, we demonstrate that OTU deubiquitinase 3 (OTUD3) suppresses pathologic activation of fibroblasts exposed to microbial cyclic GMP-AMP (3'3'-cGAMP) in the colon by deubiquitinating stimulator of interferon genes (STING). Mice harboring a UC risk missense variant in the Otud3 gene showed pathological features of UC in the colon after transplantation of a fecal microbiota with the potential to produce excessive cGAMP from patients with UC. Collectively, these results highlight a mechanism of the interaction between OTUD3 in host fibroblasts and STING-activating microbiota in UC development.}, } @article {pmid40679776, year = {2025}, author = {Clarke, H and Peer, M and Miles, S and Fitzcharles, MA}, title = {Managing Pain in Fibromyalgia: Current and Future Options.}, journal = {Drugs}, volume = {}, number = {}, pages = {}, pmid = {40679776}, issn = {1179-1950}, abstract = {Pain relief is a key element of fibromyalgia (FM) treatment. Current guidelines recommend antidepressant (i.e. serotonin-norepinephrine reuptake inhibitors) and anticonvulsant medications (gabapentin/pregabalin), drugs that provide only modest relief, with limitations primarily driven by side effects. In contrast, traditional analgesic drugs, although not sufficiently tested in FM, are commonly used by patients. This dearth of effective treatments has led to isolated, mostly small studies of less familiar drug treatments for FM-related pain. Although no single drug has emerged with appreciable effect, some agents such as cannabinoids and naltrexone, amongst others, have shown some pain modulatory effects. In the absence of drugs in the pipeline, non-pharmacological interventions such as behavioural interventions, neuromodulation techniques and faecal transplantation have been studied. This narrative review will focus on drugs and interventions that have been examined in recent years to modulate pain in FM.}, } @article {pmid40679382, year = {2025}, author = {}, title = {Correction to: Clostridioides difficile: Treating Sustained Antibiotic Responders With Fecal Microbiota Transplantation Does Not Improve Efficacy.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaf381}, pmid = {40679382}, issn = {1537-6591}, } @article {pmid40679068, year = {2025}, author = {Zhao, X and Cai, Y and Hou, Y and Wu, Y and Wei, T and Li, L and Duan, Z and Lu, X and Meng, J and Zhou, H and Wang, Q and Wang, J and Xu, C and Du, L and Fan, S and Wang, F and Liu, Q and Liu, Y}, title = {Commensal Viruses Promote Intestinal Stem Cell Regeneration Following Radiation Damage by Inhibiting Hyperactivation of RIG-I and Notch Signals.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e05204}, doi = {10.1002/advs.202505204}, pmid = {40679068}, issn = {2198-3844}, support = {82072331//National Natural Science Foundation of China/ ; 2022-I2M-2-003//CAMS Innovation Fund for Medical Sciences/ ; 2021-I2M-1-042//CAMS Innovation Fund for Medical Sciences/ ; 2023-I2M-2-008//CAMS Innovation Fund for Medical Sciences/ ; 23JCZDJC00270//Natural Science Foundation of Tianjin City/ ; }, abstract = {Radiation-induced intestinal injury is a common complication of abdominopelvic cancer radiotherapy, often associated with gut bacteriome dysbiosis. However, the involvement of gut virome in this process remains largely underexplored. Here, it was found that radiation disrupted the gut virome, altered the distribution of phages and their bacterial host. Fecal virome transplantation (FVT) from healthy donors ameliorated radiation-induced intestinal damage and promoted stem cell proliferation by enriching phages targeting Salmonella. Conversely, decreased virome load exacerbated intestinal damage, reduced proliferating stem cells, and impaired secretory lineage differentiation. Mechanistically, exacerbated intestinal injury was associated with hyperactivation of RIG-I and Notch signaling in intestinal stem cells, which was absent in RIG-I-deficient mice. Organoids from RIG-I-deficient mice displayed decreased Notch signals and increased regenerative capacity post radiation. These findings shed light on the intricate interplay between gut virome, intestinal injury, and stem cell responses, highlighting potential therapeutic interventions for targeting the virome to mitigate radiation-induced intestinal damage.}, } @article {pmid40678181, year = {2025}, author = {Zhao, M and Zhang, L and Liu, Z}, title = {Gut microbiota-mediated pain sensitization: mechanisms and therapeutic implications.}, journal = {Frontiers in pain research (Lausanne, Switzerland)}, volume = {6}, number = {}, pages = {1626515}, pmid = {40678181}, issn = {2673-561X}, abstract = {Emerging evidence has illuminated the pivotal role of gut microbiota in modulating pain sensitivity through bidirectional gut-brain interactions. Current research demonstrates that gut microbial communities significantly influence pain perception by regulating both central and peripheral sensitization mechanisms across various pain modalities. This review synthesizes current knowledge on the mechanisms underlying gut microbiota-mediated pain sensitization, encompassing: (1) cross-talk within the microbiome-gut-brain axis, (2) regulatory effects of microbial metabolites on central and peripheral sensitization pathways, and (3) bioactive compounds derived from gut microbiota that participate in pain modulation. Furthermore, we systematically evaluate the therapeutic potential of microbiota-targeted interventions including probiotic supplementation, fecal microbiota transplantation, and dietary modifications in pain management. To advance this promising field, future investigations should prioritize three key directions: establishing causal relationships through rigorous verification, accelerating clinical translation of preclinical findings, and developing personalized microbial-based therapeutic strategies.}, } @article {pmid40676635, year = {2025}, author = {Shtossel, O and Eshel, A and Fried, S and Geva, M and Danylesko, I and Yerushalmi, R and Shem-Tov, N and Fein, JA and Fabbrini, M and Shimoni, A and Turjeman, S and Louzoun, Y and Nagler, A and Koren, O and Shouval, R}, title = {Microbiome-based prediction of allogeneic hematopoietic stem cell transplantation outcome.}, journal = {Genome medicine}, volume = {17}, number = {1}, pages = {80}, pmid = {40676635}, issn = {1756-994X}, support = {K08 CA282987/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; K08CA282987//NIH-NCI K-award/ ; }, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Graft vs Host Disease/etiology ; Male ; Female ; Adult ; Middle Aged ; Transplantation, Homologous ; Saliva/microbiology ; Feces/microbiology ; Treatment Outcome ; *Gastrointestinal Microbiome ; *Microbiota ; Young Adult ; Aged ; Adolescent ; }, abstract = {BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is potentially curative for hematologic malignancies but is frequently complicated by relapse and immune-mediated complications, such as graft-versus-host disease (GVHD). Emerging evidence suggests a role for the intestinal and oral microbiome in modulating HSCT outcomes, yet predictive models incorporating microbiome data remain limited.

METHODS: We applied the RATIO (suRvival Analysis lefT barrIer lOss) model to longitudinal stool and saliva microbiome data from 204 adult HSCT recipients to predict the timing of seven outcomes: overall survival (OS), non-relapse mortality (NRM), relapse, acute GVHD (grades II-IV and III-IV), chronic GVHD, and oral chronic GVHD. A total of 514 stool and 1291 saliva samples were collected over 70 weeks post-HSCT. Model performance was evaluated using the concordance index (CI) and Spearman correlation coefficient (SCC), with SHAP (SHapley Additive exPlanations) analysis used for model interpretability.

RESULTS: Oral and stool microbial dysbiosis peaked within the first 2 weeks post-HSCT, followed by partial recovery. Using the RATIO model, we found that microbiome features from early time points (weeks 1-2) were most predictive of short-term complications such as acute GVHD, while later samples (weeks 36-70) were more informative for long-term outcomes, including overall survival. RATIO outperformed traditional survival models (Cox and Random Survival Forest) across most outcomes (median CI > 0.65), with stool microbiota showing greater predictive power than saliva. SHAP analysis identified specific stool genera, including Collinsella and Eggerthella, associated with shorter time to various complications. External validation using a pediatric GVHD cohort confirmed the model's generalizability and reproducibility. External validation using a pediatric HSCT cohort (n = 90) confirmed the reproducibility and generalizability of these microbiome-based predictions.

CONCLUSIONS: Microbiome profiling of stool and saliva samples offers robust, time-sensitive prediction of post-HSCT complications. The RATIO model enables interpretable, time-to-event prediction across multiple outcomes and may inform microbiome-guided interventions to improve transplant success.}, } @article {pmid40676526, year = {2025}, author = {Nabil, Y and Helal, MM and Qutob, IA and Dawoud, AIA and Allam, S and Haddad, R and Manasrah, GM and AlEdani, EM and Sleibi, W and Faris, A and Hassan, AK and Nandwana, V}, title = {Efficacy and safety of fecal microbiota transplantation in the management of parkinson's disease: a systematic review.}, journal = {BMC neurology}, volume = {25}, number = {1}, pages = {291}, pmid = {40676526}, issn = {1471-2377}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Parkinson Disease/therapy ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Gastrointestinal Microbiome ; }, abstract = {BACKGROUND: Parkinson's disease (PD) involves progressive neurodegeneration with motor and non-motor symptoms. Gut microbiota alterations are implicated in PD pathogenesis, leading to interest in fecal microbiota transplantation (FMT) as a therapeutic option. This systematic review assesses the efficacy and safety of FMT in managing PD symptoms.

METHODS: We conducted a comprehensive search across PubMed, Scopus, Web of Science, and Cochrane Central Controlled trials databases. Studies were screened based on predetermined inclusion criteria, focusing on randomized controlled trials (RCTs) involving FMT in PD patients. Two reviewers independently performed the data extraction and quality assessment. Key outcomes included improvements in motor and non-motor symptoms, quality of life, and adverse effects.

RESULTS: Five RCTs involving 157 patients met the inclusion criteria. Some studies reported improvements in motor and non-motor symptoms, particularly with colonic FMT, while others found no significant benefit. One trial observed motor function worsening. FMT was generally well-tolerated, with mild and transient gastrointestinal side effects.

CONCLUSION: FMT may relieve PD symptoms, but findings are inconsistent. Larger trials with standardized protocols are needed to determine its long-term efficacy and safety.}, } @article {pmid40675025, year = {2025}, author = {Cheraghi, M and Nazari, A and Souri, F}, title = {Gut microbiota and cardiac arrhythmogenesis: Unveiling the gut-heart axis.}, journal = {Pathology, research and practice}, volume = {273}, number = {}, pages = {156125}, doi = {10.1016/j.prp.2025.156125}, pmid = {40675025}, issn = {1618-0631}, abstract = {BACKGROUND: Cardiac arrhythmias, a leading cause of morbidity and mortality, have traditionally been linked to structural heart disease and genetic factors. However, growing evidence indicates that the gut microbiota, via its interactions with the cardiovascular system, may also contribute to arrhythmogenesis. The gut-heart axis, involving microbial metabolites, inflammatory signaling, and neural modulation, has emerged as a key regulator of cardiac electrophysiology.

METHODS: This review summarizes recent preclinical and clinical studies investigating the role of gut microbiota in the pathophysiology of cardiac arrhythmias. We examine mechanisms through which microbial products like short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), and bile acids influence arrhythmic risk, with a focus on their effects on ion channels, inflammation, and autonomic regulation.

RESULTS: Evidence from both animal models and human studies indicates that dysbiosis, or imbalance in the gut microbiome, is associated with an increased risk of arrhythmias, including atrial fibrillation and ventricular tachycardia. Microbial metabolites have been shown to influence cardiac electrophysiology through direct and indirect mechanisms, including immune modulation and autonomic nervous system regulation. Furthermore, microbiome-based interventions, such as dietary changes, probiotics, and fecal microbiota transplantation, show promise in reducing arrhythmic burden.

CONCLUSION: The gut microbiota's metabolic, inflammatory, and neural connections with the cardiovascular system increasingly suggest its role in arrhythmia risk. Targeting this gut-heart axis could lead to personalized arrhythmia prevention and treatment strategies.}, } @article {pmid40673781, year = {2025}, author = {You, MY and Tang, TWH and Novita, S and Liu, YW and Chang, KC and Wu, YW and Chao, YK and Ruan, SC and Lin, PJ and Chen, HC and Hsieh, PCH}, title = {Young microbiome transplantation enhances recovery after myocardial infarction.}, journal = {Aging}, volume = {17}, number = {7}, pages = {1852-1867}, pmid = {40673781}, issn = {1945-4589}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Mice ; Humans ; *Myocardial Infarction/therapy/microbiology ; Male ; Female ; Mice, Inbred C57BL ; Aged ; *Aging/physiology ; Middle Aged ; Anti-Bacterial Agents ; Disease Models, Animal ; }, abstract = {BACKGROUND: The relationship between aging, gut microbiota, and cardiac repair after myocardial infarction (MI) remains unclear. Understanding this interaction may provide novel strategies for improving cardiovascular outcomes in the elderly.

METHODS: Aged mice were treated with antibiotics followed by fecal microbiota transplantation (FMT) from young or aged donors prior to MI. Cardiac function, gut integrity, immune signaling, and metabolism were evaluated. Gut microbiota and plasma metabolites were also profiled in ST-elevation myocardial infarction (STEMI) patients across age groups.

RESULTS: Young FMT improved post-MI cardiac function and reduced infarct size in aged mice. It preserved intestinal barrier integrity, reduced IL-17A-positive immune cells, and attenuated age-related intestinal shortening. Aging was associated with decreased microbial diversity, loss of beneficial taxa such as Akkermansia, and enrichment of inflammatory pathways. Cardiac metabolomics revealed reduced oxidative metabolism and increased lipid reliance in aged mice. In STEMI patients, aging correlated with lower microbiota diversity, altered taxonomic profiles, and shifts in lipid and amino acid metabolism.

CONCLUSIONS: This study highlights the role of gut microbiota in cardiovascular health and aging. Microbiota transplantation improved cardiac recovery, suggesting its therapeutic potential and offering new insights into the gut-heart axis for future treatments in age-related cardiovascular disease.}, } @article {pmid40673140, year = {2025}, author = {Zhao, X and Xue, C and Wang, Y and Liu, X and Li, R and Yi, X}, title = {The potential of olfaction loss to induce cognitive impairment and anxiety behavior in mice via the microbiota-gut-brain axis.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1595742}, pmid = {40673140}, issn = {1664-302X}, abstract = {INTRODUCTION: Olfactory dysfunction and cognition decline are frequently observed; however, very little is known about whether olfactory disorders trigger cognitive impairment.

METHODS: Here, we induced olfactory loss in mice and investigated whether and how olfactory loss induces cognitive impairment and anxiety behavior.

RESULTS: Olfactory loss not only causes a significant decrease in food intake and body weight and an increase in O2 consumption but also induces cognitive impairment and anxiety behavior. Olfactory loss-induced alteration of the gut microbiota is associated with subsequent changes in cecal short-chain fatty acids and serum neurotransmitter levels. Hippocampus proteome and fecal microbial transplantation provide further support for the mechanisms by which olfactory loss triggers cognitive impairment and anxiety behavior via the microbiota-gut-brain axis.

DISCUSSION: Our study is expected to provide some evidence for olfactory dysfunction in triggering cognitive impairment through the microbiota-gut-brain axis.}, } @article {pmid40672832, year = {2025}, author = {Mei, H and Bao, P and Wang, Y and Wei, Z and Yang, Q and Chen, C and Sun, Y and Su, X and Kang, J and Li, W}, title = {Pulmonary cryptococcosis in the setting of immunosuppression by methylprednisolone monotherapy for oral pemphigus: a case report and literature review.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1569949}, pmid = {40672832}, issn = {2296-858X}, abstract = {Cryptococcosis is an opportunistic and potentially fatal fungal infectious disease. Pemphigus diseases are characterized by blistering of the cutaneous and mucous membranes. We report a case of pulmonary cryptococcosis (PC) following methylprednisolone treatment for pemphigus vulgaris. Additionally, we analyzed a case series of PC infections recorded in PUBMED from 2013 to 2023. A total of 229 cases of PC were included. The median age was 54 years, with 66.4% of patients being male. Those with previous use of corticosteroids or immunosuppressives accounted for 38.4% of cases. Underlying conditions included solid organ transplantations (25.7%), respiratory diseases (6.6%), malignant tumors (6.1%), rheumatoid arthritis (5.7%), hematological malignancies (4.4%), among others. The main source of infection was exposure to birds, poultry, and their feces (12.7%). Cryptococcus neoformans was most frequently isolated (76.4%). Overall mortality was 14.8%. Previous use of corticosteroids or immunosuppressants was a risk factor for disseminated cryptococcus (p < 0.05). Age, underlying disease, dissemination, and no antifungal therapy were independently associated with increased mortality (p < 0.05). Co-occurrence of pemphigus and PC is rare. Prompt diagnosis and appropriate treatment of PC are essential to prevent fatal consequences. Corticosteroids or immunosuppressive therapy are associated with the development of disseminated cryptococcal infection. Age, underlying disease, and dissemination are related to increased mortality. Timely antifungal therapy can improve prognosis.}, } @article {pmid40671981, year = {2025}, author = {Ruiz, NI and Herrera Giron, CG and Arragan Lezama, CA and Frias Redroban, SJ and Ventura Herrera, MO and Sanic Coj, GA}, title = {Timing and Protocols for Microbiome Intervention in Surgical Patients: A Literature Review of Current Evidence.}, journal = {Cureus}, volume = {17}, number = {6}, pages = {e86104}, pmid = {40671981}, issn = {2168-8184}, abstract = {Managing the gut microbiome with a personalized approach can significantly improve surgical outcomes, leading to reduced risk of infections, improved immune function, faster recovery and healing, and decreased risk of postoperative complications. This review explores microbiome-based interventions, such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, and their roles in perioperative, preoperative, and postoperative care. Electronic databases, such as PubMed, ScienceDirect, and Google Scholar, were searched using topic-related keywords and MeSH terms. The literature search was limited to English-language peer-reviewed articles within the last 10 years, but the majority of the literature was from the last five years. Microbiome interventions have been associated with reduced postoperative complications and enhanced recovery times. The study found that changing the gut microbiome in specific ways, like using probiotics and synbiotics before and after surgery, can lead to better surgical results. For example, these treatments can lower the risk of infection at the surgery site by 40%-80% compared to standard care, help patients recover their bowel function one to two days faster, and reduce hospital stays by up to 30%. They also decrease levels of important inflammation markers like IL-6 and CRP. Using probiotics and synbiotics before surgery and continuing them for two weeks can lower infection rates and enhance recovery while managing inflammation. The beneficial effects of probiotics, prebiotics, and synbiotics support their use as effective strategies in perioperative care. However, people react differently to probiotics, prebiotics, and synbiotics because of factors like genetics, age, hormonal differences between sexes, and variations in gut microbiota based on race. Future research should focus on developing personalized microbiome-based interventions and establishing standardized protocols tailored to individual patient characteristics to enhance their effectiveness.}, } @article {pmid40671646, year = {2025}, author = {Yang, T and Maki, KA and Marques, FZ and Cai, J and Joe, B and Pepine, CJ and Pluznick, JL and Meyer, KA and Kirabo, A and Bennett, BJ and , }, title = {Hypertension and the Gut Microbiome: A Science Advisory From the American Heart Association.}, journal = {Hypertension (Dallas, Tex. : 1979)}, volume = {}, number = {}, pages = {}, doi = {10.1161/HYP.0000000000000247}, pmid = {40671646}, issn = {1524-4563}, abstract = {Although substantial advancements have been made in hypertension research, translation of this research into new pharmacotherapies remains challenging. The need for new therapies is imperative: 15% to 20% of patients with hypertension have treatment-resistant hypertension, which often persists despite aggressive clinical treatments consisting of ≥3 medication classes, including a diuretic. Numerous preclinical studies have demonstrated that alterations in the gut microbiome affect blood pressure, suggesting an important role for this nonconventional cardiovascular risk factor. This innovative association suggests a novel therapeutic opportunity for hypertension: modifying the gut microbiome to control hypertension. In line with this hypothesis, clinical trials have been launched to examine whether hypertension can be managed by targeting the gut microbiome. This American Heart Association Science Advisory aims to outline clinical evidence, raise awareness among the health care community about the importance of the gut microbiome in patients with hypertension, update existing knowledge, identify research gaps, and ultimately facilitate the rapid translation of findings into clinical trials and practice.}, } @article {pmid40671079, year = {2025}, author = {Zhong, HJ and Pan, ZY and Wei, YF and Yu, Q and Wu, L and Wei, H and He, XX}, title = {Tongue-coating microbiota as a predictive biomarker of washed microbiota transplantation efficacy in pediatric autism: integration with clinical features.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {799}, pmid = {40671079}, issn = {1479-5876}, support = {2022B1111070006//Key-Area Research and Development Program of Guangdong Province/ ; JCYJ20240813140519025//Shenzhen Science and Technology Program/ ; 82201339//National Natural Science Foundation of China Youth Science Fund Project/ ; }, mesh = {Humans ; Animals ; Child ; Biomarkers/metabolism ; Female ; *Fecal Microbiota Transplantation ; *Tongue/microbiology ; Male ; Treatment Outcome ; *Microbiota ; Gastrointestinal Microbiome ; Mice ; Child, Preschool ; *Autistic Disorder/therapy/microbiology ; *Autism Spectrum Disorder/therapy/microbiology ; Feces/microbiology ; }, abstract = {BACKGROUND: Alterations in both oral and gut microbiota have been identified in children with autism spectrum disorder (ASD), but the interaction between these microbiota and their potential to predict outcomes of fecal microbiota transplantation (FMT) remain poorly understood.

METHODS: This study investigated the structure and function of the tongue-coating microbiota in children with ASD and explored its correlation with ASD symptoms and gut microbiota. Germ-free ASD mice, colonized with healthy gut microbiota, and children with ASD treated with washed microbiota transplantation (WMT) were assessed for changes in autism symptoms and microbiota composition. Predictive models were also developed based on pre-treatment tongue-coating microbiota and clinical features to forecast WMT outcomes.

RESULTS: Significant alterations were detected in the tongue-coating microbiota of children with ASD, with several bacterial species showing associations with ASD symptoms and gut microbiota composition. Following WMT, both mice and children exhibited substantial improvements in autism-related behaviors, alongside marked shifts in their gut and tongue-coating microbiota. A significant decrease in Haemophilus in the tongue-coating microbiota, which positively correlated with ASD severity, was observed. Additionally, a reduction in chemoheterotrophic and fermentation functions in the tongue-coating microbiota was identified. Predictive models utilizing pre-treatment tongue-coating microbiota and clinical data demonstrated comparable accuracy to those based on gut microbiota for forecasting WMT outcomes.

CONCLUSIONS: These findings highlight a significant interaction between gut and tongue-coating microbiota in ASD, which may play a pivotal role in treatment outcomes. Predictive models integrating pre-treatment microbiota and clinical features could improve precision treatment strategies for children with ASD undergoing WMT.}, } @article {pmid40671002, year = {2025}, author = {Liu, H and Wei, Y and Jiang, P and Fan, S and Zhao, Y and Li, Z and Wang, S and Zhang, N and Zhi, J and Wei, Q and Gu, Y and Yang, B and Feng, N and Wu, Y and Liu, F}, title = {Navigating the decision landscape: understanding interstitial cystitis/bladder pain syndrome patients' motivations and medical support needs for fecal microbiota transplantation: a qualitative research.}, journal = {BMC complementary medicine and therapies}, volume = {25}, number = {1}, pages = {268}, pmid = {40671002}, issn = {2662-7671}, support = {No. LY22H160011//Zhejiang Provincial Natural Science Foundation of China/ ; LXR22H160001//Zhejiang Provincial Natural Science Foundation of China/ ; 2021YFA1301100, 2021YFA1301101//the National Key Research and Development Program of China/ ; No. 81874142, 82073041//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Female ; Male ; Middle Aged ; *Cystitis, Interstitial/therapy/psychology ; *Fecal Microbiota Transplantation/psychology ; Qualitative Research ; Adult ; *Decision Making ; Aged ; *Motivation ; }, abstract = {BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) patients often confront limited treatment options, leading them to contemplate fecal microbiota transplantation (FMT) as an alternative therapy. Recognizing the factors influencing their decision-making process and their medical support needs is imperative. This study aimed to investigate the determinants of decision-making and the medical support requirements of IC/BPS patients considering FMT as an alternative treatment.

METHODS: Semi-structured interviews were conducted with 18 IC patients to explore their motivations for choosing FMT and their decision-making prerequisites. Data analysis was conducted using a thematic approach.

RESULTS: Two overarching themes and seven subthemes were identified. (1) Reasons for choosing FMT. ① Awareness of the complexity and intractability of the disease: Patients exhibited a profound understanding of IC's intricacy and intractability, which ignited their interest in FMT; ② Current treatment dissatisfaction boosted interest in FMT: Discontent with conventional treatments significantly impelled patients to consider FMT; ③ FMT is perceived as a side-effect-free holistic regulatory therapy; ④ Severe negative emotions drive patients to choose FMT: Strong emotions, such as anxiety and desperation, were motivating factors for patients choosing FMT. (2) Professional assistance required when choosing FMT. ① Access to Information Sources: Patients expressed a strong need for comprehensive information resources to aid their decision-making; ② Patients want to learn about peers' treatment experiences and outcomes: Patients sought insights from individuals who had undergone FMT; ③ Patients want more opportunities for communication with healthcare providers: enhanced communication channels with healthcare professionals were desired.

CONCLUSIONS: These findings emphasize the significance of addressing the intricate informational and emotional needs of IC/BPS patients when considering FMT as a treatment option. Tailored information delivery and peer support can facilitate informed decision-making within the context of FMT for IC/BPS.

TRIAL REGISTRATION: The trial registration number, CHiCTR2100048970, was registered on July 19, 2021.}, } @article {pmid40670809, year = {2025}, author = {Talat, A and Zuberi, A and Khan, AU}, title = {Unravelling the Gut-Microbiome-Brain Axis: Implications for Infant Neurodevelopment and Future Therapeutics.}, journal = {Current microbiology}, volume = {82}, number = {9}, pages = {390}, pmid = {40670809}, issn = {1432-0991}, support = {BT/PR40148/BTIS/137/20/2021//Department of Biotechnology, Ministry of Science and Technology, India/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Brain/growth & development/physiology ; Infant ; *Neurodevelopmental Disorders/therapy/microbiology ; Dysbiosis ; Probiotics ; Infant, Newborn ; Animals ; }, abstract = {The microbiome-gut-brain axis signifies the intricate interplay between gut microbiome and brain, facilitated by bidirectional communication channels. The brain modulates gut function through the hypothalamic-pituitary-adrenal axis and the autonomic nervous system, while the gut influences central nervous system (CNS) function through microbial metabolites, neurotransmitters, and gut hormones. Early brain development in infants is shaped by mother to neonate microbiome transmission, mode of birth, gestational length, breastfeeding, maternal and infant antibiotic exposure, and acquired infections. Dysbiosis in the gut microbiome is associated with various neurodevelopmental disorders in children such as attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). In this review, we elucidate the pivotal role of the microbiome-gut brain axis in a child's neural development, exploring factors modulating this intricate interaction. Furthermore, we discuss the potential future therapeutic avenues that can support optimal neurodevelopment, such as probiotics, prebiotics, synbiotics, postbiotics, CRISPR/Cas9, fecal microbiota transplant, and phage therapy.}, } @article {pmid40669701, year = {2025}, author = {Jeong, SH and Vasavada, SP and Lashner, B and Werneburg, GT}, title = {Reply to Editorial Comment on "Fecal Microbiota Transplant Is Associated With Resolution of Recurrent Urinary Tract Infection".}, journal = {Urology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.urology.2025.07.006}, pmid = {40669701}, issn = {1527-9995}, } @article {pmid40667879, year = {2025}, author = {Li, X and Wu, X and Zang, W and Zhou, Z and Cui, W and Chen, Y and Yang, H}, title = {Dietary iron attenuates Clostridioides difficile infection via modulation of intestinal immune response and gut microbiota.}, journal = {Virulence}, volume = {16}, number = {1}, pages = {2529454}, pmid = {40667879}, issn = {2150-5608}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Clostridioides difficile/drug effects/pathogenicity/immunology ; *Clostridium Infections/immunology/microbiology/prevention & control ; *Iron, Dietary/administration & dosage/pharmacology ; Disease Models, Animal ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S/genetics ; *Intestines/immunology/microbiology/drug effects ; Escherichia coli ; Male ; }, abstract = {Clostridioides difficile (C. difficile) is one of the majors causes of antibiotic-associated diarrhea globally. Host vulnerability to C. difficile infection (CDI) is largely affected by gut microbiota, which in turn is influenced by diet. However, the mechanism underlying the interplay between diet and the gut microbiota that regulates host susceptibility to CDI remains unclear. This study aimed to investigate how a high-iron diet affects the intestinal immune response, microbiota, and metabolism in mice infected with C. difficile. We explored the specific role of the unique gut microbiota and metabolites on CDI. A mouse model of CDI was constructed with or without high dietary iron treatment. The effect of high iron levels on gut microbiota was analyzed by 16S rRNA gene sequencing, and the role of gut microbiota was confirmed by fecal microbiota transplantation (FMT). High dietary iron (400 mg/kg ferrous sulfate) alleviated CDI by decreasing C. difficile pathogenicity and altering host intestinal neutrophil recruitment. Furthermore, E. coli AVS0501, enriched in the gut microbiota of iron-treated CDI mice, showed prophylactic and therapeutic effects on CDI. Moreover, the production of L-proline and tauroursodeoxycholic acid (TUDCA) in CDI mice treated with high dietary iron influenced C. difficile colonization, toxin production, and in turn, regulates the intestinal neutrophil response. Thus, high dietary iron alleviates C. difficile induced enteritis by regulating gut microbiota maintaining gut homeostasis, suggesting that high dietary iron may be an important determinant of disease control.}, } @article {pmid40666732, year = {2025}, author = {Cantas, L and Goll, R and Fenton, CG and Paulssen, RH and Sørum, H}, title = {Impact of fecal microbiota transplantation in dogs.}, journal = {Frontiers in veterinary science}, volume = {12}, number = {}, pages = {1505226}, pmid = {40666732}, issn = {2297-1769}, abstract = {BACKGROUND: The digestive tract hosts a variety of microorganisms. These microorganisms "micro-organs" play multiple crucial roles in physiological, immunological, and metabolic processes in the body. The manipulation and transplantation of "micro-organs" have lately gained increasing interest in human medicine with promising clinical outcomes, whereas much less is known in veterinary practice.

OBJECTIVES: The goals of this pilot study were to evaluate the safety and impact of Fecal Microbiota Transplantation (FMT) for dogs suffering from non-infectious digestive disorders.

ANIMALS: Seven client-owned adult dogs with idiopathic persistent diarrhea (>3 weeks) and very poor skin-coat conditions received the intervention (FMT) and were evaluated in a private veterinary clinic.

METHODS: Transplants have been taken from healthy donors and were administered rectally to recipients. Objective clinical examinations with analyses of blood and feces samples on day 0 (pre-FMT) and days 14-28 (post-FMT) were performed. Besides the conventional blood hematology and biochemistry analyses, 16S rRNA sequencing analysis was used in fecal samples.

RESULTS: No FMT-related complications occurred. Five of seven (71%) patients demonstrated improved fecal parameters associated with better overall clinical outcome, whereas four of the five (80%) recovered recipients showed molecular correlation with the donor gut microbiota after rectal FMT. There were insignificant changes shown for the conventionally analyzed blood samples. The serum cobalamin levels showed a tendency to increase in recovered recipients.

CONCLUSION: FMT was easy to apply and displayed certain health benefits in this study. Our findings reveal the important role of a "re-gained" gut microbiome balance in the overall health of dogs. Further research is needed to identify the dynamics and interplay between the different bacterial phyla that may have an impact on the stimuli of host immunologic and metabolic responses.}, } @article {pmid40664314, year = {2025}, author = {Li, Y and Zhang, S and Li, C and Shen, J and Cao, P and Sun, Y and Ma, X and An, B}, title = {Prebiotics chronotherapy alleviates depression-like behaviors in FMT mice through enhancing short-chain fatty acids receptors and intestinal barrier.}, journal = {Journal of affective disorders}, volume = {391}, number = {}, pages = {119885}, doi = {10.1016/j.jad.2025.119885}, pmid = {40664314}, issn = {1573-2517}, abstract = {BACKGROUND: Prebiotics interventions to restore microbiome homeostasis may have long-lasting benefits for mental health especially in adolescence. However, the anti-depressants of prebiotics, particularly in prebiotics chronotherapy, orchestrated remain unknown. We aimed to elucidate the underlying mechanisms of prebiotics in light of maximum antidepressant effects by appropriate dosing timing.

METHODS: Adolescent depression mouse model was made by fecal microbiota transplantation (FMT) from major depressive disorder (MDD) adolescent patients. Sodium Butyrate (SB), one of SCFAs, was intragastrically administrated to mice at Zeitgeber time 4 (ZT4: the highest short-chain fatty acids (SCFAs) receptor-activated timing) or ZT16 (the lowest SCFA receptor-activated timing) for the last 2 weeks within 4-week-FMT exposure. The success of modeling and antidepressant effects of SB chronotherapy were determined by changes in depression-like behaviors, inflammation, neurotrophy, neuron functions, circadian rhythm, and barrier systems.

RESULTS: SB alleviated depressive symptoms at ZT4 with better efficacy over ZT16. SB decreased inflammation, upregulated neurotrophy, restored functions, and re-established circadian rhythm. Notably, SB increased the expressions of SCFAs receptors to repair the intestinal barrier and blood-brain barrier, thereby alleviating depressive symptoms.

LIMITATION: Only one prebiotic with one disease was involved.

CONCLUSION: SB supplementation could be a promising therapeutic tactic for restoring the integrity of barrier systems by enhancing the intestinal SCFAs receptors. Alignment SB supplementation with circadian clocks might help to obtain better antidepressant efficacy, which may generate novel insights into diseases related to diseases with barrier system impairment and optimize interventions to improve health and human well-being.}, } @article {pmid40662222, year = {2025}, author = {Ortiz-Samur, NS and Vijaya, AK and Burokas, A and Mela, V}, title = {Exploring the Role of Microglial Cells in the Gut-Brain Axis Communication: A Systematic Review.}, journal = {Journal of neurochemistry}, volume = {169}, number = {7}, pages = {e70154}, pmid = {40662222}, issn = {1471-4159}, support = {CP22/00033//Instituto de Salud Carlos III/ ; PI24/00347//Instituto de Salud Carlos III/ ; UniversidaddeMálaga/CBUA//Open access charge/ ; }, mesh = {*Microglia/metabolism/physiology ; Animals ; *Gastrointestinal Microbiome/physiology ; Humans ; *Brain/metabolism ; *Brain-Gut Axis/physiology ; Neuroinflammatory Diseases ; }, abstract = {The gut-brain axis (GBA) is a bidirectional communication system between the gastrointestinal tract and the CNS, playing a key role in neurological function, immune response, and metabolism. Microglia, the resident immune cells in the brain, are crucial regulators of neuroinflammation and synaptic plasticity. Recent studies indicate that the gut microbiota modulates microglial activity through metabolic and immune pathways, with implications for neurodegenerative, neurodevelopmental, and psychiatric disorders. However, the mechanisms underlying microbiota-microglia interactions remain unclear. Following a systematic screening of 4481 studies, 20 preclinical studies met the inclusion criteria and were reviewed in depth to assess microbiota-microglia interactions. These studies were found by searching in PubMed, Science Direct, and Google Scholar. The findings synthesize results from 20 carefully selected studies examining the impact of gut microbiota on microglial function. Experimental models, including fecal microbiota transplantation, dietary interventions, and bacterial supplementation, were analyzed. Microglial activity was assessed through immunohistochemistry, gene expression profiling, and functional assays. Most studies suggest that gut dysbiosis promotes microglial overactivation and neuroinflammation through pathways involving microbial-derived short-chain fatty acids (SCFAs), bile acids, and neuroimmune signaling cascades such as TLR4/NF-κB and the NLRP3 inflammasomes, whereas microbiota-targeted interventions reduce inflammation and support cognitive function. Despite these promising findings, inconsistencies in study methodologies and microbiota analyses limit comparability and clinical translation. This review offers a unique synthesis of studies specifically linking gut microbiota alterations to microglial states, neuroinflammatory signatures, and cognitive outcomes across diverse experimental models. It highlights the therapeutic potential of microbiota-based strategies for modulating microglial function and mitigating neuroinflammatory diseases.}, } @article {pmid40662074, year = {2025}, author = {Jia, J and Wu, YB and Liu, SW and Chen, WJ and Li, RL and Bai, YL and Hu, L}, title = {Effectiveness and safety of non-pharmacological therapies for the treatment of inflammatory bowel disease: a network meta-analysis.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1593483}, pmid = {40662074}, issn = {2296-858X}, abstract = {BACKGROUND: Inflammatory bowel disease (IBD), encompassing both Crohn's disease (CD) and ulcerative colitis (UC), is a chronic, inflammatory, and immune-mediated disorder of the gastrointestinal tract. If left inadequately treated, IBD can lead to disease progression, resulting in severe long-term complications, including irreversible structural damage to the intestinal tissues. While clinical symptoms are traditionally used to assess treatment efficacy, they do not always align with the underlying mucosal inflammation, particularly in CD. This limitation underscores the importance of exploring alternative treatment strategies. To address this gap, the present study evaluates the effectiveness of non-pharmacological treatments (NPTs) for IBD through a network meta-analysis (NMA), providing a thorough assessment of the available evidence.

METHODS: We systematically reviewed randomized controlled trials (RCTs) from the following databases: PubMed, Embase, Springer, Cochrane Controlled Register of Trials (CENTRAL), and Web of Science, comparing various NPTs for IBD, including Cognitive Behavioral Therapy (CBT), diet interventions (DI), fecal microbiota transplantation (FMT), physical training (PT), and acupuncture and moxibustion (APMX). Outcomes assessed included clinical remission, disease activity, quality of life (QOL), serum biomarkers (fecal calprotectin [FC] and C-reactive protein [CRP]), and adverse effects. The quality assessment was assessed by Cochrane Handbook and GRADEpro software. The risk ratio (RR) was calculated for dichotomous outcomes while standardized mean difference (SMD) was used for continuous variables with 95% credible intervals (CI). Funnel plot was performed to evaluate publication bias. Surface under the cumulative ranking curve (SUCRA) was conducted to rank the included interventions. Data were analyzed with STATA 15.0 and Review Manager 5.3.

RESULTS: A total of 62 eligible RCTs were identified in this NMA. The results showed that standard medical therapy (SMT) exhibited the highest probability in inducing clinical remission, as expected. Among non-pharmacological interventions, APMX, a traditional Chinese medicine involving acupuncture and moxibustion, showed promising results in both animal models and clinical trials, reducing serum TNF-α levels and improving intestinal health. DI was most effective in maintaining clinical remission and reducing serum FC levels. FMT emerged as the most effective treatment for reducing serum CRP levels and ranked second in terms of clinical remission induction.

CONCLUSION: APMX, DI, and FMT represent promising non-pharmacological options for managing IBD. APMX was the most effective for clinical remission and symptom relief, while DI was best for maintaining remission, and FMT showed promise in reducing inflammation. Further high-quality clinical trials are needed to strengthen the evidence and guide clinical practice in IBD management.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42024596233, CRD42024596233.}, } @article {pmid40661942, year = {2025}, author = {Yin, J and Kaakoush, NO and Massey, J and Danta, M}, title = {Understanding the microbiome in autologous haemopoietic stem cell transplant for multiple sclerosis.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1590601}, pmid = {40661942}, issn = {1664-3224}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/methods ; Adult ; Female ; *Gastrointestinal Microbiome ; Male ; *Multiple Sclerosis/therapy/microbiology ; Middle Aged ; Transplantation, Autologous ; Natalizumab/therapeutic use ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; }, abstract = {BACKGROUND: MS is a chronic inflammatory and degenerative disease of the central nervous system (CNS) resulting in neurological deficits associated with physical and/or cognitive disability. The gut microbiome can interact with the CNS and immune system through various molecular pathways and has been previously implicated in MS. Autologous Haematopoietic Stem Cell Transplant (AHSCT) in MS arrests inflammatory disease and has evidence of long-term therapeutic benefit. To date, no study has explored the effect of AHSCT on the gut microbiome in people with MS.

METHOD: The microbiome of people with MS (pwMS) undergoing AHSCT was compared with pwMS on Natalizumab (NTZ). Longitudinal microbiome analysis was also conducted within the AHSCT cohort at two timepoints. Amplicon sequencing of the 16S ribosomal RNA V3-4 region (Illumina MiSeq) was used to evaluate alpha and beta diversity, oral-stool microbiota distances, and relative taxa abundances on both oral and stool microbiota.

RESULTS: The pre-transplant, baseline samples from the AHSCT cohort (n=8) was compared to the Natalizumab group (n=22). The AHSCT cohort had lower oral species richness compared to the NTZ cohort (p=0.026). There was a significant difference in oral beta diversity between the two cohorts (p=0.043). The oral taxa analysis of AHSCT subjects showed increased relative abundances of Porphyromonas and decreased Veillonella.

CONCLUSION: This pilot study identified specific microbiome changes, particularly in the oral alpha diversity and abundance of specific bacteria which may reflect treatment status or disease activity in MS.}, } @article {pmid40661744, year = {2025}, author = {Wang, X and Liu, X and Gong, F and Jiang, Y and Zhang, C and Zhou, W and Zhang, W}, title = {Targeting gut microbiota for diabetic nephropathy treatment: probiotics, dietary interventions, and fecal microbiota transplantation.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1621968}, pmid = {40661744}, issn = {1664-2392}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Probiotics/therapeutic use ; *Gastrointestinal Microbiome/physiology ; *Diabetic Nephropathies/therapy/microbiology ; Animals ; Dysbiosis/therapy ; }, abstract = {Diabetic nephropathy (DN) stands as a prominent microvascular complication of diabetes mellitus and presents a significant global health challenge. Despite advancements in glycemic control and renin-angiotensin system inhibition, current treatments merely delay disease progression without targeting fundamental pathological processes. This review explores gut microbiota modulation as a promising treatment strategy for DN through probiotic supplementation, dietary interventions, and fecal microbiota transplantation(FMT) protocols. The gut microbiota, integral to the "gut-kidney axis," is critically implicated in DN pathogenesis. DN is associated with gut dysbiosis-characterized by reduced microbial diversity, depletion of beneficial short-chain fatty acid (SCFA)-producing bacteria, and proliferation of opportunistic pathogens. This dysbiosis impairs gut barrier integrity, fostering systemic inflammation and the accumulation of uremic toxins like indoxyl sulfate. Furthermore, translocated bacterial lipopolysaccharides activate Toll-like receptors and the NLRP3 inflammasome, exacerbating kidney damage and fibrosis. Interventions targeting the microbiota, including dietary strategies (e.g., enhancing fermentable fibers, low-protein diets) and FMT, show promise in preclinical and early clinical studies, though FMT requires stringent safety and donor screening protocols. Significant challenges persist, such as managing inter-individual microbiota variability for personalized therapies, fully elucidating molecular mechanisms like SCFA-GPR43 signaling, and leveraging multiomics for biomarker discovery. Advancing microbiota-focused interventions for DN towards microbiome-centered precision medicine necessitates addressing standardization, deepening mechanistic understanding, and validating combination therapies, heralding a potential shift from traditional nephroprotective approaches.}, } @article {pmid40660288, year = {2025}, author = {Qin, W and Yin, N and Xu, B and Mei, Q and Fu, Y and Fan, J and Lu, Y and Wang, G and Ai, L and Lu, Z and Zeng, Y and Huang, C}, title = {Faecalibacterium prausnitzii enhances intestinal IgA response by host-microbe derived inecalcitol in colitis.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {425}, pmid = {40660288}, issn = {1741-7015}, support = {No. 81970555//National Natural Science Foundation of China/ ; No.CCTR-2022B02//Shanghai General Hospital/ ; 202440170//Shanghai Municipal Health Commission/ ; No.22SJKGGG28//Science and Technology Commission of Songjiang District/ ; No.KY-2023-03-02//Shanghai Jiao Tong University School of Medicine, Digestive Institute/ ; }, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome/immunology ; Humans ; *Faecalibacterium prausnitzii/immunology ; Mice, Knockout ; Mice, Inbred C57BL ; *Colitis, Ulcerative/microbiology/immunology ; Male ; *Immunoglobulin A/metabolism/immunology ; Dextran Sulfate ; Disease Models, Animal ; *Colitis/microbiology/immunology ; *Immunoglobulin A, Secretory ; Female ; Feces/microbiology ; }, abstract = {BACKGROUND: Faecalibacterium prausnitzii plays a crucial role in ulcerative colitis (UC) remission, but its action mechanism is unknown. Here, we aimed to explore the potential mechanisms focusing on the interaction of F. prausnitzii with host immune response and its potential modulation on gut microbiome.

METHODS: RNA-seq analysis together with 16S rRNA sequencing and metabolomics were performed in a dextran sodium sulfate (DSS)-induced colitis mouse model followed by F. prausnitzii gavage. To present evidence of sIgA involved in the anti-inflammatory effects of F. prausnitzii, we further applied immunoglobulin A (IgA) knockout mice and secretory IgA (sIgA) depletion mouse models using polymeric immunoglobulin receptor (pIgR) neutralizing antibody. Colonic immune cells were characterized by flow cytometry. The fecal relative abundance of F. prausnitzii, inecalcitol, and colonic IgA expression were assessed in UC patients.

RESULTS: F. prausnitzii markedly ameliorated colitis by alleviating intestinal inflammation and barrier dysfunction, with significantly decreased abundance of pro-inflammatory taxa (Enterococcus, Desulfovibrio, Escherichia-Shigella, and Enterorhabdus) and increased abundance of Lachnospiraceae NK4A136_group. Functions related to intestinal immune network for IgA production pathway were up-regulated shown by transcriptomics and KEGG pathway analysis. Increased expression of IgA production associated genes including MHCII-related genes, Aicda, and Tnfrsfl3c were verified, accompanied by up-regulated colonic IgA and pIgR. The IgA knockout mice and sIgA depletion model weakened the anti-inflammation and microbiota-modulation effects of F. prausnitzii, which was further proved by fecal microbiota transplantation (FMT). The shift profile of fecal metabolites after F. prausnitzii supplement was characterized by increased production of inecalcitol, which may account for the enhanced IgA response. In a cohort of UC patients, the relative abundance of F. prausnitzii was decreased and positively correlated with colonic IgA expression and negatively correlated with disease severity.

CONCLUSIONS: F. prausnitzii effectively alleviated colonic inflammation and modulated dysbiosis via enhancing colonic IgA response, thus showing promise as a UC treatment.}, } @article {pmid40659786, year = {2025}, author = {Lin, NY and Fukuoka, S and Koyama, S and Motooka, D and Tourlousse, DM and Shigeno, Y and Matsumoto, Y and Yamano, H and Murotomi, K and Tamaki, H and Irie, T and Sugiyama, E and Kumagai, S and Itahashi, K and Tanegashima, T and Fujimaki, K and Ito, S and Shindo, M and Tsuji, T and Wake, H and Watanabe, K and Maeda, Y and Enokida, T and Tahara, M and Yamashita, R and Fujisawa, T and Nomura, M and Kawazoe, A and Goto, K and Doi, T and Shitara, K and Mano, H and Sekiguchi, Y and Nakamura, S and Benno, Y and Nishikawa, H}, title = {Microbiota-driven antitumour immunity mediated by dendritic cell migration.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {40659786}, issn = {1476-4687}, abstract = {Gut microbiota influence the antitumour efficacy of immune checkpoint blockade[1-6], but the mechanisms of action have not been fully elucidated. Here, we show that a new strain of the bacterial genus Hominenteromicrobium (designated YB328) isolated from the faeces of patients who responded to programmed cell death 1 (PD-1) blockade augmented antitumour responses in mice. YB328 activated tumour-specific CD8[+] T cells through the stimulation of CD103[+]CD11b[-] conventional dendritic cells (cDCs), which, following exposure in the gut, migrated to the tumour microenvironment. Mice showed improved antitumour efficacy of PD-1 blockade when treated with faecal transplants from non-responder patients supplemented with YB238. This result suggests that YB328 could function in a dominant manner. YB328-activated CD103[+]CD11b[-] cDCs showed prolonged engagement with tumour-specific CD8[+] T cells and promoted PD-1 expression in these cells. Moreover, YB238-augmented antitumour efficacy of PD-1 blockade treatment was observed in multiple mouse models of cancer. Patients with elevated YB328 abundance had increased infiltration of CD103[+]CD11b[-] cDCs in tumours and had a favourable response to PD-1 blockade therapy in various cancer types. We propose that gut microbiota enhance antitumour immunity by accelerating the maturation and migration of CD103[+]CD11b[-] cDCs to increase the number of CD8[+] T cells that respond to diverse tumour antigens.}, } @article {pmid40659623, year = {2025}, author = {Wang, Z and Wang, S and Liu, S and Wang, Z and Li, F and Bu, Q and An, X}, title = {Polystyrene microplastics induce potential toxicity through the gut-mammary axis.}, journal = {NPJ science of food}, volume = {9}, number = {1}, pages = {139}, pmid = {40659623}, issn = {2396-8370}, support = {2024NC-YBXM-082//Key Research and Development Projects of Shaanxi Province/ ; K4050422535//Experimental Demonstration Base of Dairy Goat in Heshui, Northwest Agriculture and Forestry University, China/ ; }, abstract = {Microplastics (MPs), as an emerging environmental pollutant, pose a grave threat to food safety and public health. However, studies on MP toxicity to organs other than the intestine remain limited, especially its link to the intestinal microbiota. To address this gap, we evaluated the potential toxicity of polystyrene (PS)-MPs to the gut and mammary glands during lactation exposure in mice. PS-MPs (~1 μm) can disrupt the intestinal barrier and cause colonic inflammation and gut microbiota dysbiosis. Moreover, they can accumulate in mammary tissue and cause inflammatory damage. Transcriptome data suggested that PS-MPs cause maternal mammary lipid metabolism disorders and ferroptosis. Fecal microbial transplant (FMT) was then performed, and it reproduced the observed leakage of the blood-milk barrier and inflammation of the mammary gland. This study demonstrated that MPs induced gut and mammary inflammation and exacerbated inflammatory damage through the gut-mammary axis. In addition, MPs caused mammary lipid disorders and ferroptosis. The findings confirmed that PS-MPs may be transported to mammalian organs other than the intestine (e.g., mammary gland) and revealed the critical role of the intestinal microbiota. These findings will provide guidance for further studies on the potential foodborne risks of MPs.}, } @article {pmid40659561, year = {2025}, author = {Yang, L and Hua, M and Li, D and Li, F and He, Y and Miao, X and Sun, M and Niu, H and An, F and Wang, J and Yang, M and Lu, J and Xu, H and Wang, J}, title = {Protective Effects of Ginseng Soluble Dietary Fiber and Its Fecal Microbiota Extract on Antibiotic-Induced Gut Dysbiosis Obese Mice.}, journal = {Journal of microbiology and biotechnology}, volume = {35}, number = {}, pages = {e2502013}, pmid = {40659561}, issn = {1738-8872}, mesh = {Animals ; *Dysbiosis/chemically induced/drug therapy/prevention & control/microbiology ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Anti-Bacterial Agents/adverse effects ; *Panax/chemistry ; Mice, Obese ; Male ; *Dietary Fiber/pharmacology ; *Obesity/chemically induced ; *Plant Extracts/pharmacology ; Toll-Like Receptor 4/metabolism ; Feces/microbiology ; Mice, Inbred C57BL ; Bacteria/classification/drug effects ; Signal Transduction/drug effects ; Myeloid Differentiation Factor 88/metabolism ; NF-kappa B/metabolism ; Insulin Resistance ; Body Weight/drug effects ; Disease Models, Animal ; Oxidative Stress/drug effects ; }, abstract = {Prolonged or improper antibiotic use may increase the risk of obesity. Ginseng soluble dietary fiber (G-SDF) has been shown to inhibit obesity and promote the growth of intestinal probiotics. However, its role in antibiotic-induced gut dysbiosis obese mice (ADIO) remains unclear, and this study aimed to elucidate this role. The results indicated that G-SDF and its fecal microbiota extract (SDFfbs) significantly reduced body weight, insulin resistance, hepatic fat accumulation, abnormal blood and liver glucose-lipid metabolism, oxidative stress, and immune-inflammatory responses in ADIO mice. G-SDF and SDFfbs also inhibited the LPS/TLR4/MyD88/NF-κB signaling pathway, restored the expression of the gut barrier proteins Occludin and Claudin1, and protected against intestinal damage in ADIO mice. In particular, G-SDF and SDFfbs significantly increased the abundance of Firmicutes and Bacteroidetes and decreased the abundance of harmful Escherichia and Streptococcus. Additionally, they promoted the growth of beneficial bacteria, such as Enterococcus, Lactobacillus, Bifidobacterium, Parabacteroides, and Akkermansia, and these microbial shifts correlated with significant improvements in metabolic indicators in ADIO mice. Notably, SDFfbs can replicate the efficacy of SDF and has even shown stronger effects than the latter. In summary, this study demonstrated that G-SDF and SDFfbs effectively mitigate the double damage caused by obesity and antibiotic exposure by modulating the LPS/TLR4/MyD88/NF-κB pathway, protecting the intestinal barrier, and restoring the gut microbiota balance. These findings provide an important theoretical basis for the use of G-SDF and SDFfbs as fat-reducing and antibiotic-resistant ingredients in health foods.}, } @article {pmid40655582, year = {2025}, author = {Patel, SP and Bhoraniya, SJ and Kalola, SD and Rukadikar, A and Ravi, R and Farooqui, S and Rukadikar, C}, title = {Gut Microbiota and its Impact on Chronic Diseases: A Comprehensive Review.}, journal = {Journal of pharmacy & bioallied sciences}, volume = {17}, number = {Suppl 2}, pages = {S1080-S1082}, pmid = {40655582}, issn = {0976-4879}, abstract = {The intricate community of bacteria that live in the gastrointestinal system, known as the gut microbiota, is essential to preserving human health and equilibrium. The pathophysiology of several chronic illnesses, including as neurological, cardiovascular, immunological, and metabolic disorders, has been progressively associated with its dysbiosis. This thorough analysis looks at the complex relationships that exist between gut microbiota and host physiology, examining processes including metabolic signaling, immunological regulation, and gut-brain axis communication. We discuss current developments in the study of the microbiome, with an emphasis on the role that the variety and makeup of gut microbes play in the development of chronic diseases. In order to restore microbial balance and lessen the severity of the condition, the study also covers new treatment approaches such as dietary changes, probiotics, prebiotics, and fecal microbiota transplantation. The development of novel, microbiome-based diagnostic and therapeutic strategies is made possible by an understanding of the complex link between the gut microbiota and chronic illnesses, highlighting the vital role that personalized medicine plays in enhancing health outcomes.}, } @article {pmid40654576, year = {2025}, author = {Xie, H and Yu, S and Tang, M and Xun, Y and Shen, Q and Wu, G}, title = {Gut microbiota dysbiosis in inflammatory bowel disease: interaction with intestinal barriers and microbiota-targeted treatment options.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1608025}, pmid = {40654576}, issn = {2235-2988}, mesh = {Humans ; *Dysbiosis/therapy/microbiology ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Gastrointestinal Microbiome/drug effects ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use ; *Intestinal Mucosa/microbiology ; Animals ; }, abstract = {Recent studies have deepened our understanding on gut microbiota alterations and the interaction with intestinal barrier impairments, which play a crucial role in the etiology and pathophysiology of Inflammatory bowel disease (IBD). The intestinal microbiota dysbiosis in IBD including the altered microbiota composition, decreased beneficial species and increased harmful species. The disturbed gut microbiota results in the aggravation of intestinal barrier dysfunction through regulation of antimicrobial substances in mucus layer, tight junction protein in mechanical layer and inflammatory response in immune layer. The therapeutic options targeted on the microbiota including antibiotics, probiotics and fecal microbiota transplantation (FMT) exhibit efficacies and limitations in the treatment of IBD. Reasonable single or combined use of these treatments can restore intestinal microecological homeostasis, which further contributes to the treatment of IBD. This review analyzes the underlying mechanisms for the interaction between microbiota alterations and gut barrier dysfunction in IBD; meanwhile, it provides new insights into the microbiota-targeted therapeutic options IBD, including the benefits, risks and limitations of antibiotic and probiotic therapies, unresolved clinical application strategies for FMT, and combination administrations of antibiotics and FMT.}, } @article {pmid40653357, year = {2025}, author = {Meena, AS and Singh, P and Shukla, PK}, title = {Cancer and microbiome-targeted therapies.}, journal = {International review of cell and molecular biology}, volume = {395}, number = {}, pages = {99-132}, doi = {10.1016/bs.ircmb.2024.12.006}, pmid = {40653357}, issn = {1937-6448}, mesh = {Humans ; *Neoplasms/therapy/microbiology ; *Microbiota/drug effects ; Animals ; Probiotics/therapeutic use ; Tumor Microenvironment ; Fecal Microbiota Transplantation ; }, abstract = {Emerging research highlights the profound interplay between the microbiome and cancer, offering novel avenues for therapeutic interventions. This review explores the burgeoning field of microbiome-targeted therapies in oncology, focusing on how microbial communities influence cancer development, progression, and response to treatment. The microbiome's role in modulating immune responses, drug metabolism, and tumor microenvironment is examined, revealing its potential to both inhibit and promote tumorigenesis. We discuss current strategies that leverage microbiome modulation, including probiotics, prebiotics, and fecal microbiota transplantation, to enhance the efficacy of conventional cancer therapies and mitigate side effects. Additionally, the review addresses the challenges and future directions in integrating microbiome-based approaches into clinical practice. By elucidating the mechanisms through which the microbiome affects cancer and therapy outcomes, this work aims to pave the way for innovative, personalized treatment strategies that harness the power of microbial communities to improve cancer care.}, } @article {pmid40653356, year = {2025}, author = {Sarath Krishnan, MP and Goyal, B and Nampui, L and Gupta, SC}, title = {The role of microbiome in gastrointestinal cancer.}, journal = {International review of cell and molecular biology}, volume = {395}, number = {}, pages = {67-98}, doi = {10.1016/bs.ircmb.2024.12.009}, pmid = {40653356}, issn = {1937-6448}, mesh = {Humans ; *Gastrointestinal Neoplasms/microbiology/pathology/therapy ; *Gastrointestinal Microbiome ; Animals ; }, abstract = {The human microbiome consists of the diverse microorganisms with their equally diverse functional abilities that have evolved over millions of years with humans. This microbiome creates a mutually beneficial symbiotic relationship with their host. Through their varied functions, the human gut microbiota is crucial for preserving health and homeostasis. Any imbalance in this microbial population can lead to an array of diseased states, including cancer especially of the gastrointestinal system. The focus of this chapter is to discuss the mechanisms through which the gut microbiome creates a conducive environment for initiation and progression of cancer. In addition, the effect of microbial products such as short chain fatty acids, bile acids and Trimethylamine N-oxide on the formation of gastrointestinal cancer is also discussed. The various experimental methods and new molecular techniques that have facilitated the characterization and study of microorganisms is also discussed. The developments in microbiome research have shed light on the potential role of gut microbiota for novel biomarker discovery and therapeutic interventions in gastrointestinal cancer, like fecal microbiota transplantation. The prospects of these areas for further exploration are discussed.}, } @article {pmid40653352, year = {2025}, author = {Singh, K and Bhadauriya, AS}, title = {Effect of microbial dysbiosis on autoimmune associated inflammation.}, journal = {International review of cell and molecular biology}, volume = {395}, number = {}, pages = {1-22}, doi = {10.1016/bs.ircmb.2024.12.016}, pmid = {40653352}, issn = {1937-6448}, mesh = {Humans ; *Dysbiosis/complications/microbiology/immunology ; *Autoimmune Diseases/microbiology/immunology ; *Inflammation/microbiology/immunology/complications ; Animals ; *Gastrointestinal Microbiome/immunology ; }, abstract = {Trillions of microorganisms inhabit the human body, playing crucial roles in the development of the immune system, maintaining balance within the gut's immune system, and overall well-being. When these microbial communities experience imbalance, known as dysbiosis, it can lead to localized inflammatory conditions such as colitis and inflammatory bowel diseases, as well as systemic autoimmune disorders like type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. Gut microbes engage with the immune system through various means, including influencing host microRNAs to regulate gene expression and generating metabolites that interact with cellular receptors such as TLRs and GPCRs. These interactions impact critical immune processes like the differentiation of lymphocytes, the production of interleukins, and the maintenance of gut barrier function. Looking into, how gut microbes contribute to or defend against systemic autoimmune diseases is crucial for developing strategies to manage or prevent these conditions. These approaches may include dietary or lifestyle modifications, microbiome-targeted therapies such as prebiotics or probiotics, the identification of diagnostic biomarkers for predicting disease risk, and monitoring and intervening in shifts in microbial populations during autoimmune flare-ups. Recognizing the microbiome's significance in systemic autoimmune diseases offers promise for transforming these presently challenging-to-treat conditions into more controllable or preventable ones.}, } @article {pmid40651297, year = {2025}, author = {Chen, LJ and Liu, Y and Liu, JL and Chen, ZJ and Zhao, W and Li, JH and Hsu, C and Chen, L and Zeng, JH and Li, XW and Yang, JZ and Li, JH and Xie, XL and Tao, SH and Wang, Q}, title = {Lycopene ameliorates Di-(2-ethylhexyl) phthalate-induced neurotoxicity in mice via the gut-brain axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {145}, number = {}, pages = {157057}, doi = {10.1016/j.phymed.2025.157057}, pmid = {40651297}, issn = {1618-095X}, mesh = {Animals ; *Lycopene/pharmacology ; *Diethylhexyl Phthalate/toxicity ; *Gastrointestinal Microbiome/drug effects ; Mice ; Male ; *Neuroprotective Agents/pharmacology ; Brain/drug effects ; Fecal Microbiota Transplantation ; *Neurotoxicity Syndromes/drug therapy ; Mice, Inbred C57BL ; Dysbiosis ; *Brain-Gut Axis/drug effects ; }, abstract = {BACKGROUND: Di(2-ethylhexyl) phthalate (DEHP), a ubiquitous plasticizer present in numerous consumer products, poses a substantial neurotoxic risk through environmental and dietary exposure. Growing evidence highlights a critical association between DEHP-induced neurotoxicity and gut microbiota dysbiosis. Renowned for its potent antioxidant and anti-inflammatory capabilities, the natural carotenoid lycopene (Lyc) demonstrates therapeutic promise in treating various neurological disorders.

PURPOSE: The potential neuroprotective mechanisms of Lyc against DEHP-induced neurotoxicity in mice were investigated in this study, with a specific focus on its interaction with the gut-brain axis.

METHODS: For 35 consecutive days, mice received daily intragastric administrations of DEHP or Lyc. A comprehensive approach involving integrated transcriptome, microbiome, and molecular biology analyses, in conjunction with bacteriotherapy, was utilized to thoroughly investigate the underlying mechanisms.

RESULTS: Our findings demonstrated that Lyc administration or fecal microbiota transplantation (FMT) from Lyc-treated mice effectively ameliorated DEHP-induced anxiety- and depression-like behaviors. At the molecular level, Lyc mitigated neuroinflammation in the hippocampus, potentially through modulation of the NOD-like receptor signaling pathway. Furthermore, Lyc treatment improved gut microbiota composition by promoting the growth of beneficial bacteria, such as Akkermansiaceae, and enhanced intestinal barrier integrity via increased expression of tight junction proteins. Lyc also regulated the LPS-TLR4/MyD88 signaling pathway in the colon, thereby reducing local inflammation.

CONCLUSION: These results provide compelling evidence that Lyc confers protection against DEHP-induced neurotoxicity through a multifaceted strategy involving modulation of gut-brain axis, suppression of neuroinflammation, and restoration of gut homeostasis. We propose a novel therapeutic strategy to alleviate the risks posed by DEHP to both neurological and intestinal health. This approach involves either supplementation with Lyc or the application of bacteriotherapy.}, } @article {pmid40650758, year = {2025}, author = {Kearns, R}, title = {Gut modulation to regulate NF-κB in colorectal and gastric cancer therapy and inflammation.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {74}, number = {8}, pages = {264}, pmid = {40650758}, issn = {1432-0851}, mesh = {Humans ; *NF-kappa B/metabolism ; *Gastrointestinal Microbiome/immunology ; *Stomach Neoplasms/therapy/immunology/metabolism/microbiology/pathology ; *Inflammation/metabolism ; *Colorectal Neoplasms/therapy/immunology/metabolism/microbiology/pathology ; Animals ; Dysbiosis ; Fecal Microbiota Transplantation ; Signal Transduction ; }, abstract = {The nuclear factor-kappa B (NF-κB) pathway plays a pivotal role in cancer progression, immune regulation, and inflammation. Aberrant activation of this pathway, often driven by gut microbiota dysbiosis, contributes to tumorigenesis, therapy resistance, and chronic inflammation. Emerging evidence highlights the bidirectional interaction between gut microbiota and NF-κB signalling, suggesting that microbiota modulation may enhance cancer treatment efficacy and reduce treatment-induced inflammation. This review explores the mechanistic underpinnings of gut microbiota-mediated NF-κB regulation, focusing on microbial metabolites such as short-chain fatty acids (SCFAs) and microbial-associated molecular patterns, including lipopolysaccharides (LPS). It examines how conventional cancer treatments, chemotherapy, radiotherapy, and immune checkpoint inhibitors, exacerbate dysbiosis and NF-κB-driven inflammation, further complicating treatment outcomes. Additionally, this review evaluates the therapeutic potential of gut-targeted interventions, including probiotics, prebiotics, faecal microbiota transplantation (FMT), and dietary modifications, in restoring microbial homeostasis and modulating NF-κB signalling. Despite promising findings, challenges remain regarding the clinical translation of microbiota-based therapies, including the need for standardised microbiota profiling, regulatory frameworks, and long-term safety assessments. Advances in metagenomics and metabolomics are proposed as essential tools to personalise gut-targeted interventions and optimise cancer treatment strategies. Integrating gut modulation into oncology represents a paradigm shift, offering a holistic, patient-centric approach to cancer therapy. However, further research is required to validate these strategies and ensure their efficacy in clinical applications.}, } @article {pmid40649988, year = {2025}, author = {Kaltsas, A and Giannakodimos, I and Markou, E and Stavropoulos, M and Deligiannis, D and Kratiras, Z and Chrisofos, M}, title = {The Androbactome and the Gut Microbiota-Testis Axis: A Narrative Review of Emerging Insights into Male Fertility.}, journal = {International journal of molecular sciences}, volume = {26}, number = {13}, pages = {}, pmid = {40649988}, issn = {1422-0067}, mesh = {Humans ; Male ; *Gastrointestinal Microbiome/physiology ; *Infertility, Male/microbiology/metabolism ; *Testis/metabolism/microbiology ; Animals ; *Fertility ; Spermatogenesis ; Dysbiosis/microbiology ; }, abstract = {Male infertility is an under-recognized global health burden. Accumulating evidence position the intestinal microbiota as a pivotal regulator of testicular function, underpinning the emerging gut microbiota-testis axis. This narrative review introduces the conceptual term "androbactome", referring to gut microorganisms and microbial genes that are hypothesized to influence androgen biosynthesis, spermatogenesis, and broader reproductive endocrinology. The documented worldwide decline in sperm concentration heightens the urgency of clarifying microbe-mediated influences on male reproductive capacity. The synthesis of preclinical and clinical findings reveals four principal pathways by which dysbiosis compromises fertility: systemic inflammation, oxidative stress, endocrine disruption, and epigenetic alteration. Lipopolysaccharide-driven cytokinaemia, reactive oxygen species generation, hypothalamic-pituitary-gonadal axis suppression, and aberrant germ cell methylation collectively impair sperm quality and hormonal balance. Short-chain fatty acids, secondary bile acids, and indole derivatives emerge as pivotal messengers within this crosstalk. Therapeutic approaches targeting the androbactome, namely dietary optimization, probiotic or prebiotic supplementation, and fecal microbiota transplantation, have demonstrated encouraging improvements in sperm parameters and testosterone levels, yet the causal inference is constrained by predominantly cross-sectional designs and limited long-term safety data. Recognizing the androbactome as a modifiable determinant of male fertility may open new avenues for personalized diagnosis, risk stratification, and adjunctive therapy in regard to idiopathic infertility. The integration of multi-omics platforms to characterize microbial and metabolomic signatures promises to enrich diagnostic algorithms and guide precision interventions, but rigorously controlled longitudinal and interventional studies are required to secure a translational impact.}, } @article {pmid40649705, year = {2025}, author = {Borbélyová, V and Szabó, J and Sušienková, P and Potvin, J and Belvončíková, P and Groß, T and Jančovičová, A and Bačová, Z and Rašková, B and Szadvári, I and Antal, M and Pirník, Z and Karhánek, M and Šoltys, K and Gardlík, R and Celec, P and Ostatníková, D and Tomova, A}, title = {The Effect of Parental Faecal Microbiome Transplantation from Children with Autism Spectrum Disorder on Behavior and Gastrointestinal Manifestations in the Male Offspring of Shank3 Mice.}, journal = {International journal of molecular sciences}, volume = {26}, number = {13}, pages = {}, pmid = {40649705}, issn = {1422-0067}, support = {APVV-20-0114//Slovak Research and Development Agency/ ; VEGA 1/0062/21//Ministry of Education, Science, Research, and Sport of the Slovak Republic/ ; }, mesh = {Animals ; *Autism Spectrum Disorder/therapy/microbiology/genetics ; *Fecal Microbiota Transplantation ; Mice ; Male ; Female ; *Nerve Tissue Proteins/genetics/metabolism ; Humans ; Behavior, Animal ; Pregnancy ; Gastrointestinal Microbiome ; Mice, Knockout ; Disease Models, Animal ; Child ; Prenatal Exposure Delayed Effects ; Microfilament Proteins ; }, abstract = {The increasing incidence of autism spectrum disorder (ASD) increases the urgency of establishing the mechanism of its development for effective prevention and treatment. ASD's etiology includes genetic predisposition and environmental triggers, both of which can play a role in the changed microbiota. Recent research has proved the impact of maternal microbiota on the neurodevelopment of the child. To investigate the co-play of genetic and microbiota factors in ASD development, we performed fecal microbiota transplantation (FMT) from children with ASD to female Shank3b[+/-] mice and studied the autism-like symptoms in the male Shank3b[-/-] and wild-type (WT) offspring. WT animals with prenatal exposure to ASD microbiota had delayed neurodevelopment and impaired food intake behavior, but also elevated plasma leptin concentration and body weight. Shank3b[-/-] mice after FMT ASD exhibited impaired learning and exacerbated anxiety-like behavior in adulthood. Interestingly, FMT ASD improved learning in adolescent Shank3b[-/-] mice. Prenatal exposure to ASD microbiota decreased the activity of hypocretin neurons of the lateral hypothalamic area in both genotypes. The combination of genetic predisposition and FMT ASD led to an increased colon permeability, evaluated by zonula occludens (ZO1, ZO3) and claudin factors. These results suggest the effect of parental FMT exposure on shaping offspring behavior in Shank3b[-/-] mice and the potential of microbiota in the modulation of ASD.}, } @article {pmid40647353, year = {2025}, author = {Liber, A and Więch, M}, title = {The Impact of Fecal Microbiota Transplantation on Gastrointestinal and Behavioral Symptoms in Children and Adolescents with Autism Spectrum Disorder: A Systematic Review.}, journal = {Nutrients}, volume = {17}, number = {13}, pages = {}, pmid = {40647353}, issn = {2072-6643}, mesh = {Humans ; *Autism Spectrum Disorder/therapy/complications/psychology/microbiology ; *Fecal Microbiota Transplantation/methods ; Child ; Adolescent ; *Gastrointestinal Diseases/therapy/etiology ; Treatment Outcome ; Male ; Female ; Child, Preschool ; Gastrointestinal Microbiome ; *Behavioral Symptoms/therapy ; Dysbiosis/therapy ; }, abstract = {Background: Gastrointestinal (GI) symptoms, often reported by individuals with autism spectrum disorders (ASD), may impair functionality and exacerbate behavioral symptoms. Gut dysbiosis has been identified as a potential environmental factor influencing these symptoms through gut-brain axis dysregulation. Fecal microbiota transplantation (FMT) is a promising therapeutic strategy with potential to alleviate symptoms. This review systematically evaluates the efficacy and safety of FMT in GI and ASD-related symptoms. Methods: This systematic review followed PRISMA 2020 guidelines and was registered in PROSPERO. The review included clinical trials on FMT in children and adolescents with ASD, published up to October 2024. The bias assessments were performed using Cochrane tools. Outcomes focused on changes in GI and ASD-related symptoms using scales selected by the authors. Results: This systematic review included two RCTs and seven before-and-after studies. Improvements in GI and ASD-related outcomes were reported in all before-and-after studies, whereas the results of RCTs were inconsistent. The before-and-after studies showed a high risk of bias, while the RCTs demonstrated a low risk. Conclusions: Although many studies have been conducted, the methodological limitations of some and contradictory findings of others make it difficult to draw clear conclusions about the effectiveness of FMT in children with ASD. Variations in intervention protocols underscore the importance of establishing standardized FMT procedures in future rigorously designed trials.}, } @article {pmid40647217, year = {2025}, author = {Szczuko, M and Grudniewska, A and Durma, A and Małecki, R and Filipczyńska, I and Franek, E and Kędzierska-Kapuza, K}, title = {Non-Pharmacological Interventions Aimed at Changing the Gut Microbiota for Preventing the Progression of Diabetic Kidney Disease.}, journal = {Nutrients}, volume = {17}, number = {13}, pages = {}, pmid = {40647217}, issn = {2072-6643}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Diabetic Nephropathies/microbiology/therapy/prevention & control ; *Probiotics/therapeutic use/administration & dosage ; Disease Progression ; Fecal Microbiota Transplantation ; Animals ; Synbiotics/administration & dosage ; Dysbiosis/therapy ; Dietary Supplements ; }, abstract = {BACKGROUND: Diabetic kidney disease (DKD) affects 20-50% of individuals with diabetes. The aim of this review was to identify interventions that positively influence the gut microbiota in DKD.

METHODS: Identification of relevant studies was conducted via a systematic search of databases and registers using the PRISMA guidelines. This review examined the relevant literature published up to 5 January 2025, using a systematic search in PubMed and Scopus. The search was conducted with combinations of keywords including DKD and therapy, supplementation and gut microbiota, and supplementation or probiotics or fecal microbiota transplant. The initial search fielded 132 results from PubMed and 72 from Scopus, which was narrowed to 135 relevant studies. The exclusion criteria included non-English language studies, letters to the editor, and conference abstracts. Eligible studies were independently assessed by a minimum of three authors, with discrepancies resolved through consensus.

RESULTS: Gut microbiota-targeted interventions, including probiotics, synbiotics, and dietary modifications, show promise in modulating the gut microbiota, but evidence specific to DKD remains limited. Some natural food components such as polyphenols and anthocyanins modulate the composition of the gut microbiota translocation of uremic toxins, which slows down the progression of diabetic kidney disease. In animal models, fecal microbiota transplantation (FMT) has shown positive effects in regulating dysbiosis and beneficial effects in chronic kidney disease, but studies involving humans with DKD are insufficient.

CONCLUSIONS: Lactobacillus and Bifidobacterium strains, administered at doses ranging from 0.6 to 90 billion CFU, may help lower urea and creatinine levels, but outcomes vary by disease stage, duration of therapy, and amount used. High-fiber diets (>10.1 g/1000 kcal/day) and supplements such as resistant starch and curcumin (400-1500 mg/day) may reduce uremic toxins through gut microbiota modulation and reduction in oxidative stress. The effect of sodium butyrate requires further human studies.}, } @article {pmid40645350, year = {2025}, author = {Fatima, SN and Arif, F and Khalid, R and Khan, M and Naseem, K}, title = {Immunomodulatory role of gut microbiota in autoimmune disorders and the advancement of gut microbiota based therapeutic strategies.}, journal = {Microbial pathogenesis}, volume = {207}, number = {}, pages = {107882}, doi = {10.1016/j.micpath.2025.107882}, pmid = {40645350}, issn = {1096-1208}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Autoimmune Diseases/therapy/immunology/microbiology ; Probiotics/therapeutic use ; Dysbiosis/immunology/therapy ; Prebiotics/administration & dosage ; Animals ; *Immunomodulation ; T-Lymphocytes, Regulatory/immunology ; Receptors, Aryl Hydrocarbon/metabolism ; Th17 Cells/immunology ; Fecal Microbiota Transplantation ; Fatty Acids, Volatile/metabolism ; }, abstract = {This review investigates the central hypothesis that gut microbiota dysbiosis contributes to autoimmune pathogenesis via immune dysregulation, increased intestinal permeability, and aberrant metabolite signaling and many other pathways. Mechanisms such as SCFA depletion, Th17/Treg imbalance, molecular mimicry, and disrupted aryl hydrocarbon receptor (AhR) pathways plays central immunomodulatory role in the development as well as management of autoimmune disorders including RA, T1D, MS, and IBD. Emerging interventions like probiotics, prebiotics, SCFA supplementation, and FMT are critically assessed to demonstrating their modulatory effects on cytokine profiles, epithelial integrity, and Treg induction. Clinical and preclinical data support microbial restoration as a viable immunotherapeutic strategy. The review concludes that targeting gut-immune crosstalk through microbiota-directed therapies may offer precise, mechanism-based management for many autoimmune disorders.}, } @article {pmid40644647, year = {2025}, author = {Barragan-Carrillo, R and Zengin, ZB and Pal, SK}, title = {Microbiome Modulation for the Treatment of Solid Neoplasms.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {43}, number = {24}, pages = {2734-2738}, pmid = {40644647}, issn = {1527-7755}, abstract = {The interplay between the human gut microbiome and the immune system has sparked growing interest in microbiome modulation as a therapeutic strategy in oncology. Preclinical studies have identified specific bacterial species linked to improved responses to immune checkpoint inhibitors (ICIs), leading to clinical investigations in melanoma, renal cell carcinoma (RCC), and non-small cell lung cancer (NSCLC). The stool bacterial abundance of Ruminococcaceae, Akkermansia, and Bifidobacterium correlates with favorable clinical outcomes, whereas the disruption of the gut microbiome through antibiotics before or during ICI initiation is associated with higher rates of primary resistance and shorter survival. Biomarkers such as TOPOSCORE have been developed to better predict ICI benefits and estimate dysbiosis and treatment responses. Several microbiome-modulating strategies have shown potential in patients receiving treatment with ICIs-for instance, high dietary fiber intake may be linked to improved outcomes. As a separate strategy, certain probiotics appear to enhance clinical activity in early trials when incorporated into ICI-based regimens. Finally, fecal microbiota transplantation has shown safety and efficacy in ICI-refractory melanoma and yielded encouraging results in treatment-naïve patients with melanoma, NSCLC, and RCC. Although several compelling signals have been observed to date with microbiome manipulation, the field is lacking large, definitive randomized trials-these are indeed a prerequisite for any of the highlighted strategies to become a standard of care.}, } @article {pmid40643902, year = {2025}, author = {Anderer, S}, title = {Fecal Transplant Appears Noninferior to Antibiotics for Treating CDI.}, journal = {JAMA}, volume = {334}, number = {6}, pages = {477}, doi = {10.1001/jama.2025.10327}, pmid = {40643902}, issn = {1538-3598}, } @article {pmid40643244, year = {2025}, author = {Seekatz, AM}, title = {Straining to define a healthy microbiome.}, journal = {mSphere}, volume = {10}, number = {7}, pages = {e0079724}, pmid = {40643244}, issn = {2379-5042}, support = {R35 GM150609/GM/NIGMS NIH HHS/United States ; 2025541//National Science Foundation/ ; R35GM150609/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Clostridium Infections/therapy/microbiology ; *Microbiota ; }, abstract = {In 2020, I wrote an mSphere of Influence commentary on two studies that shaped my research perspective on the human gut microbiome (McNulty et al., Sci Transl Med 3:106ra106, 2011, https://doi.org/10.1126/scitranslmed.3002701; Hamilton et al., Gut Microbes 4:125, 2013, https://doi.org/10.4161/gmic.23571). The microbiome field has continued to progress since the publication of these studies over 10 years ago, emerging as a considerable factor in almost all areas focused on disease development. My previous commentary highlighted two areas that piqued my interest early on in my career: (i) that the extant microbial community should be considered when proposing to manipulate the microbiota, such as via probiotics or fecal microbiota transplantation, and (ii) that realized (i.e., transcribed) functional changes of the microbiota may occur independent of changes in its composition. Since writing that commentary, two microbiota-based therapeutics for the treatment of Clostridioides difficile infection have been approved, highlighting the potential success of using the microbiota to treat or prevent disease. Despite these wins and ever-growing evidence of the importance of the microbiome in managing our health, translating mechanistic studies into therapeutic value has been slower. In this minireview, I expand upon two large questions that would increase our ability to translate the microbiome into therapies, highlighting both historical and recent progress.}, } @article {pmid40642988, year = {2025}, author = {Wang, F and Wu, Y and Ni, J and Xie, Q and Shen, J and Chen, H and Ma, C and Yao, Y and Wang, J and Xu, L and Xiang, Q and Zhao, Y and Chen, Y and Li, L}, title = {Gut microbiota links to histological damage in chronic HBV infection patients and aggravates fibrosis via fecal microbiota transplantation in mice.}, journal = {Microbiology spectrum}, volume = {13}, number = {8}, pages = {e0076425}, pmid = {40642988}, issn = {2165-0497}, mesh = {Animals ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome/physiology ; Mice ; Humans ; *Liver Cirrhosis/pathology/microbiology ; *Hepatitis B, Chronic/microbiology/pathology/complications ; *Dysbiosis/microbiology ; Feces/microbiology ; Male ; Liver/pathology ; Bacteria/classification/genetics/isolation & purification ; Bile Acids and Salts/metabolism ; Female ; Middle Aged ; Disease Models, Animal ; Mice, Inbred C57BL ; Hepatitis B virus ; }, abstract = {Gut microbiota dysbiosis has been observed in HBV-related cirrhosis, but its role in early-stage disease and its correlation with liver pathology remain unclear. Moreover, whether dysbiosis is a cause or consequence of liver cirrhosis is still debated. We recruited 20 treatment-naïve patients with chronic HBV infection, assessing liver injury via biopsy. Fecal metagenomic sequencing was used to analyze the correlation between gut microbiota and liver histology. To explore the causality, fecal samples from an HBV-related cirrhosis patient were transplanted into mice with CCl4-induced liver fibrosis. Patients with significant histological damage exhibited reduced alpha diversity and greater microbial homogeneity. Species such as Eubacterium_sp_CAG_180, Gemmiger_formicilis, and Oscillibacter_sp_ER4 had decreased abundance, while Parabacteroides_distasonis, Bacteroides_dorei, and Bacteroides_finegoldii were enriched. Mice receiving fecal transplants from the cirrhotic patient showed aggravated liver fibrosis, with increased collagen deposition; elevated ALT, AST, and ALP levels; and heightened hepatic inflammatory gene expression. Additionally, abnormal bile acid profiles with elevated unconjugated bile acids (e.g., GCA and CA) were observed. Gut microbiota dysbiosis is closely associated with liver histological damage in chronic HBV infection and may drive fibrosis progression via microbial-bile acid interactions. These findings suggest potential for gut microbiota-based assessment and treatment strategies in chronic hepatitis B.IMPORTANCEThis study elucidates a significant association between gut microbiota dysbiosis and liver histological damage in patients with chronic hepatitis B (HBV), potentially exacerbating fibrosis progression through bile acid interactions. By analyzing patient gut microbiota and conducting fecal transplant experiments in mice, researchers have identified that gut microbiota dysbiosis contributes to hepatic fibrosis during chronic HBV infection. These findings underscore the importance of the gut-liver axis in HBV disease progression, indicating that monitoring or modulating gut bacteria may facilitate early diagnosis or therapeutic interventions. This research bridges the gap in understanding whether microbial alterations drive disease progression or result from it, providing a foundation for developing therapies targeting the microbiome to mitigate liver damage in chronic HBV infections.}, } @article {pmid40642664, year = {2025}, author = {Horwat, P and Mariowska, A and Szymanska, A and Dzieciatkowska, M and Pierudzka, W}, title = {Multimodal Interventions Targeting Gut Microbiota and Microbial Metabolites in Cognitive Impairment.}, journal = {Cureus}, volume = {17}, number = {6}, pages = {e85688}, pmid = {40642664}, issn = {2168-8184}, abstract = {Mild cognitive impairment (MCI) is a transitional stage between normal aging and Alzheimer's disease (AD). Recent studies suggest that alterations in gut microbiota and microbial metabolites are associated with cognitive decline, highlighting the gut-brain axis as a potential therapeutic target. This narrative review explores current evidence on the relationship between gut microbiota, microbial metabolites, and MCI. It summarizes intervention strategies including probiotics, prebiotics, synbiotic, fecal microbiota transplantation, dietary modifications, medicinal herbs, phytochemicals, metformin, and lifestyle factors. Probiotic strains such as Lactobacillus and Bifidobacterium have shown cognitive benefits. Adherence to the Mediterranean and MIND diets, as well as metformin use, is associated with lower MCI risk. Novel strategies, including plant-based compounds and nature exposure, show promise in modulating gut microbiota and improving cognitive outcomes. Gut microbiota modulation represents a promising avenue for early intervention in MCI. Personalized, multifactorial approaches based on individual microbiome profiles may enhance prevention and management strategies. However, more high-quality clinical trials are needed to establish evidence-based guidelines.}, } @article {pmid40642089, year = {2025}, author = {Lei, W and Cheng, Y and Liu, X and Gao, J and Zhu, Z and Ding, W and Xu, X and Li, Y and Ling, Z and Jiang, R and Chen, X}, title = {Gut microbiota-driven neuroinflammation in Alzheimer's disease: from mechanisms to therapeutic opportunities.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1582119}, pmid = {40642089}, issn = {1664-3224}, mesh = {Humans ; *Alzheimer Disease/therapy/microbiology/immunology/metabolism/etiology ; *Gastrointestinal Microbiome/immunology ; Animals ; *Neuroinflammatory Diseases/therapy/microbiology ; Dysbiosis/immunology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Brain/metabolism/immunology ; Brain-Gut Axis ; }, abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques, tau hyperphosphorylation, and chronic neuroinflammation. While neuroinflammation-mediated by microglial and astrocyte activation-has long been considered a secondary response to Aβ pathology, emerging evidence positions it as a primary driver of cognitive decline. Notably, the gut microbiota, through the microbiota-gut-brain axis (MGBA), is crucial in modulating neuroinflammation. Dysbiosis disrupts gut barrier integrity, promotes systemic inflammation, and exacerbates neuroinflammatory responses, thereby accelerating AD progression. Recent advances reveal that gut microbiota-derived metabolites (e.g., short-chain fatty acids, lipopolysaccharides) directly influence microglial activation and Aβ aggregation. These findings have opened new therapeutic possibilities, with microbiota-targeted approaches such as probiotics, prebiotics, and fecal microbiota transplantation demonstrating promising neuroprotective effects in preclinical studies by reducing neuroinflammation and preserving cognitive function. However, translating these findings into clinical applications requires further validation through randomized controlled trials. This review summarizes the current understanding of gut microbiota-driven neuroinflammation in AD, from molecular mechanisms to potential therapeutic strategies. Targeting the MGBA represents a paradigm shift in AD management, emphasizing the modulation of neuroinflammation and pathological progression through gut microbiota interventions. The discussion also addresses existing research challenges and outlines future directions to advance this promising field.}, } @article {pmid40641916, year = {2025}, author = {Daniluk, U and Świdnicka-Siergiejko, A and Daniluk, J and Rusak, M and Dąbrowska, M and Guzińska-Ustymowicz, K and Pryczynicz, A and Dąbrowski, A}, title = {The development of pancreatic cancer is accompanied by significant changes in the immune response in genetically predisposed mice.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1603293}, pmid = {40641916}, issn = {2234-943X}, abstract = {PURPOSE: The pathogenesis of pancreatic cancer (PC) is extremely complex and involves genetic and environmental factors, as well as significant changes in the immune response to tumor cells from the loss of immune surveillance to the development of immunotolerance to cancer. Currently available literature data on this subject is inconsistent. The purpose of our study was to evaluate the status of dendritic cells (DC) and other immune cells in the pancreas and blood of mice genetically predisposed to pancreatic cancer (Kras[G12D] mutation). The second objective was to assess the impact of fecal microbiota transplantation (FMT) from PC mice on pancreatic tumor development and alterations in pancreatic and blood immune cell counts in mice genetically predisposed to PC.

METHODS: We used LSL-K-Ras[G12D] mice, which possess the conditional knock-in mutant K-Ras[G12D] driven by its endogenous promoter and Ela-CreERT mice, which express tamoxifen-regulated CreERT specifically in pancreatic acinar cells under the control of a full-length elastase gene promoter. The immunophenotype of immune cells separated from pancreatic tissue and circulating blood was analyzed with the use of multicolor flow cytometry and immunochemistry staining. Fecal pellets from LSL-K-Ras[G12D] mice, that developed PC after the cerulein (CER) treatment, were collected and transplanted into animals previously treated with the antibiotic.

RESULTS: Using immunohistochemistry and flow cytometry, we found that in mice genetically predisposed to PC, cerulein (CER) administered intraperitoneally induced tumor growth and inflammatory cell infiltration in pancreatic tissue, but without affecting immune cell differentiation in the blood. In contrast, orally administered FMT activated the immune system in the gastrointestinal tract, leading to generalized immune cell activation, as observed in the blood, and local infiltration of cells in the pancreatic tissue of Kras mutant mice that developed pancreatic tumors. Interestingly, immunohistochemical evaluation of pancreatic tissue revealed that the Kras mutation alone causes increased infiltration of CD11b[+], CD20[+], CD3[+], CD4[+], and CD8[+] cells. After FMT, there was a trend toward an increased intensity of infiltration by these immune cells, with the exception of CD11b[+].

CONCLUSIONS: Our data suggest that pancreatic cancer development in genetically predisposed mice is accompanied by profound changes in immune cell composition. Treatment with tumor-inducing agents such as CER or FMT from tumor-bearing mice, accelerated PC progression. The type of immune system response, systemic or local, in mice with pancreatic cancer depends on the route of entry of the inflammatory agent. Oral administration of FMT activated the systemic immune response, in contrast to the intraperitoneal injection of CER.}, } @article {pmid40641009, year = {2025}, author = {Siegel, R and Sibert, NT and Breidenbach, C and Gani, C and Neumann, PA and Benz, SR and Post, S and Seufferlein, T and Kolb, V and Behrend, M and Blossey, RD and Bunse, J and Dahlke, M and Diller, R and Emmanouilidis, N and Ettrich, TJ and Fahlke, J and Flemming, S and Freitag, B and Fuchs, M and Haeder, L and Hollerbach, S and Höppner, J and Kim, M and Klink, C and Knuth, J and Koeppen, S and Köninger, J and Kolbe, EW and Kühn, F and Mussa, S and Oehring, R and Petzoldt, S and Piso, P and Prause, C and Prinz, C and Reißfelder, C and Riechmann, M and Ritz, JP and Rolinger, J and Rosenberg, R and Scheuerlein, H and Schilawa, D and Schneider, PM and Schwandner, T and Siech, M and Steinemann, D and Stöltzing, O and von Haeften, E and Weihs, D and Wiegering, A and Zielinski, CB and Kowalski, C}, title = {Impact of preoperative radiotherapy on patient-reported outcomes in rectal cancer.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {27}, number = {7}, pages = {e70158}, doi = {10.1111/codi.70158}, pmid = {40641009}, issn = {1463-1318}, support = {//Innovation Fund of the German Federal Joint Committee (Innovationsausschuss beim Gemeinsamen Bundesausschuss, G BA)/ ; }, mesh = {Humans ; *Rectal Neoplasms/surgery/radiotherapy ; *Patient Reported Outcome Measures ; Male ; Female ; Middle Aged ; Prospective Studies ; Quality of Life ; Aged ; *Preoperative Care/methods ; *Neoadjuvant Therapy/methods/adverse effects ; Postoperative Complications/etiology ; Proctectomy ; Radiotherapy, Adjuvant/adverse effects ; Fecal Incontinence/etiology ; Surveys and Questionnaires ; Adult ; Treatment Outcome ; }, abstract = {AIM: To prospectively evaluate the effect of preoperative radiotherapy followed by surgery versus surgery alone on patient-reported outcomes (PROs) 1 year after surgery.

METHOD: Prospective observational cohort study in 127 colorectal cancer centres. Patients with rectal cancer completed European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC-QLQ-C30) and Colorectal module (-CR29) questionnaires (thus providing PROs) before initialization of treatment [baseline (T0)] and at 12 months after surgery [follow up (T1)]. The PRO data together with sociodemographic information were linked to clinical data. Relevant confounders were identified using directed acyclic graphs. The effect of preoperative radiotherapy on selected PROs 12 months after surgery was estimated using adjusted tobit regression models.

RESULTS: Of 1635 patients with rectal cancer for whom both baseline and follow-up PROs were available, 565 (35%) received preoperative radiotherapy. Twelve months after surgery, patients with surgery alone reported better scores for global health status/Quality of Life, urinary incontinence, faecal incontinence (patients without stoma), dyspareunia (female patients) and impotence (male patients) than did patients receiving preoperative radiotherapy. The statistically significant effects ranged between 33.20 (p < 0.001, R[2] = 0.19) for impotence and 39.01 (p = 0.001, R[2] = 0.10) for dyspareunia. For global health status/QoL and urinary incontinence, no statistically significant effect could be found.

CONCLUSION: Radiotherapy in addition to surgery negatively affects selected PROs 1 year after surgery in patients with rectal cancer. Compared with surgery alone, patients report profoundly impaired bowel and sexual function after preoperative radiotherapy. However, global health status/QoL was not affected statistically significantly. These results are an important argument for limiting preoperative radiotherapy to patients with a high risk of recurrence of rectal cancer and may facilitate informed decision-making.

TRIAL REGISTRATION: German Clinical Trial Registry Number DRKS00008724 (https://drks.de/search/de/trial/DRKS00008724).}, } @article {pmid40640940, year = {2025}, author = {Wang, N and Sun, C and Yang, Y and Zhang, D and Huang, L and Xu, C and Wang, M and Xu, M and Yan, T and Wu, Y and Xu, L and Ju, Y and Sun, H and Guo, W}, title = {Gut microbiota-derived indoleacetic acid attenuates neuroinflammation and neurodegeneration in glaucoma through ahr/rage pathway.}, journal = {Journal of neuroinflammation}, volume = {22}, number = {1}, pages = {179}, pmid = {40640940}, issn = {1742-2094}, support = {SHSMU-ZDCX20210902//Innovative Research Team of High-level Local University in Shanghai/ ; 82171046//National Natural Science Foundation of China/ ; BYH20220403//Post Graduate Medical Education Program 2022/ ; 20DZ2270800//Research Grant of the Shanghai Science and Technology Committee/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; *Indoleacetic Acids/metabolism/pharmacology/therapeutic use ; Mice ; Humans ; Male ; *Receptors, Aryl Hydrocarbon/metabolism ; *Glaucoma/metabolism/pathology/microbiology ; *Neuroinflammatory Diseases/metabolism ; Signal Transduction/physiology/drug effects ; Mice, Inbred C57BL ; Female ; Fecal Microbiota Transplantation ; Microglia/metabolism/drug effects ; Middle Aged ; Aged ; }, abstract = {BACKGROUND: Gut microbiota has emerged as a promising therapeutic target for neurodegenerative disorders through regulation of neuroinflammatory responses, while its role in optic nerve degeneration remains incompletely characterized. This study elucidates the neuroprotective role of gut microbiota derived tryptophan metabolites in glaucoma through gut-eye communication and inhibition of microglia-mediated neuroinflammation.

METHODS: Gut microbiota profiling (16 S rRNA sequencing) and serum indoleacetic acid (IAA) quantification were performed in glaucoma patients versus controls. Microbiota-metabolite relationships were further validated through fecal microbiota transplantation (FMT). The neuroprotective and anti-neuroinflammatory effect of Bacteroides fragilis (B. fragilis) and IAA was assessed in both microbead-induced ocular hypertension mice model and in vitro BV-2 microglial cell inflammation model via immunofluorescence, qPCR, Western blot and mice behavioral assays. To explore the underlying mechanisms, retinal transcriptomics and microglia-neuron co-cultures were also employed.

RESULT: Glaucoma patients exhibited gut dysbiosis characterized by depleted tryptophan-metabolizing bacteria (B. fragilis, Bacteroides thetaiotaomicron, Anaerostipes hadrus) and reduced serum IAA levels. Mice receiving FMT from glaucoma patients exhibited lower systemic IAA levels. In in vivo and in vitro models, B. fragilis or IAA restored AhR activation, suppressed inflammation by inhibiting microglial activation and the release of pro-inflammatory mediators throughout the retina, reduced retinal ganglion cells (RGCs) loss and preserved visual function. Mechanistically, IAA attenuated RAGE/NF-κB pathway activation via AhR-dependent signaling, conferring neuroprotection.

CONCLUSION: Our study proposes a novel AhR-mediated gut microbiota-eye axis in glaucoma pathogenesis and demonstrates that IAA serves as an effective neuroprotective strategy with clinical potential for managing RGCs neurodegeneration.}, } @article {pmid40639338, year = {2025}, author = {Lesmana, I and Qian, C and Hsiao, EY}, title = {Fibromyalgia pain may have a gut solution.}, journal = {Neuron}, volume = {113}, number = {13}, pages = {2029-2031}, doi = {10.1016/j.neuron.2025.06.005}, pmid = {40639338}, issn = {1097-4199}, mesh = {*Fibromyalgia/therapy/microbiology ; Humans ; Animals ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Mice ; *Pain/microbiology ; }, abstract = {In this issue of Neuron, Cai et al.[1] demonstrated that transferring fecal microbiota from fibromyalgia patients to mice confers pain hypersensitivity and depression-like behavior, which is reversed by fecal microbiota transplant from healthy donors. Fibromyalgia patients experience significant symptom relief after fecal microbiota transplantation.}, } @article {pmid40639240, year = {2025}, author = {Zhai, L and Zheng, Y and Lo, CW and Xu, S and Jiang, X and Liu, Q and Ching, JY and Ning, Z and Bao, G and Yang, W and Zhang, Q and Cheng, CW and Lam, WC and Chan, KL and Zhang, X and Lam, PY and Wu, XY and Zhong, LLD and Cao, PH and Koh, M and Cheong, PK and Lin, Z and Lin, C and Zhao, L and Wong, XHL and Wu, JC and Bian, Z}, title = {Butyrate-producing commensal bacteria mediates the efficacy of herbal medicine JCM-16021 on abdominal pain in diarrhea-predominant irritable bowel syndrome: a randomized clinical trial.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {145}, number = {}, pages = {157040}, doi = {10.1016/j.phymed.2025.157040}, pmid = {40639240}, issn = {1618-095X}, mesh = {*Irritable Bowel Syndrome/drug therapy/microbiology/complications ; Animals ; *Abdominal Pain/drug therapy/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Diarrhea/drug therapy/microbiology ; Humans ; Male ; Mice ; Double-Blind Method ; Female ; Fecal Microbiota Transplantation ; Adult ; Middle Aged ; *Butyrates/metabolism ; Fatty Acids, Volatile/metabolism ; *Drugs, Chinese Herbal/therapeutic use/pharmacology ; Mice, Inbred C57BL ; Disease Models, Animal ; }, abstract = {BACKGROUND: Irritable bowel syndrome with diarrhea (IBS-D) presents significant treatment challenges due to limited therapeutic options that effectively target the underlying pathophysiological mechanisms. In this study, we performed a multi-center, double-blind randomized placebo-controlled trial to investigate the efficacy and safety of herbal medicine JCM-16021 on IBS-D with a focus on its effects on gut microbiota.

RESULTS: Our study assessed the clinical efficacy and safety of JCM-16021 in alleviating abdominal pain in IBS-D patients. The results suggested that JCM-16021 is both effective and safe, with its therapeutic effects closely linked to the modulation of short-chain fatty acid (SCFA) producers. Through fecal microbiota transplantation (FMT) experiments in mice, we showed that SCFA producers mediate the alleviation of abdominal pain symptoms by the JCM-16021 treatment. In a TNBS-induced mouse model of IBS, we showed that butyrate producers enriched by JCM-16021 significantly ameliorate abdominal pain. Importantly, baseline gut microbial profiles, such as the presence of Eubacterium rectale in IBS-D patients are predictive of their responses to JCM-16021 treatment.

CONCLUSIONS: Our findings not only affirm the efficacy of JCM-16021 in mitigating abdominal pain in IBS-D patients but also highlight a microbiota-dependent mechanism, underscoring the therapeutic potential of gut microbiota modulation in treating gastrointestinal disorders. By combining clinical trials in humans with biological experiments in mice, this study establishes a translational approach to investigate the role of gut microbiota in the treatment of herbal medicine.

CLINICALTRIALS: gov no: NCT03457324.}, } @article {pmid40637385, year = {2025}, author = {Yang, L and Yang, J and Zhang, T and Xie, X and Wu, Q}, title = {Gut microbiota: a novel strategy affecting atherosclerosis.}, journal = {Microbiology spectrum}, volume = {13}, number = {8}, pages = {e0048224}, pmid = {40637385}, issn = {2165-0497}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Atherosclerosis/microbiology/therapy ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use/administration & dosage ; Dysbiosis/microbiology/therapy ; Prebiotics/administration & dosage ; Animals ; }, abstract = {Atherosclerosis is a common chronic inflammatory cardiovascular disease affecting both coronary and peripheral arteries, which is influenced by multiple factors. It is increasingly evident that gut microbes and their byproducts play a crucial role in the development of atherosclerosis. The most representative feature of microbial dysbiosis in coronary artery disease patients is the reduction of the abundance of the phylum Bacteroidetes and the increase of the abundance of the phylum Firmicutes, which may cause changes in functional genes and metabolites. The gut microbiota and its metabolites influence the early, intermediate, and late stages of atherosclerosis mainly by inhibiting or promoting inflammatory responses. In addition, the reshaping of gut microbiota through probiotics, prebiotics, and fecal microbiota transplantation (FMT) is discussed as an alternative to traditional therapeutic methods. By summarizing how gut microbiota and their metabolites affect the process of atherosclerosis, we can better understand the complex relationship between gut microbiota and atherosclerosis.IMPORTANCEAtherosclerosis is an inflammatory cardiovascular disease, making it crucial to understand its pathogenesis and develop effective treatments. This review thoroughly examines the literature, emphasizing the gut microbiome as a key factor influencing atherosclerosis. It also explores how the gut microbiota and its metabolites impact the primary, intermediate, and advanced stages of atherosclerosis and proposes that remodeling the gut microbiota is a promising strategy for improving atherosclerosis.}, } @article {pmid40637175, year = {2025}, author = {Fahim, SM and Huey, SL and Palma Molina, XE and Agarwal, N and Ridwan, P and Ji, N and Kibbee, M and Kuriyan, R and Finkelstein, JL and Mehta, S}, title = {Gut microbiome-based interventions for the management of obesity in children and adolescents aged up to 19 years.}, journal = {The Cochrane database of systematic reviews}, volume = {7}, number = {7}, pages = {CD015875}, pmid = {40637175}, issn = {1469-493X}, mesh = {Adolescent ; Child ; Child, Preschool ; Humans ; Infant ; Young Adult ; Body Mass Index ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Overweight/therapy ; *Pediatric Obesity/therapy/microbiology ; Prebiotics/administration & dosage ; Probiotics/therapeutic use ; Randomized Controlled Trials as Topic ; Synbiotics/administration & dosage ; }, abstract = {BACKGROUND: The epidemic of overweight and obesity affects more than 390 million children and adolescents aged 5 to 19 years and 37 million children under five years of age. Overweight and obesity are associated with both short- and long-term consequences, including chronic inflammation, metabolic diseases, as well as alterations in the gut microbiome composition. Gut microbiome-based approaches may impact microbiome-related metrics such as diversity or the abundance of intestinal bacteria, which may be linked to obesity-related outcomes. However, evidence regarding the effect of gut microbiome-based interventions for the management of obesity is limited.

OBJECTIVES: To assess the effects of gut microbiome-based interventions in the management of overweight or obesity in children and adolescents in all their diversity aged 0 to 19 years.

SEARCH METHODS: We searched CENTRAL, MEDLINE, CINAHL, Web of Science Core Collection, BIOSIS Previews, Global Index Medicus (all regions), IBECS, SciELO, PAHO, PAHO IRIS, WHO IRIS, WHOLIS, Bibliomap, TRoPHI as well as ICTRP Search Portal and ClinicalTrials.gov. The date of the last search for all databases was 24 January 2025. We did not apply any language restrictions.

SELECTION CRITERIA: We included randomised controlled trials that evaluated gut microbiome-based interventions [i.e. prebiotics, probiotics, synbiotics, short-chain fatty acids (SCFAs), and faecal microbiota transplantation (FMT)] compared to standard-of-care, placebo, or control interventions in children and adolescents aged 0 to 19 years with overweight or obesity.

DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts and full texts, extracted data, and assessed the risk of bias using the Cochrane Risk of Bias 2 tool and certainty of the evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE), a framework for assessing the certainty of evidence and making recommendations in systematic reviews. Random-effects meta-analyses were performed unless only one study per outcome was available, for which fixed-effect analyses were performed.

MAIN RESULTS: We found 17 studies (838 participants) from various countries, evaluating the effects of prebiotics, probiotics, synbiotics, SCFAs, and FMT on body mass index (BMI), body weight, waist circumference, total body fat percentage (%TBF), systolic and diastolic blood pressure, and adverse events. Of the 17 studies included, five studies were in adolescents aged 10 to 19 years, and 12 studies were in children and adolescents spanning both age groups, 0 to 19 years. Upon contacting authors for data grouped by age of the participants, no studies provided separate outcomes data for children and adolescents. The included studies were funded by either academic funding sources or grants from the public and private sectors. Additionally, 15 studies were classified as currently being conducted ('ongoing'). The certainty of evidence throughout was very low. In adolescents 10 to 19 years of age, probiotics compared to placebo or no intervention may have little to no effect on BMI, body weight, waist circumference, %TBF, blood pressure, and adverse events. Similarly, FMT compared to placebo may have little to no effect on waist circumference, %TBF, blood pressure, and adverse events in this age group. According to one study with 41 participants and in children and adolescents 0 to 19 years of age, intervention with prebiotics compared to placebo may result in a small reduction in BMI (mean difference = -0.70, 95% CI = -1.25 to -0.15) and body weight (mean difference = -1.5, 95% CI = -2.61 to -0.39). Prebiotics compared to placebo may have little to no effect on waist circumference, %TBF, systolic blood pressure, and adverse events. No data were available on the effect of prebiotics on diastolic blood pressure. Probiotics compared to placebo may have little to no effect on BMI, body weight, waist circumference, %TBF, blood pressure, and adverse events in children and adolescents (0 to 19 years). Synbiotics compared to placebo may result in a reduction in systolic blood pressure (mean difference = -40.00, 95% CI = -50.63 to -29.37) in children and adolescents (0 to 19 years); according to one study with 56 participants. The evidence is very uncertain about the effects of synbiotics compared to a placebo on BMI, body weight, waist circumference, blood pressure, and adverse events. No data were available on the effect of synbiotics compared to placebo on %TBF. Synbiotics, compared to probiotics, may have little to no effect on waist circumference, %TBF, and adverse events. No data were available on the effect of synbiotics compared to probiotics on BMI, body weight, and blood pressure. According to one study with 48 participants and very low-certainty of evidence, SCFAs compared to placebo may result in a reduction in waist circumference (mean difference = -5.08, 95% CI = -7.40 to -2.76) and BMI (mean difference = -2.26, 95% CI = -3.24 to -1.28) in children and adolescents (0-19 years). SCFAs compared to placebo may have little to no effect on adverse events. No data were available on the effect of SCFAs on body weight, %TBF, and blood pressure. Adverse events, i.e. abdominal cramps, abdominal discomfort, abdominal pain, diarrhoea, vomiting, and migraine, were reported in the prebiotics group but with very low incidence. Additionally, adverse events such as nausea and headache were reported in the SCFAs group, but with low incidence.

AUTHORS' CONCLUSIONS: In adolescents aged 10 to 19 years, gut microbiome-based interventions may result in little to no difference in obesity-related outcomes. In children and adolescents aged 0 to 19 years, prebiotics may result in a small reduction in BMI and body weight; synbiotics may result in a reduction in systolic blood pressure, and SCFAs may result in a reduction in BMI and waist circumference, albeit the certainty of evidence was very low. The evidence was of very low certainty due to few studies per comparison, small sample sizes, short intervention durations, and insufficient reporting of adverse events. More rigorous research examining different types of gut microbiome-based interventions for the management of obesity is required in children and adolescents, both in clinical and community settings. Future trials should also report methods related to randomisation, blinding, and compliance, as well as include prespecified analysis plans.}, } @article {pmid40635758, year = {2025}, author = {Pan, J and Lin, S and Qian, Q and Fu, S and Liu, X}, title = {Gut-brain axis in post-traumatic stress disorder: microbial - mediated mechanisms and new therapeutic approaches - A narrative review.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1621678}, pmid = {40635758}, issn = {1663-9812}, abstract = {Post-traumatic stress disorder (PTSD) is a severe mental disorder that occurs after experiencing or witnessing a traumatic event. Not only does this disorder severely impair the quality of life and emotional wellbeing of patients, but in recent years the global rate of PTSD diagnoses has increased to 1.5-2 times, and the prevalence of PTSD associated with COVID-19 events in particular has surged to 10%-25%, underscoring the urgency of developing effective treatments. The lifetime prevalence of PTSD in the general population is estimated to be approximately 3.9%, while in high-risk populations, such as war veterans, it can be as high as 30%. As a key pathway connecting the central nervous system to peripheral organs, the gut-brain axis has received increasing attention for its role in PTSD. Although the gut-brain axis has been shown to be associated with several psychiatric disorders, especially depression, its specific role in PTSD remains undercharacterized. Existing studies suggest that specific strains of Lactobacillus (e.g., Lactobacillus reuteri) may alleviate inflammatory responses and improve PTSD-like behaviors by down-regulating the expression of pro-inflammatory factors (IL-6 and TNF-α). In this study, we used a narrative review approach to sort out the research progress of gut microbiota alteration in PTSD, and compared the characteristics of changes in specific microbial taxa (e.g., Bacteroides, Lactobacillus, etc.), the index of microbiota diversity (α/β diversity), and the levels of inflammatory markers (e.g., IL-6, TNF-α) between the animal model and the human patients, respectively, in order to We further explored the potential pathogenic mechanisms mediated by microorganisms, such as influencing the vagal pathway, hypothalamic-pituitary-adrenal (HPA) axis function, immune system and other processes involved in the pathology of PTSD, and summarized the intervention strategies targeting gut microecology, such as probiotic supplementation, dietary interventions and fecal bacteria transplantation.}, } @article {pmid40635387, year = {2025}, author = {Gragnaniello, V and Cananzi, M and Cavaliere, A and Loro, C and Cazzorla, C and Gueraldi, D and Puma, A and Burlina, AB}, title = {Early Enzyme Replacement Therapy Does Not Prevent the Protein Losing Enteropathy Syndrome in Neurovisceral Gaucher Disease.}, journal = {American journal of medical genetics. Part A}, volume = {}, number = {}, pages = {e64184}, doi = {10.1002/ajmg.a.64184}, pmid = {40635387}, issn = {1552-4833}, abstract = {Gaucher disease (GD) is a rare lysosomal storage disorder characterized by multisystemic involvement. With the advent of enzyme replacement therapy (ERT), patient survival has improved, revealing new long-term complications. We report a case of a 4-year-old male with severe neurovisceral GD who developed protein-losing enteropathy (PLE) secondary to mesenteric lymphadenopathy, despite ERT starting in the neonatal period. Furthermore, we review the literature related to this rare complication. The patient presented with severe recurrent diarrhea, abdominal distension, weight loss, and malnutrition. Abdominal CT revealed multiple enlarged mesenteric lymph nodes with calcification. Laboratory findings showed lymphopenia and increased fecal alpha-1-antitrypsin. Other causes of diarrhea were excluded. Treatment with a specific diet (high-protein, MCT-enriched) and a course of budesonide resulted in persistent clinical improvement and normalization of laboratory parameters. This case highlights the emergence of gastrointestinal complications in patients with neurovisceral GD on long-term ERT, particularly the development of PLE due to mesenteric lymphadenopathy. It underscores the need for vigilance in monitoring GD patients for such complications and demonstrates the potential efficacy of dietary interventions and anti-inflammatory therapy in managing PLE in this context. The case also emphasizes the limitations of current ERT in addressing all aspects of GD, particularly in sequestered sites like lymph nodes, and calls for new therapeutic strategies to address these challenges.}, } @article {pmid40634307, year = {2025}, author = {De Sciscio, M and Bryant, RV and Haylock-Jacobs, S and Day, AS and Pitchers, W and Iansek, R and Costello, SP and Kimber, TE}, title = {Faecal microbiota transplant in Parkinson's disease: pilot study to establish safety & tolerability.}, journal = {NPJ Parkinson's disease}, volume = {11}, number = {1}, pages = {203}, pmid = {40634307}, issn = {2373-8057}, support = {2021/23-QA253//Hospital Research Foundation/ ; 2021/23-QA253//Hospital Research Foundation/ ; 2021/23-QA253//Hospital Research Foundation/ ; }, abstract = {Emerging evidence suggests gut microbiota differences in Parkinson's Disease (PD) may impact disease progression and treatment. Faecal Microbiota Transplantation (FMT) offers a potential therapeutic approach. We conducted an open-label pilot study to assess the safety, tolerability, and symptom impact of FMT in 12 patients with mild to moderate PD, administered via enema for 6 months. FMT was safe and well tolerated, causing only mild, transient gastrointestinal symptoms. While no significant motor symptom changes were observed, there was a trend toward reduced daily OFF time at 2 months. Whilst no sustained improvement in non-motor symptoms was found after 6 months, transient improvements in quality of life and non-motor scores were noted at 2 months; these gains regressed by study end. Overall, extended FMT therapy in PD appears safe and tolerable, with reduction in daily motor OFF time and self-reported non-motor symptoms that was not sustained throughout the 6-months of treatment.}, } @article {pmid40634168, year = {2025}, author = {Lee, PC and Chang, TE and Wang, YP and Lee, KC and Lin, YT and Yang, UC and Huang, HC and Huang, YH and Luo, JC and Hou, MC}, title = {Response to commentary on 'Alteration of gut microbial composition associated with the therapeutic efficacy of fecal microbiota transplantation in Clostridium difficile infection'.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jfma.2025.05.037}, pmid = {40634168}, issn = {0929-6646}, } @article {pmid40632357, year = {2025}, author = {Arif, TB and Damianos, JA and Rahman, AU and Hasnain, N}, title = {Fecal Microbiota Transplantation for Disorders of Gut-Brain Interaction: Current Insights, Effectiveness, and Future Perspectives.}, journal = {Current gastroenterology reports}, volume = {27}, number = {1}, pages = {50}, pmid = {40632357}, issn = {1534-312X}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Dysbiosis/therapy/complications/microbiology ; *Gastrointestinal Microbiome ; *Brain-Gut Axis ; *Gastrointestinal Diseases/therapy/microbiology ; }, abstract = {PURPOSE OF REVIEW: Dysbiosis can disrupt intestinal barrier integrity and impact the immune and nervous systems, playing a significant role in developing disorders of gut-brain interaction (DGBI). This review aims to provide a comprehensive understanding of dysbiosis and its role in DGBI while examining the latest advancements in fecal microbiota transplantation (FMT). It also highlights key challenges in the field and outlines critical directions for future research to optimize FMT strategies, ultimately improving patient outcomes in this evolving treatment area.

RECENT FINDINGS: In DGBI, dysbiosis triggers immune responses, increases gut permeability, and disrupts nervous system signaling, with contributing factors including diet, antibiotics, stress, and infections. Individuals with DGBI exhibit distinct microbial imbalances, such as an increased Firmicutes-to-Bacteroidetes ratio and reduced beneficial bacteria. FMT has shown mixed results, with factors like patient selection, treatment protocols, and microbiome diversity influencing outcomes. While FMT can improve symptoms in refractory irritable bowel syndrome (IBS), effects may fade over time, requiring repeat treatments. Future FMT approaches should focus on targeted microbial interventions, considering the role of archaea, fungi, and microbial metabolites, while prioritizing optimal donor selection and large-scale trials for long-term efficacy. Despite the promising findings, FMT has not yet been widely endorsed in clinical guidelines due to the variability and heterogeneity of the data available. While much of the research has focused on IBS, studies have also explored the impact of FMT on other conditions such as functional diarrhea, functional constipation, and functional dyspepsia, which all exhibit altered microbial profiles.}, } @article {pmid40631858, year = {2025}, author = {Qu, S and Gu, Y and Hou, X and Wei, M and Wang, M and Su, Y and Miao, Y and Yang, J and Sun, Y and Zeng, Z}, title = {Dual associations of gut and oral microbial networks with kidney transplantation.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0025225}, doi = {10.1128/msystems.00252-25}, pmid = {40631858}, issn = {2379-5077}, abstract = {UNLABELLED: Gut and oral microbiomes play an essential role in the occurrence and development of kidney disease, but their changes after kidney transplantation in patients with end-stage renal disease and their relationships with host health remain unclear. Through shotgun metagenomic sequencing of fecal and saliva samples, we found that for both gut and oral microbiome, the initial loss of species diversity after kidney transplantation led to a reduction in network nodes and interactions, but strengthened the connections among the remaining species, which started to get a recovery approximately 7-14 days later. Different network modules tended to exhibit unique functions and showed different responses to transplantation. These network changes were significantly correlated with clinical indicators, especially with estimated glomerular filtration rate, suggesting that microbial networks contributed to regulating kidney function and host health from dual dimensions. Our study provides novel insights into associating microbiomes with patient recovery after kidney transplantation and offers new diagnostic strategies.

IMPORTANCE: Understanding the dynamics of gut and oral microbiomes after kidney transplantation is crucial for improving post-transplant outcomes and managing potential complications. Through shotgun metagenomic sequencing of fecal and saliva samples from patients following kidney transplantation, our study emphasizes that, in addition to focusing on the various microbial species themselves, the topological properties of gut and oral microbial networks are also critically important for kidney function. We aim to explore the relationship between host health and the oral and gut microbiomes following kidney transplantation from an ecological perspective and extend to other diseases to advance the study of the microbiome and its clinical impact.}, } @article {pmid40630283, year = {2025}, author = {Ness, C and Svistounov, D and Solbu, MD and Petrenya, N and Boardman, N and Ytrehus, K and Jenssen, TG and Holmes, A and Simpson, SJ and Zykova, SN}, title = {Gut Microbiome Diversity and Uric Acid in Serum and Urine.}, journal = {Kidney international reports}, volume = {10}, number = {6}, pages = {1683-1693}, pmid = {40630283}, issn = {2468-0249}, abstract = {INTRODUCTION: An increasing body of evidence has shown the importance of the gut microbiota in modulating serum uric acid (SUA) levels. In this study, we aimed to determine the association between gut microbiome diversity, diet, SUA, and fractional excretion of uric acid (FEUA) in the kidney.

METHODS: A cross-sectional study was conducted in 53 adults with normal or elevated SUA and estimated glomerular filtration rate (eGFR) range from 37 to 124 ml/min per 1.73 m[2]. Fecal microbiome composition was analyzed using 16S ribosomal RNA sequencing; and alpha diversity was expressed as reverse Simpson, Shannon, and Richness indices. Dietary data were collected, and dietary patterns were identified using principal component analysis. Unadjusted linear regression and models adjusted for sex, waist-hip ratio (WHR), and eGFR were used to study the association between gut microbial diversity, dietary pattern scores, and SUA/FEUA.

RESULTS: Shannon index was negatively associated with SUA after multiple adjustment (β -36.4, 95% CI [-66.2 to -6.7], P = 0.017; adjusted R[2] = 0.62, P < 0.001). Sex (standardized β = 0.52) and WHR (standardized β = 0.35) had the highest effect on SUA, followed by Shannon diversity index (standardized β = -0.22). We found that Shannon index (standardized β = 0.49, P < 0.001) was positively associated with FEUA after adjustment for sex and "sweet" dietary pattern. This model explained 40% of the variability in FEUA (P < 0.001). None of the dietary patterns were associated with SUA or FEUA.

CONCLUSION: A higher gut microbial diversity was associated with lower SUA and more efficient elimination of uric acid by the kidneys. There is a need for studies assessing efficacy and safety of interventions on the gut microbiome as a treatment of hyperuricemia.}, } @article {pmid40630180, year = {2025}, author = {Zhang, Z and Wang, R and Li, M and Lu, M}, title = {Current insights and trends in atopic dermatitis and microbiota interactions: a systematic review and bibliometric analysis.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1613315}, pmid = {40630180}, issn = {1664-302X}, abstract = {BACKGROUND: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin condition influenced by immune dysfunction, genetics, and environmental factors, with emerging evidence highlighting the critical role of skin and gut microbiota in its pathogenesis. This article uniquely integrates a systematic review with bibliometric analysis to map the research landscape of AD and microbiota interactions, offering a comprehensive synthesis of trends and future directions.

METHODS: We conducted a bibliometric analysis using the Web of Science Core Collection, retrieving 1,196 English-language articles and reviews published between 2009 and 2024, employing a detailed search strategy targeting AD and microbiota-related terms. Data were analyzed with tools like CiteSpace, VOSviewer, and Biblioshiny to assess publication trends, geographical contributions, institutional outputs, journal impacts, author networks, reference citations, and keyword evolution.

RESULTS: Research on AD and microbiota has surged since 2016, peaking at 168 publications in 2021, with the USA leading in output (360 papers) and citations (24,655). The University of Copenhagen and the Journal of Allergy and Clinical Immunology emerged as top contributors, while authors like Gallo, Richard L., and Kong, Heidi H. drove influential studies. Key findings underscore the skin and gut microbiomes as research hotspots, with Staphylococcus aureus and the gut-skin axis dominating discussions. Emerging trends from 2020 to 2024 focus on adult AD severity, prebiotics, and personalized interventions like fecal microbiota transplantation (FMT), supported by multi omics data.

CONCLUSION: This study illuminates the dynamic growth and global collaboration in AD and microbiota research, emphasizing microbial dysbiosis and immune modulation as pivotal to AD management. These insights pave the way for precision medicine and dietary interventions, promising enhanced therapeutic strategies and improved patient outcomes through continued multidisciplinary efforts.}, } @article {pmid40625834, year = {2025}, author = {Xie, W and Yan, X and Yang, X and Sun, H and Zhang, W}, title = {The regulation of neuroinflammatory response after stroke by intestinal flora microorganisms.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1594834}, pmid = {40625834}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; Animals ; Probiotics/therapeutic use ; *Neuroinflammatory Diseases/immunology/therapy/microbiology ; Fecal Microbiota Transplantation ; *Stroke/immunology/microbiology ; Brain-Gut Axis/immunology ; Immunity, Innate ; Brain/immunology ; Prebiotics/administration & dosage ; Adaptive Immunity ; Inflammation ; Blood-Brain Barrier ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Ischemic stroke (IS) is a severe central nervous system disorder characterized by high incidence, disability, mortality, and recurrence rates, along with numerous complications. The microbiota-gut-brain axis (MGBA) represents a bidirectional communication pathway between the brain and the gut, which can influence the onset and progression of IS through neural, immunoregulatory, and gut metabolite pathways. Recent preclinical and clinical evidence supports the use of fecal microbiota transplantation (FMT), probiotics and prebiotics, dietary interventions, and antibiotics as strategies to suppress neuroinflammation in IS, protect the blood-brain barrier, modulate immune responses, and improve stroke outcomes. In this review, we summarize the manifestations of innate inflammation and adaptive immunity following the onset of IS, highlight the interactions between the MGBA and post-stroke neuroinflammation, and discuss current therapeutic measures, thus providing insights for the development of novel treatment strategies in the future.}, } @article {pmid40625618, year = {2025}, author = {Hu, Y and Zheng, S and Xu, J and Zhao, Y and Wang, J and Fang, Z and Zhou, L}, title = {Gestational diabetes mellitus alters neonatal gut microbiota and increases infection susceptibility.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1600325}, pmid = {40625618}, issn = {1664-302X}, abstract = {INTRODUCTION: Gestational diabetes mellitus (GDM) affects up to 27.6% of pregnancies in certain regions and is associated with a two- to threefold increased risk of neonatal infections. Although maternal gut microbiota undergoes significant remodeling during pregnancy, the specific mechanisms governing GDM-induced microbial reprogramming in offspring and its implications for susceptibility to infections remain unclear. This study aimed to investigate the impact of GDM on the composition of neonatal gut microbiota, metabolomic profiles, and susceptibility to infections using a translational approach.

METHOD: We recruited pregnant women with and without GDM at the JinHua Municipal Central Hospital in China. Meconium and blood samples were collected from newborns within 24 h of birth. The composition of the gut microbiota was analyzed using 16S rDNA amplicon sequencing, and short-chain fatty acids (SCFAs) were quantified using gas chromatography-mass spectrometry. Serum inflammatory markers, including interleukin-6 (IL-6), C-reactive protein (CRP), lipopolysaccharides (LPS), and procalcitonin (PCT), were measured by enzyme-linked immunosorbent assay. To establish causality, fecal microbiota transplantation (FMT) was conducted in antibiotic-treated mice using pooled samples from healthy and GDM-exposed neonates, followed by assessment of inflammatory markers and intestinal barrier integrity.

RESULTS AND DISCUSSION: GDM significantly reduced the diversity of neonatal gut microbiota and altered its composition, characterized by a depletion of beneficial taxa (Bifidobacterium, Blautia, Faecalibacterium) and an enrichment of potential pathogens (Stenotrophomonas, Chryseobacterium). These alterations were accompanied by significant reductions in fecal SCFAs, particularly acetate (49.30%), butyrate (41.00%), and propionate (17.83%). GDM-exposed neonates exhibited elevated serum inflammatory markers, including IL-6, CRP, LPS, and PCT, which correlated negatively with beneficial bacteria and positively with opportunistic pathogens. FMT experiments demonstrated that mice receiving GDM-associated microbiota developed increased systemic inflammation and compromised intestinal barrier function, as evidenced by the downregulation of tight junction proteins (ZO-1, occludin, claudin-1, mucin1). These findings suggest that GDM-induced alterations in neonatal gut microbiota composition and metabolite production may compromise intestinal barrier function and increase susceptibility to infections, highlighting the potential for microbiome-targeted interventions to mitigate infection risk in GDM-exposed neonates.}, } @article {pmid40625306, year = {2025}, author = {Wu, J and Xiang, J and Song, P and Bai, Y and Che, Q and Cao, H and Guo, J and Su, Z}, title = {GOS-Modulated Gut Microbiota in Mice Ameliorates Obesity in High-Fat Diet-Fed Mice Through the Gut-Liver Axis and Bile Acid Pathway.}, journal = {Journal of food science}, volume = {90}, number = {7}, pages = {e70361}, doi = {10.1111/1750-3841.70361}, pmid = {40625306}, issn = {1750-3841}, support = {202103000089//the Science and Technology Program of Guangzhou, China/ ; //the Guangdong Demonstration BASe for Joint Cultivation of Postgraduates (2023)/ ; 2020B1515020026//the Science Foundation for Distinguished Young Scholars of Guangdong, China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Bile Acids and Salts/metabolism ; Diet, High-Fat/adverse effects ; *Obesity/metabolism/microbiology ; Mice ; *Liver/metabolism/drug effects ; Mice, Inbred C57BL ; Male ; Lipid Metabolism/drug effects ; *Oligosaccharides/pharmacology/administration & dosage ; Fibroblast Growth Factors/metabolism ; Signal Transduction/drug effects ; Feces/microbiology ; Mice, Obese ; }, abstract = {This work is meant to study the effect of galacto-oligosaccharide (GOS) intervention in the fecal microbiota of obese mice on lipid metabolism and anti-obesity in mice. A pseudo-germ-free mice model was established by administration of a mixture of antibiotics. The fecal microbiota of GOS-fed obese mice are transplanted into pseudo-germ-free mice. To investigate the effects of GOS intervention on lipid metabolism, lipid quadruple, bile acid metabolism, and intestinal microbiota in obese mice. At the same time, the expression of BAS synthase and the effects of FXR-SHP and FXR-FGF15-FGFR4 signaling pathways on BAS homeostasis were also explored. The fecal microbiota of obese mice intervened by GOS could reshape the structure of intestinal microbiota, regulate the synthesis of bile acids in the enterohepatic circulation and the expression of transport-related factors, and promote metabolic ability to exert anti-obesity effects.}, } @article {pmid40624229, year = {2025}, author = {Lau, HC and Zhang, X and Yu, J}, title = {Gut microbiome in metabolic dysfunction-associated steatotic liver disease and associated hepatocellular carcinoma.}, journal = {Nature reviews. Gastroenterology & hepatology}, volume = {}, number = {}, pages = {}, pmid = {40624229}, issn = {1759-5053}, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, affecting billions of the global population. It can gradually progress to more severe diseases, including steatohepatitis, cirrhosis and hepatocellular carcinoma. Studies have highlighted the importance of the gut microbiome in the pathogenesis and progression of MASLD. On the other hand, increasing evidence has revealed the clinical potential of targeting the gut microbiome to treat MASLD. In this Review, we summarize gut microbial alterations in MASLD, metabolic dysfunction-associated steatohepatitis and hepatocellular carcinoma. The mechanisms by which a dysregulated gut-liver axis contributes to disease progression are also described, including intestinal barrier dysfunction, chronic inflammation, and altered metabolic pathways (for example, bile acids) and microbial-derived metabolites (for example, short-chain fatty acids, tryptophan derivatives and endogenous ethanol). In addition, we discuss the clinical implications of utilizing the gut microbiome as a diagnostic biomarker and the therapeutic approaches to treat MASLD and related diseases such as faecal microbiota transplantation, probiotics and engineered bacteria, prebiotics and postbiotics, microbial-derived metabolites, antimicrobials and bacteriophages. Finally, we discuss current challenges in basic and translational research on the microbiome in MASLD and propose future directions to drive progress in this field.}, } @article {pmid40623769, year = {2025}, author = {Basoya, R and Singh, B and Basi, A and Aggarwal, S}, title = {Role of microbiome in cancer progression.}, journal = {International review of cell and molecular biology}, volume = {394}, number = {}, pages = {79-106}, doi = {10.1016/bs.ircmb.2024.12.013}, pmid = {40623769}, issn = {1937-6448}, mesh = {Humans ; *Neoplasms/microbiology/pathology/therapy ; *Disease Progression ; *Microbiota ; Animals ; }, abstract = {The human microbiome plays a crucial role in maintaining health and preventing disease. Dysbiosis, or imbalance, in the microbiome, has been linked to various diseases, including cancer. This chapter explores the influence of microbiomes on different organs, immune system modulation, and cancer development. Specific microorganisms, such as Helicobacter pylori, Escherichia coli, and human papillomavirus (HPV), contribute to gastric, colorectal, and cervical cancer through mechanisms like immunomodulation and proliferative signaling pathways. Dysbiosis-induced cancer progression involves NF-κB, Wnt/β-catenin, and JAK/STAT signaling. Recent studies highlight the microbiome's potential in cancer diagnosis and immunotherapy. Fecal Microbiota Transplantation (FMT) and predictive biomarkers, such as Porphyromonas gingivalis and Escherichia-Shigella, show promise in treating colorectal cancer. The microbiome influences tumor biology and immune response, affecting immunotherapeutic efficacy. Understanding microbiome-cancer interactions offers new opportunities for improved diagnosis and personalized therapy. This chapter provides comprehensive insights into the role of microbiome in cancer progression, emphasizing the importance of microbiome research in developing effective cancer treatments.}, } @article {pmid40621498, year = {2025}, author = {Chong, J and Zhou, Y and Li, Z and Li, X and Zhang, J and Cao, H and Ma, J and Ge, L and Zhong, H and Sun, J}, title = {Hyodeoxycholic acid modulates gut microbiota and bile acid metabolism to enhance intestinal barrier function in piglets.}, journal = {Frontiers in veterinary science}, volume = {12}, number = {}, pages = {1610956}, pmid = {40621498}, issn = {2297-1769}, abstract = {Oral bile acids, particularly hyodeoxycholic acid (HDCA), serve as critical drivers for gut microbial community maturation in mice. In the first study, Cy5-labeled HDCA combined with fluorescence imaging revealed rapid gastrointestinal transit of HDCA in piglets, contrasting with its delayed absorption observed in mice. In the second study, the effects of the oral HDCA supplementation on microbiota-host metabolic interactions were investigated using four piglet model groups: OPM-HDCA (naturally born, raised germ-free (GF), and orally administered HDCA), OPM-CON (naturally born, raised GF, and orally administered PBS), SPF-HDCA (naturally born, raised GF, and received fecal microbiota transplantation (FMT) and HDCA), and SPF-CON (naturally born, raised GF with FMT but no HDCA). The results demonstrated that HDCA administration at 0.2 mg/mL suppressed body weight gain in piglets, which was alleviated by FMT. HDCA significantly altered gut microbiota composition in SPF piglets, markedly increasing the Lactobacillus abundance (37.97% vs. 5.28% in SPF-CON) while decreasing the proportion of Streptococcus (28.34% vs. 38.65%) and pathogenic family Erysipelotrichaceae (0.35% vs. 17.15%). Concurrently, HDCA enhanced intestinal barrier integrity by upregulating tight junction proteins (ZO-1, Claudin, Occludin) and suppressing pro-inflammatory cytokines (TNF-α, IL-1β). Additionally, HDCA significantly upregulated ileal gene expression of CYP7A1 (cytochrome P450 family 7 subfamily A member 1) and TGR5 (G protein-coupled bile acid receptor 1) in both SPF-HDCA and OPM-HDCA groups compared to their respective controls (p < 0.05). These findings demonstrate that HDCA exerts microbiota-dependent effects on growth performance, intestinal barrier function, and bile acid metabolism in piglets. Although 0.2 mg/mL HDCA treatment suppressed body weight gain, it potentially enhanced intestinal barrier integrity by activating the TGR5 signaling pathway and increasing the abundance of beneficial bacteria such as Lactobacillus. These results also highlight the critical role of early-life gut microbiota in nutritional interventions, providing a basis for developing precision nutritional strategies targeting intestinal microbial ecology in piglets.}, } @article {pmid40620607, year = {2025}, author = {Liu, J and Chen, Y and Wan, Q}, title = {Immune Cell Characteristics in a Gut-Kidney Axis-Induced Mouse Model of IgA Nephropathy: The Upregulated Dendritic Cells and Neutrophils.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {8579-8592}, pmid = {40620607}, issn = {1178-7031}, abstract = {BACKGROUND: IgA nephropathy (IgAN) is the leading type of primary glomerulonephritis, significantly contributing to chronic kidney disease (CKD) and renal failure. The pathogenesis of IgAN is the multi-hit hypothesis regarding overproduction and accumulation of galactose-deficient (Gd-IgA1). Recent findings have revealed gut microbiota dysbiosis and immune responses are essential in the development of IgAN, attracting increasing attention. This study aimed to map mucosal immune cells in IgAN influenced by gut microbiota, investigating the role of innate immune cells in kidney damage.

METHODS: Fecal samples were acquired from both patients and controls for subsequent animal experiments. Mice received a broad-spectrum antibiotic cocktail to eliminate their intestinal microflora, followed by a gavage with fecal microbiota from clinical individuals. Murine intestinal and kidney tissues were collected for flow cytometry. Intestine and kidney histopathology, immunofluorescence, and inflammatory cytokine expression were assessed in the murine models. The mucosal epithelium's structure and function, along with the innate immune cell response, were analyzed.

RESULTS: Mice exhibited the IgAN phenotype following colonization with gut microbiota from IgAN patients. These mice (IgAN-FMT mice) showed renal dysfunction and increased pathology of tissue injury in both intestine and kidneys. IgAN-FMT mice showed heightened pro-inflammatory cytokine (IL-6 and TNF-α) activity, greater antibody (IgA and complement C3) deposition and decreased expression of mucosal barrier protein (ZO-1, Occludin) compared to the control group. Furthermore, CD11c[+]dendritic cells were more abundant in the murine intestine and kidneys compared to the control group.

CONCLUSION: The gut-kidney axis, including microbiota homeostasis and innate immune cell response, contributes to the pathogenesis of IgAN. Gut dysbiosis and hyperactivated immune cells like CD11c[+]dendritic cells can affect the mucosal barrier and exacerbate the renal damage, being novel insights into immunotherapeutic strategies for IgAN.}, } @article {pmid40620312, year = {2025}, author = {Sopel, A and Szczuciński, W and Gosiewski, T and Salamon, D}, title = {The role of fecal microbiota transplantation in selected neurodegenerative diseases and neurodevelopmental disorders.}, journal = {Przeglad gastroenterologiczny}, volume = {20}, number = {2}, pages = {127-141}, pmid = {40620312}, issn = {1895-5770}, abstract = {Fecal microbiota transplantation (FMT) is a medical procedure that allows to establish a stable and healthy intestinal microbiota in various diseases believed to be related to a gut dysbiosis. Currently, FMT is successfully used to treat recurrent Clostridioides difficile infection. However, in recent years there has been evidence that changes in composition of gut microbiota may also be relevant in the pathogenesis of several neuropsychiatric and neurodevelopmental conditions including Alzheimer's disease, multiple sclerosis, Parkinson's disease, autism spectrum disorders and schizophrenia. This review focuses on exploring the complex connection between gut microbiota and pathogenesis of these neurological conditions. It also presents current research on a possible use of FMT as a therapeutic intervention targeting the gut-brain axis.}, } @article {pmid40619214, year = {2025}, author = {Bai, X and Ihara, E and Tanaka, Y and Minoda, Y and Wada, M and Hata, Y and Esaki, M and Ogino, H and Chinen, T and Ogawa, Y}, title = {The interplay of gut microbiota and intestinal motility in gastrointestinal function.}, journal = {Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi}, volume = {61}, number = {}, pages = {51-58}, pmid = {40619214}, issn = {1884-8796}, mesh = {Humans ; *Gastrointestinal Motility/physiology ; *Gastrointestinal Microbiome/physiology ; Bile Acids and Salts/metabolism ; Animals ; Irritable Bowel Syndrome/microbiology/physiopathology/therapy ; Probiotics/therapeutic use ; *Gastrointestinal Tract/microbiology/physiology ; Interstitial Cells of Cajal/physiology ; Fecal Microbiota Transplantation ; Prebiotics ; Constipation/microbiology ; Gastrointestinal Diseases/microbiology/therapy ; Fatty Acids, Volatile/metabolism ; }, abstract = {The relationship between gut microbiota and intestinal motility is crucial for maintaining gastrointestinal health. Intestinal motility refers to the coordinated movements of the digestive tract, essential for effective digestion, nutrient absorption, and timely waste elimination. Recent studies have demonstrated that microbiota play a crucial role not only in the maturation of intestinal motility but also in the ongoing maintenance of established motility patterns. Disruptions in motility can lead to various disorders, such as chronic constipation, irritable bowel syndrome, and chronic idiopathic pseudo-obstruction. Gut microbiota significantly influence intestinal motility through mechanisms like bile acid metabolism and the production of short-chain fatty acids. In patients with diarrhea-predominant irritable bowel syndrome, elevated primary-to-secondary bile acid ratios suggest a complex interaction between gut bacteria and bile acids that can enhance motility via receptors like TGR5. Additionally, the role of interstitial cells of Cajal in facilitating non-neuronal contractions has revolutionized our understanding of motility regulation, highlighting both neural and non-neural factors. Various therapeutic approaches, including prebiotics, probiotics, and fecal microbiota transplantation, have been explored to improve intestinal motility, although their effectiveness has been limited. Advancements in gene-related research and innovative diagnostic methods are vital for a deeper understanding of how the gut microbiome regulates motility. This review synthesizes current knowledge on the interplay between gut microbiota and intestinal motility, emphasizing the need for interdisciplinary research to develop effective treatments targeting gut microbiota for gastrointestinal disorders. By unraveling these complex interactions, we can pave the way for novel therapeutic strategies that enhance intestinal health and improve the quality of life for those affected by motility-related disorders.}, } @article {pmid40618491, year = {2025}, author = {Tian, Y and Meng, J and Zhang, D and Zhai, B and Cheng, J and Zou, J and Shi, Y and Guo, D}, title = {Wendan Decoction exerts therapeutic effects on insomnia by regulating gut microbiota and tryptophan metabolism.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {145}, number = {}, pages = {157028}, doi = {10.1016/j.phymed.2025.157028}, pmid = {40618491}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Sleep Initiation and Maintenance Disorders/drug therapy ; *Tryptophan/metabolism ; *Drugs, Chinese Herbal/pharmacology ; Male ; Rats, Sprague-Dawley ; Rats ; Fecal Microbiota Transplantation ; Feces/chemistry ; }, abstract = {BACKGROUND: Insomnia has been a public problem threatening human health. Wendan Decoction (WDD) has good therapeutic effects on insomnia. However, its mechanism to improve sleep remains unclear.

PURPOSE: To investigate the potential mechanism of WDD in treating insomnia from the perspective of gut microbiota and metabolism.

METHODS: The chemical composition of WDD was analyzed by UHPLCOrbitrap Exploris/MS. The efficacy of WDD on PCPA-induced insomnia rats was evaluated through behavioral tests, ELISA, histopathological examination, immunofluorescence and western blotting. 16S rRNA sequencing, untargeted metabolomics, and network pharmacology were integrated to explore the mechanism of WDD in treating insomnia. The role of gut microbiota in WDD treatment was validated by antibiotic treatment and fecal microbiota transplantation (FMT). Targeted metabolomics was used to detect changes in fecal tryptophan metabolites after FMT. Additionally, RT-qPCR and western blotting were used to investigate the potential mechanisms.

RESULTS: WDD effectively shortened sleep latency, prolonged sleep duration, alleviated anxiety-like behaviors, attenuated neuronal damage, and modulated neurotransmitter levels in rats with insomnia. Moreover, WDD alleviated intestinal damage, reduced the number of Iba-1 positive cells, increased IL-10 levels and decreased IL-6, IL-1β, TNF-α and LPS levels in the colon, serum and hippocampus. It also increased the expression of Occludin, Claudin-1, and ZO-1 in both the colon and brain. 16S rRNA sequencing suggested that WDD improved gut microbiota disorders. Untargeted metabolomics and network pharmacology jointly suggested that WDD could regulate tryptophan metabolism. Antibiotic treatment and FMT confirmed the involvement of gut microbiota in the therapeutic effects of WDD in alleviating insomnia. Changes of tryptophan metabolites in feces, serum, and hippocampus confirmed the regulatory effect of WDD on tryptophan metabolism. Further mechanistic analysis suggested that WDD may correct the abnormal kynurenine pathway of tryptophan metabolism through inhibition of the expression of indoleamine 2,3-dioxygenase 1 and kynurenine-3-monooxygenase.

CONCLUSION: WDD can modulate the neurotransmitter disorders, reduce inflammatory cytokine levels, and strengthen the intestinal barrier and blood-brain barrier by regulating gut microbiota and tryptophan metabolism, thereby improving sleep. This study provides evidence for the potential therapeutic effect of WDD on insomnia via the microbiota-gut-brain axis.}, } @article {pmid40618377, year = {2025}, author = {Le, TT and Hoang, TN and Do, DH and Nguyen, XH and Huynh, C and Viet, HD and Dat, VQ and Zengler, K and Gilbert, JA and Avedissian, SN and Tran, TM and Le, J}, title = {Current state of microbiota clinical applications in neonatal and pediatric bacterial infections.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2529400}, pmid = {40618377}, issn = {1949-0984}, mesh = {Humans ; Infant, Newborn ; Child ; *Bacterial Infections/microbiology/therapy ; Dysbiosis/microbiology/therapy ; *Gastrointestinal Microbiome ; Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Infant ; Bacteria/classification/isolation & purification/genetics ; Child, Preschool ; }, abstract = {The microbiota plays a crucial role in pediatric health by shaping immune development and influencing infection susceptibility. In infants and children, an immature microbiota may compromise immune defense, increasing the risk of bacterial infections. This review evaluates clinical trials on the microbiota's role in neonatal and pediatric bacterial infections, including sepsis, infections in pediatric cancer patients, and Clostridioides difficile-associated dysbiosis. We summarized original research articles published from 2000 to May 2024 on the microbiota and bacterial infections in neonates and children. A balanced microbiota is essential for infection prevention, particularly in premature infants and immunocompromised children. Studies of microbiome signatures in the gut, oral cavity, and nasopharynx have highlighted how microbiota composition influences infection risk, treatment response, and adverse effects from antibiotics and chemotherapy. Disruptions from antibiotic exposure, chemotherapy, and hematopoietic stem cell transplantation frequently lead to dysbiosis, characterized by depletion of commensal bacteria and overgrowth of pathobionts, including antibiotic-resistant strains such as C. difficile. Conversely, microbiota-restorative interventions, such as probiotics and fecal microbiota transplantation, show promise in reducing bacterial infections by enhancing microbial resilience. The microbiota plays a critical role in predicting and potentially treating bacterial infections in children. While antibiotics remain essential, their widespread use has significant consequences for microbiota health. Striking a balance between effective infection control and microbiota preservation is crucial, particularly in vulnerable pediatric populations. Implementing judicious antibiotic use and exploring microbiota-based therapies may mitigate long-term microbiota disruptions, ultimately improving infection outcomes and overall pediatric health.}, } @article {pmid40618373, year = {2025}, author = {Li, L and Yang, Z and Yi, Y and Song, Y and Zhang, W}, title = {Gut microbiota and radiation-induced injury: mechanistic insights and microbial therapies.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2528429}, pmid = {40618373}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/radiation effects ; *Radiation Injuries/therapy/microbiology ; Animals ; Fecal Microbiota Transplantation ; Probiotics ; Signal Transduction ; Oxidative Stress ; Neoplasms/radiotherapy ; Radiotherapy/adverse effects ; Prebiotics ; }, abstract = {Radiotherapy represents a crucial therapeutic modality in cancer treatment, yet its efficacy is frequently limited by radiation-induced toxicity. Growing evidence indicates that gut microbiota and their metabolites serve as key regulators of both radioprotective and radiosensitizing effects. This review systematically examines three fundamental regulatory mechanisms through which gut microbiota and its metabolites mitigate radiation-induced injury: (1) modulation of intestinal epithelial cell regeneration and tumor cell apoptosis via Wnt/β-catenin and PI3K/AKT/mTOR pathways; (2) immunomodulation via Toll-like receptor activation and NF-κB signaling; (3) oxidative stress management via Nrf2 signaling. We also evaluate various microbiota-targeted interventions, ranging from probiotics and prebiotics to fecal microbiota transplantation and emerging engineered microbial therapies, highlighting their potential in clinical radiotherapy. Finally, we emphasize current limitations and future research directions, underscoring the need to overcome existing challenges in microbiome analysis and therapeutic durability to fully realize the potential of precision radio-microbiome medicine, which may provide valuable references for developing personalized radiotherapy strategies based on gut microbiota and their metabolites.}, } @article {pmid40617533, year = {2025}, author = {Chen, L and Li, B and Zu, M and Reis, RL and Kundu, SC and Xiao, B}, title = {Advances and mechanisms of gut microbiota modulation in enhancing immune checkpoint inhibitor efficacy.}, journal = {Seminars in cancer biology}, volume = {114}, number = {}, pages = {150-172}, doi = {10.1016/j.semcancer.2025.06.012}, pmid = {40617533}, issn = {1096-3650}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/drug effects ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology/adverse effects ; Animals ; *Neoplasms/immunology/drug therapy/microbiology/therapy ; Immunotherapy/methods ; Fecal Microbiota Transplantation ; }, abstract = {The gut microbiota is crucial for maintaining human health by regulating immune homeostasis and metabolic function. Immune checkpoint inhibitors (ICIs) have emerged as a cornerstone of cancer immunotherapy, yet their effectiveness is often hampered by treatment resistance and immune-related adverse events (irAEs). Increasing evidence highlights gut microbiota as a critical determinant of ICI efficacy. Here, we summarize the advances from preclinical mouse models and clinical trials to systematically illustrate how gut microbiota modulation strategies, such as fecal microbiota transplantation, specific microorganism supplementation, dietary and lifestyle interventions, and prebiotic/postbiotic supplementation, can enhance ICI therapeutic outcomes and mitigate irAEs. Mechanistically, the gut microbiota shape host immune responses, influencing innate, adaptive, and mucosal immunity, as well as immune checkpoint expression, through microbial translocation, microbiota-derived metabolites, and extracellular vesicles. This review elucidates the intricate interplay between gut microbiota and ICI treatment responses, laying a theoretical groundwork for developing personalized microbiota-based strategies to optimize cancer immunotherapy.}, } @article {pmid40617323, year = {2025}, author = {Lu, Y and Zhang, Z and Chen, L and Xue, P and Zhang, Y and Li, Y and Guo, H}, title = {Prospect of interdisciplinary research on gut microbiota and colorectal cancer immunotherapy.}, journal = {Critical reviews in oncology/hematology}, volume = {214}, number = {}, pages = {104832}, doi = {10.1016/j.critrevonc.2025.104832}, pmid = {40617323}, issn = {1879-0461}, abstract = {Immune checkpoint blockade (ICB) is considered as a promising therapy in a variety of cancers, while colorectal cancer (CRC) is mostly resistant to it. The ICB efficacy is proved to be associated with gut microbiota. However, the research on improving ICB outcomes of CRC by microbes or their metabolites is obstructed compared to other types of cancers. Through summarizing the main progress and limitations in previous work, we provide our proposal for further study on CRC. For preclinical basic investigation, microbial tryptophan metabolism regulates ICB therapy outcomes particularly in CRC and requires specific focus. For clinical trials, sources of recruited cohorts and donators of fecal microbiota transplantation can be diversified. For future application, interdisciplinary methods and models coupled with advanced technologies are suggested for designing precise intervention strategies based on prebiotics.}, } @article {pmid40617308, year = {2025}, author = {Dan, W and Xiong, C and Zhou, G and Chen, J and Pan, F}, title = {Gut microbiota as a mediator of cancer development and management: From colitis to colitis-associated dysplasia and carcinoma.}, journal = {Biochimica et biophysica acta. Reviews on cancer}, volume = {1880}, number = {4}, pages = {189381}, doi = {10.1016/j.bbcan.2025.189381}, pmid = {40617308}, issn = {1879-2561}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; Fecal Microbiota Transplantation ; *Colitis/microbiology/complications/pathology ; *Colitis-Associated Neoplasms/microbiology/pathology/therapy ; Animals ; Probiotics/therapeutic use ; *Colorectal Neoplasms/microbiology/pathology/therapy/etiology ; Tumor Microenvironment ; Carcinogenesis ; }, abstract = {Colitis-associated colorectal cancer (CAC) develops as a result of prolonged colitis in patients with inflammatory bowel disease. In recent years, the role of the gut microbiota in colitis-associated colorectal carcinogenesis has begun to be recognized. Specific microbes, such as enterotoxigenic Bacteroides fragilis, Fusobacterium nucleatum, and pks[+]Escherichia coli, promote carcinogenesis by regulating oncogenic signaling, epithelial-mesenchymal transition, autophagy induction, and the immune microenvironment. Conversely, commensal fungi and probiotics exert tumor-suppressive effects by inhibiting inflammatory pathways and immune cell recruitment. Emerging microbiota-targeted strategies, including precision probiotics and fecal microbiota transplantation, can restore ecological homeostasis, attenuate inflammation, and enhance the efficacy of conventional therapies. This review summarizes the current understanding of the mechanisms underlying microbiota-driven CAC pathogenesis and assesses the potential applications of gut microbiota in the development of diagnostic tools and therapeutic interventions.}, } @article {pmid40615821, year = {2025}, author = {Upadhyay, P and Kumar, S and Tyagi, A and Tyagi, AR and Barbhuyan, T and Gupta, S}, title = {Gut Microbiome rewiring via fecal transplants: Uncovering therapeutic avenues in Alzheimer's disease models.}, journal = {BMC neuroscience}, volume = {26}, number = {1}, pages = {39}, pmid = {40615821}, issn = {1471-2202}, support = {File no.R.12014/20/2018//Department of Health Research, India/ ; DBT Core grant//National Institute of Immunology New Delhi India/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation/methods ; *Alzheimer Disease/therapy/microbiology/psychology ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; Male ; Mice, Transgenic ; Oxidative Stress ; }, abstract = {BACKGROUND: Emerging evidence implicates the gut microbiome in Alzheimer's disease (AD) pathogenesis, yet the underlying mechanisms remain elusive. This study elucidates the bidirectional relationship between gut microbiota and AD using fecal microbiota transplantation (FMT) in a mouse model.

RESULT: Through meticulous experimentation, we conducted reciprocal FMT between AD (5xFAD) and healthy (C57BL/6) mice to unravel the impact of gut microbiome alterations on cognitive function and neuroinflammation. FMT from 5xFAD to C57BL/6 mice induced profound memory impairment and cognitive deficits, accompanied by elevated inflammatory cytokine levels, oxidative stress markers, and systemic inflammation, as evidenced by increased plasma cytokines. Conversely, transplanting healthy microbiota into 5xFAD mice yielded remarkable behavioral improvements, including enhanced spatial memory performance in the Morris water maze, directly correlating with cognitive recovery. Our findings underscore the pivotal role of the gut microbiome in AD pathogenesis and offer a promising therapeutic avenue.

CONCLUSION: Targeted modulation of the gut microbiome through strategies like FMT may offer potential benefits in Alzheimer's disease by influencing neuroinflammation, oxidative stress, and cognitive function. This comprehensive study provides novel insights into the gut-brain axis dynamics and paves the way for innovative microbiome-based interventions in AD management.}, } @article {pmid40615512, year = {2025}, author = {Ruan, S and Liu, J and Yuan, X and Ye, X and Zhang, Q}, title = {Aerobic exercise alleviates cognitive impairment in T2DM mice through gut microbiota.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {23917}, pmid = {40615512}, issn = {2045-2322}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Cognitive Dysfunction/therapy/etiology/microbiology ; *Physical Conditioning, Animal ; *Diabetes Mellitus, Type 2/complications/microbiology ; Male ; Mice ; Mice, Inbred C57BL ; *Diabetes Mellitus, Experimental/complications/microbiology ; Fecal Microbiota Transplantation ; }, abstract = {The risk of cognitive impairment is markedly elevated in patients with type 2 diabetes mellitus (T2DM). While exercise has been shown to mitigate cognitive deficits associated with diabetes, the underlying mechanisms remain poorly understood. Recent studies suggest that exercise can modulate the composition of the gut microbiota, which, in turn, may influence the central nervous system via the microbiota-gut-brain axis. However, the specific role of gut microbiota in mediating exercise-induced improvements in cognitive function in T2DM remains unclear. In this study, we aimed to investigate whether exercise can alleviate cognitive impairment in T2DM mice by modulating the intestinal microbiota, and to elucidate the mechanisms underlying this effect. This study was conducted using male C57BL/6J mice. Mice fed a normal diet were assigned to the non-diabetic control group (NC), while those fed a high-fat diet were intraperitoneally injected with streptozotocin (STZ) and subsequently divided into the diabetic control group (DM), an exercise group (DM-EXE), and a fecal microbiota transplantation group (DM-FMT). The DM-EXE group underwent treadmill exercise for 8 weeks. During this period, the DM-FMT group received fecal microbiota transplants from the DM-EXE group for 2 consecutive days per week. Following the 8-week intervention, stool samples were collected for 16S rDNA high-throughput sequencing. The fear conditioning test was performed to assess cognitive function. Intestinal mucosa samples were collected to evaluate the expression of intestinal tight junction proteins. Additionally, the expression levels of synaptic proteins, glucose transporters, neurotrophic factors, and inflammatory markers were measured in the hippocampus. Our findings demonstrate that T2DM mice exhibit impaired cognitive function and significant alterations in their gut microbiota compared to non-diabetic controls. Exercise partially reversed these changes in the intestinal microbiota and alleviated cognitive impairment in T2DM mice. Additionally, transplantation of intestinal microbiota from exercised mice improved cognitive function in T2DM mice. Aerobic exercise may mitigate cognitive impairment in T2DM mice by modulating the gut microbiota. The underlying mechanisms appear to involve enhanced neural synaptic plasticity, reduced neuroinflammation, and improved neuronal glucose metabolism.}, } @article {pmid40615289, year = {2025}, author = {Chen, H}, title = {Mapping the clinical trial landscape of gut microbiota modulation in neurodegenerative diseases.}, journal = {European journal of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ejim.2025.06.032}, pmid = {40615289}, issn = {1879-0828}, } @article {pmid40614920, year = {2025}, author = {Yadav, S and Raj, RG}, title = {Parkinson's disease and the gut microbiota connection: unveiling dysbiosis and exploring therapeutic horizons.}, journal = {Neuroscience}, volume = {581}, number = {}, pages = {1-15}, doi = {10.1016/j.neuroscience.2025.07.003}, pmid = {40614920}, issn = {1873-7544}, mesh = {Humans ; *Parkinson Disease/microbiology/therapy/metabolism/physiopathology ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology/therapy/metabolism ; Animals ; Probiotics/therapeutic use ; Brain/metabolism ; }, abstract = {Parkinson's disease (PD) is a progressive neurodegenerative disorder marked by dopaminergic neuronal loss, α-synuclein aggregation, and sustained neuroinflammation. Emerging evidence supports the gut-brain-microbiota axis as a pivotal player in the disease's pathogenesis. Dysbiosis, disruptions in the gut microbial composition, has been consistently observed in individuals with PD, with notable reductions in beneficial, short-chain fatty acid-producing bacteria and elevations in pro-inflammatory microbial species. These alterations contribute to increased intestinal permeability, systemic inflammation, and heightened neuroinflammatory responses that may drive α-synuclein misfolding and dopaminergic degeneration. In addition, microbial metabolites, including lipopolysaccharides and amyloid proteins such as curli, may promote neurodegeneration via immune and molecular mimicry pathways. Recent advances highlight the bidirectional influence of the microbiota-gut-brain axis on PD symptoms, ranging from motor deficits to non-motor features like constipation, depression, and cognitive decline. Several microbiota-modulating interventions, including probiotics, prebiotics, dietary strategies, antibiotics, and fecal microbiota transplantation, have demonstrated neuroprotective potential in both preclinical and clinical contexts. However, inter-individual variability, methodological heterogeneity, and the absence of longitudinal, multi-omics-integrated studies limit current understanding. The gut microbiome also holds promise as a non-invasive biomarker for early PD detection and prognosis, though standardization remains a challenge. Future research must clarify causal mechanisms, optimize therapeutic delivery, and integrate genetic, metabolic, and environmental data to advance precision medicine approaches. This review consolidates current knowledge on gut microbiota's role in PD pathophysiology and therapeutic innovation, providing a roadmap for future research directions.}, } @article {pmid40614649, year = {2025}, author = {Wang, Y and Ma, S and Wu, L and Zhao, R}, title = {Betaine promotes chicken growth through modulating gut microbiota and FXR-mediated activation of IGF genes.}, journal = {Poultry science}, volume = {104}, number = {9}, pages = {105455}, pmid = {40614649}, issn = {1525-3171}, abstract = {Betaine is a growth-promoting additive used in both the animal production and microbial fermentation industries. The primary mechanisms by which betaine promotes animal growth are well known through its direct action on the host cells. However, it remains unclear whether betaine exerts its growth-promoting effects in chickens dependent on the gut microbiota. Here, we found that betaine promotes the growth of broiler chickens while enhancing the richness and diversity of the cecal microbiota and increasing beneficial bacteria, such as Lactobacillus, Limosilactobacillus, and Prevotella (P < 0.05). However, the growth-promoting effects of betaine were abolished in broilers treated with an antibiotic cocktail. Furthermore, fecal microbiota transplantation from betaine-supplemented chickens could recapitulate the promoting effect of betaine on body weight, breast muscle weight, and hepatic insulin-like growth factors (IGFs) synthesis (P < 0.05), indicating that the gut microbiota plays an indispensable role in betaine's growth-promoting action. Mechanistically, betaine promotes (P < 0.05) the synthesis of bile acids, and microbial function predictions suggest that betaine upregulates the biosynthetic pathways of primary and secondary bile acids. Notably, the expression of the bile acid receptor farnesoid X receptor (FXR) was upregulated (P < 0.05) in the liver, promoting FXR binding to the IGFs genes promoter regions and activating the transcription of IGFs gene. Taken together, our findings suggest that betaine promotes broiler growth via microbiota-dependent mechanisms, accompanied by FXR-mediated upregulation of IGFs gene expression in the liver, providing new perspectives and theoretical support for understanding the complexity of animal growth regulation.}, } @article {pmid40613778, year = {2025}, author = {Wang, W and He, X and Liang, C and Wang, Y and Yu, Y and Zhang, F}, title = {Washed microbiota transplantation alleviates tyrosine kinase inhibitors associated gastrointestinal adverse effects.}, journal = {International journal of cancer}, volume = {}, number = {}, pages = {}, doi = {10.1002/ijc.70034}, pmid = {40613778}, issn = {1097-0215}, support = {2021YFA0717004//the National Key R&D Program of China/ ; 2023-3HIM//Nanjing Medical University Fan Daiming Research Funds for Holistic Integrative Medicine/ ; }, abstract = {Gut microbiota dysbiosis is implicated in tyrosine kinase inhibitor (TKI)-induced gastrointestinal adverse effects (GAEs), often necessitating medication adjustments or discontinuation in severe or persistent cases. This study aimed to evaluate the efficacy and safety of washed microbiota transplantation (WMT) in managing TKI-induced GAEs. This prospective study involved cancer patients presenting TKI-induced GAEs. The primary outcome was the clinical remission rate at Week 8 post-WMT, which was assessed by the common terminology criteria for adverse events grade. The secondary outcomes included the clinical asymptomatic rate, the onset time of clinical remission, and the variation of C-reactive protein (CRP) levels. Twenty-four patients undergoing 66 WMTs were analyzed. The overall clinical remission and asymptomatic rates were 75.00% (18/24) and 29.17% (7/24), respectively. GAEs, including diarrhea, abdominal pain, and abdominal distention, showed significant improvement post-WMT (all p < .05), while hematochezia exhibited a decreasing trend in severity. Median time to remission was 14.5 days (inter-quartile range, 7-24). Within 8 weeks post-WMT, three initially responsive patients experienced relapse. CRP levels significantly decreased (p < .05), and no severe adverse events were reported. This study proposes WMT as a potential treatment for TKI-induced GAEs, particularly for patients who do not respond adequately to conventional treatments.}, } @article {pmid40613520, year = {2025}, author = {Ramos Martínez, A and Gutiérrez-Villanueva, A and González-Haba Ruiz, M and Diego-Yagüe, I and Nieto-Fernández, A and Muñez, E and Fernández Cruz, A and Calderón Parra, J}, title = {Fecal microbiota transplantation for prevention of recurrent acute cholangitis. Review of four published cases.}, journal = {Revista espanola de enfermedades digestivas}, volume = {}, number = {}, pages = {}, doi = {10.17235/reed.2025.11404/2025}, pmid = {40613520}, issn = {1130-0108}, abstract = {INTRODUCTION: Recurrent acute cholangitis (RAC) constitutes a relevant clinical problem that may condition the prognosis of the patient. Chronic suppressive antibiotic therapy can be used for preventive purposes, but it is associated with adverse effects and can select resistant bacterial strains. Fecal microbiota transfer (FMT) has been shown to be effective in preventing recurrent Clostridioides difficile infection and could be a useful strategy in patients with RAC.

OBJECTIVE: To review the experience of the use of FMT in the prevention of episodes of RAC by reviewing published cases.

RESULT: Four cases were identified in which FMT significantly reduced RAC episodes. The patients were characterized by lack of efficacy of conventional treatments, had different predisposing factors for RAC and frequent colonization and infection by multidrug-resistant bacteria.

CONCLUSIONS: The four cases presented provide limited but encouraging evidence of the preventive effect of FMT on successive episodes in patients without biliary tract obstruction. Larger and more adequately designed studies will be necessary to deepen the knowledge of this possible preventive strategy.}, } @article {pmid40613134, year = {2025}, author = {Yao, Y and Ye, Y and Zheng, C}, title = {The Impact of Microbiota-Mediated Immune Regulation on Recurrent Pregnancy Loss and Intervention Strategies.}, journal = {American journal of reproductive immunology (New York, N.Y. : 1989)}, volume = {94}, number = {1}, pages = {e70121}, doi = {10.1111/aji.70121}, pmid = {40613134}, issn = {1600-0897}, support = {LHDMZ23H190002//Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China/ ; }, mesh = {Humans ; Female ; *Abortion, Habitual/immunology/microbiology/therapy ; Pregnancy ; *Gastrointestinal Microbiome/immunology ; *Dysbiosis/immunology ; *Microbiota/immunology ; *Endometrium/microbiology/immunology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Animals ; Immune Tolerance ; }, abstract = {Recurrent pregnancy loss (RPL) significantly affects reproductive health in couples of childbearing age. Its pathogenesis is complex, with nearly 50% of cases remaining unexplained, and immune regulation plays a key role in its development. This review focuses on the relationship between human microbiota (gut, reproductive tract, and endometrial microbiota), immune regulation, and RPL, systematically summarizing related research progress. RPL patients exhibit characteristic changes in the gut, reproductive tract, and endometrial microbiota, such as reduced gut microbial diversity, decreased beneficial bacteria, increased harmful bacteria in the reproductive tract, and an imbalanced endometrial microbiota structure. Dysbiosis can lead to immune regulation abnormalities, increasing the risk of RPL by disrupting immune tolerance, triggering inflammatory responses, and interfering with metabolism. Although microbiota-based interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, show potential, they face challenges related to strain selection, donor screening, and unclear mechanisms. Current research also faces limitations in detection technology and sample size, and the understanding of the microbiota-immune-RPL relationship requires further deepening. Future studies should clarify causal relationships using advanced technologies, develop more effective detection and intervention methods, and create personalized treatment plans based on individual patient characteristics to improve clinical diagnosis and treatment of RPL and safeguard women's reproductive health.}, } @article {pmid40612747, year = {2025}, author = {Wu, J and Jia, B and Gong, S and Li, Y and Wang, J and Huang, Y and Guo, J}, title = {Protective effects of Atractylodes macrocephala polysaccharides on acetaminophen-induced liver injury.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1583334}, pmid = {40612747}, issn = {1663-9812}, abstract = {BACKGROUND: Drug-induced liver injury (DILI) is a major clinical concern due to its unpredictable nature and lack of effective therapeutic options.

METHODS: This study investigated the hepatoprotective effects of Atractylodes macrocephala polysaccharides (AMPs) in a mouse model of acetaminophen (APAP)-induced liver injury. Mice were pretreated with AMPs for 7 days prior to APAP challenge, and liver injury was evaluated through histopathology, serum biochemistry, molecular assays, and gut microbiota analysis.

RESULTS: AMPs treatment significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared to the APAP group (p < 0.05). Hepatic oxidative stress was alleviated, as indicated by increased levels of glutathione (GSH, p < 0.05) and superoxide dismutase (SOD, p < 0.05), and reduced malondialdehyde (MDA, p < 0.05). AMPs also suppressed inflammatory cytokines, including Il-1β, Tnf-α, Il-6, and Nlrp3 (p < 0.05), and modulated apoptosis-related proteins by downregulating Bax and upregulating Bcl-2 and Bcl-xl expression (p < 0.05). Furthermore, AMPs improved gut microbiota diversity and enriched beneficial genera such as Roseburia, as revealed by 16S rDNA sequencing. Fecal microbiota transplantation from AMPs-treated mice replicated these hepatoprotective effects, highlighting the involvement of the gut-liver axis.

CONCLUSION: These findings support the therapeutic potential of AMPs as a multifaceted agent for DILI, exerting protective effects through modulation of oxidative stress, inflammation, apoptosis, and intestinal dysbiosis.}, } @article {pmid40612440, year = {2025}, author = {Wenjiao, D and Yurou, W and Jiaqi, X and Yan, H and Hongfang, J and Min, C and Jianjin, G}, title = {Animal studies on the modulation of differential efficacy of polyethylene glycol loxenatide by intestinal flora.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1508473}, pmid = {40612440}, issn = {1664-2392}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Male ; Mice ; Mice, Inbred C57BL ; *Fecal Microbiota Transplantation ; *Diabetes Mellitus, Experimental/microbiology/drug therapy/therapy ; *Polyethylene Glycols/pharmacology ; *Diabetes Mellitus, Type 2/microbiology/drug therapy ; *Hypoglycemic Agents/pharmacology/therapeutic use ; Diet, High-Fat/adverse effects ; Blood Glucose ; }, abstract = {BACKGROUND: Gut microbiota has demonstrated an increasingly important role in the onset and development of type 2 diabetes mellitus (T2DM), Further investigations have revealed the interactions between drugs and the gut microbiome. However, there are still gaps in research regarding the potential interactions between the gut microbiota and GLP-1 and their therapeutic response in people with T2DM. In addition, Fecal microbiota transplantation (FMT) has become a promising strategy for patients with T2DM.

50 healthy male C57BL/6 mice were fed a high-fat diet in combination with STZ to establish a T2DM mouse model. 40 mice were divided into the T2DM group (n=10) and the PEX168 group (n=30). the PEX168 group was divided into two subgroups of the IE group (HbA1c ≤6. 5%, n=12) and the SE group (HbA1c >6. 5%, n=12), 12 mice in each group. Using IE mice as fecal donors and SE mice as recipients, fecal microbiota transplantation was performed between the two groups, the FMT group (given fecal bacterial suspension, n=5) and the Sham group (given equal amounts of sterile saline, n=5). The intestinal microorganisms of mice in the IE group (donor) and SE group (recipient) were also analyzed for differences. To assess the protective effect of FMT on drug efficacy and T2DM, and to explore the underlying mechanisms.

RESULTS: After 10 weeks, compared with the control group, the HbA1c of the experimental group was significantly reduced, still, the level of HBA1c of the mice in the unsatisfactory group was significantly higher than that in the ideal group. Compared with the unsatisfactory group, fasting blood glucose, 2h postprandial blood glucose, blood glucose AUC and body weight were significantly reduced in the ideal group. 16srDNA sequencing showed that the levels of Bacteroidota, Akkermansia, Parabacteroides, Bifidobacteria and other bacteria in the ideal efficacy group were significantly higher than those in the non-ideal efficacy group (P<0.05). The levels of Firmicutes, Romboutsia, Clostridium, Turicibacter and other bacteria in the unsatisfactory group were significantly higher than those in the ideal group (P<0.05). The dominant flora of mice in the ideal drug efficacy group was negatively correlated with HbA1c and blood sugar, and the dominant flora of mice in the unsatisfactory drug efficacy group was positively correlated with pro-inflammatory factors such as blood sugar. Moreover, FMT treatment significantly improved the efficacy of PEX168 and liver steatosis in the group with unsatisfactory efficacy.

CONCLUSION: In summary, we used the combined method of 16S rDNA and metabolomics to systematically elucidate the efficacy of microflora on PEX168 and the possible mechanism of FMT in treating T2DM by PEX168. The difference in intestinal flora between individuals can affect the therapeutic effect of drugs. Moreover, FMT therapy can affect multiple metabolic pathways and colonization of beneficial bacteria to maintain the drug's therapeutic effect on T2DM mice.}, } @article {pmid40611525, year = {2025}, author = {Wang, D and Wang, H and Li, Y and Lu, J and Tang, X and Yang, D and Wang, M and Zhao, D and Liu, F and Zhang, S and Sun, L}, title = {Alistipes senegalensis is Critically Involved in Gut Barrier Repair Mediated by Panax Ginseng Neutral Polysaccharides in Aged Mice.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e16427}, doi = {10.1002/advs.202416427}, pmid = {40611525}, issn = {2198-3844}, support = {U24A20795//National Natural Science Foundation of China/ ; 82204709//National Natural Science Foundation of China/ ; 82004099//National Natural Science Foundation of China/ ; JJKH20230991KJ//Jilin Provincial Department of Education Project/ ; 20240404018ZP//Jilin Provincial Scientific and Technological Development Program/ ; }, abstract = {Ginseng polysaccharides (GPs) are known to have beneficial effects on the gut epithelium and age-related systemic-inflammation through regulation of gut microbiota. However, the underlying pathways and key members of the microbial community involved in this process are poorly understood. In this study, administration of ginseng neutral polysaccharide (GPN) is found to alleviate gut leak and low-grade inflammation, concomitantly with improving the physiological function aged mice. Fecal microbiota transplantation and fecal conditioned medium are used to assess the specific involvement of gut bacterial metabolites in the effects of GPNs. Comprehensive multi-omics analyses showed that GPN significantly enriched the abundance of Alistipes senegalensis, an indole-producing commensal bacterium. Increased expression of tight junction-associated proteins, as well as activation of gut stem cells, are found to be mediated by the AhR pathway, indicating the causal mechanism by which GPN reduced increases in gut permeability. The results are verified in Caco-2/THP-1 cells, Caenorhabditis elegans, and enteroids. To the knowledge, this is the first identification of an integral functional axis through which GPN and functional metabolites of A. senegalensis influence the gut barrier and reduce systemic inflammation, providing clues for the potential development of innovative plant polysaccharide treatment strategies to promote healthy aging.}, } @article {pmid40611207, year = {2025}, author = {Wang, Q and Zhang, M and Meng, M and Luo, Z and Pan, Z and Deng, L and Qin, J and Guo, B and Zhu, D and Zhang, Y and Guo, H and Liang, Y and Su, Z}, title = {Integration bile acid metabolomics and gut microbiome to study the anti-liver fibrosis effects of total alkaloids of Corydalis saxicola Bunting.}, journal = {Chinese medicine}, volume = {20}, number = {1}, pages = {106}, pmid = {40611207}, issn = {1749-8546}, support = {82060763//National Natural Science Foundation of China/ ; GXFCDP-PS-2022//Guangxi First-class Discipline Project for Pharmaceutical Sciences/ ; GXQH202409//Guangxi Youth Qihuang Scholars Training Project/ ; }, abstract = {BACKGROUND: Bile acids and gut microbiota participate in the pathogenesis of liver fibrosis (LF). The total alkaloids of Corydalis saxicola Bunting (TACS) is a traditional Chinese medicine extract that has been used to treat LF, but the underlying mechanisms are not clear. This study performed integrated metabolomics and gut microbiome analysis to study the anti-LF mechanism of TACS using a rat model.

METHODS: Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to identify the chemical compounds in TACS. Biochemical and histopathological analysis were performed to determine the efficacy of TACS. Bile acid-targeted metabolomics was used to assess changes in the bile acid (BA) profiles in TACS-treated LF rats. 16S rRNA gene sequencing and metagenomics were used to assess changes in the gut microbiota of the TACS-treated LF rats. Antibiotic cocktail treatment and fecal microbiota transplantation (FMT) were used to determine the relationship between the gut microbiota and the anti-LF effects of TACS. Metagenomics was used to identify significantly enriched gut microbiota after TACS treatment and its correlation with the anti-LF effects was verified by in vivo experiments.

RESULTS: TACS treatment significantly reduced the levels of serum liver enzymes, fibrosis and pro-inflammatory cytokines in the liver. TACS significantly increased the levels of chenodeoxycholic acid (CDCA) and taurochenodeoxycholic acid (TCDCA) in the cecum and decreased the levels of cholic acid (CA) and deoxycholic acid (DCA) in the liver of the LF rats. TACS significantly increased the abundances of Lactobacillus and Akkermansia in the LF rats. Antibiotic cocktail treatment and FMT have shown that the effect of TACS cure liver fibrosis depends on the gut microbiota. The abundance of Lactobacillus reuteri was significantly increased by TACS. Administration of Lactobacillus reuteri via gavage ameliorated LF.

CONCLUSIONS: TACS exerted anti-LF effects in rats by modulating bile acid metabolism and gut microbiome.}, } @article {pmid40609706, year = {2025}, author = {Daneri, L and Urbano, A and Escudero-Sánchez, R and Halperin, AV and Moreno-Blanco, A and Corbacho, MD and Suárez-Carantoña, C and Rodríguez-Jiménez, C and Serrano-Villar, S and Campo, RD and Cobo, J}, title = {Lyophilised fecal microbiota transfer in capsules for recurrent Clostridioides difficile infection.}, journal = {International journal of antimicrobial agents}, volume = {66}, number = {4}, pages = {107561}, doi = {10.1016/j.ijantimicag.2025.107561}, pmid = {40609706}, issn = {1872-7913}, abstract = {BACKGROUND: Recent guidelines recommend fecal microbiota transplantation (FMT) for patients who experience multiple episodes of Clostridioides difficile infection (CDI). The availability of lyophilised and encapsulated FMT in recent years has greatly improved patient comfort and convenience. While the effectiveness of FMT in oral capsules seems comparable to that achieved through other routes, further experience is needed, particularly in Europe, where there is currently limited published experience. The objective of this study was to present our experience with this therapeutic modality.

METHODS: A retrospective cohort study on patients with recurrent CDI treated by lyophilised, encapsulated FMT. All patients were followed for a minimum of 12 weeks. The primary outcome was recurrence at three months.

RESULTS: A total of 36 patients received 38 FMTs. The median age of the cohort was 78.5 years, with a median of four previous episodes. At the three-month follow-up, 27 of the 36 patients (75.0%) were free of CDI. One patient exhibited recurrence before the six-month mark. Two of the ten patients with FMT failure were successfully rescued with a second FMT. Of the nine patients who underwent rescue attempts, seven did not experience recurrence, resulting in a cure rate of 91.7% for the 36 patients. We did not detect severe adverse effects related to the FMT.

CONCLUSION: We confirm an acceptable effectiveness of lyophilised capsulated oral FMT. Interestingly, most patients with FMT failure can be cured with a new treatment, which need not necessarily be a new FMT.}, } @article {pmid40607920, year = {2025}, author = {Pan, Y and Shen, L and Wu, Z and Wang, X and Liu, X and Zhang, Y and Luo, Q and Liu, S and Fang, X and Shu, Q and Chen, Q}, title = {Hepcidin sustains Kupffer cell immune defense against bloodstream bacterial infection via gut-derived metabolites in mice.}, journal = {The Journal of clinical investigation}, volume = {}, number = {}, pages = {}, doi = {10.1172/JCI189607}, pmid = {40607920}, issn = {1558-8238}, abstract = {Bloodstream bacterial infections cause one-third of deaths from bacterial infections, and eradication of circulating bacteria is essential to prevent disseminated infections. We here found that hepcidin, the master regulator of systemic iron homeostasis, affected Kupffer cell (KC) immune defense against bloodstream bacterial infections by modulating the gut commensal bacteria-derived tryptophan derivative indole-3-propionic acid (IPA). Hepcidin deficiency impaired bacterial capture by KCs and exacerbated systemic bacterial dissemination through morphological changes in KCs. Gut microbiota depletion and fecal microbiota transplantation revealed that the gut microbiota mediated the alteration of KCs volume. Mechanistically, hepcidin deficiency led to a decreased abundance of the IPA-producing commensal Lactobacillus intestinalis and a concomitant reduction in the gut-to-liver shuttling of its metabolite IPA. IPA supplementation or Lactobacillus intestinalis colonization restored the KC volume and hepatic immune defense against bloodstream bacterial infection in hepcidin-deficient mice. Moreover, hepcidin levels in patients with bacteremia were associated with days of antibiotic usage and hospitalization. Collectively, our findings described a previously unappreciated role of hepcidin in sustaining KC-mediated hepatic defense against bloodstream bacterial infections through the gut commensal Lactobacillus intestinalis and its tryptophan derivative IPA. More importantly, restoring the crosstalk between the gut microbiota and liver through IPA-inspired therapies may offer a promising strategy for enhancing the host defense against bloodstream bacterial infections in those with low hepcidin levels and a high risk for bacterial infections.}, } @article {pmid40607758, year = {2025}, author = {Wei, Y and Mao, J and Tang, W and Ma, Y and Li, J and Su, S and Ni, Z and Wu, J and Liu, D and Wang, H}, title = {Targeting Catenibacterium mitsuokai with icariin modulates gut microbiota and improves hepatic lipid metabolism in intrauterine growth restriction.}, journal = {The ISME journal}, volume = {19}, number = {1}, pages = {}, pmid = {40607758}, issn = {1751-7370}, support = {32372891//National Natural Science Foundation of China/ ; 2022YFD1300602//National Key R&D Program of China/ ; 2023C02026//Key R&D Projects of Zhejiang Province/ ; 2022C02015//Key R&D Projects of Zhejiang Province/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Fetal Growth Retardation/microbiology/metabolism ; Male ; *Lipid Metabolism/drug effects ; *Flavonoids/pharmacology/administration & dosage ; *Liver/metabolism/drug effects ; Swine ; Fecal Microbiota Transplantation ; Female ; Feces/microbiology ; }, abstract = {Male offspring with intrauterine growth restriction (IUGR) exhibit more pronounced hepatic lipid metabolism abnormalities than females, necessitating earlier intervention. Icariin (ICA) has been shown to effectively modulate hepatic lipid metabolism in male piglets with IUGR. However, the role of gut microbiota in this process remains to be elucidated. This study aimed to explore the influence of gut microbiota on ICA-induced enhancement of hepatic lipid metabolism. By examining changes in microbiota composition and hepatic lipid metabolism following ICA intervention, the study demonstrated an association between microbial alterations and hepatic lipid regulation through fecal microbiota transplantation. The impact of Catenibacterium on gut microbiota structure and hepatic lipid metabolism was assessed in vivo, and the direct effect of ICA on Catenibacterium was explored in vitro. Results revealed that ICA intervention modified fecal, ileal, and colonic microbiota in male piglets with IUGR, enhanced gut morphology and barrier function, and normalized the expression of hepatic peroxisome proliferator-activated receptor signaling pathway-related genes. Fecal microbiota transplantation from piglets with IUGR impaired intestinal barrier function and led to hepatic lipid deposition, whereas transplantation from ICA-treated donors showed no pathological changes, an outcome associated with reduced abundance of Catenibacterium. Mechanistically, ICA inhibits adenosine triphosphate synthesis to suppress Catenibacterium, remodels gut microbiota, reduces lipopolysaccharide production and translocation, and activates the hepatic PPARα/CD36 axis. In conclusion, ICA intervention alleviates hepatic lipid metabolic disorders in male offspring with IUGR by suppressing Catenibacterium, restoring gut microbial balance, and enhancing intestinal barrier integrity to limit lipopolysaccharide translocation.}, } @article {pmid40606926, year = {2025}, author = {Pandey, H and Goel, P and Srinivasan, VM and Tang, DWT and Wong, SH and Lal, D}, title = {Gut microbiota in non-alcoholic fatty liver disease: Pathophysiology, diagnosis, and therapeutics.}, journal = {World journal of hepatology}, volume = {17}, number = {6}, pages = {106849}, pmid = {40606926}, issn = {1948-5182}, abstract = {Non-alcoholic fatty liver disease (NAFLD), also referred to as metabolic-associated fatty liver disease, is among the most prevalent chronic liver conditions. In some cases, NAFLD may lead to liver inflammation and non-alcoholic steatohepatitis, which can eventually progress to liver cirrhosis and hepatocellular carcinoma. The pathophysiology of NAFLD is complex, involving both genetic and environmental factors. NAFLD is a multisystem disease linked to a higher likelihood of developing metabolic disorders such as type 2 diabetes, obesity, and cardiovascular and chronic kidney diseases. The gut-liver axis represents a key connection between the gut microbiota and the liver, and its disruption has been linked to NAFLD. Growing evidence underscores the significant role of gut microbiota in the onset and progression of NAFLD, with alterations in the gut microbiome and impaired gut barrier function. Studies have identified key microbiota signatures and metabolites linked to NAFLD, implicating oxidative stress, endotoxemia, and inflammatory pathways that further strengthen the connection between gut microbiota and NAFLD. Modulation of gut microbiota through diet and microbiota-centered therapies, such as next-generation probiotics and fecal microbiota transplantation, holds promise for treating NAFLD. In this review, we explore the key link between gut microbiota and the development and progression of NAFLD, as well as its potential applications in the diagnosis and treatment of the disease.}, } @article {pmid40606817, year = {2025}, author = {Li, X and Lei, Q and Xie, J and Li, F and Liu, J and Chen, Y and Mao, Q}, title = {Research on functional constipation with anxiety or depression: a bibliometric analysis.}, journal = {Frontiers in psychiatry}, volume = {16}, number = {}, pages = {1607297}, pmid = {40606817}, issn = {1664-0640}, abstract = {BACKGROUND: Although the phenomenon of functional constipation (FC) that accompanies anxiety or depression has been extensively investigated worldwide, no bibliometric studies are available in this regard. This study therefore aimed to analyze the current status and extent of research and areas of interest in the study of FC with anxiety or depression.

METHODS: Data from studies on FC with anxiety or depression, that were performed between 2003 and 2024, were retrieved from the Web of Science Core Collection database. Data regarding the annual number of publications, authors, countries, and references were assessed using CiteSpace v6.3.R1 (64-bit) and Microsoft Excel, and those pertaining to keywords and cited authors were evaluated using VOSviewer 1.6.20. The co-occurrence and clustering functions were then used to generate visual knowledge maps.

RESULTS: The overall annual publication volume demonstrated an upward trend between 2003 and 2024; this was indicative of promising research prospects. The 427 publications identified included 6 types of papers, among which original research articles represented the highest proportion (357 [83.61%] articles published across 200 journals). Neurogastroenterology and Motility had the highest publication volume (30 articles, 7.02%). The United States of America had published most of the papers (135 articles, 31.61%) on the topic. Harvard University was the research institution with the most published papers (21 articles, 4.92%), and Michel Bouchoucha had authored the highest number of articles (13 articles, 3.04%).

CONCLUSION: Future studies in the field of basic medicine need to determine the etiology and pathogenesis of FC with anxiety or depression; in particular, they need to evaluate the role of opioid drugs as a key etiological factor. The role played by the brain-gut axis also warrants investigation. From the clinical perspective, studies need to focus on evidence-based medicine; particular emphasis needs to be placed on randomized double-blind controlled trials with stringent quality control, high-quality meta-analyses, and evaluation of questionnaires and scales. Treatment techniques need to be explored in greater detail; in this context, it is recommended that fecal microbiota transplantation and biofeedback therapy are adopted in the clinic. Furthermore, Patients with FC, especially those with a history of anxiety or depression, tend to have overlapping dyspepsia symptoms.}, } @article {pmid40606527, year = {2025}, author = {Paaske, SE and Baunwall, SMD and Rubak, T and Rågård, N and Kelsen, J and Hansen, MM and Lødrup, AB and Erikstrup, LT and Mikkelsen, S and Erikstrup, C and Dahlerup, JF and Hvas, CL}, title = {Clinical management of Clostridioides difficile infection with faecal microbiota transplantation: a real-world cohort study.}, journal = {EClinicalMedicine}, volume = {85}, number = {}, pages = {103302}, pmid = {40606527}, issn = {2589-5370}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) causes high morbidity and mortality. Faecal microbiota transplantation (FMT) is well-established for CDI, but therapeutic strategies may be optimised. We aimed to evaluate clinical outcomes by analysing therapeutic strategies in a real-life cohort of patients with CDI treated with FMT.

METHODS: We conducted a multi-site cohort study, including 1170 patients with CDI, treated with FMT through capsules, colonoscopy, or nasojejunal tube between May 2016 and December 2023. The primary outcome was cure of C. difficile-associated diarrhea (CDAD) eight weeks after treatment. We investigated antibiotic pretreatment type and length, FMT dosing and administration, and post-FMT prophylactic vancomycin during non-CDI antibiotic use, applying multivariable mixed-effect regression analysis including the patient as a random effect. The study was preregistered at ClinicalTrials.gov, NCT03712722.

FINDINGS: The 1170 patients received 1643 FMT treatments. Patients' median age was 71 years (interquartile range 56-80 years). Following their first FMT treatment, 699 patients (60% (95% confidence interval: 57-63%)) were cured of CDAD. After repeated FMT treatments, 944 patients (81% (78-83%)) were cured. Prolonged antibiotic pretreatment was associated with higher cure rates (65% (59-70%), odds ratio (OR): 1.22 (1.10-1.36), p < 0.001). FMT administration through oral, multi-dose capsules (69% (63-74%), OR: 1.19 (1.11-1.27), p < 0.001) or colonoscopy (69% (61-76%), OR: 1.14 (1.04-1.24), p = 0.01) resulted in the highest cure rates. Neither antibiotic pretreatment type nor prophylactic vancomycin during non-CDI antibiotics affected cure rates. In patients for whom FMT was initially unsuccessful, repeated FMT was more effective than antibiotic treatment alone.

INTERPRETATION: CDI outcomes could be improved by optimising antibiotic pretreatment duration, selecting appropriate FMT delivery methods, and repeating FMT.

FUNDING: Innovation Fund Denmark (j.no. 8056-00006B).}, } @article {pmid40605266, year = {2025}, author = {Herman, C and Barker, BM and Bartelli, TF and Chandra, V and Krajmalnik-Brown, R and Jewell, M and Li, L and Liao, C and McAllister, F and Nirmalkar, K and Xavier, JB and Caporaso, JG}, title = {A review of engraftment assessments following fecal microbiota transplant.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2525478}, pmid = {40605266}, issn = {1949-0984}, support = {U24 CA248454/CA/NCI NIH HHS/United States ; }, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Gastrointestinal Microbiome ; *Clostridium Infections/therapy/microbiology ; Clostridioides difficile/physiology ; Animals ; Feces/microbiology ; Bacteria/classification/genetics/isolation & purification ; }, abstract = {Fecal Microbiota Transplant (FMT) is a treatment for recurrent Clostridium difficile infections and is being explored for other clinical applications, from alleviating digestive and neurological disorders, to restoring microbiomes impacted by cancer treatment. Quantifying the extent of engraftment following an FMT is important in understanding a recipient's response to treatment. Engraftment and clinical response need to be investigated independently to evaluate an FMT's role (or lack thereof) in achieving a clinical response. Standardized bioinformatics methodologies for quantifying engraftment extent would not only improve assessment and understanding of FMT outcomes, but also facilitate comparison of FMT results and protocols across studies. Here we review FMT studies, integrating three concepts from microbial ecology as framework to discuss how these studies approached assessing engraftment extent: 1) Community Coalescence investigates microbiome shifts following FMT engraftment, 2) Indicator Features tracks specific microbiome features as a signal of engraftment, and 3) Resilience examines how resistant post-FMT recipients' microbiomes are to reverting back to baseline. These concepts explore subtly different questions about the microbiome following FMT. Taken together, they provide holistic insight into how an FMT alters a recipient's microbiome composition and provide a clear framework for quantifying and communicating about microbiome engraftment.}, } @article {pmid40604869, year = {2025}, author = {Rychlik, A and Kaczmar, E and Mikulska, I and Makowska, K}, title = {Assessment of the effect of prokinetic drugs on transit time and gastrointestinal cleanliness in capsule endoscopy.}, journal = {BMC veterinary research}, volume = {21}, number = {1}, pages = {417}, pmid = {40604869}, issn = {1746-6148}, mesh = {Animals ; *Metoclopramide/pharmacology ; *Capsule Endoscopy/veterinary/methods ; Dogs ; *Gastrointestinal Transit/drug effects ; *Gastrointestinal Agents/pharmacology ; *Cisapride/pharmacology ; Male ; Female ; *Gastrointestinal Tract/drug effects ; }, abstract = {BACKGROUND: Endoscopic examinations are increasingly used in veterinary medicine. Examination using flexible endoscopes is limited to the anterior gastrointestinal tract (panendoscopy) and colon (colonoscopy), while a significant part of the small intestine remains unexamined. Capsular endoscopy is increasingly used, allowing macroscopic assessment of the entire digestive tract. The current study assessed the effect of prokinetic drugs on transit time and cleanliness of the tested part of the digestive tract in capsule endoscopy.

METHODS: The study aimed to evaluate the usefulness of two prokinetic drugs (metoclopramide and cisapride) in capsule endoscopy studies while assessing the quality of the macroscopic image. Each animal included into the study had endoscopic examination three times - without the administration of prokinetic drugs, after receiving metoclopramide and after receiving cisapride.

RESULTS: The total passage time of the capsule through the gastrointestinal tract was the longest in the group receiving metoclopramide (691.33 min) and the shortest in the group receiving cisapride (584.17 min). The best quality images were observed in the control group.

CONCLUSION: This research has confirmed the hypothesis that administration of prokinetic drugs increases the probability of recording the entire macroscopic image of the gastrointestinal tract during endoscopy in dogs. A negative feature of their administration is significantly reduced recording quality because of the level of cleanliness of the tested gastrointestinal section.}, } @article {pmid40602277, year = {2025}, author = {Wu, H and Li, YL and Wang, Y and Wang, YG and Hong, JH and Pang, MM and Liu, PM and Yang, JJ}, title = {Anemoside B4 alleviates ulcerative colitis by attenuating intestinal oxidative stress and NLRP3 inflammasome via activating aryl hydrocarbon receptor through remodeling the gut microbiome and metabolites.}, journal = {Redox biology}, volume = {85}, number = {}, pages = {103746}, pmid = {40602277}, issn = {2213-2317}, abstract = {Ulcerative colitis (UC) is a chronic, non-specific inflammatory disease of the intestines with a significant increase in global incidence in recent years. Oxidative stress and inflammation are two hallmarks of UC pathogenesis. Anemoside B4 (AB4), a pentacyclic triterpenoid saponin, exhibits significant antioxidant and anti-inflammatory properties and shows potential for preventing UC. Here, an animal model induced by dextran sodium sulfate (DSS) was used to investigate the effect of AB4 on UC. The results demonstrated that AB4 significantly reduces intestinal oxidative stress and inflammation in UC mice, while also protecting intestinal barrier function. Furthermore, AB4 helps restore intestinal microbial balance primarily by modulating the abundance of Lactobacillus, which enhances the metabolism of short-chain fatty acids and upregulates the production of butyric acid (BA). Pseudogerm-free mice and fecal microbiota transplantation (FMT) demonstrated that AB4 significantly mitigated UC in a gut microbe-dependent manner. Both AB4 and BA markedly activate the aromatic hydrocarbon receptor (AhR). The intestinal organoid results suggest BA may activate the AhR to inhibit ROS production and activation of NLRP3 inflammasome, thereby protecting intestinal integrity. Administration of AhR antagonists abolished the protective effects, thus confirming the involvement of AhR in the underlying mechanism. Overall, these results indicate that AB4 is an effective agent against UC mainly by activating the AhR through gut microbial short-chain fatty acid metabolites to inhibit intestinal oxidative stress and inflammation.}, } @article {pmid40601184, year = {2025}, author = {Rico-Caballero, V and Romero-Rivera, M and Moreno-Blanco, A and Aira, A and Casals-Pascual, C and Rodríguez-Jiménez, C and Quereda, C and Soriano, A and Del Campo, R}, title = {Fecal microbiota transplant as treatment for recurrent urinary tract infections: a proof-of-concept study.}, journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {}, number = {}, pages = {}, pmid = {40601184}, issn = {1435-4373}, } @article {pmid40600295, year = {2025}, author = {Shao, H and Min, F and Bai, T and Liu, Y and Zheng, S and Wu, Y and Di, C and Lin, M and Li, X and Chen, H}, title = {Bifidobacterium breve M-16V alleviates cow's milk allergy by regulating the gut microbiota and metabolites in human microbiota-associated mice.}, journal = {Food & function}, volume = {16}, number = {14}, pages = {5885-5899}, doi = {10.1039/d5fo02012c}, pmid = {40600295}, issn = {2042-650X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Milk Hypersensitivity/microbiology/therapy/immunology/metabolism ; *Bifidobacterium breve/physiology ; *Probiotics/administration & dosage/pharmacology ; Humans ; Female ; Male ; Disease Models, Animal ; Feces/microbiology ; }, abstract = {Cow's milk allergy (CMA) is one of the most common food allergies, especially in infants and young children. Growing evidence from animal studies has shown that some specific probiotics can alleviate CMA, but clinical evidence remains insufficient due to certain limitations. In the present study, we transplanted fecal material from three CMA children into antibiotic-pretreated mice (hum-CMA mice) to mimic the intestinal microecology of allergic individuals, followed by allergen sensitization and Bifidobacterium breve (B. breve) M-16V intervention. Our results showed that B. breve M-16V effectively ameliorated CMA symptoms and allergy-related indicators in hum-CMA mice. Moreover, B. breve M-16V differentially affected the composition of intestinal microbes, but the abundance of beneficial bacteria, such as short-chain fatty acid-producing bacteria, was consistently elevated in all three groups of hum-CMA mice. Subsequent untargeted metabolomics analyses revealed that B. breve M-16V improved the pattern of serum metabolites, and these differential metabolites were mainly involved in glutathione metabolism, glycerophospholipid metabolism, and tryptophan metabolism. All the findings indicate that B. breve M-16V can alleviate the anaphylactic reaction in hum-CMA mice by regulating the intestinal microbiota and metabolites, providing a valuable scientific basis for the clinical application of probiotics in food allergy.}, } @article {pmid40600174, year = {2025}, author = {Ebrahimi, R and Shahrokhi Nejad, S and Fekri, M and Nejadghaderi, SA}, title = {Advancing prostate cancer treatment: the role of fecal microbiota transplantation as an adjuvant therapy.}, journal = {Current research in microbial sciences}, volume = {9}, number = {}, pages = {100420}, pmid = {40600174}, issn = {2666-5174}, abstract = {Prostate cancer (PCa) is a major cause of cancer-related deaths worldwide. While current treatments such as surveillance, surgery, and radiation are effective, they have their limitations. These can include patient incompliance due to side effects or resistance to hormonal changes, highlighting the need for alternative approaches. Human microbiota, a complex and dynamic host, plays a significant role in the homeostasis and is associated with several diseases or cancers in cases of dysregulation and dysbiosis. Research on fecal microbiota profiling and its association with certain cancers has opened new possibilities for preventing and managing tumor progression. One such possibility is fecal microbial transplantation (FMT). Studies show that different composition of urinary microbiota is found in various urinary tract diseases. Gut microbiota can regulate immune response against tumors; therefore, FMT may help modulate gut microbiota in a way that potentially enhances responses to immune checkpoint inhibitors, as suggested by emerging evidence in other cancers, though this needs further validation in PCa. Nevertheless, long-term complications and the safety of FMT are still questioned. We reviewed the roles of gut microbiota in PCa and suggested FMT as a potential tool in the treatment of PCa, which needs further investigations.}, } @article {pmid40599506, year = {2025}, author = {Alnahwi, HH and AlGhawi, RJ and Alsahaf, HAA and Ahmed, E}, title = {Recurrent Clostridioides difficile Infection (CDI) in Patients Treated With Vancomycin at Johns Hopkins Aramco Healthcare (JHAH), Dhahran, Saudi Arabia.}, journal = {Cureus}, volume = {17}, number = {5}, pages = {e85116}, pmid = {40599506}, issn = {2168-8184}, abstract = {Introduction Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated diarrhea with a significant risk of recurrence, posing challenges for patient management and infection control. Identifying risk factors for recurrence is essential to improve outcomes and prevent relapses. Methods This retrospective cohort study included 860 adult patients (≥18 years) treated with vancomycin for CDI at Johns Hopkins Aramco Healthcare (JHAH) in Dhahran, Saudi Arabia, between January 2015 and December 2020. Patients with confirmed CDI based on stool polymerase chain reaction (PCR) or toxin assays, complete medical records, and adequate follow-up data were included. The study excluded those not treated with vancomycin, under 18 years of age, with incomplete records, those who received fecal microbiota transplantation or experimental treatments, and those lacking follow-up data. Data on demographics, comorbidities, hospitalization, medication use, and recurrence were analyzed using univariate and multivariate logistic regression models. Results Univariate analysis showed that age 40-65 years (OR = 1.53; 95% CI: 1.024-2.285; p = 0.038), age >65 years (OR = 1.894; 95% CI: 1.282-2.799; p = 0.001), cirrhosis (OR = 9.104; 95% CI: 1.233-67.192; p = 0.03), hospitalization (OR = 1.974; 95% CI: 1.417-2.749; p < 0.0001), and type 2 diabetes mellitus (OR = 1.65; 95% CI: 1.106-2.462; p = 0.014) were significantly associated with CDI recurrence. After adjusting for confounders, only hospitalization remained a statistically significant independent predictor (OR = 1.597; 95% CI: 1.098-2.325; p = 0.014). Conclusion Hospitalization was identified as the most significant independent risk factor for CDI recurrence. These findings highlight the need for enhanced infection control practices and close monitoring of hospitalized patients with CDI. Future prospective and multicenter studies are recommended to validate these results and explore additional modifiable risk factors to reduce recurrence rates.}, } @article {pmid40599494, year = {2025}, author = {Boton, N and Patel, PK and Beekmann, SE and Polgreen, PM and Buckel, WR and Mahoney, MV and Mehrotra, P and Lee, MSL}, title = {Clinician Management Preferences for Clostridioides difficile Infection in Adults: A 2024 Emerging Infections Network Survey.}, journal = {Open forum infectious diseases}, volume = {12}, number = {7}, pages = {ofaf335}, pmid = {40599494}, issn = {2328-8957}, abstract = {BACKGROUND: The 2021 Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) guidelines for Clostridioides difficile infection (CDI) introduced new recommendations for managing initial and recurrent CDI. Since then, new microbiome-based therapies for preventing recurrent CDI have become available. We surveyed infectious diseases (ID) clinicians to understand their experiences, practices, and challenges in CDI management.

METHODS: An electronic survey was distributed to members of the IDSA Emerging Infections Network in May 2024, targeting ID physicians and healthcare professionals in the United States who manage adult CDI. The survey assessed treatment preferences, clinical practices, and barriers to accessing and prescribing CDI therapies.

RESULTS: Of the 500 respondents who reported treating CDI in the past year, 83% (417/500) indicated that vancomycin was their most frequently prescribed agent for initial, nonfulminant CDI. Additionally, 72% (357/498) reported that their institutional guidelines recommended vancomycin as the first-line agent. The most common barrier to fidaxomicin use was challenges with outpatient insurance coverage (82% [408/496]). Bezlotoxumab was available to 74% (370/500) of respondents, though 33% (165/497) indicated they do not use bezlotoxumab routinely. Most clinicians (87% [437/500]) had previously recommended fecal microbiota transplantation (FMT) for recurrent CDI, though only 48% (239/500) had current access to FMT using donor stool. Fecal microbiota live-jslm was available to 36% (179/500), and fecal microbiota spores live-brpk was available to 30% (150/500).

CONCLUSIONS: Significant barriers, including high costs, insurance challenges, and limited availability of CDI therapies, impact clinical decision-making and adherence to guideline recommendations.}, } @article {pmid40597484, year = {2025}, author = {Zhang, C and Zhang, X and Qiu, H and Song, Q and Wang, Y and Zhang, C and Zhang, Q}, title = {Fermented Gastrodia elata Bl. Intervenes gut microbiota and amino acid metabolism in zebrafish to promote 5-HT homeostasis against sleep disturbances.}, journal = {Food research international (Ottawa, Ont.)}, volume = {217}, number = {}, pages = {116757}, doi = {10.1016/j.foodres.2025.116757}, pmid = {40597484}, issn = {1873-7145}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Zebrafish ; *Amino Acids/metabolism ; *Serotonin/metabolism ; *Gastrodia/chemistry ; Homeostasis/drug effects ; *Fermented Foods ; Fermentation ; *Sleep Wake Disorders/prevention & control ; Sleep Initiation and Maintenance Disorders/chemically induced ; Fecal Microbiota Transplantation ; }, abstract = {Sleep disturbances (SD) is a prevalent health issue in modern society. Consequences involve negative impacts on numerous aspects of physical, psychological, and daily life. This study aimed to elucidate the protective effects of Fermented Gastrodia elata Bl. (FGE) against pentylenetetrazole (PTZ)-induced SD and uncover the underlying molecular mechanisms. Our findings revealed that FGE significantly attenuated PTZ-induced insomnia behavior, circadian rhythm disturbances, and compromised gut barrier functions. Mechanistically, gut microbiota and 5-HT within the microbiota-gut-brain axis are the key regulators in short-term SD. Fecal microbiota transplantation (FMT) experiment identified gut microbiota as a key mediator and potential therapeutic target for FGE. The comprehensive analysis of 16S rRNA sequencing and metabolomic analysis showed that amino acid metabolism-related pathways as key factors of FGE intervention. Notably, omics joint analysis demonstrated a strong association between the variations of the intestinal microbiota among different groups and the notable alterations in the brain metabolomic landscape. Meanwhile, the remodeling of intestinal microbial structure and metabolites drove the homeostasis of 5-HT levels in different tissues. Importantly, exogenous keystone bacteria supplementation to sleep-deprived zebrafish restored insomnia responses and amino acid metabolism. Targeted amino acid metabolism further confirmed amino acid metabolism as the central mechanistic pathway through which FGE exerts its protective function. Collectively, Collectively, these findings suggested that FGE showed a significant preventative action on short-term SD by intervening gut microbiota and amino acid metabolism in zebrafish to promote 5-HT homeostasis, which offers perspectives into new preventive strategies of traditional Chinese medicine dietary supplements for transient insomnia.}, } @article {pmid40596796, year = {2025}, author = {Liu, K and Wang, Y and Zhou, J and van der Meij, JJ and van der Laan, LJW and Li, P and Pan, Q}, title = {Decoding the role of the intestinal epithelium in hepatitis E virus infection using a human organoid prototype of "gut-liver" axis.}, journal = {Virology}, volume = {610}, number = {}, pages = {110615}, doi = {10.1016/j.virol.2025.110615}, pmid = {40596796}, issn = {1096-0341}, mesh = {Humans ; *Organoids/virology ; *Hepatitis E virus/physiology ; Virus Replication ; *Liver/virology ; *Intestinal Mucosa/virology/metabolism ; *Hepatitis E/virology/transmission ; Bile Acids and Salts/metabolism ; Host-Pathogen Interactions ; Coculture Techniques ; }, abstract = {Hepatitis E virus (HEV), a leading cause of acute viral hepatitis worldwide, is primarily transmitted via the fecal-oral route. A clinical study has reported that the intestine of a chronic hepatitis E patient is positive for HEV. However, whether the intestinal epithelium acts as a barrier for HEV transmission or whether productive enteric infection enhances transfer of the virus to the liver remains unclear. The advent of organoid technology provides a valuable platform for advancing the study of HEV-host interactions in a more physiologically relevant context. In this study, we demonstrate that primary human intestinal organoids (HIOs) efficiently support HEV replication. The infection was sustained in differentiated HIOs with specific phenotypes of intestinal cell types, namely enterocyte, goblet cell, and enteroendocrine cell lineages. Next, we constructed a gut-liver axis model using a transwell system by co-culturing HIOs with human liver-derived organoids. Importantly, infectious viral particles produced in HIOs were capable of transmission to human liver-derived organoids in this model. Bile acids are essential mediators of gut-liver crosstalk. We found that supplementing human bile or the primary bile acid chenodeoxycholic acid inhibited HEV replication in organoids via the farnesoid X receptor (FXR) signaling pathway. The effects of the secondary bile acid, ursodeoxycholic acid, were opposite and promoted viral replication. In conclusion, this model provides a novel approach to study the gut-liver axis in HEV transmission and the impact of bile acids in modulating HEV infection.}, } @article {pmid40596758, year = {2025}, author = {Wang, J and Tan, H and Ye, Z and Weng, S and Shi, Y and Xu, J and Liu, H and Li, J and Huang, L and Zhai, L and Luo, H and Lin, Z and Zhong, C and Tang, J and Wang, Z and Zhang, H and Zhang, B and Huang, C}, title = {Gut microbial Nordihydroguaiaretic acid suppresses macrophage pyroptosis to regulate epithelial homeostasis and inflammation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2518338}, pmid = {40596758}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; Fecal Microbiota Transplantation ; *Colitis/microbiology/chemically induced ; Homeostasis/drug effects ; *Macrophages/drug effects ; *Masoprocol/pharmacology/metabolism ; *Pyroptosis/drug effects ; Mice, Inbred C57BL ; Dysbiosis/microbiology ; Male ; Dextran Sulfate ; Disease Models, Animal ; Intestinal Mucosa/drug effects ; Aging ; Inflammatory Bowel Diseases/microbiology ; Bacteria/classification/genetics/isolation & purification/metabolism ; Humans ; }, abstract = {BACKGROUND: Aging is associated with increased severity of inflammatory bowel disease (IBD). Gut senescence and altered environmental factors contribute to changes in the intestinal metabolome, particularly in frail older individuals. However, the role of age-associated dysbiosis, characterized by a decline in beneficial gut microbiota and their metabolites, in exacerbating IBD remains unclear.

METHODS: To investigate the impact of aging-associated dysbiosis on colitis development, we employed fecal microbiota transplantation (FMT) in wild-type and IL-10-deficient mice. Aged mice were treated with gut microbiota from either young or aged mice and then subjected to dextran sulfate sodium (DSS) to induce experimental colitis. 16S rDNA sequencing and metabolomics were used to analyze microbial and metabolite profiles. Single-cell RNA sequencing (scRNA-seq) was performed to characterize lamina propria CD45[+] immune cell composition.

RESULTS: Aged mice receiving microbiota from young mice exhibited less severe colitis than those receiving microbiota from aged mice, as evidenced by reduced disease activity, weight loss, and colonic shortening. Besides, aged mice displayed a significant decrease in the Lactobacillus population, accompanied by a reduction in Nordihydroguaiaretic acid (NDGA) levels. Decreased fecal NDGA levels were also observed in both IBD patients and elderly individuals. Administration of NDGA alleviated experimental colitis by downregulating the GSDMD/NR4A1/NLRP3 axis-mediated macrophage pyroptosis. Deletion of GSDMD in macrophages significantly diminished the protective effect of NDGA on colitis.

CONCLUSIONS: Our findings demonstrate that aging is associated with dysbiosis and reduced NDGA production, which increases susceptibility to intestinal inflammation. Gut microbial NDGA exhibits potential anti-inflammatory activity in colitis, suggesting a promising therapeutic target for aged-related IBD.}, } @article {pmid40593111, year = {2025}, author = {Zhou, X and Wei, C and Liu, J and Xia, X and Wang, L and Li, X}, title = {Cold environment regulates ischemic stroke through modulation of gut microbiota.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {21558}, pmid = {40593111}, issn = {2045-2322}, support = {42275197//National Natural Science Foundation of China/ ; TJYXZDXK-065B//Tianjin Key Medical Discipline (Specialty) Construction Project/ ; TJWJ2023XK007//the Key Projects of Tianjin Municipal Health Commission/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; *Cold Temperature/adverse effects ; Animals ; Fecal Microbiota Transplantation ; Mice ; Male ; Mice, Inbred C57BL ; Humans ; Dysbiosis/microbiology ; *Ischemic Stroke/microbiology/etiology ; Female ; Middle Aged ; Platelet Aggregation ; Aged ; Methylamines ; }, abstract = {Many diseases are influenced by environmental temperature, and recent studies have confirmed that cold exposure increases the risk of conditions such as ischemic stroke (IS). However, direct evidence supporting this hypothesis is lacking, and the molecular mechanisms through which cold exposure affects IS remain unclear. In this study, we found that chronic cold exposure increased platelet aggregation and the levels of certain inflammatory factors in high-risk stroke patients (HR), thereby increasing the risk of IS. Furthermore, before and after a cold wave, we observed gut microbiota dysbiosis in the HR group, including reduced relative abundance differences in Lachnospiraceae and Ruminococcaceae. The relative abundances of the Prevotella_9 and Catenibacterium genera increased, whereas that of Anaerostipes decreased. Notably, the results of fecal microbiota transplantation (FMT) indicated that cold-adapted microbiota transplantation partially replicated the microbiota characteristics of each donor subject and replicated the effects of cold exposure in C57BL/6J mice. Cold exposure impaired intestinal barrier function and interfered with microbial functions, such as increased lipid metabolism and LPS production, particularly by increasing the levels of TMAO derived from the gut microbiota. Our findings identify the significant role of abnormal gut microbiota-derived metabolites in cold exposure-related IS and highlight the potential opportunity to prevent or treat cold-related IS through the modulation of the gut microbiota.}, } @article {pmid40593020, year = {2025}, author = {Yue, Y and Yao, B and Liao, F and He, Z and Sangsawad, P and Yang, S}, title = {Fecal microbiota transplantation improves Sansui duck growth performance by balancing the cecal microbiome.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {22403}, pmid = {40593020}, issn = {2045-2322}, support = {31960682//The National Nature Science Foundation of China/ ; 31960682//The National Nature Science Foundation of China/ ; 31960682//The National Nature Science Foundation of China/ ; 31960682//The National Nature Science Foundation of China/ ; 31960682//The National Nature Science Foundation of China/ ; }, mesh = {Animals ; *Ducks/growth & development/microbiology ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; *Cecum/microbiology ; Feces/microbiology ; }, abstract = {Improving growth performance is vital in poultry production. Although several studies have established associations between gut microbiota and growth, the direct impacts remain unclear. A total of 120 1-day-old Sansui ducks were randomly assigned to the FMT and CON groups. From the 1st day, ducks in the FMT group were orally administrated with 0.5 mL fecal microbiota suspension for three consecutive days, while sterile PBS solution was used as a substitute in the CON group. The results revealed that FMT improved average daily gain (ADG) (P < 0.001) and body weight (BW) (P < 0.001), with a tendency for a better feed conversion rate (FCR) (P = 0.062). LEfSe analysis indicated a significant increase in the abundance of the Lactobacillus (P < 0.001), Bifidobacterium (P = 0.006), Megamonas (P = 0.008), and Subdoligranulum (P = 0.005) in the FMT group. Similarly, the phyla Firmicutes/Bacteroidetes ratio was higher in the FMT group compared to the CON group. Additionally, the ACE, Chao, and Shannon indices were also significantly higher in the FMT group (P < 0.001). To sum up, FMT enhanced growth performance, which could be associated with reducing proinflammatory pathogen colonization in the duck cecum. This modulating effect likely results from increased microbial diversity and the enrichment of beneficial bacteria.}, } @article {pmid40592776, year = {2025}, author = {Zhang, X and Ishikawa, D and Nagahara, A}, title = {Fecal Microbiota Transplantation for Immune Regulation: Improving Ulcerative Colitis and Enhancing Cancer Immunotherapy.}, journal = {International immunology}, volume = {}, number = {}, pages = {}, doi = {10.1093/intimm/dxaf038}, pmid = {40592776}, issn = {1460-2377}, abstract = {The gut microbiota plays an integral role in maintaining health and regulating various host functions, including immune responses. Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach to restore gut microbial balance. Although widely recognized for its efficacy in treating ulcerative colitis (UC), FMT is now being investigated as an adjuvant therapy to enhance the efficacy of immune checkpoint inhibitors (ICIs) in cancer treatment. This review summarizes the clinical applications of FMT in UC treatment and its potential role in cancer immunotherapy. FMT exhibits varying degrees of efficacy in the treatment of UC, with differences in outcomes attributed to variations in administration methods and donor selection. In cancer therapy, FMT has demonstrated the potential to improve ICI responses, particularly in patients with melanoma. However, its effects on other cancers remain unclear. Although FMT holds promise for UC and cancer immunotherapy, challenges such as inconsistent clinical outcomes and methodological variations persist. Standardized protocols and mechanistic studies are crucial to optimize FMT-based therapeutic strategies, and further research is required to establish its efficacy under diverse clinical conditions.}, } @article {pmid40592615, year = {2025}, author = {Sasaki, K and Takeshima, Y and Fujino, A}, title = {Reproducing in vitro artificial gut microbiota using glycerol stocks of fecal cultures combined with different prebiotic additives.}, journal = {Journal of bioscience and bioengineering}, volume = {140}, number = {3}, pages = {154-161}, doi = {10.1016/j.jbiosc.2025.06.002}, pmid = {40592615}, issn = {1347-4421}, mesh = {*Glycerol/metabolism ; *Gastrointestinal Microbiome/drug effects/genetics ; *Feces/microbiology ; Humans ; *Prebiotics ; Fermentation ; Bacteria/genetics/classification/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Oligosaccharides/metabolism ; Galactans/metabolism ; Mannans/metabolism ; Plant Gums ; Pectins/metabolism ; }, abstract = {Artificial human microbiota can be produced in gut simulators from cryopreserved stocks. They are used for in vitro fermentation models and as alternative material for fecal microbiota transplantation therapy. However, current methods have limited information on microbial structure at the genus level and present challenges during cryopreservation. In this study, we used an edible glycerol stock of fecal batch culture instead of fresh feces to create artificial gut microbiota. Three glycerol stocks, generated through in vitro fecal fermentation with different prebiotic additives (such as fructooligosaccharide, xylan, pectin, and guar gum), were combined. Profiling via 16S rRNA gene amplicon sequencing revealed that the artificial gut microbiota derived from the combined glycerol stocks showed more amplicon sequence variants than those from a single glycerol stock. In the artificial microbiota, relative abundance values of common genera such as Bifidobacterium, Bacteroides, Prevotella, Faecalibacterium, and Escherichia were more than 10 % of those found in the original feces. Other commensal genera such as Collinsella, Anaerobutyricum hallii (formerly Eubacterium hallii) group, Anaerostipes, Blautia, Dorea, Lachnospiraceae UCG-004, and Oscillospiraceae UCG-003 were similarly maintained. Our data indicated that combining glycerol stocks of fecal cultures with different additives in a batch-type gut simulator is a useful option for producing artificial gut microbiota, the taxonomic compositions of which are comparable to those of the original feces.}, } @article {pmid40592538, year = {2025}, author = {Cymbal, M and Chatterjee, A and Baggott, B}, title = {Fecal microbiota transplantation: Current evidence and future directions.}, journal = {Cleveland Clinic journal of medicine}, volume = {92}, number = {7}, pages = {421-428}, doi = {10.3949/ccjm.92a.24107}, pmid = {40592538}, issn = {1939-2869}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/trends ; *Clostridium Infections/therapy ; *Gastrointestinal Microbiome ; Clostridioides difficile ; Dysbiosis/therapy ; }, abstract = {As we advance our understanding of the gut microbiota, the implications of dysbiosis are becoming increasingly apparent. Fecal microbiota transplantation (FMT), a well-established procedure, is recognized for effectively treating recurrent Clostridioides difficile infection, prompting further investigation into its other possible clinical applications. Donor selection and screening are essential to ensure safety and efficacy. Product development and standardization, such as the US Food and Drug Administration-approved live biotherapeutic products Rebyota and Vowst, are helping efforts to evaluate FMT for other gastrointestinal and extraintestinal diseases. However, additional clinical trials are needed to support its use beyond recurrent C difficile infection.}, } @article {pmid40591032, year = {2025}, author = {Abebaw, D and Akelew, Y and Adugna, A and Tegegne, BA and Teffera, ZH and Belayneh, M and Fenta, A and Selabat, B and Kindie, Y and Baylie, T and Mekuriaw, MG and Jemal, M and Atnaf, A}, title = {Immunomodulatory properties of the gut microbiome: diagnostic and therapeutic potential for rheumatoid arthritis.}, journal = {Clinical and experimental medicine}, volume = {25}, number = {1}, pages = {226}, pmid = {40591032}, issn = {1591-9528}, mesh = {Humans ; *Arthritis, Rheumatoid/therapy/diagnosis/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Dysbiosis/immunology ; Probiotics/therapeutic use ; *Immunomodulation ; Fecal Microbiota Transplantation ; Biomarkers ; Animals ; }, abstract = {Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent joint inflammation, synovial hyperplasia, and progressive joint destruction. Despite advancements in biologic disease-modifying antirheumatic drugs (bDMARDs) and TNF-α blockers, many RA patients still require more effective treatment options. Although genetic and environmental factors play a role in RA development, recent studies have emphasized the influence of the gut microbiota on disease onset and progression. Dysbiosis, or an imbalance in the gut microbial composition, has been linked to immune dysregulation, increased intestinal permeability, and systemic inflammation, all contributing to RA development. Research has revealed changes in the gut microbiome of RA patients, including an increased prevalence of Prevotella copri and a decreased presence of beneficial microbes such as Bifidobacterium, Bacteroides, and Lactobacillus. RA patients exhibit altered metabolite profiles, with reduced levels of short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, which are linked to immune regulation and intestinal barrier function. Specific metabolites, such as L-arginine, phosphorylcholine, and arachidonic acid, have potential as RA biomarkers, with predictive value for diagnosis. Therapeutic approaches focusing on the microbiome, including probiotics, fecal microbiota transplantation, and traditional medicines, show promise in alleviating RA symptoms and regulating immune function. This review provides an updated overview of the immunomodulatory effects of the gut microbiome and explores its potential applications in the diagnosis and treatment of RA.}, } @article {pmid40589476, year = {2025}, author = {Olajide, TS and Ijomone, OM}, title = {Targeting gut microbiota as a therapeutic approach for neurodegenerative diseases.}, journal = {Neuroprotection}, volume = {3}, number = {2}, pages = {120-130}, pmid = {40589476}, issn = {2770-730X}, support = {K43 TW011920/TW/FIC NIH HHS/United States ; }, abstract = {Recent evidence suggests a more important role of the gut microbiota in neurodegenerative diseases (NDDs) given its relationship through the microbiota-gut-brain as an active communication system aiding in maintaining homeostasis between the brain and the gut. This review focuses on how modulation of gut microbiota can serves as a therapeutic strategy for NDDs, emphasizing the neuroprotective effects of probiotics. Probiotics are live microorganisms that confer health benefits, and their interaction with gut-microbiota influences neurogenesis, neurotransmitter regulation, and neuroinflammation. Recent advancements, including germ-free animal models, fecal microbiota transplantation (FMT), and diverse probiotic strains, have revealed the underlying mechanisms linking gut health to brain function. Notably, several Lactobacillus and Bifidobacterium species have been shown to exert neuroprotective effects via the upregulation of neurotrophic factors such as brain-derived neurotrophic factor and enhancing mitochondrial function through reducing the impacts of oxidative stress. Interestingly, FMT has exhibited a degree of success in overcoming cognitive impairment and motor deficits in preclinical studies and clinical trials. However, further research is warranted to explore its therapeutic potential in humans. Overall, this review highlights the significant role of gut microbiota in NDDs and advocates for gut-targeted interventions as innovative approaches to mitigate these diseases.}, } @article {pmid40589142, year = {2025}, author = {Tiwari, R and Paswan, A and Tiwari, G and Reddy, VJS and Posa, MK}, title = {Perspectives on Fecal Microbiota Transplantation: Uses and Modes of Administration.}, journal = {Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology}, volume = {41}, number = {}, pages = {e20250014}, doi = {10.62958/j.cjap.2025.014}, pmid = {40589142}, issn = {1000-6834}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; Feces/microbiology ; *Nervous System Diseases/therapy ; }, abstract = {Fecal microbiota Transplantation (FMT), often referred to as stool transplantation, fecal transfusion, and fecal bacteria therapy, is considered one of the most medical innovations of the 20th century. Fecal microbiota Transplantation entails filtering and dilution of a healthy donor's feces before injecting it into the recipient's digestive system. In China, it was first administered orally in the fourth century for diarrhea and food poisoning under the name "Yellow Soup." It has recently been widely employed in a variety of clinical settings, including cases of Clostridium difficile infection that are recurring and resistant. By replacing the unhealthy intestinal microbiota with a healthy bacterial community, the FMT treatment aims to enhance the intestinal flora. It also looks at neurological conditions where alterations in gut microbiota are prevalent. We have discussed FMT in the context of its use in conditions affecting the nerve system, such as neurological and other conditions (multiple sclerosis, Parkinson's disease, Alzheimer's disease, stroke, epilepsy, Amyotrophic lateral sclerosis, Tourette syndrome, neuropathic pain, Huntington's diseases, etc.), as well as the role of gut microbiota in many neurological disorders.}, } @article {pmid40589086, year = {2025}, author = {Yadav, M and Gupta, A and Mathew, B and Tripathi, G and Dalal, N and Sharma, N and Yadav, P and Yadav, G and Singh, R and Bindal, V and Saif, R and Yadav, S and Sharma, N and Pandey, S and Bhat, SH and Singh, R and Kumar, J and Kushwaha, M and Khan, T and Sharma, NK and Bhaskar, A and Dwivedi, VP and Kumar, A and Kumar, N and Tripathi, DM and Trehanpati, N and Kumari, A and Sharma, S and Sarin, SK and Maras, JS}, title = {Circulating urobilinogen augments inflammation and corticosteroid non-response in severe alcohol-induced hepatitis.}, journal = {Molecular therapy : the journal of the American Society of Gene Therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ymthe.2025.06.041}, pmid = {40589086}, issn = {1525-0024}, abstract = {Severe alcohol-associated hepatitis (SAH) is a life-threatening condition with high mortality rates and poor response to prednisolone therapy. Identifying reliable early predictors of therapy response and survival is critical. Plasma metabolomics was conducted on 70 SAH patients (50 responders and 20 non-responders) to identify biomarkers for non-response and early mortality. These findings were validated in a cohort of 153 patients and an independent cohort of 245 patients using high-resolution mass spectrometry, machine learning, and severity indices. Temporal metabolic changes indicated interactions between the host and microbiome, with a focus on inflammation and intestinal permeability. Plasma metabolomics revealed that non-responders had significantly higher urobilinogen levels (3.6-fold change). Additionally, a decrease in alpha/beta diversity and temporal metabolic inactivity characterized non-responders. Plasma urobilinogen levels predicted non-response (area under the curve [AUC] > 0.97) and identified non-survivors (AUC = 0.94) with a threshold of >0.07 mg/mL. Urobilinogen levels correlated with bacterial peptides belonging to Firmicutes and Proteobacteria, neutrophil activation, oxidative stress, and pro-inflammatory cytokine production. These changes contributed to non-response by increasing glucocorticoid receptor β expression and compromising intestinal permeability. Fecal microbiota transplantation decreased urobilinogen levels by reducing bilirubin reductase gene-containing microbiota. Plasma urobilinogen >0.07 mg/mL could predict early mortality, and modulation of the gut microbiome may improve outcomes in SAH patients.}, } @article {pmid40588803, year = {2025}, author = {Hu, J and Feng, T and Zhang, L and Zhou, Q and Zhu, L}, title = {Leveraging gut microbiota for enhanced immune checkpoint blockade in solid tumor therapy.}, journal = {Chinese medical journal}, volume = {}, number = {}, pages = {}, pmid = {40588803}, issn = {2542-5641}, abstract = {Gut microbiota can modulate antitumor immunity and influence immune checkpoint blockade (ICB) therapy efficacy and treatment-associated toxicity. Variations in the therapeutic effect of ICB among individuals are partially attributed to microbiota. This review summarizes current knowledge on how specific bacterial species enhance or hinder ICB outcomes by regulating immune cell activation, antigen presentation, and systemic inflammation. The review further outlines translational strategies to optimize ICB, including microbiota-targeted interventions (e.g., prebiotics, fecal microbiota transplantation, and metabolite therapies) to overcome resistance and mitigate treatment-related toxicities, focusing on immune-related colitis. Additionally, emerging microbial biomarkers in melanoma, lung cancer, and hepatobiliary cancers that predict ICB response are discussed, highlighting the gut microbiome as a potential target for personalized cancer immunotherapy. By integrating mechanistic insights with clinical evidence, this review underscores the potential of microbiota-centered approaches to improve patient outcomes in ICB-based treatments, emphasizing the pivotal role of the gut microbiota in modulating both therapeutic efficacy and immune-related adverse events.}, } @article {pmid40586386, year = {2025}, author = {Li, K and Arbab, S and Du, Q and Zhou, J and Chen, Y and Tian, Y and Qijie, L and Ullah, H and Zhang, B}, title = {Regulatory and Influencing Factors of Digestive Function in Elderly People: Roles of the Gut Microbiota and Nutritional Interventions.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2025.0565}, pmid = {40586386}, issn = {2152-5250}, abstract = {Aging is a natural and gradual biological process through which living organisms undergo physical, physiological, and sometimes psychological changes over time. Aging is commonly associated with a decline in gastrointestinal function, leading to various digestive disorders that impact the quality of life of older adults. The gut microbiota is a highly complex ecosystem that plays crucial roles in digestion, metabolic processes, immune functions, and overall health. However, emerging evidence indicates that many elderly individuals maintain relatively stable digestive health, suggesting the influence of modifiable regulatory factors. In this review, we describe the key physiological, microbial, and nutritional factors that regulate and influence digestive function in an aging population. Additionally, we explored the impact of age-associated alterations in the gut microbiota on digestive health challenges in older adults and emphasized the therapeutic potential of targeted nutritional intervention approaches, such as dietary modifications, prebiotics, probiotics, and symbiotic and fecal microbiota transplantation, which have shown promise in rebalancing the gut microbiome and reducing inflammation.}, } @article {pmid40585700, year = {2025}, author = {Hamza Saeed, M and Qamar, S and Ishtiaq, A and Umaira Khan, Q and Atta, A and Atta, M and Ishtiaq, H and Khan, M and Saeed, MR and Iqbal, A}, title = {Fecal Microbiota Transplantation (FMT) in Clostridium difficile Infection: A Paradigm Shift in Gastrointestinal Microbiome Modulation.}, journal = {Cureus}, volume = {17}, number = {5}, pages = {e85054}, pmid = {40585700}, issn = {2168-8184}, abstract = {Clostridium difficile (C. difficile) infection (CDI) poses a tremendous clinical challenge, especially in patients with recurrent disease and antibiotic resistance. Fecal microbiota transplantation (FMT) has become a new therapeutic strategy for restoring gut microbiota and decreasing CDI recurrence. The study aims to assess the clinical effectiveness of FMT in adult subjects with recurrent or refractory CDI, determine its effect on gut microbiome diversity, and track safety outcomes and rates of recurrence post-treatment. FMT was compared against standard antibiotic treatments to establish its efficacy in decreasing infection persistence and improving patients' quality of life. This study examines the efficacy, safety, and modulation of microbiota by FMT in an ensemble of 250 patients diagnosed with CDI, with equal gender distribution and a mean age of 55.61. Among the study participants, 131 (52.4%) underwent FMT by various routes of administration, including 66 (25.2%) through colonoscopy, 73 (29.2%) via a nasogastric tube, 60 (24.0%) via enema, and 54 (21.6%) through oral capsule administration. The success rate for FMT was reported as 88 (35.2%), partial success at 74 (29.6%), and treatment failure at 88 (35.2%). CDI recurrence was reported in 130 (52.0%) of patients after FMT. The gut microbiome enhanced diversity, measured in terms of the Shannon Diversity Index, increased significantly from 3.96 before FMT to 5.88 after FMT, thus indicating a favorable impact on gut microbial composition. Furthermore, 132 (52.8%) converted from C. difficile polymerase chain reaction (PCR) toxin positive to negative, corroborating successful pathogen clearance. On secondary outcomes, the quality of life in patients improved in 90 (36%), antibiotic dependence was reduced in 88 (35.2%), and hospitalization was lessened in 72 (28.8%). Inflammatory markers, such as white blood cell (WBC) counts and C-reactive protein (CRP), went downward but did not reach statistical significance. Logistic regression analysis identified age, severity of CDI, and prior exposure to antibiotics as the main predictors for the efficacy of FMT (p < 0.05). It is concluded that FMT is a promising alternative treatment for recurrent CDI through modulation of gut microbiota and decreasing the severity of infection. Future work is, however, required to establish treatment protocols with optimized results for long-term effectiveness and minimized recurrence risks.}, } @article {pmid40585508, year = {2025}, author = {Zhu, B and Wu, H and Zhang, H and Song, Q and Xiao, Y and Yu, B}, title = {Gut microbiota from voluntary exercised mice protects the intestinal barrier by inhibiting neutrophil extracellular trap formation.}, journal = {iScience}, volume = {28}, number = {6}, pages = {112763}, pmid = {40585508}, issn = {2589-0042}, abstract = {Ulcerative colitis is an inflammatory bowel disease characterized by impaired intestinal barrier function, dysregulated immune responses, and alterations in the gut microbiota. Excessive formation of neutrophil extracellular traps (NETs), driven by peptidyl arginine deiminase 4 (PAD4) activity, contributes to inflammation modulated by the gut microbiota. In this study, we used a mouse model of dextran sulfate sodium-induced colitis to investigate the effects of voluntary exercise and its underlying mechanisms. Exercise preconditioning attenuated colitis severity, maintained intestinal barrier integrity, normalized gut microbiota composition, and suppressed NET formation. PAD4 inhibition further enhanced these effects. By contrast, the depletion of the gut microbiota by antibiotics largely abolished the benefits of exercise. Additionally, fecal microbiota transplantation from exercised mice recapitulated these protective effects. These findings elucidate the interplay among exercise, gut microbiota, and PAD4-mediated NET formation. Targeting these pathways may offer promising therapeutic strategies for colitis.}, } @article {pmid40584885, year = {2025}, author = {Guo, M and Gao, H and Wang, Y and Xiang, Y}, title = {Exploring the role of gut microbiota in Parkinson's disease: insights from fecal microbiota transplantation.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1574512}, pmid = {40584885}, issn = {1662-4548}, abstract = {As a common neurodegenerative disease, Parkinson's disease (PD) is typified by α-synuclein (α-syn) aggregation and progressive degeneration of dopaminergic neurons within the substantia nigra. Clinical manifestations encompass motor symptoms and non-motor aspects that severely impair quality of life. Existing treatments mainly address symptoms, with no effective disease-modifying therapies available. The gut microbiota refers to the community of microorganisms that colonize the intestinal tract. The gut microbiota, gut, and brain are all connected via a complicated, mutual communication pathway known as the "gut microbiota-gut-brain axis." Gut microbiota dysbiosis is strongly linked to the onset and course of PD, according to growing data. In individuals with PD, gut dysbiosis correlates with clinical phenotype, disease duration, severity, and progression rates. Mechanistically, gut dysbiosis contributes to PD through enhanced intestinal permeability, increased intestinal inflammation and neuroinflammation, abnormal α-syn aggregation, oxidative stress, and reduced neurotransmitter synthesis. Therefore, focusing on the gut microbiota is regarded as a potentially effective treatment strategy. Fecal microbiota transplantation (FMT) is an emerging approach to modulate gut microbiota, with the goal of recovering microbiota diversity and function by transferring functional intestinal flora from healthy individuals into patients' gastrointestinal tracts. FMT is expected to become a promising therapy of PD and has a broad research and application prospect. Evidence suggests that FMT may restore gut microbiota, ease clinical symptoms, and provide potential neuroprotective benefits. However, the precise therapeutic mechanisms of FMT in PD remain uncertain, necessitating further research to clarify its effectiveness. This review examines alterations in gut microbiota linked to PD, mechanisms through which gut dysbiosis influences the disease, and the latest advancements in FMT research for treating PD, setting the stage for its clinical application.}, } @article {pmid40583967, year = {2025}, author = {Wang, H and Tian, J and Mi, J}, title = {Clinical effectiveness of fecal microbial transplantation for metabolic syndrome: Advances in clinical efficacy and multi-omics research.}, journal = {Current research in microbial sciences}, volume = {9}, number = {}, pages = {100415}, pmid = {40583967}, issn = {2666-5174}, abstract = {Even though metabolic syndrome (MetS) poses a serious risk to human health and life, existing treatment approaches are not very effective. The impact of gut bacteria on host metabolism has been the subject of numerous research, and fecal microbial transplantation (FMT) has demonstrated great promise in reducing insulin resistance and abdominal obesity in individuals with metabolic syndrome. These FMT investigations have connected alterations in the gut microbiota to clinical indicators of insulin resistance and obesity, in addition to using high-throughput methods to analyze the gut microbiome, metabolome, and epigenome of peripheral blood mononuclear cells in patients with MetS. It is still necessary to clarify and assess the clinical effectiveness and mode of action of FMT in the management of MetS. This review examines the connection between gut bacteria and MetS, the effectiveness of FMT as a treatment, and the changes in the gut microbiome, metabolome, epigenome, and other histones following the intervention. We also discuss the safety of FMT and suggest areas for further investigation.}, } @article {pmid40582671, year = {2025}, author = {Bi, R and Abbas, W and Li, J and Huang, J and Hu, J and Guo, F and Wang, Z}, title = {Yeast β-glucan ameliorated Salmonella-induced gut impairment in broiler chickens by modulating gut microbiome.}, journal = {International journal of biological macromolecules}, volume = {319}, number = {Pt 4}, pages = {145630}, doi = {10.1016/j.ijbiomac.2025.145630}, pmid = {40582671}, issn = {1879-0003}, mesh = {Animals ; Chickens/microbiology ; *Gastrointestinal Microbiome/drug effects ; *beta-Glucans/pharmacology ; *Poultry Diseases/microbiology ; *Salmonella enteritidis/drug effects ; Fecal Microbiota Transplantation ; *Salmonella Infections, Animal/microbiology ; }, abstract = {Yeast β-glucan (YG) was reported to control Salmonella infection in poultry. Gut microbiota plays an important role in regulating immune functions and intestinal health. However, it is still unclear whether YG protects chickens from Salmonella infection by regulating gut microbiota. The impacts of YG on gut health of chickens infected with Salmonella enteritidis (SE) was investigated through histochemical and immunological methods, along with microbiomics. The role of gut microbiome induced by YG treatment in combating Salmonella infection was explored through fecal microbiota transplantation (FMT). Our findings showed that YG administration significantly ameliorated SE-induced gut impairment by decreasing gut permeability, enhancing intestinal barrier function, inhibiting intestinal inflammation, reducing Salmonella colonization and invasion, lowering g_Streptococcus and g_Ligilactobacillus but increasing g_Blautia, g_Bacillus5555555555555555555555 and g_Faecalibacterium relative abundance. Transplantation fecal microbiota from YG-treated healthy donor chickens to antibiotic-treated recipient chicks significantly attenuated gut injury caused by SE infection through decreasing Salmonella colonization and invasion along with intestinal permeability, improving gut morphology, upregulating intestinal tight junction genes and proteins expression, downregulating pro-inflammatory cytokines expression. Additionally, FMT remarkably increased g_Bacteroides and g_Faecalibacterium relative abundances and butyric acid level, decreased g_Ruminococcus-torque-group relative abundance in the cecum. Collectively, we assume that yeast β-glucan alleviated Salmonella-induced gut impairment, a mechanism that is dependent on the gut commensal g_Bacteroides and g_Faecalibacterium.}, } @article {pmid40581627, year = {2025}, author = {Nørgaard, JC and Marandi, RZ and Ilett, EE and Gulay, A and Paredes, R and Lundgren, JD and Jørgensen, M and Sengeløv, H}, title = {The gut microbiome and its resistome as predictors of clinical infections and phenotypic antibiotic resistance in hematopoietic stem cell transplant recipients.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiaf330}, pmid = {40581627}, issn = {1537-6613}, abstract = {A relationship between the gut microbiome composition, its resistome, and risk of clinical infections may exist and was explored here using 663 shotgun-sequenced fecal samples from 276 stem cell transplant patients. E. faecium, E. coli, and E. faecalis were the three most prevalent causes of clinical infection, with vancomycin resistance in E. faecium as the most common antibiotic resistance feature. Associations between the gut microbiome, resistome, and clinical infections were tested, with significant findings (FDR<0.05) evaluated in multivariable analysis. A 10% increase in gut abundance of E. faecium was positively associated with subsequent clinical infection with E. faecium (OR=1.14, p=0.02). Additionally, a 1% increase in vanA gene abundance was positively associated with vancomycin-resistant E. faecium infection (OR=1.27, p<0.01). Here we used metagenomics to enhance the understanding of infectious sources and to identify patients at risk of clinical infection with antibiotic-resistant bacterial strains.}, } @article {pmid40580532, year = {2025}, author = {Urbonas, T and Petrauskas, D and Kiudelis, V and Jonaitis, L and Skieceviciene, J and Gedgaudas, R and Kiudeliene, E and Valantiene, I and Zykus, R and Varkalaite, G and Inciuraite, R and Trapenske, E and Kulokiene, U and Jonaitis, P and Ramonaite, R and Velickiene, J and Zvirbliene, A and Morkunas, E and Kuliaviene, I and Sumskiene, J and Adamonis, K and Macas, A and Kupcinskiene, K and Lukosiene, L and Janciauskas, D and Poskiene, L and Vitkauskiene, A and Ianiro, G and Gasbarrini, A and Kiudelis, G and Kupcinskas, J}, title = {Fecal Microbiome Transplantation for Recurrent CDI: Treatment Efficacy and Safety with Oral Capsules.}, journal = {Journal of gastrointestinal and liver diseases : JGLD}, volume = {34}, number = {2}, pages = {199-204}, doi = {10.15403/jgld-5990}, pmid = {40580532}, issn = {1842-1121}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; Male ; Female ; Retrospective Studies ; Middle Aged ; Treatment Outcome ; Administration, Oral ; *Clostridium Infections/therapy/microbiology/diagnosis ; Aged ; Capsules ; Recurrence ; *Clostridioides difficile ; Adult ; Anti-Bacterial Agents/administration & dosage ; Time Factors ; Feces/microbiology ; }, abstract = {BACKGROUND AND AIMS: Fecal microbiota transplantation is an effective treatment method for recurrent Clostridioides difficile infection. Widely used enteric tube and colonoscopy methods demonstrate excellent efficacy and safety results. Recent data suggest that new fecal microbiota transplantation methods using oral capsules may provide a less invasive approach. In this study, we aimed to compare primary fecal microbiota transplantation efficacy as well as short- and long-term safety of two different administration routes: oral capsules and enteric tube.

METHODS: This retrospective study included 60 consecutive patients who underwent fecal microbiota transplantation for recurrent Clostridioides difficile infection. Thirty participants received 50 oral capsules containing frozen material for a single day and 30 patients received fecal microbiota transplantation via nasoenteric tube. All patients received standard treatment with oral vancomycin 500 mg q.i.d. for at least five days before the procedure. After intervention, patients were followed up for at least six months. Data on Clostridioides difficile infection recurrences and health status were collected and analyzed.

RESULTS: The oral capsules group consisted of 30 patients. Among them, 22 (73.3%) participants experienced resolution of symptoms after a single fecal microbiota transplantation, while eight (26.7%) patients developed recurrent diarrhea within eight weeks. The other 30 patients received treatment via nasoenteric tube. Among them, 24 (80%) patients were cured after a single fecal microbiota transplantation, while six (20%) experienced recurrent disease within eight weeks. The primary efficacy did not show significant differences between the two groups (p=0.85). Throughout the follow-up period, no serious adverse events or fecal microbiota transplantation related deaths were reported in both groups.

CONCLUSIONS: Fecal microbiota transplantation with frozen oral capsules is a safe, less invasive method with comparable efficacy to nasoenteric administration route.}, } @article {pmid40579140, year = {2025}, author = {Zhu, Y and Zhu, Z and Wu, P}, title = {[Pentosan polysulfate alleviates cyclophosphamide-induced interstitial cystitis/bladder pain syndrome in mice by modulating gut microbiota and bile acid metabolism].}, journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University}, volume = {45}, number = {6}, pages = {1270-1279}, pmid = {40579140}, issn = {1673-4254}, support = {82370782//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Cystitis, Interstitial/chemically induced/drug therapy ; *Gastrointestinal Microbiome/drug effects ; *Pentosan Sulfuric Polyester/pharmacology/therapeutic use ; Cyclophosphamide/adverse effects ; Mice, Inbred C57BL ; Female ; Mice ; *Bile Acids and Salts/metabolism ; Urinary Bladder ; Fecal Microbiota Transplantation ; Humans ; }, abstract = {OBJECTIVES: To investigate the therapeutic efficacy and mechanism of pentosan polysulfate (PPS) for cyclophosphamide (CYP)-induced interstitial cystitis/bladder pain syndrome (IC/BPS) in mice.

METHODS: Female C57BL/6 mice (6-8 weeks old) were randomized into control group, PPS treatment (25 mg/kg via gavage for 3 weeks) group, CYP treatment (3 separate intraperitoneal injections at 50 mg/kg in week 4), and CYP+PPS treatment group. Gut microbiota alterations of the mice were analyzed using 16S rDNA sequencing and non-targeted metabolomics. Fecal microbiota transplantation (FMT) was performed in CYP-treated recipient mice and those treated with both CYP and PPS. In the in vitro experiment, LPS-stimulated human bladder epithelial cells (SV-HUC-1) were used to assess the effects of deoxycholic acid (DCA) and TGR5 signaling inhibitor SBI-115 on barrier functions of bladder epithelial cells.

RESULTS: PPS treatment significantly improved the mechanical pain thresholds, restored the urodynamic parameters, and attenuated bladder inflammation and barrier dysfunction in CYP-treated mice. Mechanistically, PPS enriched the abundance of Eubacterium xylanophilum and increased DCA levels in the intestines of CYP-treated mice. FMT experiments confirmed microbiota-dependent therapeutic effects of PPS, shown by reduced bladder pathology in the recipient mice treated with both CYP and PPS. In SV-HUC-1 cells, DCA obviously alleviated LPS-induced inflammation and barrier disruption, and treatment with SBI-115 abolished these protective effects of DCA.

CONCLUSIONS: PPS ameliorates IC/BPS in mice by remodeling gut microbiota to enhance DCA production and activate TGR5 signaling, suggesting a novel microbiota-bile acid-TGR5 axis that mediates the therapeutic effect of PPS and a therapeutic strategy for IC/BPS by targeting gut-bladder crosstalk.}, } @article {pmid40578039, year = {2025}, author = {Wen, Y and Li, M and Hao, Y and Peng, J and Wei, X and Zhang, Z and Liu, B and Wang, Y and Peng, T and Ma, Y}, title = {HDAC/NF-κB signaling pathway mediates gut microbiota dysbiosis in rheumatoid arthritis: Intervention mechanisms of Fengshining decoction.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {145}, number = {}, pages = {156976}, doi = {10.1016/j.phymed.2025.156976}, pmid = {40578039}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Arthritis, Rheumatoid/drug therapy/microbiology/metabolism ; *Dysbiosis/drug therapy/microbiology ; *Drugs, Chinese Herbal/pharmacology ; *NF-kappa B/metabolism ; Mice ; *Arthritis, Experimental/drug therapy/microbiology ; Signal Transduction/drug effects ; Male ; *Histone Deacetylases/metabolism ; Fecal Microbiota Transplantation ; Butyrates/pharmacology ; Fatty Acids, Volatile/metabolism ; Mice, Inbred DBA ; }, abstract = {BACKGROUND: Gut microbiota dysbiosis has been associated with the development of rheumatoid arthritis (RA). Fengshining (FSN) is a traditional Chinese medicine decoction that can effectively alleviate RA. However, how FSN modulates the gut microbiota to mitigate RA has not been comprehensively studied. This study evaluated the gut microecological mechanisms underlying FSN's effects on RA, focusing on the impact of gut-derived short-chain fatty acids (SCFAs), specifically butyrate, in RA treatment.

METHODS: The pharmacological effects of FSN on type II collagen-induced arthritis (CIA) in mice were assessed via pathological indicators, metagenomics, and metabolomics analyses. Furthermore, the impact of FSN on gut microbiota and metabolic profiles was also evaluated. Moreover, a pseudo-germ-free CIA model was established to validate whether exogenous butyrate alleviates RA. This study also elucidated whether fecal microbiota transplantation (FMT) from FSN-treated mice could mitigate RA symptoms.

RESULTS: The data showed that FSN markedly alleviated CIA symptoms and reduced serum inflammatory cytokine levels. Metagenomic and metabolomic analyses revealed that FSN-enriched SCFA-producing bacteria, including Butyrivibrio, Faecalicatena, and Lacrimispora. Furthermore, FSN increased the activity of carbohydrate metabolism-related enzymes and upregulated the expression patterns of homologous protein families. Moreover, exogenous butyrate supplementation suppressed pro-inflammatory factors, modulating immune responses, and enhanced intestinal barrier function. Further, Western blot analysis validated that FSN inhibited the HDAC/NF-κB pathway.

CONCLUSION: This study indicated that the gut microecological mechanism of FSN might be associated with its herbal components, which regulate gut microbiota diversity, restore the intestinal barrier, and boost microbial metabolite production. Furthermore, butyrate was observed to modulate intestinal mucosa, inhibit inflammatory responses, repair the intestinal barrier, and mitigate joint damage, thus alleviating RA symptoms.}, } @article {pmid40576702, year = {2025}, author = {Shtrozberg, S and Bazzichi, L and Sarzi-Puttini, P and Aloush, V and Ablin, JN}, title = {Is the gut microbiome of importance in fibromyalgia? A critical review of emerging evidence.}, journal = {Clinical and experimental rheumatology}, volume = {43}, number = {6}, pages = {990-998}, doi = {10.55563/clinexprheumatol/pmajsv}, pmid = {40576702}, issn = {0392-856X}, mesh = {Animals ; Humans ; Brain-Gut Axis ; Fecal Microbiota Transplantation ; *Fibromyalgia/microbiology ; *Gastrointestinal Microbiome ; Inflammation/microbiology ; Nutritional Status ; Prebiotics ; Probiotics/therapeutic use ; Dysbiosis/complications ; }, abstract = {Fibromyalgia (FM) is a multifaceted chronic pain syndrome, predominantly affecting women, and characterised by a constellation of symptoms including diffuse musculoskeletal pain, fatigue, cognitive impairment and poor sleep quality. Its complex pathophysiology likely involves genetic, environmental and psychosocial factors. Recent studies have raised the possibility that the gut microbiome may influence FM symptoms via the gut-brain axis, although this hypothesis remains unconfirmed. This review aims to explore potential associations between gut microbiome alterations, nutrition, and FM, with particular attention to the limitations of current evidence. While certain studies have reported differences in the gut microbiota composition of patients with FM, these findings are preliminary and often derive from small, heterogeneous cohorts. Likewise, faecal microbiota transplantation studies in animals and limited human trials suggest a possible link to pain sensitivity, but further validation is needed.Nutritional interventions, including prebiotics, probiotics and specific dietary strategies, have shown early promise in modulating gut microbiota and alleviating FM symptoms. Nutrients such as magnesium, selenium and omega-3 fatty acids, as well as antioxidant compounds, may influence pain and inflammation pathways, but definitive clinical recommendations are lacking. Given the emerging nature of this field, larger and better-controlled studies are required to clarify the role of the gut microbiome and nutrition in FM. A multidisciplinary management strategy, integrating nutritional approaches cautiously and based on individual profiles, may offer benefits, although no standard therapeutic guidelines currently exist.}, } @article {pmid40576662, year = {2025}, author = {Goldschmidt, I and Kramer, M and Junge, N and Ouro-Djobo, N and Poets, A and Rathert, M and Geffers, R and Baumann, U and Hartleben, B and Schulze, KD and Woltemate, S and Vital, M}, title = {Short- and long-term development of gut microbiota in children after liver transplantation - a prospective observational trial.}, journal = {Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society}, volume = {}, number = {}, pages = {}, doi = {10.1097/LVT.0000000000000659}, pmid = {40576662}, issn = {1527-6473}, abstract = {In children, little is known on gut microbiota (GM) in end-stage liver disease and its association with graft function after pediatric liver transplantation (pLT). We analyzed GM composition and function in children before pLT, longitudinally post-pLT and in long-term survivors (LT-pLT) in order to assess the impact of disease severity, treatment and pLT on GM and delineate associations with graft and patient health. Fecal samples (FS) of 29 children (17f, age 2.6 [0.2-15.7] years) awaiting pLT were included with longitudinal follow-ups until 12M post-transplant in 18, and compared with 38 LT-pLT (21f, age 11 [2.7-17.7] years, 7.8 [1.0-17.0] years post-pLT) and 94 healthy controls (HC). Samples were analyzed using quantitative 16S rRNA gene analyses combined with shotgun metagenomics (subset of samples). Pre-pLT patients showed reduced alpha-diversities and altered GM composition compared with LT-pLT and HC, associated with disease severity and anti-pruritic treatment with Rifampicin. Dysbiosis increased after pLT and started to recover after 3M. Although bacterial concentrations, alpha diversity and gene richness increased post-pLT, levels remained below those of HC. Abundances of key functions, e.g. the capacity to synthesize butyrate, also remained reduced. Quantitative analyses revealed true extent of differences between patients and HC that were underestimated using relative abundance data. GM diversity and functional capacities correlated negatively with transaminase levels mid- and long-term after pLT. Random Forest analyses based on GM were able to predict hepatocellular damage at high accuracy (AUC: 0.89). We provide comprehensive, quantitative insights into GM composition and function before and after pLT. A link between GM alterations with (long-term) graft health was uncovered providing possible targets to modulate GM function in order to increase graft and patient health.}, } @article {pmid40575995, year = {2025}, author = {Zhang, D and Dong, B and Chen, J and Zhang, Z and Zeng, W and Liao, L and Xiong, X and Qin, X and Fan, X}, title = {Fecal Microbiota Transplantation Modulates Th17/Treg Balance via JAK/STAT Pathway in ARDS Rats.}, journal = {Advanced biology}, volume = {}, number = {}, pages = {e00028}, doi = {10.1002/adbi.202500028}, pmid = {40575995}, issn = {2701-0198}, support = {2022NSFSC0046//Natural Science Foundation of Sichuan Province of China/ ; 2022QN074//Southwest Medical University School-Level Project/ ; 2023JYJ049//Luzhou City Science and Technology Program Project/ ; LRYGCC202120//Guangxi Key Specialty Construction Project Funding, Liuzhou City People's Hospital High-Level Talent Research Startup Fund/ ; lry202408//Liuzhou People's Hospital In-house Project Funding/ ; lry202409//Liuzhou People's Hospital In-house Project Funding/ ; lry202411//Liuzhou People's Hospital In-house Project Funding/ ; GXZYB20240601//Guangxi Autonomous Region Traditional Chinese Medicine Self-Funded Project/ ; 2024YB0103B003//Liuzhou City Science and Technology Program Project/ ; }, abstract = {This study evaluated the therapeutic effects of fecal microbiota transplantation (FMT) on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) in rats. The study focused on the balance of T-helper 17 (Th17) and regulatory T (Treg) cells, as well as the modulation of the JAK/STAT pathway. This study established a rat ARDS model using intranasal LPS instillation, administering interventions such as FMT, Treg cell depletion, and JAK inhibitors. Assessments included histopathological examination of lung and intestinal tissues, flow cytometry for Th17 and Treg cell proportions, qPCR and Western blot for gene and protein expression, ELISA for inflammatory cytokines, and correlation analysis using Spearman's method for cytokine-immune cell interactions. Results indicated that FMT and JAK inhibitors significantly reduce lung damage induced by LPS, reduced alveolar destruction and inflammation, restored Th17/Treg balance, and inhibited JAK/STAT pathway activity. Notably, FMT decreased pro-inflammatory cytokines (IL-2, IL-6, IL-8, IL-17A, IL-23, TGF-β1) and increased anti-inflammatory cytokines (IL-10, IL-35) in serum. Spearman correlation analysis indicated that FMT restored immune balance by modulating the interactions between cytokines and immune cells. In conclusion, FMT effectively alleviates lung and intestinal injury in LPS-induced ARDS rat models by modulating Th17/Treg balance and inhibiting JAK/STAT pathway activity, demonstrating promising therapeutic potential for ARDS treatment.}, } @article {pmid40575647, year = {2025}, author = {Tüsüz Önata, E and Özdemir, Ö}, title = {Microbiome, dysbiosis and use of probiotics in various diseases.}, journal = {World journal of virology}, volume = {14}, number = {2}, pages = {99574}, pmid = {40575647}, issn = {2220-3249}, abstract = {The community of microorganisms that colonize certain areas of the human body is called microbiota. Microorganisms such as bacteria, fungi and viruses make up the microbiota. The sum of the genomes of these microorganisms and microorganisms refers to the microbiome. It has been shown that microbiota has important effects such as protecting the organ from pathogens, contributing to metabolic functions (such as vitamin synthesis, carbohydrate digestion) and providing immunoregulation. Dysbiosis refers to compositional and functional changes in the microbiota. At the beginning of the 21[st] century, numerous studies have investigated the human microbiota and its imbalance in relation to various diseases and found that dysbiosis is associated with many diseases. The aim of this mini-review article is to provide brief information about dysbiosis and its care and to raise awareness.}, } @article {pmid40575364, year = {2025}, author = {Bangolo, A and Amoozgar, B and Habibi, M and Simms, E and Nagesh, VK and Wadhwani, S and Wadhwani, N and Auda, A and Elias, D and Mansour, C and Abbott, R and Jebara, N and Zhang, L and Gill, S and Ahmed, K and Ip, A and Goy, A and Cho, C}, title = {Exploring the gut microbiome's influence on cancer-associated anemia: Mechanisms, clinical challenges, and innovative therapies.}, journal = {World journal of gastrointestinal pharmacology and therapeutics}, volume = {16}, number = {2}, pages = {105375}, pmid = {40575364}, issn = {2150-5349}, abstract = {BACKGROUND: Anemia is a prevalent and challenging complication in patients with hematologic and solid malignancies, which stems from the direct effects of malignancy, treatment-induced toxicities, and systemic inflammation. It affects patients' survival, functional status, and quality of life profoundly. Recent literature has highlighted the emerging role of the gut microbiome in the pathogenesis of cancer-associated anemia. The gut microbiota, through its intricate interplay with iron metabolism, inflammatory pathways, and immune modulation, may either exacerbate or ameliorate anemia depending on its composition, and functional integrity. Dysbiosis, characterized by disruption in the gut microbial ecosystem, is very common in cancer patients. This microbial imbalance is implicated in anemia causation through diminished iron absorption, persistent low-grade inflammation, and suppression of erythropoiesis.

AIM: To consolidate current evidence regarding the interplay between gut microbiome and anemia in the setting of malignancies. It aims to provide a detailed exploration of the mechanistic links between dysbiosis and anemia, identifies unique challenges associated with various cancer types, and evaluates the efficacy of microbiome-focused therapies. Through this integrative approach, the review seeks to establish a foundation for innovative clinical strategies aimed at mitigating anemia and improving patient outcomes in oncology.

METHODS: A literature search was performed using multiple databases, including Google Scholar, PubMed, Scopus, and Web of Science, using a combination of keywords and Boolean operators to refine results. Keywords included "cancer-associated anemia", "gut microbiome", "intestinal microbiota", "iron metabolism", "gut dysbiosis", "short-chain fatty acids", "hematopoiesis", "probiotics", "prebiotics", and "fecal microbiota transplantation". Articles published in English between 2000 and December 2024 were included, with a focus on contemporary and relevant findings.

RESULTS: Therapeutic strategies aimed at restoration of gut microbial homeostasis, such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation (FMT), can inhibit anemia-causing pathways by enhancing microbial diversity, suppressing detrimental flora, reducing systemic inflammation and optimizing nutrient absorption.

CONCLUSION: Gut dysbiosis causes anemia and impairs response to chemotherapy in cancer patients. Microbiome-centered interventions, such as probiotics, prebiotics, dietary modifications, and FMT, have shown efficacy in restoring microbial balance, reducing inflammation, and enhancing nutrient bioavailability. Emerging approaches, including engineered probiotics and bacteriophage therapies, are promising precision-based, customizable solutions for various microbiome compositions and imbalances. Future research should focus on integrating microbiome-targeted strategies with established anemia therapies.}, } @article {pmid40574876, year = {2025}, author = {Odenwald, MA and Ramaswamy, R and Lin, H and Lehmann, C and Moran, A and Mullowney, MW and Sidebottom, AM and Hernandez, A and McMillin, M and Rose, A and Moran, D and Little, J and Sulakhe, D and D'Souza, M and Woodson, C and Tanveer, T and de Porto, A and Dylla, N and Sundararajan, A and Burgo, V and Cantoral, J and Jadczak, C and Adler, E and Aronsohn, A and Pamer, EG and Rinella, ME}, title = {Fecal Butyrate and Deoxycholic Acid Concentrations Correlate With Mortality in Patients With Liver Disease.}, journal = {Gastro hep advances}, volume = {4}, number = {8}, pages = {100695}, pmid = {40574876}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: The intestinal microbiome produces metabolites, including short chain fatty acids (SCFAs) and secondary bile acids (BAs), that impact host physiology. Loss of intestinal microbiome diversity is associated with cirrhosis progression, but the impact of microbiome-associated metabolites on liver disease remains largely undefined. We aimed to correlate fecal metabolite concentrations with the severity and progression of liver disease.

METHODS: In this cross-sectional study, fecal samples from patients hospitalized with liver disease were analyzed by shotgun metagenomic sequencing to determine microbiome compositions and targeted mass spectrometry to quantify SCFAs and BAs. Random survival forest and logistic regression models identified clinical, metagenomic, and metabolomic features associated with rehospitalization and survival.

RESULTS: This cross-sectional study included 24 chronic liver disease, 18 compensated cirrhosis, 225 decompensated cirrhosis and 40 acute-on-chronic liver failure patients and 27 control fecal donors. Microbiome sequencing and metabolite profiling correlated microbial diversity and SCFA and BA concentrations with liver disease severity. Butyrate and deoxycholic acid (DCA) were more important features than individual microbial species in random survival forest models predicting 30-day transplant-free survival, and low butyrate and DCA were associated with 30-day mortality (P < .0001). After controlling for model for end stage liver disease (MELD)-sodium score, disease stage, age and gender, low fecal concentrations of butyrate and DCA remained significant risk factors for death (Cox 1.38, P = .027). Bacterial species associated with butyrate and DCA concentrations included Bifidobacterium spp. and F. prausnitzii.

CONCLUSION: Mass spectrometry rapidly identifies patients with low fecal butyrate and DCA concentrations who are at increased risk of 30-day mortality. These findings set the stage for clinical trials of microbiome reconstitution with butyrate and DCA-producing bacterial species.}, } @article {pmid40574831, year = {2025}, author = {Guo, X and Wang, K and Liu, Q and Baran, N and Ma, W}, title = {The gut-immune axis in primary immune thrombocytopenia (ITP): a paradigm shifts in treatment approaches.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1595977}, pmid = {40574831}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Purpura, Thrombocytopenic, Idiopathic/therapy/immunology/microbiology ; Dysbiosis/immunology ; Fecal Microbiota Transplantation ; Animals ; Blood Platelets/immunology ; Probiotics/therapeutic use ; }, abstract = {Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by platelet destruction and impaired production, leading to bleeding risk. While immunosuppressive therapies are standard, many patients experience relapses or refractory disease, highlighting the need for novel approaches. Emerging evidence suggests the gut microbiota plays a role in immune regulation, yet its impact on ITP remains unclear. Dysbiosis has been linked to immune dysfunction in other autoimmune diseases, but whether it drives or results from immune dysregulation in ITP is debated. This review explores the gut-immune axis in ITP, focusing on microbiota-driven immune modulation, cytokine signaling, and platelet homeostasis. We assess microbiota-targeted interventions, including fecal microbiota transplantation (FMT), probiotics, and dietary modifications, while addressing key controversies and knowledge gaps. Advances in microbiome sequencing and artificial intelligence may facilitate personalized interventions. Standardizing microbiota-based diagnostics and validating their efficacy in clinical trials are crucial for their integration into ITP management. Bridging these gaps may lead to microbiota-driven strategies that enhance immune regulation and improve patient outcomes.}, } @article {pmid40574570, year = {2025}, author = {Yang, D and Yang, X and Zhou, Y and Wang, H and Wang, R}, title = {Fecal Microbiota Transplantation from Noni Fruit Phenolic-Rich Extract Intervention Mouse Donors Ameliorates Lipid Metabolism Disorder by Regulating the FXR-FGF15 Pathway in a Gut Microbiota-Dependent Manner.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {28}, pages = {17672-17684}, doi = {10.1021/acs.jafc.5c05184}, pmid = {40574570}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Fecal Microbiota Transplantation ; Male ; *Phenols/administration & dosage ; *Fibroblast Growth Factors/metabolism/genetics ; Fruit/chemistry ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; *Plant Extracts/administration & dosage/chemistry ; Mice, Inbred C57BL ; Bile Acids and Salts/metabolism ; *Lipid Metabolism Disorders/metabolism/therapy/genetics/microbiology/drug therapy ; Humans ; Lipid Metabolism/drug effects ; Bacteria/isolation & purification/classification/genetics/metabolism ; Cholesterol 7-alpha-Hydroxylase/metabolism/genetics ; Feces/microbiology ; Liver/metabolism ; }, abstract = {Noni fruit phenolic-rich extract (NFE) has been confirmed to alleviate lipid metabolism disturbance, with emerging evidence implicating bile acids (BAs) metabolism in a gut microbiota-dependent manner in mediating the effect. The effect and potential mechanism of fecal microbiota transplantation from NFE intervention mouse donors (FMT-NFE) on lipid metabolism disorder were investigated. The results reveal FMT-NFE intervention regulated the body weight, lipid profile levels, and liver damage. FMT-NFE intervention upgraded the abundance of bile salt hydrolase (BSH)-expressing bacteria and short-chain fatty acid (SCFA)-producing bacteria in feces, which is accompanied by changes of BSH activity and BAs profile as well as elevation of the SCFA level. Moreover, western blotting and immunofluorescence results confirmed the intestinal FXR-FGF15 pathway was activated by FMT-NFE intervention, which was accompanied by activation of the liver FXR and inhibition of CYP7A1 expression to control cholesterol-to-BAs conversion. These findings underscore the mechanisms behind maintaining BAs and lipid metabolism homeostasis of NFE.}, } @article {pmid40573435, year = {2025}, author = {Ajileye, TG and Akinleye, TE and Faleye, TOC and De Coninck, L and George, UE and Onoja, AB and Agbaje, ST and Ifeorah, IM and Olayinka, OA and Oni, EI and Oragwa, AO and Popoola, BO and Olayinka, OT and Osasona, OG and George, OA and Ajayi, PG and Suleiman, AA and Muhammad, AI and Komolafe, I and Adeniji, AJ and Matthijnssens, J and Adewumi, MO}, title = {Ten Previously Unassigned Human Cosavirus Genotypes Detected in Feces of Children with Non-Polio Acute Flaccid Paralysis in Nigeria in 2020.}, journal = {Viruses}, volume = {17}, number = {6}, pages = {}, pmid = {40573435}, issn = {1999-4915}, mesh = {Humans ; *Feces/virology ; Nigeria/epidemiology ; Phylogeny ; *Genotype ; Child ; Child, Preschool ; *Picornaviridae/genetics/classification/isolation & purification ; Genome, Viral ; Infant ; *Picornaviridae Infections/virology/epidemiology ; Genetic Variation ; Adolescent ; Female ; Male ; Metagenomics ; *Paralysis/virology ; }, abstract = {Since its discovery via metagenomics in 2008, human cosavirus (HCoSV) has been detected in the cerebrospinal fluid (CSF) and feces of humans with meningitis, acute flaccid paralysis (AFP), and acute gastroenteritis. To date, 34 HCoSV genotypes have been documented by the Picornaviridae study group. However, the documented genetic diversity of HCoSV in Nigeria is limited. Here we describe the genetic diversity of HCoSV in Nigeria using a metagenomics approach. Archived and anonymized fecal specimens from children (under 15 years old) diagnosed with non-polio AFP from five states in Nigeria were analyzed. Virus-like particles were purified from 55 pools (made from 254 samples) using the NetoVIR protocol. Pools were subjected to nucleic acid extraction and metagenomic sequencing. Reads were trimmed and assembled, and contigs classified as HCoSV were subjected to phylogenetic, pairwise identity, recombination analysis, and, when necessary, immuno-informatics and capsid structure prediction. Fifteen pools yielded 23 genomes of HCoSV. Phylogenetic and pairwise identity analysis showed that all belonged to four species (eleven, three, three, and six members of Cosavirus asiani, Cosavirus bepakis, Cosavirus depakis, and Cosavirus eaustrali, respectively) and seventeen genotypes. Ten genomes belong to seven (HCoSV-A3/A10, A15, A17, A19, A24, D3, and E1) previously assigned genotypes, while the remaining thirteen genomes belonged to ten newly proposed genotypes across the four HCoSV species, based on the near-complete VP1 region (VP1*) of the cosavirus genome. Our analysis suggests the existence of at least seven and eight Cosavirus bepakis and Cosavirus eaustrali genotypes, respectively (including those described here). We report the first near-complete genomes of Cosavirus bepakis and Cosavirus depakis from Nigeria, which contributes to the increasing knowledge of the diversity of HCoSV, raising the number of tentative genotypes from 34 to over 40. Our findings suggest that the genetic diversity of HCoSV might be broader than is currently documented, highlighting the need for enhanced surveillance.}, } @article {pmid40573341, year = {2025}, author = {Hu, J and Zhang, Q and Liu, D and Cui, X and Wang, Q and Gong, W and Wang, X}, title = {Inhibition of Bovine Enterovirus Infection by Magnolol via Modulating the Gut Microbiota in Mice.}, journal = {Viruses}, volume = {17}, number = {6}, pages = {}, pmid = {40573341}, issn = {1999-4915}, support = {2016YFD0500904 and 2017YFD0500104//National Key Research & Development Program/ ; }, mesh = {Animals ; *Lignans/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Biphenyl Compounds/pharmacology/therapeutic use ; *Enterovirus Infections/drug therapy/virology/veterinary/microbiology ; Cattle ; Disease Models, Animal ; Feces/microbiology ; Fecal Microbiota Transplantation ; *Antiviral Agents/pharmacology ; Viral Load/drug effects ; Enterovirus/drug effects ; }, abstract = {Bovine enterovirus (BEV) infection is one of the important infectious diseases that cause digestive and respiratory symptoms in cattle, posing a significant threat to the cattle industry. Currently, no vaccines or therapeutic drugs are available for this disease. In our study, we utilized a mouse model to investigate the effects of BEV infection on the gut microbiota and examine the therapeutic potential of magnolol (Mag), a polyphenolic bioactive substance, in terms of BEV infection. BEV infection significantly altered the microbiota composition, where the abundance of some beneficial bacteria, such as Lactobacillaceae and Lactobacillus, was markedly reduced. Mag effectively inhibited BEV infection in vivo. Upon BEV infection, Mag treatment reduced the α-diversity of the microbiota, with statistically significant differences on day 3 post-infection compared to the Mag-untreated group. More interestingly, Mag treatment significantly reversed the effect of BEV infection on the Lactobacillaceae and Lactobacillus abundance, indicating that Mag positively regulates beneficial bacteria. The fecal microbiota transplantation (FMT) experiment demonstrated that feces from Mag-treated mice significantly decreased the virus loads in the small intestine samples of BEV-infected mice. These findings demonstrate the interaction between BEV infection and the gut microbiota and highlight the important regulatory role of the gut microbiota in Mag's anti-BEV effects, opening up a new avenue for preventing and controlling BEV infection via targeted modulation of the gut microbiota.}, } @article {pmid40573072, year = {2025}, author = {Wakino, S and Hasegawa, K and Tamaki, M and Minato, M and Inagaki, T}, title = {Kidney-Gut Axis in Chronic Kidney Disease: Therapeutic Perspectives from Microbiota Modulation and Nutrition.}, journal = {Nutrients}, volume = {17}, number = {12}, pages = {}, pmid = {40573072}, issn = {2072-6643}, mesh = {Humans ; *Renal Insufficiency, Chronic/microbiology/therapy/physiopathology ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/therapy/microbiology ; Probiotics/therapeutic use ; Prebiotics/administration & dosage ; *Kidney/physiopathology ; Synbiotics/administration & dosage ; Fecal Microbiota Transplantation ; Uremia/microbiology ; *Nutrition Therapy/methods ; }, abstract = {Chronic kidney disease (CKD) has a high prevalence worldwide, with an increasing incidence. One of the mechanisms of CKD progression involves a disordered inter-organ relationship between the kidneys and the intestine, known as the kidney-gut axis. In CKD, two pathological gut conditions-disturbed gut microbiota composition called uremic dysbiosis and leaky gut-contribute to the progression of CKD. Dysbiosis is associated with the increased production of gut-derived uremic toxins, leaky gut, and chronic systemic inflammation, leading to worsening uremia, which in turn aggravates the gut condition. This vicious cycle should be a target of the therapeutic strategy against CKD. The modulation of uremic dysbiosis, including prebiotics, probiotics, and synbiotics, has been a typical treatment approach, although clinical evidence for their efficacy has been insufficient. Some non-antibiotic drugs have an impact on human gut bacteria that are believed to play a role in their clinical efficacy on kidney function. Nutrition therapies, including a low-protein diet, dietary fiber, a Mediterranean diet, and whole grains, positively influence gut microbiota composition and have been linked to a decreased risk of CKD. Novel strategies are currently being explored, involving the use of postbiotics, microbiome sequencing techniques, and fecal microbiota transplantation, although clinical application remains to be tested. Human trials investigating the above-mentioned interventions remain inconclusive due to several limitations, including dietary variability and genetic factors. Future research should focus on the development of more effective probiotics, prebiotics, and microbial metabolism-modifying drugs, not only for CKD but for other systemic diseases as well.}, } @article {pmid40572299, year = {2025}, author = {Cintoni, M and Palombaro, M and Zoli, E and D'Agostino, G and Pulcini, G and Leonardi, E and Raoul, P and Rinninella, E and De Maio, F and Capristo, E and Gasbarrini, A and Mele, MC}, title = {The Interplay Between the Gut Microbiota and Colorectal Cancer: A Review of the Literature.}, journal = {Microorganisms}, volume = {13}, number = {6}, pages = {}, pmid = {40572299}, issn = {2076-2607}, abstract = {Lifestyle, diet, and genetics are established risk factors for developing colorectal cancer (CRC). In recent years, the role of the gut microbiota (GM) has been increasingly highlighted in several studies, suggesting an effect on both the disease's pathogenesis and the efficacy and tolerability of treatments. We conducted a search on Medline, aiming to identify published studies exploring the role of the GM in the development and treatment of CRC. Dysbiosis, an imbalance in GM, is common in CRC patients and is associated with precancerous lesions, aggressive tumors, and varied therapy outcomes. Restoring GM balance can reduce treatment complications and may improve prognosis. The review details how GM influences CRC through metabolite production, inflammation modulation, and immune response alteration. Diet significantly impacts GM composition, with processed meats and high-fat diets increasing CRC risk, while fiber-rich diets are protective. The role of the GM in CRC treatments like surgery, chemotherapy, radiotherapy, and immunotherapy is also explored, noting its influence on complications, chemoresistance, and treatment efficacy. Future strategies involving GM modulation through diet, probiotics, and fecal microbiota transplantation (FMT) show promise for CRC prevention and treatment, warranting further research.}, } @article {pmid40572244, year = {2025}, author = {Roy, S and Alizadeh Bahmani, AH and Davids, M and Herrema, H and Nieuwdorp, M}, title = {Modulating the Gut-Muscle Axis: Increasing SCFA-Producing Gut Microbiota Commensals and Decreasing Endotoxin Production to Mitigate Cancer Cachexia.}, journal = {Microorganisms}, volume = {13}, number = {6}, pages = {}, pmid = {40572244}, issn = {2076-2607}, abstract = {Cancer cachexia is a multi-organ and multifactorial syndrome characterized by muscle wasting (with or without adipose tissue loss) and systemic inflammation in patients with advanced malignancies. Gut microbiota dysbiosis, particularly the depletion of short-chain fatty acid (SCFA)-producing bacteria, may contribute to the progression of cancer cachexia. Studies in both murine models and humans consistently associate cachexia with a decline in SCFA-producing gut microbiota commensals and an overgrowth of pro-inflammatory pathobionts. These microbial imbalances may lead to reduced levels of SCFAs and branched-chain amino acids (BCAAs) and alter the normal bile acid profile. BCAAs and the maintenance of a normal bile acid profile are associated with muscle synthesis and decreased breakdown. While SCFAs (acetate, propionate, and butyrate), contribute to intestinal barrier integrity and immune regulation. SCFA depletion may increase gut permeability, allowing bacterial endotoxins, such as lipopolysaccharide (LPS), to enter the bloodstream. This may lead to chronic inflammation, muscle catabolism, and impairment of anabolic pathways. Interventions targeting gut microbiota in preclinical models have mitigated inflammation and muscle loss. While clinical data are limited, it suggests an improvement in immune functions and better tolerance to anticancer therapies. Current evidence is predominantly derived from cross-sectional studies suggesting associations without causality. Thus, future longitudinal studies are needed to identify biomarkers and optimize personalized therapy.}, } @article {pmid40572178, year = {2025}, author = {Maniscalco, I and Bartochowski, P and Priori, V and Iancau, SP and De Francesco, M and Innamorati, M and Jagodzinska, N and Giupponi, G and Masucci, L and Conca, A and Mroczek, M}, title = {The Effects of Fecal Microbial Transplantation on the Symptoms in Autism Spectrum Disorder, Gut Microbiota and Metabolites: A Scoping Review.}, journal = {Microorganisms}, volume = {13}, number = {6}, pages = {}, pmid = {40572178}, issn = {2076-2607}, abstract = {The bilateral interaction between the brain and the gut has recently been on the spectrum of researchers' interests, including complex neural, endocrinological, and immunological signaling pathways. The first case reports and clinical studies have already reported that delivering microbes through fecal microbial transplantation (FMT) may alleviate symptoms of psychiatric disorders. Therefore, modifying the gut microbiota through FMT holds promise as a potential treatment for psychiatric diseases. This scoping review assessed studies from PubMed related to FMT in autism spectrum disorder and attention deficit hyperactivity disorder. The evaluation included nine clinical studies and case reports. The beneficial and persistent effect on the autism spectrum disorder (ASD) symptoms has been reported. Also, an increased microflora diversity and altered levels of neurometabolites in serum were identified, albeit with a tendency to return to baseline over time. The microbiome-gut-brain axis could provide new targets for preventing and treating psychiatric disorders. However, a recent large randomized clinical trial has shed light on the previously collected data and suggested a possible contribution of the placebo effect. This highlights the necessity of large randomized double-blind studies to reliably assess the effect of FMT in ASD.}, } @article {pmid40571138, year = {2025}, author = {Chen, QZ and Shang, JM and Jiang, YQ and Yang, Y and Zang, CX and Ma, JW and Dong, YR and Wang, JR and Zhou, N and Yang, X and Li, FF and Bao, XQ and Zhang, D}, title = {Gut microbial dysbiosis aggravated Parkinson-like pathology induced by MPTP/probenecid.}, journal = {Physiology & behavior}, volume = {299}, number = {}, pages = {115008}, doi = {10.1016/j.physbeh.2025.115008}, pmid = {40571138}, issn = {1873-507X}, mesh = {Animals ; *Dysbiosis/complications/microbiology/chemically induced ; *Gastrointestinal Microbiome/physiology/drug effects ; Mice ; Male ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Probenecid ; Disease Models, Animal ; *Parkinsonian Disorders/pathology/microbiology ; Dopaminergic Neurons/pathology ; Anti-Bacterial Agents ; }, abstract = {Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by resting tremor, bradykinesia, rigidity and postural instability. Recent studies have proved that gut microbiota (GM) dysbiosis exists in PD patients. However, the causal relationship between gut microbial dysbiosis and pathogenesis of PD remains unexplored. Here, using MPTP/probenecid-induced PD mouse model and an antibiotic cocktail (ABX)-induced pseudo-germ-free status, we observed that GM diversity and abundance significantly decreased in feces of ABX-treated PD mice by 16S rRNA sequencing. Remarkably, gut microbial dysbiosis induced by ABX aggravated GI dysfunction and motor deficits in PD mice. Moreover, ABX treatment caused more severe inflammation, and dopaminergic (DAergic) neuronal loss in both the gut and brain. Further study showed that fecal microbiota transplantation (FMT) corrected gut microbial dysbiosis, along with increased short-chain fatty acids (SCFAs). Additionally, GI and motor dysfunctions were improved, peripheral and central inflammation were also attenuated when PD mice were treated with FMT. These findings revealed that gut microbial dysbiosis could aggravate PD pathological damages, and highlighted that gut microbial dysbiosis might be an important factor that impacts PD pathogenesis through the microbiota-gut-brain axis.}, } @article {pmid40570572, year = {2025}, author = {Ordóñez, C and Zurita, S and Ramírez, G and Cordeiro, F and Garcia-Matamoros, K and Huaman-Garaicoa, F and Orellana-Manzano, A and Sandoya-Onofre, L and Pogo, J and Carvajal-Aldaz, D}, title = {Are we there yet? Gut microbiota for cancer diagnosis, prognosis and treatment.}, journal = {Seminars in oncology}, volume = {52}, number = {4}, pages = {152376}, doi = {10.1016/j.seminoncol.2025.152376}, pmid = {40570572}, issn = {1532-8708}, abstract = {Cancer remains as one of the leading causes of death worldwide, emphasizing the need for innovative diagnostic and therapeutic tools. The gut microbiota has emerged as a factor that influences cancer progression, prognosis, and treatment outcomes. This review analyzes observational and interventional studies conducted with human subjects over the past 5 years, highlighting significant advancements in gut microbiota research for cancer management. Observational studies consistently demonstrated differences in gut microbial composition between cancer patients and healthy controls. Moreover, microbial diversity, particularly at the species and strain level, correlated significantly with clinical outcomes. Interventional studies showed the potential of probiotics and fecal microbiota transplantation (FMT) as adjuncts in cancer therapy by restoring microbial diversity, reducing inflammation, and alleviating chemotherapy-induced complications. Collectively, these findings suggest the gut microbiota's potential as a tool for cancer care. Future research should focus on standardizing taxonomic-level analyses, optimizing probiotic formulations, and validating FMT/AFMT clinical protocols to fully harness the gut microbiota's diagnostic and therapeutic capabilities in oncology.}, } @article {pmid40570072, year = {2025}, author = {Shatova, OP and Shestopalov, AV and Zlatnik, EY and Novikova, IA and Goncharova, AS and Maksimov, AY}, title = {The effect of fecal microbiota transplantation on levels of tryptophan metabolites in intestine and serum of gnotobiotic mice.}, journal = {Biomeditsinskaia khimiia}, volume = {71}, number = {3}, pages = {209-216}, doi = {10.18097/PBMCR1554}, pmid = {40570072}, issn = {2310-6972}, mesh = {Animals ; *Tryptophan/metabolism/blood ; Mice ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Germ-Free Life ; Indoles/metabolism/blood ; *Intestines/microbiology ; Feces/microbiology ; Male ; Kynurenine/blood/metabolism ; Quinolinic Acid/metabolism/blood ; }, abstract = {Gut microbiota is one of the key suppliers of tryptophan metabolites, which perform various functions in the host organism, including their role as signaling molecules. Fecal microbiota transplantation (FMT) is widely used as a method for determining the contribution of microorganisms to the content of various metabolites in the holoorganism. In this regard, the aim of our study was to investigate the effect of FMT on the level of tryptophan metabolites in feces and blood in gnotobiotic mice. It was found that both before and after FMT, indole-3-lactate, and quinolinic acid were the dominant tryptophan metabolites in the intestine. FMT increased the content of both indoles (indole-3-acetate, indole-3-acrylate, indole-3-butyrate, indole-3-lactate) and kynurenines (anthranilic and xanthurenic acids) in the intestine. In serum of mice after FMT, indole metabolites (indole-3-butyrate, indole-3-carboxaldehyde, indole-3-lactate, indole-3-propionate) predominantly increased; however, tryptamine and xanthurenic acid also demonstrated a clear increase. The use of FMT demonstrates that the intestinal microbiota is a source of not only indole derivatives of tryptophan, but also metabolites of the kynurenine pathway.}, } @article {pmid40569502, year = {2025}, author = {Mortezaee, K}, title = {Microbiota interaction with Tregs: a target for colitis.}, journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico}, volume = {}, number = {}, pages = {}, pmid = {40569502}, issn = {1699-3055}, abstract = {Gut-resident microbiota associate with host immune system to promote homeostasis, and regulatory T cells (Tregs) are critical in the maintenance of immune balance. Tregs have immunosuppressive activity, and their presence hampers the development of inflammatory diseases. This review aims to unravel microbiome impact on Tregs in bowel inflammation and harnessing such interaction to combat colitis as a separate disease or a consequence of immune checkpoint inhibitor (ICI) therapy of cancer. Short-chain fatty acids (SCFAs) are microbial-derived metabolites associated positively with Treg generation and maintenance and being effective for hampering bowel inflammation. Treg induction shapes gut microbiota profile and support microorganism colonization in their niche and protect the host from inflammation, while suppression of Treg differentiation and activity directs microbiota-induced Th17 expansion and inducing inflammation. Thus, balancing Treg representation with Th17 cells and Treg reprogramming through manipulation of gut microbiota can offer therapy. Microbiota epithelial attachment/detachment and interaction with antigen-presenting cells (APCs) are important for the final fate of T cell signature. Fecal microbial transplantation (FMT) is a strategy for promoting normobiosis and represents a navel approach to targeting colitis. FMT with appropriate microbiota from healthy donors can reinforce microbial diversity, density and persistence to enrich their environment with transforming growth factor (TGF)-β, induce IL-10 producing APCs and reinforce gut barrier, with all these being effective for recovering Tregs, restoring intestinal homeostasis and hampering colitis. ICI therapy of cancer may predispose subjects to colitis due to the impact on microbiome and reducing Treg population. FMT promotes local Treg reorchestration, being advantageous in cancer patients.}, } @article {pmid40568731, year = {2025}, author = {Masetti, R and Barbara, G and Muratore, E and Marasco, G and Cremon, C and Marangoni, A and Brigidi, P and Putignani, L and Angelino, G and Quagliarella, F and Galaverna, F and Leardini, D and Lazzarotto, T and Gabelli, M and Savarino, E and Zecca, M and Faraci, M and Prete, A and Biffi, A and Locatelli, F and Merli, P}, title = {Fecal microbiota transplantation for decolonization from multidrug-resistant bacteria in pediatric allogeneic hematopoietic stem cell transplantation recipients: a retrospective real-word data study.}, journal = {Haematologica}, volume = {}, number = {}, pages = {}, doi = {10.3324/haematol.2025.288067}, pmid = {40568731}, issn = {1592-8721}, abstract = {Not available.}, } @article {pmid40568683, year = {2025}, author = {Wang, C and Fan, Y and Zhang, L and Zhao, Z and Luo, F and Sun, K and Zeng, M and Tian, H and Peng, M and Luo, Y and Zhao, H and He, S and Sun, H}, title = {Deciphering the contributions of fecal microbiota from patients with high-grade glioma to tumor development in a humanized microbiome mouse model of glioma.}, journal = {Neuro-oncology advances}, volume = {7}, number = {1}, pages = {vdaf085}, pmid = {40568683}, issn = {2632-2498}, abstract = {BACKGROUND: Recent studies have revealed associations between gut microbiota and glioma. However, the underlying mechanisms remain poorly understood. This study primarily aims to elucidate the impact of altered gut microbiota on tumor progression in glioma-bearing mice.

METHODS: Fecal samples were collected from glioma patients and healthy controls to compare the effects of human-derived gut microbiota on glioma development in mice. We also analyzed the associations between these microbiota profiles and plasma metabolites.

RESULTS: Significant differences were observed in both the composition and diversity of the gut microbiota between glioma patients and healthy controls. Mice transplanted with gut microbiota from high-grade glioma patients (HGG-FMT) exhibited accelerated glioma progression compared to those transplanted with microbiota from healthy individuals (HC-FMT). Specifically, Eisenbergiella, Mailhella, and Merdimonas were significantly enriched in HGG-FMT mice, while Limosilactobacillus and Anaerospora increased in HC-FMT mice. Furthermore, Merdimonas showed a positive correlation with sphingosine, sphingosine 1-phosphate, and D-sphingosine in HGG-FMT mice. Conversely, Limosilactobacillus was positively correlated with stearidonic acid and eicosapentaenoic acid in HC-FMT mice.

CONCLUSIONS: Our findings demonstrate that gut microbiota from high-grade glioma patients can promote glioma progression in mice, potentially through mechanisms involving sphingosine 1-phosphate. This metabolite may enter the bloodstream and accelerate glioma growth, offering novel insights into glioma pathogenesis and potential treatment options.}, } @article {pmid40564914, year = {2025}, author = {Wong, JKC and Patel, BK and Tai, YK and Tan, TZ and Khine, WWT and Chen, WC and Kukumberg, M and Ching, J and Lee, LS and Chua, KV and Tan, TY and Wu, KY and Bai, X and Iversen, JN and Purnamawati, K and Abdul Jalil, R and Kumar, AP and Lee, YK and Moochhala, SM and Franco-Obregón, A}, title = {Fecal Microbiota Transplantation from Mice Receiving Magnetic Mitohormesis Treatment Reverses High-Fat Diet-Induced Metabolic and Osteogenic Dysfunction.}, journal = {International journal of molecular sciences}, volume = {26}, number = {12}, pages = {}, pmid = {40564914}, issn = {1422-0067}, support = {A-0001177-01-00//iHealthtech Microbiome in Health, Disease and Aging 2018 Joint Research Grant/ ; MOE-T2EP30120-0016//Ministry of Education/ ; NUHSRO/2023/039/RO5+6/Seed-Mar/04//National University Health System/ ; }, mesh = {Animals ; *Diet, High-Fat/adverse effects ; Mice ; *Fecal Microbiota Transplantation/methods ; Male ; *Osteogenesis ; Mice, Inbred C57BL ; Ceramides/metabolism ; Gastrointestinal Microbiome ; *Magnetic Field Therapy/methods ; Liver/metabolism ; *Metabolic Diseases/therapy/etiology/metabolism ; Bone Density ; }, abstract = {This study compared the metabolic consequences of fecal microbiota transplantation (FMT) from donor mice that had been either administered pulsed electromagnetic field (PEMF) therapy or exercised to recipient mice fed a high-fat diet (HFD). Eight weeks of PEMF treatment (10 min/week) enhanced PGC-1α-associated mitochondrial and metabolic gene expression in white and brown adipose to a greater degree than eight weeks of exercise (30-40 min/week). FMT from PEMF-treated donor mice recapitulated these adipogenic adaptations in HFD-fed recipient mice more faithfully than FMT from exercised donors. Direct PEMF treatment altered hepatic phospholipid composition, reducing long-chain ceramides (C16:0) and increasing very long-chain ceramides (C24:0), which could be transferred to PEMF-FMT recipient mice. FMT from PEMF-treated mice was also more effective at recovering glucose tolerance than FMT from exercised mice. PEMF treatment also enhanced bone density in both donor and HFD recipient mice. The gut Firmicutes/Bacteroidetes (F/B) ratio was lowest in both the directly PEMF-exposed and PEMF-FMT recipient mouse groups, consistent with a leaner phenotype. PEMF treatment, either directly applied or via FMT, enhanced adipose thermogenesis, ceramide levels, bone density, hepatic lipids, F/B ratio, and inflammatory blood biomarkers more than exercise. PEMF therapy may represent a non-invasive and non-strenuous method to ameliorate metabolic disorders.}, } @article {pmid40564903, year = {2025}, author = {Chung, BS and Yang, K and Park, C and Ryu, T}, title = {Prolonged Intestinal Ethanol Absorption and Oxidative Stress: Revisiting the Gut-Liver Axis in Alcohol-Associated Disease.}, journal = {International journal of molecular sciences}, volume = {26}, number = {12}, pages = {}, pmid = {40564903}, issn = {1422-0067}, support = {RS-2023-00238039//National Research Foundation of Korea/ ; }, mesh = {Humans ; *Oxidative Stress/drug effects ; *Ethanol/pharmacokinetics/metabolism ; *Intestinal Absorption ; Animals ; *Liver/metabolism/drug effects ; Gastrointestinal Microbiome ; *Liver Diseases, Alcoholic/metabolism ; Intestinal Mucosa/metabolism ; *Alcoholism/metabolism ; Dysbiosis ; }, abstract = {Chronic alcohol consumption induces oxidative stress not only in the liver but also in the gastrointestinal tract, where prolonged intestinal ethanol absorption plays a pivotal and underrecognized role. This review reframes ethanol pharmacokinetics to emphasize sustained jejunal and ileal uptake, which maintains elevated blood alcohol levels and perpetuates redox imbalance across the gut-liver axis. We integrate recent findings on ethanol-induced barrier dysfunction, CYP2E1-mediated ROS production, microbial dysbiosis, and mitochondrial disruption, proposing that the intestine is an active site of injury and a driver of systemic inflammation. Key mechanistic insights reveal that gut-derived endotoxins, compromised epithelial integrity, and microbiome-mitochondria interactions converge to exacerbate hepatic and extrahepatic damage. We further explore emerging therapeutic strategies-ranging from NAD[+] repletion and probiotics to fecal microbiota transplantation-that target this upstream pathology. Recognizing prolonged intestinal ethanol absorption as a clinically meaningful phase offers new directions for early intervention and redox-based treatment in alcohol-associated disease.}, } @article {pmid40564111, year = {2025}, author = {Bieganska, EA and Kosinski, P and Wolski, M}, title = {Possible Applications of Fecal Microbiota Transplantation in the Pediatric Population: A Systematic Review.}, journal = {Biomedicines}, volume = {13}, number = {6}, pages = {}, pmid = {40564111}, issn = {2227-9059}, abstract = {Background: The potential therapeutic role of fecal microbiota transplantation (FMT) in various diseases has been thoroughly studied over the last few decades. However, the majority of studies focus on the adult population, therefore, conclusions regarding the application of FMT in the pediatric population are much less clear. This systematic review aims to summarize the research conducted so far on the efficacy and safety of FMT in the pediatric population, assess the quality of the evidence of its effectiveness, and outline the most promising areas for future research. Methods: We performed a systematic literature search from the index date to 8 June 2024 on the Embase, PubMed, and Web of Science databases. One author screened the resulting 121 articles. Eventually, 35 eligible studies that reported FMT use in seven different diseases were identified. Results: All of the studies assessed FMT as a safe procedure without many serious adverse effects. The best-documented application, which is the only one recommended in official guidelines, is recurrent Clostridioides difficile infection. Other disease entities in which the use of FMT has been studied with good clinical effects are inflammatory bowel disease, allergic colitis, autism, Tourette syndrome, and colonization with multi-drug-resistant organisms. However, it should be noted that the majority of studies are cohort and case-control studies, without randomization, which translates into low evidence quality. In one randomized, controlled trial focusing on the effect of FMT on weight loss in obese individuals, a lack of effect was found. Conclusions: While FMT and subsequent iterations of gut microbiota-targeted interventions hold promising therapeutic potential for various disease entities in the pediatric population, the current evidence behind this conclusion is of low quality. Based on current studies, these methods appear to be both effective and safe. However, further randomized clinical trials are necessary, especially within the pediatric population, for which such studies remain scarce.}, } @article {pmid40564097, year = {2025}, author = {Severino, A and Porcari, S and Rondinella, D and Capuano, E and Rozera, T and Kaitsas, F and Gasbarrini, A and Cammarota, G and Ianiro, G}, title = {The Multi-Faceted Role of Gut Microbiota in Alopecia Areata.}, journal = {Biomedicines}, volume = {13}, number = {6}, pages = {}, pmid = {40564097}, issn = {2227-9059}, abstract = {Alopecia areata (AA) is a complex autoimmune disorder with multifactorial pathogenesis. Recent research highlights the gut microbiota as a possible key player in AA pathogenesis through the gut-skin axis: gut dysbiosis may disrupt intestinal barrier integrity and immune tolerance by affecting T regulatory cells, potentially contributing to disease onset and progression. The purpose of this review is to analyze the current evidence on the correlation between gut microbiota and AA, dissecting both the pathogenetic role of its alterations in the onset and progression of disease and its potential role as a therapeutic target.}, } @article {pmid40563141, year = {2025}, author = {Zhang, Y and Qing, J and Saed, YA and Li, Y}, title = {Gut microbiota implication in diabetic kidney disease: mechanisms and novel therapeutic strategies.}, journal = {Renal failure}, volume = {47}, number = {1}, pages = {2517402}, doi = {10.1080/0886022X.2025.2517402}, pmid = {40563141}, issn = {1525-6049}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/complications/microbiology/therapy ; *Diabetic Nephropathies/microbiology/therapy/etiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; *Diabetes Mellitus, Type 2/complications ; Synbiotics/administration & dosage ; Disease Progression ; }, abstract = {Diabetic kidney disease (DKD) is one of the leading causes of chronic kidney disease and end-stage renal disease worldwide, predominantly driven by the rise in type 2 diabetes mellitus. Recent evidence highlights the crucial role of gut microbiota dysbiosis in the development and progression of DKD. Dysbiosis, characterized by a reduction in beneficial short-chain fatty acid-producing bacteria and an increase in pathogenic species such as Proteobacteria and Bacteroides, exacerbates systemic inflammation, insulin resistance, and kidney damage through mechanisms like increased intestinal permeability and the production of pro-inflammatory metabolites like lipopolysaccharides. This review explores the impact of specific bacterial taxa on DKD risk and progression, such as Alistipes, Subdoligranulum, and their interactions with metabolic pathways. Furthermore, we discuss novel therapeutic strategies targeting gut microbiota, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, which have shown promise in ameliorating DKD symptoms. However, the heterogeneity of gut microbiota across individuals and the challenges in treatment standardization call for personalized approaches and further research into the gut-kidney axis.}, } @article {pmid40563092, year = {2025}, author = {Amimo, JO and Kunyanga, CN and Raev, SA and Kick, M and Micheal, H and Saif, LJ and Vlasova, AN}, title = {Stunting is associated with persistent and transferable alterations in the gut microbiome.}, journal = {Gut pathogens}, volume = {17}, number = {1}, pages = {49}, pmid = {40563092}, issn = {1757-4749}, support = {OPP1117467//Bill and Melinda Gates Foundation/ ; R01A1099451//National Institute of Allergy and Infectious Diseases/ ; }, abstract = {As robust animal models to study the pathophysiology of stunting are absent, we have comparatively characterized the gut microbiota of malnourished/stunted vs. clinically healthy/normal Kenyan toddlers (12-24 months old) and established a gnotobiotic (Gn) pig fecal transplant model to gain understanding of microbial community structure associated with stunting. As expected, the bacterial composition between the two toddler groups was distinct: Actinobacteria was most prevalent in healthy toddlers, whereas Proteobacteria dominated in stunted toddlers. Although the diversity indices showed no significant differences, unique bacterial genera were found in each toddler group: three genera unique to stunted toddlers and ten unique to healthy toddlers, with eight genera shared between the groups. We observed a higher number of enriched bacterial virulence genes in healthy vs. stunted toddlers suggesting that the microbiome plasticity and functional characteristics of the healthy toddlers allow for the pathogen/pathobiont control. In contrast, we noted the presence of more genes associated with antimicrobial-resistance (AMR) bacteria in stunted toddlers, possibly due to early-life antibiotic treatments. Of interest, functional analysis showed that CAZymes associated with carbohydrate biosynthesis, and a few metabolic pathways related to protein/amino acid, carbohydrate and fat catabolism were enriched in stunted toddlers. In contrast carbohydrate degradation CAZymes and numerous anabolic pathways were prevalent in healthy toddlers. These patterns were also evident in the Gn pigs transplanted with stunted/healthy human fecal microbiota (HFM). Overall, our findings suggest that the microbiota transplanted Gn pigs represent a valuable model for studying the infant microbial community structure and the impacts of stunting on the child gut microbiota. Additionally, this is the first study to demonstrate that the healthy vs. stunted microbiota composition and function remained different in the Gn pigs throughout the study. This information and the Gn pig model are vital for developing and testing targeted interventions for malnourished/stunted populations, consequently advancing microbiome-based diagnosis and personalized medicine.}, } @article {pmid40561430, year = {2025}, author = {Ung, W and Bonavida, B}, title = {Review Article: Fecal Microbiota Transplantation in Melanoma: Mechanisms-Mediated Enhancement of Anti-Tumor Immunotherapy.}, journal = {Critical reviews in oncogenesis}, volume = {30}, number = {2}, pages = {23-35}, doi = {10.1615/CritRevOncog.2025058249}, pmid = {40561430}, issn = {0893-9675}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Melanoma/therapy/immunology/microbiology/etiology ; *Immunotherapy/methods ; *Gastrointestinal Microbiome/immunology ; Immune Checkpoint Inhibitors/therapeutic use ; Animals ; *Skin Neoplasms/therapy/immunology/microbiology ; }, abstract = {The gut microbiota is integral to human health, influencing nutrition, metabolism, and immunity. Dysbiosis has been implicated in cancer development and resistance to therapies, highlighting the potential of microbiota modulation as a therapeutic strategy. Melanoma, while comprising only 1% of skin cancer diagnoses, accounts for over 80% of skin cancer related deaths, emphasizing the need for innovative approaches to enhance treatment efficacy. Although immune checkpoint inhibitors (ICIs) such as anti-programmed cell death protein (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) blockade therapies have significantly improved survival for some melanoma patients, the majority fails to achieve durable responses and often develops long-term resistance to these treatments. Fecal microbiota transplantation (FMT) is emerging as a promising intervention to restore microbial balance and enhance treatment efficacy. This review explores the historical evolution and current applications of FMT in oncology, with a focus on its ability to modulate the gut microbiome, augment antitumor immunity, and overcome resistance to checkpoint blockade therapy in melanoma. Despite its promise, significant challenges remain, including ensuring the safety of the procedure, selecting suitable donors, and addressing regulatory hurdles. Future research aimed at optimizing FMT protocols, identifying key microbial strains, and understanding the mechanisms underlying microbiota-immune interactions will be essential to fully harness the potential of FMT as a transformative adjunct in cancer treatment.}, } @article {pmid40559778, year = {2025}, author = {Nishigaki, A and Marchesi, JR and Previdelli, RL}, title = {Faecal Microbiota Transplantation as an Adjuvant Treatment for Extraintestinal Disorders: Translating Insights from Human Medicine to Veterinary Practice.}, journal = {Veterinary sciences}, volume = {12}, number = {6}, pages = {}, pmid = {40559778}, issn = {2306-7381}, abstract = {Faecal microbiota transplantation (FMT) has emerged as a transformative therapy in human medicine, particularly for managing recurrent Clostridioides difficile infections and other gastrointestinal (GI) disorders. Beyond the GI tract, FMT has shown potential in addressing extraintestinal conditions in people, including metabolic, immune-mediated, dermatological, neurological, and infectious diseases. Research in people has highlighted its efficacy in decolonising multidrug-resistant organisms in infection, mitigating autoimmune diseases, and improving outcomes in metabolic disorders such as obesity and diabetes. Furthermore, FMT has also been linked to enhanced responses to immunotherapy in cancer and improved management of hepatic and renal conditions. These findings underscore the intricate connections between the gut microbiome and systemic health, opening novel therapeutic avenues. In veterinary medicine, while FMT has demonstrated benefits for GI disorders, its application in extraintestinal diseases remains largely unexplored. Emerging evidence suggests that conditions such as atopic dermatitis, chronic kidney disease, immune-mediated diseases, and behavioural disorders in companion animals could benefit from microbiome-targeted therapies. However, significant gaps in knowledge persist, particularly regarding the long-term safety and efficacy for veterinary applications. This review synthesises findings from human medicine to assess their relevance for veterinary applications and future research.}, } @article {pmid40559592, year = {2025}, author = {Egrek, S and Knapp, J and Sacheli, R and El Moussaoui, K and Léonard, P and Larranaga Lapique, E and Millon, L and Engelskirchen, S and Detry, O and Linden, A and Hayette, MP}, title = {EmsB Microsatellite Analysis of Echinococcus multilocularis Specimens Isolated from Belgian Patients with Alveolar Echinococcosis and from Animal Hosts.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {6}, pages = {}, pmid = {40559592}, issn = {2076-0817}, mesh = {Animals ; *Echinococcus multilocularis/genetics/isolation & purification/classification ; Humans ; Foxes/parasitology ; *Microsatellite Repeats ; Belgium/epidemiology ; *Echinococcosis/parasitology ; Retrospective Studies ; Zoonoses/parasitology ; *Echinococcosis, Hepatic/parasitology ; Genotype ; Rodentia/parasitology ; Feces/parasitology ; }, abstract = {Alveolar echinococcosis (AE), caused by Echinococcus multilocularis (E. multilocularis), is a severe parasitic zoonosis that is potentially fatal for humans. The parasite is primarily transmitted by wildlife, with red foxes acting as definitive hosts and rodents as intermediate hosts, while humans can become accidental but dead-end hosts. The aim of this study is to use EmsB typing on E. multilocularis isolates from human AE cases and local animals such as foxes and rodents. In this study, retrospective EmsB typing was performed on 39 samples, including 11 tissue samples from 10 patients, 18 fecal swabs from foxes, and 10 tissue samples from rodents. A dendrogram was created to determine the EmsB profiles present. The results showed that all the rodent samples were associated with the EmsB P1 profile (10/10), while the human and fox samples shared the EmsB profile P1 (5/11 humans and 8/18 foxes), a profile near P4 (2/11 humans and 3 foxes), and a profile near P8 (1/11 humans and 1/18 foxes). The study demonstrates that the same EmsB profiles circulate among humans and animals, confirming that wildlife reservoirs play a key role in transmission.}, } @article {pmid40559436, year = {2025}, author = {Domilescu, I and Miutescu, B and Horhat, FG and Popescu, A and Nica, C and Ghiuchici, AM and Gadour, E and Sîrbu, I and Hutanu, D}, title = {Gut-Microbiome Signatures Predicting Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review.}, journal = {Metabolites}, volume = {15}, number = {6}, pages = {}, pmid = {40559436}, issn = {2218-1989}, abstract = {BACKGROUND AND OBJECTIVES: Rectal cancer management increasingly relies on watch-and-wait strategies after neoadjuvant chemoradiotherapy (nCRT). Accurate, non-invasive prediction of pathological complete response (pCR) remains elusive. Emerging evidence suggests that gut-microbiome composition modulates radio-chemosensitivity. We systematically reviewed primary studies that correlated baseline or on-treatment gut-microbiome features with nCRT response in locally advanced rectal cancer (LARC).

METHODS: MEDLINE, Embase and PubMed were searched from inception to 30 April 2025. Eligibility required (i) prospective or retrospective human studies of LARC, (ii) faecal or mucosal microbiome profiling by 16S, metagenomics, or metatranscriptomics, and (iii) response assessment using tumour-regression grade or pCR. Narrative synthesis and random-effects proportion meta-analysis were performed where data were homogeneous.

RESULTS: Twelve studies (n = 1354 unique patients, median sample = 73, range 22-735) met inclusion. Four independent machine-learning models achieved an Area Under the Receiver Operating Characteristic curve AUROC ≥ 0.85 for pCR prediction. Consistently enriched taxa in responders included Lachnospiraceae bacterium, Blautia wexlerae, Roseburia spp., and Intestinimonas butyriciproducens. Non-responders showed over-representation of Fusobacterium nucleatum, Bacteroides fragilis, and Prevotella spp. Two studies linked butyrate-producing modules to radiosensitivity, whereas nucleotide-biosynthesis pathways conferred resistance. Pooled pCR rate in patients with a "butyrate-rich" baseline profile was 44% (95% CI 35-54) versus 21% (95% CI 15-29) in controls (I[2] = 18%).

CONCLUSIONS: Despite heterogeneity, convergent functional and taxonomic signals underpin a microbiome-based radiosensitivity axis in LARC. Multi-centre validation cohorts and intervention trials manipulating these taxa, such as prebiotics or live-biotherapeutics, are warranted before clinical deployment.}, } @article {pmid40558164, year = {2025}, author = {Han, X and Qin, Y and Guo, J and Huang, W and You, Y and Zhan, J and Yin, Y}, title = {IgA Dysfunction Induced by Early-Lifetime Low-Dose Antibiotics Exposure Aggravates Diet-Induced Metabolic Syndrome.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {6}, pages = {}, pmid = {40558164}, issn = {2079-6382}, support = {82330017 and 82270610//National Natural Science Foundation/ ; }, abstract = {Background: Low-dose antibiotic contamination in animal feed is a persistent global food safety challenge. Transient early-life exposure to low-dose penicillin (LDP) is known to induce metabolic syndrome (MetS) in adult mice, but the underlying mechanisms are unclear. Introduction: This study investigated the role of gut microbiota (GM) and intestinal immunity in mediating the long-term metabolic effects of early-life LDP exposure. Methods: Mice were exposed to LDP transiently during early life. GM composition was analyzed. Intestinal IgA responses were quantified. Bacterial encroachment, systemic and adipose tissue inflammation, and diet-induced MetS were assessed. Germ-free (GF) mice received GM transplants from LDP-exposed or control mice to test causality and persistence. Results: Early-life LDP exposure significantly disrupted GM composition, particularly in the ileum, in 30-day-old mice. These GM alterations caused persistent suppression of intestinal IgA responses, evidenced by reduced IgA-producing cells and sIgA levels. This suppression was constrained to early-life exposure: transferring LDP-modified GM to GF mice produced only a transient reduction in fecal sIgA. The LDP-induced sIgA reduction decreased IgA binding of bacteria, leading to increased bacterial encroachment and systemic and adipose tissue inflammation. These pathological changes exacerbated diet-induced MetS. Discussion: Our findings demonstrate that early-life LDP exposure induces persistent intestinal IgA deficiency through lasting GM alterations initiated in early development. This deficiency drives bacterial encroachment, inflammation, and ultimately exacerbates MetS. Conclusions: The exacerbation of diet-induced metabolic syndrome by early-life LDP exposure occurs through an intestinal sIgA-dependent pathway triggered by persistent GM disruption. This highlights a critical mechanism linking early-life antibiotic exposure, gut immune dysfunction, and long-term metabolic health, with significant implications for food safety.}, } @article {pmid40554893, year = {2025}, author = {You, L and Peng, H and Liu, J and Sai, N and Zhao, W and Li, X and Yang, C and Guo, P and Ni, J}, title = {Xiaoer Huanglong pellets remodels the periphery microenvironment to improve attention deficit hyperactivity disorder based on the microbiota-gut-brain axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {145}, number = {}, pages = {157007}, doi = {10.1016/j.phymed.2025.157007}, pmid = {40554893}, issn = {1618-095X}, mesh = {Animals ; *Attention Deficit Disorder with Hyperactivity/drug therapy/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology ; Rats ; Male ; Rats, Sprague-Dawley ; *Brain/drug effects ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Brain-Gut Axis/drug effects ; }, abstract = {BACKGROUND: Recently, research interest in attention deficit hyperactivity disorder (ADHD) has grown significantly, driven by its increasing incidence and substantial societal impact. Among the various pathogenic mechanisms under investigation, the microbiota-gut-brain axis has emerged as a crucial area of focus. In the context of ADHD treatment, Xiaoer Huanglong Pellets (XRHLP), a traditional Chinese herbal formulation, have demonstrated therapeutic efficacy, although the underlying mechanisms remain partially understood.

PURPOSE: This study aimed to analyze and compare the therapeutic effects and underlying mechanisms of XRHLP, including gastric release (WR_HL), enteric release (CR_HL), and colon release (JCR_HL) pellets, for ADHD treatment.

METHODS: This study employed a multi-modal approach to investigate the effects of XRHLP on ADHD. Behavioral assessments combined with Enzyme-linked immunosorbent assay and Western-blot analyses were conducted to evaluate the therapeutic outcomes in model rats with ADHD. Comprehensive profiling of the gut-brain axis was performed using 16S ribosomal RNA sequencing and untargeted and targeted metabolomic analyses. The causal role of the gut microbiota was further validated using fecal microbiota transplantation (FMT).

RESULTS: WR_HL, CR_HL, and JCR_HL improved ADHD-like behaviors and neurotransmission dysfunction, with JCR_HL exhibiting superior intervention effects compared to WR_HL and CR_HL. These therapeutic effects are mediated through multiple pathways, including the restoration of gut microbial homeostasis, attenuation of inflammatory cascades, and repair of compromised intestinal and blood-brain barrier. The intervention also corrected systemic metabolic imbalances by specifically addressing the abnormalities in amino acid metabolism, neurotransmitter regulation, and short-chain fatty acid production. FMT experiments further confirmed the critical role of microbial modulation in mediating the behavioral and microbial regulatory effects of XRHLP.

CONCLUSION: In summary, XRHLP exerts anti-ADHD effects by improving the microbiota-gut-brain axis and correcting amino acid metabolic disorders, providing new insights into the molecular mechanisms by which traditional Chinese medicine influences ADHD and offers potential avenues for drug development.}, } @article {pmid40554061, year = {2025}, author = {Yang, W and Zou, P and He, S and Cui, H and Yang, Z and An, H and Chen, Q and Huang, W and Guo, H and Liu, J and Ling, X and Cao, J and Ao, L}, title = {Perfluorooctane sulfonic acid impairs spermatogenesis via the liver-gut microbiota-testis axis: a central role of chenodeoxycholic acid metabolism.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.06.037}, pmid = {40554061}, issn = {2090-1224}, abstract = {INTRODUCTION: Perfluorooctane sulfonic acid (PFOS) as a global contaminant is ubiquitously presented in the environmental media and human body. The association between PFOS exposure and reduced male fertility has been recently discovered. However, the relevant mechanism remains unexplored.

OBJECTIVES: Our study aimed to investigate the effect and mechanism of PFOS exposure on male reproductive function.

METHODS: In a murine PFOS exposure model, single-nucleus transcriptome sequencing was performed to delineate the transcriptomic landscape of mouse testes at the single-cell resolution. We examined the serum metabolomic profile and conducted in-depth analysis of hepatic transcriptome datasets to explore the metabolic connections between liver and testis under PFOS exposure. Through integrating chenodeoxycholic acid intervention, fecal microbiota transplantation (FMT), metagenomic sequencing, testicular metabolome, Ligilactobacillus murinus (L. murinus) metabolome, and administration of L. murinus, we confirmed the role of the liver-gut microbiota-testis axis and screened the critical gut microbiota involved in PFOS-mediated spermatogenic disorders.

RESULTS: The results showed that PFOS exposure led to spermatogenic arrest and abnormal spermatogenic microenvironment in the mouse testis. The PFOS-repressed hepatic chenodeoxycholic acid (CDCA) synthesis contributed to the reduced serum/testicular levels of essential fatty acid (linoleic acid) and lipid-soluble vitamins (retinol, vitamin D3), which was responsible for the spermatogenic arrest. Beyond this, PFOS-mediated impaired CDCA production decreased the abundance of gut L. murinus, which affected spermatogenesis through the potential involvement of aspartic acid metabolism. For the first time to our knowledge, we comprehensively assessed the effects of PFOS exposure on the spermatogenic process and elucidated the unrecognized role of liver-gut microbiota-testis axis in PFOS-induced abnormal spermatogenesis.

CONCLUSIONS: The unveiled organ crosstalks provide new insights into the metabolism-disrupting properties, hepatotoxicity, and reproductive toxicity of PFOS, which may facilitate the development of molecule-, metabolite-, and microbe-based strategies for PFOS-induced metabolic diseases and reproductive disorders.}, } @article {pmid40553742, year = {2025}, author = {Frutkoff, YA and Plotkin, L and Pollak, D and Livovsky, J and Focht, G and Lev-Tzion, R and Ledder, O and Assa, A and Yogev, D and Orlanski-Meyer, E and Broide, E and Kierkuś, J and Kang, B and Weiss, B and Aloi, M and Schwerd, T and Shouval, DS and Bramuzzo, M and Griffiths, AM and Yassour, M and Turner, D}, title = {Whole Food Diet Induces Remission in Children and Young Adults With Mild to Moderate Crohn's Disease and Is More Tolerable Than Exclusive Enteral Nutrition: A Randomized Controlled Trial.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2025.06.011}, pmid = {40553742}, issn = {1528-0012}, abstract = {BACKGROUND & AIMS: Tasty&Healthy (T&H) is a whole food diet for Crohn's disease (CD) that excludes processed food, gluten, red meat, and dairy, without requiring formula or mandatory ingredients. TASTI-MM was a clinician-blinded, randomized controlled trial comparing tolerability and effectiveness of T&H vs exclusive enteral nutrition (EEN).

METHODS: Patients with biologic-naïve mild to moderate CD and aged 6-25 years were randomized to either T&H or EEN for 8 weeks, receiving weekly dietary support. Tolerability was evaluated by weekly interviews, questionnaires, and intake diaries. Other outcomes included symptomatic remission, Mucosal-Inflammation Noninvasive index, calprotectin, C-reactive protein, and erythrocyte sedimentation rate. Fecal microbiome was analyzed by metagenomics at baseline, week 4, and week 8. Data were analyzed by the intention-to-treat approach unless specified otherwise.

RESULTS: Among 83 included patients (n = 41 T&H, n = 42 EEN; mean ± SD age, 14.5 ± 3.7 years), 88% tolerated T&H vs 52% for EEN (adjusted odds ratio [aOR], 7.7; 95% CI, 2.4-25; P < .001). Calprotectin, C-reactive protein, and erythrocyte sedimentation rate decreased significantly in both groups, with no between-group differences. Symptomatic remission was achieved in 56% of the T&H group vs 38% of the EEN group (aOR, 2.5; 95% CI, 0.98-6.3; P = .1; per-protocol: 67% vs 76%; P = .47). Calprotectin <250 μg/g was achieved in 34% vs 33% (aOR, 0.97; 95% CI, 0.37-2.6; P = .84) and Mucosal-Inflammation Noninvasive index score <8 in 44% vs 31% (aOR, 1.8; 95% CI, 0.7-4.5; P = .33). Microbiome α-diversity improved in the T&H arm and declined in the EEN arm, showing superior species richness at both week 4 and week 8. Species associated with bowel inflammation, such as Ruminococcus gnavus, decreased in T&H and increased in EEN (q < .001).

CONCLUSIONS: T&H demonstrated better tolerability than EEN for inducing remission in mild to moderate CD, while positively affecting the microbiome.

CLINICALTRIALS: gov, Number: NCT04239248.}, } @article {pmid40552988, year = {2025}, author = {Park, JM and Beckman, I and Delaney, CL}, title = {Narrative review of the association between gut microbiota and peripheral artery disease.}, journal = {Vascular medicine (London, England)}, volume = {}, number = {}, pages = {1358863X251346062}, doi = {10.1177/1358863X251346062}, pmid = {40552988}, issn = {1477-0377}, abstract = {It has been posited that the inflammatory process seen in atherosclerosis is underpinned by gut dysbiosis. Dysbiosis refers to alterations in the function, composition, and diversity of the human gut microbiota, all of which are influenced by endogenous and exogenous stimuli. Currently there is limited literature describing the association between gut microbiota and peripheral artery disease (PAD). This review summarizes the evidence surrounding the role of gut microbiota in the initiation of atherosclerosis (through direct infection of atherosclerotic plaque or systemic immune response to bacterial products and metabolites) and how dysbiosis may influence the various treatment modalities for PAD, including medical therapy (pharmacotherapy, lifestyle changes, and supervised exercise training) and surgery (endovascular and open revascularization). In particular, the role of short chain fatty acids (SCFAs), the effects of exercise on SCFA-producing and lactic acid bacteria (LAB) and, consequently, the lack of targeted research into dietary interventions and supplementation are highlighted in this review. This review highlights the potential for gut microbiota as not only a therapeutic target in patients with PAD, but also as a diagnostic and screening tool. It is imperative that the focus of future research is on the potential for personalized treatment which targets the gut microbiota (such as synbiotics, postbiotics, nicotinamide adenine dinucleotide (NAD) supplementation, selective antibiotics, resistance exercise, senolytics, and fecal microbial transplantation [FMT]) to be utilized as adjuncts to already existing treatment options for PAD. This review also highlights the potential role of biobanks and analysis of atherosclerotic plaques in further advancing knowledge and research in this area.}, } @article {pmid40552775, year = {2025}, author = {Yang, T and Shao, Y and Wang, Z and Liu, C and Gu, M}, title = {Epigallocatechin-3-Gallate Attenuates Benign Prostatic Hyperplasia Development via Regulating Firmicutes to Inhibit Gastric Secretion of Insulin-Like Growth Factor-1.}, journal = {Cell biology international}, volume = {49}, number = {8}, pages = {952-964}, doi = {10.1002/cbin.70032}, pmid = {40552775}, issn = {1095-8355}, support = {//The work was sponsored by the Interdisciplinary Program of Shanghai Jiao Tong University (Project Number YG2024QNB17) and the National Natural Science Foundation of China (Grant Nos. 82170788 and 81900687)./ ; }, mesh = {Male ; Animals ; *Catechin/analogs & derivatives/pharmacology ; *Prostatic Hyperplasia/metabolism/drug therapy/microbiology/pathology ; Mice ; *Insulin-Like Growth Factor I/metabolism ; Humans ; Gastrointestinal Microbiome/drug effects ; Mice, Inbred C57BL ; Signal Transduction/drug effects ; Disease Models, Animal ; Phosphatidylinositol 3-Kinases/metabolism ; Cell Proliferation/drug effects ; Prostate/metabolism/drug effects/pathology ; Insulin-Like Peptides ; }, abstract = {Benign prostatic hyperplasia (BPH), a prevalent age-related condition in men, is increasingly linked to metabolic syndrome (MetS) and gut microbiota dysbiosis. This study reveals how Firmicutes-dominant microbial imbalance drives BPH progression via IGF-1 signaling and identifies the green tea polyphenol epigallocatechin-3-gallate (EGCG) as a dual-action therapeutic. Using MetS-BPH mouse models and human prostate cell lines, we demonstrated that BPH-associated gut microbiota-particularly elevated Firmicutes and an increased Firmicutes/Bacteroidetes ratio-promotes prostate hyperplasia by upregulating IGF-1. Both BPH mice and recipient mice transplanted with BPH microbiota showed elevated serum and prostate IGF-1 levels, mirroring findings in human BPH patients. Mechanistically, IGF-1 stimulated prostate cell proliferation (RWPE-1/WPMY-1) and suppressed apoptosis via PI3K/AKT/mTOR activation, while the IGF-1 antagonist Linsitinib reversed these effects. EGCG emerged as a potent modulator of this gut-prostate axis: it selectively reduced Firmicutes overgrowth in BPH mice, normalized IGF-1 levels, and inhibited downstream PI3K/AKT/mTOR signaling. In fecal microbiota transplantation experiments, EGCG counteracted IGF-1-driven prostate enlargement and microbial dysbiosis, underscoring its dual role in rebalancing gut flora and blocking growth factor pathways. Our findings position EGCG as a promising intervention for MetS-associated BPH, simultaneously targeting microbial dysbiosis and IGF-1 signaling. This study not only elucidates the Firmicutes-IGF-1 axis in BPH pathogenesis but also highlights the therapeutic potential of dietary polyphenols in metabolic urological disorders.}, } @article {pmid40552763, year = {2025}, author = {Claypool, J and Lindved, G and Myers, PN and Ward, T and Nielsen, HB and Blount, KF}, title = {Microbiome compositional changes and clonal engraftment in a phase 3 trial of fecal microbiota, live-jslm for recurrent Clostridioides difficile infection.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2520412}, doi = {10.1080/19490976.2025.2520412}, pmid = {40552763}, issn = {1949-0984}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Bacteria/classification/genetics/isolation & purification ; *Clostridioides difficile/physiology ; *Clostridium Infections/therapy/microbiology ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Recurrence ; }, abstract = {Live microbiota therapies have shown promise in many gastrointestinal diseases, including in the prevention of recurrent Clostridioides difficile infections (rCDI); however, frameworks for their pharmacokinetic and pharmacodynamic analysis are not fully established. Fecal microbiota, live-jslm (RBL) is the first microbiota-based product approved by the US Food and Drug Administration for the prevention of rCDI and was superior to placebo in the PUNCH™ CD3 phase 3 clinical trial (NCT03244644). In this analysis, deep shotgun metagenomic sequencing was used to assess changes in gut microbiome compositions of participants and engraftment of bacterial clonal populations (i.e. strains) from RBL to recipients. Among RBL responders, gut microbiota shifted toward compositions that resembled healthy donors as early as 1 week after RBL administration; the resulting microbiota compositions included clonal populations that engrafted from RBL to recipients. Engraftment was higher in RBL responders compared with non-responders, and many clonally engrafted populations persisted for ≥ 6 months. Bacteroidia species were among the most effectively engrafted species from RBL. This study utilizes data from a large clinical trial to establish a method with high specificity for exploring clonal engraftment from microbiota-based treatments to facilitate future pharmacokinetic and pharmacodynamic analyses.Clinicaltrials Registration: NCT03244644.}, } @article {pmid40552153, year = {2025}, author = {Sun, L and Shang, B and Lv, S and Liu, G and Wu, Q and Geng, Y}, title = {Effects of semaglutide on metabolism and gut microbiota in high-fat diet-induced obese mice.}, journal = {Frontiers in pharmacology}, volume = {16}, number = {}, pages = {1562896}, pmid = {40552153}, issn = {1663-9812}, abstract = {BACKGROUND: The purpose of this study was to explore how semaglutide, a GLP-1RA, regulates serum metabolism and gut microbiota to improve obesity in mice and whether fecal microbiota transplantation (FMT) can transmit the beneficial effects of semaglutide to recipient mice.

METHODS: Male C57BL/6J mice were given standard diet (ND), high-fat diet (HFD), or high-fat diet with semaglutide (SHF, 100 μg/kg). Fecal microbiota transplantation was used to transplant the fecal suspension supernatant (MT) and bacteria (FMT) from SHF group mice to antibiotic-induced pseudo-germ-free mice.

RESULTS: Results showed that semaglutide significantly reduced the body weight, body fat, FBG, and insulin levels induced by high-fat diet, and improved insulin resistance and sensitivity damage (p < 0.05). This was achieved by regulating the expression of genes related to lipid metabolism such as Pparα, Pparγ, Cpt1a, and Pgc1α in the liver and adipose tissue, as well as the appetite-related genes Leptin, Agrp, Npy, and Pomc in the hypothalamus. After stopping semaglutide intervention 4 weeks, the body weight of the mice rebounded significantly. Fecal microbiota transplantation could transmit the beneficial effects of semaglutide to recipient mice. Semaglutide and fecal microbiota transplantation affected metabolic pathways such as serum amino acid metabolism and pyrimidine metabolism in obese mice, and reshaped the composition and proportion of fecal gut microbiota in obese mice.

CONCLUSION: In summary, semaglutide could inhibit food intake and improve obesity, regulate serum metabolism and the composition of gut microbiota in mice. Bacterial transplantation is key to transmitting the improvement brought about by fecal microbiota transplantation of semaglutide to recipient mice.}, } @article {pmid40550813, year = {2025}, author = {Song, B and Azad, MAK and Zhu, Q and Cheng, Y and Ding, S and Yao, K and Kong, X}, title = {Lactobacillus regulate muscle fiber type conversion in Chinese native pigs via tryptophan metabolism.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {114}, pmid = {40550813}, issn = {2055-5008}, support = {32350410424//National Natural Science Foundation of China/ ; 2022JJ30643//Hunan Province Natural Science Foundation/ ; 092GJHZ2022044FN//Future Partner Special Network Fund of Chinese Academy of Sciences/ ; 2023YFD1301305//National Key Research and Development Project/ ; }, mesh = {Animals ; *Tryptophan/metabolism ; Swine/microbiology ; *Lactobacillus/metabolism/physiology ; Mice ; Gastrointestinal Microbiome ; Kynurenic Acid/metabolism ; *Muscle Fibers, Slow-Twitch/metabolism ; Feces/microbiology ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism/genetics ; AMP-Activated Protein Kinases/metabolism ; *Muscle Fibers, Skeletal/metabolism ; Metabolome ; }, abstract = {Identifying potential gut microbes and metabolites that can influence muscle fiber type is gaining interest in meat quality research. In this study, muscle fiber characteristics, muscle metabolite profiles, and gut microbiota and metabolome were compared among three pig breeds (Taoyuan black, TB; Xiangcun black, XB; and Duroc pigs). The results showed that the slow-twitch fiber percentage was higher (P < 0.05) in native pigs (TB and XB pigs) compared to Duroc pigs. The differences were mainly regulated by Lactobacillus abundance and tryptophan metabolism. Further, fecal microbiota transplantation from XB pigs transferred a higher slow-twitch fiber percentage, Lactobacillus abundance, kynurenic acid level, and AMPK/PGC-1α expression to mice. These findings suggest that Lactobacillus in the colon of TB and XB pigs, through kynurenic acid production, may promote slow-twitch fiber formation via the AMPK/PGC-1α signaling pathway.}, } @article {pmid40550671, year = {2025}, author = {Zhang, S and Liu, X and Zhong, Y and Fu, Y}, title = {[Association between gut microbiota and hyperuricemia: insights into innovative therapeutic strategies].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {41}, number = {6}, pages = {2290-2309}, doi = {10.13345/j.cjb.250060}, pmid = {40550671}, issn = {1872-2075}, mesh = {*Hyperuricemia/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome/physiology ; Probiotics/therapeutic use ; Uric Acid/metabolism/blood ; Fecal Microbiota Transplantation ; Prebiotics ; Medicine, Chinese Traditional ; }, abstract = {Uric acid (UA) is the final metabolite of purines in the human body. An imbalance in UA production and excretion that disrupts homeostasis leads to elevated blood UA levels and the development of hyperuricemia (HUA). Approximately one-third of UA is excreted through the intestinal tract. As a crucial component of the intestinal microenvironment, the gut microbiota plays a pivotal role in regulating blood UA levels. Alterations or imbalances in gut microbiota composition are linked to the onset of HUA, which implies the potential of gut microbiota as a novel target for the prevention and treatment of HUA. This review introduces the occurrence mechanism and damage of hyperuricemia, examines the association between HUA and the gut microbiota and their metabolites, and explores the molecular mechanisms underlying gut microbiota-targeted therapies for HUA. Furthermore, it discusses the potential applications of probiotics, prebiotics, and traditional Chinese medicine (including both single herbs and compound formulas) with UA-lowering effects, along with cutting-edge technologies such as fecal microbiota transplantation and machine learning in HUA treatment. This review provides valuable perspectives and strategies for improving the prevention and treatment of HUA.}, } @article {pmid40550654, year = {2025}, author = {Zhang, ZW and Ye, YJ and Shen, ZL}, title = {[Pathogenesis and progress in diagnosis and treatment of diversion colitis after colorectal cancer surgery].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {6}, pages = {627-632}, doi = {10.3760/cma.j.cn441530-20250326-00125}, pmid = {40550654}, issn = {1671-0274}, support = {82272841//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Colorectal Neoplasms/surgery ; *Colitis/diagnosis/therapy/etiology ; *Postoperative Complications/therapy/diagnosis/etiology ; Fecal Microbiota Transplantation ; }, abstract = {Diversion colitis (DC) is a non-specific inflammation caused by the lack of fecal flow stimulation in the distal intestine after intestinal diversion surgery. It is mainly related to factors such as intestinal flora imbalance, deficiency of short-chain fatty acid (SCFA) and immune abnormalities. The clinical manifestations of diversion colitis include abdominal pain, mucus and bloody stools, diarrhea and other symptoms, but most patients may have no obvious symptoms. Diagnosis mainly relies on endoscopic examination and pathological characteristics. Common endoscopic findings include mucosal congestion, edema, and increased fragility, and the histological manifestation is mainly lymphoid follicle hyperplasia. Other intestinal inflammatory diseases need to be excluded. The treatment options include surgical and conservative medical therapies, among which stoma reversal is the most effective treatment to restore intestinal continuity. Conservative treatments such as SCFA, 5-aminosalicylic acid (5-ASA), steroid or cellulose solution enema, leukocyte removal therapy and fecal microbiota transplantation (FMT) can be used for those who cannot undergo surgery, combined with diet and lifestyle support to improve symptoms. This article summarized the pathogenesis, status, clinical features, diagnostic strategy and treatment progress of DC, hoping to provide reference for the diagnosis and treatment of DC.}, } @article {pmid40550557, year = {2025}, author = {Huang, CT and Wang, YC and Lin, SC and Lai, YC and Chen, SH and Feng, ST and Tsai, YJ}, title = {Impact of Gut Microbiota Alterations on Mitochondrial Bioenergetics in Cortical Astrocytes and Sensorimotor Impairment in a Rat Model of Lipopolysaccharide-Associated Encephalopathy.}, journal = {Shock (Augusta, Ga.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/SHK.0000000000002637}, pmid = {40550557}, issn = {1540-0514}, abstract = {PURPOSE: Brain dysfunction is a significant complication of sepsis, commonly referred to as sepsis-associated encephalopathy (SAE). Alterations in gut microbiota during sepsis may contribute to development of SAE through the gut-brain axis. This study investigated effects of fecal transplantation from healthy or endotoxemic individuals on gut microbiota and brain function in a rat model of lipopolysaccharide (LPS)-associated encephalopathy.

METHODS: Following LPS induction, rats received daily oral gavage of fecal microbiota transplants for three days. Sensory and motor functions were assessed daily throughout the seven-day study period after LPS exposure. On day seven post-LPS, the study examined gut microbiota structure and composition, serum and fecal short-chain fatty acids (SCFAs) levels, ileal villus length, intestinal permeability, neuronal and glial ultrastructure, cytokine concentrations (pro-inflammatory and anti-inflammatory), and mitochondrial bioenergetics.

RESULTS: Administration of healthy donor feces preserved gut microbial structure and composition, maintained ileal villus length, and improved intestinal permeability following LPS treatment. Additionally, it increased SCFA levels, reduced pro-inflammatory cytokines, enhanced anti-inflammatory cytokine release, and restored sensitivity to mechanical and thermal stimuli, as well as motor function. Rats treated with healthy donor feces also exhibited reduced neuronal necrosis and a decreased density of mitochondria in cortical astrocytes. Notably, mitochondrial metabolism in LPS-treated rats returned to near-normal levels following treatment with healthy donor feces. In contrast, administration of endotoxemic donor feces exacerbated these effects in LPS-treated rats.

CONCLUSION: Ameliorating gut dysbiosis prevents mitochondrial dysfunction in astrocytes by promoting SCFA production and enhancing anti-inflammatory cytokine release. This process preserves neuronal integrity and mitigates the severity of encephalopathy.}, } @article {pmid40550284, year = {2025}, author = {Biggs, GAY}, title = {Editorial Comment on "Fecal Microbiota Transplant Is Associated With the Resolution of Recurrent Urinary Tract Infections".}, journal = {Urology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.urology.2025.06.040}, pmid = {40550284}, issn = {1527-9995}, } @article {pmid40549339, year = {2025}, author = {Bulut, SD and Döndaş, HA and Celebioglu, HU and Sansano, JM and Döndaş, NY}, title = {Recent Insights About Probiotics Related Pharmabiotics in Pharmacology: Prevention and Management of Diseases.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {40549339}, issn = {1867-1314}, abstract = {The science of pharmacology investigates the effects of drugs on living organisms and vice versa. The frequency of side effects of some drugs used in traditional pharmacological treatment approaches and/or their inability to provide adequate treatment has led to the importance of new drug research and development (R&D) studies. Recently, due to the discovery that some diseases are associated with an imbalanced microbiota (dysbiosis), there has been a surge of interest in therapeutic approaches that can restore balance (biosis) to the microbiota. This review discusses the current status of the pharmabiotic potential of probiotics, prebiotics, synbiotics, paraprobiotics, postbiotics, metabiotics, next-generation probiotics, and fecal microbiota transplantation; describes their pharmacological functions from gastrointestinal disorders to neurodegenerative diseases; and also discusses the developments in pharmaceutical applications of probiotics and their derivatives.}, } @article {pmid40548224, year = {2025}, author = {Tüsüz Önata, E and Özdemir, Ö}, title = {Fecal microbiota transplantation in allergic diseases.}, journal = {World journal of methodology}, volume = {15}, number = {2}, pages = {101430}, pmid = {40548224}, issn = {2222-0682}, abstract = {Microorganisms such as bacteria, fungi, viruses, parasites living in the human intestine constitute the human intestinal microbiota. Dysbiosis refers to compositional and quantitative changes that negatively affect healthy gut microbiota. In recent years, with the demonstration that many diseases are associated with dysbiosis, treatment strategies targeting the correction of dysbiosis in the treatment of these diseases have begun to be investigated. Faecal microbiota transplantation (FMT) is the process of transferring faeces from a healthy donor to another recipient in order to restore the gut microbiota and provide a therapeutic benefit. FMT studies have gained popularity after probiotic, prebiotic, symbiotic studies in the treatment of dysbiosis and related diseases. FMT has emerged as a potential new therapy in the treatment of allergic diseases as it is associated with the maintenance of intestinal microbiota and immunological balance (T helper 1/T helper 2 cells) and thus suppression of allergic responses. In this article, the definition, application, safety and use of FMT in allergic diseases will be discussed with current data.}, } @article {pmid40548146, year = {2025}, author = {Vermeulen, A and Bootsma, E and Proost, S and Vieira-Silva, S and Kathagen, G and Vázquez-Castellanos, JF and Tito, RY and Sabino, J and Vermeire, S and Matthys, C and Raes, J and Falony, G}, title = {Dietary convergence induces individual responses in faecal microbiome composition.}, journal = {eGastroenterology}, volume = {3}, number = {2}, pages = {e100161}, pmid = {40548146}, issn = {2976-7296}, abstract = {BACKGROUND: Dietary variation has been identified as a key contributor to microbiome diversification. However, assessing its true impact in a cross-sectional setting is complicated by biological confounders and methodological hurdles. We aimed to estimate the impact of a reduction of dietary variation (dietary convergence) on faecal microbiota composition among individuals consuming a Western-type diet.

METHODS: 18 healthy volunteers recruited in the region of Flanders (Belgium) were followed up for 21 days. Participants were allowed to consume their habitual diet during a baseline and follow-up period (7 and 8 days, respectively), intersected by a 6-day intervention during which dietary options were restricted to oat flakes, whole milk and still water. Faecal samples were collected on a daily basis. Quantitative microbiome profiles were constructed, combining 16S rRNA gene amplicon sequencing with flow cytometry cell counting. Blood samples were taken at the beginning and end of each study week.

RESULTS: While the intervention did not affect transit time (as assessed through the analysis of stool moisture), consumption of the restricted diet resulted in an increased prevalence of the Bacteroides2 microbiome community type. Microbial load and Faecalibacterium abundance decreased markedly. Despite dietary restrictions, no convergence of microbial communities (reduction of interindividual and intraindividual variation) was observed. The effect size (ES) of the intervention on genus-level microbiome community differentiation was estimated as 3.4%, but substantial interindividual variation was observed (1.67%-16.42%).

CONCLUSION: The impact of dietary variation on microbiome composition in a Western population is significant but limited in ES, with notable individual exceptions. Dietary convergence does not invariably translate into interindividual convergence of faecal microbial communities.}, } @article {pmid40546666, year = {2025}, author = {Jeyaraman, N and Jeyaraman, M and Dhanpal, P and Ramasubramanian, S and Nallakumarasamy, A and Muthu, S and Santos, GS and da Fonseca, LF and Lana, JF}, title = {Integrative review of the gut microbiome's role in pain management for orthopaedic conditions.}, journal = {World journal of experimental medicine}, volume = {15}, number = {2}, pages = {102969}, pmid = {40546666}, issn = {2220-315X}, abstract = {The gut microbiome, a complex ecosystem of microorganisms, has a significant role in modulating pain, particularly within orthopaedic conditions. Its impact on immune and neurological functions is underscored by the gut-brain axis, which influences inflammation, pain perception, and systemic immune responses. This integrative review examines current research on how gut dysbiosis is associated with various pain pathways, notably nociceptive and neuroinflammatory mechanisms linked to central sensitization. We highlight advancements in meta-omics technologies, such as metagenomics and metaproteomics, which deepen our understanding of microbiome-host interactions and their implications in pain. Recent studies emphasize that gut-derived short-chain fatty acids and microbial metabolites play roles in modulating neuroinflammation and nociception, contributing to pain management. Probiotics, prebiotics, synbiotics, and faecal microbiome transplants are explored as potential therapeutic strategies to alleviate pain through gut microbiome modulation, offering an adjunct or alternative to opioids. However, variability in individual microbiomes poses challenges to standardizing these treatments, necessitating further rigorous clinical trials. A multidisciplinary approach combining microbiology, immunology, neurology, and orthopaedics is essential to develop innovative, personalized pain management strategies rooted in gut health, with potential to transform orthopaedic pain care.}, } @article {pmid40546462, year = {2025}, author = {Inayat, N and Zahir, A and Hashmat, AJ and Khan, A and Ahmad, A and Sikander, M and Zakir, S and Ahmad, S and Awan, SK and Raza, SS and Varrassi, G}, title = {Gut Microbiota as a Key Modulator of Chronic Disease: Implications for Diabetes, Autoimmunity, and Cancer.}, journal = {Cureus}, volume = {17}, number = {5}, pages = {e84687}, pmid = {40546462}, issn = {2168-8184}, abstract = {The gut microbiota (GM) represents an intricate, dynamic, and complex ecosystem. It plays a key role in health and disease. The GM interacts with the host and modulates various physiological functions, including metabolism, immune regulation, and neurological function. This narrative review comprehensively analyses the role of the GM in the development and progression of three major chronic conditions, namely diabetes, autoimmune disorders, and cancer. Using a structured literature search strategy across databases such as Google Scholar, PubMed, Scopus, and Web of Science, relevant studies published between 2000 and 2025 were identified and analysed. This review highlights that dysbiosis contributes significantly to the pathogenesis of these chronic conditions. In type 2 diabetes mellitus (T2DM), alterations in the GM are associated with systemic inflammation, insulin resistance, and decreased microbial diversity. Similarly, in autoimmune disorders such as rheumatoid arthritis (RA), multiple sclerosis (MS), and inflammatory bowel disease (IBD), dysbiosis disrupts immune homeostasis, which in turn causes sustained inflammation and aberrant immune responses. Lastly, dysbiosis has been linked to the onset and progression of various gastrointestinal cancers through mechanisms including chronic inflammation and the production of carcinogenic metabolites. Fecal microbiota transplantation (FMT), probiotics, prebiotics, and dietary modifications are being explored for their potential to restore microbial balance and improve clinical outcomes. In conclusion, this review highlights the GM's pivotal role in the pathogenesis of chronic diseases and its potential as a therapeutic target.}, } @article {pmid40546285, year = {2025}, author = {Pei, X and Liu, M and Yu, S}, title = {How is the human microbiome linked to kidney stones?.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1602413}, pmid = {40546285}, issn = {2235-2988}, mesh = {Humans ; *Kidney Calculi/microbiology ; *Microbiota ; Dysbiosis/microbiology ; Gastrointestinal Microbiome ; Bacteria/classification/metabolism/isolation & purification ; }, abstract = {In recent years, the incidence of kidney stones has continued to rise worldwide, and conventional treatments have limited efficacy in treating stones associated with recurrent or metabolic abnormalities. The microbiome, as the 'second genome' of the host, is involved in the development of kidney stones through metabolic regulation, immune homeostasis and inflammatory response. Studies have shown that the urinary microbiome of healthy people is dominated by commensal bacteria such as Lactobacillus and Streptococcus, which maintain microenvironmental homeostasis, whereas patients with renal stones have a significantly reduced diversity of intestinal and urinary microbiomes, with a reduced abundance of oxalic acid-degrading bacteria (e.g., Bifidobacterium oxalicum, Bifidobacterium bifidum), and a possible concentration of pathogenic bacteria (e.g., Proteus mirabilis). The microbiome regulates stone formation through mechanisms such as metabolites (e.g., short-chain fatty acids), changes in urine physicochemical properties (e.g., elevated pH), and imbalances in the inflammatory and immune microenvironments. For example, urease-producing bacteria promote magnesium ammonium phosphate stone formation through the breakdown of urea, whereas dysbiosis of the intestinal flora increases urinary oxalic acid excretion and exacerbates the risk of calcium oxalate stones. Microbiome-based diagnostic markers (e.g., elevated abundance of Aspergillus phylum) and targeted intervention strategies (e.g., probiotic supplementation, faecal bacteria transplantation) show potential for clinical application. However, technical bottlenecks (e.g., sequencing bias in low-biomass samples), mechanistic complexity (e.g., multistrain synergism), and individual heterogeneity remain major challenges for future research. Integration of multi-omics data, development of personalised therapies and interdisciplinary research will be the core directions to decipher the relationship between microbiome and kidney stones.}, } @article {pmid40546239, year = {2025}, author = {Liang, J and Dong, X and Yang, J and Hu, N and Luo, X and Cong, S and Chen, J and Zhao, W and Liu, B}, title = {Buyang Huanwu Decoction Modulates the Gut Microbiota-C/EBPβ/AEP Axis to Ameliorate Cognitive Impairment in Alzheimer's Disease Mice.}, journal = {CNS neuroscience & therapeutics}, volume = {31}, number = {6}, pages = {e70480}, pmid = {40546239}, issn = {1755-5949}, support = {2024yjscx013//Innovative Research Project for Postgraduate Students of Heilongjiang University of Traditional Chinese Medicine/ ; LH2022H059//Natural Science Foundation of Heilongjiang Province of China/ ; LH2023H073//Natural Science Foundation of Heilongjiang Province of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/physiology ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Alzheimer Disease/drug therapy/metabolism/pathology/psychology ; Mice ; *Cognitive Dysfunction/drug therapy/metabolism ; Mice, Transgenic ; *CCAAT-Enhancer-Binding Protein-beta/metabolism ; Male ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Signal Transduction/drug effects ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and behavioral disturbances. Buyang Huanwu Decoction (BYHWD), a traditional Chinese herbal formulation, has demonstrated potential neuroprotective effects. This study aims to evaluate the therapeutic impact of BYHWD on cognitive impairments in 3×Tg mice and to investigate its underlying mechanism through modulation of the gut microbiota-C/EBPβ/AEP signaling pathway.

METHODS: In two independent experiments, we assessed the effects of BYHWD and its derived fecal microbiota transplantation (FMT-BYHWD) on behavioral performance, neuropathological alterations, and signaling pathways in 3×Tg mice.

RESULTS: Treatment with BYHWD significantly improved cognitive function in 3×Tg mice and mitigated AD-like pathological changes. By suppressing the C/EBPβ/AEP signaling pathway, BYHWD reduced pathological Aβ plaque deposition, diminished tau hyperphosphorylation, and inhibited the release of pro-inflammatory cytokines. Further analysis revealed that BYHWD restored gut microbiota balance and suppressed the activation of the C/EBPβ/AEP pathway in the hippocampus. Moreover, transplanting FMT-BYHWD from BYHWD-treated mice to germ-free 3×Tg mice also ameliorated their cognitive deficits and AD-like pathology, suggesting that the anti-AD effects of BYHWD are mediated through the gut-brain axis by regulating the interplay between gut microbiota and the C/EBPβ/AEP signaling pathway.

CONCLUSION: This study uncovers the mechanism by which BYHWD improves cognitive deficits and neuropathological changes in 3×Tg mice via the gut-brain axis, mediated by the modulation of the gut microbiota-C/EBPβ/AEP signaling pathway, providing a novel therapeutic strategy for AD.}, } @article {pmid40544256, year = {2025}, author = {Mannavola, CM and De Maio, F and Marra, J and Fiori, B and Santarelli, G and Posteraro, B and Sica, S and D'Inzeo, T and Sanguinetti, M}, title = {Bloodstream infection by Lactobacillus rhamnosus in a haematology patient: why metagenomics can make the difference.}, journal = {Gut pathogens}, volume = {17}, number = {1}, pages = {47}, pmid = {40544256}, issn = {1757-4749}, support = {PE00000007, INF-ACT//EU funding for the MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases/ ; }, abstract = {BACKGROUND: Bloodstream infections (BSIs) pose a persistent threat to hospitalized patients, particularly those who are immunocompromised and susceptible to infections caused by anaerobic or facultative anaerobic bacteria. Alterations in gut microbiota composition can predispose individuals to intestinal domination by one or more pathobionts, increasing the risk of bacterial translocation into the bloodstream and subsequent bacteremia.

CASE PRESENTATION: We report the case of a 20-year-old female with multiple relapsed/refractory Philadelphia-negative B-cell acute lymphoblastic leukemia, initially referred to our hematology center for CAR-T cell therapy. The patient ultimately underwent allogeneic hematopoietic stem cell transplantation, which was complicated by infections, moderate-to-severe graft-versus-host disease, hepatic sinusoidal obstruction syndrome, and transplant-associated thrombotic microangiopathy, all contributing to a fatal outcome. Blood cultures obtained in the final week before the patient succumbed to multi-organ toxicity grew Lactobacillus rhamnosus. A fecal sample collected concurrently for intestinal microbiota characterization revealed a marked predominance of Bacillota (98.5%), with Lacticaseibacillus dominating at 47.9%, followed by Pediococcus (18.59%) and Staphylococcus (3.5%) at the genus level. We performed genomic comparison between the L. rhamnosus isolated from blood cultures and the best-matched strain detected in the intestinal microbiota.

CONCLUSIONS: We report the isolation of L. rhamnosus from blood cultures in a patient post hematopoietic cell transplantation, with genomic similarity to a gut-dominant L. rhamnosus strain. This case highlights the potential link between intestinal domination and subsequent bloodstream infection, supporting the value of gut microbiota profiling as an adjunctive tool for monitoring high-risk patients, such as hematopoietic cell transplant recipients.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13099-025-00722-3.}, } @article {pmid40544212, year = {2025}, author = {Lv, J and Hao, P and Zhou, Y and Liu, T and Wang, L and Song, C and Wang, Z and Liu, Z and Liu, Y}, title = {Role of the intestinal flora-immunity axis in the pathogenesis of rheumatoid arthritis-mechanisms regulating short-chain fatty acids and Th17/Treg homeostasis.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {617}, pmid = {40544212}, issn = {1573-4978}, support = {2024ZKZ009//Southwest Medical University (SWMU) School-level Scientific Research Program/ ; }, mesh = {*Fatty Acids, Volatile/metabolism/immunology ; *T-Lymphocytes, Regulatory/immunology/metabolism ; Humans ; *Th17 Cells/immunology/metabolism ; *Gastrointestinal Microbiome/immunology ; *Arthritis, Rheumatoid/immunology/microbiology/metabolism ; Animals ; Homeostasis/immunology ; Dysbiosis/immunology ; }, abstract = {BACKGROUND: The pathogenesis of rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is closely linked to the interactions between intestinal flora and metabolites. Recent research has shown that the "gut-joint axis" is an important regulator of immune homeostasis, gut microbiota dysbiosis not only causes pro-inflammatory bacteria to proliferate abnormally, but it also decreases the biosynthesis of short-chain fatty acids (SCFAs). This dual imbalance ultimately exacerbates synovial inflammation and encourages bone destruction by upsetting the balance of Th17/Treg cells, that is, the over-activation of Th17 cells and the impaired function of regulatory T cells (Treg).

OBJECTIVE: To clarify the molecular mechanism by which intestinal flora-derived SCFAs alter the pathogenic process of RA by controlling Th17/Treg balance, and to establish a theoretical foundation for targeted treatments.

METHODS: We integrated multidisciplinary evidence to create a "flora-SCFAs-immunity-joints" by conducting a systematic search of domestic and international literature in PubMed, Web of Science, and other databases over the past ten years, with a focus on intestinal flora composition, SCFA biosynthesis, Th17/Treg immunoregulation, and RA animal model research. We create a "flora-SCFAs-immunity-joint" network by integrating information from many disciplines.

OUTCOMES: Dietary fiber is broken down by intestinal flora to produce SCFAs (acetic, propionic, and butyric acids), which control Th17/Treg balance in two ways: (1) Encourage Treg differentiation: propionic acid activates the GPR43-cAMP/PKA-CREB pathway, which promotes Treg expansion and secretion of IL-10/TGF-β; (2) Inhibit Th17 polarization, SCFAs inhibited Th17 cell differentiation, down-regulated IL-23 secretion from dendritic cells, and blocked IL-6/STAT3 and RORγt signaling. Butyric acid also inhibits histone deacetylase (HDAC) activity, Foxp3 expression, and epigenetic stability. In a collagen-induced arthritis (CIA) paradigm, animal studies shown that fecal transplantation or SCFA supplementation dramatically decreased bone degradation and joint inflammatory scores. Its therapeutic translational potential was suggested by the negative correlation found between the Th17/Treg ratio and the amount of SCFAs in the gut of RA patients.

CONCLUSION: Through multi-target control of Th17/Treg balance, SCFAs show distinct benefits over conventional immunosuppression in the treatment of RA. Verification is still required for the pharmacokinetic constraints of SCFAs, variations in individual flora, and causative processes. To support the specific immune intervention in RA, it will be important in the future to integrate multi-omics technology to evaluate the trans-organ regulatory network of the "gut-joint axis" and to create nano-delivery methods or modified bacterial tactics to increase the targeting of SCFAs.}, } @article {pmid40542451, year = {2025}, author = {Ji, S and Ahmad, F and Peng, B and Yang, Y and Su, M and Zhao, X and Vatanen, T}, title = {Engrafting gut bacteriophages have potential to modulate microbial metabolism in fecal microbiota transplantation.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {149}, pmid = {40542451}, issn = {2049-2618}, support = {U22A20365//Joint Funds of National Natural Science Foundation of China/ ; T2341019//National Natural Science Foundation of China/ ; 2023A1515012429//Natural Science Foundation of Guangdong Province/ ; 2024B03J1343//Guangzhou Science and Technology Plan Project/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Bacteriophages/genetics/classification/physiology/isolation & purification ; *Gastrointestinal Microbiome ; Feces/microbiology/virology ; *Clostridium Infections/therapy/microbiology ; Clostridioides difficile/virology ; Bacteria/metabolism/virology/genetics/classification ; Metagenome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is widely used to treat severe infections and investigated for the treatment of complex diseases. The therapeutic efficacy of FMT is related to the successful engraftment of bacteriophages from healthy donors to recipients. However, gut bacteriophage contributions to FMT engraftment and treatment outcomes remain unclear.

METHODS: The gut phageome from previously published metagenomes of donors and recipients across 23 FMT studies was assembled and functionally annotated for a meta-analysis.

RESULTS: Gut phageome profiles of FMT recipients, especially those with recurrent Clostridioides difficile infection (rCDI), shifted toward donor phageomes, accompanied by increased phageome alpha diversity. Engraftment of donor phages varied between recipient conditions with the highest engraftment rate, overrepresented by putative temperate phage, in patients with rCDI. Consistently, a higher proportion of auxiliary metabolic genes (AMGs), with the potential to support and modulate bacterial metabolism, were annotated on putative temperate phages.

CONCLUSIONS: FMT leads to significant taxonomic, functional, and lifestyle shifts in recipient phageome composition. Future FMT studies should include gut phageome characterization and consider it as a potential factor in microbial community shifts and treatment outcomes. Video Abstract.}, } @article {pmid40540980, year = {2025}, author = {Noviello, D and Amoroso, C and Vecchi, M and Facciotti, F and Caprioli, F}, title = {Curing inflammatory bowel diseases: breaking the barriers of current therapies- emerging strategies for a definitive treatment.}, journal = {Current opinion in immunology}, volume = {95}, number = {}, pages = {102593}, doi = {10.1016/j.coi.2025.102593}, pmid = {40540980}, issn = {1879-0372}, mesh = {Humans ; *Inflammatory Bowel Diseases/therapy/immunology/etiology ; Animals ; Gastrointestinal Microbiome/immunology ; Fecal Microbiota Transplantation ; Hematopoietic Stem Cell Transplantation ; Intestinal Mucosa/immunology ; }, abstract = {Chronic intestinal inflammation in inflammatory bowel diseases (IBD) reflects the interplay of genetic predisposition, immune dysregulation, microbial imbalance, and epithelial barrier defects. Current therapies for IBD primarily focus on controlling inflammation necessitating lifelong treatment and face a 'therapeutic ceiling' due to primary and secondary loss of efficacy over time. Immune-mediated approaches do not address additional pathogenic mechanisms, such as impairment of epithelial barrier and gut microbial ecology. Thus, innovative strategies are required to foster the field closer to a definitive cure. This review discusses novel strategies to overcome current therapeutic limitations, including immune reset via hematopoietic stem cell transplantation and B cell-targeted therapies, antigen-specific interventions such as chimeric antigen receptor T cells and tolerogenic vaccines, and intestinal epithelial barrier restoration. We also explore microbiota-based strategies - ranging from fecal microbiota transplantation to engineered consortia and bacteriophages - and discuss the adjunctive role of diet. Together, we outline a potential research roadmap toward a potential cure for IBD.}, } @article {pmid40538711, year = {2025}, author = {Lathakumari, RH and Vajravelu, LK and Gopinathan, A and Vimala, PB and Panneerselvam, V and Ravi, SSS and Thulukanam, J}, title = {The gut virome and human health: From diversity to personalized medicine.}, journal = {Engineering microbiology}, volume = {5}, number = {1}, pages = {100191}, pmid = {40538711}, issn = {2667-3703}, abstract = {The human gut virome plays a crucial role in the gut and overall health; its diversity and regulatory functions influence bacterial populations, metabolism, and immune responses. Bacteriophages (phages) and eukaryotic viruses within the gut microbiome contribute to these processes, and recent advancements in sequencing technologies and bioinformatics have greatly expanded our understanding of the gut virome. These advances have led to the development of phage-based therapeutics, diagnostics, and artificial intelligence-driven precision medicine. The emerging field of phageomics shows promise for delivering personalized phage therapies that combat antimicrobial resistance by specifically targeting pathogenic bacteria while preserving beneficial microbes. Moreover, CRISPR-Cas systems delivered via phages have shown success in selectively targeting antibiotic resistance genes and enhancing treatment effectiveness. Phage-based diagnostics are highly sensitive in detecting bacterial pathogens, offering significant benefits for human health and zoonotic disease surveillance. This synthesis of the current knowledge highlights the pivotal role of the gut virome in regulating microbial communities and its transformative potential in personalized medicine, emphasizing its importance in advancing therapeutic and diagnostic strategies for improving health outcomes.}, } @article {pmid40535532, year = {2025}, author = {Wang, Q and Xu, G and Yan, O and Wang, S and Wang, X}, title = {Radiation-induced injury and the gut microbiota: insights from a microbial perspective.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848251347347}, pmid = {40535532}, issn = {1756-283X}, abstract = {Although radiotherapy is the second most effective cancer treatment, radiation injuries limit its use. About 80% of abdominal-pelvic radiotherapy patients develop acute radiation enteritis, with 20% discontinuing radiotherapy. The lack of effective mitigation measures restricts its clinical application. Recent studies have proposed gut microbiota as a potential biomarker for radiation injuries. However, the interaction between gut microbiota and radiation injuries remains poorly understood. This review summarizes two forms of interaction between gut microbiota and radiation injuries based on the location of the radiation field. One type of interaction, referred to as "direct interaction," involves changes in the diversity and composition of gut microbiota, alterations in microbiota-derived metabolites, disruption of the intestinal barrier, activation of inflammatory responses within the intestine, and involvement of the host's immune system. The second form, called "indirect interaction," includes the influence of the gut microbiota on various body systems, such as gut microbiota-brain axis, gut microbiota-cardiopulmonary axis, and gut microbiota-oral axis. Additionally, we examine promising interventions aimed at reshaping the gut microbiota, including the use of probiotics, prebiotics, and fecal microbiota transplantation. The interaction between radiation injuries and gut microbiota is more complex than previously understood. Therefore, further clarification of the underlying mechanisms will facilitate the application of gut microbiota in preventing and alleviating radiation injuries.}, } @article {pmid40535011, year = {2025}, author = {Wu, N and Ning, K and Liu, Y and Wang, Q and Li, N and Zhang, L}, title = {Relationship between high-fat diet, gut microbiota, and precocious puberty: mechanisms and implications.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1564902}, pmid = {40535011}, issn = {1664-302X}, abstract = {Precocious puberty (PP) is the second most common pediatric endocrine disorder globally and poses a growing public health concern, particularly among girls. While the exact biological mechanisms underlying PP remain unclear, unhealthy dietary patterns, particularly the consumption of a high-fat diet (HFD), are recognized as significant modifiable risk factors. The gut microbiota (GM) is an environmental factor that is disrupted by HFD and may modulate the onset and progression of PP. This review explored the intricate relationship between HFD, GM, and PP, and elucidated the potential mechanisms by which HFD may promote PP development by summarizing evidence from preclinical to clinical research, focusing on the role of GM and its derived metabolites, including short-chain fatty acids, bile acids, lipopolysaccharides, and neurotransmitters. Mechanistic exploration provides novel insights for developing microbiota-targeted therapeutic strategies, such as dietary and lifestyle interventions, fecal microbiota transplantation, probiotics, and traditional Chinese medicine, paving the way for promising approaches to prevent and manage PP.}, } @article {pmid40534699, year = {2025}, author = {Yu, JX and Wu, J and Chen, X and Zang, SG and Li, XB and Wu, LP and Xuan, SH}, title = {Gut microbiota in liver diseases: initiation, development and therapy.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1615839}, pmid = {40534699}, issn = {2296-858X}, abstract = {The gut microbiota plays a pivotal role in the pathogenesis and progression of various liver diseases, including viral hepatitis, alcoholic fatty liver disease, metabolic dysfunction-associated steatotic liver disease, drug-induced hepatitis, liver cirrhosis, hepatocellular carcinoma, and other hepatic disorders. Research indicates that dysbiosis of the gut microbiota can disrupt the integrity of the intestinal barrier and interfere with the immune functions of the gut-liver axis, thereby mediating the progression of liver diseases. Analysis of microbial composition and metabolites in fecal samples can assess the diversity of gut microbiota and the abundance of specific microbial populations, providing auxiliary diagnostic information for liver diseases. Furthermore, interventions such as fecal microbiota transplantation, probiotics, prebiotics, bacteriophages, and necessary antibiotic treatments offer multiple approaches to modulate the gut microbiota, presenting promising new strategies for the prevention and treatment of liver diseases. This review summarizes the latest research advances on the role of gut microbiota in liver diseases, offering novel theoretical foundations and practical directions for the diagnosis and treatment of hepatic disorders.}, } @article {pmid40533850, year = {2025}, author = {Ye, Q and Hu, Y and Jiang, H and Luo, T and Han, L and Chen, Y and Chen, J and Ma, L and He, Z and Yan, X}, title = {Maternal intestinal L. vaginalis facilitates embryo implantation and survival through enhancing uterine receptivity in sows.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {145}, pmid = {40533850}, issn = {2049-2618}, support = {32202700//National Natural Science Foundation of China/ ; 31925037//National Natural Science Foundation of China/ ; 2022YFD1300405//National Key Research and Development Program of China/ ; 2022YFD1300405//National Key Research and Development Program of China/ ; 2022YFD1300405//National Key Research and Development Program of China/ ; 2022020801020232//Knowledge Innovation Program of Wuhan-Shuguang Project/ ; AML2023B06//National Key Laboratory of Agricultural Microbiology/ ; 2662023DKPY002//Fundamental Research Funds for the Central University/ ; }, mesh = {Animals ; Female ; *Embryo Implantation/physiology ; Swine ; *Gastrointestinal Microbiome/physiology ; Pregnancy ; Mice ; *Uterus/physiology ; RNA, Ribosomal, 16S/genetics ; Litter Size ; Metabolomics ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: The embryo implantation quality during early pregnancy is the predominant factor for embryo survival and litter performance in sows. Gut microbiota is demonstrated to show a correlation to pregnancy outcomes by participating in regulating maternal metabolism. However, the specific functional microbiota and its mechanical effects on regulating embryo implantation and survival remain unclear. The objective of this study was to clarify whether embryo implantation and litter performance were affected by maternal intestinal microbiota, and to identify specific microbial communities and its mechanism in regulating embryo implantation.

RESULTS: In this study, we first conducted 16S rRNA sequencing and metabolomic analysis revealing the intestinal microbiota and metabolism of 42 sows with different litter size to select the potential functional microbiota that may contribute to embryo survival. Then, we explored the effects of that microbiota on embryo implantation and litter performance through microbiota transplantation in mice and sows. We found that maternal intestinal L. vaginalis exhibits enrichment in sows with higher litter size, which could facilitate embryo implantation and survival and ultimately increases litter size in mice. We further employed transcriptomic analysis to determine the characteristics of uterus, which found an enhanced uterine receptivity after L. vaginalis gavage. The plasma untargeted metabolomic analysis after L. vaginalis gavage in mice and targeted metabolomics analysis of in vitro cultured medium of L. vaginalis were used to evaluate the metabolic regulation of L. vaginalis and to reveal the underlying functional metabolites. Next, an increasing adhesion rate of endometrial-embryonic cells and an obvious increasing formation of pinopodes in cell surface of porcine endometrial epithelial cells were observed after treatments of L. vaginalis metabolites, especially galangin and daidzein. Also, the gene expression levels related to uterine receptivity were increased after treatments of L. vaginalis metabolites in porcine endometrial epithelial cells. Finally, we found that L. vaginalis or its metabolites supplementation during early gestation significantly increased the litter performance in sows.

CONCLUSIONS: Overall, intestinal microbial-host interactions can occur during early pregnancy and may be contribute to maternal metabolic changes and influence pregnancy outcomes in mammals. Our study provides insights of maternal intestinal L. vaginalis to enhance uterine receptivity and to benefit embryo/fetal survival through a gut-uterus axis, contributing to advanced concept and novel strategy to manipulate gut microbiota during early pregnancy, and in turn to improve embryo implantation and reduce embryo loss in sows. Video Abstract.}, } @article {pmid40532535, year = {2025}, author = {Wang, Z and He, Y and Luo, M and Liu, S and Hou, J and Cao, B and An, X}, title = {Transfer toxicity of polystyrene microplastics in vivo: Multi-organ crosstalk.}, journal = {Environment international}, volume = {202}, number = {}, pages = {109604}, doi = {10.1016/j.envint.2025.109604}, pmid = {40532535}, issn = {1873-6750}, abstract = {The accumulation of microplastics (MPs) within the environment caused serious ecological and health problems. Nevertheless, its systemic toxicity to organisms and its mechanisms lack effective evidence. This study established a model of MP exposure through the gavage of polystyrene (PS)-MPs particles to maternal mice on days 1 to 21 of lactation. The results demonstrated that PS-MPs were distributed widely in maternal mice, occurring mainly in the feces, colon, liver and mammary glands. Further experiments revealed that the gut and blood-milk barriers were disrupted, and pathological injury and inflammatory reactions were observed in the liver, gut, and mammary glands. Metabolomic and metagenome analysis indicated abnormalities in hepatic bile acid metabolism and significant alterations in the gut microbiota after exposure to PS-MPs. These alterations led to increased disruption of the intestine-liver axis. Notably, with fecal microbiota transplantation and antibiotic experiments, we observed that elimination of the intestinal microbiota reduced tissue inflammation and improved gut and blood-milk barrier leakage. These findings demonstrated that PS-MPs exaggerated intestine-liver axis disorders by inducing colonic injury, intestinal ecological dysregulation and abnormal hepatic bile acid metabolism. Furthermore, PS-MPs translocated via the intestine-liver axis and exerted broader toxic effects on mammary tissue. Overall, our study uncovered the transfer toxicity of PS-MPs in mice, proposing the possibility of a gut-liver-mammary axis.}, } @article {pmid40532322, year = {2025}, author = {Zhao, Y and Gong, N and Wang, S and Yuan, Q and Chen, X and Li, B and Zhang, L and Li, W and Zhu, R and Zhang, J and Zhang, W}, title = {Dynamic changes in intestinal microbiota mediate mechanical hyperalgesia in surgical menopause model: a potential mechanism of DRG neuroinflammation.}, journal = {International immunopharmacology}, volume = {161}, number = {}, pages = {115098}, doi = {10.1016/j.intimp.2025.115098}, pmid = {40532322}, issn = {1878-1705}, mesh = {Animals ; *Hyperalgesia/microbiology/metabolism/etiology ; Female ; *Ganglia, Spinal/immunology/metabolism ; *Gastrointestinal Microbiome ; Mice ; Ovariectomy ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Menopause ; *Neuroinflammatory Diseases/microbiology ; Pain Threshold ; Mice, Inbred C57BL ; }, abstract = {The role of the intestinal microbiota in hyperalgesia in ovariectomized mice remains unclear. This study aimed to investigate pain behavior and dynamic changes in the intestinal microbiota and the levels of related metabolites in a model of surgical menopause and to verify the hypothesis that the intestinal microbiota mediates the occurrence and persistence of hyperalgesia through neuroinflammation. An ovariectomy (OVX) model was constructed to assess the intestinal microbiota composition, the levels of related metabolites, and inflammation levels in the spinal dorsal root ganglion (DRG). Fecal microbiota transplantation (FMT) was used to alter the intestinal microbiota, and its impact on pain-related behaviors and the level of inflammation in the DRG was evaluated. The mechanical pain threshold was significantly lower in the OVX group compared with the sham group at 4-8 w after surgery, and the thermal pain threshold was greater at 5 and 8 w after surgery. A decrease in the mechanical pain threshold was observed in the OVX group 5, and 7-9 weeks after FMT, indicating hyperalgesia. PCoA and OPLS-DA revealed differences in the composition of the microbiota and the abundance of related metabolites between the OVX and sham groups. Correlation analysis revealed an association between pain thresholds and the levels and metabolites of certain bacterial genera. The expression of C/EBPβ and IL-1β in the OVX group was greater than that in the sham group, and the expression of IL-6, IL-1β, and TRPV1 in the sham group was greater than that in the OVX group after FMT. In conclusion, the dynamic changes in the intestinal microbiota in female mice induced by surgical menopause result in hyperalgesia, possibly due to an increase in the severity of inflammation in the spinal DRG.}, } @article {pmid40531376, year = {2025}, author = {Wu, Y and Wong, OWH and Chen, S and Ng, SC and Su, Q and Chan, FKL}, title = {Gastrointestinal health and nutritional strategies in autism spectrum disorder.}, journal = {Journal of gastroenterology}, volume = {60}, number = {8}, pages = {933-946}, pmid = {40531376}, issn = {1435-5922}, support = {R4030-22//Research Grants Council-Research Impact Fund/ ; NCI202346//New Cornerstone Science Foundation/ ; PF22-77807//Hong Kong PhD Fellowship Scheme (HKPFS) of the Research Grants Council of Hong Kong/ ; }, mesh = {*Autism Spectrum Disorder/complications/diet therapy ; Humans ; *Gastrointestinal Diseases/complications/diet therapy ; Gastrointestinal Microbiome ; *Diet ; Dietary Supplements ; Analgesics, Opioid ; Prebiotics/administration & dosage ; Probiotics/administration & dosage ; Brain-Gut Axis ; Algorithms ; }, abstract = {Beyond the hallmark social and sensory difficulties in autism spectrum disorder (ASD), the comorbid gastrointestinal (GI) conditions and their potential link to the severity of core symptoms require clinical attention. Although evidence indicates that autistic children face a greater risk of GI disorders and require more intensive nutritional management compared to neurotypical peers, standard guidelines for managing GI symptoms in this population remain lacking. This review seeks to pinpoint critical considerations for the implementation of nutrition-based strategies aimed at addressing GI dysfunction in individuals with ASD. By emphasizing clinical translation and the mechanistic understanding of these strategies, it highlights the importance of restoring gut homeostasis as a pathway to improve functional independence and overall well-being. Furthermore, we outline priorities for clinical research aimed at developing evidence-based nutritional recommendations to support GI health in autistic individuals, emphasizing personalized and population-specific needs.}, } @article {pmid40530459, year = {2025}, author = {Kabage, AJ and Haselhorst, PJ and Khoruts, A}, title = {Donor-centric administration of the stool donor program is vital to its feasibility and patient safety.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2508950}, pmid = {40530459}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/ethics/adverse effects/standards ; *Clostridium Infections/therapy ; *Patient Safety ; *Feces/microbiology ; *Tissue Donors ; Gastrointestinal Microbiome ; Clostridioides difficile ; }, abstract = {Human stool-based products composed of fecal microbiota are a new frontier of medical therapeutics development. The development of standardized manufacturing protocols of donor microbiota has transformed fecal microbiota transplantation (FMT) from a crude and rarely used procedure to a widely accepted and highly effective option for treatment Clostridioides difficile infections. There is also a growing interest in using microbiota transplant therapies for multiple other clinical indications. In this manuscript, we review the logistical challenges experienced by various stool banks and our own group in establishing and administering a stool donor program. Furthermore, we explore and highlight the multiple ethical considerations that are ultimately essential to product safety and efficacy and propose basic principles that are necessary to maintain stool donor program integrity.}, } @article {pmid40529581, year = {2025}, author = {Xu, D and Lu, Z and Li, Q and Cheng, Y and Yang, Z}, title = {Decoding the gut-sleep Nexus: a bibliometric mapping of gut microbiota and sleep disorders.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1598173}, pmid = {40529581}, issn = {1664-302X}, abstract = {BACKGROUND: An increasing number of studies have focused on the interaction between gut microbiota and sleep disorders. However, there is currently no bibliometric analysis of the literature on gut microbiota and sleep disorders. This study employs bibliometric methods to analyze the current research status and hotspots in the field of gut microbiota and sleep disorders, providing a reference for future research in this area.

METHODS: Articles related to gut microbiota and sleep disorders were retrieved from the WOS core database, covering the period from the database's inception to December 31, 2024. After rigorous screening, VOSviewer and CiteSpace were used to conduct analyses on quantity, collaboration networks, clustering, and citation bursts.

RESULTS: The number of articles on gut microbiota and sleep disorders has increased annually, with a significant surge after 2022. China has the highest number of publications, while the United States has the highest citation count. The institution with the most publications is Shanghai Jiao Tong University, and the institution with the most citations is Deakin University. The top 10 journals by publication volume are all ranked above Q2 in the JCR. The most cited article is "Gut microbiome diversity is associated with sleep physiology in humans" by Smith et al., published in PLOS ONE in 2019. The top 10 most frequent keywords are gut microbiota, sleep, depression, inflammation, chain fatty acids, anxiety, brain, oxidative stress, obesity, and health. The keyword cluster "obstructive sleep apnea" is a focal research direction, while fecal microbiota transplantation is a current research hotspot.

CONCLUSION: This study reveals the publication trends, collaboration relationships among countries, regions, and authors, and recent research hotspots in the field of gut microbiota and sleep disorders through bibliometric methods, providing an objective data reference for scientific research in this domain.}, } @article {pmid40529577, year = {2025}, author = {Wu, S and Chen, N and Wang, C and So, KF}, title = {Research focus and trends of the association between gut microbiota and neuroinflammation.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1564717}, pmid = {40529577}, issn = {1664-302X}, abstract = {BACKGROUND: The interaction between the gut microbiota and neuroinflammation plays a crucial role in the pathogenesis of many diseases, particularly neurodegenerative diseases, and has become one of the focal points of research in recent years. Despite the large number of related studies, there is currently a lack of comprehensive analysis and prediction of these data to drive the field forward. This study aims to systematically analyze the clinical practices and research hotspots of the underlying mechanisms in this field using bibliometric and visualization methods, and to explore the future development pathways.

METHODS: CiteSpace, VOSviewer, GraphPad Prism and other software were used to analyze 1,404 studies on gut microbiota and neuroinflammation collected by the core of the Web of Science since 2000, to visually present the collaborative network between literatures, structure of authors and countries, co-occurrence of keywords, emerging reference literature, and research hotspots.

RESULTS: From 2000 to 2024, the number of related papers on this topic showed an overall upward trend, and the annual citation peaked in 2020, with significant contributions from China and the United States. Research focused on the relationship between gut microbiota and neuroinflammation, with a particular emphasis on investigating the mechanisms of the microbiota-gut-brain axis through both basic and clinical research. Treatment strategies include probiotic therapy, fecal microbiota transplantation and traditional Chinese medicine.

CONCLUSION: This study comprehensively reviews the research progress on the association between gut microbiota and neuroinflammation, and discusses the current research focus and frontier directions of this relationship, so as to provide reference for the development of this field.}, } @article {pmid40529304, year = {2025}, author = {Chen, Z and Jin, D and Hu, J and Guan, D and Bai, Q and Gou, Y}, title = {Microbiota and gastric cancer: from molecular mechanisms to therapeutic strategies.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1563061}, pmid = {40529304}, issn = {2235-2988}, mesh = {*Stomach Neoplasms/therapy/microbiology/pathology ; Humans ; *Gastrointestinal Microbiome ; Dysbiosis/complications/microbiology ; Tumor Microenvironment ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Gastric cancer, a prevalent malignancy globally, is influenced by various factors. The imbalance in the gut microbiome and the existence of particular intratumoural microbiota could have a strong connection with the onset and progression of gastric cancer. High-throughput sequencing technology and bioinformatics analysis have revealed a close correlation between abnormal abundance of specific microbial communities and the risk of gastric cancer. These microbial communities contribute to gastric cancer progression through mechanisms including increasing cellular genomic damage, inhibiting DNA repair, activating abnormal signaling pathways, exacerbating tumor hypoxia, and shaping a tumor immune-suppressive microenvironment. This significantly impacts the efficacy of gastric cancer treatments, including chemotherapy and immunotherapy. Probiotic, prebiotic, antibiotic, carrier-based, dietary interventions, fecal microbiota transplantation, and traditional Chinese medicine show potential applications in gastric cancer treatment. However, the molecular mechanisms regarding dysbiosis of microbiota, including gut microbiota, and intra-tumoral microbiota during the progression of gastric cancer, as well as the therapeutic efficacy of microbiota-related applications, still require extensive exploration through experiments.}, } @article {pmid40528217, year = {2025}, author = {Ruszkowski, J and Kachlik, Z and Walaszek, M and Storman, D and Podkowa, K and Garbarczuk, P and Jemioło, P and Łyzińska, W and Nowakowska, K and Grych, K and Dębska-Ślizień, AM}, title = {Fecal microbiota transplantation from patients into animals to establish human microbiota-associated animal models: a scoping review.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {662}, pmid = {40528217}, issn = {1479-5876}, support = {"Medical University of Gdansk Excellence Initiative- Research University" program//Gdański Uniwersytet Medyczny/ ; }, mesh = {Animals ; Humans ; Mice ; *Disease Models, Animal ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) from humans with specific medical conditions to animal models can demonstrate causality by inducing or exacerbating pathophenotypes, linking the gut microbiota to health outcomes.

METHODS: We conducted a scoping review searching MEDLINE, EMBASE, Scopus, and Web of Science through July 2024 to identify human noninfectious diseases studied using FMT in animal models, investigate FMT methodologies, and assess the feasibility of systematic reviews on the role of the microbiota in specific diseases.

RESULTS: From 605 reports of 489 studies, we found that inflammatory bowel diseases, irritable bowel syndrome, obesity, colorectal cancer, and depression were the most commonly studied, with cancer research focusing on immunotherapy non-responsiveness. In a random sample of studies, gastrointestinal outcomes were most frequently reported, with remarkably high rates (> 80%) of successful induction of disease-specific alterations for intestinal barrier function, gastrointestinal inflammation, circulating immune parameters, and fecal metabolites. Most studies used C57BL/6 mice and oral gavage administration, with recipients being either germ-free or antibiotic-pretreated. We created tables linking conditions with publications to facilitate future systematic reviews.

CONCLUSIONS: Although human-to-animal FMT studies cover diverse conditions, methodological heterogeneity and inconsistent reporting hinder comparability. Standardized protocols and guidelines are needed. For several conditions, sufficient literature exists to assess the role of the gut microbiota in human health through systematic reviews.}, } @article {pmid40528179, year = {2025}, author = {Chen, K and Wang, H and Yang, Y and Tang, C and Sun, X and Zhou, J and Liu, S and Li, Q and Zhao, L and Gao, Z}, title = {Common mechanisms of Gut microbe-based strategies for the treatment of intestine-related diseases: based on multi-target interactions with the intestinal barrier.}, journal = {Cell communication and signaling : CCS}, volume = {23}, number = {1}, pages = {288}, pmid = {40528179}, issn = {1478-811X}, support = {82274343//National Natural Science Foundation of China/ ; 82405302//National Natural Science Foundation of China/ ; ZR2024QH032//Shandong Provincial Natural Science Foundation/ ; 24-4-4-zrjj-111-jch//Qingdao Natural Science Foundation/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Animals ; *Intestinal Mucosa/microbiology/metabolism ; Probiotics/therapeutic use ; *Intestinal Diseases/microbiology/therapy ; Fecal Microbiota Transplantation ; }, abstract = {The concurrent occurrence and exacerbation of multiple diseases, including geriatric diseases and chronic diseases, impose a heavy burden on human health and medical expenses. Clarifying the common mechanisms of related multifarious diseases and developing preventive and therapeutic strategies with synergistic effects for multiple diseases are of great significance in alleviating the burden on the medical system and reducing patients' burden of drug metabolism. Recent studies have revealed that gut microbiota disorders and intestinal barrier damage, which consequently cause metabolic and immunological disorders, may be a common pathological basis underlying various intestinal-related diseases. In this review, we focus on the intestinal barrier function, summarizing the multi-target interactions and common mechanisms involved in diseases related to the gut such as ulcerative colitis, colorectal cancer, and type 2 diabetes. We identified gut microbe-based strategies, including probiotics, prebiotics, synbiotics, postbiotics, as well as potential targets in faecal microbiota transplant and berberine. The common mechanisms and key targets in the treatment of these diseases mainly include increasing the abundance of beneficial genera Bifidobacterium and Lactobacillus, increasing the levels of Short Chain Fatty Acids, restoring the intestinal mechanical barrier, and suppressing gut inflammation infiltration. We aim to provide a crucial basis and direction for the development of novel drugs with therapeutic effects for multiple diseases, thereby alleviating the patients' burden of medication and enhancing the efficacy of treatment.}, } @article {pmid40527176, year = {2025}, author = {Wang, Z and Wang, Y and Zhang, J and Yin, K and Luo, H and Huang, W}, title = {Multi-omics approaches to explore the therapeutic mechanism for ginsenoside Rg1 against MASLD.}, journal = {Biochemical and biophysical research communications}, volume = {776}, number = {}, pages = {152161}, doi = {10.1016/j.bbrc.2025.152161}, pmid = {40527176}, issn = {1090-2104}, mesh = {*Ginsenosides/pharmacology/therapeutic use ; Animals ; Gastrointestinal Microbiome/drug effects ; Mice ; Male ; Mice, Inbred C57BL ; Receptors, Aryl Hydrocarbon/metabolism ; Disease Models, Animal ; *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism/microbiology ; Metabolomics/methods ; Tryptophan/metabolism ; Fecal Microbiota Transplantation ; Liver/drug effects/pathology/metabolism ; RNA, Ribosomal, 16S/genetics ; Multiomics ; }, abstract = {Ginsenoside Rg1 (G-Rg1), a traditional Chinese medicine, alleviates metabolic dysfunction-associated steatotic liver disease (MASLD). However, the mechanism by which G-Rg1 improves metabolic disorders in MASLD by regulating the gut microbiota remains ambiguous‌. We constructed a diet-induced murine MASLD model and employed 16S rRNA sequencing and non-targeted metabolomic analysis to ‌investigate the mechanism of G-Rg1 in treating MASLD, focusing on its regulatory effect on the gut microbiota. Our results revealed that G-Rg1 significantly increased the 5-hydroxyindoleacetic acid levels and activated the aryl hydrocarbon receptor (AHR) by enhancing intestinal permeability, modulating the gut microbiota composition, and influencing tryptophan metabolism. Therefore, G-Rg1 improved immune function and reduced liver inflammation and lipid deposition in the MASLD mouse model. In contrast, the effect of G-Rg1 was impaired upon removal of the gut microbiota. Furthermore, fecal microbiota transplantation in G-Rg1-treated mice improved MASLD. These finding s suggest that regulating the gut microbiota may play an important role in G-Rg1's ability to protect against MASLD. G-Rg1 may exert its anti-MASLD effects through the gut microbiota, tryptophan metabolism, AHR activation, and interleukin-22 signaling, offering a novel approach for G-Rg1-mediated MASLD treatment.}, } @article {pmid40523286, year = {2025}, author = {Juul, FE and Bretthauer, M and Johnsen, PH and Samy, F and Tonby, K and Berdal, JE and Hoff, DAL and Ofstad, EH and Abraham, A and Seip, B and Wiig, H and Rognstad, ØB and Glad, IF and Valeur, J and Nissen-Lie, AE and Ness-Jensen, E and Lund, KMA and Skjevling, LK and Hanevik, K and Skudal, H and Melsom, EJ and Boyar, R and Cooper, TJ and Ranheim, TE and Riise, EM and Adami, HO and Kalager, M and Løberg, M and Garborg, KK}, title = {Fecal Microbiota Transplantation Versus Vancomycin for Primary Clostridioides difficile Infection : A Randomized Controlled Trial.}, journal = {Annals of internal medicine}, volume = {178}, number = {7}, pages = {940-947}, doi = {10.7326/ANNALS-24-03285}, pmid = {40523286}, issn = {1539-3704}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Anti-Bacterial Agents/therapeutic use/adverse effects ; Clostridioides difficile ; *Clostridium Infections/therapy/drug therapy ; *Fecal Microbiota Transplantation/adverse effects ; Recurrence ; Treatment Outcome ; *Vancomycin/therapeutic use/adverse effects ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is recommended for recurrent Clostridioides difficile infection (CDI), but its role in primary CDI is unclear.

OBJECTIVE: To investigate the efficacy and safety of FMT in primary CDI.

DESIGN: Randomized, open-label, noninferiority, multicenter trial. (ClinicalTrials.gov: NCT03796650).

SETTING: Hospitals and primary care facilities in Norway.

PATIENTS: Adults with CDI (C difficile toxin in stool and ≥3 loose stools daily) and no previous CDI within 365 days before enrollment.

INTERVENTION: FMT without antibiotic pretreatment versus oral vancomycin, 125 mg 4 times daily for 10 days.

MEASUREMENTS: The primary end point was clinical cure (firm stools or <3 bowel movements daily) at day 14 and no disease recurrence within 60 days with the assigned treatment alone.

RESULTS: Of 104 randomly assigned patients, 100 received FMT or the first dose of vancomycin and were eligible for analysis. Clinical cure and no disease recurrence within 60 days without additional treatment was observed in 34 of 51 patients (66.7%) with FMT versus 30 of 49 (61.2%) with vancomycin (difference, 5.4 percentage points [95.2% CI, -13.5 to 24.4 percentage points]; P for noninferiority < 0.001, rejecting the hypothesis that response to FMT is 25 percentage points lower than response to vancomycin). Eleven patients in the FMT group and 4 in the vancomycin group had additional C difficile treatment. Clinical cure at day 14 and no recurrence with or without additional treatment was observed in 40 of 51 patients (78.4%) with FMT and 30 of 49 (61.2%) with vancomycin (difference, 17.2 percentage points [95.2% CI, -0.7 to 35.1 percentage points]). No significant differences in adverse events were observed between groups.

LIMITATIONS: Open-label design and reliance on clinical end points.

CONCLUSION: FMT may be considered as first-line therapy in primary CDI.

PRIMARY FUNDING SOURCE: South-East Norway Health Trust.}, } @article {pmid40522165, year = {2025}, author = {Huang, JN and Wen, B and Wang, ZN and Gao, JZ and Chen, ZZ}, title = {Microplastics Change the Food Utilization of Filter-Feeding Fish via Gut Microbiota.}, journal = {Environmental science & technology}, volume = {59}, number = {29}, pages = {15353-15363}, doi = {10.1021/acs.est.5c02067}, pmid = {40522165}, issn = {1520-5851}, mesh = {Animals ; *Carps/growth & development/microbiology/parasitology ; *Environmental Pollutants/toxicity ; Fecal Microbiota Transplantation ; *Feeding Behavior/drug effects ; *Gastrointestinal Microbiome/drug effects ; *Microplastics/toxicity ; Multiomics ; Zebrafish ; Phytoplankton ; Zooplankton ; Food Chain ; }, abstract = {Microplastics (MPs) are ubiquitous in aquatic environments, while their effects on filter-feeding fish are poorly understood. This study aims to explore how MPs change the feeding of planktivorous silver carp. After exposure to MPs, the utilization efficiency of zooplankton by carp increased from 28.45% to 38.63-40.20%, while that of phytoplankton decreased from 50.64% to 40.47-43.32%. MPs did not cause changes in the phytoplankton and zooplankton communities that carp consumed but altered its gut microbiota, leading to increased abundance of genes encoding proteases but decreased carbohydrase genes. Gut metabolomics further showed corresponding metabolic changes especially with increased levels of l-tyrosine, citrulline, succinic acid, and propionic acid, which are significantly correlated with the isotopic signatures of carp utilizing zooplankton. Germ-free zebrafish transplanted with feces of MPs-exposed carp showed metabolic changes like those of carp, verifying that the gut microbiota mediated the effects induced by MPs, while silver carp transplanted with feces of MPs-exposed carp exhibited increased protease activity and enhanced zooplankton utilization efficiency, confirming that MPs could alter its food utilization via gut microbiota. Our findings fill a knowledge gap regarding the ecological risk of MPs to the feeding of planktivorous fish, with potential cascading effects on aquatic ecosystems.}, } @article {pmid40522093, year = {2025}, author = {Dolo, O and Coulibaly, F and Somboro, AM and Sun, S and Diarra, M and Maiga, A and Bore, S and Fofana, DB and Marcelin, A-G and Diakite, B and Kassogue, Y and Holl, JL and Calvez, V and Traoré, CB and Murphy, R and Fodor, AA and Maiga, M and Maiga, AI}, title = {The human gut microbiome and its metabolic pathway dynamics before and during HIV antiretroviral therapy.}, journal = {Microbiology spectrum}, volume = {13}, number = {8}, pages = {e0220524}, pmid = {40522093}, issn = {2165-0497}, support = {D43 CA260658/CA/NCI NIH HHS/United States ; U54 EB027049/EB/NIBIB NIH HHS/United States ; R21 AI148033/AI/NIAID NIH HHS/United States ; D43 TW010350/TW/FIC NIH HHS/United States ; U01 CA275129/CA/NCI NIH HHS/United States ; D43 TW010543/TW/FIC NIH HHS/United States ; UM1 AI069471/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *HIV Infections/drug therapy/microbiology ; *Dysbiosis/microbiology ; *Metabolic Networks and Pathways ; Male ; Adult ; Female ; Middle Aged ; *Bacteria/classification/genetics/metabolism/isolation & purification ; *Anti-HIV Agents/therapeutic use ; Feces/microbiology ; *Anti-Retroviral Agents/therapeutic use ; Whole Genome Sequencing ; }, abstract = {The human gut microbiome consists of highly complex microbial populations that play important roles in disease pathogenesis. Changes in the gut microbiome are associated with HIV infection. However, it is unclear whether gut microbiome dysbiosis is causally linked to disease or whether it simply reflects disease-induced changes in the host immune and metabolic systems. This study aims to describe and compare intestinal microbial compositions and derived metabolic pathways in people living with HIV (PL-HIV) from prior to antiretroviral therapy (ART) to 6 and 12 months after ART initiation, compared to HIV-negative individuals. Whole-genome microbiome sequencing coupled with bioinformatics analysis was used to characterize participants' intestinal microbial structures and derived metabolic pathways. Pre- and post-ART gut microbiota characterization of PL-HIV revealed substantial dysbiosis compared to HIV-negative people. An enrichment of pro-inflammatory microorganisms was the hallmark of dysbiosis in the PL-HIV pre-ART, with a decline in Proteobacteria at 6 months of ART, continuing until 12 months of ART. Lower proportions of Bacteroidetes were noted pre-ART, but they increased slightly at 6 months of ART before decreasing again at 12 months of ART. Additionally, we reported metabolic changes that are particularly important for health and are associated with dysbiosis both before and post-ART. Alteration of the pyruvate fermentation to the isobutanol metabolic pathway persisted in PL-HIV after 12 months of ART, and this mechanism was correlated with a decrease in Ruminococcus bromii species. ART initiation appears to lead to changes in several crucial metabolic pathways and may not entirely restore the dysbiosis of the gut microbiota caused by HIV.IMPORTANCEResearchers are facing a major challenge in the treatment of HIV infection due to the continuous use of antiretroviral (ARV) molecules. However, regularly monitoring these molecules is necessary because they are not without consequences. They have toxicity and side effects and could also destabilize the intestinal microbiota, which could harm the metabolic pathways essential to good health. This study reveals that ARV treatment only partially restores gut microbiota dysbiosis and alters metabolic pathways due to pathogenic taxa. This provides additional insights into the relationship between antiretroviral therapy and the microbiome, potentially leading to new prevention and treatment strategies such as probiotic/prebiotic or microbiota transplants.}, } @article {pmid40520768, year = {2025}, author = {Feng, Z and Burgermeister, E and Philips, A and Zuo, T and Wen, W}, title = {The gut virome in association with the bacteriome in gastrointestinal diseases and beyond: roles, mechanisms, and clinical applications.}, journal = {Precision clinical medicine}, volume = {8}, number = {2}, pages = {pbaf010}, pmid = {40520768}, issn = {2516-1571}, abstract = {The gut virome, an essential component of the intestinal microbiome, constitutes ∼0.1% of the total microbial biomass but contains a far greater number of particles than bacteria, with phages making up 90%-95% of this virome. This review systematically examines the developmental patterns of the gut virome, focusing on factors influencing its composition, including diet, environment, host genetics, and immunity. Additionally, it explores the gut virome's associations with various diseases, its interactions with gut bacteria and the immune system, and its emerging clinical applications.}, } @article {pmid40520290, year = {2025}, author = {Meng, D and Kong, W and Cheng, S and Liu, H and Huang, C}, title = {Gut-brain-liver axis in growth hormone deficiency: role of microbiota-derived short-chain fatty acids in ethnic variability and therapeutic development.}, journal = {Frontiers in public health}, volume = {13}, number = {}, pages = {1541654}, pmid = {40520290}, issn = {2296-2565}, mesh = {Humans ; *Fatty Acids, Volatile/metabolism ; *Gastrointestinal Microbiome/physiology ; *Liver/metabolism ; *Human Growth Hormone/deficiency ; Animals ; *Brain/metabolism ; }, abstract = {Growth hormone deficiency (GHD) is a pediatric endocrine disorder characterized by dysregulated growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis activity and gut microbiota imbalance. Emerging evidence highlights the gut-brain-liver axis as a critical modulator of growth, with microbiota-derived short-chain fatty acids (SCFAs) playing dual roles in GH suppression and IGF-1 enhancement. This review synthesizes preclinical and clinical data to address ethnic variability in microbiota composition and therapeutic challenges. Key findings reveal that Chinese GHD cohorts exhibit reduced Bifidobacterium and fecal butyrate, whereas Spanish cohorts show minimal differences, potentially due to dietary fiber intake (e.g., Prevotella-enriched diets in Asia) or methodological variations in microbiota sequencing. Mechanistically, propionate (>500 μM) inhibits pituitary GH synthesis via GPR41/43-cAMP signaling, while butyrate enhances hepatic IGF-1 through GPR109A-mediated IL-6 secretion and osteoblastic histone deacetylase (HDAC) inhibition. Interventions such as probiotics (e.g., Lactobacillus plantarum increased IGF-1 by 1.2-1.8-fold in murine models) and high-fiber diets demonstrate preclinical efficacy but face clinical barriers, including poor adherence (<30%) and limited GHD-specific trials. Fecal microbiota transplantation (FMT) shows hormonal restoration in animal models but induces gastrointestinal adverse effects (22% bloating, 15% diarrhea) in humans. Multi-omics approaches are proposed to identify biomarkers (e.g., low butyrate + elevated trimethylamine N-oxide). These approaches also aim to optimize precision therapies, such as nanoparticle-delivered SCFAs. This review underscores the need for multicenter randomized controlled trials to validate synbiotics or engineered microbial consortia, bridging mechanistic insights into the microbiota-SCFA-endocrine axis with clinical translation for GHD management.}, } @article {pmid40519780, year = {2025}, author = {Marrocco, F and Khan, R and Reccagni, A and Lin, X and Delli Carpini, M and Iebba, V and D'Alessandro, G and Limatola, C}, title = {Fecal or bacterial transplantation in mice transfer environment-induced brain plasticity and associated behavioral changes.}, journal = {Frontiers in physiology}, volume = {16}, number = {}, pages = {1572854}, pmid = {40519780}, issn = {1664-042X}, abstract = {INTRODUCTION: Recent studies have shown that lifestyle factors, including diet and environmental stimuli, significantly alter the composition of gut microbiota and the metabolites they produce. Specifically, housing mice in an enriched environment (EE) enhances the production of short-chain fatty acids, which in part mediate the effects of EE on brain plasticity. In this study, we tested the hypothesis that the gut microbial composition of EE-exposed mice could be transplanted into mice housed in a standard environment (SE) to replicate the environmental effects on behavior, gene expression and neurogenesis.

METHODS: To test this hypothesis, we transplanted either a specific bacterial mixture or fecal material from EE-housed mice into SE-housed mice.

RESULTS: Our data show that both bacterial and fecal transplants reduce anxiety-like behaviors in mice. Additionally, we observed increased expression of hippocampal neurotrophins and enhanced neurogenesis.

DISCUSSION: These findings support the idea that gut microbiota influence brain functions, including anxiety-like behavior. Further research is necessary to clarify the underlying mechanisms. Moreover, the results suggest that fecal material transplantation (FMT) from individuals with healthy lifestyles may represent a promising strategy for the treatment of mood disorders.}, } @article {pmid40519640, year = {2025}, author = {You, W and Ji, J and Wen, D and Wang, C and Sun, X and Zhao, P}, title = {Unlocking therapeutic potential of amlexanox in MASH with insights into bile acid metabolism and microbiome.}, journal = {Npj gut and liver}, volume = {2}, number = {}, pages = {}, pmid = {40519640}, issn = {3004-9806}, support = {R00 HL143277/HL/NHLBI NIH HHS/United States ; R00 HL148504/HL/NHLBI NIH HHS/United States ; R01 DK133304/DK/NIDDK NIH HHS/United States ; }, abstract = {Metabolic dysfunction-associated steatohepatitis (MASH) has become a global health issue associated with obesity and diabetes. It is becoming a leading cause of end-stage liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). Despite its increasing prevalence, effective pharmacotherapies for MASH remain limited, underscoring the urgent need for novel interventions. Amlexanox, an inhibitor of noncanonical IκB kinases, has demonstrated potential in restoring insulin sensitivity and glucose homeostasis in obese mice and human patients, as shown in our earlier studies. Here, we aimed to assess the therapeutic potential of amlexanox in dyslipidemia-associated diseases, particularly MASH and HCC, and to elucidate the underlying mechanism. We employed GAN diet-fed Ldlr [-/-] mice, which simultaneously develop obesity, MASH, and atherosclerosis, to recapitulate human metabolic syndrome and associated complications. Amlexanox was administrated orally to these mice after disease onset to examine its therapeutic efficacy. Our study demonstrates that even a low dose of amlexanox significantly reversed MASH and nearly completely prevented the progression from MASH to HCC. Both phenotypic and transcriptomic studies revealed that amlexanox markedly improved MASH-related dyslipidemia, hepatic steatosis, inflammation, liver injury, and hepatic fibrosis. Furthermore, multi-omics analysis revealed that amlexanox enhances hepatic bile acid synthesis and promotes fecal bile acid excretion. Notably, amlexanox reprogrammed gut microbiota, robustly increasing the abundance of Akkermansia muciniphila, a probiotic known to improve metabolic dysfunction. These findings uncover the multifaceted therapeutic potential of amlexanox in treating MASH and atherosclerosis by targeting bile acid metabolism, gut microbiota, hepatic inflammation, and fibrosis. Our study highlights amlexanox as a promising candidate for clinical applications.}, } @article {pmid40519616, year = {2025}, author = {Zhang, Y and Liang, S and Choi, S and Li, G}, title = {Effects of maternal rumen microbiota on the development of the microbial communities in the gastrointestinal tracts of neonatal sika deer.}, journal = {Journal of animal science and technology}, volume = {67}, number = {3}, pages = {619-635}, pmid = {40519616}, issn = {2055-0391}, abstract = {This study investigated whether the microbial assemblages in the gastrointestinal tracts (GITs) of sika deer calves can be manipulated by maternal rumen microbiota transplantation (MRMT). The results suggest that MRMT had no significant effect on the growth of calves but markedly lowered the duration of diarrhea and increased rumen fermentation in sika deer calves. Sequencing analysis of 16S rRNA gene amplicons revealed that MRMT increased the ability of some microbial taxa to colonize the GIT or enabled the colonization of others, which caused the ruminal microbial communities in sika deer calves to shift such that they resembled those of their mothers and promoted the temporal development of gut microbial diversity in deer calves. Moreover, after inoculation, 7 inoculum-dominant taxa (Butyrivibrio, Tenericutes, RFP12, SR1, Verrucomicrobia, Verruco_5, and WCHB1_41) and one inoculum-dominant taxon (Butyrivibrio) were significantly enriched in the rumen and feces of the sika deer calves, respectively. These data suggest that MRMT may be an effective approach for promoting microbial establishment in the GIT and preventing diarrhea in sika deer calves.}, } @article {pmid40519460, year = {2025}, author = {Suvvari, TK and Vallurupalli, V and Koneru, KS and Ingawale, S and Yegurla, RR}, title = {The Lasting Imprint of Antibiotics on Gut Microbiota: Exploring Long-Term Consequences and Therapeutic Interventions.}, journal = {Cureus}, volume = {17}, number = {5}, pages = {e84114}, pmid = {40519460}, issn = {2168-8184}, abstract = {The widespread use of antibiotics has significantly impacted gut microbiota, often leading to long-term dysbiosis with profound health consequences. Antibiotics not only target pathogenic bacteria but also disrupt beneficial microbial communities, reducing diversity and increasing susceptibility to metabolic disorders, immune dysfunction, and opportunistic infections like Clostridioides difficile. The antibiotic-induced microbiota alterations can persist for weeks or even months post-treatment, contributing to ongoing health challenges. Restorative strategies, including probiotics, prebiotics, fecal microbiota transplantation, and dietary modifications, offer potential solutions to mitigate these effects. A balanced approach to antibiotic use, coupled with targeted interventions, is essential to preserving gut microbial health and minimizing long-term complications. Further research is needed to optimize therapeutic strategies and enhance patient outcomes. So, this editorial aims to examine the long-term consequences of antibiotic-induced gut microbiota disruption, highlight clinical and subclinical implications, and evaluate emerging therapeutic interventions aimed at microbiota restoration.}, } @article {pmid40518557, year = {2025}, author = {Oppenheimer, M and Tao, J and Moidunny, S and Roy, S}, title = {Anxiety-like behavior during protracted morphine withdrawal is driven by gut microbial dysbiosis and attenuated with probiotic treatment.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2517838}, pmid = {40518557}, issn = {1949-0984}, support = {R01 DA043252/DA/NIDA NIH HHS/United States ; R01 DA044582/DA/NIDA NIH HHS/United States ; R01 DA050542/DA/NIDA NIH HHS/United States ; R01 DA037843/DA/NIDA NIH HHS/United States ; R01 DA034582/DA/NIDA NIH HHS/United States ; T32 DA045734/DA/NIDA NIH HHS/United States ; R01 DA047089/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; *Probiotics/administration & dosage/therapeutic use ; *Dysbiosis/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Substance Withdrawal Syndrome/microbiology/psychology ; Mice ; *Anxiety/microbiology/etiology ; *Morphine/adverse effects ; Male ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Behavior, Animal ; Morphine Dependence ; }, abstract = {The development of anxiety during protracted opioid withdrawal heightens the risk of relapse into the cycle of addiction. Understanding the mechanisms driving anxiety during opioid withdrawal could facilitate the development of therapeutics to prevent negative affect and promote continued abstinence. Our lab has previously established the gut microbiome as a driver of various side effects of opioid use, including analgesic tolerance and somatic withdrawal symptoms. We therefore hypothesized that the gut microbiome contributes to the development of anxiety-like behavior during protracted opioid withdrawal. In this study, we first established a mouse model of protracted morphine withdrawal, characterized by anxiety-like behavior and gut microbial dysbiosis. Next, we used fecal microbiota transplantation (FMT) to show that gut dysbiosis alone is sufficient to induce anxiety-like behavior. We further demonstrated that probiotic therapy during morphine withdrawal attenuated the onset of anxiety-like behavior, highlighting its therapeutic potential. Lastly, we examined transcriptional changes in the amygdala of morphine-withdrawn mice treated with probiotics to explore mechanisms by which the gut-brain axis mediates anxiety-like behavior. Our results support the use of probiotics as a promising therapeutic strategy to prevent gut dysbiosis and associated anxiety during opioid withdrawal, with potential implications for improving treatment outcomes in opioid recovery programs.}, } @article {pmid40518001, year = {2025}, author = {Xu, Y and Mo, Y and Zhou, W and Qin, M and Li, M and Yin, G and Yu, H and Chen, Y and Du, H and Jin, Y and Huang, H and Ma, C and Xia, J and Li, H and Xie, Z and Wang, P and Hong, Y}, title = {Sorafenib induces intestinal toxicity by disturbing gut microbiota and activating the LPS/TLR4/NF-κB signaling pathway in mice.}, journal = {Toxicology}, volume = {517}, number = {}, pages = {154220}, doi = {10.1016/j.tox.2025.154220}, pmid = {40518001}, issn = {1879-3185}, mesh = {Animals ; *Sorafenib/toxicity ; *Gastrointestinal Microbiome/drug effects ; *NF-kappa B/metabolism ; Signal Transduction/drug effects ; *Toll-Like Receptor 4/metabolism ; Mice ; *Lipopolysaccharides/metabolism ; Male ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; *Antineoplastic Agents/toxicity ; *Intestines/drug effects/pathology/microbiology ; *Protein Kinase Inhibitors/toxicity ; Anti-Bacterial Agents/pharmacology ; }, abstract = {Sorafenib is a multitargeted tyrosine kinase inhibitor approved by the FDA as a standard first-line therapy for advanced hepatocellular carcinoma. Nevertheless, the high incidence rate of gastrointestinal (GI) adverse effects substantially limits its clinical application. The molecular mechanisms underlying the GI damage remain poorly understood. In this study, we explored the critical role of gut microbiota in sorafenib-induced intestinal toxicity using a mouse model and proposed a potential therapeutic intervention strategy. Sorafenib administration caused intestinal pathological damage, systemic inflammation, and oxidative stress in mice. Antibiotic (ABX) treatment and fecal microbiota transplantation (FMT) experiments demonstrated that the GI toxicity induced by sorafenib was mediated by the gut microbiota. 16S rRNA sequencing analysis revealed that sorafenib dramatically disturbed gut microbial homeostasis, leading to an increased abundance of Gram-negative bacteria and upregulated biosynthesis of lipopolysaccharide (LPS). Intestinal transcriptomic sequencing further indicated that sorafenib induced Gram-negative bacterial-derived LPS leakage via the compromised intestinal barrier and exacerbated inflammation via TLR4/NF-κB pathway activation. Notably, the TLR4-specific inhibitor TAK-242 effectively attenuated sorafenib-induced intestinal damage. Taken together, our study unveils a novel mechanism by which sorafenib exacerbates intestinal injury through gut microbiota dysbiosis and LPS/TLR4/NF-κB signaling pathway, while proposing TAK-242 as a promising therapeutic strategy. This study underscores the critical role of the gut microbiota in sorafenib-induced intestinal damage and offers new avenues for clinical intervention.}, } @article {pmid40517921, year = {2025}, author = {Wang, Y and Huang, J and Tong, H and Jiang, Y and Jiang, Y and Ma, X}, title = {Nutrient acquisition of gut microbiota: Implications for tumor immunity.}, journal = {Seminars in cancer biology}, volume = {114}, number = {}, pages = {88-103}, doi = {10.1016/j.semcancer.2025.06.003}, pmid = {40517921}, issn = {1096-3650}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Nutrients/metabolism ; *Colorectal Neoplasms/immunology/microbiology/metabolism ; Animals ; Prebiotics ; Probiotics ; *Neoplasms/immunology/microbiology ; Fecal Microbiota Transplantation ; }, abstract = {The gut microbiota is essential in colorectal cancer (CRC) development, progression, and therapeutic responsiveness through its metabolic acquisitions and immunomodulatory functions. The composition of gut microbiota is shaped by habitat filters such as oxygen availability, dietary components, and host-derived factors, which influence both bacterial colonization and metabolic strategies. Furthermore, microbial metabolism of carbohydrates, proteins, and lipids produces metabolites, including short-chain fatty acids (SCFAs), polyamines, ammonia, hydrogen sulfide, and secondary bile acids (BAs). These microbial metabolites can either support anti-tumor immune surveillance or promote tumorigenesis depending on their type, concentration, and the host context. Consequently, interventions such as high-fiber diets, prebiotic and probiotic supplementation, and fecal microbiota transplantation (FMT) have emerged as promising strategies to reshape the gut ecosystem and improve CRC treatment efficacy. This review summarizes current insights into microbial nutrient metabolism, discusses the immune-regulatory effects of key microbial metabolites, and explores microbiota-targeted strategies for enhancing antitumor efficacy. Understanding these interactions offers new therapeutic opportunities for cancer prevention and treatment.}, } @article {pmid40517506, year = {2025}, author = {Li, Y and Yue, D and Zhao, Y and Liu, P and Li, M and Chen, J and Yan, X and Fan, L and Song, G and Tian, X and Lv, Y and Zhao, Q and Qiu, Y and Yan, X}, title = {Fecal microbiota transplantation alleviates female offspring's ovarian inflammation in arsenic and fluoride co-exposed rats through the PI3K/ Akt /NF-κB pathway.}, journal = {Ecotoxicology and environmental safety}, volume = {301}, number = {}, pages = {118508}, doi = {10.1016/j.ecoenv.2025.118508}, pmid = {40517506}, issn = {1090-2414}, mesh = {Animals ; Female ; NF-kappa B/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; *Arsenic/toxicity ; *Fecal Microbiota Transplantation ; *Inflammation/chemically induced/therapy ; Ovary/drug effects ; *Fluorides/toxicity ; Phosphatidylinositol 3-Kinases/metabolism ; Rats, Sprague-Dawley ; Signal Transduction ; }, abstract = {Numerous studies have shown that exposure to arsenic (As) or fluoride(F) can damage the reproductive system, but limited evidence exists regarding the combined toxicity and pathogenesis of As and F co-exposure in female reproduction. Moreover, the role of gut microbiota in mediating such toxicity remains unclear. This study investigated the effects of As and F co-exposure on ovarian development and the potential protective role of fecal microbiota transplantation (FMT). We established an animal model of ovarian injury induced via co-exposure to NaAsO2 and NaF from birth to postnatal day 120(PND120) and introduced FMT from PND60. Co-exposure reduced serum levels of estradiol(E2) and luteinizing hormone (LH), along with morphological alterations in ovarian tissue. Meanwhile, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear transcription factor-κB (NF-κB) pathway, a known mediator of inflammation-related ovarian dysfunction, was significantly upregulated. Interestingly, with prolonged exposure, the inflammatory indicators (Akt, IL-1β, IL-6, TNF-α) on PND120 were significantly higher than those on PND60. Notably, FMT alleviated ovarian inflammation, potentially by improving colonic barrier function, thereby indirectly mitigating ovarian damage. Taken together, this study reveals that NaAsO2 and NaF co-exposure induces progressive ovarian inflammation via the PI3K/Akt/NF-κB pathway, and that FMT may offer protective effects. Our findings provide new insights into the environmental risks to female reproductive health.}, } @article {pmid40516560, year = {2025}, author = {Assmann, SL and Keszthelyi, D and Kimman, ML and Breukink, SO and , }, title = {Faecal incontinence core outcome set: an international Delphi consensus exercise among patients, health-care professionals, and researchers.}, journal = {The lancet. Gastroenterology & hepatology}, volume = {10}, number = {8}, pages = {769-778}, doi = {10.1016/S2468-1253(25)00013-5}, pmid = {40516560}, issn = {2468-1253}, mesh = {Humans ; *Fecal Incontinence/therapy/psychology ; Delphi Technique ; Consensus ; Quality of Life ; Health Personnel ; Adult ; Female ; Male ; *Outcome Assessment, Health Care ; Research Personnel ; Middle Aged ; Treatment Outcome ; }, abstract = {Faecal incontinence is a debilitating anorectal disorder that can severely affect a person's quality of life. The variability in reported outcomes in studies on treatments for faecal incontinence complicates the synthesis of evidence, thereby weakening treatment recommendations. Furthermore, the emphasis on clinical outcomes often neglects outcomes that are crucial to patients' daily lives. Incorporating diverse stakeholder perspectives, we aimed to develop a core outcome set (COS)-a minimum set of outcomes that should be measured in future studies evaluating the efficacy of a treatment in adults with faecal incontinence. Following guidelines from the COMET initiative, this study proceeded through three steps: identifying outcomes via patient interviews and a systematic literature review; ranking and refining outcomes through two rounds of Delphi surveys involving patients, health-care professionals, and researchers; and finalising the COS through a consensus meeting with relevant stakeholders. Round 1 of the Delphi survey included 109 participants (73 health-care professionals and researchers and 36 patients) and round 2 involved 74 participants (54 and 20, respectively). In both rounds, participants ranked the importance of potential outcomes on a 9-point Likert scale. Of the 58 outcomes that entered round 1 and the three that were later added, 27 outcomes were voted out and the remaining 34 were discussed during a consensus meeting to finalise the COS. The final COS encompasses 13 outcomes: seven quality of life-related outcomes (quality of life, influence on daily activities, social functioning, treatment satisfaction, enjoyment in life, embarrassment, and peace of mind) and six clinical outcomes (severity of faecal incontinence, number of faecal incontinence episodes, urgency, stool consistency, adverse events, and adherence to therapy). This study establishes what outcomes should be included in a COS for use in faecal incontinence research, but future research is needed to identify the appropriate measurement instruments for each outcome and to establish appropriate timing for their assessment, which will further refine outcome definitions before this COS can be implemented. Once these aspects are clarified, the COS can be adopted into faecal incontinence research, which we hope will ultimately improve clinical care.}, } @article {pmid40514640, year = {2025}, author = {Almulla, AF and Maes, M}, title = {Peripheral Immune-Inflammatory Pathways in Major Depressive Disorder, Bipolar Disorder, and Schizophrenia: Exploring Their Potential as Treatment Targets.}, journal = {CNS drugs}, volume = {39}, number = {8}, pages = {739-762}, pmid = {40514640}, issn = {1179-1934}, support = {RA66/016//FF66 grant and a Sompoch Endowment Fund (Faculty of Medicine), MDCU/ ; BG-RRP-2.004-0007-С01//Strategic Research and Innovation Program for the Development of MU - PLOVDIV-(SRIPD-MUP)", Creation of a network of research higher schools, National plan for recovery and sustainability, European Union - NextGenerationEU/ ; }, mesh = {Humans ; *Schizophrenia/drug therapy/immunology ; *Bipolar Disorder/drug therapy/immunology ; *Depressive Disorder, Major/drug therapy/immunology ; Animals ; *Anti-Inflammatory Agents/pharmacology/therapeutic use ; Inflammation/drug therapy/immunology ; }, abstract = {Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are major mental disorders linked to substantial morbidity. Traditional monoamine-based pharmacotherapies frequently produce inadequate outcomes for many patients. The elevated levels of treatment resistance require the exploration of new pharmacological targets. Evidence indicates that peripheral immune-inflammatory dysregulation, characterized by an imbalance between immunological responses and compensatory immune-regulatory systems (IRS/CIRS), together with increased oxidative and nitrosative stress (O&NS), significantly contributes to the pathogenesis of these disorders. This review examines IRS/CIRS/O&NS pathways as new drug targets and highlights novel pharmacological trials. Antiinflammatory drugs have been repurposed as augmentation strategies for the treatment of MDD/BD and SCZ, including nonsteroidal antiinflammatory medications, such as cyclooxygenase-2 (COX-2) inhibitors; cytokine-targeting biologics, such as tumor necrosis factor-α monoclonal antibodies; and minocycline, an antibiotic that attenuates neuroinflammation. N-acetylcysteine, curcumin, and omega-3 polyunsaturated fatty acids demonstrate some efficacy as augmentation therapies in MDD, likely by diminishing IRS activation and O&NS. Strategies aimed at the gut-brain axis and gut dysbiosis, including fecal microbiota transplantation, are under investigation for their capacity to restore immunological homeostasis by improving gut barrier integrity and microbiome composition. This review examines new potential therapeutic targets arising from recent discoveries in neuro-immune interactions and oxidative stress, including particular lymphocyte surface markers, the CIRS, and intracellular network molecules in both affective and psychotic disorders. The evidence underscores the clinical importance of immune-targeted augmentation treatments in psychiatric disorders and supports the ongoing development of these novel pharmacotherapies within a precision medicine paradigm.}, } @article {pmid40513921, year = {2025}, author = {Zhang, X and Sheng, N and Wang, Z and Cao, Y and Jiang, X and Yan, H and Cheng, F and Geng, T and Wei, K and Zhang, L and Gao, M and Zhou, G and Chen, P}, title = {Exploring the mechanism of Carbonized Typhae Pollen in treating blood stasis syndrome through metabolic profiling: the synergistic effect of hemostasis without blood stasis.}, journal = {Journal of ethnopharmacology}, volume = {351}, number = {}, pages = {120124}, doi = {10.1016/j.jep.2025.120124}, pmid = {40513921}, issn = {1872-7573}, mesh = {Animals ; Zebrafish ; Male ; Rats ; Rats, Sprague-Dawley ; *Pollen/chemistry ; *Hemostasis/drug effects ; *Typhaceae/chemistry ; Metabolomics ; *Drugs, Chinese Herbal/pharmacology ; Medicine, Chinese Traditional ; Disease Models, Animal ; }, abstract = {Removing blood stasis and stopping bleeding traditional Chinese medicines (RBSB-TCM) formed a unique class of TCM, characterized by vasodilating, removing stasis and hemostatic effects. Carbonized Typhae Pollen (CTP), derived from Typhae Pollen (TP) through carbonization, has emerged as a particularly valuable therapeutic agent. It has been widely used in clinical practice to treat hemorrhagic disorders caused by blood stasis syndrome (BSS). However, the potential mechanism for CTP to achieve the dual synergistic effect of promoting blood flow and hemostasis remains unclear.

AIM OF THE STUDY: From the standpoint of metabolite profiles, this study attempts to investigate the fundamental mechanism of CTP in the elimination of blood stasis and the cessation of bleeding.

MATERIALS AND METHODS: First, chemical constituents, absorbed constituents and metabolites in rats following oral administration of CTP were identified by ultra-high performance liquid chromatography coupled with the quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) method combined with MetabolitePilot 2.0.4 software. Subsequently, the pharmacological effects of CTP were systematically investigated using rat models with BSS and zebrafish with cerebral hemorrhage. Specifically, the impact on coagulation function and histopathology in rats, as well as the effect on cerebral hemorrhage in zebrafish, were thoroughly evaluated. Untargeted metabolomics based on rat plasma was applied to analyze the metabolic profile changes, revealing the potential action mechanism. The underlying mechanism was furtherly confirmed by gut microbiome analysis and systemic molecular biology experiments.

RESULTS: 34 prototype chemicals and 71 metabolites from the liver, heart, spleen, lung, kidney, small intestine, uterus, and serum were found. CTP improved the abnormal coagulation system, promoted blood circulation, and reduced pathological damage caused by BSS. Plasma metabolomics revealed that BSS significantly altered bile acid (BA) metabolism and arachidonic acid (AA) metabolism. Gut microbiome analysis and fecal microbiota transplantation (FMT) experiments further demonstrated that CTP modulated the gut microbiota. This modulation promoted BA production and activated endothelial nitric oxide synthase (eNOS), leading to increased nitric oxide (NO) levels. These changes contributed to the therapeutic effect of CTP in removing blood stasis. Systemic molecular biology experiments showed that CTP activated key components of the AA metabolic pathway. It promoted PLCγ1 phosphorylation, increased intracellular Ca[2+] levels, and upregulated COX-2 expression. In addition, CTP enhanced the production of AA-related metabolites, including 6-keto-prostaglandin F1α (6-keto-PGF1α), prostaglandin E2 (PGE2), and thromboxane B2 (TXB2). It also increased the transcription of AA metabolism-related genes, such as PLCγ1, PTGS2a, PTGS2b, PTGIS, PTGES, TXBAS, and vWF.

CONCLUSIONS: CTP could promote the generation of AA metabolites through PLCγ1/Ca[2+]/COX-2 to stop bleeding, while also enhancing eNOS activity and NO synthesis through gut microbiota-bile acid axis to remove blood stasis. These two effect were balanced to achieve hemostasis without blood stasis.}, } @article {pmid40511533, year = {2025}, author = {Mo, X and Shen, L and Wang, X and Ni, W and Li, L and Xia, L and Liu, H and Cheng, R and Wen, L and Xu, J and Liu, L}, title = {Melatonin Mitigates Sarcopenic Obesity via Microbiota and Short-Chain Fatty Acids: Evidence From Epidemiologic and In Vivo Studies.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {16}, number = {3}, pages = {e13869}, pmid = {40511533}, issn = {2190-6009}, support = {82230112//National Natural Science Foundation of China/ ; 82273631//National Natural Science Foundation of China/ ; 2024M761026//China Postdoctoral Science Foundation/ ; 2022YFA0806100//National Key Research and Development Program of China/ ; }, mesh = {Animals ; *Melatonin/pharmacology/therapeutic use ; *Sarcopenia/drug therapy/epidemiology/etiology ; *Obesity/drug therapy/epidemiology ; *Fatty Acids, Volatile/metabolism ; *Gastrointestinal Microbiome/drug effects ; Humans ; Male ; Rats ; Middle Aged ; Female ; Case-Control Studies ; Aged ; }, abstract = {INTRODUCTION: Gut dysbiosis is closely related to the development of sarcopenic obesity (SO). Melatonin (MLT) regulates gut microbiota and promotes the production of short-chain fatty acids (SCFAs). However, whether MLT affects SO through the gut microbiota and SCFAs remains unclear. This study aimed to investigate the effect and mechanism of MLT in SO induced by a high-fat diet (HFD).

METHODS: First, a case-control study was conducted to explore the potential association between serum MLT levels and SO-related parameters in 31 patients. Next, rats fed with a HFD were orally administered with MLT for 16 weeks, and obesity-related metabolic disorders and muscle atrophy were measured. 16S rRNA gene sequencing and gas chromatography-mass spectrometry were used to detect gut microbiota and SCFAs, respectively. Gut barrier integrity was assessed by the expression of the Muc-2 protein and tight junction proteins. Finally, faecal microbiota transplantation and SCFAs administration were performed to confirm the causal role of the gut microbiota and SCFAs in the effect of MLT on SO.

RESULTS: The serum levels of MLT decreased in patients with SO (29.87 ± 6.71 vs. 24.94 ± 5.68, p < 0.01) and were closely associated with appendicular skeletal muscle mass index (r = 0.3514, p < 0.01) and handgrip strength (r = 0.2824, p < 0.05). MLT ameliorated obesity-related metabolic disorders (p < 0.05), poor muscle mass (p < 0.05), strength (p < 0.05) and function (p < 0.05) and muscle atrophy (p < 0.05) in HFD-fed rats. MLT regulated HFD-induced gut dysbiosis, which was mainly characterized by increases in SCFAs-related bacteria and SCFAs (p < 0.05). MLT recovered HFD-induced impairment of gut barrier integrity by promoting the expression levels of Muc-2, claudin-1, occludin and zonula occluden-1 proteins in the colon (p < 0.05). Correlation analysis showed that SCFAs-related bacteria and SCFAs were negatively associated with SO. Faecal suspension from MLT-treated rats promoted the production of SCFAs in recipient rats (p < 0.05). In addition, faecal suspension from MLT-treated rats partially mitigated metabolic disorders (p < 0.05), poor muscle mass and function (p < 0.05) and muscle atrophy (p < 0.05) in recipient rats. SCFAs treatment alleviated the development of SO in HFD-fed rats by suppressing metabolic disorders (p < 0.05), reducing muscle oxidative stress and inflammation (p < 0.05) and promoting protein synthesis through the AKT/mTOR/p70S6k signalling pathway (p < 0.05).

CONCLUSIONS: MLT mitigated HFD-induced SO by regulating the gut microbiota and promoting the production of SCFAs. MLT might be a novel strategy for delaying the progression of SO.}, } @article {pmid40510802, year = {2025}, author = {Tan, S and Peng, C and Lin, X and Peng, C and Yang, Y and Liu, S and Huang, L and Bian, Y and Li, Y and Xu, C}, title = {Clinical efficacy of non-pharmacological treatment of functional constipation: a systematic review and network meta-analysis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1565801}, pmid = {40510802}, issn = {2235-2988}, mesh = {Humans ; Acupuncture Therapy/methods ; *Constipation/therapy ; Fecal Microbiota Transplantation/methods ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {INTRODUCTION: The purpose of this study is to compare the relative effectiveness and safety of non-pharmacological interventions for the treatment of functional constipation (FC).

METHODS: We searched Pubmed, Embase, Cochrane, and Web of Science databases for randomized controlled trials published from 2010 to November 2024. The quality of the included studies was evaluated using the Cochrane bias risk tool and Review Manager 5.4, and the evidence was graded using GRADEPro. A network meta-analysis (NMA) was conducted using R Studio, and the surface under the cumulative ranking curve (SUCRA) was used to rank the included drugs for each outcome measure to compare the clinical efficacy of different treatment methods for chronic functional constipation.

RESULTS: A total of 29 RCT studies were included, with a total of 4389 patients with functional constipation who were randomly assigned to receive placebo or one of the nine different non-pharmacological treatment methods. The assessment of bias risk showed that the bias risk of most included studies was low. The results showed that the first-ranked treatment method for clinical efficacy was acupuncture; the first-ranked treatment method for changes in spontaneous bowel movement (SBM) and complete spontaneous bowel movement (CSBM) was fecal microbiota transplantation (FMT); the first-ranked treatment method for changes in the Bristol Stool Form Scale (BSFS) score was FMT; the first-ranked treatment method for changes in the Patient Assessment of Constipation Quality of Life (PAC-QOL) score after treatment was the Vibration capsule; the first-ranked treatment method for changes in the Patient Assessment of Constipation Symptoms (PAC-SYM) score after treatment was percutaneous electrical stimulation; and the treatment method with the lowest incidence of adverse reactions was probiotics.

CONCLUSION: Based on the SUCRA values and NMA results, we found that FMT showed better effects and higher safety on BSFS scores, SBM, and CSBM. In addition, acupuncture showed a good clinical efficacy. We hypothesize that the combination of FMT and acupuncture may be an effective and safe treatment option for functional constipation, but further high-quality clinical studies are needed to confirm this.

https://www.crd.york.ac.uk/prospero/, identifier CRD42024625747.}, } @article {pmid40510588, year = {2025}, author = {He, S and Chen, H and Xi, H and Sun, G and Du, B and Liu, X}, title = {Gut Microbiota-Derived Butyric Acid Alleviates Glucocorticoid-Associated Osteonecrosis of the Femoral Head via Modulating Inflammatory Cytokines in Bone Marrow Mesenchymal Stem Cells.}, journal = {Mediators of inflammation}, volume = {2025}, number = {}, pages = {8742817}, pmid = {40510588}, issn = {1466-1861}, mesh = {Animals ; *Butyric Acid/metabolism/therapeutic use/pharmacology ; *Gastrointestinal Microbiome/physiology/drug effects ; Rats, Sprague-Dawley ; Rats ; *Mesenchymal Stem Cells/metabolism/drug effects ; *Glucocorticoids/adverse effects ; *Cytokines/metabolism ; Male ; *Osteonecrosis/chemically induced/metabolism/drug therapy ; }, abstract = {Background: The role of gut microbiota and its metabolites in regulating bone metabolism has been well established, with inflammatory immune responses potentially playing a critical role. Glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH), caused by high-dose glucocorticoid use for inflammatory or immune-related diseases, is a prevalent condition of bone metabolic imbalance. However, the regulatory role and mechanisms of gut microbiota and its metabolites in the development and progression of GA-ONFH remain unclear. This study aims to investigate the intervention effects of gut microbiota and its metabolite butyric acid on GA-ONFH through a series of multi-omics in vitro and in vivo experiments. Methods: Sprague Dawley rats were randomly divided into four groups. The gut microbial composition of the groups was analyzed through 16S rDNA sequencing. Targeted metabolomics was employed to assess differences in short-chain fatty acids (SCFAs) among the groups. Butyric acid, identified as a key differential metabolite, was then selected for further exploration of its effects on bone marrow mesenchymal stem cells (BMSCs) and GA-ONFH rat models through in vitro and in vivo experiments. Results: 16S rDNA sequencing revealed alterations in gut microbiota structure in GA-ONFH rats. Micro-CT and HE staining demonstrated that depletion of gut microbiota with broad-spectrum antibiotics prior to GA-ONFH modeling exacerbated the disease's development. In contrast, fecal microbiota transplantation (FMT) was shown to alleviate GA-ONFH progression. Targeted metabolomics indicated that FMT mitigated the reduction in butyric acid levels induced by dexamethasone (DXM). Subsequent in vitro cell experiments confirmed that butyric acid promotes BMSC proliferation, migration, and osteogenic differentiation. RNA sequencing revealed that butyric acid regulates T cell-mediated inflammatory cytokine genes in BMSCs, while Western blot and immunofluorescence assays confirmed that butyric acid modulates the expression of TNF-α and IL-2/IL-4 in BMSCs. Finally, in vivo experiments demonstrated that butyric acid supplementation attenuated the progression of GA-ONFH and improved the expression of inflammation-related cytokines in femoral head tissue. Conclusions: Our study demonstrates that gut microbiota depletion exacerbates GA-ONFH, while FMT restores butyric acid levels and alleviates disease severity. Butyric acid reduced the expression of TNF-α and IL-2 while increasing the level of IL-4 in vivo and in vitro, thereby improving the local inflammatory environment of the femoral head and alleviating the progression of GA-ONFH. These findings highlight that reduction in butyric acid levels due to gut microbiota dysbiosis is a crucial factor in the progression of GA-ONFH.}, } @article {pmid40509521, year = {2025}, author = {Zhang, M and Wang, W and Li, W and Wang, Z and Bi, K and Li, Y and Wu, Y and Zhao, Y and Yang, R and Du, Q}, title = {Ultrasonic-Assisted Extraction of Polysaccharides from Brassica rapa L. and Its Effects on Gut Microbiota in Humanized Mice.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, pmid = {40509521}, issn = {2304-8158}, support = {32260586//the National Natural Science Foundation of China - Regional Fund Project/ ; }, abstract = {This study optimized ultrasound-assisted extraction (UAE) for polysaccharide isolation from Brassica rapa L. using Box-Behnken design, achieving a maximum yield of 41.12% under conditions of 60 °C, 60 min, 175 W ultrasonic power, and 30 mL/g liquid-solid ratios. The crude polysaccharide (BRAP) was purified via DEAE-52 cellulose and Sephadex G-100 chromatography, yielding BRAP1-1 with the highest recovery rate. Structural analyses (FT-IR, HPGPC, SEM, SEC-MALLS-RI) identified BRAP1-1 as a β-glycosidic pyranose polysaccharide (32.55 kDa) composed of fucose, rhamnose, arabinose, galactose, and galacturonic acid (molar ratio 0.81:4.30:3.61:1.69:89.59). In a humanized mouse model via fecal microbiota transplantation (FMT), BRAP1-1 significantly increased α-diversity indices (ACE, Chao1; p < 0.05) and altered β-diversity, with PCA explaining 73% variance (PC1: 60.70%, PC2: 13.53%). BRAP1-1 elevated beneficial genera (Lysinibacillus, Solibacillus, Bacteroides, etc.) while suppressing pathogens (Treponema, Flavobacterium, etc.). Six genera, including [Eubacterium]_coprostanoligenes_group and Bacteroidales (p < 0.05), correlated with acetic/propionic acid production. These findings demonstrate BRAP1-1's potential to modulate gut microbiota composition and enhance intestinal homeostasis.}, } @article {pmid40509464, year = {2025}, author = {Gong, H and Zhao, H and Mao, X}, title = {Sea Cucumber Hydrolysates Alleviate Cognitive Deficits in D-Galactose-Induced C57BL/6J Aging Mice Associated with Modulation of Gut Microbiota.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, pmid = {40509464}, issn = {2304-8158}, support = {2023YFF1104502//National Key R&D Program of China/ ; }, abstract = {As the global elderly population is rising, concerns about cognitive decline and memory loss are becoming urgent. This study evaluated the potential of sea cucumber hydrolysates (SCH) from Stichopus japonicus in alleviating cognitive deficits using a D-galactose-induced murine aging model. The effects of SCH on behavior, hippocampal morphology, gut microbiota, hippocampal cholinergic system, brain-derived neurotrophic factor (BDNF) signaling, and neuroinflammatory pathways were investigated. Results showed that SCH ameliorated learning and memory deficits and reduced neuronal damage in aging mice. SCH also modulated gut microbiota, along with increased fecal short-chain fatty acids levels. Functional prediction revealed that alterations in gut microbiota were related to signal transduction. Further, SCH enhanced hippocampal cholinergic function through elevating acetylcholine (ACh) levels and inhibiting acetylcholinesterase (AChE) activity and activated BDNF signaling, consistent with predictions of gut microbiota function. Restoration of cholinergic homeostasis and transmission of the BDNF pathway might contribute to the inhibition of hippocampal neuroinflammation via suppressing microglial activation and the nuclear factor kappa-B (NF-κB) pathway. In summary, SCH attenuated cognitive deficits through suppressing neuroinflammation, which might be correlated with the signal transduction caused by regulating gut microbiota. Further validation will be conducted through microbiota depletion and fecal microbiota transplantation. These findings suggest that SCH is a promising functional component for counteracting aging-related cognitive deficits.}, } @article {pmid40509391, year = {2025}, author = {Zang, R and Zhou, R and Li, Y and Liu, Z and Wu, H and Lu, L and Xu, H}, title = {Oleuropein Regulates Bile Acid Metabolism via Modulating the Gut Microbiota, Thereby Alleviating DSS-Induced Ulcerative Colitis in Mice.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, pmid = {40509391}, issn = {2304-8158}, abstract = {The pathogenesis of ulcerative colitis (UC) involves genetic, immunological, and environmental factors as well as gut microbiota dysbiosis. As a natural antioxidant with various pharmacological activities widely present in Oleaceae plants, oleuropein (OLE) exhibits anti-inflammatory, anti-tumor, antiviral, hypoglycemic, and cardioprotective effects. It has been validated that OLE extracted from olive oil can ameliorate UC. However, it remains unclear if and how OLE modulates the gut microbiota in the alleviation of UC. Therefore, this study was conducted to explore the mechanisms for OLE to alleviate UC induced by dextran sulfate sodium (DSS), with the focus placed on its regulatory function in the gut microbiota. The results indicated that OLE mitigated DSS-induced UC by enhancing the intestinal barrier function, reshaping the gut microbiota, and modulating bile acid metabolism. The fecal microbiota transplantation (FMT) experiment results further confirmed that the protective effect of OLE against UC could be mediated by alterations in the gut microbiota and their metabolites induced by OLE. Additionally, OLE increased the abundance of Lactobacillus and certain bile acid metabolites in the colon, including hyodeoxycholic acid (HDCA). HDCA could upregulate the expression of ZO-1 and claudin-3, restoring intestinal barrier integrity. Simultaneously, HDCA could inhibit the activation of the nuclear factor kappa-B (NF-κB) signaling pathway in the colon and relieve colonic inflammation. Overall, it was corroborated that OLE alleviated DSS-induced UC by modulating the gut microbiota and altering bile acid metabolism.}, } @article {pmid40508089, year = {2025}, author = {Ai, P and Xu, S and Yuan, Y and Xu, Z and He, X and Mo, C and Zhang, Y and Yang, X and Xiao, Q}, title = {Targeted Gut Microbiota Modulation Enhances Levodopa Bioavailability and Motor Recovery in MPTP Parkinson's Disease Models.}, journal = {International journal of molecular sciences}, volume = {26}, number = {11}, pages = {}, pmid = {40508089}, issn = {1422-0067}, support = {82171246//National Natural Science Foundation of China/ ; 82371251//National Natural Science Foundation of China/ ; 2022YFE0210100//National Key R&D Program of China/ ; 22QA1405700//Shanghai Rising-Star Program/ ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Levodopa/pharmacokinetics/pharmacology/therapeutic use ; Mice ; Fecal Microbiota Transplantation ; Biological Availability ; Male ; Humans ; Disease Models, Animal ; *Parkinson Disease/drug therapy/metabolism ; Dopamine/metabolism ; Mice, Inbred C57BL ; Female ; }, abstract = {Emerging evidence highlights the gut microbiota as a pivotal determinant of pharmacological efficacy. While Enterococcus faecalis (E. faecalis)-derived tyrosine decarboxylases (tyrDCs) are known to decarboxylate levodopa (L-dopa), compromising systemic bioavailability, the causal mechanisms underlying microbiota-mediated pharmacodynamic variability remain unresolved. In our study, we employed antibiotic-induced microbiota depletion and fecal microbiota transplantation (FMT) to interrogate microbiota-L-dopa interactions in MPTP-induced Parkinson's disease (PD) mice. The study demonstrated that antibiotic-mediated microbiota depletion enhances L-dopa bioavailability and striatal dopamine (DA) level, correlating with improved motor function. To dissect clinical heterogeneity in the L-dopa response, PD patients were stratified into moderate responders and good responders following standardized L-dopa challenges. In vitro bioconversion assays revealed greater L-dopa-to-DA conversion in fecal samples from moderate responders versus good responders. FMT experiments confirmed mice receiving good-responder microbiota exhibited enhanced L-dopa bioavailability, higher striatal DA concentrations, and a heightened therapeutic effect of L-dopa relative to moderate-responder recipients. Collectively, our study provided evidence that the gut microbiota directly modulates L-dopa metabolism and microbial composition determines interindividual therapeutic heterogeneity. Targeted microbial modulation-through precision antibiotics or donor-matched FMT-is a viable strategy to optimize PD pharmacotherapy, supporting the potential for microbiota-targeted adjuvant therapies in PD management.}, } @article {pmid40507919, year = {2025}, author = {Belvončíková, P and Macáková, K and Tóthová, N and Babál, P and Tarabčáková, L and Gardlík, R}, title = {Investigating the Role of Gut Microbiota in the Pathogenesis and Progression of Rheumatoid Arthritis in a Collagen-Induced Arthritis Mouse Model.}, journal = {International journal of molecular sciences}, volume = {26}, number = {11}, pages = {}, pmid = {40507919}, issn = {1422-0067}, support = {APVV-21-0370//Slovak Research and Development Agency/ ; VEGA 1/0706/25//Ministry of Education, Science, Research and Sport of the Slovak Republic/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Arthritis, Rheumatoid/microbiology/pathology/therapy/etiology ; *Arthritis, Experimental/microbiology/pathology/therapy ; Mice ; Disease Models, Animal ; RNA, Ribosomal, 16S/genetics ; Disease Progression ; Humans ; Mice, Inbred DBA ; Male ; Fecal Microbiota Transplantation ; Female ; }, abstract = {Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder whose precise etiology remains unclear, though growing evidence implicates gut microbiota in its pathogenesis. This study aimed to investigate the role of gut microbiota in the onset and progression of RA by employing fecal microbiota transplantation (FMT) in a collagen-induced arthritis (CIA) mouse model using DBA/1J and Aire[-]/[-] strains. Mice received FMT from healthy donors, treatment-naïve RA patients, or treated RA patients in relapse, followed by assessment of microbiota composition via 16S rRNA sequencing, arthritis severity scoring, histological evaluations, and systemic inflammatory markers. The findings revealed distinct microbiota clustering patterns post-FMT across experimental groups, highlighting strain-specific colonization effects. Notably, genera such as Bifidobacterium and Paraprevotella correlated positively with arthritis severity in DBA/1J mice, whereas Corynebacterium, Enterorhabdus, and Odoribacter exhibited negative correlations, suggesting potential protective roles. Despite these microbial differences, minor variations in arthritis scores, paw inflammation, or systemic inflammation were observed among FMT groups. This indicates that although gut microbiota alterations are associated with RA pathogenesis, further investigation with larger cohorts and comprehensive sequencing approaches is essential to elucidate the therapeutic potential of microbiome modulation in autoimmune diseases.}, } @article {pmid40506454, year = {2025}, author = {Runge, S and von Zedtwitz, S and Maucher, AM and Bruno, P and Osbelt, L and Zhao, B and Gernand, AM and Lesker, TR and Gräwe, K and Rogg, M and Schell, C and Boerries, M and Strowig, T and Andrieux, G and Hild, B and Rosshart, SP}, title = {Laboratory mice engrafted with natural gut microbiota possess a wildling-like phenotype.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {5301}, pmid = {40506454}, issn = {2041-1723}, support = {491676693//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 256073931//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 446316360//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 431984000//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 241702976//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 438496892//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 501370692//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 256073931//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 256073931//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 491676693//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 259373024//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 431984000//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 441891347//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 471011418//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 493802833-P7//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 390874280//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 2023.010.1//Wilhelm Sander-Stiftung (Wilhelm Sander Foundation)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/immunology/physiology ; Mice ; Phenotype ; Specific Pathogen-Free Organisms ; Mice, Inbred C57BL ; Male ; Female ; *Fecal Microbiota Transplantation/methods ; Models, Animal ; }, abstract = {Conventional laboratory mice housed under specific pathogen-free (SPF) conditions are the standard model in biomedical research. However, in recent years, many rodent-based studies have been deemed irreproducible, raising questions about the suitability of mice as model organisms. Emerging evidence indicates that variability in SPF microbiota plays a significant role in data inconsistencies across laboratories. Although efforts have been made to standardize microbiota, existing microbial consortia lack the complexity and resilience necessary to replicate interactions in free-living mammals. We present a robust, feasible and standardizable approach for transplanting natural gut microbiota from wildlings into laboratory mice. Following engraftment, these TXwildlings adopt a structural and functional wildling-like microbiota and host physiology toward a more mature immune system, with characteristics similar to those of adult humans. We anticipate that adopting wild mouse-derived microbiota as standard for laboratory mouse models will improve the reproducibility and generalizability of basic and preclinical biomedical research.}, } @article {pmid40505989, year = {2025}, author = {Mehta, N and Little, K and Woodworth, MH and Goodenough, D and Dhonau, R and Fridkin, SK}, title = {Evaluating Disparities in Recurrent Clostridioides difficile Infection and Fecal Microbiota Transplant Treatment Using Geospatial and Social Vulnerability Analytic Tools.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2025.05.028}, pmid = {40505989}, issn = {1528-0012}, } @article {pmid40505847, year = {2025}, author = {Yadav, A and Tadas, M and Kale, M and Wankhede, N and Umekar, M and Kotagale, N and Taksande, B}, title = {Gut microbiota and behavioral ontogeny in autism spectrum disorder: a pathway to therapeutic innovations.}, journal = {Physiology & behavior}, volume = {299}, number = {}, pages = {114989}, doi = {10.1016/j.physbeh.2025.114989}, pmid = {40505847}, issn = {1873-507X}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Autism Spectrum Disorder/microbiology/therapy/physiopathology/psychology ; Animals ; Probiotics/therapeutic use ; Dysbiosis ; Prebiotics ; Fecal Microbiota Transplantation ; Brain ; Female ; Brain-Gut Axis ; }, abstract = {Autism Spectrum Disorder (ASD) is a multifaceted neurodevelopmental condition characterized by deficits in social communication, repetitive behaviors, and restricted interests. Emerging evidence suggests that gut-brain axis a dynamic, bidirectional communication network between gut microbiota and central nervous system, is critical in shaping behavioral ontogeny in ASD. Dysbiosis of gut microbiota, commonly observed in individuals with ASD, has been associated with alterations in neurodevelopmental trajectories and symptom severity. Furthermore, disturbances in maternal microbiome during pregnancy are increasingly recognized as key factors influencing fetal brain development, potentially heightening risk of ASD and behavioral manifestations. Mechanistic research reveals that gut-derived metabolites modulate blood-brain barrier integrity, neuroinflammatory processes, and neuronal circuit formation, contributing to behavioral outcomes. These findings emphasize gut microbiota's profound influence on emergence and progression of ASD-related behaviors. Promising therapeutic strategies, including probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, have demonstrated potential in modulating the gut microbiome and improving behavioral symptoms in ASD. However, challenges such as individual variability in microbiome composition, limited clinical evidence, and an incomplete understanding of causative mechanisms remain significant barriers to clinical translation. This review explores the interplay between gut microbiota and ASD-associated behaviors, focusing on key mechanisms such as microbial regulation of neurotransmitter production, immune signaling, and neuroinflammation. It further highlights gut microbiota's potential as a modifiable factor influencing neurodevelopmental and behavioral outcomes in ASD. By advancing our understanding of gut-brain axis, we can pave the way for personalized and targeted interventions aimed at improving behavioral ontogeny and developmental trajectories in individuals with ASD.}, } @article {pmid40505719, year = {2025}, author = {Zhu, X and Xu, Y}, title = {Gut microbiome contributes to 6PPD-quinone induced cognitive impairment through PI3K/Akt signaling.}, journal = {Toxicology}, volume = {517}, number = {}, pages = {154217}, doi = {10.1016/j.tox.2025.154217}, pmid = {40505719}, issn = {1879-3185}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/physiology ; *Cognitive Dysfunction/chemically induced/microbiology ; *Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/drug effects ; Male ; Mice ; *Phosphatidylinositol 3-Kinases/metabolism ; *Phenylenediamines/toxicity ; Hippocampus/drug effects/pathology ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Benzoquinones ; }, abstract = {Studies show that N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) accumulates in the central nervous system, but its role in cognitive impairment and underlying mechanisms remain unclear. Morris water maze assay revealed that 6-PPDQ significantly impairs cognitive function, particularly learning and memory. HE staining revealed alterations in the hippocampal DG and CA3 regions of exposed mice, including sparse cell arrangement, blurred boundaries, nuclear condensation, and a reduction in Nissl bodies. Fecal microbiota transplantation from 6-PPDQ-exposed mice to normal mice induced cognitive deficits and hippocampal pathological damage. Western Blot assay showed that 6-PPDQ exposure resulted in inhibition of PI3K/AKT signaling. Moreover, blunted PI3K/AKT signaling was observed in mice transplanted with 6-PPDQ-associated mice fecal microbiota. Further analysis of 16S rDNA assay identified a total of 30 differential bacteria at the genus level, including 8 upregulated bacteria such as g_Helicobacter and 22 downregulated bacteria such as g_Prevotellaceae_NK3B31_group. In conclusion, this study uncovers gut microbiome mediates 6PPD-Q-induced cognitive impairment through inhibiting of PI3K/Akt signaling, and provides a basis for further investigation into gut microbiome's protective effects on 6-PPDQ-induced nervous system injury.}, } @article {pmid40502301, year = {2025}, author = {Bhandari, P and Berezovskiy, R and Makhani, S and Gausman, V and Rastogi, N and Braude, S}, title = {Discordance in Clinical Indicators With Sequential Fecal Microbiota Transplantation: A Case of Fulminant Clostridioides Difficile Infection.}, journal = {ACG case reports journal}, volume = {12}, number = {6}, pages = {e01731}, pmid = {40502301}, issn = {2326-3253}, abstract = {Fulminant Clostridioides difficile infection (CDI) is a rare, severe type of CDI, often associated with extended hospitalizations, significant healthcare costs, and elevated mortality rates. Fecal microbiota transplantation remains an effective treatment modality for patients with fulminant CDI, with high cure rates reported after multiple treatments. Stool frequency, pseudomembrane resolution, and inflammatory markers are routinely monitored to evaluate disease severity and treatment responsiveness. Our case highlights a discordance in these indicators and demonstrates C-reactive protein as an important marker in assessing residual colitis and disease resolution. Comprehensive scoring systems should consider incorporating C-reactive protein and other biomarkers to optimize CDI management.}, } @article {pmid40502184, year = {2025}, author = {Verna, G and De Santis, S and Islam, B and Sommella, EM and Licastro, D and Zhang, L and De Almeida Celio, F and Merciai, F and Caponigro, V and Campiglia, P and Pizarro, TT and Chieppa, M and Cominelli, F}, title = {A missense mutation in Muc2 promotes gut microbiome- and metabolome-dependent colitis-associated tumorigenesis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.05.31.657160}, pmid = {40502184}, issn = {2692-8205}, abstract = {UNLABELLED: Colitis-associated cancer (CAC) arises from a complex interplay between host and environmental factors, including the gut microbiome. Since ulcerative colitis (UC), a significant risk factor for CAC, is rising in prevalence worldwide, an integrative approach is essential to identify potential triggers linking inflammation to cancer. In the present study, we investigated the role of the gut microbiome using Winnie mice, a UC-like model with a relevant missense mutation in the Muc2 gene. Upon transfer from a conventional (CONV) to a specific-pathogen-free (SPF) facility, Winnie mice exhibited a more severe colitis phenotype, and notably, spontaneous CAC as early as four weeks of age, which progressively worsened over time. In contrast, CONV Winnie developed only mild colitis but with no overt signs of tumorigenesis. Notably, when rederived into germ-free (GF) conditions, SPF Winnie mice were protected from colitis or colon tumor development, indicating an essential role for the gut microbiome in the initiation and progression of CAC in these mice. Using shotgun metagenomics, metabolomics, and lipidomics, we identified a distinct pro-inflammatory microbial and metabolic signature that potentially drives the transition from colitis to CAC. Fecal microbiota transplantation (FMT), using either SPF Winnie or WT (Bl/6) donors into GF Winnie recipients, demonstrated that while colitis developed regardless of donor, only FMT from SPF Winnie donors resulted in CAC, revealing a microbiota-driven, host-specific susceptibility to tumorigenesis in Winnie mice. Our studies present a novel and relevant model of CAC, providing further evidence that the microbiome plays a key role in the pathogenesis of CAC, thereby challenging the concept of colon cancer as a strictly non-transmissible disease.

LAY SUMMARY: This study reveals a distinct metagenomic, metabolomic, and lipidomic profile associated with tumorigenesis in a murine model of ulcerative colitis, highlighting the risks of specific intestinal dysbiosis in genetically predisposed subjects.

WHAT YOU NEED TO KNOW: Background and context: Colitis-associated colorectal cancer arises from complex host-environment interactions, including gut microbiome influences, driving chronic inflammation, with the intestinal lumen environment remaining a largely unexplored potential risk factor in cancer development.New findings: Winnie mice in specific pathogen-free conditions developed severe colitis, and a novel juvenile colon dysplasia and cancer, with gut microbiome changes driving colitis-associated cancer initiation and progression.Limitations: We identified a pro-inflammatory microbial/metabolic signature promoting colitis-to-CAC transition in Winnie mice, with FMT confirming microbiota-driven tumor susceptibility. However, further research is needed to pinpoint the key bacteria-metabolite-lipid combination driving CAC.Clinical research relevance: This newly characterized microbiota-metabolome-based model of CAC, challenges the dogma of cancer as a non-transmittable disease, providing a foundation for developing microbiota-based strategies for CAC prevention and treatment.Basic research relevance: Unlike genetic or chemically induced models, the Winnie mouse model uniquely serves as a dual model for spontaneous colitis and juvenile CAC, offering a fast, 100% penetrant phenotype that enhances reliability, accelerates research, and provides valuable insights into IBD and CAC.}, } @article {pmid40501499, year = {2025}, author = {Chen, L and Song, Y and Huang, Y and Hu, J and Meng, Y and Yuan, M and Zheng, G and Wang, X and Zhang, C and Qiu, Z}, title = {Cornus officinalis Extract Ameliorates Fructose-Induced Hepatic Steatosis in Mice by Sustaining the Homeostasis of Intestinal Microecology and Lipid Metabolism.}, journal = {Food science & nutrition}, volume = {13}, number = {6}, pages = {e70425}, pmid = {40501499}, issn = {2048-7177}, abstract = {Cornus officinalis Sieb. et Zucc. (Cornus officinalis), an edible natural plant fruit, has beneficial effects on a multitude of metabolic diseases, but the mechanism to improve hepatic steatosis remains elusive. In this study, the curative effect of Cornus officinalis extract (COE) is evaluated in a fructose-induced NAFLD mouse model using biochemical indicators monitoring, histological staining, 16S rRNA sequencing analysis, and fecal microbiota transplantation. Our results showed that COE attenuates hepatic steatosis in fructose-fed mice. Mechanistically, COE repairs intestinal barrier damage and gut flora dysbiosis to suppress proinflammatory microbe-derived metabolite transportation to the liver, thus inhibiting the hepatic inflammation and lipid metabolic dysfunction. Notably, transplantation of fecal microbiota isolated from the fructose-fed mice could reverse the beneficial effect of COE on attenuating NAFLD. Therefore, our study demonstrates that COE delays the progression of fructose-driven NAFLD by suppressing lipid metabolic dysfunction and gut microbiota-mediated liver inflammation, highlighting the potential of C. officinalis as a resource for the treatment of NAFLD drugs.}, } @article {pmid40501442, year = {2025}, author = {Maor, M and Levy Barazany, H and Kolodkin-Gal, I}, title = {The ladder of regulatory stringency and balance: an application to the US FDA's regulation of bacterial live therapeutics.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2517377}, pmid = {40501442}, issn = {1949-0984}, mesh = {Humans ; United States ; United States Food and Drug Administration/legislation & jurisprudence ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation ; Bacteria/genetics ; Gastrointestinal Microbiome ; }, abstract = {The three main types of live bacterial therapies - probiotics, fecal/microbiome transplants, and engineered bacterial therapies - hold immense potential to revolutionize medicine. While offering targeted and personalized treatments for various diseases, these therapies also carry risks such as adverse immune reactions, antibiotic resistance, and the potential for unintended consequences. Therefore, developing and deploying these therapies necessitates a robust regulatory framework to protect public health while fostering innovation. In this paper, we propose a novel conceptual tool - the Ladder of Regulatory Stringency and Balance-which can assist in the design of robust regulatory regimes which encompass medicine practices based not only on definitive Randomized Controlled Trials (RCTs), but also on meta-analyses, observational studies, and clinicians experience. Regulatory stringency refers to the strictness of regulations, while regulatory balance concerns the degree of alignment between the regulatory framework governing a technology and the actual risks posed by specific products within that technology. Focusing on the US regulatory environment, we subsequently position the three types of live bacterial therapies on the Ladder. The insight gained from this exercise demonstrates that probiotics are generally positioned at the bottom of the Ladder, corresponding to low-stringency regulation, with a proportionate regulatory balance. However, probiotics intended for high-risk populations are currently subject to low-stringency regulations, resulting in under-regulation. Our analysis also supports the conclusion that fecal microbiota transplants (FMT) for recurrent Clostridium difficile infection should be positioned close to but below the threshold for under regulation by the U.S. Food and Drug Administration (FDA), and we recommend improved donor screening procedures, preservation and processing, storage, and distribution. Our framework can serve as a scale to assess regulatory gaps for live bacterial therapies and to identify potential solutions where such gaps exist.}, } @article {pmid40500780, year = {2025}, author = {Liu, J and Jing, C and Guo, Y and Shang, Z and Zhang, B and Zhou, X and Zhang, J and Lian, G and Tian, F and Li, L and Chen, Y}, title = {The central signaling pathways related to metabolism-regulating hormones of the gut-brain axis: a review.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {648}, pmid = {40500780}, issn = {1479-5876}, support = {ZR2022MH085//Natural Science Foundation of Shandong Province/ ; ZR2022MH070//Natural Science Foundation of Shandong Province/ ; 202134027//Jinan Science and Technology Bureau/ ; }, abstract = {Obesity is a widespread metabolic disorder linked to various conditions, including type 2 diabetes, hypertension, fatty liver disease, sleep apnea, and hyperuricemia. It significantly impacts quality of life and economic productivity. Traditional methods like diet and lifestyle changes often fail to produce substantial weight loss. Consequently, emerging treatments such as anti-obesity medications, bariatric surgery, and fecal microbiota transplantation are becoming more prominent. Recent research emphasizes the role of hormones that communicate with the hypothalamus through the gut-brain axis, affecting appetite, insulin secretion, and body weight via specific signaling pathways. This review explores the role of key gastrointestinal hormones (GLP-1, PYY, ghrelin, CCK, GIP, leptin, and bile acids) and their signaling pathways in metabolic regulation. The present research systematically evaluates the impact of bariatric surgery on appetite modulation and certain metabolic functions through key signaling pathways, including GLP-1R, GHS-R1a, and FXR/TGR5.}, } @article {pmid40500750, year = {2025}, author = {Yang, B and Li, X and Wang, J and Xu, Y and Wang, L and Wu, Z and Zhao, D and Huang, L and Li, N and Chen, Q and Liu, Z}, title = {The efficacy and safety of fecal microbiota transplantation in the treatment of sarcopenia: a retrospective study.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {645}, pmid = {40500750}, issn = {1479-5876}, support = {2022YFA1304100//National Key R&D Program of China/ ; 2022YFC2010101//National Key R&D Program of China/ ; 82470701//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Sarcopenia/therapy/physiopathology/microbiology ; *Fecal Microbiota Transplantation/adverse effects ; Male ; Female ; Aged ; Retrospective Studies ; Treatment Outcome ; Middle Aged ; Resistance Training ; Inflammation ; }, abstract = {BACKGROUND: Sarcopenia, a prevalent geriatric syndrome, is influenced by factors such as inflammation, immune deficiency, and oxidative stress. In elderly individuals, alterations in the microbiome, including reduced biodiversity and functional changes, significantly contribute to the progression of the disease. Targeting the gut-muscle axis has emerged as a promising therapeutic strategy to mitigate age-related muscle atrophy and dysfunction.

METHODS: This study employed fecal microbiota transplantation (FMT) to restore intestinal homeostasis in patients with sarcopenia. Muscle mass was measured using bioelectrical impedance analysis, while muscle function was assessed through grip strength and the five-time sit-to-stand test. Inflammatory markers, including tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP), were also analyzed. Eighty-seven patients received resistance training (RT) treatment, while eighty-five patients received FMT combined with RT treatment, with a follow-up period of 24 weeks.

RESULTS: After 24 weeks, the resistance training (RT) group showed a partial remission (PR) rate of 54.7% and a complete remission (CR) rate of 32.4%. The FMT plus RT group demonstrated a PR rate of 66.5% and a CR rate of 46.7%. Significant improvements induced by FMT treatment were observed in clinical markers of muscle mass, function, and inflammation.

CONCLUSIONS: These results underscore the promise of microbial-based therapies, including fecal microbiota transplantation (FMT), as groundbreaking strategies for addressing sarcopenia. The research indicates that integrating FMT with resistance training could improve muscle mass and function while alleviating inflammation in sarcopenia patients, presenting a hopeful avenue for effective management of the condition.}, } @article {pmid40497058, year = {2025}, author = {Zhang, Q and Gao, Z and Deng, Y and Xu, X and Sun, W and Liu, R and Zhang, T and Sun, X}, title = {Current status and trends in the study of intestinal flora in cognitive disorders: a bibliometric and visual analysis.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1577597}, pmid = {40497058}, issn = {1664-302X}, abstract = {BACKGROUND: Cognitive impairment is a decline in people's ability to think, learn, and remember, which has some impact on an individual's daily activities or social functioning. Microbial toxins and metabolites from dysregulated gut microbiota directly interact with the intestinal epithelium. This interaction triggers neuroinflammation and neurodegeneration in the central nervous system, ultimately impairing cognitive function. It has been found that modulation of gut flora can be an effective intervention to improve cognitive dysfunction. This study is the first to summarize and outline the global research status and trends in this field from a bibliometric perspective, providing reference and guidance for future research in this field.

METHODS: Based on the Web of Science Core Collection (WoSCC) database, Literature on gut flora and cognitive impairment published between 1999-2025 was searched. Bibliometric analysis was performed using VOSviewer and CiteSpace software to analyze the data on countries, institutions, authors, journals, keywords, citations, and to generate visual maps.

RESULTS: A total of 1,702 pieces of related literature were retrieved. The overall trend of publication is increasing. China has published the largest number of papers, and Huazhong University of Science & Technology and Kim, Dong-Hyun were the institutions and individuals with more publications. The most frequently cited journal is SCI REP-UK. The most frequent keywords are gut microbiota, followed by Alzheimer's disease, cognitive impairment, Brain, oxidative stress and Inflammation.

CONCLUSION: In recent years, the research application of gut flora in the treatment of cognitive impairment has made remarkable progress. Oxidative stress and inflammatory response have become the main research hotspots for gut flora to improve cognitive impairment in patients. The gut-brain axis plays an important role in the study of the mechanism of action. Short-chain fatty acids are the focus of research on gut microbial metabolism. Fecal microbial transplantation technology is increasingly being used as an emerging method for the application of intestinal flora. Modifying the gut flora by modifying diet and exercise may be an effective strategy to prevent and improve cognitive dysfunction in the future. Future studies may focus more on gender differences in the role of gut flora in the modulation of cognitive function.}, } @article {pmid40497049, year = {2025}, author = {Ren, X and Zheng, L and Huang, L and Zhao, J}, title = {The role of the gut microbiota in shaping the tumor microenvironment and immunotherapy of breast cancer.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1591745}, pmid = {40497049}, issn = {1664-302X}, abstract = {Breast cancer is the most prevalent malignancy among women worldwide and is a major contributor to cancer-related mortality. The tumor microenvironment (TME), composed of tumor cells, immune infiltrates, fibroblasts, and vascular components, is critically involved in tumor initiation, metastatic progression, and therapeutic response. In recent years, therapies targeting the TME have undergone rapid advancements, with the objective of enhancing antitumor immunity. Concurrently, mounting evidence underscores the pivotal role of the gut microbiota and its metabolites in modulating host immunity, influencing metabolic homeostasis, inflammation, and immune equilibrium. The composition and diversity of the gut microbiome influence breast cancer progression and patients' responses to immunotherapy. Therefore, modulating the gut microbiota is a promising strategy to enhance the clinical outcomes of TME-targeted immunotherapies. In this review, we discuss the influence of gut microbiota and its derived metabolites on breast cancer progression and immunotherapy prognosis and explore potential strategies to optimize immunotherapy through gut microbiota modulation.}, } @article {pmid40497047, year = {2025}, author = {Rivero, MR and Vissio, C and Feliziani, C and De Angelo, C and Touz, MC and Tiranti, K and Lombardelli, JA and Duartez, FJ and Curletto, L}, title = {Cryptosporidium spp. in Argentina: epidemiology and research advances in human, animal, and environmental settings during the 21st century.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1592564}, pmid = {40497047}, issn = {1664-302X}, abstract = {INTRODUCTION: Cryptosporidium spp. is an intestinal protozoan causing cryptosporidiosis, a diarrheal disease affecting humans and animals, with zoonotic potential. In immunocompromised individuals, infections can be severe or fatal. It is a major waterborne parasite and a leading cause of neonatal diarrhea in calves. This study systematically reviews Cryptosporidium spp. research in Argentina during the 21st century, highlighting its epidemiological significance and research gaps.

METHODS: A systematic review following PRISMA guidelines was conducted using LILACS, PubMed, Scopus, and SciELO Argentina. Eligible studies (2001-2024) included human (community and hospital-based), animal (domestic, wild, and captive), and environmental (water, soil and vegetable) surveys. The review analyzed epidemiology, diagnosis, treatment, genetic diversity, distribution, and risk factors.

RESULTS: Of 277 articles reviewed, 66 met eligibility criteria. Cryptosporidium spp. was detected in 17 of Argentina's 23 provinces, mainly in the Pampean region. Five species were identified (C. hominis, C. parvum, C. suis, C. scrofarum, and C. varanii), though genetic diversity studies remain limited. Human cryptosporidiosis primarily affects immunocompromised individuals (HIV/AIDS, transplant recipients, hematologic cancer patients). The parasite was found in feces, duodenal biopsies, blood, sputum, and cerebrospinal fluid, with complications such as cholangiopathy and pulmonary cryptosporidiosis. Infections with C. hominis and C. parvum (including co-infections) were observed, with multiple subtypes documented. In animals, C. parvum was prevalent in Pampean calves, while C. suis and C. scrofarum were found in domestic pigs. Wildlife, including non-human primates and coypu, also tested positive. Cryptosporidium was detected in recreational and drinking water samples. No Cryptosporidium spp. oocysts were detected in soil. Risk factors included socio-economic conditions and animal management practices.

CONCLUSION: Cryptosporidium spp. is widely distributed in Argentina, yet eco-epidemiological transmission factors remain poorly understood, hindering control strategies. Limited research on genetic diversity and distribution highlights the need for further studies, particularly in vulnerable populations and areas of close human-animal interaction, such as productive systems. The presence of Cryptosporidium spp. in water underscores the importance of improving public health policies and water treatment standards. From a One Health perspective, these findings emphasize the need for enhanced epidemiological surveillance and research to strengthen prevention and control in Argentina.}, } @article {pmid40495848, year = {2025}, author = {Iqbal, A and Bokhari, SFH and Rehman, MU and Faizan Sattar, SM and Bakht, D and Dost, W and Basit, A}, title = {Gut-brain connection in schizophrenia: A narrative review.}, journal = {World journal of psychiatry}, volume = {15}, number = {5}, pages = {103751}, pmid = {40495848}, issn = {2220-3206}, abstract = {Schizophrenia is a complex neuropsychiatric disorder characterized by cognitive, emotional, and behavioral impairments. The microbiota-gut-brain axis is crucial in its pathophysiology, mediating communication between the gut and brain through neural, immune, endocrine, and metabolic pathways. Dysbiosis, or an imbalance in gut microbiota, is linked to neuroinflammation, systemic inflammation, and neurotransmitter disruptions, all of which contribute to the symptoms of schizophrenia. Gut microbiota-derived metabolites, such as short-chain fatty acids, influence brain function, including immune responses and neurotransmitter synthesis. These findings suggest that microbial imbalances exacerbate schizophrenia, providing a novel perspective on the disorder's underlying mechanisms. Emerging microbiota-targeted therapies-such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation-show promise as adjunctive treatments, aiming to restore microbial balance and improve clinical outcomes. While further research is needed, targeting the microbiota-gut-brain axis offers an innovative approach to schizophrenia management, with the potential to enhance patient outcomes and quality of life.}, } @article {pmid40495179, year = {2025}, author = {Liu, W and Zhou, X and Xiao, L and Huang, X and Chang, D and Zhong, X and Zeng, M and Xian, Y and Zheng, Y and Huang, W and Huang, R and Huang, M}, title = {The gut microbiota-mediated ferroptosis pathway: a key mechanism of ginsenoside Rd against metabolism-associated fatty liver disease.}, journal = {Chinese medicine}, volume = {20}, number = {1}, pages = {83}, pmid = {40495179}, issn = {1749-8546}, support = {2022YFC3501200//National Key Research and Development Program of China/ ; 82274080//National Natural Science Foundation of China Projects/ ; X2024019//School Management Project of Fujian University of Traditional Chinese Medicine/ ; X2024035//School Management Project of Fujian University of Traditional Chinese Medicine/ ; 2024Y9511//Fujian Provincial Science and Technology Innovation Joint Fund Project/ ; }, abstract = {BACKGROUND: Ginsenoside Rd (G-Rd), found in Panax species, has shown therapeutic potential against metabolism-associated fatty liver disease (MAFLD), but its mechanism has not been well elucidated. This study investigated the key mechanisms of G-Rd in modulating the gut microbiome and lipid peroxidation-mediated ferroptosis pathway in MAFLD.

METHODS: A high-fat diet-induced MAFLD model was established. Ultrastructural changes in liver tissue were observed using transmission electron microscopy. Metagenomics were employed to detect alterations in gut microbiota and their metabolites. Biochemical analysis and immunohistochemistry were used to examine liver injury, blood lipids, lipid peroxidation-related indicators, and tissue iron content.

RESULTS: G-Rd significantly reduced liver injury and steatosis in MAFLD mice and downregulated the elevated relative abundance of Firmicutes and the Firmicutes/Bacteroidetes ratio. It also significantly reduced the abundances of Faecalibaculum rodentium while increasing Muribaculum intestinale, with its functional role being relevant to lipid metabolism regulation. Moreover, G-Rd ameliorated mitochondrial damage and inhibited the ferroptosis pathway in the liver, which was associated with antioxidant-related factors mediated by Nrf2 signaling. The liver protective effect of G-Rd was driven by the regulation of gut microbiota, as demonstrated by antibiotic cocktail treatment and fecal microbiota transplantation.

CONCLUSIONS: G-Rd attenuated HFD-induced MAFLD by alleviating liver oxidative stress, lipid peroxidation, and ferroptosis through modulation of the gut microbiota. The antioxidant and anti-ferroptotic actions of G-Rd, mediated via the Nrf2 pathway, were found to contribute to the amelioration of liver injury and hepatic steatosis in MAFLD.}, } @article {pmid40494686, year = {2025}, author = {von Muhlenbrock, C and Núñez, P and Herrera, K and Pacheco, N and Quera, R}, title = {Fecal microbiota transplantation through colonoscopy for the management of severe refractory irritable bowel syndrome: Preliminary results.}, journal = {Revista de gastroenterologia de Mexico (English)}, volume = {90}, number = {2}, pages = {334-337}, doi = {10.1016/j.rgmxen.2025.03.001}, pmid = {40494686}, issn = {2255-534X}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Irritable Bowel Syndrome/therapy ; Pilot Projects ; *Colonoscopy/methods ; Female ; Male ; Adult ; Middle Aged ; }, abstract = {Recent studies have explored the role of the microbiota in disorders of gut-brain interaction, opening pathways for therapies, such as dietary adjustments, probiotics, and fecal microbiota transplantation (FMT). We present herein a pilot study on 4 patients with severe irritable bowel syndrome (IBS), refractory to conventional treatment, in which FMT through colonoscopy showed improvement in pain, bloating, and stool consistency that was maintained during the 6-month follow-up. To establish the broader clinical application of FMT, more research on its efficacy according to instillation site and patient results is needed.}, } @article {pmid40494661, year = {2025}, author = {Räisänen, L and Balouch, F and Reilly, C and Burgess, C and Lewindon, P}, title = {Oral vancomycin solution is superior to capsule in inducing clinical biomarker and endoscopic remission in children with atypical ulcerative colitis.}, journal = {British journal of clinical pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1002/bcp.70121}, pmid = {40494661}, issn = {1365-2125}, support = {240050//Lastentautien Tutkimussäätiö/ ; //Orionin Tutkimussäätiö/ ; T63344/50621//State funding for university-level health research, Tampere University Hospital, Wellbeing services county of Pirkanmaa/ ; }, abstract = {AIMS: Atypical colitis (presenting reverse gradient colitis, backwash ileitis or rectal sparing) is associated with primary sclerosing cholangitis-ulcerative colitis (PSC). Oral vancomycin has been used to manage paediatric atypical colitis with/without confirmed PSC. Different preparations had shown different efficacy. We compared oral vancomycin solution to capsules in inducing remission in children with atypical colitis, while assessing other potential confounders.

METHODS: Children using oral vancomycin for at least 3 months to manage atypical colitis were retrospectively identified. Factors associated with colitis remission (Paediatric Ulcerative Colitis Activity Index [PUCAI], faecal calprotectin, colonoscopy and histology) were explored.

RESULTS: Of 32/48 children with elevated PUCAI, 27/32 achieved PUCAI < 10 (20/23 after solution vs. 7/9 after capsules, P = .520). Faecal calprotectin <100 μg/g was achieved in 35/48 (28/35 after solution vs. 6/13 after capsules, P = .022). Follow-up colonoscopy during treatment (n = 25) showed reduced Mayo from median 2 to 0 (P < .001) after solution vs. from 2 to 1 (P = .257) after capsules. Pan-colonic histological remission was seen in 14/25 (12/20 after solution vs. 1/5 after capsules, P = .109). In adjusted analysis, use of oral vancomycin solution was a significant predictor for biomarker (adjusted odds ratio 23.1, 95% confidence interval 2.11-253) and pan-colonic histological remission (adjusted odds ratio 900, 95% confidence interval 1.61-504 929). No other predictors were identified. Within 12 months after ceasing oral vancomycin in children who achieved remission, 52% relapsed. No clinical predictors, including vancomycin preparation, were established.

CONCLUSION: Oral vancomycin solution was superior to capsules for inducing biomarker and colonoscopic remission in children with atypical colitis with/without confirmed PSC. This finding warrants further investigation to ensure optimal use.}, } @article {pmid40491765, year = {2025}, author = {Tang, Y and Xie, X and Guo, Y and Chen, Y and Huang, X and Dai, D and Wu, X}, title = {Exploring correlation between preoperative gut microbiota and PONV using 16S absolute quantitative sequencing: a prospective observational study.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1563329}, pmid = {40491765}, issn = {2296-858X}, abstract = {BACKGROUND: Postoperative nausea and vomiting (PONV) is a common complication following surgery. Despite various preventive measures, satisfactory outcomes have not been achieved. This study explores the potential of gut microbiota interactions with the host in understanding and preventing PONV, using 16S absolute quantitative sequencing technology to uncover new insights.

METHODS: Patients who experienced nausea and vomiting within 24 h after surgery were divided into a PONV group (n = 22) and a non-PONV group (n = 22). Microbial communities linked to PONV were assessed through bioinformatics analysis. Fecal samples from both groups were transplanted into rats, which were then anesthetized with isoflurane for 100 min. Pica behavior was monitored over the next 24 h to assess nausea and vomiting in the rats.

RESULTS: Significant differences in α- and β-diversity were observed between the PONV and non-PONV groups. Six key microorganisms were identified, with Bifidobacterium, Bilophila, and Oscillibacter showing a negative correlation with PONV severity. Receiver operating characteristic (ROC) analysis demonstrated that Bifidobacterium could reliably predict PONV. Rats receiving feces from the PONV group exhibited significantly higher kaolin consumption within 24 h post-anesthesia compared to those receiving feces from the non-PONV group.

CONCLUSION: These results suggest a potential new mechanism for PONV involving gut microbiota, offering a theoretical basis for preoperative prediction of PONV based on gut microbial composition.}, } @article {pmid40491530, year = {2025}, author = {Jian, S and Jian, X and Ye, L and Yang, K and Zhang, L and Xie, Y and Deng, J and Yin, Y and Deng, B}, title = {Gallic acid prevents obesity in mice on a high-fat diet via the gut microbiota-adipose tissue axis.}, journal = {Current research in food science}, volume = {10}, number = {}, pages = {101084}, pmid = {40491530}, issn = {2665-9271}, abstract = {Obesity is closely related to the gut microbiota, and gallic acid (GA) has anti-obesity properties, but its relationship with the gut microbiota is unclear. The aim of this study was to investigate the role of gut microbiota in the anti-obesity mechanism of GA by fecal microbiota transplantation (FMT). Here, we found that high-fat diet (HFD) promoted lipid deposition and gut microbiota dysbiosis in mice, whereas GA slowed down lipid deposition and restored gut microbiota dysbiosis and its functional profile, as evidenced by the reduction of the obesity-causing bacterium Desulfovibrio and the enrichment of the beneficial bacterium Lachnospiraceae_NK4A136_group, Clostridiales_unclassified, Oscillospira and Adlercreutzia. These gut microbiota and metabolites produced positive feedback effects on body weight, glucose tolerance, insulin resistance, as well as glycemic and lipid parameters. Mechanistically, GA significantly enhanced lipid and energy metabolism in obese mice by promoting the expression of uncoupling protein 1 (UCP1), adiponectin, and adiponectin receptor 2 in white adipose tissue of the epididymal white adipose tissue, as well as promoting thermogenesis in interscapular brown adipose tissue by stimulating UCP1 expression. Interestingly, GA failed to alleviate lipid accumulation in HFD of antibiotic-treated mice. In contrast, after FMT treatment, the fecal microbiota of GA-treated donor mice significantly alleviated lipid metabolism in HFD-fed mice, which is mechanistically consistent with direct addition of GA. Collectively, GA can alleviate HFD-induced obesity by modulating the gut microbiota, and the specific mechanism may be through the gut microbiota-adipose tissue axis.}, } @article {pmid40488649, year = {2025}, author = {Park, JH and Lee, YK and Lee, CK and Lee, HS and Kim, JH and Lee, MH and Seo, YJ and Cho, H and Park, CS}, title = {The preventive effect of solubilized sturgeon oil on dextran sulfate sodium-induced ulcerative colitis via inflammation attenuation and intestinal microbiota regulation.}, journal = {Food & function}, volume = {16}, number = {13}, pages = {5421-5434}, doi = {10.1039/d5fo01038a}, pmid = {40488649}, issn = {2042-650X}, mesh = {Animals ; *Colitis, Ulcerative/chemically induced/prevention & control/drug therapy/microbiology ; *Gastrointestinal Microbiome/drug effects ; Dextran Sulfate/adverse effects ; Mice ; *Fish Oils/pharmacology/administration & dosage ; Male ; Fishes ; Disease Models, Animal ; Mice, Inbred C57BL ; *Anti-Inflammatory Agents/pharmacology ; Colon/drug effects ; Inflammation ; }, abstract = {Ulcerative colitis (UC), an inflammatory bowel disease, causes inflammation in the colonic mucosa. The pathogenesis of UC is closely linked to abnormalities in the gastrointestinal microbiota and immune response. Current treatments for UC primarily alleviate symptoms but are associated with several drawbacks, particularly with prolonged use. Therefore, there is a crucial need to explore novel treatment strategies. Solubilized sturgeon oil (SSO) has gained prominence for its anti-inflammatory effects in various contexts; however, its efficacy in UC has not yet been investigated. In this study, we investigated the preventive effects and underlying mechanisms of SSO in a dextran sulfate sodium-induced UC model. Oral administration of SSO significantly alleviated colitis severity by improving weight, disease activity index, and colon length. Moreover, SSO significantly downregulated the expression of interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha, cyclooxygenase-2, and nitric oxide synthase, while enhancing the expression of tight junction-related proteins such as occludin and ZO-1 in colonic tissues. Additionally, SSO inhibited the activation of lipopolysaccharide-stimulated dendritic cells and macrophages and induced alterations in the gut microbiota, with increased Firmicutes and decreased Bacteroidetes abundances. Furthermore, colitis and gastrointestinal inflammation were alleviated in recipient mice that received fecal transplants from SSO-treated mice. These findings indicate that SSO is a promising natural therapeutic agent for preventing colitis by regulating the gastrointestinal microbiota and suppressing the hyperactivation of myeloid cells.}, } @article {pmid40487274, year = {2025}, author = {Roy, K and Moncada, E and Reddivari, L}, title = {Ulcerative Colitis but Not Dextran Sodium Sulfate-Induced Colitis-Associated Microbiota Promotes Early Biomarkers of Colitis in Interleukin-10 -/- Mice.}, journal = {Gastro hep advances}, volume = {4}, number = {6}, pages = {100636}, pmid = {40487274}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis (UC), are inflammatory gastrointestinal conditions in which the pathogenesis is influenced by immune dysfunction, genetics, and environmental factors. Of the 2 conditions, UC is more prevalent, and there is a positive correlation between bacterial dysbiosis and colitis severity and incidence. Therefore, we hypothesize that mice that are genetically predisposed to colitis when colonized with colitic associated bacteria will exhibit an early onset of colitis biomarkers.

METHODS: Four sets of germ-free interleukin-10 -/- mice were gavaged orally with pooled fecal samples from 2 healthy individuals or an individual with severe colitis or healthy mice or dextran sodium sulfate (DSS)-induced colitis mice. The disease activity index was used to rank colitis severity weekly in transplanted mice for eight weeks.

RESULTS: There were significant differences in alpha (Shannon Index) and beta diversity (Bray-Curtis) between healthy and colitic-associated microbiota recipients, indicating dysbiosis (human fecal microbial transplantation P = 8.09∗10[-6], P = .001); (Mice fecal microbiota transplant P = .0197, P = .025). Despite the lack of colitis development, UC-associated microbiota recipients had reduced mucus thickness and increased expression of proinflammatory cytokines in the distal colon compared to healthy-associated microbiota recipients. However, DSS-induced colitis associated microbiota recipients did not show an increase in colitis biomarkers compared to healthy associated microbiota recipients.

CONCLUSION: This study demonstrates that UC-associated bacterial dysbiosis induces colonic inflammation and mucus thinning, biomarkers of early colitis onset, in interleukin-10 -/- mice compared to mice with healthy human associated bacteria.Colitis induction depends on bacterial community stability as DSS-induced colitis associated microbiota recipients did not show an increase in colitis or colitis biomarkers in the absence of DSS.}, } @article {pmid40486846, year = {2025}, author = {Shang, M and Ning, J and Zang, C and Ma, J and Yang, Y and Wan, Z and Zhao, J and Jiang, Y and Chen, Q and Dong, Y and Wang, J and Li, F and Bao, X and Zhang, D}, title = {Microbial metabolite 3-indolepropionic acid alleviated PD pathologies by decreasing enteric glia cell gliosis via suppressing IL-13Rα1 related signaling pathways.}, journal = {Acta pharmaceutica Sinica. B}, volume = {15}, number = {4}, pages = {2024-2038}, pmid = {40486846}, issn = {2211-3835}, abstract = {Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.}, } @article {pmid40486731, year = {2025}, author = {Zhou, C and Feng, X and Liu, H and Cai, T and Li, Y and Fan, H}, title = {Bidirectional modulation of Alzheimer's disease via gut microbiota: rescue by fecal transplantation from healthy donors and aggravation by colitis-associated dysbiosis.}, journal = {Frontiers in neuroscience}, volume = {19}, number = {}, pages = {1593854}, pmid = {40486731}, issn = {1662-4548}, abstract = {INTRODUCTION: Emerging evidence implicates gut microbiota dysbiosis as a key modulator for the pathogenesis of Alzheimer's disease (AD) via the gut-brain axis. To investigate the causal role of microbial communities in AD progression, we performed fecal microbiota transplantation (FMT) in APP/PS1 transgenic mice using donor microbiota from healthy wild-type mice or dextran sulfate sodium (DSS)-induced colitis mice.

METHODS: Cognitive function, amyloid-beta (Aβ) pathology, and pro-inflammatory cytokine levels were assessed in mice. 16S ribosomal RNA sequencing of gut microbiota and bioinformatic functional analyses were applied to identify the specific microbial communities potentially involved in AD progression.

RESULTS: FMT-WT mice (fecal microbiota transplantation from healthy wild-type mice) exhibited significant improvements in spatial memory (Morris Water Maze), exploratory behavior (Y-maze), and locomotor activity (Open Field Test), alongside reduced Aβ plaque burden and normalized expression of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) in both gut and brain tissues. Conversely, FMT-DSS mice (fecal microbiota transplantation from DSS-treated donors) displayed exacerbated cognitive deficits, heightened Aβ deposition, and elevated pro-inflammatory cytokine levels. Microbial profiling revealed stark contrasts: FMT-WT mice harbored beneficial taxa (Bacteroides, Lachnospiraceae) linked to anti-inflammatory products like short-chain fatty acid, while FMT-DSS mice showed blooms of pathogenic genera (Erysipelatoclostridium, Enterobacteriaceae) associated with neurotoxic metabolites. Functional analyses predicted enrichment of neuroprotective pathways (e.g., lysine metabolism) in FMT-WT and pro-inflammatory pathways (e.g., carbon metabolism) in FMT-DSS. Crucially, neuroinflammation occurred independently of gut barrier disruption, implicating circulating microbial metabolites as key mediators.

DISCUSSION: Our findings demonstrate that gut microbiota composition bidirectionally influences AD progression, with FMT from healthy donors attenuating neuroinflammation and pathology, while colitis-associated dysbiosis exacerbates disease hallmarks. Our study positions microbiota-targeted therapies as a promising strategy to modulate AD progression through the gut-brain axis.}, } @article {pmid40485937, year = {2025}, author = {Liu, Y and Zhang, P and Sun, H}, title = {A narrative review of research advances in gut microbiota and microecological agents in children with attention deficit hyperactivity disorder (ADHD).}, journal = {Frontiers in psychiatry}, volume = {16}, number = {}, pages = {1588135}, pmid = {40485937}, issn = {1664-0640}, abstract = {The role of gut microecology in attention deficit hyperactivity disorder (ADHD) has garnered growing attention. Studies have suggested a potential link between ADHD development and an imbalance in gut microbiota composition. This review aims to analyze the characteristics of the gut microbiota in children with ADHD, explore how changes in the gut microbiota affect ADHD through nervous, neuroendocrine, and immune pathways, and discuss the potential application of microecological agents and fecal microbiota transplantation in the prevention and treatment of ADHD in children. Pubmed, Google Scholar, EBSCO, Scopus and Medline were utilized to conduct searches using the following key terms:Attention Deficit Hyperactivity Disorder OR ADHD AND gut microbiota OR probiotics OR prebiotics OR synbiotics OR fecal microbiota transplantation OR FMT. Studies published in English from all years were included. A thorough review of numerous papers and their references was conducted to identify relevant articles. Sorting and analysis revealed that the gut microbiota of children with ADHD has changed to some extent, and targeting the gut microbiota, using microecological agents or fecal microbiota transplantation, especially in combination with central nervous system stimulants, may provide additional benefits for children with ADHD.}, } @article {pmid40485663, year = {2025}, author = {Radford-Smith, DE and Oke, K and Costa, CFFA and Anthony, DC}, title = {Systematic review and meta-analysis of microbiota-gut-astrocyte axis perturbation in neurodegeneration, brain injury, and mood disorders.}, journal = {Brain, behavior, & immunity - health}, volume = {46}, number = {}, pages = {101013}, pmid = {40485663}, issn = {2666-3546}, abstract = {BACKGROUND: Astrocytes are essential for preserving homeostasis, maintaining the blood-brain barrier, and they are a key element of the tripartite neuronal synapse. Despite such multifaceted roles, their importance as contributors to the microbiota-gut-brain axis studies, which typically focus on microglia and neurons, has been largely overlooked. This meta-analysis provides the first systematic review of the microbiota-gut-astrocyte (MGA) axis in vivo, integrating findings across distinct neurological diseases.

METHODS: A systematic narrative review was conducted per PRISMA guidelines. The search term employed for PubMed was "Microbiota"[MeSH] AND (astrocyte OR glial) NOT (Review[Publication Type]) and for Web of Science, Embase, and Scopus, "Microbio∗ AND (astrocyte OR glial)" with filters applied to exclude review articles. Searches were completed by May 9th[,] 2024. Data extracted included study models, interventions, and outcomes related to astrocyte biology and rodent behaviour. SYRCLE's risk of bias tool was used to assess individual study designs.

RESULTS: 53 studies met the inclusion criteria, covering rodent models of stroke and traumatic (acute) brain injury, chronic neurodegenerative diseases including Alzheimer's and Parkinson's disease and other heterogeneous models of cognitive impairment and affective disorders. Significant heterogeneity in methodology was observed between studies. Five studies had a high risk of bias, and 15 were low risk. Astrocyte biology, typically measured by GFAP expression, was increased in neurodegeneration and acute brain injury models but varied significantly in mood disorder models, depending on the source of stress. Common findings across diseases included altered gut microbiota, particularly an increased Bacteroidetes/Firmicutes ratio and compromised gut barrier integrity, linked to increased GFAP expression. Faecal microbiota transplants and microbial metabolite analyses suggested a direct impact of the gut microbiota on astrocyte biology and markers of neuroinflammation.

CONCLUSIONS: This review and meta-analysis describes the impact of the gut microbiota on astrocyte biology, and argues that the MGA axis is a promising therapeutic target for neurological disorders. However, it is clear that our understanding of the relationship between the gut microbiota and astrocyte behaviour is incomplete, including how different subtypes of astrocytes may be affected. Future studies must adopt new, multi-dimensional studies of astrocyte function and dysfunction, to elucidate their role in disease and explore the therapeutic potential of gut microbiota modulation.}, } @article {pmid40484955, year = {2025}, author = {Lin, A and Huang, L and Jiang, A and Zhu, L and Mou, W and Li, Y and Zhang, C and Liu, Z and Zhang, J and Cheng, Q and Wei, T and Luo, P}, title = {Microbiota boost immunotherapy? A meta-analysis dives into fecal microbiota transplantation and immune checkpoint inhibitors.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {341}, pmid = {40484955}, issn = {1741-7015}, support = {2021A1515012593//Natural Science Foundation of Guangdong Province/ ; 82373129//National Natural Science Foundation of China/ ; 82172750//National Natural Science Foundation of China/ ; 2022A1515111212//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 2023A04J1257//Science and Technology Program of Guangzhou/ ; NO.2023RC3074//Hunan Youth Science and Technology Talent Project/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Immune Checkpoint Inhibitors/therapeutic use ; *Immunotherapy/methods ; *Neoplasms/therapy ; Treatment Outcome ; }, abstract = {BACKGROUND: Immune checkpoint inhibitors (ICIs) are a cornerstone of modern cancer treatment, but their effectiveness is limited. Fecal microbiota transplantation (FMT), which alters the gut microbiome, has shown promise in enhancing ICIs' therapeutic effects.

METHODS: We conducted a comprehensive search of relevant studies available up to September 30, 2024, to analyze the clinical efficacy and safety of combining FMT with ICIs in cancer treatment. The primary endpoint was the objective response rate (ORR), with secondary evaluations of survival outcomes and safety.

RESULTS: A total of 10 studies involving 164 patients with solid tumors were included. The pooled ORR was 43% (95% CI: 0.35-0.51). Subgroup analysis revealed that the combination of anti-PD-1 and anti-CTLA-4 therapies was associated with a significantly higher ORR (60%) compared to anti-PD-1 monotherapy (37%; P = 0.01). The incidence of grade 1-2 adverse events (AEs) was 42% (95% CI: 0.32-0.52), while grade 3-4 AEs occurred in 37% of patients (95% CI: 0.28-0.46).

CONCLUSIONS: This meta-analysis provides preliminary evidence supporting the use of FMT as a strategy to enhance the efficacy of ICIs in patients with advanced or refractory solid tumors. However, larger-scale randomized controlled trials with long-term follow-up are required to confirm and optimize treatment protocols.}, } @article {pmid40484558, year = {2025}, author = {Liu, W and Yu, L and Chen, Q and Zhang, C and Wang, L and Yu, N and Peng, D and Ou, J and Chen, W and Zhang, Y and Wang, Y}, title = {Poria cocos polysaccharides alleviate obesity-related adipose tissue insulin resistance via gut microbiota-derived short-chain fatty acids activation of FGF21/PI3K/AKT signaling.}, journal = {Food research international (Ottawa, Ont.)}, volume = {215}, number = {}, pages = {116671}, doi = {10.1016/j.foodres.2025.116671}, pmid = {40484558}, issn = {1873-7145}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Insulin Resistance ; *Obesity/metabolism ; *Polysaccharides/pharmacology ; Mice ; Proto-Oncogene Proteins c-akt/metabolism ; Male ; *Fatty Acids, Volatile/metabolism ; Fibroblast Growth Factors/metabolism ; Signal Transduction/drug effects ; Diet, High-Fat/adverse effects ; *Adipose Tissue/metabolism/drug effects ; Mice, Inbred C57BL ; Phosphatidylinositol 3-Kinases/metabolism ; *Wolfiporia/chemistry ; }, abstract = {Obesity is a chronic condition that increases the risk of metabolic disorders, with intestinal dysbiosis and adipose tissue insulin resistance (Adipose-IR) playing key roles in its pathogenesis. Poria cocos polysaccharides (PCP), derived from traditional Chinese medicine, have shown potential in improving glucose metabolism and modulating gut microbiota. However, whether PCP can alleviate obesity-induced Adipose-IR and its dependence on gut microbiota remain unclear. This study investigated the effects of PCP on Adipose-IR in high-fat diet (HFD)-induced obese mice. PCP supplementation reduced body weight, adipose tissue mass, and improved glucose tolerance and lipid metabolism. Histological analysis showed alleviation of adipocyte hypertrophy and colonic barrier damage. PCP also modulated gut microbiota, enhancing the abundance of Lactobacillus, Allobaculum, and Phascolarctobacterium, and increased fecal short-chain fatty acids (SCFAs). These changes activated fibroblast growth factor 21 (FGF21), phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and glucose transporter 4 (GLUT4) expression, improving insulin sensitivity. Antibiotic treatment and fecal microbiota transplantation (FMT) further confirmed that PCP's effects on glucose and lipid metabolism are gut microbiota-dependent. Our findings suggest that PCP may serve as a prebiotic agent to alleviate obesity-induced Adipose-IR and metabolic disorders, supporting its potential for functional food development.}, } @article {pmid40484213, year = {2025}, author = {Zbóril, S and Schmidt, AP and Ramos Maia, DR and Sanches, TR and Neto, AND and Andrade, L and Oses, JP and Moreira, FP and Auler, JOC and Otsuki, DA}, title = {Treatment with mesenchymal stem cells in a porcine model of sepsis: Assessment of the central nervous system.}, journal = {Neuroscience letters}, volume = {862}, number = {}, pages = {138294}, doi = {10.1016/j.neulet.2025.138294}, pmid = {40484213}, issn = {1872-7972}, mesh = {Animals ; Swine ; *Mesenchymal Stem Cell Transplantation/methods ; *Sepsis/therapy/pathology/physiopathology ; Disease Models, Animal ; *Mesenchymal Stem Cells ; Cytokines/blood/cerebrospinal fluid ; Humans ; Hippocampus/pathology ; Hemodynamics ; }, abstract = {Sepsis remains a leading cause of intensive care unit admissions and a significant public health challenge worldwide. Despite efforts, the development of specific therapies for sepsis has been limited. Mesenchymal stem cell therapy, particularly with cells derived from the human umbilical cord (hUC-MSC), has shown promise in animal studies. This study evaluated the use of hUC-MSC in a porcine model of sepsis induced by fecal peritonitis, focusing on hemodynamic and metabolic effects, inflammatory response, and central nervous system impact. Twenty-two pigs were randomized into a control group receiving fluids, vasopressors, and antibiotics, and a treatment group receiving the same interventions plus hUC-MSC infusion. Hemodynamic parameters, acid-base status, cytokine levels in serum and cerebrospinal fluid (CSF), and neuron-specific enolase were assessed over 24 h. Histopathological analysis of the hippocampus was performed post-mortem. No significant differences were observed between groups regarding hemodynamic and metabolic parameters or serum cytokine levels. While interleukin-1β levels in CSF increased in all animals' post-sepsis induction, interleukin-10 levels were significantly higher in hUC-MSC-treated animals. Histopathological analysis revealed reduced congestion, vasodilation, and neuronal karyolysis in the hippocampus of the treatment group. These findings suggest that while hUC-MSC therapy does not significantly impact hemodynamics, metabolism, systemic inflammation, or mortality in septic shock, it may offer neuroprotective effects. Further studies are required to elucidate the mechanisms underlying these potential neuroprotective properties of hUC-MSC in sepsis.}, } @article {pmid40482880, year = {2025}, author = {Conrad, MA and Kaplan, AL and Weinbrom, S and Nastasio, S and Jo, D and Conover, K and Lo, K and Liu, E and Crawford, M and Michail, S and Nicholson, M and Hourigan, SK and Kelsen, JR and Kahn, SA}, title = {Fidaxomicin Treatment of Clostridioides difficile Infections and Recurrences in Children and Adolescents: A Retrospective Multicenter Study.}, journal = {The Journal of pediatrics}, volume = {285}, number = {}, pages = {114681}, doi = {10.1016/j.jpeds.2025.114681}, pmid = {40482880}, issn = {1097-6833}, abstract = {OBJECTIVE: To report the effectiveness and tolerability of treating children with primary and recurrent Clostridioides difficile infection (CDI) with fidaxomicin in a real-world, multicenter cohort.

STUDY DESIGN: We performed a multicenter, retrospective, observational study of fidaxomicin treatment for primary or recurrent CDI in children ages 12 months to 18 years old identified from 2013 to 2021 at 5 centers via electronic medical records. Outcomes included assessment of clinical response at day 14 after initiation of fidaxomicin treatment and clinical and microbiologic outcomes at day 60 after initiation of fidaxomicin treatment in the initial responders.

RESULTS: Of the 95 patients included in this study, 84 (88.4%) were treated with fidaxomicin for a recurrent CDI, and 82 (86.3%) had at least one medical or surgical comorbidity. At the completion of fidaxomicin treatment (ie, by day 14 after initiation), 50 patients (52.6%) had a clinical cure and an additional 29 (30.5%) had improvement of symptoms. Among 79 patients who responded to fidaxomicin treatment, 17 (21.5%) had a clinical and microbiologically confirmed recurrence of CDI by day 60, likely representing relapse. Patients with inflammatory bowel disease were less likely to achieve clinical cure at day 14 (OR 0.27 (95% CI 0.11, 0.70)), but 20 patients with inflammatory bowel disease who had initial clinical cure or response did not have a demonstrable increased risk of recurrence at day 60. The most common adverse events reported during therapy were abdominal pain and nausea.

CONCLUSIONS: In this retrospective, real-world study, fidaxomicin for children with CDI appears to be well tolerated and is associated with low rates of treatment failure.}, } @article {pmid40482640, year = {2025}, author = {DeLeon, O and Mocanu, M and Tan, A and Sidebottom, AM and Koval, J and Ceccato, HD and Kralicek, S and Colgan, JJ and St George, MM and Lake, JM and Cooper, M and Xu, J and Moore, J and Su, Q and Xu, Z and Ng, SC and Chan, FKL and Tun, HM and Cham, CM and Liu, CY and Rubin, DT and Martinez-Guryn, K and Chang, EB}, title = {Microbiome mismatches from microbiota transplants lead to persistent off-target metabolic and immunomodulatory effects.}, journal = {Cell}, volume = {188}, number = {15}, pages = {3927-3941.e13}, pmid = {40482640}, issn = {1097-4172}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 DK138072/DK/NIDDK NIH HHS/United States ; T32 DK007074/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; Mice ; *Fecal Microbiota Transplantation/methods/adverse effects ; Humans ; Male ; Mice, Inbred C57BL ; Female ; Transcriptome ; Anti-Bacterial Agents/pharmacology ; Specific Pathogen-Free Organisms ; Duodenum/microbiology ; }, abstract = {Fecal microbiota transplant (FMT) is an increasingly used intervention, but its suitability to restore regional gut microbiota, particularly in the small bowel (SB), must be questioned because of its predominant anaerobic composition. In human subjects receiving FMT by upper endoscopy, duodenal engraftment of anaerobes was observed after 4 weeks. We hypothesized that peroral FMTs create host-microbe mismatches that impact SB homeostasis. To test this, antibiotic-treated specific-pathogen-free (SPF) mice were given jejunal, cecal, or fecal microbiota transplants (JMTs, CMTs, or FMTs, respectively) and studied 1 or 3 months later. JMT and FMT altered regional microbiota membership and function, energy balance, and intestinal and hepatic transcriptomes; JMT favored host metabolic pathways and FMT favored immune pathways. MTs drove regional intestinal identity (Gata4, Gata6, and Satb2) and downstream differentiation markers. RNA sequencing (RNA-seq) of metabolite-exposed human enteroids and duodenal biopsies post-FMT confirmed transcriptional changes in mice. Thus, regional microbial mismatches after FMTs can lead to unintended consequences and require rethinking of microbiome-based interventions.}, } @article {pmid40481571, year = {2025}, author = {Feng, Y and Zhao, Q and Zhao, Y and Ma, C and Tian, M and Hu, X and Chen, F and Li, D}, title = {Lactobacillus plantarum-derived extracellular vesicles from dietary barley leaf supplementation attenuate Citrobacter rodentium infection and intestinal inflammation.}, journal = {Journal of nanobiotechnology}, volume = {23}, number = {1}, pages = {426}, pmid = {40481571}, issn = {1477-3155}, support = {32371511 and 32001677//the National Natural Science Foundation of China/ ; 2020M680256//the China Postdoctoral Science Foundation/ ; }, mesh = {Animals ; *Citrobacter rodentium ; Mice ; *Enterobacteriaceae Infections/microbiology ; *Extracellular Vesicles/metabolism/chemistry ; *Lactobacillus plantarum/metabolism/chemistry ; *Hordeum/chemistry ; Gastrointestinal Microbiome/drug effects ; Colitis/microbiology ; *Plant Leaves/chemistry ; Mice, Inbred C3H ; *Dietary Supplements ; Male ; Inflammation ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a gastrointestinal inflammatory disorder characterized by disturbed interactions between gut microbiota and host immune response. Barley leaf (BL) is a traditional Chinese herb recorded to have health-promoting effects. However, little is known about the beneficial role of BL against enteric infection-induced intestinal inflammation. Here, we uncover that BL protects against Citrobacter rodentium (C. rodentium)-induced infectious colitis by improving host-microbiota interactions.

METHODS: C3H/HeN mice were fed a diet with/without BL and infected with C. rodentium. Transcriptome sequencing, anti-CD4 antibody treatment, and flow cytometry were conducted to investigate the mechanisms of T cell immune modulation. The intervention involved administering anti-CD4 antibody at 500 µg each time for three times before and during C. rodentium infection. Analysis of gut microbiota composition was performed by 16S rRNA gene sequencing on fecal samples. Fecal microbiota transplantation was conducted by administering microbiota from donor group to recipient group via oral gavage to investigate the role of intestinal microbiota in immune modulation.

RESULTS: BL ameliorated the severity of C. rodentium-induced colitis, and this effect was linked to improved gut homeostasis and enhanced mucosal barrier function. BL enriched the pathways of T helper 1 (Th1)/Th2 and Th17 cell differentiation in the colon, suggesting the involvement of CD4[+] T cells. Consistent with this, anti-CD4 antibody treatment abrogated the effect of BL and flow cytometry analysis revealed that BL mitigated C. rodentium-induced pro-inflammatory Th1 immune response. Moreover, the protective effect of BL was associated with alleviation of gut microbiota dysbiosis and increased abundance of Lactobacillus. Our in vivo studies further revealed that live Lactobacillus plantarum (L. plantarum) administration attenuated the pathogenic effects induced by C. rodentium infection, whereas heat-inactivated L. plantarum did not show the same results. Mechanistically, BL supplementation enriched L. plantarum, which subsequently released nanosized extracellular vesicles (EVs) that serve as a key mediator in alleviating C. rodentium-associated pathology and Th1 cell dysregulation.

CONCLUSIONS: Our work thus provides evidence for utilizing BL and L. plantarum-derived EVs to manage enteric infection-associated IBD.}, } @article {pmid40478639, year = {2025}, author = {Bathobakae, L and Bashir, R and Koodirile, A and Villegas, K and Rajab, I and Perez, EW and Cavanagh, Y and El-Sedfy, A and Suh, JS}, title = {Clostridioides difficile enteritis: a targeted review of current literature.}, journal = {Scandinavian journal of gastroenterology}, volume = {60}, number = {7}, pages = {675-685}, doi = {10.1080/00365521.2025.2515423}, pmid = {40478639}, issn = {1502-7708}, mesh = {Humans ; *Clostridium Infections/diagnosis/therapy/epidemiology/physiopathology/complications ; *Enteritis/microbiology/therapy/diagnosis/epidemiology/physiopathology ; *Clostridioides difficile ; Anti-Bacterial Agents/therapeutic use ; Male ; Female ; Middle Aged ; Adult ; Diarrhea/microbiology ; Aged ; Aged, 80 and over ; Adolescent ; Abdominal Pain/etiology ; Young Adult ; }, abstract = {Clostridioides difficile enteritis (CDE) is a rare but clinically significant form of Clostridioides difficile infection (CDI) affecting the small intestine. CDE poses a diagnostic challenge owing to its rarity, complexity, and nonspecific presentation. The current data is retrospective in the form of case reports and conference proceedings. The lack of widespread awareness and limited literature on CDE often result in diagnostic delays, contributing to increased morbidity. This targeted narrative review sought to consolidate the current knowledge on the epidemiology, pathophysiology, clinical presentation, and management of CDE, addressing a critical gap in the existing literature. Electronic databases, including PubMed, Embase, and Web of Science, were searched for published cases from inception to April 2024. The initial search yielded 2,120 articles, which were filtered using study design, English language, and human subjects. After screening for duplicates and excluding irrelevant articles, 44 articles comprising 49 patients were included in the final review. Of the 49 individual cases reviewed, 25 (51%) were male and 24 (49%) were female. The patients' ages ranged from 16 to 91 years, with a mean age of 53.4 years. Abdominal pain and diarrhea were the chief complaints reported in 37/49 (76%) and 35/49 (71%) cases, respectively. About 42/49 (86%) cases were effectively treated with antibiotics, while some cases required fecal microbiota transplantation or surgical exploration. Given its grave course, CDE warrants prompt and appropriate treatment to prevent complications such as fulminant enteritis, compartment syndrome, and bowel perforation.}, } @article {pmid40478172, year = {2025}, author = {Lasagna, A}, title = {Mitigation strategies for gastrointestinal (GI) immune-related adverse events for patients with solid tumors receiving immunotherapy.}, journal = {Immunotherapy}, volume = {17}, number = {8}, pages = {595-603}, pmid = {40478172}, issn = {1750-7448}, mesh = {Humans ; *Immunotherapy/adverse effects/methods ; *Neoplasms/therapy/immunology ; *Immune Checkpoint Inhibitors/adverse effects/therapeutic use ; Gastrointestinal Microbiome/immunology ; *Gastrointestinal Diseases/etiology/prevention & control ; Artificial Intelligence ; *Drug-Related Side Effects and Adverse Reactions ; }, abstract = {Over the past decade, immunotherapy has revolutionized the treatment algorithm for solid tumors. Immune checkpoint inhibitors (ICIs) demonstrated efficacy against several tumor types, but they can favor the development of immune-related adverse events (irAEs). IrAEs can sometimes be life-threatening. In this review, we will briefly analyze the main gastro-intestinal toxicities and focus on potential strategies for mitigating irAEs, particularly through the modification of gut microbiota (GM) composition. Finally, we will briefly dwell on the potential role of artificial intelligence (AI) in the prediction of irAEs.}, } @article {pmid40475999, year = {2025}, author = {Hwang, D and Chong, E and Li, Y and Li, Y and Roh, K}, title = {Deciphering the gut microbiome's metabolic code: pathways to bone health and novel therapeutic avenues.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1553655}, pmid = {40475999}, issn = {1664-2392}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Bone and Bones/metabolism ; Animals ; Probiotics/therapeutic use ; *Bone Remodeling/physiology ; *Osteoporosis/metabolism/microbiology/therapy ; Prebiotics ; Fecal Microbiota Transplantation ; Bone Diseases/metabolism/microbiology/therapy ; }, abstract = {The gut microbiome plays an important role in the protection against various systemic diseases. Its metabolic products profoundly influence a wide range of pathophysiological events, including the regulation of bone health. This review discusses the recently established connections between the gut microbiome and bone metabolism, focusing on the impact of microbiome-derived metabolites such as SCFAs, Bile Acids, and tryptophan to the control of bone remodeling and immunoreactions. Recent advances in metagenomics and microbiome profiling have unveiled new exciting therapeutic opportunities, ranging from the use of probiotics, prebiotics, engineered microbes, and to fecal microbiota transplantation. Understanding of the interplay among diet, microbiota, and bone health provides new avenues for tailored interventions aimed at reducing disease risk in osteoporosis and other related disorders. By drawing knowledge from microbiology, metabolism, and bone biology, this review highlights the potential of microbiome-targeted therapies to transform skeletal health and the management of bone diseases.}, } @article {pmid40472289, year = {2025}, author = {Lim, LWZ and Toh, KY and Cook, AR and Lee, JWJ and Lim, JFY}, title = {Public knowledge, awareness and perception of gut microbiome and faecal microbiota transplantation in Singapore: a survey study.}, journal = {Singapore medical journal}, volume = {}, number = {}, pages = {}, pmid = {40472289}, issn = {2737-5935}, abstract = {INTRODUCTION: Despite the exponential increase in microbiome research, knowledge and beliefs about the gut microbiome and faecal microbiota transplantation (FMT) remain unclear. The aim of this study was to identify the extent of knowledge, awareness and perception among the general public regarding the gut microbiome and FMT.

METHODS: An online questionnaire on knowledge and beliefs about the gut microbiome and FMT was administered to 1831 participants. Data analysis software was used to generate descriptive statistics and explore associations between knowledge and sociodemographic variables.

RESULTS: Even though only 33% of participants had heard of the gut microbiome, more than 92% had consumed probiotic drinks or supplements. While 85% had not heard of the FMT procedure, 72% of respondents would consider having FMT to treat Clostridioides difficile infection (CDI). Willingness to receive FMT depended mainly on recommendation from healthcare providers (77%). Knowledge and awareness regarding the gut microbiome and FMT were relatively low, despite most participants having prior gut health-related behaviours.

CONCLUSION: This study identified the public's perceptions of FMT and the potential barriers to its uptake. Insights from the study highlight the need for health education to enhance acceptance of FMT and the importance of using information supported by medical professionals to immunise the public against poorly validated science.}, } @article {pmid40471587, year = {2025}, author = {Wei, M and Huang, Q and Yu, F and Luo, YF and Feng, X and Liao, D and Li, J and Zhang, B and Liu, ZY and Xia, J}, title = {Elevated phenylacetylglutamine caused by gut dysbiosis associated with type 2 diabetes increases neutrophil extracellular traps formation and exacerbates brain infarction.}, journal = {Clinical science (London, England : 1979)}, volume = {}, number = {}, pages = {}, doi = {10.1042/CS20242943}, pmid = {40471587}, issn = {1470-8736}, support = {2022YFC3602400, 2022YFC3602401//National Key Research and Development Projects/ ; 82271369; 82301514; 82471365//National Natural Science Foundation of China/ ; 2021JJ31109; 2023JJ41018//Natural Science Foundation of Hunan Province/ ; }, abstract = {Type 2 diabetes (T2D) aggravates ischemic stroke. The association between gut microbiota-derived metabolite phenylacetylglutamine (PAGln) and ischemic stroke patients with T2D remains unclear. Therefore, we aimed to explore the change of gut microbiota and its metabolite, PAGln in ischemic stroke patients with T2D, as well as investigate the role of PAGln in this disease. We performed two clinical cohort studies to investigate the changes of gut microbiota and PAGln in ischemic stroke patients with T2D. Then, we transplanted fecal microbiota from patients into rats and established a middle cerebral artery occlusion model. Finally, an intraperitoneal injection of PAGln was administered to rats to test whether it exacerbates brain infarction. Plasma PAGln levels were significantly higher in stroke patients with T2D compared to those without T2D. There was a positive correlation of Plasma PAGln with NETs. Enterobacteriaceae, Verrucomicrobiota, and Klebsiella were enriched in stroke patients with T2D and showed a significant positive correlation with PAGln levels. The rats transplanted with fecal microbes from stroke patients with T2D developed a more severe brain injury and had higher levels of plasma PAGln and NETs compared to the rats transplanted with fecal microbes from stroke patients without T2D. Additionally, rats treated with PAGln exhibited more severe brain injury accompanied by increased systemic inflammation, oxidative stress and NET formation. Our results suggest elevated circulating PAGln levels, resulting from gut dysbiosis in stroke patients with T2D, may exacerbate brain infarction through NETs formation, systemic inflammation, and oxidative stress.}, } @article {pmid40470286, year = {2025}, author = {Hetterich, J and Pees, M}, title = {Case Report: Oral fecal microbiota transplantation in a Mediterranean spur-thighed tortoise (Testudo graeca) suffering from chronic gastrointestinal disease-procedure, clinical outcome and follow-up.}, journal = {Frontiers in veterinary science}, volume = {12}, number = {}, pages = {1560689}, pmid = {40470286}, issn = {2297-1769}, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) is the process of transferring fecal microbiota from a healthy donor into the gastrointestinal tract of a recipient. Although many mechanisms of FMT are still not completely understood at present, it has been described that the treatment of various gastrointestinal diseases in different species, including humans, is significantly improved by FMT therapy. Since the first report on FMT therapy in veterinary medicine in small mammals numerous cases have been reported, but little information has been published on the therapeutic effects of FMT treatment in reptiles. The present case report describes the effects of orally administered fecal microbiota transplantation in a Mediterranean spur-thighed tortoise (Testudo graeca) suffering from chronic gastrointestinal disorders.

CASE PRESENTATION: A nine-year-old, 330 g, intact female Mediterranean spur-thighed tortoise (Testudo graeca) from the animal owner's own offspring was presented for consultation due to decreased general condition, anorexia and sialorrhea following oral intake of a lettuce species (Lactuca virosa) known for its poisonous plant ingredients (sesquiterpene lactones) 3 weeks prior to presentation. Pre-existing conditions were not reported. Clinical examination revealed sialorrhea and a reduced general condition. Diagnostic procedures included blood chemistry, radiography and ultrasonography. Despite repeated treatment attempts with various medical regimes over 158 days, the tortoise continued showing variable recurring gastrointestinal symptoms. An orally administered FMT was initiated and continued for a total of 3 weeks. Gastrointestinal signs improved rapidly within 1 week and resolved completely after 3 weeks. Over a follow up period of 9 months, no symptom recurrence or adverse effects were monitored.

CONCLUSION: This case report describes the first successful trial of fecal microbiota transplantation in chelonians. The outcome indicates that this therapeutic approach may be beneficial not only to small animals but also for the therapy of gastrointestinal disorders in reptiles, especially those cases with insufficient conventional therapy results.}, } @article {pmid40469520, year = {2025}, author = {Yu, L and Chen, Z and Yin, S and Guo, Q and Chen, Y and Li, J and Wang, Y and Liu, X and Xu, Z and Zhang, Y and Zhang, Y and Zheng, Z and Chen, K and Ding, Y and Fan, H and Liu, Z and Ding, Y}, title = {Gut-derived Lactobacillus from exceptional responders mitigates chemoradiotherapy-induced intestinal injury through methionine-driven epigenetic modulation.}, journal = {iMeta}, volume = {4}, number = {3}, pages = {e70043}, pmid = {40469520}, issn = {2770-596X}, abstract = {Acute chemoradiotherapy-induced intestinal injury (ACRIII) is a common and debilitating complication in patients with colorectal cancer, significantly impairing both quality of life and treatment outcomes. This study aimed to investigate the role of the gut microbiome in mitigating ACRIII. Through bioinformatics analysis of clinical fecal samples and fecal microbiota transplantation (FMT) experiments in mice, we identified a strong association between a high abundance of Lactobacillus species and the absence of ACRIII. From the fecal samples of rectal cancer patients who achieved complete remission without experiencing ACRIII during chemoradiotherapy, 10 novel Lactobacillus strains were isolated and characterized. Among these, Lacticaseibacillus rhamnosus DY801 exhibited a robust capacity to synthesize methionine through metB. This microbial methionine production modulated methionine metabolism in host gut lymphoid tissue inducer (Lti) cells, without diminishing the therapeutic efficacy of chemoradiotherapy. Supplementation with methionine increased intracellular levels of S-adenosylmethionine and enhanced histone H3 lysine 4 trimethylation (H3K4me3) in Lti cells. These epigenetic modifications led to the suppression of pro-inflammatory cytokines interleukin-17A (IL-17A) and interleukin-22 (IL-22), ultimately reducing ACRIII severity. Our findings suggest that specific Lactobacillus strains derived from patients with exceptional treatment responses may offer a novel therapeutic avenue for preventing or alleviating ACRIII. This microbiome-based approach holds significant potential for improving patient outcomes and enhancing the tolerability of chemoradiotherapy in colorectal cancer.}, } @article {pmid40469517, year = {2025}, author = {Zhang, F and Li, R and Liu, Y and Liang, J and Gong, Y and Xiao, C and Cai, J and Wang, T and You, Q and Zhang, J and Chen, H and Xiao, J and Zhang, Y and Yang, Y and Li, H and Yao, J and Zhang, Q and Zheng, J}, title = {Integrative cross-tissue analysis unveils complement-immunoglobulin augmentation and dysbiosis-related fatty acid metabolic remodeling during mammalian aging.}, journal = {iMeta}, volume = {4}, number = {3}, pages = {e70027}, pmid = {40469517}, issn = {2770-596X}, abstract = {Aging-related decline and adaptation are complex, multifaceted processes that affect various tissues and increase risk of chronic diseases. To characterize key changes in cross-tissue aging, we performed comprehensive proteomic and metabolomic analyses across 21 solid tissues and plasma samples, alongside shotgun metagenomic profiling of fecal microbial communities in young and aged mice. Our findings revealed widespread aging-rewired chronic inflammation, characterized by complement system activation in plasma and universal immunoglobulins accumulation across multiple solid tissues. This inflammatory remodeling significantly enhanced vulnerability to aging-related tissue injury. Moreover, we identified organ-specific and organ-enriched proteins with high functional specificity. Among these, aging-related proteins were closely linked to disorders arising from lipid metabolism dysfunction. Analysis of multi-tissue metabolomic and fecal metagenomic profiles revealed that aging significantly disrupted inter-tissue metabolic coupling, activities of polyunsaturated fatty acids metabolism, and gut microbiota homeostasis. Aged mice exhibited a marked decrease in Escherichia and an increase in Helicobacter, strongly correlating with alterations in omega-3 and omega-6 fatty acid abundances. Through multi-omics integration, we identified key molecular hubs driving organismal responses to aging. Collectively, our study uncovers extensive aging-associated alterations across tissues, emphasizing the interplay between systemic inflammation and dysbiosis-driven fatty acid remodeling. These findings provide deeper insights into the development of healthy aging from a cross-tissue perspective.}, } @article {pmid40469413, year = {2025}, author = {Shimizu, K and Ogura, H and Oda, J}, title = {Gut dysbiosis and its treatment in patients with critical illness.}, journal = {Acute medicine & surgery}, volume = {12}, number = {1}, pages = {e70068}, pmid = {40469413}, issn = {2052-8817}, abstract = {The gut is a target organ that functions as the "motor" of critical illness. In patients with critical illness, the disrupted gut microbiota following infection and injury could cause diarrhea, pneumonia, and systemic inflammation. For maintaining the gut microbiota, therapeutic approaches are required to modulate host responses and prevent systemic inflammation. Probiotics and synbiotics could maintain the gut microbiota and decrease not only the incidence of diarrhea but also that of ventilator-associated pneumonia. The effects of probiotics/synbiotics differ with the type of bacteria and disease severity. Adverse effects of probiotics have been reported; therefore, the selection of safe and effective probiotics/synbiotics is warranted. Refractory diarrhea with prolonged dysbiosis may require a novel intestinal therapy, such as fecal microbiota transplantation, to alleviate gut dysbiosis.}, } @article {pmid40468650, year = {2025}, author = {Cha, RR and Sonu, I}, title = {Fecal microbiota transplantation: present and future.}, journal = {Clinical endoscopy}, volume = {58}, number = {3}, pages = {352-359}, pmid = {40468650}, issn = {2234-2400}, support = {//Gyeongsang National University Fund/ ; }, abstract = {Fecal microbiota transplantation (FMT) involves transplanting fecal matter from healthy donors into patients with gut dysbiosis to restore microbial balance. It has been proven to be highly effective in treating recurrent Clostridioides difficile infection (CDI), and United States Food and Drug Administration-approved microbiome-based therapies, such as REBYOTA (fecal microbiota live-jslm) and VOWST (fecal microbiota spores live-brpk), offer promising treatment options. Although FMT is widely used to treat recurrent CDI, its use in gastrointestinal and metabolic diseases remains limited. Future research directions include optimizing donor selection, understanding microbial mechanisms, and exploring the potential of FMT for treating other diseases. Ongoing research not only aims to broaden its indications but also improves its safety and efficacy. Emerging therapies such as VE303 (Vedanta) are being studied to refine treatment approaches and expand the use of microbiota-based therapies. Further studies are needed to standardize guidelines, improve patient outcomes, and better define the role of FMT in the treatment of diseases beyond recurrent CDI.}, } @article {pmid40466419, year = {2025}, author = {Zhang, K and Dong, Y and Ding, Y and Wang, X and Liu, T and Zhong, W and Cao, H}, title = {Illuminating prospects of probiotic Akkermansia muciniphila in intestinal inflammation and carcinogenesis.}, journal = {Microbiological research}, volume = {299}, number = {}, pages = {128240}, doi = {10.1016/j.micres.2025.128240}, pmid = {40466419}, issn = {1618-0623}, mesh = {*Probiotics/therapeutic use ; Humans ; Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/microbiology/therapy ; *Carcinogenesis ; Animals ; Akkermansia ; Colorectal Neoplasms/microbiology ; *Inflammation/microbiology ; Mucins/metabolism ; Intestines/microbiology ; }, abstract = {Akkermansia muciniphila (A. muciniphila) is portrayed as an advantageous enteric bacterium with a particular property of mucin utilization. Emerging data suggest A. muciniphila can reshape gut chronic inflammation, enhance intestinal epithelial tight junctions, and sensitize toll-like receptors 2 (TLR2) and TLR4 to restrain the infiltrating cytotoxic T lymphocytes and macrophages. As well, analogous role is detected in surface A. muciniphila-coated pili, outer-membrane protein Amuc_1100, β-galactosidase enzyme Amuc_2172, and extracellular vesicles. We rendered insights into empirical evidence on molecular mechanisms mediated by A. muciniphila in inflammatory bowel disease and intestinal cancers which include colitis-associated colorectal cancer and colorectal cancer. We discussed its potential preventive and therapeutic benefits on immune checkpoint inhibitors therapy. A. muciniphila supplementation through diet, probiotics-prebiotics, fecal microbiota transplantation, and certain drugs, would be a promising therapeutic strategy. Nevertheless, data profiles decipher A. muciniphila is linked to multiple sclerosis and Parkinson's disease occurrence and evolvement. Thus, how to avoid the deleterious effects triggered by A. muciniphila warrants further exploration. It ought to be considered to conduct a critical and cautious analysis of the next-generation beneficial microbe manipulation ahead of clinical application.}, } @article {pmid40464639, year = {2025}, author = {Zhang, Q and Liu, Y and Li, Y and Bai, G and Pang, J and Wu, M and Li, J and Zhao, X and Xia, Y}, title = {Implications of gut microbiota-mediated epigenetic modifications in intestinal diseases.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2508426}, pmid = {40464639}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Epigenesis, Genetic ; Animals ; Dysbiosis/microbiology/therapy ; DNA Methylation ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; *Intestinal Diseases/microbiology/genetics/therapy ; Probiotics ; Inflammatory Bowel Diseases/microbiology/genetics/therapy ; Colorectal Neoplasms/microbiology/genetics ; }, abstract = {Intestinal diseases are highly prevalent, affecting millions worldwide and significantly contributing to global morbidity. The treatment of complex disorders, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), remains challenging due to multifactorial etiologies, diverse patient responses, and the limitations of current therapeutic strategies. Although the gut microbiota clearly plays a role in regulating the onset of intestinal diseases, few studies have explored the epigenetic factors by which the microbiota contributes to disease development. Here, the latest insights into the molecular mechanisms underlying the bidirectional influence between gut microbiota and epigenetic modifications are discussed, including DNA methylation, histone modifications, non-coding RNAs, and N6-methyladenosine (m[6]A). Importantly, mechanistic studies based on animal models or human cells have demonstrated that the gut microbiota, and other environmental factors, influence targeted gene expression and activate immune pathways through host epigenetic dysregulation, which are closely associated with the development of IBD and CRC. Furthermore, potential microbiome interventions, including probiotics, prebiotics and postbiotics, fecal microbiota transplantation (FMT), dietary modifications, and phage therapy, have been proposed as innovative therapeutic strategies to correct these abnormal epigenetic patterns associated with the diseases. Overall, addressing microbiome dysbiosis and its epigenetic consequences presents a promising frontier in the treatment of intestinal diseases, offering the potential to not only restore microbial balance but also provide more targeted and personalized therapeutic strategies for better patient outcomes.}, } @article {pmid40464558, year = {2025}, author = {Ruan, Y and Zhu, T and Yang, R and Su, F and An, C and Hu, Z and Li, X and Li, Y and Chen, P and Shao, X and Qin, J and Chen, H and Chen, R}, title = {Donor-derived microbial engraftment and gut microbiota shifts associated with weight loss following fecal microbiota transplantation.}, journal = {Applied and environmental microbiology}, volume = {91}, number = {7}, pages = {e0012025}, pmid = {40464558}, issn = {1098-5336}, support = {82100860//National Natural Science Foundation of China/ ; 82370864//National Natural Science Foundation of China/ ; 2019A1515110658//Natural Science Foundation of Guangdong Province/ ; 2024A04J4869//Science and Technology Program of Guangzhou/ ; }, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Bacteria/classification/genetics/isolation & purification ; Dysbiosis/therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; *Obesity/therapy/microbiology ; Overweight/therapy/microbiology ; Tissue Donors ; *Weight Loss ; }, abstract = {Fecal microbiota transplantation (FMT) is a promising treatment for microbiota dysbiosis and may provide metabolic benefits for obesity. However, its mechanisms and variability in clinical outcomes remain poorly understood. This 12-week multicenter, single-arm study evaluated the efficacy of FMT for weight loss and explored the role of donor-derived microbial engraftment and functional shifts in mediating weight loss among overweight and obese individuals. Twenty-three participants (body mass index ≥24 kg/m[2]) without diabetes received three biweekly FMT sessions via a nasojejunal tube. Fecal samples from participants and donors were analyzed using metagenomic sequencing. By week 12, 52% of participants were classified as responders, achieving significant weight loss of ≥5% from baseline, with an average weight loss of 7.98 ± 2.69 kg (P < 0.001). In contrast, non-responders lost 2.90 ± 1.89 kg (P < 0.001). Responders exhibited a significantly higher proportion of donor-derived microbial strains post-FMT compared to non-responders (37.8% vs 15.2%, P = 0.020). Notably, key taxa, including Phascolarctobacterium (P = 0.034) and Acidaminococcaceae (P = 0.012), increased significantly in abundance in responders post-FMT, indicating successful microbial engraftment as a critical determinant of therapeutic success. These findings suggest that FMT is a viable intervention for weight loss in obese individuals. Successful donor-derived microbial engraftment strongly correlates with weight loss efficacy, highlighting the potential of microbiota-targeted therapies in obesity management and providing insights into the mechanisms underlying FMT outcomes.IMPORTANCEPrior research indicates that fecal microbiota transplantation (FMT) is a promising treatment for diseases related to microbiota imbalance, potentially providing metabolic benefits for obesity. However, the specific role of donor-derived microbial engraftment in driving clinical efficacy has remained unclear. In this study, we evaluated the efficacy of FMT in promoting weight loss and explored the role of donor-derived bacterial strains in this process. Our findings demonstrate that the successful engraftment of specific donor-derived taxa, such as Phascolarctobacterium and Acidaminococcaceae, is strongly associated with significant weight loss. This highlights the critical interplay between donor microbiota and recipient gut environment. These findings underscore the potential of microbiota-targeted therapies as a novel strategy for obesity management.CLINICAL TRIALSThis study is registered with the Chinese Clinical Trial Registry as ChiCTR1900024760.}, } @article {pmid40463945, year = {2025}, author = {Wu, C and Mi, Y and Song, J and Zhang, M and Wang, C}, title = {The Regulatory Effect of Human Umbilical Cord Mesenchymal Stem Cells on the Gut Microbiota in Diabetic Nephropathy Rats.}, journal = {Iranian journal of biotechnology}, volume = {23}, number = {1}, pages = {}, pmid = {40463945}, issn = {1728-3043}, abstract = {BACKGROUND: Chronic inflammation is increasingly recognized as a key factor in the progression of diabetic kidney disease (DKD). By discovering that the regulation of gut microbiota plays an important role in diabetic kidney disease, human umbilical cord mesenchymal stem cells (HU-MSCs) explore the mechanism of fibrosis in diabetic kidney disease through the regulation of chronic inflammation, providing new clinical insights for the prediction, diagnosis, and treatment of diabetic kidney disease.

OBJECTIVES: This study explores the regulatory effects of HU-MSCs on gut microbiota and their protective role on the intestinal barrier in diabetic nephropathy rats.

MATERIAL AND METHOD: Diabetic kidney disease (DKD) was induced in SD rats via intraperitoneal injection of streptozotocin. Three groups were established: control group, diabetic kidney disease (DKD) group, and treatment group (DKD+HU-MSCs) (10 rats each). After diabetic kidney disease (DKD) modeling, rats in the treatment group (DKD+HU-MSCs) received 2×10[6] HU-MSCs via tail vein injection weekly for four weeks. Blood, urine, kidney, and colon tissues were collected post-treatment. Pathological changes were observed microscopically; immunohistochemistry detected tight junction proteins ZO-1 and Occludin in colon tissues. DiR-labeled HU-MSCs distribution was assessed with in vivo imaging, and immunohistochemistry evaluated human mesenchymal stem cell markers CD44 and CD90. Fecal samples underwent metagenomic sequencing for gut microbiota analysis.

RESULTS: HU-MSCs transplantation significantly reduced Blood Urea Nitrogen (BUN), Serum Creatinine (SCr), and 24-hour urinary protein levels (all P < 0.05) and improved renal pathology. Markers CD44 and CD90 were present in DKD rat colon tissues. Tight junction proteins Occludin and ZO-1 were decreased in DKD rats but increased following HU-MSCs treatment. Metagenomic analysis showed enhanced abundance of beneficial bacteria (Bifidobacterium and Lactobacillus) with HU-MSCs. Urinary protein was positively correlated with Prevotella and negatively with Ligilactobacillus (p < 0.05).

CONCLUSIONS: HU-MSCs may improve intestinal barrier function in diabetic kidney disease (DKD) rats by restoring gut microbiota structure and increasing intestinal tight junction proteins, offering a potential pathway for enhancing renal function.}, } @article {pmid40462220, year = {2025}, author = {Chen, M and Pan, J and Song, Y and Liu, S and Sun, P and Zheng, X}, title = {Correction: Effect of inulin supplementation in maternal fecal microbiota transplantation on the early growth of chicks.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {138}, pmid = {40462220}, issn = {2049-2618}, } @article {pmid40462165, year = {2025}, author = {Gao, H and Bai, H and Su, Y and Gao, Y and Fang, H and Li, D and Yu, Y and Lu, X and Xia, D and Mao, D and Luo, Y}, title = {Fecal microbiota transplantation from Helicobacter pylori carriers following bismuth quadruple therapy exacerbates alcohol-related liver disease in mice via LPS-induced activation of hepatic TLR4/NF-κB/NLRP3 signaling.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {627}, pmid = {40462165}, issn = {1479-5876}, support = {42377426//National Natural Science Foundation of China/ ; 42077382//National Natural Science Foundation of China/ ; 21JCYBJC01200//Tianjin Municipal Natural Science Foundation/ ; 2023220//Research Project on Integrated Traditional Chinese and Western Medicine of Tianjin Municipal Health Commission/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/adverse effects ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Helicobacter pylori/physiology/drug effects ; *Signal Transduction/drug effects ; Lipopolysaccharides/pharmacology ; *Bismuth/therapeutic use/pharmacology ; *Toll-Like Receptor 4/metabolism ; Gastrointestinal Microbiome/drug effects ; *NF-kappa B/metabolism ; *Liver/pathology/metabolism/drug effects ; *Liver Diseases, Alcoholic/microbiology/therapy/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Helicobacter Infections/microbiology ; Disease Models, Animal ; Humans ; Dysbiosis ; }, abstract = {BACKGROUND: Helicobacter pylori infection is common in patients with alcohol-related liver disease (ALD), and bismuth quadruple therapy (BQT) is widely used for eradication. However, its impact on ALD remains unclear. This study aims to characterize BQT-induced gut microbiota alterations in asymptomatic H. pylori carriers and evaluate their effect on an ALD mouse model.

METHODS: Metagenomic sequencing was conducted to assess the gut microbiota composition of individuals before and after BQT. Fecal microbiota transplantation (FMT) from these donors was performed in an ALD mouse model. Gut microbiota in mice was analyzed by 16S rRNA sequencing. Liver and intestinal parameters were assessed using western blot, RT-qPCR, histopathology, ELISA, and flow cytometry.

RESULTS: BQT treatment significantly altered the gut microbiota in H. pylori carriers, increasing the abundance of opportunistic pathogens, including Klebsiella pneumoniae, Escherichia coli, Klebsiella quasipneumoniae, and Klebsiella variicola, while decreasing beneficial bacteria such as Bifidobacterium, Eubacterium, Bacteroides, Faecalibacterium, and Blautia. In ALD mice receiving FMT from post-BQT donors, exacerbated gut dysbiosis was observed, marked by an enrichment of Enterobacteriaceae and Escherichia-Shigella. These microbiota changes were associated with impairment of intestinal barrier integrity, as evidenced by reduced levels of mucins, tight junction proteins, and antimicrobial peptides, along with a decrease in Treg cells and an increase in Th17 and Th1 cells. Additionally, this dysbiosis led to elevated serum lipopolysaccharide (LPS) levels, which activated the hepatic NLRP3 inflammasome pathway and subsequently increased IL-18 and IL-1β levels. Furthermore, liver function and oxidative stress markers, including ALT, AST, MDA, GSSG/GSH ratio, and SOD, were significantly elevated, indicating severe liver dysfunction and increased oxidative stress. Finally, probiotic supplementation effectively mitigated the negative effects of BQT-induced gut microbiota remodeling on ALD in mice.

CONCLUSIONS: BQT markedly alters the gut microbiota in H. pylori carriers, promoting dysbiosis that exacerbates ALD in mice via LPS-mediated activation of hepatic inflammatory pathways. These findings highlight the need for careful consideration of BQT use in ALD patients.}, } @article {pmid40461622, year = {2025}, author = {Ferreira, J}, title = {Fecal microbiota transplantation therapy.}, journal = {Lab animal}, volume = {54}, number = {6}, pages = {133}, doi = {10.1038/s41684-025-01564-x}, pmid = {40461622}, issn = {1548-4475}, } @article {pmid40461059, year = {2025}, author = {Laiola, M and Koppe, L and Larabi, A and Thirion, F and Lange, C and Quinquis, B and David, A and Le Chatelier, E and Benoit, B and Sequino, G and Chanon, S and Vieille-Marchiset, A and Herpe, YE and Alvarez, JC and Glorieux, G and Krukowski, H and Huys, GR and Raes, J and Fouque, D and Massy, ZA and Ehrlich, SD and Stengel, B and Wagner, S and , }, title = {Toxic microbiome and progression of chronic kidney disease: insights from a longitudinal CKD-Microbiome Study.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2024-334634}, pmid = {40461059}, issn = {1468-3288}, abstract = {BACKGROUND: The gut microbiota has been linked to non-communicable diseases, including chronic kidney disease (CKD). However, the relationships between gut microbiome composition changes, uraemic toxins (UTs) accumulation, and diet on CKD severity and progression remain underexplored.

OBJECTIVE: To characterise relationships between gut microbiome composition and functionality, UTs diet, and CKD severity and progression, as well as assess microbial contributions to UTs accumulation through mice faecal microbiota transplantation (FMT).

DESIGN: This study profiled the gut microbiome of 240 non-dialysis patients with CKD (CKD-REIN cohort) using shotgun metagenomics, with follow-up in 103 patients after 3 years, with comparisons with healthy volunteers from the Milieu Intérieur cohort. A multiomics approach identifies features associated with CKD severity (and progression), with validation in an independent Belgian cohort. Experimental models used FMT to test CKD gut microbiome effects on UTs and kidney fibrosis. Changes in gut microbiome over time were evaluated, and the impact of diet on these changes was assessed.

RESULTS: Compared with matched healthy controls, patients with CKD exhibited gut microbiota alteration, with enrichment of UT precursor-producing species. Patients with severe CKD exhibited higher UT levels and greater enrichment of UT (precursor)-producing species in the microbiota than patients with moderate CKD. Over time, UT (precursor)-producing species increased, and a plant-based low protein diet appeared to mitigate these changes. FMT from patients with CKD to antibiotic-treated CKD model mice increased serum UT levels and exacerbated kidney fibrosis.

CONCLUSIONS: This study highlights the role of the microbiome and UTs in CKD, suggesting a potential therapeutic target to slow disease progression.}, } @article {pmid40460824, year = {2025}, author = {Gogokhia, L and Tran, N and Grier, A and Nagayama, M and Xiang, G and Funez-dePagnier, G and Lavergne, A and Ericsson, C and Ben Maamar, S and Zhang, M and Battat, R and Scherl, E and Lukin, DJ and Longman, RS}, title = {Donor composition and fiber promote strain engraftment in a randomized controlled trial of fecal microbiota transplant for ulcerative colitis.}, journal = {Med (New York, N.Y.)}, volume = {}, number = {}, pages = {100707}, pmid = {40460824}, issn = {2666-6340}, support = {R01 DK128257/DK/NIDDK NIH HHS/United States ; T32 DK116970/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an emerging treatment for ulcerative colitis (UC), but the impact of prebiotic fiber on FMT efficacy for UC is unclear. We performed a randomized, double-blind, placebo-controlled clinical trial to examine the efficacy of FMT with and without dietary fiber supplementation in patients with UC.

METHODS: 27 patients with mild to moderate UC were randomized to receive a single FMT or placebo with or without psyllium fiber supplementation for 8 weeks. The primary outcome was clinical response at week 8, and secondary outcomes included endoscopic improvement and clinical remission. Metagenomic sequencing of fecal DNA was analyzed to determine taxonomic profiles and donor strain engraftment.

FINDINGS: The trial was terminated early due to manufacturer discontinuation of FMT product. FMT induced clinical response, remission, and endoscopic improvement in UC patients compared to placebo (p < 0.05), but fiber did not improve clinical outcomes of FMT. Recipient microbiome composition post-FMT shifted toward donor composition in responders and non-responders, but the durability of this change was stronger in responders. Clinical response and durable change in microbiome composition following FMT was donor dependent. Strain tracking analysis also demonstrated a donor-dependent variability in the rate of successful engraftment and identified a consortium of engrafted bacteria associated with treatment response or fiber supplementation.

CONCLUSIONS: Single-dose FMT demonstrated clinical efficacy for mild to moderate UC compared to placebo but revealed no benefit of fiber supplementation. These results highlight proof of concept that donor selection and prebiotic fiber can shape strain-level engraftment. This study was registered at ClinicalTrials.gov: NCT03998488.

FUNDING: National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK128257, to R.S.L.).}, } @article {pmid40458824, year = {2025}, author = {Huang, Y and Huang, J and Li, Y and Xu, T and Quan, G and Xu, P and Yang, X and Liu, Z and Xie, W}, title = {Therapeutic efficacy of fecal microbiota transplantation in severe food intolerance: a case report.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1594022}, pmid = {40458824}, issn = {2296-861X}, abstract = {This report presents the first documented application of fecal microbiota transplantation (FMT) for the management of extensive multi-food intolerance involving 52 specific foods in a pediatric patient with autism spectrum disorder (ASD). A 7 years-old autistic child was diagnosed with food intolerance to 52 items, presenting with generalized rashes, diarrhea, and malnutrition (BMI of 12.9) upon exposure or ingestion of the implicated foods. The child received oral fecal microbiota capsule treatment, with a daily dose of nine capsules (a total of 120 capsules per course) for two consecutive treatment courses. The rashes resolved, the child regained tolerance to previously intolerable foods, nutritional status improved, and stool consistency normalized. This case suggests that FMT may hold therapeutic potential for managing food intolerance in autistic patients.}, } @article {pmid40457025, year = {2025}, author = {Elkrief, A and Pidgeon, R and Maleki Vareki, S and Messaoudene, M and Castagner, B and Routy, B}, title = {The gut microbiome as a target in cancer immunotherapy: opportunities and challenges for drug development.}, journal = {Nature reviews. Drug discovery}, volume = {}, number = {}, pages = {}, pmid = {40457025}, issn = {1474-1784}, abstract = {The gut microbiome has a critical role in shaping the patient's immune response and influencing the efficacy of anticancer immunotherapy. Emerging evidence suggests that modulating the gut microbiome through interventions such as faecal microbiota transplantation, probiotics, prebiotics and lifestyle modifications may enhance therapeutic outcomes. Consequently, drug development efforts in immuno-oncology have expanded to explore microbiome-based therapeutic strategies. In this Review, we examine the rationale for targeting the microbiome in cancer treatment, highlighting key advances in clinical microbiome characterization and their implications for immunotherapy. We discuss findings from recent clinical trials evaluating microbiome-based interventions and address the challenges associated with translating these approaches into clinical practice. Finally, we outline future directions for the development and integration of microbiome-targeted therapies in oncology, with a focus on optimizing efficacy, safety and patient stratification strategies.}, } @article {pmid40456559, year = {2025}, author = {Hu, Y and Wang, Y and Gao, H and Yang, G and Xie, J and He, Z and Lv, S and Gu, F and Huang, C and Hu, W}, title = {Piperine Improves DSS-Induced Colitis in Mice via Inhibition of Inflammation and Modulation of Gut Microbiota.}, journal = {Phytotherapy research : PTR}, volume = {39}, number = {7}, pages = {3197-3211}, doi = {10.1002/ptr.8491}, pmid = {40456559}, issn = {1099-1573}, support = {ZDYF2024XDNY177//Hainan Province Science and Technology Special Fund/ ; 2023YFD1600200//National Key Research and Development Program of China/ ; 1630012025119//China Central Public-Interest Scientific Institution Basal Research Fund/ ; }, mesh = {Animals ; *Alkaloids/pharmacology ; *Polyunsaturated Alkamides/pharmacology ; *Piperidines/pharmacology ; *Gastrointestinal Microbiome/drug effects ; *Benzodioxoles/pharmacology ; *Colitis/drug therapy/chemically induced/microbiology ; Mice ; Dextran Sulfate ; Male ; Mice, Inbred C57BL ; Inflammation/drug therapy ; NF-kappa B/metabolism ; Fecal Microbiota Transplantation ; *Anti-Inflammatory Agents/pharmacology ; Colon/drug effects/pathology ; Cytokines/metabolism ; Disease Models, Animal ; }, abstract = {Inflammatory bowel disease (IBD) is a global health concern with limited therapeutic options. Previous studies have demonstrated that piperine exhibited anti-inflammatory effects both in vitro and in vivo. However, its potential to ameliorate colitis in mice through modulation of gut microbiota has not been explored. This study aimed to investigate the role of gut microbiota in the protective effects of piperine against colitis using a dextran sulfate sodium (DSS)-induced mouse model. Mice were administered piperine (12.5 and 25 mg/kg) prior to DSS exposure. Fecal microbiota transplantation (FMT) was then performed, after which we evaluated colitis symptoms, inflammation levels, and intestinal barrier function. Subsequently, 16S rDNA-based high-throughput sequencing was employed to analyze the microbial composition of the mouse cecal contents. Piperine administration increased the colon length, decreased the spleen index, and improved colon histopathology. Furthermore, piperine modulated inflammatory responses by inhibiting NF-κB signaling, thereby reducing the release of pro-inflammatory cytokines and mediators. It also enhanced intestinal barrier integrity by increasing the expression of claudin-1, claudin-3, ZO-1, occludin, and mucin 2. Notably, the 16S rDNA sequencing results revealed that piperine increased the abundance of Dubosiella in the gut. Piperine effectively protected mice from DSS-induced colitis, suppressed inflammation, and improved poor intestinal barrier function. It reshaped the intestinal microbiota, ultimately alleviating DSS-induced colitis in mice. Our research highlighted the significant role of gut microbiota in the piperine-mediated alleviation of intestinal damage and suggested its therapeutic potential for promoting gut health and reducing the risk of colitis.}, } @article {pmid40455241, year = {2025}, author = {Yi, LT and Wang, XY and Zhou, L and Cheng, J and Xu, GH and Zhu, JX}, title = {Polysaccharides from Black Mulberry Attenuate Colitis through Gut Microbiota Mediated TNF-α/pNF-κB/ICAM-1 Signaling Pathway.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {23}, pages = {14314-14332}, doi = {10.1021/acs.jafc.5c01870}, pmid = {40455241}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Morus/chemistry ; *Colitis/drug therapy/microbiology/genetics/metabolism/immunology ; *Polysaccharides/administration & dosage ; Mice ; *NF-kappa B/genetics/metabolism/immunology ; *Tumor Necrosis Factor-alpha/genetics/immunology/metabolism ; Signal Transduction/drug effects ; *Plant Extracts/administration & dosage ; Male ; Humans ; Mice, Inbred C57BL ; Dextran Sulfate/adverse effects ; Bacteria/classification/isolation & purification/genetics ; }, abstract = {Colitis is characterized by immune dysregulation and gut microbiota imbalance. This study investigates the therapeutic effects of polysaccharides from black mulberry (PBM) on dextran sulfate sodium-induced colitis in mice. PBM administration significantly alleviated colitis symptoms, including body weight loss, histological damage, and inflammation, while enhancing antioxidant capacity and strengthening tight junction protein expression. PBM modulated gut microbiota composition, notably increasing Weissella spp., which correlated with elevated short-chain fatty acids (SCFAs) and decreased pro-inflammatory markers. Colonic RNA sequencing revealed the role of PBM in attenuating colitis via the TNF-α/NF-κB/ICAM-1 signaling pathway. Fecal microbiota transplantation (FMT) from PBM-treated mice confirmed that microbiota modulation from PBM contributed to these therapeutic effects. These findings suggest PBM as a natural therapeutic agent for colitis, offering a multifaceted approach to restoring gut homeostasis through microbiota modulation and inflammatory pathway regulation. This study provides new insights into dietary polysaccharides as potential adjunctive therapies for colitis.}, } @article {pmid40454811, year = {2025}, author = {Millard, SA and Vendrov, KC and Young, VB and Seekatz, AM}, title = {Host origin of microbiota drives functional recovery and Clostridioides difficile clearance in mice.}, journal = {mBio}, volume = {16}, number = {7}, pages = {e0110825}, pmid = {40454811}, issn = {2150-7511}, support = {P20GM146584, P20GM139769/NH/NIH HHS/United States ; U19 AI090871/AI/NIAID NIH HHS/United States ; P20 GM146584/GM/NIGMS NIH HHS/United States ; K01-DK111794/NH/NIH HHS/United States ; AI124255, AI090871/NH/NIH HHS/United States ; K01 DK111794/DK/NIDDK NIH HHS/United States ; U01 AI124255/AI/NIAID NIH HHS/United States ; R35 GM150609/GM/NIGMS NIH HHS/United States ; P20 GM139769/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Clostridium Infections/therapy/microbiology ; *Fecal Microbiota Transplantation ; Mice ; *Clostridioides difficile/physiology ; *Gastrointestinal Microbiome ; Humans ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; Disease Models, Animal ; Mice, Inbred C57BL ; Female ; Male ; Metagenomics ; Metabolomics ; }, abstract = {UNLABELLED: Colonization resistance provided by the gut microbiota is essential for resisting both initial Clostridioides difficile infection (CDI) and potential recurrent infection (rCDI). Although fecal microbiota transplantation (FMT) has been successful in treating rCDI by restoring microbial composition and function, mechanisms underlying the efficacy of standardized stool-derived products remain poorly understood. Using a combination of 16S rRNA gene-based and metagenomic sequencing alongside metabolomics, we investigated microbiome recovery following FMT from human and murine donor sources in a mouse model of rCDI. We found that a human-derived microbiota was less effective in clearing C. difficile compared to a mouse-derived microbiota, despite recovery of taxonomic diversity, compositional changes, and bacterial functions typically associated with clearance. Metabolomic analysis revealed deficits in secondary metabolites compared to those that received murine FMT, suggesting a functional remodeling between human microbes in their new host environment. Collectively, our data revealed additional environmental, ecological, or host factors to consider in FMT-based recovery from rCDI.

IMPORTANCE: Clostridioides difficile is a significant healthcare-associated pathogen, with recurrent infections presenting a major treatment challenge due to further disruption of the microbiota after antibiotic administration. Despite the success of fecal microbiota transplantation (FMT) for the treatment of recurrent infection, the mechanisms mediating its efficacy remain underexplored. This study reveals that the effectiveness of FMT may be compromised by a mismatch between donor microbes and the recipient environment, leading to deficits in key microbial metabolites. These findings highlight additional factors to consider when assessing the efficacy of microbial-based therapeutics for C. difficile infection (CDI) and other conditions.}, } @article {pmid40454495, year = {2025}, author = {Bjørklund, G and Butnariu, M and Dadar, M and Semenova, Y}, title = {The Gut Microbiota-anxiety Connection: Evidence, Mechanisms, and Therapeutic Strategies.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0109298673356125250409182218}, pmid = {40454495}, issn = {1875-533X}, abstract = {The gut-brain axis (GBA), a bidirectional communication system between the gut and the brain, has emerged as a critical player in mental health. The interest in the connection between anxiety disorders (AD) and the gut microbiota is growing. This paper provides an overview of gut microbiota's role in dysregulation in anxiety, including alterations in gut microbiota (dysbiosis), leaky gut, metabolic endotoxemia, and the effect of antipsychotic medications. The mechanisms underlying the gut microbiota-anxiety (GMA) connection, such as neurotransmitter production, immune dysregulation, and GBA communication, are discussed. Furthermore, the paper explores gut microbiota- based therapeutic strategies, including probiotics, prebiotics, symbiotics, fecal microbiota transplantation, and dietary interventions, as potential approaches for anxiety management. This research field's clinical implications and future directions are also examined, underscoring that more studies are needed on gut microbiota's role in anxiety disorders. The conclusion highlights the importance of this ongoing research and the potential for personalized therapeutic interventions, instilling hope and optimism for the future of anxiety management and providing reassurance about the potential for personalized therapeutic interventions in this field.}, } @article {pmid40454186, year = {2025}, author = {Sharma, VK}, title = {Diabetes-induced depression: unravelling the role of gut dysbiosis.}, journal = {Journal of diabetes and metabolic disorders}, volume = {24}, number = {1}, pages = {129}, pmid = {40454186}, issn = {2251-6581}, abstract = {Depression is a prevalent yet often underdiagnosed neuropsychiatric comorbidity of type 2 diabetes mellitus (T2DM), significantly complicating disease management, treatment adherence, and overall well-being. Emerging evidence suggests that gut microbiota dysbiosis plays a pivotal role in linking T2DM and depression through mechanisms such as epithelial barrier dysfunction, systemic inflammation, neurotransmitter imbalances, hypothalamic-pituitary-adrenal (HPA) axis dysregulation, and impaired neurogenesis. This review aims to explore the mechanistic pathways through which diabetes-induced dysbiosis contributes to depression and to appraise the therapeutic potential of microbiota-targeted interventions, including probiotics, prebiotics, and fecal microbiota transplantation, in mitigating depressive symptoms and improving metabolic outcomes. Understanding this gut-brain interplay may provide novel insights into therapeutic strategies for managing the dual burden of diabetes and depression.}, } @article {pmid40448308, year = {2025}, author = {Gu, BH and Jung, HY and Rim, CY and Kim, TY and Lee, SJ and Choi, DY and Park, HK and Kim, M}, title = {Comparative Colonisation Ability of Human Faecal Microbiome Transplantation Strategies in Murine Models.}, journal = {Microbial biotechnology}, volume = {18}, number = {6}, pages = {e70173}, pmid = {40448308}, issn = {1751-7915}, support = {2024-ER2113-00//the Korea National Institute of Health (KNIH) research project/ ; 20019505//the Ministry of Trade, Industry & Energy (MOTIE, Korea)/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Humans ; Mice ; *Gastrointestinal Microbiome ; *Feces/microbiology ; Disease Models, Animal ; *Bacteria/classification/growth & development/isolation & purification/genetics ; Dysbiosis/therapy/microbiology ; Male ; Models, Animal ; }, abstract = {The gut microbiome plays a crucial role in maintaining intestinal homeostasis and influencing immune-mediated diseases. Human faecal microbiota transplantation (FMT) is often employed in murine models to investigate the role of human microbes in disease regulation, but methods for effective colonisation require refinement. This study aimed to assess the colonisation efficiency of human microbiota in a murine model using FMT with human faeces, focusing particularly on the impact of gut microbiota depletion via polyethylene glycol (PEG) and comparing oral-gastric gavage with enema administration routes. Our findings revealed that PEG-induced depletion enhanced human microbiome colonisation in mice. Oral-gastric gavage prolonged colonisation, while enema administration facilitated quicker resolution of dysbiosis, both inducing selective human microbial colonisation in a time-dependent manner. Notably, genera such as Bacteroides, Blautia, Medicaternibacter and Bifidobacteria were successfully colonised, whereas Roseburia, Anaerostipes, Anaerobutyricum and Faecalibacterium failed to establish in the murine gut post-FMT. These findings highlight the challenges of replicating human gut microbiota in murine models and underscore the importance of selecting appropriate FMT methods based on desired outcomes. This study provides valuable insights into the colonisation dynamics of human microbiota in mice, contributing to the development of more effective FMT strategies for disease treatment.}, } @article {pmid40448218, year = {2025}, author = {Gao, ZK and Fan, CY and Zhang, BW and Geng, JX and Han, X and Xu, DQ and Arshad, M and Sun, HX and Li, JY and Jin, X and Mu, XQ}, title = {Cardiac function of colorectal cancer mice is remotely controlled by gut microbiota: regulating serum metabolites and myocardial cytokines.}, journal = {Animal microbiome}, volume = {7}, number = {1}, pages = {53}, pmid = {40448218}, issn = {2524-4671}, support = {NSFC81903631//The National Natural Science Foundation of China/ ; }, abstract = {Several studies have indicated that the dysregulation of microbial metabolites and the inflammatory environment resulting from microbial dysbiosis may contribute to the occurrence and progression of cardiovascular diseases. Therefore, restoring the disordered gut microbiota in patients with colorectal cancer by fecal microbiota transplantation (FMT) has the potential to reduce the incidence of cardiac disease. In this study, we identified cardiac dysfunction in azomethane and dextran sodium sulfate-induced colorectal cancer mice. Intestinal microbes from healthy mice were transferred to colorectal cancer mice, which vastly reversed the disorder of the gut microbiota and effectively alleviated cardiac dysfunction. Moreover, FMT regulated the expression of serum metabolites such as uridine triphosphate (UTP), tiamulin, andrographolide, and N-Acetyl-D-glucosamine, as well as cytokines like TGF-β, IRF5, and β-MHC in the heart. These findings uncover that the disturbed gut microbiota causes cardiac dysfunction in colorectal cancer mice by modulating the expression of serum metabolites and cytokines, which could be alleviated by treatment with FMT.}, } @article {pmid40447159, year = {2025}, author = {Jeong, SH and Vasavada, SP and Lashner, B and Werneburg, GT}, title = {Fecal Microbiota Transplant Is Associated With Resolution of Recurrent Urinary Tract Infection.}, journal = {Urology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.urology.2025.05.052}, pmid = {40447159}, issn = {1527-9995}, abstract = {OBJECTIVE: To investigate the association of fecal microbiota transplant (FMT) therapy, an effective treatment for recurrent Clostridoides difficile colitis, with resolution of recurrent UTI (rUTI).

METHODS: A prospectively accrued database of patients who underwent FMT for recurrent C difficile colitis was retrospectively reviewed for individuals with rUTI in the 2 years prior to FMT. rUTI status (defined as two UTI episodes in 6 months or three UTI episodes in 1 year) and UTI frequency in the 2 years prior to the FMT were compared to those in the 2 year follow up period after FMT using the two-tailed Wilcoxin matched pairs signed rank test. A P value <.05 was considered statistically significant.

RESULTS: Of 11 patients who had rUTI in the 2 years preceding FMT, no patient had rUTI over the follow up period following FMT (P = .001). The average number of UTIs in the two years prior to FMT was 3.7 (range 2-6), and the average number of UTIs in the follow up period was 0.27 (range 0-1) (P = .001). The Kaplan-Meier estimate, the median time to UTI recurrence, was 19.6 months (95% CI: 15.2-23.9). There was no marked difference in antibiotic susceptibility profiles before and after FMT.

CONCLUSION: FMT was associated with resolution of rUTI and reduction in UTI frequency in this cohort. The results of this study support the hypothesis that modulation of the gut microbiome may reduce rUTI risk and support a clinical trial to further assess the safety and efficacy of FMT for rUTI.}, } @article {pmid40446472, year = {2025}, author = {Chen, L and Ahmad, M and Li, J and Li, J and Yang, Z and Hu, C}, title = {Gut microbiota manipulation to mitigate the toxicities of environmental pollutants.}, journal = {Aquatic toxicology (Amsterdam, Netherlands)}, volume = {285}, number = {}, pages = {107425}, doi = {10.1016/j.aquatox.2025.107425}, pmid = {40446472}, issn = {1879-1514}, mesh = {*Gastrointestinal Microbiome/drug effects ; Probiotics ; Animals ; Prebiotics/administration & dosage ; *Environmental Pollutants/toxicity ; Fecal Microbiota Transplantation ; Humans ; }, abstract = {The gut microbiome, commonly termed as a "super organ", plays a crucial role in the modulation of various biological functions associated with metabolism, endocrinology, immunology, and neurology. However, gut microbiome is extremely susceptible to the risks of environmental pollutants, which will drive gut microbial community to dysbiosis. Simultaneously, restoring healthy gut microbiome can protect the hosts from the health hazards of pollutants. It is increasingly verified that probiotics, prebiotics, and fecal microbiota transplantation (FMT) are efficacious measures to manipulate and remediate gut microecosystem. Among various probiotic strains, lactic acid bacteria are the most extensively applied in toxicity mitigation, which is characterized by shaping gut microbiota structure and metabolism, increasing gut epithelial barrier integrity, promoting fecal elimination of pollutants, suppressing inflammation symptoms, and then improving host systemic physiology. Prebiotics are dietary fibers that cannot be digested by the host, but can be fermented by specific gut bacteria to produce short chain fatty acids, which are identified as the key effect molecules in the manifestation of prebiotic toxicity mitigation actions. In addition, by transplanting the entire community of healthy gut microbiota, FMT also shows effective performances in counteracting the adverse effects of environmental pollutants and recovering host animal health. Intriguingly, FMT from young donors is even found to inhibit the toxic disturbances in healthy aging progression. Based on current evidence, this review summarized the findings about using probiotics, prebiotics, and FMT to manipulate gut microbiota and alleviate the health impairment of environmental pollutants. Key mechanistic insights into the interactive behaviors were underlined. Furthermore, the challenges and future directions in harnessing gut microbiota manipulation as a novel therapeutic approach to mitigate pollutant-induced toxicities were postulated. This review is expected to advocate comprehensive scientific research and literally favor the application of health intervention strategies.}, } @article {pmid40446358, year = {2025}, author = {Porcari, S and Ng, SC and Zitvogel, L and Sokol, H and Weersma, RK and Elinav, E and Gasbarrini, A and Cammarota, G and Tilg, H and Ianiro, G}, title = {The microbiome for clinicians.}, journal = {Cell}, volume = {188}, number = {11}, pages = {2836-2844}, doi = {10.1016/j.cell.2025.04.016}, pmid = {40446358}, issn = {1097-4172}, mesh = {Humans ; *Microbiota ; Clinical Trials as Topic ; }, abstract = {Despite promising evidence in diagnostics and therapeutics, microbiome research is not yet implemented into clinical medicine. Several initiatives, including the standardization of microbiome research, the refinement of microbiome clinical trial design, and the development of communication between microbiome researchers and clinicians, are crucial to move microbiome science toward clinical practice.}, } @article {pmid40444969, year = {2025}, author = {Xie, J and Kim, T and Liu, Z and Panier, H and Bokoliya, S and Xu, M and Zhou, Y}, title = {Young gut microbiota transplantation improves the metabolic health of old mice.}, journal = {mSystems}, volume = {10}, number = {6}, pages = {e0160124}, pmid = {40444969}, issn = {2379-5077}, support = {R01 AG068860/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation/methods ; Mice ; Male ; *Aging/metabolism ; Mice, Inbred C57BL ; Body Composition ; }, abstract = {UNLABELLED: The gut microbiota evolves over a lifetime and significantly impacts the aging process. Targeting the gut microbiota represents a novel avenue to delay aging and aging-related physical and mental decline. However, the underlying mechanism by which the microbiota modulates the aging process, particularly age-related physical and behavioral changes is not completely understood. We conducted fecal microbiota transplantation (FMT) from young or old male donor mice to the old male recipients. Old recipients with young microbiota had a higher alpha diversity than the old recipients with old microbiota. Compared to FMT with old microbiota, FMT with young microbiota reduced body weight and prevented fat accumulation in the old recipients. FMT with young microbiota also lowered frailty, increased grip strength, and alleviated depression and anxiety-like behavior in the old recipients. Consistent with observed physical changes, untargeted metabolomic analysis of serum and stools revealed that FMT with young microbiota lowered age-related long-chain fatty acid levels and increased amino acid levels in the old recipients. Bulk RNAseq analysis of the amygdala of the brain showed that FMT with young microbiota downregulated inflammatory pathways and upregulated oxidative phosphorylation in the old recipients. Our results demonstrate that FMT with young microbiota has substantial positive influences on age-related body composition, frailty, and psychological behaviors. These effects are associated with changes in host lipid and amino acid metabolism in the periphery and transcriptional regulation of neuroinflammation and energy utilization in the brain.

IMPORTANCE: The gut microbiome is a key hallmark of aging. Fecal microbiota transplantation (FMT) using young microbiota represents a novel rejuvenation strategy to delay aging. Our study provides compelling evidence that transplanting microbiota from young mice significantly improved grip strength, frailty, and body composition in aged recipient mice. At the molecular level, FMT improved aging-related metabolic markers in the gut and circulation. Additionally, FMT from young microbiota rejuvenated the amygdala of the aged brain by downregulating inflammatory pathways. This study highlights the importance of metabolic reprogramming via young microbiota FMT in improving physical and metabolic health in elderly recipients.}, } @article {pmid40443229, year = {2025}, author = {Lee, MA and Slead, T and Suchodolski, J and Tolbert, MK and Marsilio, S}, title = {Adverse events after fecal microbiota transplantation in nine cats: a case series.}, journal = {Journal of feline medicine and surgery}, volume = {27}, number = {5}, pages = {1098612X251337274}, pmid = {40443229}, issn = {1532-2750}, mesh = {Animals ; Cats ; *Cat Diseases/therapy ; *Fecal Microbiota Transplantation/veterinary/adverse effects ; Female ; Male ; Diarrhea/veterinary/therapy ; }, abstract = {This case series describes nine cases of fecal microbiota transplantation in cats and associated adverse events (AEs) from two tertiary referral hospitals. AEs were graded according to criteria established by the Veterinary Cooperative Oncology Group's Common Terminology Criteria for Adverse Events (VCOG-CTCAE v2) for clinical trials. Cats received 5-6 g/kg donor feces 2-6 times for chronic enteropathy (n = 4) or therapy-resistant diarrhea (n = 5). AEs included lethargy (n = 7), vomiting (n = 5), diarrhea (n = 5), weight loss (n = 5), inappetence (n = 5), dehydration (n = 5), abdominal pain (n = 2), gastroenterocolitis based on ultrasound (n = 2) and anorexia (n = 1). Temperatures of up to 103.4°F were noted but did not meet the criteria for AEs (>103.5°F). Cats responded to antimicrobials (metronidazole, marbofloxacin), anthelmintics (fenbendazole), supportive care with fluids, ondansetron and mirtazapine (n = 5), gabapentin (n = 2), pradofloxacin (n = 1) or self-resolved (n = 1). Positive response to fecal microbiota transplantation for the presenting complaint was seen in eight cats (seven complete, one partial and transient).Relevance and novel informationFecal microbiota transplantation is increasing in usage among companion animals. Fecal microbiota transplantations in cats have been rarely described in the literature as have AEs after administration. This case series represents the first description of AEs after fecal microbiota transplantation in cats.}, } @article {pmid40443227, year = {2025}, author = {Green, GBH and Cox-Holmes, AN and Marlow, GH and Potier, ACE and Wang, Y and Zhou, L and Chen, D and Morrow, CD and McFarland, BC}, title = {Human microbiota influence the immune cell composition and gene expression in the tumor environment of a murine model of glioma.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2508432}, pmid = {40443227}, issn = {1949-0984}, support = {P30 CA013148/CA/NCI NIH HHS/United States ; R01 CA270750/CA/NCI NIH HHS/United States ; T32 NS121721/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Glioma/immunology/microbiology/genetics ; Mice ; Humans ; *Gastrointestinal Microbiome/immunology ; Disease Models, Animal ; *Tumor Microenvironment/immunology/genetics ; *Brain Neoplasms/immunology/microbiology/genetics ; Cell Line, Tumor ; Feces/microbiology ; Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology ; RNA, Ribosomal, 16S/genetics ; Bacteria/classification/genetics/isolation & purification ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Immunotherapy has shown success against other cancers but not glioblastoma. Previous data has revealed that microbiota influences anti-PD-1 efficacy. We have previously found that, when using gnotobiotic mice transplanted with human fecal microbiota, the gut microbial composition influenced the response to anti-PD-1 in a mouse model of glioma. However, the role of the human microbiota in influencing the mouse immune cells in the glioma microenvironment and anti-PD-1 response was largely unknown. Using two distinct humanized microbiome (HuM) lines, we used single-cell RNA sequencing (scRNA-seq) to determine how gut microbiota affect immune infiltration and gene expression in a murine glioma model.

METHODS: 16S rRNA sequencing was performed on fecal samples from HuM1 (H1) and HuM2 (H2) mice. Mice were intracranially injected with murine glioma cells (GL261), and on day 13 treated with one dose of isotype control or anti-PD1. Mice were euthanized on day 14 for analysis of all immune cells in the tumors by scRNA-seq.

RESULTS: HuM1 and HuM2 mice had different microbial populations, with HuM1 being primarily dominated via Alistipes, and HuM2 being primarily composed of Odoribacter. Sc-RNA-seq of the tumor immune cells revealed 21 clusters with significant differences between H1 and H2 samples with a larger population of M1 type macrophages in H1 samples. Gene expression analysis revealed higher expression of inflammatory markers in the M1 population in H2 mice treated with anti-PD-1.

CONCLUSIONS: Microbial gut communities influence the presence and gene activation patterns of immune cells in the brain tumors of mice both under control (isotype) and following anti-PD-1 treatment.}, } @article {pmid40441587, year = {2025}, author = {Luo, M and Du, Y and Liu, X and Zhang, S and Zhu, W and Liu, K and Ren, X and Zhang, N}, title = {Fecal microbiota transplantation alleviates cirrhotic portal hypertension in rats via butyrate-mediated HDAC3 inhibition and PI3K/Akt/eNOS signaling regulation.}, journal = {European journal of pharmacology}, volume = {1002}, number = {}, pages = {177781}, doi = {10.1016/j.ejphar.2025.177781}, pmid = {40441587}, issn = {1879-0712}, mesh = {Animals ; *Hypertension, Portal/therapy/etiology/microbiology ; *Fecal Microbiota Transplantation ; Proto-Oncogene Proteins c-akt/metabolism ; Rats, Sprague-Dawley ; Male ; *Histone Deacetylases/metabolism ; Rats ; Signal Transduction/drug effects ; Nitric Oxide Synthase Type III/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; *Butyrates/pharmacology/metabolism ; *Histone Deacetylase Inhibitors/pharmacology ; Gastrointestinal Microbiome ; *Liver Cirrhosis/therapy/complications ; Liver/pathology ; Endothelial Cells/metabolism ; }, abstract = {BACKGROUND: Portal hypertension (PHT) is a severe complication of liver cirrhosis, with limited therapeutic options. Despite emerging evidence linking gut microbiota dysbiosis to PHT progression, the mechanisms by which microbial metabolites modulate liver sinusoidal endothelial cells (LSECs) dysfunction and the therapeutic efficacy of fecal microbiota transplantation (FMT) remain poorly understood. This study investigated the potential of FMT to alleviate PHT in cirrhotic rats, exploring the underlying mechanisms involving butyrate-mediated HDAC3 inhibition and PI3K/Akt/eNOS signaling regulation in LSECs.

METHODS: Cirrhosis with PHT was induced in Sprague-Dawley rats via intraperitoneal carbon tetrachloride injection, followed by FMT or butyrate supplementation via oral gavage. Analyses included portal hemodynamic measurements, gut microbiota sequencing, serum SCFA metabolomics profiling, HDAC3 activity assays, NO level quantification, and assessments of liver fibrosis, liver function, and LSEC ultrastructure. LSECs were isolated for PI3K/Akt/eNOS signaling analysis via qRT-PCR, Western blotting, and immunofluorescence staining.

RESULTS: A two-week FMT intervention in cirrhotic rats with PHT enriched butyrate-producing bacteria and increased serum butyrate levels, which were associated with reduced portal pressure and intrahepatic vascular resistance, without affecting liver fibrosis, function, or LSEC ultrastructure. FMT reduced HDAC3 activity by 2.17-fold and increased Akt and eNOS phosphorylation in primary LSECs by 1.69-fold and 1.25-fold, respectively, elevating plasma NO levels by 1.66-fold compared to untreated controls. In vitro experiments with primary LSECs confirmed these butyrate-mediated effects.

CONCLUSION: FMT alleviates cirrhotic PHT through butyrate-mediated HDAC3 inhibition and subsequent PI3K/Akt/eNOS signaling activation in LSECs, highlighting the therapeutic potential of targeting the gut-liver axis via microbial metabolites for PHT management.}, } @article {pmid40441086, year = {2025}, author = {Sharma, P and Das, S and Rituraj, R and Bhagyashree, B}, title = {Understanding oncobiosis in ovarian cancer: Emerging concepts in tumor progression.}, journal = {Pathology, research and practice}, volume = {271}, number = {}, pages = {156026}, doi = {10.1016/j.prp.2025.156026}, pmid = {40441086}, issn = {1618-0631}, mesh = {Humans ; Female ; *Ovarian Neoplasms/pathology/microbiology ; *Tumor Microenvironment ; *Dysbiosis/microbiology ; Disease Progression ; *Microbiota ; }, abstract = {Ovarian cancer is a leading cause of gynecologic cancer mortality and has recently been linked to microbial dysbiosis or oncobiosis. Tumorigenesis is a highly complex process, and recent research has revealed numerous new mechanisms showing how tumors interact with their surrounding microenvironment. The inclusion of microbiome studies has significantly advanced this field revealing the important role microbes play, not only in maintaining normal physiological functions of the human body but also in influencing oncogenic pathways. This expanding knowledge is deepening our understanding of tumor pathophysiology and is helping to create new diagnostic, prognostic, therapeutic and preventive strategies for specific cancers. This review explores the role of the microbiome in ovarian carcinogenesis, focusing on its interaction with the tumor microenvironment (TME) and its influence on inflammation, immune regulation and metabolic signaling. This review studied dysbiosis in several anatomical compartments such as the gut, oral cavity, lower and upper genital tracts and ovarian tissues, in relation to ovarian oncobiosis. Emerging clinical implications of these studies include the use of microbial profiles as diagnostic or prognostic biomarkers. Therapeutic strategies such as fecal microbiota transplantation and probiotics are also discussed for their ability to restore microbial balance and enhance treatment efficacy. This review highlights the importance of continued research to explore causal relationships between the microbiome and tumorigenesis, positioning microbiome studies as promising tools in ovarian cancer management and improving patient care.}, } @article {pmid40438840, year = {2025}, author = {Saleem, MM and Masood, S and Rahmatullah, MM and Ayesha Imdad, I and Mohammed Aslam Sange, A and Nasr, D}, title = {Gut Microbiota Dysbiosis and Its Role in the Development of Irritable Bowel Syndrome.}, journal = {Cureus}, volume = {17}, number = {4}, pages = {e83084}, pmid = {40438840}, issn = {2168-8184}, abstract = {The gut microbiota refers to the diverse community of symbiotic and pathogenic microorganisms inhabiting the host digestive tract. This microbiome plays a vital role in maintaining the integrity of the digestive system. Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID) characterized by chronic abdominal pain and altered bowel habits. Although the pathophysiology of IBS remains unclear, recent studies suggest that the disruption of the gut microbiota (dysbiosis) may play a significant role. This study aims to examine the role of the gut microbiota in the development of IBS, analyze factors influencing the gut microbiome, and explore the potential for microbiota-targeted therapies. Relevant literature published from 2014 until 2024 was sourced from Google Scholar, PubMed, and Scopus using the keywords "microbiome", "irritable bowel syndrome", "dysbiosis", "faecal transplantation", and "probiotics". This review revealed consistent evidence of gut microbiota dysbiosis in individuals with IBS, characterized by altered microbial diversity, composition, and metabolic function. Contributing factors included a reduced abundance of beneficial commensals, overgrowth of potentially pathogenic species, and disrupted host-microbiota interactions. This dysbiosis was also frequently associated with symptom severity and specific IBS subtypes. Emerging evidence further highlights the role of diet, stress, and genetic factors in modulating gut microbiota and influencing IBS development. The growing body of research supports a strong link between dysbiosis and the pathogenesis and symptomatology of IBS. Understanding the microbial underpinnings of IBS opens avenues for potential diagnostic biomarkers and innovative therapeutic interventions aimed at restoring a balanced gut microbiota. However, further research is needed to elucidate the underlying mechanisms and translate these insights into effective clinical strategies for the management of IBS. This review underscores the significance of gut microbiota in IBS and its potential as a target for future therapeutic interventions.}, } @article {pmid40438215, year = {2025}, author = {Hanna, A and Abbas, H and Yassine, F and AlBush, A and Bilen, M}, title = {Systematic review of gut microbiota composition, metabolic alterations, and the effects of treatments on PCOS and gut microbiota across human and animal studies.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1549499}, pmid = {40438215}, issn = {1664-302X}, abstract = {INTRODUCTION: Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting around 12% of women globally, associated with infertility and various comorbidities. Emerging evidence suggests a crucial role of gut microbiota in PCOS pathophysiology, prompting research to investigate alterations in gut microbial composition in patients with PCOS.

METHODS: This systematic review aims to analyze human and animal studies that compare gut microbiota composition, gut-derived metabolites, and treatment interventions in PCOS patients versus healthy controls. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science, yielding studies examining gut microbiota, metabolomic shifts, and treatment responses in PCOS models and human populations.

RESULTS: Our analysis revealed decreases in alpha diversity in PCOS patients, with more pronounced changes in beta diversity in animal models. Specific bacterial taxa, such as Bacteroides vulgatus, Escherichia-Shigella and Lactobacillus, showed implication in PCOS pathogenesis, suggesting potential microbial markers. Furthermore, discrepancies between human and animal studies show the need for humanized mouse models to bridge this gap. Interventions like probiotics and fecal microbiota transplantation (FMT) showed varying levels of efficacy, with FMT emerging as a more promising but invasive option, offering live bacteriotherapy as a potential therapeutic alternative. Alterations in gut-derived metabolites, including short-chain fatty acids and bile acids, highlighted the multifaceted nature of PCOS, with implications extending to metabolic, hormonal, and gut-brain axis disruptions.

DISCUSSION: In conclusion, PCOS exhibits complex interactions between gut microbiota and metabolic pathways, necessitating further research with standardized methods and larger sample sizes to elucidate the microbiome's role in PCOS.}, } @article {pmid40437401, year = {2025}, author = {Unrug-Bielawska, K and Sandowska-Markiewicz, Z and Pyśniak, K and Piątkowska, M and Czarnowski, P and Goryca, K and Mróz, A and Żeber-Lubecka, N and Wójcik-Trechcińska, U and Bałabas, A and Dąbrowska, M and Surynt, P and Radkiewicz, M and Mikula, M and Ostrowski, J}, title = {Western Diet and fecal microbiota transplantation alter phenotypic, liver fatty acids, and gut metagenomics and metabolomics in Mtarc2 knockout mice.}, journal = {Genes & nutrition}, volume = {20}, number = {1}, pages = {13}, pmid = {40437401}, issn = {1555-8932}, support = {2018/29/B/NZ7/00809//Narodowe Centrum Nauki/ ; }, abstract = {BACKGROUND: The mitochondrial amidoxime-reducing component-2 (Mtarc) enzyme complex is located on the outer mitochondrial membrane and may be involved in lipid metabolism regulation.

AIM: This study evaluated the impact of fecal microbiota transplantation (FMT) on phenotypic outcomes, liver accumulation of fatty acids (FAs), and modifications to the gut microbial community, as well as the abundance of short-chain fatty acids (SCFAs) and amino acids (AAs), in both sexes of Mtarc2 knockout (Mtarc2-KO) and C57BL/6 N mice fed a Western Diet (WD).

METHODOLOGY: Mice were fed a WD (study groups) or normal diet (control groups) and were subjected to intestinal flushing with either a polyethylene glycol (PEG) solution (study groups) or water (control groups); this was followed by intragastrical administration of a human feces suspension (study groups) or water (control groups). Liver FA composition and fecal SCFAs and AAs were measured by mass spectrometry. Metagenomic-based analysis was performed by sequencing the variable V3 and V4 regions of the bacterial 16 S rRNA gene.

PRINCIPAL FINDINGS: Weight gain in C57BL/6 N mice fed a WD was significantly higher than in Mtarc2-KO mice. Compared with water only, intestinal cleansing with PEG resulted in significantly lower weight gain in C57BL/6 N mice but not in Mtarc2-KO mice. FMT did not affect body weight in C57BL/6 N mice, and decreased in Mtarc2-KO females and males fed a ND and a WD, respectively. No significant differences in liver FAs composition were found between mouse strains. While PEG treatment significantly affected liver FAs composition, FMT modulated FAs levels to a much smaller extent. However, neither intestinal cleansing nor FMT affected the microscopic findings of fatty liver. WD feeding affected bacterial diversity, taxonomy and SCFAs and AAs abundances in Mtarc2-KO and C57BL/6 N mice not subjected to PEG treatment. Both intestinal cleansing alone and FMT modulated gut bacterial composition, especially in C57BL/6 N mice, and metabolite abundances in Mtarc2-KO mice.

CONCLUSION: WD and FMT differentially modified phenotypic parameters, liver FA composition, and gut bacteria in comparisons between Mtarc2-KO and C57BL/6 N. This suggests the Mtarc complex plays a significant role in regulating energy metabolism in mice.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12263-025-00772-x.}, } @article {pmid40436727, year = {2025}, author = {Qingsong, L}, title = {Comment on "Alteration of gut microbial composition associated with the therapeutic efficacy of fecal microbiota transplantation in Clostridium difficile infection".}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jfma.2025.05.033}, pmid = {40436727}, issn = {0929-6646}, } @article {pmid40433559, year = {2025}, author = {Zhang, J and Chen, K and Chen, F}, title = {Exploring the impact of the liver-intestine-brain axis on brain function in non-alcoholic fatty liver disease.}, journal = {Journal of pharmaceutical analysis}, volume = {15}, number = {5}, pages = {101077}, pmid = {40433559}, issn = {2214-0883}, abstract = {This study investigates the molecular complexities of non-alcoholic fatty liver disease (NAFLD)-induced brain dysfunction, with a focus on the liver-intestine-brain axis and potential therapeutic interventions. The main objectives include understanding critical microbiota shifts in NAFLD, exploring altered metabolites, and identifying key regulatory molecules influencing brain function. The methods employed encompassed 16S ribosomal RNA (rRNA) sequencing to scrutinize stool microbiota in NAFLD patients and healthy individuals, non-targeted metabolomics using LC-MS to uncover elevated levels of deoxycholic acid (DCA) in NAFLD mice, and single-cell RNA sequencing (scRNA-seq) to pinpoint the pivotal gene Hpgd in microglial cells and its downstream Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. Behavioral changes and brain function were assessed in NAFLD mice with and without Fecal microbiota transplantation (FMT) treatment, utilizing various assays and analyses. The results revealed significant differences in microbiota composition, with increased levels of Bacteroides in NAFLD patients. Additionally, elevated DCA levels were observed in NAFLD mice, and FMT treatment demonstrated efficacy in ameliorating liver function and brain dysfunction. Hpgd inhibition by DCA activated the JAK2/STAT3 pathway in microglial cells, leading to inflammatory activation, inhibition of mitochondrial autophagy, induction of neuronal apoptosis, and reduction in neuronal action potentials. This study elucidates the intricate molecular mechanisms underlying the liver-gut-brain axis in NAFLD, and the identification of increased DCA and the impact of JAK2/STAT3 signaling on microglial cells highlight potential therapeutic targets for addressing NAFLD-induced brain dysfunction.}, } @article {pmid40431274, year = {2025}, author = {Schiavone, N and Isoldi, G and Calcagno, S and Rovida, E and Antiga, E and De Almeida, CV and Lulli, M}, title = {Exploring the Gut Microbiota-Retina Axis: Implications for Health and Disease.}, journal = {Microorganisms}, volume = {13}, number = {5}, pages = {}, pmid = {40431274}, issn = {2076-2607}, abstract = {The gut microbiota represents a rich and adaptive microbial network inhabiting the gastrointestinal tract, performing key functions in nutrient processing, immune response modulation, intestinal wall protection, and microbial defense. Its composition remains highly personalized and responsive to external influences, including lifestyle patterns, physical activity, body composition, and nutritional intake. The interactions of the gut microbiota with bodily systems are conventionally interpreted as broad systemic impacts on organ balance. Yet, emerging research-exemplified by the gut microbiota-brain axis-suggests the potential existence of more targeted and direct communication mechanisms. Dysbiosis, characterized by microbial ecosystem disturbance, generates multiple metabolic compounds capable of entering systemic circulation and reaching distant tissues, notably including ocular structures. This microbial imbalance has been associated with both systemic and localized conditions linked to eye disorders. Accumulating scientific evidence now supports the concept of a gut-retina axis, underscoring the significant role of microbiota disruption in generating various retinal pathologies. This review comprehensively investigates gut microbiota composition, functional dynamics, and dysbiosis-induced alterations, with specific focus on retinal interactions in age-related macular degeneration, diabetic retinopathy, glaucoma, and retinal artery occlusion. Moreover, the review explores microbiota-targeted therapeutic strategies, including precision nutritional interventions and microbial transplantation, as potential modulators of retinal disease progression.}, } @article {pmid40431196, year = {2025}, author = {Harder, JW and Ma, J and Collins, J and Alard, P and Jala, VR and Bodduluri, H and Kosiewicz, MM}, title = {Characterization of Sex-Based Differences in Gut Microbiota That Correlate with Suppression of Lupus in Female BWF1 Mice.}, journal = {Microorganisms}, volume = {13}, number = {5}, pages = {}, pmid = {40431196}, issn = {2076-2607}, support = {Target Identification in Lupus Grant//Alliance for Lupus Research/ ; R01AR067188/NH/NIH HHS/United States ; }, abstract = {Systemic lupus erythematosus (SLE) is more prevalent in female mice and humans and is associated with microbiota dysbiosis. We analyzed the fecal microbiota composition in female and male NZBxNZWF1 (BWF1) mice, a model of SLE, using 16S RNA gene sequencing. Composition of gut microbiota differed between adult disease-prone female (pre-disease) and disease-resistant male mice. Transfer of male cecal contents by gavage into female mice suppressed kidney disease (decreased proteinuria) and improved survival. After our mouse colony was moved to a new barrier facility with similar housing, male cecal transplants failed to suppress disease in female recipients. After two years, the protective phenotype reemerged: male cecal transplants once again suppressed disease in female mice. We compared the gut microbiota composition in female and male BWF1 mice for the three different periods, during which the male microbiota either protected or failed to protect female recipients. In female vs. male mice and in female mice receiving male cecal transplants, we found Bacteroides was high, Clostridium was low (high Bacteroides/Clostridium ratio), and Alistipes was present during periods when male cecal transplants suppressed disease. These data suggest that specific bacterial populations may have opposing effects on disease suppression in a model of microbiota transplantation.}, } @article {pmid40431182, year = {2025}, author = {Matsumoto, H and Gu, T and Yo, S and Sasahira, M and Monden, S and Ninomiya, T and Osawa, M and Handa, O and Umegaki, E and Shiotani, A}, title = {Fecal Microbiota Transplantation Using Donor Stool Obtained from Exercised Mice Suppresses Colonic Tumor Development Induced by Azoxymethane in High-Fat Diet-Induced Obese Mice.}, journal = {Microorganisms}, volume = {13}, number = {5}, pages = {}, pmid = {40431182}, issn = {2076-2607}, support = {JP 19K11484//Japanese Grant-in-Aid Scientific Reserach/ ; }, abstract = {The gut microbiota plays an important role in the development of colorectal tumors. However, the underlying mechanisms remain unclear. In this study, we examined the effects of fecal microbiota transplantation (FMT) on azoxymethane (AOM)-induced colorectal tumors in obese mice. We divided the study subjects into the following five groups: high-fat diet (HFD), normal diet (ND), ND+exercise (Ex), HFD+FMT from ND-alone donor (HFD+FMT(ND alone)), and HFD+FMT from ND+Ex donor (HFD+FMT(ND+Ex)). The Ex group performed treadmill exercise for 15 weeks. Thereafter, fecal and colonic mucus samples were extracted for microbiome analysis. The deoxyribonucleic acid sample was collected from the feces and colonic mucosa, and V3-V4 amplicon sequencing analysis of the 16S rRNA gene was performed using MiSeq. The number of polyps was significantly lower in the ND (6.0 ± 1.6) and ND+Ex (1.8 ± 1.3) groups than in the HFD group (11.4 ± 1.5). The ND+Ex group had significantly fewer polyps than the ND group. The HFD+FMT(ND alone) (5.2 ± 0.8) and HFD+FMT(ND+Ex) (2.8 ± 2.6) groups also had significantly fewer polyps than the HFD group. The IL-15 mRNA levels in the colonic tissues were significantly higher in the HFD+FMT(ND alone) group than in the ND group. Fecal ω-muricholic acid concentrations were significantly higher in the HFD+FMT(ND alone) group than in the ND group and in the HFD+FMT(ND+Ex) group than in the ND+Ex group. The ND, ND+Ex, HFD+FMT(ND alone), and HFD+FMT(ND+Ex) groups had a significantly higher abundance of Lacyobacillaceae than the HFD group. In the FMT group, Erysipelotrichaceae and Tannerellaceae were significantly less abundant. Compared with the HFD group, the ND, ND+Ex, HFD+FMT(ND alone), and HFD+FMT(ND+Ex) groups had a significantly higher abundance of Muribaculaceae and a significantly higher abundance of Lactobacillaceae and Rikenellaceae in common among the ND and ND+Ex groups. The common and significantly less common species were Bacteroidaceae in the FMT group and Lactobacillaceae and Rikenellaceae in the ND alone and ND+Ex groups. Bacteroidaceae and Lachnospiraceae were significantly less common in the FMT group. We found that FMT inhibited AOM-induced colorectal tumorigenesis in obese mice. Furthermore, the fecal concentrations of short-chain fatty acids, bile acids, microbiota, and mucosa-associated microbiota differed between the FMT and diet/EX groups, suggesting that the inhibitory effect of FMT on colorectal tumorigenesis may be due to mechanisms different from those of ND alone and ND+Ex.}, } @article {pmid40430481, year = {2025}, author = {Zhou, Q and Yang, C and Jia, M and Qu, Q and Peng, X and Ren, W and Li, G and Xie, Y and Li, B and Shi, X}, title = {Gut Microbiota-Targeted Intervention of Hyperlipidemia Using Monascus-Fermented Ginseng.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {18}, number = {5}, pages = {}, pmid = {40430481}, issn = {1424-8247}, support = {82174093//National Natural Science Foundation of China/ ; }, abstract = {Background/Objectives: Hyperlipidemia (HLP) encompasses a spectrum of poorly understood lipid metabolism disorders that are frequently overlooked or misdiagnosed, potentially leading to multiple complications. While the gut microbiota has been implicated in HLP pathogenesis, the causal relationships and molecular mechanisms remain elusive. This study aimed to investigate the therapeutic mechanisms of Monascus-fermented ginseng (MFG) on HLP through gut microbiota modulation and explore treatment potential via fecal microbiota transplantation (FMT). Methods: The MFG-modulated gut microbiota was transplanted into HLP mice. Systemic evaluations, including serum biochemical parameter detection, histopathological section analysis, 16S rRNA sequencing, and fecal metabolomics, were conducted to assess therapeutic efficacy and identify associated metabolic pathways. Results: FMT significantly improved lipid profiles, reduced body weight, and attenuated hepatic lipid accumulation in HLP mice. Mechanistically, it enhanced cholesterol excretion and fatty acid β-oxidation while suppressing lipogenic regulators, concurrently promoting primary-to-secondary bile acid conversion. Gut microbiota analysis revealed that the MFG intervention effectively normalized the Firmicutes/Bacteroidetes ratio and enriched beneficial microbiota. Conclusions: These findings demonstrate FMT's therapeutic value in HLP management and provide new perspectives on utilizing fermented herbal medicines for metabolic disorders via gut microbiota reprogramming.}, } @article {pmid40428769, year = {2025}, author = {Datkhayeva, Z and Iskakova, A and Mireeva, A and Seitaliyeva, A and Skakova, R and Kulniyazova, G and Shayakhmetova, A and Koshkimbayeva, G and Sarmuldayeva, C and Nurseitova, L and Koshenova, L and Imanbekova, G and Maxutova, D and Yerkenova, S and Shukirbayeva, A and Pernebekova, U and Dushimova, Z and Amirkhanova, A}, title = {The Multifactorial Pathogenesis of Endometriosis: A Narrative Review Integrating Hormonal, Immune, and Microbiome Aspects.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {5}, pages = {}, pmid = {40428769}, issn = {1648-9144}, mesh = {Humans ; *Endometriosis/physiopathology/microbiology/immunology/etiology ; Female ; *Gastrointestinal Microbiome/physiology/immunology ; Estrogens/metabolism ; Dysbiosis/complications ; Inflammation ; }, abstract = {Endometriosis (EM) is a common estrogen-dependent chronic inflammatory disorder affecting reproductive-aged women, yet its pathogenesis remains incompletely understood. Recent evidence suggests that the gut microbiota significantly influence immune responses, estrogen metabolism, and systemic inflammation, potentially contributing to EM progression. This narrative review explores the relationship between the gut microbiota and EM, emphasizing microbial dysbiosis, inflammation, estrogen regulation, and potential microbiome-targeted therapies. Studies published within the last 30 years were included, focusing on the microbiota composition, immune modulation, estrogen metabolism, and therapeutic interventions in EM. The selection criteria prioritized peer-reviewed articles, clinical trials, meta-analyses, and narrative reviews investigating the gut microbiota's role in EM pathophysiology and treatment. Microbial dysbiosis in EM is characterized by a reduced abundance of beneficial bacteria (Lactobacillus, Bifidobacterium, and Ruminococcaceae) and an increased prevalence of pro-inflammatory taxa (Escherichia/Shigella, Streptococcus, and Bacteroides). The gut microbiota modulate estrogen metabolism via the estrobolome, contributing to increased systemic estrogen levels and lesion proliferation. Additionally, lipopolysaccharides (LPS) from Gram-negative bacteria activate the TLR4/NF-κB signaling pathway, exacerbating inflammation and EM symptoms. The interaction between the gut microbiota, immune dysregulation, and estrogen metabolism suggests a critical role in EM pathogenesis. While microbiota-targeted interventions offer potential therapeutic benefits, further large-scale, multi-center studies are needed to validate microbial biomarkers and optimize microbiome-based therapies for EM. Integrating microbiome research with precision medicine may enhance the diagnostic accuracy and improve the EM treatment efficacy.}, } @article {pmid40427529, year = {2025}, author = {Daude, N and Machado, I and Arce, L and Yang, J and Westaway, D}, title = {Microbial Composition, Disease Trajectory and Genetic Background in a Slow Onset Model of Frontotemporal Lobar Degeneration.}, journal = {Biomolecules}, volume = {15}, number = {5}, pages = {}, pmid = {40427529}, issn = {2218-273X}, support = {N/A//Nanostring AD panel/ ; N/A//SynAD ADRD/ ; 16308/CAPMC/CIHR/Canada ; 173286/CAPMC/CIHR/Canada ; NIF 21633//Canada Foundation for Innovation/ ; NIF 39588//Canada Foundation for Innovation/ ; N/A//Campus Alberta Neuroscience/ ; APRIIEP201600033//Alberta Prion Research Institute/ ; N/A//Hope for Tomorrow/ ; }, mesh = {Animals ; Mice ; Mice, Transgenic ; Disease Models, Animal ; tau Proteins/metabolism/genetics ; *Frontotemporal Lobar Degeneration/genetics/microbiology/pathology/metabolism ; Mice, Inbred C57BL ; *Gastrointestinal Microbiome/genetics ; Genetic Background ; Humans ; Male ; }, abstract = {Slow-onset neurodegenerative disease in a low-expresser 2N4R P301L transgenic (Tg) mouse model is marked by neuroinflammation and by differing patterns of CNS deposition and accumulation of tau conformers, with such heterogeneities present even within inbred backgrounds. Gut microbial genotypes were notably divergent within C57BL6/Tac or 129SvEv/Tac congenic (Cg) sublines of TgTau[P301L] mice, and these sublines differed when challenged with antibiotic treatment and fecal microbial transplantation. Whereas aged, transplanted Cg 129SvEv/Tac TgTau[P301L] mice had neuroanatomical deposition of tau resembling controls, transplanted Cg C57BL6/Tac TgTau[P301L] mice had different proportions of rostral versus caudal tau accumulation (p = 0.0001). These data indicate the potential for environmental influences on tau neuropathology in this model. Furthermore, Cg C57BL6/Tac TgTau[P301L] cohorts differed from 129SvEv/Tac counterparts by showing 28% versus 9% net intercurrent loss (p = 0.0027). While the origin of this phenomenon is not established, it offers a parallel to differing patterns of frailty observed in C57BL6 versus 129 SvEv Tg mice expressing the 695 amino acid isoform of human amyloid precursor protein. We infer that generalized responses to protein aggregation might account for similar reductions in viability even when expressing different human proteins in the same inbred strain background.}, } @article {pmid40427424, year = {2025}, author = {Golenia, A and Olejnik, P}, title = {The Role of Oxidative Stress in Ischaemic Stroke and the Influence of Gut Microbiota.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {14}, number = {5}, pages = {}, pmid = {40427424}, issn = {2076-3921}, abstract = {Ischaemic stroke is the most prevalent stroke subtype, accounting for 80-90% of all cases worldwide, and remains a leading cause of morbidity and mortality. Its pathophysiology involves complex molecular cascades, with oxidative stress playing a central role. During cerebral ischaemia, reduced blood flow deprives neurons of essential oxygen and nutrients, triggering excitotoxicity, mitochondrial dysfunction, and excessive production of reactive oxygen and nitrogen species (RONS). Not only do these species damage cellular components, but they also activate inflammatory pathways, particularly those mediated by the transcription factor nuclear factor kappa-B (NF-κB). The pro-inflammatory milieu intensifies neuronal damage, compromises blood-brain barrier integrity, and exacerbates reperfusion-induced damage. Recent findings highlight the importance of the gut microbiota in modulating stroke outcomes, primarily through metabolic and immunological interactions along the gut-brain axis. Dysbiosis, characterised by reduced microbial diversity and an imbalance between beneficial and harmful strains, has been linked to increased systemic inflammation, oxidative stress, and worse prognoses. Specific gut-derived metabolites, including short-chain fatty acids (SCFAs) and trimethylamine N-oxide (TMAO), appear to either mitigate or intensify neuronal injury. SCFAs may strengthen the blood-brain barrier and temper inflammatory responses, whereas elevated TMAO levels may increase thrombotic risk. This narrative review consolidates both experimental and clinical data demonstrating the central role of oxidative stress in ischaemic stroke pathophysiology and explores the gut microbiota's ability to modulate these damaging processes. Therapeutic strategies targeting oxidative pathways or rebalancing gut microbial composition, such as antioxidant supplementation, dietary modulation, probiotics, and faecal microbiota transplantation, present promising paradigms for stroke intervention. However, their widespread clinical implementation is hindered by a lack of large-scale, randomised trials. Future efforts should employ a multidisciplinary approach to elucidate the intricate mechanisms linking oxidative stress and gut dysbiosis to ischaemic stroke, thereby paving the way for novel, mechanism-based therapies for improved patient outcomes.}, } @article {pmid40426604, year = {2025}, author = {Xia, YM and Zhang, MX and Ma, XY and Tan, LL and Li, T and Wu, J and Li, MA and Zhao, WJ and Qiao, CM and Jia, XB and Shen, YQ and Cui, C}, title = {Intranasal Transplantation of Microbiota Derived from Parkinson's Disease Mice Induced Astrocyte Activation and Neurodegenerative Pathology from Nose to Brain.}, journal = {Brain sciences}, volume = {15}, number = {5}, pages = {}, pmid = {40426604}, issn = {2076-3425}, support = {82171429//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Parkinson's disease (PD) is characterized by early-onset olfactory dysfunction preceding motor symptoms, yet its mechanisms remain elusive. Based on the studies on microbiota-gut-brain axis, the microbiota-nose-brain axis might be involved in the pathogenesis of PD. However relative studies are rare.

METHODS: By consecutive 14-days intranasally transplanting bacteria, we established mice models exhibiting nasal microbiota dysbiosis (NMD), including animal group received intranasal drops of fecal bacterial suspension from normal mice (NB group) and animal group received intranasal drops of fecal bacterial suspension from PD mice (PB group), with animals that only received anesthesia used as the control group. Then we analyzed the nasal microbiota composition via 16S rRNA sequencing, evaluated the olfactory and motor functions through behavioral experiments, including buried food test, open field test, pole descent test, and traction test. The neuropathology in olfactory-related and PD-related brain regions, including olfactory bulb, pyriform cortex, hippocampus, substantia nigra and striatum, was also detected by western blotting, immunofluorescence and immunohistochemical experiments using the antibodies of NeuN, TH and GFAP.

RESULTS: 16S rRNA sequencing revealed that PB mice were primarily characterized by an increase in bacteria associated with inflammation and PD. Behavioral assessments revealed that mice with NMD demonstrated impairments in the buried food test and pole descent test, indicative of olfactory and motor dysfunction. By detecting NeuN and GFAP expression, we identified neuronal loss and astrocytes activation in olfactory-related brain regions and adjacent structures, including the olfactory bulb, pyriform cortex, hippocampus, substantia nigra and striatum of both NMD groups, which may contribute to the observed functional disorders. Notably, animals exposed to PD-derived bacteria exhibited more pronounced changes in nasal bacteria, with more severe neuropathology.

CONCLUSIONS: We present evidence supporting the microbiota-nose-brain axis, and the NMD-induced astrocyte activation and neurodegenerative pathology along the olfactory pathway may serve as a link between nose and brain.}, } @article {pmid40424882, year = {2025}, author = {Huang, YY and Qin, SM and Nguyen, MT and Chen, W and Si, XM and Huang, YQ and Zhang, HY}, title = {The protective effects of dietary resistant starch against post-antibiotic bone loss in meat ducks associated with the recovery of caecal microbiota dysbiosis.}, journal = {Poultry science}, volume = {104}, number = {8}, pages = {105238}, pmid = {40424882}, issn = {1525-3171}, mesh = {Animals ; *Ducks ; *Gastrointestinal Microbiome/drug effects ; Animal Feed/analysis ; *Anti-Bacterial Agents/adverse effects ; Diet/veterinary ; *Dysbiosis/veterinary/chemically induced/microbiology ; *Bone Resorption/veterinary/chemically induced/prevention & control ; *Resistant Starch/administration & dosage/metabolism ; Cecum/microbiology ; Fecal Microbiota Transplantation/veterinary ; Male ; Dietary Supplements/analysis ; Random Allocation ; *Poultry Diseases/prevention & control/chemically induced ; }, abstract = {Compromised bone quality increases the risk of fractures in domesticate birds, resulting in pain and altered behaviour. Although dietary resistant starch (RS) supplementation show promise for improving inferior bone mass, the diet-mediated gut microbiota alterations as a potential mechanism underlying RS positive roles in bone remains uncertain. With a post-antibiotic model and faecal microbiota transplantation (FMT), this study investigated the effects of a RS diet on antibiotic-induced bone loss and gut microbial composition in meat ducks. Ducklings were assigned to 4 treatments with 6 replicate pens until 21 d, including the control group (Ctrl, feeding a basal diet) and the RS-fed group, and post-antibiotic treatment following the gavage of phosphate-buffered saline (Post-anti-PBS) or faecal microbiota transplantation (Post-anti-FMT). The RS diet increased the proportion of Firmicutes, improved intestinal integrity, and reduced inflammation-induced bone resorption, all of which contributed to an increase in tibial bone volume (P < 0.05). Post-antibiotic treatment was found to reduce tibial quality by stimulating bone resorption and inhibiting bone formation, accompanied by gut microbiota dysbiosis, increased intestinal permeability (P = 0.059), and inflammatory flare compared to control birds. FMT from RS-fed ducks into the antibiotic-treated birds reversed bone loss by primarily blocking osteoclastic frequency and activity. Furthermore, FMT increased the ratio of Firmicutes to Bacteroidetes (P < 0.05) and suppressed the release of pro-osteoclastogenic cytokines such as tumour necrosis factor-α (P = 0.062) and interleukin-1β (P < 0.05) in the bone marrow. These results demonstrated the involvement of gut microbiota in improving bone quality of meat ducks by RS, and FMT of RS-fed birds corrected the imbalance of ceca microbiota and attenuated bone loss in meat ducks with enhanced bone resorption.}, } @article {pmid40422666, year = {2025}, author = {Gaspar, BS and Roşu, OA and Enache, RM and Manciulea Profir, M and Pavelescu, LA and Creţoiu, SM}, title = {Gut Mycobiome: Latest Findings and Current Knowledge Regarding Its Significance in Human Health and Disease.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {11}, number = {5}, pages = {}, pmid = {40422666}, issn = {2309-608X}, abstract = {The gut mycobiome, the fungal component of the gut microbiota, plays a crucial role in health and disease. Although fungi represent a small fraction of the gut ecosystem, they influence immune responses, gut homeostasis, and disease progression. The mycobiome's composition varies with age, diet, and host factors, and its imbalance has been linked to conditions such as inflammatory bowel disease (IBD) and metabolic disorders. Advances in sequencing have expanded our understanding of gut fungi, but challenges remain due to methodological limitations and high variability between individuals. Emerging therapeutic strategies, including antifungals, probiotics, fecal microbiota transplantation, and dietary interventions, show promise but require further study. This review highlights recent discoveries on the gut mycobiome, its interactions with bacteria, its role in disease, and potential clinical applications. A deeper understanding of fungal contributions to gut health will help develop targeted microbiome-based therapies.}, } @article {pmid40421334, year = {2025}, author = {Ponce Alencastro, JA and Salinas Lucero, DA and Solis, RP and Herrera Giron, CG and Estrella López, AS and Anda Suárez, PX}, title = {Molecular Mechanisms and Emerging Precision Therapeutics in the Gut Microbiota-Cardiovascular Axis.}, journal = {Cureus}, volume = {17}, number = {4}, pages = {e83022}, pmid = {40421334}, issn = {2168-8184}, abstract = {A microbiome in the gut plays a significant role in cardiovascular health and disease. Dysbiosis is an imbalance in the gut microbiome, leading to multiple cardiovascular diseases (CVD) such as atherosclerosis, hypertension, and heart failure. Gut microbe-derived metabolites such as trimethylamine-N-oxide (TMAO) and short-chain fatty acids (SCFAs) are important mediators of the gut-heart axis. Evaluation of the relationship between the gut microbiome and host biomarkers with CVD requires the integration of metagenomics and metabolomics with meta-omics approaches. The literature review found that microbes and metabolic signatures are associated with the risk and progression of CVD. The development of precision therapeutic approaches for targeting gut microbiota includes preventing adverse microbial effects using probiotics, prebiotics, and the drug-as-bug approach to inhibit harmful metabolites of microbiomes, and fecal microbiota transplantation (FMT). However, the implication and practice of these findings in clinical settings face challenges due to the heterogeneity of study designs, difficulty in the determination of causality, and the impact of confounding factors such as diet, medication, and potential inter-individual gut microbiome variability. Future researchers are recommended to conduct longitudinal studies to further establish both gut microbiome associations with CVD and develop successful precision therapeutics approaches based on the microbiome for the treatment of CVD.}, } @article {pmid40420583, year = {2025}, author = {He, X and Luthuli, S and Wen, Q and Wang, C and Ding, J and Cui, B and Zhang, F}, title = {Washed microbiota transplantation for ribotype 027 Clostridioides difficile infection in a pregnant woman with two-year follow-up: a case report.}, journal = {Journal of biomedical research}, volume = {}, number = {}, pages = {1-4}, doi = {10.7555/JBR.39.20250063}, pmid = {40420583}, issn = {1674-8301}, abstract = {Clostridioides difficile (C. difficile) is one of the major causes of nosocomial infections. The pregnant women, who were considered at low risk for C. difficile infection (CDI), have attracted attention with increasing reports. Oral vancomycin, the only first-line treatment for the pregnant women infected with C. difficile, came with the problem of increasing strains resistance that was associated with decreased efficacy. Fecal microbiota transplantation (FMT) is recommended for severe, fulminant and recurrent CDI, while it is avoided in the pregnant women due to safety concerns. We reported a pregnant woman case with primary ribotype 027 CDI, who got a successful outcome with washed microbiota transplantation (WMT), an improved FMT, via enema. The specific strain of ribotype 027 was related to severe outcomes but was not reported in the pregnant women. The follow-up lasted two years, the patient's diarrhea was fully alleviated without recurrence. The baby had normal growth and development and no adverse events were recorded in both of them. This case provides evidence for the efficacy and safety of WMT in the pregnant women infected with C. difficile, indicating that WMT via enema may be a strategy for this population in treating CDI.}, } @article {pmid40419682, year = {2025}, author = {Nishinarita, Y and Miyoshi, J and Kuronuma, S and Wada, H and Oguri, N and Hibi, N and Takeuchi, O and Akimoto, Y and Lee, STM and Matsuura, M and Kobayashi, T and Hibi, T and Hisamatsu, T}, title = {Characteristic gene expression profile of intestinal mucosa early in life promotes bacterial colonization leading to healthy development of the intestinal environment.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {18437}, pmid = {40419682}, issn = {2045-2322}, support = {19K23977//Japan Society for the Promotion of Science/ ; 21K07900//Japan Society for the Promotion of Science/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/genetics ; Mice ; *Intestinal Mucosa/microbiology/metabolism ; Fecal Microbiota Transplantation ; *Bacteria/genetics/growth & development/classification ; Germ-Free Life ; *Transcriptome ; Male ; Gene Expression Profiling ; Female ; Feces/microbiology ; Mice, Inbred C57BL ; }, abstract = {The gut microbiome early in life plays a crucial role in development of the host and affects health throughout life. The definition of a healthy microbiome early in life has not been established, and the underlying mechanism of how a young host selects appropriate microbes for colonization remains unclear. Understanding the mechanism may provide insights into novel preventive and therapeutic strategies by correcting dysbiosis early in life. We employed germ-free mice early in life (4 weeks of age) and later in life (10 weeks of age) for fecal microbiota transfer (FMT) from specific pathogen-free mice. We performed age-unmatched FMT between recipients early in life and donors early or later in life, in addition to common age-matched FMT. Age-matched FMT resulted in significantly different bacterial compositions between recipients early vs. later in life. When the gut microbiome from donors early or later in life was transferred to recipients early in life, bacterial compositions of recipients from donors later in life were similar to those of recipients from donors early in life. This finding suggests that the host early in life has mechanisms to select microbes appropriate for age from the exposed microbiome. We hypothesized that the age-specific intestinal environment promotes age-appropriate intestinal microbiome colonization and examined gene expression in the intestinal mucosa of germ-free mice. We observed that gene expression profiles were different between early vs. later in life. Correlation analysis demonstrated that genera Lachnospiraceae NK4A136 group and Roseburia were positively correlated to genes expressed predominantly early in life, but negatively with genes expressed predominantly later in life. We confirmed that the relative abundance of these genera was significantly higher in specific pathogen-free mice early in life compared with mice later in life. The characteristic gene expression of the intestinal mucosa early in life might play roles in selecting specific bacteria in the intestinal microbiome early in life.}, } @article {pmid40419041, year = {2025}, author = {Chen, L and Zhao, S and Chen, Q and Luo, P and Li, X and Song, Y and Pan, S and Wu, Q and Zhang, Y and Shen, X and Chen, Y}, title = {Poria cocos polysaccharides ameliorate AOM/DSS-induced colorectal cancer in mice by remodeling intestinal microbiota composition and enhancing intestinal barrier function.}, journal = {International journal of biological macromolecules}, volume = {315}, number = {Pt 2}, pages = {144477}, doi = {10.1016/j.ijbiomac.2025.144477}, pmid = {40419041}, issn = {1879-0003}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Colorectal Neoplasms/chemically induced/drug therapy/pathology/microbiology/metabolism ; Azoxymethane/adverse effects ; Dextran Sulfate/adverse effects ; *Fungal Polysaccharides/pharmacology/chemistry ; *Intestinal Mucosa/drug effects/metabolism ; Male ; *Wolfiporia/chemistry ; *Polysaccharides/pharmacology ; Cytokines/metabolism ; *Poria/chemistry ; Intestinal Barrier Function ; }, abstract = {Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, necessitating the development of novel therapeutic strategies. Poria cocos polysaccharides (PCP), bioactive components of the traditional medicinal fungus Poria cocos, exhibit significant anticancer potential. This study investigates the protective effects of PCP against azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC in mice, with a focus on its impact on intestinal microbiota composition, intestinal barrier integrity, and inflammatory responses. PCP treatment significantly reduced tumor incidence, tumor size, and tumor burden while improving histopathological features and inhibiting Ki67-positive cell proliferation. Mechanistically, PCP enhanced intestinal barrier function by restoring tight junction proteins (E-cadherin, ZO-1, Claudin-3) and mucin secretion (MUC2), thereby reducing intestinal permeability and systemic lipopolysaccharide (LPS) levels. Furthermore, PCP exhibited potent anti-inflammatory effects by downregulating pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and upregulating the anti-inflammatory cytokine IL-10. 16S rRNA sequencing results revealed that PCP modulated the intestinal microbiota, decreasing pathogenic bacteria such as Helicobacter and Eisenbergiella while promoting beneficial taxa including Limosilactobacillus, Paraprevotella, and Muribaculum. Fecal microbiota transplantation (FMT) further confirmed the microbiota-mediated protective effects of PCP, as FMT from PCP-treated donors significantly suppressed tumorigenesis, restored intestinal barrier integrity, and alleviated inflammation in CRC mice. Additionally, PCP demonstrated a favorable safety profile, with no adverse effects on major organs. These findings highlight PCP as promising natural agents for CRC prevention and therapy, acting through modulation of the intestinal microbiota, enhancement of intestinal barrier function, and suppression of inflammation.}, } @article {pmid40415934, year = {2025}, author = {Liu, L and Zhao, W and Zhang, H and Shang, Y and Huang, W and Cheng, Q}, title = {Relationship between pediatric asthma and respiratory microbiota, intestinal microbiota: a narrative review.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1550783}, pmid = {40415934}, issn = {1664-302X}, abstract = {Pediatric asthma is a common chronic airway inflammatory disease that begins in childhood and its impact persists throughout all age stages of patients. With the continuous progress of detection technologies, numerous studies have firmly demonstrated that gut microbiota and respiratory microbiota are closely related to the occurrence and development of asthma, and related research is increasing day by day. This article elaborates in detail on the characteristics, composition of normal gut microbiota and lung microbiota at different ages and in different sites, as well as the connection of the gut-lung axis. Subsequently, it deeply analyzes various factors influencing microbiota colonization, including host factor, delivery mode, maternal dietary and infant feeding patterns, environmental microbial exposure and pollutants, and the use of antibiotics in early life. These factors are highly likely to play a crucial role in the onset process and disease progression of asthma. Research shows that obvious changes have occurred in the respiratory and gut microbiota of asthma patients, and these microbiomes exhibit different characteristics according to the phenotypes and endotypes of asthma. Finally, the article summarizes the microbiota-related treatment approaches for asthma carried out in recent years, including the application of probiotics, nutritional interventions, and fecal microbiota transplantation. These treatment modalities are expected to become new directions for future asthma treatment and bring new hope for solving the problem of childhood asthma.}, } @article {pmid40415928, year = {2025}, author = {Karimianghadim, R and Satokari, R and Yeo, S and Arkkila, P and Kao, D and Pakpour, S}, title = {Prolonged effect of antibiotic therapy on the gut microbiota composition, functionality, and antibiotic resistance genes' profiles in healthy stool donors.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1589704}, pmid = {40415928}, issn = {1664-302X}, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) is highly effective in preventing Clostridioides difficile recurrence by restoring gut microbiota composition and function. However, the impact of recent antibiotic use, a key exclusion criterion for stool donors, on gut microbiota recovery is poorly understood.

METHODS: We investigated microbial recovery dynamics following antibiotic use in three long-term stool donors from Canada and Finland. Using longitudinal stool sampling, metagenomic sequencing, and qPCR, we assessed changes in bacterial diversity, community composition, microbial functions, the gut phageome, and the risk of transmitting antibiotic-resistant genes (ARGs).

RESULTS: Antibiotics caused lasting disruption to bacterial communities, significantly reducing important taxa like Bifidobacterium bifidum, Blautia wexlerae, Akkermansia muciniphila, Eubacterium sp. CAG 180, and Eubacterium hallii, with effects persisting for months. Functional analyses revealed alterations in housekeeping genes critical for energy production and biosynthesis, with no direct links to key health-related pathways. Antibiotics also disrupted viral populations, decreasing diversity and increasing crAssphage abundance, reflecting disrupted host-bacteriophage dynamics. No significant increase in clinically important ARGs was detected.

DISCUSSION: These findings highlight the unpredictable and complex recovery of gut microbiota post-antibiotics. Individualized suspension periods in donor programs, guided by metagenomic analyses, are recommended to optimize FMT outcomes in various indications by considering antibiotic spectrum, duration, and host-specific factors.}, } @article {pmid40414934, year = {2025}, author = {Jan, A and Bayle, P and Mohellibi, N and Lemoine, C and Pepke, F and Béguet-Crespel, F and Jouanin, I and Tremblay-Franco, M and Laroche, B and Serror, P and Rigottier-Gois, L}, title = {A consortium of seven commensal bacteria promotes gut microbiota recovery and strengthens ecological barrier against vancomycin-resistant enterococci.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {129}, pmid = {40414934}, issn = {2049-2618}, support = {COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; COOPERATE project (2021-2022)//Poc'UP program of SATT Paris-Saclay/ ; PhD scholarship AJ (2020-2023)//INRAE Metaprogram HOLOFLUX and doctoral school ABIES at University Paris-Saclay/ ; Travel grants from Graduate schools Life sciences and Health (LSH) and Biosphera from University Paris-Saclay//France 2030 program "ANR-11-IDEX-0003"/ ; REMOVE project (2018-2019)//INRAE MICA division/ ; REMOVE project (2018-2019)//INRAE MICA division/ ; REMOVE project (2018-2019)//INRAE MICA division/ ; REMOVE project (2018-2019)//INRAE MICA division/ ; REMOVE project (2018-2019)//INRAE MICA division/ ; Key action MIND (2017)//INRAE Metaprogram MEM/ ; Key action MIND (2017)//INRAE Metaprogram MEM/ ; Key action MIND (2017)//INRAE Metaprogram MEM/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Vancomycin-Resistant Enterococci/growth & development ; Mice ; Symbiosis ; Dysbiosis/microbiology/chemically induced ; Anti-Bacterial Agents ; *Gram-Positive Bacterial Infections/microbiology ; Feces/microbiology ; *Bacteria/classification/genetics/isolation & purification ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Vancomycin-resistant enterococci (VRE) often originate from the gastrointestinal tract, where their proliferation precedes dissemination into the bloodstream, and can lead to systemic infection. Uncovering the actors and mechanisms reducing the intestinal colonisation by VRE is essential to control infection. We aimed to identify commensal bacteria that interfere with VRE gut colonisation or act as an ecological barrier.

RESULTS: We performed a 3-week longitudinal analysis of the gut microbiota composition and VRE carriage levels during microbiota recovery in mice colonised with VRE after antibiotic-induced dysbiosis. By combining biological data and mathematical modelling, we identified 15 molecular species (OTUs) that negatively correlated with VRE overgrowth. Six strains representative of these OTUs were collected, cultivated and used in mixture with a seventh strain (Mix7) in two different mouse lines challenged with VRE. Of the seven strains, three belonged to Lachnospiraceae, one to Muribaculaceae, one to Ruminococcaceae and two to Lactobacillaceae. We found that Mix7 led to a better recovery of the gut microbiota composition and reduced VRE carriage. Differences in the effect of Mix7 were observed between responder and non-responder mice. These differences were associated with variations in the composition of the initial microbiota and during recovery and represent potential biomarkers for predicting response to Mix7. In a mouse model of alternative stable state of dysbiosis, response to Mix7 was associated with higher concentrations of short-chain fatty acids (acetate, propionate, butyrate) and a range of metabolites including bile acids, reflecting the recovery of the microbiota back to initial state. Furthermore, Muribaculum intestinale strain was required to obtain the Mix7 effect on VRE reduction in vivo, but the presence of at least one of the other six strains was needed. None of the supernatant of the seven strains, alone or in combination, inhibited VRE growth in vitro. Interestingly, five strains belong to species shared among humans and mice, and the other two have human functional equivalents.

CONCLUSIONS: An innovative approach based on mathematical modelling of the microbiota composition permitted to identify a mixture of commensal bacterial strains, which improves the ecological barrier effect against VRE. The mechanisms are dependent on the recovery and initial composition of the microbiota. Ultimately, this work will enable a move towards a personalised medicine by targeting predisposed patients presenting a risk of infection, such as neutropenic or bone-marrow transplant patients, and likely to respond to supplementation with commensal strains, providing new live biotherapeutic products and biomarkers to predict response to supplementation. Video Abstract.}, } @article {pmid40414635, year = {2025}, author = {Kumar, R and Kumar, R}, title = {Intestinal dysbiosis leads to the reduction in neurochemical production in Parkinson's disease (PD).}, journal = {International review of neurobiology}, volume = {180}, number = {}, pages = {25-56}, doi = {10.1016/bs.irn.2025.03.004}, pmid = {40414635}, issn = {2162-5514}, mesh = {Humans ; *Dysbiosis/metabolism/therapy ; *Parkinson Disease/metabolism/therapy/physiopathology/microbiology ; *Gastrointestinal Microbiome/physiology ; Animals ; }, abstract = {Parkinson's Disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, with emerging research suggesting a critical link between intestinal dysbiosis and PD progression. This review explores the pathophysiological mechanisms underlying PD, such as alpha-synuclein aggregation, mitochondrial dysfunction, neuroinflammation, and oxidative stress, while focusing on the impact of gut dysbiosis on intestinal barrier function and its role in reduced neurochemical production. The clinical features of PD, including dopamine, serotonin, and GABA deficiencies, are examined, with a focus on how dysbiosis contributes to neurotransmitter depletion. Current treatments of PD, such as levodopa and dopamine agonists, are discussed alongside gut health therapies such as probiotics, prebiotics, and Fecal Microbiota Transplantation (FMT). Future therapeutic directions, including synbiotics, engineered microbes, phage therapy, and the integration of machine learning (ML) and artificial intelligence (AI), are explored. The chapter also considers preventive strategies, such as lifestyle adjustments and early gut health monitoring using modern diagnostic tools and biosensors. Furthermore, a strong need for continued research into the gut-brain axis (GBA) to develop more effective, gut-targeted therapies for managing PD is discussed.}, } @article {pmid40414634, year = {2025}, author = {Singh, S and Saini, V and Jha, HC}, title = {The role of secondary genomes in neurodevelopment and co-evolutionary dynamics.}, journal = {International review of neurobiology}, volume = {180}, number = {}, pages = {245-297}, doi = {10.1016/bs.irn.2025.03.008}, pmid = {40414634}, issn = {2162-5514}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neurodevelopmental Disorders/genetics/microbiology ; *Biological Evolution ; Animals ; *Brain/growth & development ; }, abstract = {This chapter examines how human biology and microbial "secondary genomes" have co-evolved to shape neurodevelopment through the gut-brain axis. Microbial communities generate metabolites that cross blood-brain and placental barriers, influencing synaptogenesis, immune responses, and neural circuit formation. Simultaneously, Human Accelerated Regions (HARs) and Endogenous Retroviruses (ERVs) modulate gene expression and immune pathways, determining which microbes thrive in the gut and impacting brain maturation. These factors converge to form a dynamic host-microbe dialogue with significant consequences for neurodevelopmental disorders (NDD), including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and schizophrenia. Building on evolutionary perspectives, the chapter elucidates how genetic and immune mechanisms orchestrate beneficial and pathological host-microbe interactions in early brain development. It then explores therapeutic strategies, such as probiotics, prebiotics, fecal microbiota transplantation, and CRISPR-driven microbial engineering, targeting gut dysbiosis to mitigate or prevent neurodevelopmental dysfunctions. Furthermore, innovative organ-on-chip models reveal mechanistic insights under physiologically relevant conditions, offering a translational bridge between in vitro experiments and clinical applications. As the field continues to evolve, this work underscores the translational potential of manipulating the microbiome to optimize neurological outcomes. It enriches our understanding of the intricate evolutionary interplay between host genomes and the microbial world.}, } @article {pmid40414573, year = {2025}, author = {Yu, F and Ji, JL and Wang, Y and Liu, YD and Lian, YM and Wang, MZ and Cai, ZX}, title = {Anti-epileptic and gut-protective effects of trioctanoin and the critical role of gut microbiota in a mouse model of epilepsy.}, journal = {Brain research bulletin}, volume = {227}, number = {}, pages = {111401}, doi = {10.1016/j.brainresbull.2025.111401}, pmid = {40414573}, issn = {1873-2747}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/physiology ; Mice ; *Epilepsy/drug therapy/chemically induced/microbiology/metabolism ; Disease Models, Animal ; Male ; *Anticonvulsants/pharmacology ; Pentylenetetrazole ; Fecal Microbiota Transplantation/methods ; Hippocampus/drug effects/metabolism ; Mice, Inbred C57BL ; Seizures/drug therapy ; }, abstract = {Gut microbiota structure and function affect metabolism, gut health, and behavioral responses and are regulated by dietary factors. Recent research suggests the association of the gut-brain axis with epilepsy pathogenesis, thus offering potential new therapeutic targets. This study evaluated the anti-epileptic effect of trioctanoin and explored the potential role of the gut microbiota in a chronic pentylentetrazol (PTZ)-induced seizure mouse model. Behavioral assessments, electroencephalogram monitoring, immunofluorescence staining, neurotransmitter detection, gut microbiota sequencing, intestinal barrier function tests, and Fecal Microbiota Transplantation (FMT) were performed to systematically study the anti-epileptic effects of trioctanoin and the potential role of microbiota. Trioctanoin significantly restored glial cell proliferation to normal levels in chronic PTZ mice. Moreover, trioctanoin reduced elevated glutamate levels in the hippocampus of PTZ mice and improved gut microbiota imbalance and gut health by restoring the abundance of Dubosiella and Faecalibaculum genera, upregulating tight junction protein expression in the colon, and decreasing elevated levels of the inflammatory markers. Antibiotics(Abx) pre-treatment abolished the anticonvulsant protective effect of Trioctanoin. Although the FMT experiment did not transfer the anticonvulsant protection to the Abx+PTZ group mice, the results suggest that FMT still partially restored the gut microbiota imbalance in the chronic PTZ-induced epilepsy mouse model. These results provide new insights into dietary and gut microbiota-based therapeutic strategies for epilepsy.}, } @article {pmid40413728, year = {2025}, author = {Kousgaard, SJ and Dall, SM and Albertsen, M and Nielsen, HL and Thorlacius-Ussing, O}, title = {Fecal microbiota transplantation from a healthy pouch donor for chronic pouchitis: a proof-of-concept study.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2510464}, pmid = {40413728}, issn = {1949-0984}, mesh = {Humans ; *Pouchitis/therapy/microbiology ; *Fecal Microbiota Transplantation/adverse effects/methods ; Male ; Female ; Adult ; Middle Aged ; Feces/microbiology ; Quality of Life ; Chronic Disease/therapy ; Gastrointestinal Microbiome ; Proof of Concept Study ; Treatment Outcome ; Tissue Donors ; Denmark ; }, abstract = {Chronic pouchitis is a common complication after ileal pouch-anal anastomosis (IPAA) with limited treatment options. In this case series, we aimed to investigate clinical and microbiome changes, as well as adverse events, associated with using fecal microbiota transplantation (FMT) from a donor with a normal functioning IPAA to induce remission in patients with chronic pouchitis. Methods The study was a case-series including a 4-week intervention period and 12-month follow-up. Patients with chronic pouchitis who met the inclusion criteria were recruited from the Department of Gastrointestinal Surgery at Aalborg University Hospital, Denmark. Participants received FMT derived from a donor with a normal functioning IPAA. Treatment was administered by enema daily for two weeks, then every other day for two more weeks. Disease severity and quality of life (QoL) were accessed at baseline and 30-day follow-up. Clinical remission was defined as Pouchitis Disease Activity Index (PDAI) <7. Fecal samples from participants, healthy donors, and the IPAA donor were analyzed using shotgun metagenomic sequencing. Results Three patients with chronic pouchitis were included and completed the treatment protocol and follow-up visits. At the 30-day follow-up, all participants achieved clinical remission with reduced endoscopic inflammation. The median total PDAI score decreased from 8 (range 10-8) at baseline to 6 (range 6-5) at 30 days. Two participants reported improved QoL, while one reported no change. Few mild, self-limited adverse events were reported by all participants during treatment, with no serious events. Principal component analysis of fecal samples distinguished two clusters: healthy donors and the IPAA donor, with participant samples forming a separate cluster Conclusion We observed that all participants achieved clinical remission with reduced endoscopic inflammation following a 4-week FMT intervention. Adverse events were mild and self-limited. Metagenomic analysis revealed distinct microbiome clusters between IPAA donor and recipients, both of which differed from those of healthy donors.}, } @article {pmid40413726, year = {2025}, author = {Zhang, DY and Li, D and Chen, SJ and Zhang, LJ and Zhu, XL and Chen, FD and Chen, C and Wang, Q and Du, Y and Xiong, JX and Huang, SM and Zhang, XD and Lv, YT and Zeng, F and Chen, RX and Huang, X and Mao, F and Zhou, S and Yao, Q and Huang, Y and Chen, R and Mo, Y and Xie, Y and Jiang, YH and Chen, Z and Mo, CY and Chen, JJ and Bai, FH}, title = {Bacteroides uniformis-generated hexadecanedioic acid ameliorates metabolic-associated fatty liver disease.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2508433}, pmid = {40413726}, issn = {1949-0984}, mesh = {Humans ; Gastrointestinal Microbiome ; Animals ; *Bacteroides/metabolism/genetics ; Mice ; Male ; Female ; Middle Aged ; Feces/microbiology ; Liver/metabolism ; *Fatty Liver/microbiology/metabolism ; Fecal Microbiota Transplantation ; Prospective Studies ; Adult ; Metabolomics ; Mice, Inbred C57BL ; }, abstract = {Gut microbiota exerts a pivotal influence on the development of Metabolic Associated Fatty Liver Disease (MAFLD), although the specific contributions of individual bacterial strains and their metabolites remain poorly defined. We conducted stool shotgun metagenomic sequencing and plasma untargeted metabolomics in a large prospective cohort comprising 120 MAFLD patients and 120 matched healthy controls. The mechanisms and microbial-derived metabolites involved in MAFLD were further investigated through multi-omics analyses in vitro and in vivo. Distinct differences were identified in both the microbial community structure and metabolomic profiles between MAFLD patients and healthy controls. Bacteroides uniformis (B. uniformis) was the most significantly depleted species in MAFLD and negatively correlated with hepatic steatosis and BMI. MAFLD was characterized by marked disruptions in fatty acid and amino acid metabolism. Combined analysis of metabolomic and metagenomic data achieved high diagnostic accuracy for MAFLD and hepatic steatosis severity (AUC = 0.93). Transplantation of fecal microbiota from MAFLD subjects into ABX mice led to the onset of MAFLD-like symptoms, whereas B. uniformis administration alleviate disease progression by inhibiting intestinal fat absorption, FFA from eWAT influx into liver via the gut-liver axis, and IRE1α-XBP1s-mediated flipogenesis and ferroptosis, as confirmed by hepatic transcriptomic and proteomic analyses. Hexadecanedioic acid (HDA), potentially identified as a key metabolite produced by B. uniformis, ameliorated MAFLD symptoms. Mechanistically, B. uniformis-derived HDA also inhibited fat absorption and transported, and entered the liver via the portal vein to suppress IRE1α-XBP1s-mediated flipogenesis and ferroptosis. B. uniformis and its potential putative metabolite HDA may contribute to MAFLD progression modulation, through regulation of the IRE1α-XBP1s axis. This study provides new insights into the gut-liver axis in MAFLD and offers promising therapeutic targets based on specific microbes and their metabolites.}, } @article {pmid40412060, year = {2025}, author = {Lin, Z and Wang, J and Luo, H and Huang, L and Pan, Z and Yang, S and Zhong, C and Shan, NC and Ye, Z and Tan, H and Yang, X and Zhang, B and Huang, C and Zhang, H}, title = {Changdiqing decoction (CDQD) ameliorates colitis via suppressing inflammatory macrophage activation and modulating gut microbiota.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {143}, number = {}, pages = {156856}, doi = {10.1016/j.phymed.2025.156856}, pmid = {40412060}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology ; Mice ; *Macrophage Activation/drug effects ; Dextran Sulfate ; *Colitis, Ulcerative/drug therapy ; Male ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Disease Models, Animal ; *Colitis/drug therapy ; *Anti-Inflammatory Agents/pharmacology ; Macrophages/drug effects ; }, abstract = {BACKGROUND: Ulcerative colitis (UC) is a non-specific inflammatory bowel disease. Unlike any single form of cell death reported previously, macrophage PANoptosis, a unique programmed cell death characterized by inflammation and necrosis, plays a crucial role in the pathogenesis of colitis. Changdiqing Decoction (CDQD), an empirical hospital prescription enema, has been used to treat UC for decades. This study aimed to investigate the multi-target anti-colitic effects of CDQD by examining its impact on intestinal homeostasis and its anti-inflammatory properties.

METHODS: A dextran sulfate sodium (DSS)-induced mouse model of acute colitis was employed. Interferon-gamma (IFN-γ) and KPT-330 were used to induce macrophage PANoptosis. Ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLCHRMS) was utilized to identify the chemical constituents of CDQD. Multi-omics analysis and fecal microbiota transplantation (FMT) were used to explore the therapeutic targets and gut microbiota alterations induced by CDQD.

RESULTS: CDQD treatment significantly alleviated colitis symptoms in mice, with a dose-dependent therapeutic effect. The decoction mitigated PANoptosis in colon tissues and bone marrow-derived macrophages (BMDMs). 16S rRNA sequencing analysis and metabonomics revealed that CDQD administration significantly altered the gut microbiota composition and metabolite profiles. Notably, CDQD-modulated gut microbiota exhibited anti-colitic effects through FMT. Integrated transcriptomics and network pharmacology analysis revealed that CDQD significantly downregulated the PI3K/Akt signaling pathway in colitis. This finding was further validated using the inhibitors LY294002 and MK2206.

CONCLUSIONS: CDQD alleviates colitis by suppressing inflammatory macrophage activation and modulating the gut microbiota. Our research provides a novel traditional Chinese medicine strategy for the treatment of UC via enema administration.}, } @article {pmid40411710, year = {2025}, author = {Chen, L and Chen, C and Bai, Y and Li, C and Wei, C and Wei, R and Luo, R and Li, R and Ma, Q and Geng, Y}, title = {Evaluation of the effects of different formulations of protectants on the preservation of the microbiota in fecal microbiota transplantation.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {}, number = {}, pages = {}, pmid = {40411710}, issn = {1618-1905}, abstract = {BACKGROUND: With the increasing indications for fecal microbiota transplantation for the treatment of diseases, there is a growing demand for the preparation of frozen or lyophilized fecal microbiota products that are viable and can stably colonize the recipient. The addition of protective agents plays an important role in the preparation. However, there has been no systematic evaluation of the protective agents used in fecal microbiota sample transplantation preparation for transplantation.

METHODS: We were used the donor bacterial flora containing 10 different formulations of protective agents were frozen, lyophilized, and stored. Plate counting, CCK8 assay, flow cytometry after LIVE/DEAD staining, and fluorescence intensity were used to assess viable bacteria in vitro. In addition, the donor bacterial flora samples containing different formulations protective agents were transplanted into antibiotic-treated SPF mice, with 3 mice in each group and a total of 5 groups. Fecal samples were collected for metagenomic sequencing to observe the colonization of the bacterial flora in the recipient mice.

RESULTS: The preliminary screening results showed that the survival rate of bacteria in the 5% trehalose (T) groups, and 5% sucrose, 5% inulin, and 1% cysteine hydrochloride (SI) groups was slightly higher than that in the other groups. SI groups tended to be more protective against anaerobes than T groups. The donor gut microbiota containing the SI groups protective agent exhibited the best colonization of the recipient mice. The protective effects of different formulations of protective agents on the colonized probiotic strains and the metabolic function of the bacterial flora in recipient mice were found to be species specific.

CONCLUSIONS: SI groups can not only better protect the activity of anaerobic bacteria in the intestine, but also effectively promote the effective colonization of donor intestinal bacteria in the recipient mice, and the effect of frozen storage method is less, and can be used at the same time as frozen and freeze-dried preparation. It can be used as a reference for the selection of protective agents in the preparation of fecal microbiota transplantation samples.}, } @article {pmid40411629, year = {2025}, author = {Nezhadi, J and Lahouty, M and Rezaee, MA and Fadaee, M}, title = {Clostridium difficile as a potent trigger of colorectal carcinogenesis.}, journal = {Discover oncology}, volume = {16}, number = {1}, pages = {910}, pmid = {40411629}, issn = {2730-6011}, abstract = {Clostridium difficile, traditionally recognized as a cause of antibiotic-associated colitis, has emerged as a potential oncogenic factor in colorectal cancer (CRC). This article explores the mechanisms by which C. difficile toxins, TcdA and TcdB, contribute to CRC pathogenesis through epithelial barrier disruption, DNA damage, and chronic inflammation via NF-κB and STAT3 activation. Dysbiosis further exacerbates tumorigenesis by altering microbial metabolites. Understanding these interactions highlights potential therapeutic strategies, including toxin-neutralizing antibodies, fecal microbiota transplantation, and anti-inflammatory interventions, to mitigate CRC risk associated with C. difficile.}, } @article {pmid40410854, year = {2025}, author = {Fan, L and Chen, J and Zhang, Q and Ren, J and Chen, Y and Yang, J and Wang, L and Guo, Z and Bu, P and Zhu, B and Zhao, Y and Wang, Y and Liu, X and Wang, W and Chen, Z and Gao, Q and Zheng, L and Cai, J}, title = {Fecal microbiota transplantation for hypertension: an exploratory, multicenter, randomized, blinded, placebo-controlled trial.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {133}, pmid = {40410854}, issn = {2049-2618}, support = {82300564//National Natural Science Foundation of China/ ; 81630014//National Natural Science Foundation of China/ ; BRWEP2024W012060100//Beijing Research Ward Excellence Program/ ; BRWEP2024W012060100//Beijing Research Ward Excellence Program/ ; 2024ZD0526804//National Science and Technology Major Project for the Prevention and Treatment of Cancer, Cardiovascular and Cerebrovascular Diseases, Respiratory Diseases and Metabolic Diseases/ ; 2024ZD0526800//National Science and Technology Major Project for the Prevention and Treatment of Cancer, Cardiovascular and Cerebrovascular Diseases, Respiratory Diseases and Metabolic Diseases/ ; BRWEP2024W012060105//Beijing Research Ward Excellence Program，BRWEP/ ; CIFMS, 2021-I2M-1-007//CAMS Innovation Fund for Medical Sciences/ ; 81825002//National Outstanding Youth Science Fund Project of National Natural Science Foundation of China/ ; BJJWZYJH01201910023029//Beijing Outstanding Young Scientist Program/ ; Z231100004623009//Beijing Municipal Science & Technology Commission/ ; CI2021A00920//Key project of Science and Technology Innovation Project of China Academy of Chinese Medical Sciences/ ; ZLRK202511//Beijing Hospitals Authority Clinical medicine Development of special funding support/ ; L248105//Beijing Natural Science Foundation/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; Male ; Female ; *Hypertension/therapy/microbiology ; Adult ; *Gastrointestinal Microbiome/physiology ; Middle Aged ; Feces/microbiology ; Blood Pressure ; China ; Treatment Outcome ; }, abstract = {BACKGROUND: On the basis of the contribution of the gut microbiota to hypertension development, a novel strategy involving fecal microbiota transplantation (FMT) has been proposed to treat hypertension, but its efficacy has not been investigated in the clinic.

METHODS: In a randomized, blinded, placebo-controlled clinical trial (2021/03-2021/12, ClinicalTrials.gov, NCT04406129), hypertensive patients were recruited from seven centers in China, and received FMT or placebo capsules orally at three visits. The patients were randomized at a 1:1 ratio in blocks of four and stratified by center by an independent statistician. The intention-to-treat principle was implemented, as all randomized participants who received at least one intervention were included. The primary outcome was the decrease in office systolic blood pressure (SBP) from baseline to the day 30 visit. Adverse events (AEs) were recorded through the 3-month follow-up to assess safety measures. Alterations in BP, the fecal microbiome, and the plasma metabolome were assessed via exploratory analyses.

RESULTS: This study included 124 patients (mean age 43 years, 73.4% men) who received FMT (n = 63) or placebo (n = 61) capsules. The numbers of participants who experienced AEs (13 (20.6%) vs. 9 (14.8%), p = 0.39) and the primary outcome (6.28 (11.83) vs. 5.77 (10.06) mmHg, p = 0.62) were comparable between the groups. The FMT group presented a decrease in SBP after 1 week of FMT, with a between-arm difference of - 4.34 (95% CI, - 8.1 to - 0.58; p = 0.024) mmHg, but this difference did not persist even after repeated intervention. After FMT, shifts in microbial richness and structure were identified and the abundance of the phyla Firmicutes and Bacteroidetes was altered. Decreases in the abundances of Eggerthella lenta, Erysipelatoclostridium ramosum, Anaerostipes hadrus, Gemella haemolysans, and Streptococcus vestibularis and increases in the abundances of Parabacteroides merdae, Prevotella copri, Bacteroides galacturonicus, Eubacterium sp. CAG 180, Desulfovibrio piger, Megamonas hypermegale, Collinsella stercoris, Coprococcus catus, and Allisonella histaminiformans were identified and correlated with office SBP. Those species were also correlated with responding and inversely office SBP-associated metabolites including tyrosine, glutamine, aspartate, phenylalanine, methionine, serine, sarcosine, and/or asparagine.

CONCLUSIONS: Safety but unsustainable BP reduction was observed in the first trial of the effects of FMT on hypertension. Additional intervention studies on specific microbes with metabolite-targeting and BP-modulating features are needed. Video Abstract.}, } @article {pmid40409520, year = {2025}, author = {Sen, U}, title = {Gut microbiota and well-being: A comprehensive summary of the special issue.}, journal = {Pharmacological research}, volume = {216}, number = {}, pages = {107791}, doi = {10.1016/j.phrs.2025.107791}, pmid = {40409520}, issn = {1096-1186}, mesh = {Humans ; *Gastrointestinal Microbiome ; Animals ; Dysbiosis/therapy/microbiology ; Probiotics/therapeutic use ; Prebiotics ; }, abstract = {Gut microbes play an immense role in digesting ingested food, providing nutrients to the host, and producing several bioactive metabolites that not only help maintain health but can also elicit disease during dysbiotic conditions. The bioactive compounds derived from gut microbiota metabolites include trimethylamine-N-oxide (TMAO), uremic toxins, short chain fatty acids (SCFAs), phytoestrogens, anthocyanins, bile acids, lipopolysaccharide - to name a few. Once these compounds enter the host cells, tissues, and organs they can cause diseases such as epigenetic, metabolic, neurodegenerative, psychiatric, cardiovascular, hypertension, respiratory, gastrointestinal, kidney, bone, cancer, and others. Regulating healthy gut microbiota thus provides a potential option for the prevention, reversal, or even treatment of these diseases. Towards this end, various interventional strategies are postulated in this field of emerged and rapidly expanding health research arena that includes fecal microbiota transplantation, prebiotics, and probiotics, and to introduce the concept that correcting gut dysbiosis can ameliorate disease symptoms, thus offering a new approach towards dysbiosis-related disease mitigation and treatment. In the special issue of Pharmacological Research titled "Gut Microbiota and Well-Being," several outstanding research findings and review articles are published, covering a broad spectrum of topics related to the influence of gut microbiota on health and disease. This editorial summarizes each of these contributions, prioritizing research findings before discussing the review articles. The summaries are restructured abstracts of relevant articles focusing on major findings or thematic topics.}, } @article {pmid40409481, year = {2025}, author = {Chen, E and Zhou, W}, title = {Immunotherapy in microsatellite-stable colorectal cancer: Strategies to overcome resistance.}, journal = {Critical reviews in oncology/hematology}, volume = {212}, number = {}, pages = {104775}, doi = {10.1016/j.critrevonc.2025.104775}, pmid = {40409481}, issn = {1879-0461}, mesh = {Humans ; *Colorectal Neoplasms/therapy/genetics/immunology ; Tumor Microenvironment/immunology/drug effects ; *Immunotherapy/methods ; *Drug Resistance, Neoplasm ; *Microsatellite Instability ; Immune Checkpoint Inhibitors/therapeutic use ; Cancer Vaccines/therapeutic use ; Animals ; }, abstract = {Colorectal cancer (CRC) is among the foremost causes of cancer-related mortality worldwide; however, individuals with microsatellite-stable (MSS) disease-who constitute most CRC diagnoses-derive limited benefit from existing immunotherapeutic approaches. Here, we outline emerging methods designed to address the inherent resistance of MSS CRC to immune checkpoint inhibitors (ICIs). Recent findings emphasize how the immunosuppressive tumor microenvironment (TME) in MSS CRC, marked by diminished immunogenicity and high levels of regulatory T cells and myeloid-derived suppressor cells, restricts effective antitumor immune activity. Combination regimens that merge ICIs with chemotherapy, anti-angiogenic agents, or targeted blockade of pathways such as TGF-β and VEGF have shown encouraging early outcomes, including enhanced antigen presentation and T-cell penetration. Novel immunomodulatory platforms-such as epigenetic modifiers, oncolytic viruses, and engineered probiotic vaccines-are under assessment to further reprogram the TME and boost therapeutic efficacy. Concurrently, progress in adoptive cell therapies (for example, chimeric antigen receptor (CAR) T cells) and the development of cancer vaccines targeting tumor-associated and neoantigens promise to extend immune control over MSS CRC. In parallel, improving patient selection through predictive biomarkers-from circulating tumor DNA (ctDNA) to gene expression signatures and specific molecular subtypes-could refine individualized treatment strategies. Finally, interventions that alter the gut microbiome, including probiotics and fecal transplantation, serve as complementary tools to strengthen ICI responses. Taken together, these insights and combined treatment strategies lay the foundation for more successful immunotherapeutic interventions in MSS CRC, ultimately aiming to provide sustained clinical benefits to a broader spectrum of patients.}, } @article {pmid40406094, year = {2025}, author = {Eslami, M and Naderian, R and Bahar, A and Babaeizad, A and Rezanavaz Gheshlagh, S and Oksenych, V and Tahmasebi, H}, title = {Microbiota as diagnostic biomarkers: advancing early cancer detection and personalized therapeutic approaches through microbiome profiling.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1559480}, pmid = {40406094}, issn = {1664-3224}, mesh = {Humans ; Precision Medicine/methods ; *Gastrointestinal Microbiome/immunology ; *Neoplasms/diagnosis/therapy/microbiology ; *Early Detection of Cancer/methods ; *Biomarkers, Tumor ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {The important function of microbiota as therapeutic modulators and diagnostic biomarkers in cancer has been shown by recent developments in microbiome research. The intricate interplay between the gut microbiota and the development of cancer, especially in colorectal and breast cancers, emphasizes how microbial profiling may be used for precision treatment and early diagnosis. Important microbial signatures, including Bacteroides fragilis and Fusobacterium nucleatum, have been linked to the development and progression of cancer, providing important information on the processes behind carcinogenesis. Additionally, the influence of microbiota on the effectiveness of treatments such as immunotherapy and chemotherapy highlights its dual function in improving treatment outcomes and reducing side effects. To optimize treatment results, strategies including dietary changes and fecal microbiota transplantation (FMT) are being investigated. Despite these developments, there are still issues, such as individual variations in microbial composition, a lack of standardized procedures, and the requirement for reliable biomarkers. Integrating microbiome-based diagnostics with conventional approaches, such as liquid biopsies and machine learning algorithms, could revolutionize cancer detection and management. This review provides an overview of the current understanding of the host-microbe immunological axis and discusses emerging therapeutic strategies centered on microbiota modulation to support human health. Further research is essential to overcome existing challenges and fully realize the promise of microbiota-driven innovations in oncology.}, } @article {pmid40402463, year = {2025}, author = {Li, L and Hu, M and Zhu, X and Huang, X and Chen, H}, title = {Microbiota Transplantation in Tumor Immunology Studies.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2930}, number = {}, pages = {295-306}, pmid = {40402463}, issn = {1940-6029}, mesh = {*Neoplasms/immunology/therapy/microbiology/pathology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/immunology ; Animals ; Humans ; Mice ; Feces/microbiology ; }, abstract = {This protocol outlines the standardized procedures for utilizing fecal microbiota transplantation (FMT) in tumor immunology studies. FMT, the process of transferring gut microbiota from a healthy donor to a recipient, has shown potential in modulating the immune response against tumors. This protocol details the selection criteria for donors and recipients, preparation and processing of fecal material, and the administration routes for transplantation. Additionally, it describes the pre- and posttransplantation monitoring of microbiota composition, immune parameters, and tumor progression. By following this protocol, researchers can systematically investigate the impact of microbiota on tumor growth and immune modulation, contributing to the development of microbiota-based therapeutic strategies in oncology.}, } @article {pmid40401951, year = {2025}, author = {Huang, J and Qiao, H and Li, Q and Zhang, Y and Zhang, C and Su, H and Sun, X}, title = {Osteopontin protects from ovalbumin-induced asthma by preserving the microbiome and the intestinal barrier function.}, journal = {mSystems}, volume = {10}, number = {6}, pages = {e0038925}, pmid = {40401951}, issn = {2379-5077}, mesh = {Animals ; *Osteopontin/genetics/metabolism ; *Asthma/chemically induced/microbiology/prevention & control/immunology/metabolism ; Mice ; *Gastrointestinal Microbiome ; Ovalbumin ; Mice, Knockout ; Lung/microbiology/immunology ; Mice, Inbred C57BL ; Disease Models, Animal ; Intestinal Mucosa/metabolism ; Dysbiosis ; T-Lymphocytes, Regulatory/immunology ; Female ; Intestinal Barrier Function ; }, abstract = {UNLABELLED: The gut and lung microbiota are associated with asthma. Osteopontin (OPN) is an important cytokine associated with several inflammatory diseases. The potential role of OPN in the asthma-associated microbiome remains poorly understood. Here, we investigated whether OPN could moderate asthma by affecting the gut and lung microbiota. Our results showed that compared with wild-type (WT) mice, Spp1[-/-] mice exhibited immune cell infiltration in the lung, OVA-specific IgG1, increased levels of Th2- and Th17-related inflammatory factors, and decreased levels of Th1-related inflammatory factors and forkhead box P3 (FOXP3) expression, resulting in a Th1/Th2 and Th17/Treg imbalance. In addition, gut structure was impaired, and expression of tight junction-related proteins was reduced in Spp1[-/-] mice, which disrupted gut barrier function. Importantly, OPN-deficient significantly aggravated gut and lung microbiota dysbiosis in OVA-induced asthmatic mice. The results of high-throughput 16S rRNA sequencing demonstrated that OPN-deficient mice showed a substantial reduction in beneficial gut and lung bacteria (Bacteroidetes, Lactobacillus, Allobaculum), and an OVA-induced increase in the abundance of bacteria associated with potentially pathogenic gut and lung (Epsilonbacteraeota, Helicobacter, Desulfovibrio, Oscillibacter)-associated bacteria was elevated in abundance. Allobaculum was negatively correlated with interleukin-4 and GATA-3 and was positively correlated with interferon gamma and FOXP3. Moreover, through fecal microbiota transplantation, we found that OVA-induced IgE and IgG1 levels were reduced in OPN-deficient asthmatic mice, Th1/Th2 and Th17/Treg balance was maintained, gut barrier function was improved, and microbiome changes in OPN-deficient mice were compensated for, with an elevated abundance of Allobaculum and reduced abundance of Desulfovibrio and Oscillibacter. We further discovered that OPN deficiency reduces FOXP3 expression and decreases Lactobacillus colonization through activation of the PD-1/PD-L1 pathway in the intestine and lung. The present study suggests that OPN may moderate OVA-induced asthma by modulating the gut and lung microbiota.

IMPORTANCE: Osteopontin deficiency exacerbated asthmatic airway inflammation, an effect associated with microbiota dysbiosis, impaired intestinal barrier function, and increased PD-1/PD-L1 expression and thus decreased Treg cell function. The study provides clinicians with new insights into asthma mechanisms and can also lead to new ideas for asthma treatment.}, } @article {pmid40401932, year = {2025}, author = {McMullen, BN and Chen See, J and Baker, S and Wright, JR and Anderson, SLC and Yochum, G and Koltun, W and Portolese, A and Jeganathan, NA and Lamendella, R}, title = {Metatranscriptomic analysis of colonic mucosal samples exploring the functional role of active microbial consortia in complicated diverticulitis.}, journal = {Microbiology spectrum}, volume = {13}, number = {7}, pages = {e0243124}, pmid = {40401932}, issn = {2165-0497}, mesh = {Humans ; Middle Aged ; Male ; *Gastrointestinal Microbiome/genetics ; Female ; Aged ; *Bacteria/genetics/classification/isolation & purification ; *Colon/microbiology/pathology ; *Intestinal Mucosa/microbiology ; *Microbial Consortia/genetics ; RNA, Ribosomal, 16S/genetics ; *Diverticulitis/microbiology ; Aged, 80 and over ; Adult ; Feces/microbiology ; Transcriptome ; }, abstract = {In this study, we investigated complicated diverticulitis, an inflammatory condition associated with abscesses, fistulas, intestinal obstructions, perforations, and primarily affects adults over the age of 60. Although the exact etiology remains unclear, the gut microbiome has been suggested as a contributing factor. Previous studies have used 16S rRNA gene analysis from patient fecal samples, which is limited to identifying the bacterial communities present. Herein, we employed shotgun metatranscriptomics on 40 patient-matched samples of diseased and adjacent normal colonic mucosal tissues from 20 patients with complicated diverticulitis to gain a more comprehensive understanding of active microbial taxa and gene expression patterns that may be involved in this disease state. Our findings revealed distinct beta diversity and a conglomerate of pathogenic microbiota in the diseased tissues, including Staphylococcus cohnii, Corynebacterium jeikeium, Kineococcus, Talaromyces rugulosus, Campylobacteraceae, and Ottowia, among others. The adjacent normal tissues were a stark contrast, harboring anti-inflammatory taxa such as Streptococcus salivarius and housekeeping genes and pathways such as the ABC-2 type transport system ATP-binding protein. These results align with previous amplicon sequencing studies and provide novel functional insights that may be crucial for understanding the etiology of complicated diverticulitis.IMPORTANCEComplicated diverticulitis is a virulent condition with no clear cause other than the association with colonic diverticulosis. We assessed the microbial gene expression in complicated diverticulitis patients using colonic tissue samples, revealing microbes in the diseased tissue known to exacerbate the diverticular condition and to live in extreme places, and microbes in patients' normal tissue known to maintain normal bodily functions. This functional information is therefore important for understanding what microbial taxa are present and what they are doing. It is possible clinicians could someday harness this information to more effectively treat complicated diverticulitis symptoms. For example, clinicians may suggest dietary changes and prescribe probiotics to increase beneficial bacteria. Clinicians may also prescribe targeted antibiotics or consider the emerging treatment option of fecal transplants in complicated diverticulitis patients. While not curing complicated diverticulitis, each potential treatment option mentioned addresses balancing out dysbiosis of the gut microbiome, therefore alleviating associated symptoms.}, } @article {pmid40400677, year = {2025}, author = {Men, J and Cui, C and Li, H and Li, Z and Zhang, Y and Liu, Z and Wang, Q and Liu, P and Zou, S and Yu, Z and Zhang, Y and Wu, S and Zhu, G and Wang, P and Huang, X}, title = {Cold water swimming reshapes gut microbiome to improve high-fat diet-induced obesity.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1589902}, pmid = {40400677}, issn = {1664-302X}, abstract = {Hypothermia and swimming have been shown to alleviate high-fat diet (HFD)-induced obesity, with effects linked to the gut microbiota (GM). However, whether the effects of cold water swimming (CWS) on GM can be effectively transferred through fecal microbiota transplantation (FMT) has not been investigated. This study established mice models of obesity, CWS and FMT to investigate the mechanism by which CWS reshapes GM to improve HFD-induced obesity. Additionally, we analyzed the relationship between obesity phenotypes, GM composition, gene expression and CWS. The study found that HFD induced obesity phenotypes and GM dysbiosis in mice, while CWS produced opposite effects. The FMT results confirmed that CWS effectively alleviated HFD-induced lipid accumulation, metabolic disorders, and chronic inflammatory responses, which are associated with increased GM diversity, enrichment of beneficial bacteria, and the repair of intestinal barrier damage. Furthermore, these beneficial effects can be effectively transferred via FMT. The evidence from this study suggests that GM plays a critical role in the anti-obesity effects of CWS, with intestinal barrier repair emerging as a potential therapeutic target. This also provides scientific evidence for the feasibility of FMT as a strategy to combat obesity.}, } @article {pmid40399878, year = {2025}, author = {Qian, S and Su, Z and Lin, J and Hou, Q and Wang, X and Li, Y and Wang, J and Huang, C and Wang, Z and Cubero, FJ and Wang, X and Liao, L}, title = {Inhibition of Farnesoid-x-receptor signaling during abdominal sepsis by dysbiosis exacerbates gut barrier dysfunction.}, journal = {Cell communication and signaling : CCS}, volume = {23}, number = {1}, pages = {236}, pmid = {40399878}, issn = {1478-811X}, support = {81971814//the National Natural Science Foundation of China/ ; 81971814//the National Natural Science Foundation of China/ ; 81971814//the National Natural Science Foundation of China/ ; 81971814//the National Natural Science Foundation of China/ ; 20192BAB205013//the Natural Science Foundation of Jiangxi Province/ ; 20192BAB205013//the Natural Science Foundation of Jiangxi Province/ ; 20192BAB205013//the Natural Science Foundation of Jiangxi Province/ ; PWRd2020-06//Academic medicine leader's training Program in health systems of Pudong New Area/ ; PWYgf2021-03//Shanghai Pudong New Area Summit (emergency medicine and critical care) construction project/ ; 23Y11908300//Medical Innovation Research Special Project of Shanghai 2023 Science and Technology Innovation Action Plan/ ; 2020PJD050//Shanghai Pujiang Program/ ; }, mesh = {Animals ; *Receptors, Cytoplasmic and Nuclear/metabolism/agonists ; *Sepsis/metabolism/pathology/microbiology ; *Signal Transduction ; *Dysbiosis/metabolism/pathology ; Mice ; Myeloid Differentiation Factor 88/metabolism ; Fibroblast Growth Factors/metabolism ; Mice, Inbred C57BL ; Gastrointestinal Microbiome ; Male ; *Intestinal Mucosa/metabolism ; Liver/metabolism ; Bile Acids and Salts/metabolism ; }, abstract = {BACKGROUND AND AIMS: Bacterial translocation and intestinal dysbiosis due to gut barrier dysfunction are widely recognized as major causes of the initiation and development of intra-abdominal sepsis. Systemic bacterial translocation and hepatic activation of the myeloid differentiation primary response gene 88 (Myd88) can disturb bile acids (BAs) metabolism, further exacerbating intestinal dysbiosis. The farnesoid X receptor (FXR) and fibroblast growth factor (FGF) 15/19 are well known to be involved in the control of BAs synthesis and enterohepatic circulation. However, the influence of intestinal microbiota on intestinal Myd88 signaling, the FXR/FGF15 axis, as well as gut-liver crosstalk during sepsis remains unclear. The present study aims to decipher the role of intestinal Myd88 in abdominal sepsis, its impact on intestinal FXR signaling and FGF15-mediated gut-liver crosstalk.

METHODS: Expression levels of FXR and FGF15 in the liver and intestines, alongside assessments of gut barrier function, were evaluated in septic wild-type (WT) mice 24 h post-cecal ligation and puncture (CLP) surgery. Subsequently, the FXR agonist INT-747 was administered to explore the relationship between FXR activation and gut barrier function. Further investigations involved Myd88-deficient mice with specific deletion of Myd88 in intestinal epithelial cells (Myd88[△IEC]), subjected to CLP to examine the interplay among intestinal Myd88, FXR, gut barrier function, microbiota, and BA composition. Additionally, fecal microbiota transplantation (FMT) from septic mice to Myd88[△IEC] mice was conducted to study the impact of dysbiosis on intestinal Myd88 expression during sepsis, using floxed (Myd88[fl/fl]) mice as controls. Finally, the effects of the probiotic intervention on gut barrier function and sepsis outcomes in CLP mice were investigated.

RESULTS: Induction of sepsis via CLP led to hepatic cholestasis, suppressed FXR-FGF15 signaling, altered gut microbiota composition, and compromised gut barrier function. Administration of INT-747 increased intestinal FXR and FGF15 expression, strengthened gut barrier function, and enhanced barrier integrity. Interestingly, Myd88[△IEC] mice exhibited partial reversal of sepsis-induced changes in FXR signaling, BA metabolism, and intestinal function, suggesting enhanced FXR expression upon Myd88 knockdown. Moreover, FMT from septic mice activated intestinal Myd88, subsequently suppressing FXR-FGF15 signaling, exacerbating cholestasis, and ultimately compromising gut barrier function. Probiotic treatment during abdominal sepsis mitigated flora disturbances, reduced Myd88 activation in the intestinal epithelium, increased FXR expression, alleviated cholestasis, and consequently reduced barrier damage.

CONCLUSIONS: This study highlights the critical role of Myd88/FXR signaling in intestinal epithelial cells as a pivotal mediator of the detrimental effects induced by sepsis-related intestinal dysbiosis on barrier function and bile acid metabolism. In summary, disordered intestinal flora in septic mice specifically triggers intestinal epithelial Myd88 activation, inhibit the FXR-FGF15 axis, and then worsen intestinal barrier function impairment.}, } @article {pmid40398680, year = {2025}, author = {Zhou, YD and Komnick, MR and Sepulveda, F and Liu, G and Nieves-Ortiz, E and Meador, K and Ndatabaye, O and Fatkhullina, A and Bozicevich, A and Juengel, B and Wu-Woods, NJ and Naydenkov, PM and Kent, J and Christiansen, N and Madariaga, ML and Witkowski, P and Ismagilov, RF and Esterházy, D}, title = {Inducible, but not constitutive, pancreatic REG/Reg isoforms are regulated by intestinal microbiota and pancreatic diseases.}, journal = {Mucosal immunology}, volume = {18}, number = {4}, pages = {918-936}, doi = {10.1016/j.mucimm.2025.05.003}, pmid = {40398680}, issn = {1935-3456}, support = {R01 DK133393/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; Protein Isoforms/genetics/metabolism ; *Pancreatitis-Associated Proteins/genetics/metabolism ; *Gastrointestinal Microbiome/immunology ; *Pancreas/immunology/metabolism ; Disease Models, Animal ; Gene Expression Regulation ; Immunity, Innate ; *Pancreatitis/immunology ; Mice, Inbred C57BL ; Mice, Knockout ; *Pancreatic Diseases/immunology ; *Carcinoma, Pancreatic Ductal/immunology ; }, abstract = {The REG/Reg gene locus encodes a conserved family of potent antimicrobial but also pancreatitis-associated proteins. Here we investigated whether REG/Reg family members differ in their baseline expression levels and abilities to be regulated in the pancreas and gut upon perturbations. We found, in humans and mice, the pancreas and gut differed in REG/Reg isoform levels and preferences, with the duodenum most resembling the pancreas. Pancreatic acinar cells and intestinal enterocytes were the dominant REG producers. Intestinal symbiotic microbes regulated the expression of the same, select Reg members in gut and pancreas. These Reg members had the most STAT3-binding sites close to the transcription start sites and were partially IL-22 dependent. We thus categorized them as "inducible" and others as "constitutive". Indeed, in pancreatic ductal adenocarcinoma and pancreatitis models, only inducible Reg members were upregulated in the pancreas. While intestinal Reg expression remained unchanged upon pancreatic perturbation, pancreatitis altered the microbial composition of the duodenum and feces shortly after disease onset. Our study reveals differential usage and regulation of REG/Reg isoforms as a mechanism for tissue-specific innate immunity, highlights the intimate connection of pancreas and duodenum, and implies a gut-to-pancreas communication axis resulting in a coordinated Reg response.}, } @article {pmid40398524, year = {2025}, author = {He, X and Wei, X and He, Z and Yao, C and Nie, M and Ma, X and Chen, Q and Guo, DA}, title = {Biotransformation of artemisinin by human intestinal fungi and cytotoxicity against breast cancer cells of its metabolites.}, journal = {Phytochemistry}, volume = {238}, number = {}, pages = {114551}, doi = {10.1016/j.phytochem.2025.114551}, pmid = {40398524}, issn = {1873-3700}, mesh = {Humans ; *Artemisinins/metabolism/pharmacology/chemistry ; Biotransformation ; Mice ; Animals ; Female ; Drug Screening Assays, Antitumor ; *Breast Neoplasms/drug therapy/pathology ; *Intestines/microbiology ; MCF-7 Cells ; Molecular Structure ; *Antineoplastic Agents/pharmacology/metabolism/chemistry ; Cell Proliferation/drug effects ; *Rhizopus/metabolism ; *Fungi/metabolism ; *Candida/metabolism ; }, abstract = {Artemisinin widely exists in the Artemisia annua L. and is the front-line of antimalarial drugs. In this study, microbial transformation of artemisinin was performed based on seventeen human intestinal fungal species. Our findings revealed that isomerization and deoxygenation were the most prevalent metabolic pathways in fungi. Incubation of artemisinin with Rhizopus microspores (PT2906) and Candida boidinii (M7017B) afforded three new compounds (P3, P5 and P6) along with seven known metabolites which were elucidated by extensive spectroscopic data analysis. All metabolites were evaluated for their cytotoxicity against MCF-7 cells, and the results showed that 3β-hydroxydeoxyartemisinin (P5) suppressed the growth of MCF-7 cells better than artemisinin. In addition, ten artemisinin isomers were found in the feces of antibiotic-treated mice after M7017B transplantation, demonstrating that human intestinal fungi have the potential to participate in the in vivo intestinal transformation of artemisinin.}, } @article {pmid40398303, year = {2025}, author = {Xu, Y and Chen, K and Huang, Y and Yan, Y and Zhang, W and Tian, J and Zhang, D and Liu, M and Nie, Q}, title = {Fecal microbiota transplantation improves growth performance of chickens by increasing the intestinal Lactobacillus and glutamine.}, journal = {Poultry science}, volume = {104}, number = {8}, pages = {105243}, pmid = {40398303}, issn = {1525-3171}, mesh = {Animals ; *Chickens/growth & development/microbiology/genetics ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/veterinary ; *Lactobacillus/physiology ; *Glutamine/metabolism ; Intestines/microbiology ; }, abstract = {Chicken meat is an essential source of high-quality animal protein, mainly derived from slow-growth chicken (SC) and fast-growth chicken (FC) breeds. Skeletal muscle is a highly adaptable tissue that is influenced by breed differences and the gut microbiome. Investigation whether remodeling the gut microbiota by fecal microbiota transplantation (FMT) improves chicken growth is an interesting question. We compared the gut microbial composition of eight breeds of SC (Xinghua chicken, Yangshan chicken, Zhongshan Salan chicken, Qingyuan Partridge chicken, Huiyang Bearded chicken and Huaixiang chicken) and FC (Xiaobai chicken and White rock chicken). Fecal microbiota from donor FC (Xiaobai chickens) with superior growth performance were transferred to SC (Xinghua chickens). The effects of FMT on growth performance, metabolic profile and gut microbiome of recipient chickens were evaluated. We found significant differences in gut microbial composition, with a higher abundance of Bacteroidetes in SC and a higher abundance of Firmicutes in FC. Xiaobai chickens with better growth performance and abundant Lactobacillus, and FMT significantly enhanced growth performance, the expression of mRNA (MYOG, MYF5, MYF6 and IGF1) related to breast and leg muscle development and improved the villus/crypt ratio in the jejunum. FMT altered the microbiota in the duodenum, jejunum, and ileum, increased Lactobacillus abundance, decreased the relative mRNA expression of the intestinal inflammatory factors (IL-1β, IL-6 and TNF-α), increased glutamine levels in the host, including in muscle tissues and intestinal contents, and Spearman correlation analysis indicated that the relative abundance of Lactobacillus was positively correlated with glutamine levels. Additionally, antibiotic treatment reduces glutamine levels in the intestines, blood, and muscle tissues of chickens. Glutamine can increase the expression of cyclinD1, cyclinD2, cyclinB2, MYOG, MYF5, MYF6 and IGF1 mRNA to promote chicken myoblasts proliferation and differentiation. This study found that the SC and FC gut microbes were significantly different, and the FC chicken gut microbes were able to reshape the FC gut microbiota through FMT, i.e., higher Lactobacillus, promoted chicken myoblasts proliferation and differentiation and growth performance by increasing glutamine levels.}, } @article {pmid40398302, year = {2025}, author = {Yu, M and Xu, M and Wang, G and Feng, J and Zhang, M}, title = {Effect of cecal microbiota transplantation on peripheral 5-hydroxytryptamine and breast muscle glucose metabolism in long-photoperiod broilers.}, journal = {Poultry science}, volume = {104}, number = {8}, pages = {105225}, pmid = {40398302}, issn = {1525-3171}, mesh = {Animals ; *Chickens/physiology/metabolism/microbiology ; *Glucose/metabolism ; Male ; *Serotonin/metabolism ; *Photoperiod ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/veterinary ; *Muscle, Skeletal/metabolism ; Random Allocation ; Cecum/microbiology ; }, abstract = {Prolonged light periods resulted in up-regulation of cecal 5-hydroxytryptamine (5-HT) synthesis and secretion, disorders of breast muscle glucose metabolism and alteration in gut microbiota composition. The present study was conducted to investigate the effects of cecal microbiota on peripheral 5-HT metabolism and breast muscle glucose metabolism in broiler chickens underlying prolonged light periods. A total of 144 5-day-old male Arbor Acres (AA) broiler chickens were randomly divided into four treatment groups i.e., 12 hours light: 12 hours dark (12L:12D) photoperiod group, 18 hours light: 6 hours dark (18L:6D) photoperiod group, 18L:6D photoperiod with phosphate buffered saline (PBS) solution administration group (18L:6D+PBS) and 18L:6D photoperiod with cecal microbiota transplantation (CMT) group (18L:6D+CMT) for 14 days. The results demonstrated that the 18L:6D photoperiod increased breast muscle rate (P < 0.05) but induced the morphological damage of breast muscle, dysregulation of breast muscle glucose metabolism and higher peripheral 5-HT synthesis (P < 0.05). In contrast, CMT significantly improved breast muscle weight and breast muscle ratio while reducing the breast muscle injury. Furthermore, CMT alleviated glucose metabolism dysregulation, as evidenced by significant reductions in serum glucose (P < 0.05), insulin (INS) (P < 0.05), homeostasis model assessment of insulin resistance (HOMA-IR) (P < 0.05), and the lactic acid-to-pyruvate ratio (L/P) (P < 0.05), as well as an increase in muscle glycogen concentrations (P < 0.05). Additionally, the expression of glycogen synthase (GS), pyruvate dehydrogenase (PDH) and glucose transporter-4 (GLUT4) up-regulated, while the expression of glycogen phosphorylase L (PYGL), hexokinase (HK), 6-phosphofructokinase (PFK), pyruvate kinase (PK) and lactate dehydrogenase (LDH) down-regulated (P < 0.05) in breast muscle of CMT-treated broiler chickens. Notably, both peripheral 5-HT concentrations and cecal 5-HT synthesis was significantly reduced (P < 0.05) in the 18L:6D+CMT group. In summary, these findings indicate that CMT promotes breast muscle rate, reduces breast muscle injury, alleviates breast muscle glucose metabolism disorder in broiler chickens exposed to prolonged light periods. Moreover, peripheral 5-HT metabolism may serve as a key pathway through which cecal microbiota regulates skeletal muscle glucose metabolism.}, } @article {pmid40395920, year = {2025}, author = {Ishikawa, D and Zhang, X and Nagahara, A}, title = {Current Applications and Future Prospects of Fecal Microbiota Transplantation.}, journal = {Juntendo medical journal}, volume = {71}, number = {2}, pages = {68-75}, pmid = {40395920}, issn = {2759-7504}, abstract = {In recent years, the impact of gut microbiota on human health has gained increasing recognition, highlighting the potential benefits of regulating gut microbiota for patient care. Consequently, fecal microbiota transplantation (FMT) has emerged as a novel treatment for improving dysbiosis. It is necessary to summarize and discuss the current research and future development possibilities. This advanced microbial therapy restores the gut microbiome by introducing a diverse array of microorganisms from healthy donors, thereby correcting dysbiosis and re-establishing a fully functional ecosystem. Ongoing research on FMT is actively conducted in various fields worldwide. This study provides an overview of the progress of clinical research on the effects of FMT in gastrointestinal diseases, immune checkpoint inhibitors, allergic diseases, and central nervous system diseases, as well as the results of our ongoing clinical study on "FMT combined with antibiotics for ulcerative colitis."}, } @article {pmid40395507, year = {2025}, author = {Shabani, M and Ghoshehy, A and Mottaghi, AM and Chegini, Z and Kerami, A and Shariati, A and Taati Moghadam, M}, title = {The relationship between gut microbiome and human diseases: mechanisms, predisposing factors and potential intervention.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1516010}, pmid = {40395507}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology ; Probiotics ; Prebiotics ; Metabolic Diseases/microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Diseases/microbiology ; Nervous System Diseases/microbiology ; Disease Susceptibility ; Diet ; Diabetes Mellitus, Type 2/microbiology ; }, abstract = {The complex interrelation of gut microbiota with human health underlines the profound influence this microbial ecosystem has on mechanisms of disease and wellness. The gut microbiome profoundly impacts various human diseases, encompassing gastrointestinal disorders, metabolic disorders, neurological disorders, and immune-related diseases. Gastrointestinal disorders are closely linked to microbial imbalances in the gut. Metabolic disorders, including obesity and type 2 diabetes, are influenced by the gut microbiota's role in energy regulation and glucose metabolism. Furthermore, the gut-brain axis highlights the correlation between gut microbiota and neurological conditions such as Alzheimer's and Parkinson's. Moreover, the gut microbiome assumes a pivotal function in regulating the immune system, whereby dysbiosis is implicated in developing immunological-related ailments, including allergies and autoimmune disorders. Predisposing factors, including diet, medicines, lifestyle, and environmental influences, are described as having an important role in the composition of the gut microbiome. By understanding these factors, we can get valuable insights into how to intervene to reduce the chances of a disease. Current interventions, including probiotics, prebiotics, fecal microbiota transplants, and lifestyle modification, show promise, but there are still challenges and unanswered questions in this evolving field that may lead to improvements. This review interrelates the complicated gut microbiome with various human diseases, mechanisms, predisposing factors, and potential interventions.}, } @article {pmid40394204, year = {2025}, author = {Oliver, PJ and Civitelli, L and Hu, MT}, title = {The gut-brain axis in early Parkinson's disease: from prodrome to prevention.}, journal = {Journal of neurology}, volume = {272}, number = {6}, pages = {413}, pmid = {40394204}, issn = {1432-1459}, mesh = {Humans ; *Parkinson Disease/prevention & control/metabolism/microbiology/physiopathology ; *Gastrointestinal Microbiome/physiology ; alpha-Synuclein/metabolism ; *Prodromal Symptoms ; *Brain-Gut Axis/physiology ; *Brain/metabolism ; Dysbiosis ; Animals ; }, abstract = {Parkinson's disease is the second most common neurodegenerative disorder and fastest growing neurological condition worldwide, yet its etiology and progression remain poorly understood. This disorder is characterized pathologically by the prion-like spread of misfolded neuronal alpha-synuclein proteins in specific brain regions leading to Lewy body formation, neurodegeneration, and progressive neurological impairment. It is unclear what triggers Parkinson's and where α-synuclein protein aggregation begins, although proposed induction sites include the olfactory bulb and dorsal motor nucleus of the vagus nerve. Within the last 20 years, there has been increasing evidence that Parkinson's could be triggered by early microbiome changes and α-synuclein accumulation in the gastrointestinal system. Gut microbiota dysbiosis that alters gastrointestinal motility, permeability, and inflammation could enable prion-like spread of α-synuclein from the gut-to-brain via the enteric nervous system. Individuals with isolated rapid eye movement sleep behavior disorder have a high likelihood of developing Parkinson's and might represent a prodromal 'gut-first' subtype of the condition. The gut-first model of Parkinson's offers novel gut-based therapeutic avenues, such as anti-, pre-, and pro-biotic preparations and fecal microbiota transplants. Crucially, gut-based interventions offer an avenue to treat Parkinson's at early prodromal stages with the aim of mitigating evolution to clinically recognizable Parkinson's disease characterized by motor impairment.}, } @article {pmid40393939, year = {2025}, author = {Zhang, X and He, Q and Zhang, C and Ji, Z and Yang, D and Wang, X and Liu, C and Zhang, C and Yuan, J and Xu, N and Chu, J}, title = {Gegen Qinlian Decoction protects kidney in diabetic rats by improving intestinal barrier and regulating intestinal microbiota.}, journal = {The Journal of pharmacy and pharmacology}, volume = {77}, number = {8}, pages = {1109-1119}, doi = {10.1093/jpp/rgaf030}, pmid = {40393939}, issn = {2042-7158}, support = {82204707//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology ; *Diabetes Mellitus, Experimental/drug therapy/microbiology ; Male ; Rats, Sprague-Dawley ; Rats ; *Kidney/drug effects/pathology ; *Diabetic Nephropathies/prevention & control ; Fecal Microbiota Transplantation ; Intestinal Mucosa/drug effects/metabolism ; Oxidative Stress/drug effects ; Isoflavones/pharmacology ; Tight Junctions/drug effects ; Flavonoids/pharmacology ; Glucosides ; Flavanones ; }, abstract = {OBJECTIVES: To investigate the renoprotective effects of Gegen Qinlian Decoction (GQD) in Diabetes mellitus (DM) rats via the intestinal barrier and microbiota.

METHODS: GQD was analyzed by UPLC. STZ-induced DM rat models and antibiotic-induced sterile DM rat models were established, and fecal microbiota transplantation was performed in the latter. Renal function, oxidative stress, serum inflammatory factors, and pathological alterations were assessed. Intestinal cells and tight junction were observed by transmission electron microscopy. Inflammatory factors in the colon and tight junction protein expression were evaluated. The gut microbiota and its abundance were assessed by 16sRNA sequencing.

KEY FINDINGS: Four components were determined in the GQD, including puerarin, baicalin, berberine, and liquiritin. After GQD treatment, Scr and BUN were reduced, renal pathological changes were attenuated, intestinal cell swelling was reduced, intestinal tight junctions were improved, and GQD modulated the intestinal microbiota. Furthermore, a fecal bacterial solution containing GQD reduced renal lesions, improved intestinal tight junctions, and regulated intestinal microbiota in DM rats.

CONCLUSIONS: GQD regulated the intestinal microbiota of DM rats, reduced intestinal inflammation, and repaired the intestinal barrier, thus reducing the burden on the kidneys, and exerting a protective effect on the kidneys of DM rats.}, } @article {pmid40393246, year = {2025}, author = {Liu, X and Li, Y and Yuan, C and Zhao, Y and Zhou, L and Yan, Y and Ren, J and Liu, Q}, title = {Sophocarpine suppresses MAPK-mediated inflammation by restoring gut microbiota in colorectal cancer.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {143}, number = {}, pages = {156833}, doi = {10.1016/j.phymed.2025.156833}, pmid = {40393246}, issn = {1618-095X}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Colorectal Neoplasms/drug therapy/microbiology ; Animals ; Humans ; Mice ; *Alkaloids/pharmacology ; Fecal Microbiota Transplantation ; Inflammation/drug therapy ; Cell Line, Tumor ; Male ; Mice, Inbred BALB C ; *Antineoplastic Agents, Phytogenic/pharmacology ; MAP Kinase Signaling System/drug effects ; Dysbiosis/drug therapy ; Xenograft Model Antitumor Assays ; Mice, Nude ; p38 Mitogen-Activated Protein Kinases/metabolism ; Matrines ; }, abstract = {BACKGROUND: Colorectal cancer (CRC), as one of the most common cancers globally, poses a significant challenge to public health due to its high incidence and mortality rates. This underscores the need for continuous exploration of new therapeutic targets and effective drugs. Sophocarpine (SC), a natural compound derived from traditional Chinese medicine, holds considerable therapeutic potential in the treatment of CRC, however, the relevant mechanisms remains unclear.

PURPOSE: This study aims to explore the anti-tumor effects of SC against CRC by modulating gut microbiota, and uncover potential mechanisms linking SC's therapeutic effects to gut microbiota regulation by analyzing the impact of SC on microbiota composition and CRC progression.

MATERIAL: This study explores the impact of SC on the gut microbiota in CRC by constructing subcutaneous xenograft tumors of CRC and integrating 16S rRNA sequencing and RNA transcriptomic sequencing. The fecal microbiota transplantation (FMT) mouse model was used to validate the biological function of SC in correcting gut microbiota dysbiosis to treat CRC. Subsequently, we conducted in vitro studies on the molecular mechanisms by which SC regulates the gut microbiota as an effective hallmark of CRC treatment, using lipopolysaccharide (LPS) to simulate an inflammatory gut microbiota environment and P38 MAPK knockdown cell line.

RESULTS: SC significantly inhibited CRC cell proliferation with IC50 values of 2.547±0.256 μM for HCT116 and 2.851±0.332 μM for LoVo cells. In vivo experiments demonstrated that SC effectively suppressed tumor growth in xenograft models. 16S rRNA sequencing revealed that SC modulated gut microbiota composition, particularly affecting Bacteroides and Alistipes populations. SC significantly reduced the levels of inflammatory factors and inhibited the MAPK signaling pathway, as evidenced by decreased p-JNK, p-p38 MAPK, and p-NF-κB p65 expression.

CONCLUSIONS: Current clinical practice still lacks effective therapeutic agents targeting CRC through gut microbiota modulation. This study presents the first evidence that SC, a natural compound, exhibits dual-action therapeutic efficacy against CRC progression by simultaneously modulating gut microbial composition and suppressing MAPK pathway-mediated inflammatory responses. These findings highlight SC's novel therapeutic potential as a promising microbiota-regulating candidate for CRC intervention, offering an innovative approach that bridges microbial ecology with cancer signaling pathways.}, } @article {pmid40392289, year = {2025}, author = {Piteková, B and Hric, I and Baranovičová, E and Zieg, J and Planet, PJ and Bielik, V}, title = {The effect of fecal microbial transplantation in a pediatric patient after 28 episodes of febrile urinary tract infection.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {}, number = {}, pages = {}, pmid = {40392289}, issn = {1432-198X}, support = {VEGA 1/0313/25//Ministerstvo školstva, vedy, výskumu a športu Slovenskej republiky/ ; VEGA 1/0022/26//Ministerstvo školstva, vedy, výskumu a športu Slovenskej republiky/ ; APVV-22-0047//Agentúra Ministerstva Školstva, Vedy, Výskumu a Športu SR/ ; }, abstract = {Recurrent febrile urinary tract infections (fUTIs) in children can lead to serious complications such as renal scarring and progressive chronic kidney disease (CKD), with growing evidence indicating that gut microbiome dysbiosis may play a key role in their development. Fecal microbial transplantation (FMT) is an established therapeutic approach for restoring gut microbial balance; however, its use in patients with recurrent fUTIs remains limited and underexplored. This case study describes a 10-year-old boy with recurrent fUTIs and CKD secondary to a posterior urethral valve (PUV) anomaly. The patient was administered a total of seven doses of FMT. FMT reduced pathogenic Enterobacteriaceae, increased beneficial short-chain fatty acid (SCFA)-producing genera, and correspondingly raised SCFA levels, indicating restoration of gut microbiota balance. FMT presents an innovative therapeutic option for pediatric patients with recurrent fUTIs, demonstrating outstanding clinical outcomes.}, } @article {pmid40391506, year = {2025}, author = {Ai, R and Jin, Y and Zhang, F and Cui, B and Ji, G}, title = {Washed microbiota transplantation effectively treats a case of acute severe ulcerative colitis combined with viral myocarditis.}, journal = {Journal of biomedical research}, volume = {39}, number = {4}, pages = {430-434}, pmid = {40391506}, issn = {1674-8301}, abstract = {Viral myocarditis is a rare but life-threatening complication in patients with ulcerative colitis. Management of myocarditis is primarily supportive, because there are currently no established targeted therapies. Recent studies have increasingly highlighted the association between the gut microbiota and myocarditis. Here, we report a case of acute severe ulcerative colitis complicated by cytomegalovirus and Epstein-Barr virus co-infections that led to viral myocarditis. The patient experienced rapid remission of both intestinal and cardiac symptoms following washed microbiota transplantation, suggesting this intervention may serve as a potential alternative treatment for these life-threatening conditions.}, } @article {pmid40390988, year = {2025}, author = {Abdulaal, R and Tlaiss, Y and Jammal, F and Moussbah, TH and Tarchichi, A and Hteit, A and Tlais, M and Nassif, D}, title = {The role of microbiome dysbiosis in cardiovascular disease: Mechanisms and therapeutic implications.}, journal = {Global cardiology science & practice}, volume = {2025}, number = {1}, pages = {e202503}, pmid = {40390988}, issn = {2305-7823}, abstract = {The gut microbiome plays a critical role in cardiovascular disease (CVD) pathogenesis through systemic inflammation, disrupted lipid metabolism, and proatherogenic metabolites like trimethylamine-N-oxide (TMAO). Dysbiosis contributes to increased intestinal permeability, platelet hyperreactivity, and reduced short-chain fatty acids (SCFAs), exacerbating cardiovascular risk. Emerging microbiome-targeted therapies, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary interventions, show promise in mitigating CVD. However, challenges remain in translating these findings into clinical practice due to strain-specific effects and interindividual variability. The gut-heart axis represents a transformative avenue for CVD prevention and management, warranting further research to optimize long-term efficacy and safety.}, } @article {pmid40390224, year = {2025}, author = {Adedayo, SI and Riethmacher, E}, title = {Emerging New Treatments for Colon Cancer.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0109298673372776250505155945}, pmid = {40390224}, issn = {1875-533X}, abstract = {Colorectal cancer includes cancer of the rectum and colon. It is the primary cause of cancer-related deaths among men under 50 years of age. In 2022, over 1.9 million cases of CRC were reported, resulting in approximately 904,000 deaths worldwide. Factors like smoking, alcohol consumption, obesity, familial history, and inflammation significantly contribute to the risk of CRC development. Additionally, bacterial infections from organisms like Bacteroides fragilis, Fusobacterium nucleatum, and Helicobacter pylori also play a role in increasing this risk. Conventional treatment methods for CRC typically involve surgery/polypectomy, chemotherapy, and radiotherapy. Because of limitations like lack of target specificity, the risk of tumor relapse, and the potential for tumor resistance, there is a growing necessity for more individually tailored treatment strategies to improve the outcomes of patients with CRC. As such, emerging treatments like cancer vaccine, (CAR) T-cells, CAR-NK cells, macrophages, and stem cell engineering (particularly mesenchymal stem cells), dendritic vaccine, siRNA, and miRNA, hold significant promise in enhancing outcomes for CRC patients. Moreover, specific gut microbiomes like Bacteroides fragilis, Streptococcus gallolyticus, Enterococcus faecalis, and Escherichia coli, linked to CRC development, have been identified. Hence, modulating the gut microbiome to potentially enhance responses to CRC in high- -risk populations could be a new line of treatment. This modulation can be accomplished through dietary interventions, prebiotics, probiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT). This review summarizes the most promising new emerging treatments in the fight against colon cancer.}, } @article {pmid40390189, year = {2025}, author = {Krynicka, P and Koulaouzidis, G and Marlicz, W and Koulaouzidis, A}, title = {Innovations in the diagnosis, treatment, and management of disorders of gut-brain interaction (DGBI).}, journal = {Expert review of gastroenterology & hepatology}, volume = {19}, number = {6}, pages = {657-670}, doi = {10.1080/17474124.2025.2508967}, pmid = {40390189}, issn = {1747-4132}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Irritable Bowel Syndrome/therapy/physiopathology/diagnosis/microbiology ; *Brain-Gut Axis ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; *Dyspepsia/therapy/physiopathology/diagnosis/microbiology ; Prebiotics/administration & dosage ; }, abstract = {INTRODUCTION: Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are the most prevalent disorders of gut-brain interaction (DGBI), frequently overlapping and associated with complex pathophysiological mechanisms. Increasing evidence implicates gut microbiota alterations in driving symptoms via immune activation, altered motility, gut vascular barrier and gut-brain axis disruption.

AREAS COVERED: This review explores the role of gut microbiota in FD and IBS pathogenesis and symptomatology. A comprehensive literature search was conducted using PubMed, EMBASE, and Google Scholar databases, including studies published between January 2013 and March 2025. Particular focus is given to microbiota-targeted therapies such as prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT). The review also discusses multidimensional treatment strategies combining dietary and lifestyle modification, cognitive-behavioral therapy, and pharmacological neuromodulation. Recent advances in diagnostic methods, including capsule-based microbiota sampling and digital tools for remote psychogastroenterology care, are highlighted.

EXPERT OPINION: Despite scientific progress, current DGBI management remains insufficiently personalized. Future approaches should integrate individualized microbiota profiling with targeted interventions and utilize innovative diagnostic and digital health technologies to enhance clinical outcomes in FD and IBS.}, } @article {pmid40390033, year = {2025}, author = {Teng, T and Huang, F and Xu, M and Li, X and Zhang, L and Yin, B and Cai, Y and Chen, F and Zhang, L and Zhang, J and Geng, A and Chen, C and Yu, X and Sui, J and Zhu, ZJ and Guo, K and Zhang, C and Zhou, X}, title = {Microbiota alterations leading to amino acid deficiency contribute to depression in children and adolescents.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {128}, pmid = {40390033}, issn = {2049-2618}, support = {82301714//the National Natural Science Foundation of China/ ; 22425404//the National Natural Science Foundation of China/ ; 82271565//the National Natural Science Foundation of China/ ; 2023TQ0398//the China Postdoctoral Science Foundation/ ; CSTB2023NSCQ-BHX0106//Natural Science Foundation of Chongqing, China/ ; 2208013341918508//Postdoctoral Innovation Talents Support Program of Chongqing, China/ ; 2022YFC3400702//National Key R&D Program of China/ ; 2024YFC2707800//National Key R&D Program of China/ ; 2022ZD0212900//STI2030-Major Projects/ ; }, mesh = {Humans ; Adolescent ; Child ; *Gastrointestinal Microbiome/physiology ; Male ; *Depressive Disorder, Major/microbiology/metabolism ; Female ; *Amino Acids/deficiency/blood/metabolism ; Magnetic Resonance Imaging ; Animals ; Rats ; Brain/diagnostic imaging/metabolism ; Feces/microbiology ; Metagenomics/methods ; Metabolomics/methods ; *Depression/microbiology ; }, abstract = {BACKGROUND: Major depressive disorder (MDD) in children and adolescents is a growing global public health concern. Metabolic alterations in the microbiota-gut-brain (MGB) axis have been implicated in MDD pathophysiology, but their specific role in pediatric populations remains unclear.

RESULTS: We conducted a multi-omics study on 256 MDD patients and 307 healthy controls in children and adolescents, integrating plasma metabolomics, fecal metagenomics, and resting-state functional magnetic resonance imaging (rs-fMRI) of the brain. KEGG enrichment analysis of 360 differential expressed metabolites (DEMs) indicated significant plasma amino acid (AA) metabolism deficiencies (p-value < 0.0001). We identified 58 MDD-enriched and 46 MDD-depleted strains, as well as 6 altered modules in amino acid metabolism in fecal metagenomics. Procrustes analysis revealed the association between the altered gut microbiome and circulating AA metabolism (p-value = 0.001, M[2] = 0.932). Causal analyses suggested that plasma AAs might mediate the impact of altered gut microbiota on depressive and anxious symptoms. Additionally, rs-fMRI revealed that connectivity deficits in the frontal lobe are associated with depression and 22 DEMs in AA metabolism. Furthermore, transplantation of fecal microbiota from MDD patients to adolescent rats induced depressive-like behaviors and 14 amino acids deficiency in the prefrontal cortex (PFC). Moreover, the dietary lysine restriction increased depression susceptibility in adolescent rats by reducing the expression of excitatory amino acid transporters in the PFC.

CONCLUSIONS: Our findings highlight that gut microbiota alterations contribute to AAs deficiency, particularly lysine, which plays a crucial role in MDD pathogenesis in children and adolescents. Targeting AA metabolism may offer novel therapeutic strategies for pediatric depression. Video Abstract.}, } @article {pmid40390010, year = {2025}, author = {Han, J and Meng, X and Kong, H and Li, X and Chen, P and Zhang, XA}, title = {Links between short-chain fatty acids and osteoarthritis from pathology to clinic via gut-joint axis.}, journal = {Stem cell research & therapy}, volume = {16}, number = {1}, pages = {251}, pmid = {40390010}, issn = {1757-6512}, support = {Grant No. 32371184//National Natural Science Foundation of China/ ; No. 2023JH2/101300072//the Liaoning Province Applied Basic Research Program/ ; LJKQZ20222425//the basic scientific research project of higher education institutions of Liaoning Province/ ; }, mesh = {Humans ; *Osteoarthritis/metabolism/pathology ; *Fatty Acids, Volatile/metabolism ; *Gastrointestinal Microbiome ; Animals ; *Joints/metabolism/pathology ; }, abstract = {Short-chain fatty acids (SCFAs), the primary metabolites produced by the microbial fermentation of dietary fibers in the gut, have a key role in protecting gut health. Increasing evidence indicates SCFAs can exert effects on distant tissues and organs beyond the gut via blood circulation. Osteoarthritis (OA) is a chronic inflammatory joint disease that severely diminishes the physical function and quality of life. However, effective clinical treatments for OA remain elusive. Recent studies have shown that SCFAs can exert beneficial effects on damaged joints in OA. SCFAs can mitigate OA progression by preserving intestinal barrier function and maintaining the integrity of cartilage and subchondral bone, suggesting that they have substantial potential to be the adjunctive treatment strategy for OA. This review described the SCFAs in the human body and their cellular signaling mechanism, and summarized the multiple effects of SCFAs (especially butyrate, propionate, and acetate) on the prevention and treatment of OA by regulating the gut-joint axis, providing novel insights into their promising clinical applications.}, } @article {pmid40388727, year = {2025}, author = {Kong, J and Han, X and Wei, C}, title = {Causal relationship between metabolic dysfunction-associated fatty liver disease and endotoxin biomarkers: A Mendelian randomization study.}, journal = {Medicine}, volume = {104}, number = {20}, pages = {e42311}, pmid = {40388727}, issn = {1536-5964}, support = {[No. (2022)4].//Shandong Provincial Key Laboratory of Traditional Chinese Medicine/ ; }, mesh = {Humans ; Mendelian Randomization Analysis ; *Non-alcoholic Fatty Liver Disease/genetics/blood ; Biomarkers/blood ; *Lipopolysaccharides/blood ; Genome-Wide Association Study ; Acute-Phase Proteins/genetics ; Obesity ; Carrier Proteins/blood ; Membrane Glycoproteins/blood ; *Metabolic Syndrome/genetics ; Risk Factors ; Triglycerides/blood ; Cholesterol, HDL/blood ; *Endotoxins/blood ; }, abstract = {Although the relationship among lipopolysaccharides (LPS), LPS-binding proteins, and metabolic dysfunction-associated fatty liver disease (MAFLD) is widely studied, no conclusive evidence is available. In this study, we used mendelian randomization (MR) to study the causal relationship of LPS, LPS-binding proteins, and MAFLD. Using bidirectional two-sample MR method, we evaluated data from the genome wide association study; for this analysis, nonalcoholic fatty liver disease (NAFLD), liver fat percentage, and other metabolic syndromes were employed as outcomes. Furthermore, MR analysis mainly involved the inverse variance weighted method. Heterogeneity and pleiotropy tests were also conducted. LPS was found to have a causal relationship with NAFLD, obesity, high density lipoprotein cholesterol, and TG levels. Furthermore, TG levels and LBP had significant causal relationships. This study mainly concluded that LPS is a risk factor for NAFLD, obesity, high density lipoprotein cholesterol, and TG, corroborating it's the LPS role in MAFLD pathogenesis. Hence, optimizing the gut microbiota using proper diet, probiotics, or fecal microbiota transplantation may help to reduce inflammation and (IR), thereby improving lipid and glucose metabolism disorders. Although a causal relationship between TG and LBP was observed, further studies are required to determine a specific mechanism.}, } @article {pmid40388258, year = {2025}, author = {Ebadpour, N and Abavisani, M and Sahebkar, A}, title = {Microbiome-driven precision medicine: advancing drug development with pharmacomicrobiomics.}, journal = {Journal of drug targeting}, volume = {}, number = {}, pages = {1-16}, doi = {10.1080/1061186X.2025.2509283}, pmid = {40388258}, issn = {1029-2330}, abstract = {Pharmacomicrobiomics investigates the complicated relationship between the gut microbiome and medications. Microbial communities can influence the metabolism and efficacy of many medications in two primary ways: directly and indirectly. Direct mechanisms typically entail the induction of biochemical alterations and multiple transformations directly on the drug, whereas indirect mechanisms encompass modifications in host metabolism, alterations in the gut microbial community, the synthesis of various metabolites, and interactions with the host immune system, which indirectly influence the drug's metabolism, absorption, and efficacy. For instance, microbial communities play an important part in activating prodrugs like sulfasalazine, improving the outcomes of immunotherapy, and minimising toxicity through specific interventions. Nonetheless, barriers can also emerge from the microbial breakdown of medications, reducing their therapeutic efficacy, along with adverse reactions mediated by microbiota. Innovations like probiotics, faecal microbiota transplantation, and microbiota profiling have shown promise in enhancing these interactions. Utilising the distinct microbiota composition of individuals, pharmacomicrobiomics offers a route to personalised, precise, and safer therapies, signalling an important evolution in drug development and clinical practice. This study aims to provide a comprehensive overview of microbiome-drug interactions.}, } @article {pmid40387516, year = {2025}, author = {Kochkarian, T and Nagy, HI and Li, Q}, title = {Gut-heart axis: cardiac remodeling and heart failure in the context of inflammatory bowel disease and dysbiosis.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {329}, number = {1}, pages = {G122-G137}, pmid = {40387516}, issn = {1522-1547}, support = {R01 HL152683/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Dysbiosis/metabolism ; *Heart Failure/metabolism/physiopathology/microbiology ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/microbiology/metabolism/complications/physiopathology ; Animals ; *Ventricular Remodeling ; MicroRNAs/metabolism ; }, abstract = {Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, are debilitating and complex chronic gastrointestinal disorders that affect not only the gut but also extraintestinal organs, including the heart. The gut-heart cross talk has garnered increasing attention in recent years; however, the molecular mechanisms underlying this complex interplay remain poorly understood. This review explores the gut-heart axis, focusing on how IBD disrupts gut microbiota homeostasis and promotes cardiac remodeling through systemic inflammation and various mediators, ultimately contributing to the onset or progression of heart failure. IBD compromises the integrity of the intestinal barrier, allowing microbial metabolites such as trimethylamine N-oxide and phenylacetylglutamine, along with inflammatory cytokines and microRNAs (miRNAs) (e.g., miR-155, miR-21, and let-7a), to enter the circulation and contribute to cardiac remodeling and heart failure. We identify dysfunction of nucleotide-binding oligomerization domain-containing protein 2 as a critical link between gut immunity and cardiovascular pathology. In addition, we discuss emerging microbiome-based therapeutic strategies, including fecal microbiota transplantation and IL-23 inhibitors, aimed at restoring gut homeostasis and mitigating cardiovascular risk. By integrating molecular mechanisms, clinical evidence, and therapeutic approaches, this review underscores the pivotal role of gut dysbiosis in cardiac dysfunction and offers new perspectives for managing cardiac dysfunction in patients with IBD.}, } @article {pmid40386180, year = {2025}, author = {Fang, Y and Min, S and Wu, Y and Xu, F and Chen, H and Li, Y and Lu, Y and Hu, J and Zhu, L and Shen, H}, title = {Integration of Multi-Omics and Network Pharmacology Analysis Reveals the Mechanism of Qingchang Huashi Jianpi Bushen Formula in Repairing the Epithelial Barrier of Ulcerative Colitis.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {6167-6189}, pmid = {40386180}, issn = {1178-7031}, abstract = {PURPOSE: Derivation of Qingchang Huashi formula, named Qingchang Huashi Jianpi Bushen (QCHS_JPBS) formula, has shown significant therapeutic effect on patients with ulcerative colitis (UC). In this study, the potential mechanism of QCHS_JPBS formula in repairing mucosal damage was explored from the perspective of intestinal stem cell (ISCs) differentiation, and potential targets of the QCHS_JPBS formula to improve UC were predicted using network pharmacology analysis.

METHODS: The therapeutic efficacy of QCHS_JPBS formula was evaluated in a mouse model of 2.5% dextran sulfate sodium (DSS) induced colitis. The effect of this formula on the ISC differentiation was evaluated using tissue transmission electron microscopy, immunofluorescence, and RT-qPCR. The cecal contents were subjected to 16s RNA sequencing analysis and non-target metabolomics analysis using LC-MS/MS. The fecal microbiota transplantation method verified the essential role of gut microbiota in promoting ISC differentiation and repairing mucosal damage.

RESULTS: The results indicated that QCHS_JPBS formula suppressed the inflammatory response and repaired the damaged intestinal epithelial barrier in DSS-induced colitis mice. QCHS_JPBS formula promoted ISC differentiation, particularly in the direction of goblet cells. QCHS_JPBS formula restored gut dysbiosis and regulated metabolic disorders in DSS-induced colitis mice. And then, the results of fecal microbiota transplantation indicated that QCHS_JPBS formula promoted differentiation of intestinal stem cells to repair mucosal damage through gut microbiota. Finally, a total of 79 active ingredients of QCHS_JPBS formula were identified based on LC-MS analysis and EGFR, STAT3, SRC, AKT1, and HSP90AA1 were considered as potential therapeutic UC targets of QCHS_JPBS formula based on network pharmacology analysis.

CONCLUSION: The present study demonstrated that QCHS_JPBS formula promoted the differentiation of ISCs through gut microbiota to repair the damaged intestinal epithelial barrier in UC mice.}, } @article {pmid40385744, year = {2025}, author = {Truong, MH and Ngo, T and Nguyen, QT and Le, H}, title = {Diagnosis and Treatment Outcomes of Fournier's Gangrene at a Tertiary Hospital.}, journal = {Cureus}, volume = {17}, number = {4}, pages = {e82344}, pmid = {40385744}, issn = {2168-8184}, abstract = {Introduction Fournier's gangrene (FG) is a severe necrotizing fasciitis caused by polymicrobial agents. This study aims to evaluate the clinical and paraclinical characteristics, treatment outcomes, and factors related to mortality in patients with FG at People's Hospital 115, Vietnam. Methods A retrospective cohort study was conducted on all adult patients diagnosed with FG at People's Hospital 115 from January 2018 to October 2024. Variables, including sociodemographic, clinical features, laboratory tests, and treatment outcomes, were collected. Data analysis was performed using SPSS version 26.0 (IBM Corp, Armonk, NY, USA). Results A total of 60 patients (47 males and 13 females) were enrolled; the mean age was 58.2 ± 12.6 years. The most common infection origins were from skin infections (36.7%), followed by the gastrointestinal tract (31.7%) and the genitourinary tract (30%). Most patients presented with symptoms such as perineal pain (98.3%), perianal swelling (91.7%), fever (48.3%), lower abdominal fluid collection (43.3%), and purulent discharge or perineal necrosis (31.7%). The most prevalent risk factor was diabetes mellitus (61.8%). Pathogenic bacteria that were commonly Escherichia coli, Klebsiella, and Proteus species could be isolated. Treatment involved both medical management (resuscitation, broad-spectrum antibiotics, and wound care) and surgical interventions (debridement, necrotic tissue excision, and fecal and urinary diversion). The overall mortality rate was 18.3%. Factors significantly associated with mortality included advanced age, female sex, a history of long-term corticosteroid use, high severity index scores, and septic shock. Conclusion FG is an uncommon urological emergency that is a rapidly progressing disease with a high mortality rate. Early detection and aggressive treatment approaches to achieve better outcomes.}, } @article {pmid40383915, year = {2025}, author = {Kim, YJ and Lee, J and Lee, E and Park, SJ and Kim, JH}, title = {Impact of stool transplantation and metformin on polyp reduction and inflammation in an APC Min mouse model.}, journal = {Intestinal research}, volume = {23}, number = {3}, pages = {382-389}, pmid = {40383915}, issn = {1598-9100}, support = {2020R1C1C1012694//National Research Foundation of Korea/ ; //Ministry of Science and ICT/ ; }, abstract = {BACKGROUND/AIMS: Familial adenomatous polyposis is a hereditary condition characterized by numerous adenomatous polyps in the colon and rectum, significantly increasing colorectal cancer risk. Current management strategies, such as prophylactic colectomy, are invasive and have long-term consequences, highlighting the need for alternative therapies. This study aimed to evaluate whether stool transplantation and metformin therapy synergistically reduce polyp formation and inflammation.

METHODS: APC Min mice were divided into 4 groups: control, anti-control (antibiotic pretreatment), stool (stool transplantation), and stool+metformin. Polyp burden, bacterial abundance, inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, IL-10), and tumorigenic markers (NF-κB, Cox2, c-myc, β-catenin) were assessed using messenger RNA (mRNA) and protein analyses of intestinal tissues, along with serum and fecal microbiota evaluations.

RESULTS: Stool transplantation combined with metformin significantly reduced bacterial abundance and polyp burden. The anti-control group showed similar reductions, suggesting suppression of gut microbiota re-establishment. TNF-α and IL-10 levels remained unchanged, but a significant increase in IL-6 was observed in the stool+metformin group's intestinal tissues, indicating localized immune activation. Intestinal Cox2 mRNA expression was reduced in the combination group, correlating with polyp suppression. Protein levels of NF-κB, Cox2, and β-catenin showed no significant changes in vivo, while in vitro experiments revealed a decrease in NF-κB and an increase in Cox2, suggesting complex regulation of inflammation-related pathways.

CONCLUSIONS: Stool transplantation combined with metformin reduces polyp burden in APC Min mice through gut microbiota modulation and localized immune activation. These findings support the therapeutic potential of this combination treatment for familial adenomatous polyposis.}, } @article {pmid40383790, year = {2025}, author = {Chen, J and Feng, R and Gong, BB and Wu, WK and Dai, BS and Tan, R and Xu, WL and Meng, T and Wang, XB and Xiao, YZ and Yang, C and Zhang, L and Liang, CZ}, title = {High-salt-driven gut microbiota dysfunction aggravates prostatitis by promoting AHR/SGK1/FOXO1 axis-mediated Th17 cell differentiation.}, journal = {Military Medical Research}, volume = {12}, number = {1}, pages = {21}, pmid = {40383790}, issn = {2054-9369}, support = {82300872//National Natural Science Foundation of China/ ; 82170787//National Natural Science Foundation of China/ ; T000529//Supporting Projects for Innovative Leading Talents/ ; 2021-108-10//Distinguished Young Scholar of Anhui Colleges/ ; 2022AH020073//Science Foundation for Outstanding Young Scholar of Anhui Colleges/ ; SZSM20210300//Sanming Project of Medicine in Shenzhen Nanshan/ ; 2408085Y038//Anhui Provincial Natural Science Foundation/ ; }, mesh = {Male ; Animals ; Mice ; *Prostatitis/physiopathology/etiology ; *Gastrointestinal Microbiome/drug effects/physiology ; *Th17 Cells/metabolism/drug effects ; Receptors, Aryl Hydrocarbon/metabolism ; Humans ; Cell Differentiation/drug effects ; Protein Serine-Threonine Kinases/metabolism ; Immediate-Early Proteins/metabolism ; Sodium Chloride, Dietary/adverse effects ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a frequently encountered disorder characterized by voiding symptoms and pelvic or perineal pain. Proinflammatory T helper 17 (Th17) cells are essential for triggering the development of CP/CPPS. High-salt diet (HSD) consumption has been found to cause an accumulation of sodium chloride in peripheral organs, inducing autoimmune responses via the Th17 cell axis. It is currently unknown whether HSD affects the etiology and course of CP/CPPS.

METHODS: Patients diagnosed with CP/CPPS were evaluated with the National Institutes of Health Chronic Prostatitis Symptom Index scoring system, and the correlation between the symptoms of CP/CPPS with HSD was analyzed. The experimental autoimmune prostatitis (EAP) mouse was established and the mice were fed either a normal-salt diet (NSD) or HSD for 6 weeks to investigate the impact of HSD on CP/CPPS. Then, 16S ribosomal RNA sequencing and untargeted metabolomics were introduced to detect the differences in the gut microflora composition and metabolite profiles between NSD-fed and HSD-fed mice, followed by fecal microbiota transplantation, 5-hydroxyindole acetic acid (5-HIAA) supplementation, aryl hydrocarbon receptor (AHR) inhibition, and in vitro Th17 differentiation experiments, which were performed to explore the mechanisms underlying HSD-aggravated CP/CPPS. Finally, chromatin immunoprecipitation assay and quantitative polymerase chain reaction were conducted to validate whether AHR can serve as a transcription factor by interacting with the serum and glucocorticoid-regulated kinase 1 (Sgk1) promoter in CD4[+] T cells.

RESULTS: Increased salt consumption had a positive correlation with symptom scores of CP/CPPS patients, which was validated by feeding EAP mice with HSD, and HSD worsened the prostate inflammation and tactile allodynia in EAP mice through promoting the differentiation of CD4[+] T cells to Th17 cells. HSD exacerbated EAP by significantly reducing the relative abundance of beneficial gut microflora, such as Lactobacillaceae, and gut microbiota metabolite 5-HIAA, which is related to tryptophan metabolism. The prostate inflammation, tactile allodynia, and proportion of Th17 cells in mice that received fecal suspensions from the EAP + HSD group were significantly more severe or higher than those in mice that received fecal suspensions from the EAP + NSD group. However, 5-HIAA supplementation ameliorated the symptoms of EAP caused by HSD through inhibiting the differentiation of CD4[+] T cells to Th17 cells, while AHR inhibition abrogated the protective effects of 5-HIAA supplementation on EAP mice fed a HSD through promoting the differentiation of CD4[+] T cells to Th17 cells. Mechanistically, it has been revealed that the SGK1/forkhead box protein O1 (FOXO1) pathway was significantly activated during cytokine-induced Th17 cell differentiation, and AHR has been shown to inhibit SGK1 transcription by interacting with the Sgk1 promoter in CD4[+] T cells to inhibit FOXO1 phosphorylation, consequently restoring the equilibrium of Th17 cell differentiation.

CONCLUSION: Our findings indicated that high salt intake represented a risk factor for the development of CP/CPPS as it promoted the differentiation of CD4[+] T cells to Th17 cells through the 5-HIAA/AHR/SGK1/FOXO1 axis, which might be a potential therapeutic target for CP/CPPS.}, } @article {pmid40383397, year = {2025}, author = {Merrick, B and Prossomariti, D and Allen, E and Bisnauthsing, K and Kertanegara, M and Sergaki, C and Le Guennec, AD and Delord, M and Bell, JT and Conte, MR and Moyes, DL and Shankar-Hari, M and Douiri, A and Goodman, AL and Shawcross, DL and Goldenberg, SD}, title = {Faecal microbiota transplant to ERadicate gastrointestinal carriage of Antibiotic-Resistant Organisms (FERARO): A feasibility randomised controlled trial.}, journal = {The Journal of infection}, volume = {91}, number = {1}, pages = {106504}, doi = {10.1016/j.jinf.2025.106504}, pmid = {40383397}, issn = {1532-2742}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; Male ; Female ; Middle Aged ; Feasibility Studies ; *Carrier State/therapy/microbiology ; Aged ; Adult ; *Gastrointestinal Tract/microbiology ; Feces/microbiology ; Gastrointestinal Microbiome ; Drug Resistance, Multiple, Bacterial ; Treatment Outcome ; Anti-Bacterial Agents ; *Enterobacteriaceae Infections/therapy/microbiology ; }, abstract = {OBJECTIVES: The gastrointestinal tract (GIT) is a reservoir of multidrug-resistant organisms (MDRO). Colonisation with MDRO precedes invasive infections, which can be challenging to treat with excess morbidity and mortality compared to antimicrobial-susceptible infections. Currently, there are no effective GIT decolonisation strategies. Whilst faecal microbiota transplant (FMT) has emerged as a potential therapeutic, there remains uncertainty about its feasibility, safety, and efficacy.

METHODS: Population: Patients with invasive infection with extended-spectrum beta-lactamase (ESBL-) or carbapenem-resistant Enterobacterales (CRE) and persistent GIT carriage.

INTERVENTION: Three doses of encapsulated lyophilised FMT.

COMPARATOR: Matched placebo capsules.

OUTCOMES: Primary outcome was participant consent rate as a proportion of those approached to be screened for GIT carriage of ESBL-E/CRE. Secondary outcomes were additional feasibility, safety and tolerability, and efficacy metrics. Exploratory outcomes included stool metagenomic analysis.

RESULTS: Of 460 approached individuals, 124 (27%) consented. 53/124 participants (43%) fulfilled all eligibility criteria. 44/53 (83%) of those eligible were randomised and 41/44 (93%) received investigational medicinal product (IMP): 20 FMT and 21 placebo. 39/41 (95%) completed IMP dosing. Abdominal bloating and skin and subcutaneous tissue disorders were more common following FMT, but there were no unanticipated harms. MDRO carriage decreased over time across arms but was lower at all time points in the FMT arm. FMT increased microbiome diversity and microbiome-based health measures. FMT recipients' samples clustered into two groups, with those with more dissimilar community composition to donors more likely to decolonise post-FMT (3/5 vs. 0/12, p = 0.01). Patients that decolonised exhibited a trend towards increased proportional representation of donor-derived strains in their post-FMT samples (p = 0.05) and change in strain dominance within MDRO at the species-level.

CONCLUSIONS: Progression to a substantive trial is feasible with modifications to the existing FERARO protocol. FMT was safe, well tolerated, and acceptable to patients colonised with MDRO. Microbiome analysis infers that greater donor-recipient microbiome dissimilarity at baseline and higher rates of donor-derived strain engraftment favour MDRO decolonisation, which in turn maybe facilitated by conspecific strain replacement.}, } @article {pmid40383206, year = {2025}, author = {Stensvold, CR and Tomiak, J and Seyoum, Y and Nielsen, HV and van der Giezen, M}, title = {Letter to the Editor: Comment to 'Assessment of Dientamoeba fragilis interhuman transmission by faecal microbiota transplantation' by Moreno-Sabater et al. (2025).}, journal = {International journal of antimicrobial agents}, volume = {66}, number = {3}, pages = {107541}, doi = {10.1016/j.ijantimicag.2025.107541}, pmid = {40383206}, issn = {1872-7913}, } @article {pmid40381961, year = {2025}, author = {Zhao, X and Lei, C and Wang, Y and Zhang, L and Tang, W and Li, Z and Jiang, L and Li, X}, title = {Impact of TLR5 overexpression on gut microbiota and metabolites: Insights into Salmonella infection outcomes.}, journal = {Microbial pathogenesis}, volume = {205}, number = {}, pages = {107708}, doi = {10.1016/j.micpath.2025.107708}, pmid = {40381961}, issn = {1096-1208}, mesh = {*Toll-Like Receptor 5/genetics/metabolism ; Animals ; *Gastrointestinal Microbiome/genetics ; Mice ; RNA, Ribosomal, 16S/genetics ; *Salmonella Infections/microbiology/immunology/metabolism ; Feces/microbiology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Metabolomics ; Mice, Inbred C57BL ; Intestines/microbiology/immunology ; Flagellin ; Metabolome ; }, abstract = {BACKGROUND: The gut microbiome and the host immune system work together to maintain intestinal health and protect against infections. Toll-like receptor 5 (TLR5) recognizes bacterial flagellin and plays a crucial role in this network. However, the precise role of TLR5 in regulating gut microbiota and resistance to infection remains unclear. This study utilized a TLR5 intestine-specific overexpression mouse model to explore these interactions and their impact on Salmonella infection.

METHODS: TLR5 intestine-specific overexpression mice (TLR5+/+) and wild-type (WT) mice were infected with Salmonella to assess TLR5's protective role. Survival time, fecal Salmonella load, and intestinal tissue integrity were evaluated. Subsequently, 16S rRNA sequencing and LC-MS-based metabolomics were performed to analyze gut microbiota composition and fecal metabolites. Fecal microbiota transplantation (FMT) and metabolite transplantation experiments were conducted to evaluate the functional impact of microbiota and metabolites on resistance to infection.

RESULTS: TLR5 overexpression significantly improved survival time and reduced fecal Salmonella load, demonstrating its protective role against infection. 16S rRNA sequencing revealed enrichment of beneficial taxa, while metabolomic analysis identified altered metabolites in TLR5+/+ mice. Although fecal microbiota and metabolite transplantation did not fully replicate the protective effects, these experiments highlighted the important roles of microbiota and metabolites in infection outcomes, with limitations in transplantation likely affecting the results. These findings underscore the significance of microbiota and metabolites in TLR5-mediated gut immunity.

CONCLUSION: TLR5 overexpression significantly alters gut microbiota and metabolite profiles, contributing to improved infection outcomes. These findings highlight the critical roles of microbiota and metabolites in TLR5-mediated immunity and provide a foundation for exploring targeted strategies to enhance resistance against enteric pathogens.}, } @article {pmid40381958, year = {2025}, author = {Bolte, LA and Björk, JR and Gacesa, R and Weersma, RK}, title = {Pharmacomicrobiomics: The Role of the Gut Microbiome in Immunomodulation and Cancer Therapy.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2025.04.025}, pmid = {40381958}, issn = {1528-0012}, abstract = {There is a large heterogeneity among individuals in their therapeutic responses to the same drug and in the occurrence of adverse events. A key factor increasingly recognized to contribute to this variability is the gut microbiome. The gut microbiome can be regarded as a second genome, holding significant metabolic capacity. Consequently, the field of pharmacomicrobiomics has emerged as a natural extension of pharmacogenomics for studying variations in drug responses. Pharmacomicrobiomics explores the interaction of microbiome variation with drug response and disposition. The interaction between microbes and drugs is, however, complex and bidirectional. While drugs can directly alter microbial growth or influence gut microbiome composition and functionality, the gut microbiome also modulates drug responses directly through enzymatic activities and indirectly via host-mediated immune and metabolic mechanisms. Here we review recent studies that demonstrate the interaction between drugs and the gut microbiome, focusing on cancer immunotherapy and immunomodulation in the context of inflammatory bowel disease and solid organ transplantation. Because the gut microbiome is modifiable, pharmacomicrobiomics presents promising opportunities for optimizing therapeutic outcomes, with recent clinical trials highlighting fecal microbiota transplantation as a strategy to enhance the efficacy of immune checkpoint blockade. We also shed light on the future perspectives for patients arising from this field. Although multiple lines of evidence already demonstrate that the gut microbiome interacts with drugs, and vice versa, thereby affecting treatment efficacy and safety, well-designed clinical studies and integrated in vivo and ex vivo models are necessary to obtain consistent results, improve clinical translation, and further unlock the gut microbiome's potential to improve drug responses.}, } @article {pmid40381872, year = {2025}, author = {Barlowe, TS and Desai, S and Sanderford, AE and Holowka, T and Peery, AF and Mcgill, SK}, title = {Fulminant Clostridioides difficile Infection Following Fecal Microbiota Spores Compared to Fecal Microbiota Transplant.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2025.03.027}, pmid = {40381872}, issn = {1542-7714}, } @article {pmid40381501, year = {2025}, author = {Jia, Y and Liu, X and Gao, X and Yin, S and Wu, K and Meng, X and Ren, H and Liu, J and Liu, Z and Li, H and Jiang, Y}, title = {Plantamajoside alleviates DSS-induced ulcerative colitis by modulating gut microbiota, upregulating CBS, and inhibiting NF-κB.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {143}, number = {}, pages = {156827}, doi = {10.1016/j.phymed.2025.156827}, pmid = {40381501}, issn = {1618-095X}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Colitis, Ulcerative/drug therapy/chemically induced/microbiology ; Dextran Sulfate ; *NF-kappa B/metabolism/antagonists & inhibitors ; Mice ; Male ; Up-Regulation ; Mice, Inbred C57BL ; *Glucosides/pharmacology ; Colon/drug effects/pathology ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Plantamajoside (PMS) is a natural bioactive compound derived from medicinal, food homologous plants of the genus Plantago.

PURPOSE AND METHODS: This study aimed to investigate the protective effects of PMS on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice and explore the associated mechanisms.

RESULTS: We found that PMS treatment significantly alleviated UC symptoms in mice by preventing body weight loss, increasing colon length, and reducing disease activity index scores. Moreover, PMS alleviated colonic lesions, increased the number of goblet cells, upregulated the expression of intestinal barrier proteins (ZO-1, occludin, and claudin-3), and decreased the levels of pro-inflammatory factors. PMS treatment modulated the gut microbiota by increasing the relative abundance of Bacteroidota and Verrucomicrobiota and decreasing that of Firmicutes and Proteobacteria at the phylum level. At the genus level, PMS suppressed the abundance of pathogenic bacteria, such as Turicibacter and upregulated the abundance of [Eubacterium]_xylanophilum_group. Fecal microbiota transplantation experiments further confirmed that PMS treatment alleviated UC by modulating the gut microbiota. Transcriptomic analysis of colon tissues, coupled with reverse transcription-quantitative polymerase chain reaction and western blotting, showed that PMS treatment upregulated cystathionine beta-synthase (CBS) expression and inhibited NF-κB pathway activation. In a lipopolysaccharide-induced inflammation model in RAW264.7 cells, PMS treatment inhibited the secretion of pro-inflammatory cytokines, upregulated CBS expression, and prevented NF-κB pathway activation.

CONCLUSION: PMS protects against UC in mice via multiple mechanisms, including modulating the gut microbiota, increasing the expression levels of CBS, and inhibiting the NF-κB pathway.}, } @article {pmid40380157, year = {2025}, author = {Deng, M and Li, X and Wu, H and Xue, D and Wang, Y and Guo, R and Cui, Y and Jin, C and Luo, F and Li, H}, title = {The current status and prospects of gut microbiota combined with PD-1/PD-L1 inhibitors in the treatment of colorectal cancer: a review.}, journal = {BMC gastroenterology}, volume = {25}, number = {1}, pages = {380}, pmid = {40380157}, issn = {1471-230X}, support = {2021XM22//Key Research and Development (R&D) Projects of Shanxi Province/ ; 202103021224346//Fundamental Research Program of Shanxi Province/ ; }, mesh = {*Colorectal Neoplasms/therapy/microbiology/genetics ; *Gastrointestinal Microbiome ; Humans ; *Immune Checkpoint Inhibitors/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; B7-H1 Antigen/antagonists & inhibitors ; Microsatellite Instability ; }, abstract = {BACKGROUND: Colorectal cancer (CRC) is a common malignant tumor. Immune checkpoint inhibitors (ICIs), particularly those targeting programmed cell death protein 1(PD-1) and programmed cell death ligand 1(PD-L1), have shown promising potential in the treatment of CRC. Specific gut microbiota can modulate the efficacy of ICIs through immune or metabolic pathways. This review summarizes recent advances in the combined application of gut microbiota and PD-1/PD-L1 inhibitors in the treatment of CRC, aiming to provide insights for expanding clinical treatment options for CRC.

MATERIALS AND METHODS: We employed a systematic search strategy to screen relevant literature from databases such as PubMed, EMBASE, Medline, Cochrane Library, and Clinical Trial registries, with the search period covering from the inception of each database to October 2024. This study includes animal models and human trial subjects. Data extraction and literature screening were strictly carried out by two independent researchers.

RESULTS: A total of 8 animal studies and 5 clinical trials were included to evaluate the effects of gut microbiota combined with PD-1/PD-L1 inhibitors in CRC. Tumor types included Microsatellite Stability(MSS), Microsatellite Instability-Low(MSI-L), and MSI-H CRC. Main outcomes were tumor volume, weight, and incidence; one study reported survival. Study durations ranged from 20 days to 26 weeks. Two studies used human fecal microbiota transplantation(FMT), and six applied experimental microbial interventions. The 5 clinical trials used ORR as the primary endpoint.Some also reported DCR, PFS, and OS. Two studies targeted Microsatellite Instability-High(MSI-H)/Deficient Mismatch Repair(dMMR), two MSS/Proficient Mismatch Repair(pMMR), and one lacked molecular subtype specification. All trials used full microbiota transplantation; one has released preliminary data.

CONCLUSION: The treatment regimen combining gut microbiota with PD-1/PD-L1 inhibitors has shown promising therapeutic prospects in both animal studies and clinical research, although most clinical trials are data remain limited. Future studies should focus on: (1) gene-edited probiotic strains with targeted modifications; (2) the synergistic effects of multiple probiotics; and (3) conducting high-quality, multicenter clinical trials.}, } @article {pmid40376856, year = {2025}, author = {Takyi, E and Nirmalkar, K and Adams, J and Krajmalnik-Brown, R}, title = {Interventions targeting the gut microbiota and their possible effect on gastrointestinal and neurobehavioral symptoms in autism spectrum disorder.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2499580}, pmid = {40376856}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Autism Spectrum Disorder/therapy/microbiology ; Probiotics/therapeutic use/administration & dosage ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; *Gastrointestinal Diseases/therapy/microbiology ; Gastrointestinal Tract/microbiology ; Child ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Autism spectrum disorder (ASD) is a developmental disorder that is characterized by deficits in social communication and restricted, repetitive, and stereotyped behaviors. In addition to neurobehavioral symptoms, children with ASD often have gastrointestinal symptoms (e.g. constipation, diarrhea, gas, abdominal pain, reflux). Several studies have proposed the role of gut microbiota and metabolic disorders in gastrointestinal symptoms and neurodevelopmental dysfunction in ASD patients; these results offer promising avenues for novel treatments of this disorder. Interventions targeting the gut microbiota - such as fecal microbiota transplant (FMT), microbiota transplant therapy (MTT), probiotics, prebiotics, synbiotics, antibiotics, antifungals, and diet - promise to improve gut health and can potentially improve neurological symptoms. The modulation of the gut microbiota using MTT in ASD has shown beneficial and long-term effects on GI symptoms and core symptoms of autism. Also, the modulation of the gut microbiota to resemble that of typically developing individuals seems to be the most promising intervention. As most of the studies carried out with MTT are open-label studies, more extensive double-blinded randomized control trials are needed to confirm the efficacy of MTT as a therapeutic option for ASD. This review examines the current clinical research evidence for the use of interventions that target the microbiome - such as antibiotics, antifungals, probiotics/prebiotics, synbiotics, and MTT - and their effectiveness in changing the gut microbiota and improving gastrointestinal and neurobehavioral symptoms in ASD.}, } @article {pmid40375906, year = {2025}, author = {Finotto, T and Chevenet, C and Fayard, A}, title = {Fecal Microbiota Transplantation as a Salvage Therapy for Concomitant Resistant Digestive Graft Versus Host Disease and Cryptosporidiosis in a Patient Post Hematopoietic Stem Cell Transplant: about a Case.}, journal = {Mediterranean journal of hematology and infectious diseases}, volume = {17}, number = {1}, pages = {e2025035}, pmid = {40375906}, issn = {2035-3006}, } @article {pmid40375326, year = {2025}, author = {Liu, J and Zhang, D and Zhou, Y and Wu, J and Feng, W and Peng, C}, title = {Fuzi alleviates cold-related rheumatoid arthritis via regulating gut microbiota and microbial bile acid metabolism.}, journal = {Chinese medicine}, volume = {20}, number = {1}, pages = {64}, pmid = {40375326}, issn = {1749-8546}, support = {82104409//National Natural Science Foundation of China/ ; 82304850//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Rheumatoid arthritis (RA) with cold pattern is an important type of RA according to the theory of traditional Chinese medicine. Fuzi (also known as the lateral roots of Aconitum carmichaelii Debx.) represents a typical traditional Chinese medicine that has been clinically used for treatment of the RA especially cold-related RA for thousands of years, yet its mechanism remains unknown.

PURPOSE: The purpose of the research was to study the therapeutic effects of Fuzi on cold-related RA, and to investigate the mechanism of its action.

METHODS: Here, we investigated the pharmacological effects of Fuzi on cold-related RA using micro-CT, histopathological analysis, and inflammatory cytokine test. Then, a gut microbiota composition analysis in combination with fecal microbiota transplantation were used to confirm the role of gut microbiota in the therapeutic effects of Fuzi. Further, targeted bile acid metabolomics was used to screen the possible differential microbial bile acids involved in the mechanism of Fuzi. In vitro bioactivity analysis of differential bile acids was used to assess their anti-inflammation activity. Finally, western blot was used to investigate the signaling pathways of Fuzi in reducing the inflammation of cold-related RA.

RESULTS: The results showed that Fuzi alleviates cold-related RA by improving arthritis index, paw swelling, bone damage, and inflammatory cytokines. In addition, the ameliorative effect of Fuzi is dependent on gut microbiota such as the taxa Lachnospiraceae and Ruminococcaceae. Targeted analysis of fecal and serum bile acids showed that TCA and THDCA were the main differential metabolites. In vitro, TCA and THDCA showed anti-inflammation effects on RAW264.7 cells. Western blot showed that Fuzi regulates TGR5-cAMP-PKA signaling and NLRP3 inflammasome to reduce cold-related arthritis.

CONCLUSION: Overall, our results demonstrated that Fuzi could regulate gut microbiota and microbial bile acid metabolism, the microbial metabolite THDCA acts on TGR5-cAMP-PKA signaling pathway and NLRP3 inflammasome to reduce cold-related arthritis. Our study suggests that supplementation of Fuzi or THDCA can be of great value for the prevention and clinical treatment of cold-related RA.}, } @article {pmid40375187, year = {2025}, author = {Bai, XJ and Mei, YC and Zhao, JT and Chen, ZR and Yang, CX and Dong, XJ and Yu, JW and Xiang, LB and Zhou, EZ and Chen, Y and Hao, JY and Zhang, ZJ and Liuyang, YX and Ren, L and Yao, YM and Zhang, L and Lv, Y and Lu, Q}, title = {Changes in microbiome composition after fecal microbiota transplantation via oral gavage and magnetic navigation technology-assisted proximal colon/cecum enema in antibiotic knock-down rats: a comparative experimental study.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {295}, pmid = {40375187}, issn = {1471-2180}, support = {92048202//Major Research Plan of the National Natural Science Foundation of China/ ; 2021GXLH-Z-047//Key R&D Plan of Shaanxi Province/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Rats ; Feces/microbiology ; *Gastrointestinal Microbiome ; Rats, Sprague-Dawley ; *Colon/microbiology ; *Enema/methods ; Male ; *Cecum/microbiology ; Anti-Bacterial Agents ; *Bacteria/classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Administration, Oral ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) transfers fecal matter from a donor into the gastrointestinal tract of a recipient to induce changes to the gut microbiota for therapeutic benefit; however, differences in the composition of gut microbiota after FMT via different donor material delivery routes are poorly understood. In this study, we first developed a novel technique for FMT, magnetic navigation technology(MAT)-assisted proximal colon enemas, in healthy Sprague-Dawley rats. Besides, the difference in fecal microbiota composition after FMT via oral gavage and proximal colon/cecum enemas was determined in antibiotic knock-down rats, in addition to the impact on intestinal barrier function.

METHODS: A device consisting of an external magnet and a magnet-tipped 6 Fr tube was used in the MAT group (n = 6), and the control group (n = 6) where fecal matter was delivered without magnetic navigation. The feasibility and safety of this method were assessed by angiography and histology. Next, the fecal microbiota of donor rats was transplanted into antibiotic knock-down rats via oral gavage (n = 6) and MAT-assisted proximal colon/cecum enema (n = 6) for a week. Analysis of fecal 16 S rRNA was conducted to determine differences in the composition of gut microbiota between different groups. The rat intestinal barrier integrity were evaulated by H&E and ZO-1/MUC2 immunofluorescence staining.

RESULTS: The end of the fecal tube could be placed in the cecum or proximal colon of rats in MAT group; however, this was rarely achieved in the control group. No colon perforation or bleeding was detected in either group. After fecal microbiota transplantation, the microbiota α-diversity and β-diversity were comparable among the different delivery routes.At the family level, the relative abundances of Muribaculaceae, Oscillospiraceae, and Erysipelotrichaceae were higher in the gavage treatment group, whereas Lactobacillaceae and Saccharimonadaceae were higher in the enema treatment group (all p < 0.05). FMT by enema was superior to gavage in maintaining the integrity of the rat intestinal barrier, as assessed by an elevation in the density of goblet cells and increased expression of mucin-2.

CONCLUSIONS: Fecal microbiota tube placement using magnetic navigation was safe and feasible in rats.Different delivery route for FMT affects the gut microbiota composition and the integrity of the rat intestinal barrier. Future experimental designs should consider the colonization outcomes of critical microbial taxa to determine the optimal FMT delivery routes in scientific research as well as clinical practise.}, } @article {pmid40373043, year = {2025}, author = {Cassir, N and Benech, N and Galperine, T and Alric, L and Scanzi, J and Bleibtreu, A and Kapel, N and Sokol, H}, title = {A Randomized Controlled Trial of Efficacy and Safety of Fecal Microbiota Transplant for Preventing Recurrent Clostridioides difficile Infection: The Failure of a Procedure, not of a Therapy.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaf249}, pmid = {40373043}, issn = {1537-6591}, } @article {pmid40371968, year = {2025}, author = {Jansen, D and Deleu, S and Caenepeel, C and Marcelis, T and Simsek, C and Falony, G and Machiels, K and Sabino, J and Raes, J and Vermeire, S and Matthijnssens, J}, title = {Virome drift in ulcerative colitis patients: faecal microbiota transplantation results in minimal phage engraftment dominated by microviruses.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2499575}, pmid = {40371968}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Colitis, Ulcerative/therapy/virology/microbiology ; *Virome ; Male ; Female ; Feces/virology ; Adult ; Gastrointestinal Microbiome ; Middle Aged ; *Bacteriophages/genetics/isolation & purification/classification ; Young Adult ; }, abstract = {Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent colonic inflammation. Standard treatments focus on controlling inflammation but remain ineffective for one-third of patients. This underscores the need for alternative approaches, such as fecal microbiota transplantation (FMT), which transfers healthy donor microbiota to patients. The role of viruses in this process, however, remains underexplored. To address this, we analyzed the gut virome using metagenomic sequencing of enriched viral particles from 320 longitudinal fecal samples of 44 patients enrolled in the RESTORE-UC FMT trial. Patients were treated with FMTs from healthy donors (allogenic, treatment) or themselves (autologous, control). We found that colonic inflammation, both its presence and location, had a greater impact on the gut virome than FMT itself. In autologous FMT patients, the virome was unstable and showed rapid divergence over time, a phenomenon we termed virome drift. In allogenic FMT patients, the virome temporarily shifted toward the healthy donor, lasting up to 5 weeks and primarily driven by microviruses. Notably, two distinct virome configurations were identified and linked to either healthy donors or patients. In conclusion, inflammation strongly affects the gut virome in UC patients, which may lead to instability and obstruct the engraftment of allogeneic FMT.}, } @article {pmid40371237, year = {2025}, author = {Singh, A and Young, E and Maurya, A and Rajagopalan, A}, title = {Nasogastric Delivery of Fecal Microbiota Transplantation for the Treatment of Fulminant Clostridioides difficile Infection: A Case Report.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {9}, number = {5}, pages = {e70177}, pmid = {40371237}, issn = {2397-9070}, abstract = {INTRODUCTION: Clostridioides difficile infection (CDI) is a significant cause of antibiotic-associated diarrhea with high morbidity and mortality, particularly in cases of fulminant disease. Fecal microbiota transplantation (FMT) has demonstrated efficacy in treating severe and refractory CDI, typically administered via colonoscopy. However, in cases complicated by toxic megacolon, alternative methods of FMT delivery may be necessary.

CASE REPORT: This case report describes a 46-year-old female with cirrhosis and fulminant CDI complicated by toxic megacolon. Due to the patient's hemodynamic instability and contraindications to endoscopic FMT delivery, a novel approach of nasogastric FMT administration was utilized. The patient received a combination of enema-delivered and nasogastric FMT alongside standard antibiotic therapy. This approach resulted in rapid clinical improvement, with resolution of toxic megacolon, normalization of inflammatory markers, and avoidance of colectomy.

DISCUSSION: This report highlights the successful use of nasogastric FMT in a patient with fulminant CDI, offering a potential alternative delivery route when colonoscopic administration is contraindicated. To our knowledge, this is the first reported case of nasogastric FMT successfully resolving C. difficile-associated toxic megacolon.}, } @article {pmid40370465, year = {2025}, author = {Cui, X and Li, C and Zhong, J and Liu, Y and Xiao, P and Liu, C and Zhao, M and Yang, W}, title = {Gut microbiota - bidirectional modulator: role in inflammatory bowel disease and colorectal cancer.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1523584}, pmid = {40370465}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Colorectal Neoplasms/microbiology/immunology/therapy/etiology ; *Inflammatory Bowel Diseases/microbiology/immunology/therapy/etiology ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; }, abstract = {The gut microbiota is a diverse ecosystem that significantly impacts human health and disease. This article focuses on how the gut microbiota interacts with inflammatory bowel diseases and colorectal tumors, especially through immune regulation. The gut microbiota plays a role in immune system development and regulation, while the body's immune status can also affect the composition of the microbiota. These microorganisms exert pathogenic effects or correct disease states in gastrointestinal diseases through the actions of toxins and secretions, inhibition of immune responses, DNA damage, regulation of gene expression, and protein synthesis. The microbiota and its metabolites are essential in the development and progression of inflammatory bowel diseases and colorectal tumors. The complexity and bidirectionality of this connection with tumors and inflammation might render it a new therapeutic target. Hence, we explore therapeutic strategies for the gut microbiota, highlighting the potential of probiotics and fecal microbiota transplantation to restore or adjust the microbial community. Additionally, we address the challenges and future research directions in this area concerning inflammatory bowel diseases and colorectal tumors.}, } @article {pmid40369623, year = {2025}, author = {Hu, J and Liu, D and Liao, G and Guo, Y and Li, M and Liao, J and Chen, H and Zhou, S and Yang, S and Li, S and Liu, Y and Zhao, M}, title = {Fecal microbiota transplantation alleviates immunosuppressant-associated diarrhea and recurrent urinary tract infection in kidney transplant recipients: a retrospective analysis.}, journal = {Gut pathogens}, volume = {17}, number = {1}, pages = {28}, pmid = {40369623}, issn = {1757-4749}, abstract = {BACKGROUND: Immunosuppressant administration subsequent to organ transplantation exerts a substantial influence on gut microbiota composition, thereby affecting patients' prognosis and quality of life.

METHODS AND RESULTS: We conducted a retrospective analysis involving 18 patients who experienced severe diarrhea or recurrent urinary tract infection (rUTI) due to prolonged immunosuppressant usage after kidney transplantation. Following episodes of severe diarrhea or rUTI, these individuals underwent fecal microbiota transplantation (FMT), resulting in notable alleviation of clinical symptoms. No unexpected adverse or serious adverse events were reported. In comparison to the pre-FMT period, the α-diversity of the intestinal microbiota in patients did not exhibit a significant difference following FMT; however, there was a notable distinction in the β-diversity and analysis of similarity (ANOSIM). In addition, our findings indicated a significant decline in the relative abundance of the bacterial genera Veillonella, Enterococcus, and Oribacterium, whereas a marked elevation was observed in the relative abundance of Faecalibacterium, Roseburia, Sutterella, Parasutterella, and Ruminiclostridium 5 after FMT in patients. Furthermore, there was a notable alteration in the metabolic pathway of gut microbiota in patients following FMT, with a significant enrichment observed in pathways such as Flavone and flavonol biosynthesis, Cytoskeleton proteins, Chromosome-related processes, NOD-like receptor signaling pathway, Progesterone-mediated oocyte maturation, and Antigen processing and presentation.

CONCLUSION: FMT exhibited an effective approach for managing rUTI and diarrhea arising from postoperative immunosuppressant exposure in kidney transplant recipients.}, } @article {pmid40369317, year = {2025}, author = {Gao, YQ and Tan, YJ and Fang, JY}, title = {Roles of the gut microbiota in immune-related adverse events: mechanisms and therapeutic intervention.}, journal = {Nature reviews. Clinical oncology}, volume = {22}, number = {7}, pages = {499-516}, pmid = {40369317}, issn = {1759-4782}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/drug effects ; *Immune Checkpoint Inhibitors/adverse effects ; *Neoplasms/drug therapy/immunology ; Colitis/chemically induced/microbiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Tumor Microenvironment/immunology/drug effects ; }, abstract = {Immune checkpoint inhibitors (ICIs) constitute a major breakthrough in the field of cancer therapy; their use has resulted in improved outcomes across various tumour types. However, ICIs can cause a diverse range of immune-related adverse events (irAEs) that present a considerable challenge to the efficacy and safety of these treatments. The gut microbiota has been demonstrated to have a crucial role in modulating the tumour immune microenvironment and thus influences the effectiveness of ICIs. Accumulating evidence indicates that alterations in the composition and function of the gut microbiota are also associated with an increased risk of irAEs, particularly ICI-induced colitis. Indeed, these changes in the gut microbiota can contribute to the pathogenesis of irAEs. In this Review, we first summarize the current clinical challenges posed by irAEs. We then focus on reported correlations between alterations in the gut microbiota and irAEs, especially ICI-induced colitis, and postulate mechanisms by which these microbial changes influence the occurrence of irAEs. Finally, we highlight the potential value of gut microbial changes as biomarkers for predicting irAEs and discuss gut microbial interventions that might serve as new strategies for the management of irAEs, including faecal microbiota transplantation, probiotic, prebiotic and/or postbiotic supplements, and dietary modulations.}, } @article {pmid40368261, year = {2025}, author = {Murayama, R and Cai, Y and Nakamura, H and Hashimoto, K}, title = {Demyelination in psychiatric and neurological disorders: Mechanisms, clinical impact, and novel therapeutic strategies.}, journal = {Neuroscience and biobehavioral reviews}, volume = {174}, number = {}, pages = {106209}, doi = {10.1016/j.neubiorev.2025.106209}, pmid = {40368261}, issn = {1873-7528}, mesh = {Humans ; *Mental Disorders/therapy/complications ; *Nervous System Diseases/therapy/complications ; *Demyelinating Diseases/therapy/metabolism/physiopathology ; Animals ; }, abstract = {Demyelination, defined as the loss of myelin sheaths around neuronal axons, is increasingly recognized as a key factor in a broad range of psychiatric and neurological disorders, including schizophrenia, major depressive disorder, bipolar disorder, post-traumatic stress disorder, autism spectrum disorder, substance use disorders, Alzheimer's disease, Parkinson's disease, and multiple sclerosis. This review investigates the core mechanisms driving demyelination, its clinical impact, and emerging therapeutic strategies aimed at maintaining or restoring myelin integrity. Disruption of myelin impairs crucial neural communication pathways, resulting in cognitive, motor, and behavioral deficits that substantially reduce quality of life and create significant economic and social challenges. Key contributors to demyelination include genetic predisposition, environmental triggers, immune dysregulation, neuroinflammation, and alterations in the gut-brain axis mediated by the vagus nerve. Promising therapies include sphingosine 1-phosphate receptor modulators and muscarinic acetylcholine receptor antagonists, both of which diminish immune-related myelin damage and may enhance neuroprotection. In addition, the novel antidepressant arketamine appears to boost myelination through transforming growth factor-β1 signaling pathways. Approaches targeting the gut-brain axis, such as noninvasive transcutaneous auricular vagus nerve stimulation and fecal microbiota transplantation, may also help reduce inflammation and support myelin repair. Future research should center on clarifying the precise molecular mechanisms of demyelination, developing targeted therapies, and leveraging advanced neuroimaging for earlier detection and personalized treatment. By combining immunomodulatory and neuroprotective strategies, there is potential to significantly improve outcomes for individuals affected by demyelinating psychiatric and neurological disorders.}, } @article {pmid40364844, year = {2025}, author = {Nazir, A and Hussain, FHN and Nadeem Hussain, TH and Al Dweik, R and Raza, A}, title = {Therapeutic targeting of the host-microbiota-immune axis: implications for precision health.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1570233}, pmid = {40364844}, issn = {1664-3224}, mesh = {Humans ; *Precision Medicine/methods ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; *Gastrointestinal Microbiome/immunology ; Animals ; *Host Microbial Interactions/immunology ; *Microbiota/immunology ; Immunomodulation ; }, abstract = {The human body functions as a complex ecosystem, hosting trillions of microbes that collectively form the microbiome, pivotal in immune system regulation. The host-microbe immunological axis maintains homeostasis and influences key physiological processes, including metabolism, epithelial integrity, and neural function. Recent advancements in microbiome-based therapeutics, including probiotics, prebiotics and fecal microbiota transplantation, offer promising strategies for immune modulation. Microbial therapies leveraging microbial metabolites and engineered bacterial consortia are emerging as novel therapeutic strategies. However, significant challenges remain, including individual microbiome variability, the complexity of host-microbe interactions, and the need for precise mechanistic insights. This review comprehensively examines the host microbiota immunological interactions, elucidating its mechanisms, therapeutic potential, and the future directions of microbiome-based immunomodulation in human health. It will also critically evaluate challenges, limitations, and future directions for microbiome-based precision medicine.}, } @article {pmid40364435, year = {2025}, author = {Zhang, Y and Wei, Y and Han, X and Shi, L and Yu, H and Ji, X and Gao, Y and Gao, Q and Zhang, L and Duan, Y and Li, W and Yuan, Y and Shi, J and Cheng, L and Li, Y}, title = {Faecalibacterium prausnitzii prevents age-related heart failure by suppressing ferroptosis in cardiomyocytes through butyrate-mediated LCN2 regulation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2505119}, pmid = {40364435}, issn = {1949-0984}, mesh = {Animals ; *Myocytes, Cardiac/metabolism/drug effects/microbiology ; *Ferroptosis/drug effects ; *Heart Failure/prevention & control/microbiology/metabolism ; Rats ; Gastrointestinal Microbiome ; Humans ; *Butyrates/metabolism ; Fecal Microbiota Transplantation ; Male ; *Faecalibacterium prausnitzii/physiology/genetics ; *Lipocalin-2/metabolism/genetics ; Aged ; Aging ; Dysbiosis/microbiology ; Female ; Rats, Sprague-Dawley ; }, abstract = {Aging is a primary driver of the escalating prevalence of heart failure (HF). Age-associated gut microbiota dysbiosis has been implicated in various age-related diseases, yet its role in age-related HF remains largely unexplored. In this study, we sought to explore the potential link between age-related gut microbiota alterations and HF in the elderly. We analyzed a publicly available single-cell sequencing dataset, which revealed markedly increased ferroptosis activity in cardiac myocytes of elderly individuals compared to their younger counterparts. Notably, treatment with the ferroptosis inhibitor, ferrostatin-1, mitigated cardiac ferroptosis and prevented cardiac dysfunction in aging rats. Furthermore, fecal microbiota transplantation from elderly HF patients significantly increased cardiac ferroptosis activity and induced cardiac dysfunction in healthy recipient rats. Integrated 16S rRNA sequencing and PCR quantification revealed a marked depletion of Faecalibacterium prausnitzii (F. prausnitzii) in elderly individuals, with a more pronounced decline in elderly patients with HF. Oral administration of F. prausnitzii or its metabolite butyrate effectively attenuated age-related HF through inhibiting ferroptosis. Additionally, gene-editing techniques were employed to generate F. prausnitzii BCoAT mutant deficient in butyrate production. Intriguingly, the protective effect was lost in the butyrate-deficient F. prausnitzii strain. Mechanistically, butyrate reduced intracellular iron accumulation and suppressed ferroptosis by downregulating LCN2 expression in senescent cardiomyocytes. Our findings highlight the critical role of aged microbiota-induced ferroptosis in HF and propose F. prausnitzii or butyrate may serve as potential targets for the prevention and treatment of age-related HF.}, } @article {pmid40361641, year = {2025}, author = {Mafe, AN and Büsselberg, D}, title = {Could a Mediterranean Diet Modulate Alzheimer's Disease Progression? The Role of Gut Microbiota and Metabolite Signatures in Neurodegeneration.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {9}, pages = {}, pmid = {40361641}, issn = {2304-8158}, support = {NPRP 14S0311-210033//Qatar National Research Fund/ ; }, abstract = {Neurodegenerative disorders such as Alzheimer's disease (AD), the most common form of dementia, represent a growing global health crisis, yet current treatment strategies remain primarily palliative. Recent studies have shown that neurodegeneration through complex interactions within the gut-brain axis largely depends on the gut microbiota and its metabolites. This review explores the intricate molecular mechanisms linking gut microbiota dysbiosis to cognitive decline, emphasizing the impact of microbial metabolites, including short-chain fatty acids (SCFAs), bile acids, and tryptophan metabolites, on neuroinflammation, blood-brain barrier (BBB) integrity, and amyloid-β and tau pathology. The paper highlights major microbiome signatures associated with Alzheimer's disease, detailing their metabolic pathways and inflammatory crosstalk. Dietary interventions have shown promise in modulating gut microbiota composition, potentially mitigating neurodegenerative processes. This review critically examines the influence of dietary patterns, such as the Mediterranean and Western diets, on microbiota-mediated neuroprotection. Bioactive compounds like prebiotics, omega-3 fatty acids, and polyphenols exhibit neuroprotective effects by modulating gut microbiota and reducing neuroinflammation. Furthermore, it discusses emerging microbiome-based therapeutic strategies, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation (FMT), as potential interventions for slowing Alzheimer's progression. Despite these advances, several knowledge gaps remain, including interindividual variability in microbiome responses to dietary interventions and the need for large-scale, longitudinal studies. The study proposes an integrative, precision medicine approach, incorporating microbiome science into Alzheimer's treatment paradigms. Ultimately, cognizance of the gut-brain axis at a mechanistic level could unlock novel therapeutic avenues, offering a non-invasive, diet-based strategy for managing neurodegeneration and improving cognitive health.}, } @article {pmid40361238, year = {2025}, author = {Maschek, S and Østergaard, TH and Krych, L and Zachariassen, LF and Sørensen, DB and Junker Mentzel, CM and Hansen, AK and Sjögren, JM and Barfod, KK}, title = {Investigating fecal microbiota transplants from individuals with anorexia nervosa in antibiotic-treated mice using a cross-over study design.}, journal = {Journal of eating disorders}, volume = {13}, number = {1}, pages = {82}, pmid = {40361238}, issn = {2050-2974}, abstract = {Anorexia nervosa (AN) is a complex and serious mental disorder, which may affect individuals of all ages and sex, but primarily affecting young women. The disease is characterized by a disturbed body image, restrictive eating behavior, and a lack of acknowledgment of low body weight. The underlying causes of AN remain largely unknown, and current treatment options are limited to psychotherapy and nutritional support. This paper investigates the impact of Fecal Microbiota Transplants (FMT) from patients with AN on food intake, body weight, behavior, and gut microbiota into antibiotic-treated mice. Two rounds of FMT were performed using AN and control (CO) donors. During the second round of FMT, a subset of mice received gut microbiota (GM) from a different donor type. This split-group cross-over design was chosen to demonstrate any recovery effect of FMT from a non-eating disorder state donor. The first FMT, from donors with AN, resulted in lower food intake in mice without affecting body weight. Analysis of GM showed significant differences between AN and CO mice after FMT1, before cross-over. Specific bacterial genera and families Ruminococcaceae, Lachnospiraceae, and Faecalibacterium showed different abundances in AN and CO receiving mice. Behavioral tests showed decreased locomotor activity in AN mice after FMT1. After FMT2, serum analysis revealed higher levels of appetite-influencing hormones (PYY and leptin) in mice receiving AN-GM. Overall, the results suggest that AN-GM may contribute to altered food intake and appetite regulation, which can be ameliorated with FMT from a non-eating disorder state donor potentially offering FMT as a supportive treatment for AN.}, } @article {pmid40359452, year = {2025}, author = {Yang, G and Li, M and Zheng, X and Chen, X and Peng, Y and Li, J and Yang, S and Chen, H and Wang, Y and Zhang, H and Gong, C and Hu, F and Wan, J and Zhu, Z and Zhang, L and Li, R}, title = {Trehalose Acts as a Mediator: Imbalance in Brain Proteostasis Induced by Polystyrene Nanoplastics via Gut Microbiota Dysbiosis during Early Life.}, journal = {ACS nano}, volume = {19}, number = {20}, pages = {19233-19254}, doi = {10.1021/acsnano.5c01639}, pmid = {40359452}, issn = {1936-086X}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Proteostasis/drug effects ; Mice ; *Dysbiosis/metabolism/chemically induced ; *Brain/metabolism/drug effects ; *Trehalose/metabolism/pharmacology ; *Polystyrenes/chemistry/toxicity ; Male ; *Nanoparticles/toxicity/chemistry ; *Microplastics/toxicity/chemistry ; Mice, Inbred C57BL ; }, abstract = {As an emerging contaminant, nanoplastics have evolved into a global ecological issue. Studies have shown that nanoplastics induce neurotoxicity across species, however, the causal mechanism remains unknown. This study aimed to explore the mechanism underlying the neurotoxicity caused by polystyrene nanoplastics (PS-NPs) via microbiota-gut-brain axis in immature mice, which serve as a model of infants and young children who are at higher exposure risk to NPs. The results indicated that while only a minority of PS-NPs reached the brain after exposure, they still had significant neurotoxic effects, as reflected by abnormalities in behavior, biochemical marker levels and histopathology. Proteomics and quantification analyses revealed that a proteostasis imbalance mediated by lysosomal and proteasome dysfunction in the brain is the key reason for the induced neurotoxicity. Further, we confirmed the indirect role of gut microbiota in the neurotoxicity induced by PS-NPs through 16S rDNA analyses and fecal microbiota transplantation. Crucial bacterial species such as Eubacterium coprostanoligenes potentially act as indicators for gut dysbiosis after PS-NPs exposure. Notably, we first estimated the indirect effect of gut microbiota on neurotoxicity attributed to PS-NPs in immature mice as 39.20% by high-dimensional mediation analysis. Trehalose was identified as a mediator connecting the gut microbiota and the brain, and the crucial role of trehalose supplementation was highlighted in remodeling the brain proteostasis to alleviate the neurotoxicity in immature mice. These findings are expected to contribute to a deeper understanding of the risk assessment and health protection of the nervous system from exposure to PS-NPs early in life.}, } @article {pmid40359297, year = {2025}, author = {Pakuwal, E and Tan, JL and Page, AJ and Stringer, AM and Woodman, RJ and Chinnaratha, MA}, title = {A systematic review and meta-analysis on the efficacy of fecal microbiome transplantation in patients with severe alcohol-associated hepatitis.}, journal = {European journal of gastroenterology & hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MEG.0000000000003003}, pmid = {40359297}, issn = {1473-5687}, abstract = {BACKGROUND: Severe alcohol-associated hepatitis (sAH) has a high short-term mortality, with limited treatment options. Fecal microbiota transplantation (FMT) has shown benefits in small, uncontrolled studies.

AIM: Perform a systematic review and meta-analysis to provide updated evidence on the efficacy and safety of FMT in sAH patients.

METHOD: Electronic databases were searched till 4 December 2023 for studies comparing FMT with standard of care (SOC) in sAH patients. Sensitivity analysis (leave-one-out method) and subgroup analyses were performed. Pooled risk ratio (RR) was used to compare the survival outcomes.

RESULTS: Eight studies with 444 patients (FMT: 218; SOC: 226) met the eligibility criteria and were included in this meta-analysis. The 28- and 90-day survival range was higher in the FMT group (75-100% and 53-87%) compared to the SOC group (48-80% and 25-56%). The random-effects model showed a statistically significant increase in survival in the FMT arm at 28 days [RR (95% confidence interval) 2.30 (1.24-4.28), P = 0.01] and 90 days [2.53 (1.34-4.77), P < 0.001]. However, there was no statistically significant change in survival at the 6-month [1.89 (0.89-4.05), P = 0.10] and the 12-month time [1.86 (0.68-5.08), P = 0.23]. Sensitivity analysis showed no major changes in the overall effect sizes, and subgroup analysis showed that the survival benefit was restricted only to the retrospective studies. No serious treatment-related adverse events were reported.

CONCLUSION: FMT is a safe and efficacious treatment option that improves short-term survival in sAH patients, without major adverse events. A multicentre randomized controlled trial with an adequate sample size is required to confirm these findings.}, } @article {pmid40357397, year = {2025}, author = {Xing, G and Cui, Y and Guo, Z and Han, B and Zhao, G}, title = {Progress on the mechanism of intestinal microbiota against colorectal cancer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1565103}, pmid = {40357397}, issn = {2235-2988}, mesh = {*Colorectal Neoplasms/therapy/microbiology/prevention & control/immunology ; Humans ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; Immunotherapy ; Signal Transduction ; }, abstract = {The intestinal microbiota plays a crucial role in the occurrence and development of colorectal cancer, and its anti - colorectal cancer mechanism has become a research hotspot. This article comprehensively expounds on the molecular mechanisms of the intestinal microbiota in anti - colorectal cancer, including aspects such as immune regulation, activation of carcinogenic signaling pathways (it should be noted that it is more reasonable to be "inhibition of carcinogenic signaling pathways"), metabolite - mediated effects, and maintenance of intestinal barrier function. At the same time, it explores the roles and potential mechanisms of intervention methods such as probiotic supplementation therapy, immunotherapy, and fecal microbiota transplantation. In addition, it analyzes the impact of the intestinal flora on the therapeutic efficacy of colorectal cancer. The existing research results are summarized, and the future research directions are prospected, with the aim of providing new theoretical bases and treatment ideas for the prevention and treatment of colorectal cancer.}, } @article {pmid40356099, year = {2025}, author = {Zhang, Y and Ni, P and Chen, H and Tang, L and Song, H and Wen, H and Miao, Y and Li, W and Li, X}, title = {Vitamin D3 ameliorates hyperglycemia by modulating gut microbiota and metabolites in prediabetic KKay mice.}, journal = {Food research international (Ottawa, Ont.)}, volume = {211}, number = {}, pages = {116369}, doi = {10.1016/j.foodres.2025.116369}, pmid = {40356099}, issn = {1873-7145}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Prediabetic State/metabolism/drug therapy/microbiology ; *Hyperglycemia/drug therapy/metabolism ; *Cholecalciferol/pharmacology ; Male ; Blood Glucose/metabolism/drug effects ; Diet, High-Fat/adverse effects ; Toll-Like Receptor 4/metabolism ; Glucose Tolerance Test ; Signal Transduction/drug effects ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Feces/microbiology ; Proto-Oncogene Proteins c-akt/metabolism ; }, abstract = {Prediabetes represents a pivotal stage in the development and pathogenesis of diabetes, during which notable alterations in the gut microbiota can be observed. Vitamin D (VD) showed anti-diabetic properties, but it is unknown whether the improvement of VD on hyperglycemia is associated with gut microbiota. Thus, our objective was to investigate and verify the effects of VD3 on glucose metabolism in prediabetes, as well as to elucidate the underlying mechanisms. In this study, different concentrations of VD3 were intraperitoneally administered to prediabetic mice induced by high fat diet for 16 weeks. Biochemical analyses, oral glucose tolerance test, 16S rRNA and untargeted metabolomics were used, the mechanism was explored. Then, fecal suspensions collected from the above donors were transplanted into KKay mice for 6 weeks, and the relevant indicators were measured. The results showed that VD3 intervention alleviated glucose metabolism in KKay mice. It increased the protein expression of colon tight junction proteins, alleviated metabolic endotoxemia and inflammation, so that reduced tumor necrosis factor alpha (TNFα) induced toll-like receptor 4/nuclear factor kappa-B (TLR4/NFκB) and improvement of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) insulin signaling pathway. VD3 affected the structure of gut microbiota and metabolites, and functional prediction analysis suggested that VD3 may affect carbohydrate. Besides, the effect of VD3 could be delivered by fecal microbiota transplantation (FMT). Consequently, VD3 ameliorate glucose metabolism by modulating gut microbiota and metabolites in KKay mice, and this ability could be transferred by FMT.}, } @article {pmid40355758, year = {2025}, author = {Saeedi Saravi, SS and Pugin, B and Constancias, F and Shabanian, K and Spalinger, M and Thomas, A and Le Gludic, S and Shabanian, T and Karsai, G and Colucci, M and Menni, C and Attaye, I and Zhang, X and Allemann, MS and Lee, P and Visconti, A and Falchi, M and Alimonti, A and Ruschitzka, F and Paneni, F and Beer, JH}, title = {Gut microbiota-dependent increase in phenylacetic acid induces endothelial cell senescence during aging.}, journal = {Nature aging}, volume = {5}, number = {6}, pages = {1025-1045}, pmid = {40355758}, issn = {2662-8465}, support = {/WT_/Wellcome Trust/United Kingdom ; #21A053//Novartis Stiftung für Medizinisch-Biologische Forschung (Novartis Foundation for Medical-Biological Research)/ ; #310030_21A053//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; #CRSK-3_229134//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; *Phenylacetates/metabolism/blood ; *Cellular Senescence/physiology/drug effects ; *Aging/metabolism ; Humans ; Mice ; *Endothelial Cells/metabolism ; Male ; Clostridium/metabolism ; Mice, Inbred C57BL ; Hydrogen Peroxide/metabolism ; Female ; Glutamine/analogs & derivatives/metabolism ; Feces/microbiology/chemistry ; Aged ; Mitochondria/metabolism ; Sirtuin 1/metabolism ; }, abstract = {Endothelial cell senescence is a key driver of cardiovascular aging, yet little is known about the mechanisms by which it is induced in vivo. Here we show that the gut bacterial metabolite phenylacetic acid (PAA) and its byproduct, phenylacetylglutamine (PAGln), are elevated in aged humans and mice. Metagenomic analyses reveal an age-related increase in PAA-producing microbial pathways, positively linked to the bacterium Clostridium sp. ASF356 (Clos). We demonstrate that colonization of young mice with Clos increases blood PAA levels and induces endothelial senescence and angiogenic incompetence. Mechanistically, we find that PAA triggers senescence through mitochondrial H2O2 production, exacerbating the senescence-associated secretory phenotype. By contrast, we demonstrate that fecal acetate levels are reduced with age, compromising its function as a Sirt1-dependent senomorphic, regulating proinflammatory secretion and redox homeostasis. These findings define PAA as a mediator of gut-vascular crosstalk in aging and identify sodium acetate as a potential microbiome-based senotherapy to promote healthy aging.}, } @article {pmid40354906, year = {2025}, author = {Zain, NMM and Merrick, B and Martin-Lilley, T and Edwards, LA and Ter Linden, D and Tsoka, S and Mason, AJ and Hatton, GB and Allen, E and Royall, PG and Lilley, AK and Bruce, KD and Shawcross, DL and Goldenberg, SD and Forbes, B}, title = {Bacterial diversity, viability and stability in lyophilised faecal microbiota capsules support ongoing clinical use.}, journal = {International journal of pharmaceutics}, volume = {678}, number = {}, pages = {125703}, doi = {10.1016/j.ijpharm.2025.125703}, pmid = {40354906}, issn = {1873-3476}, mesh = {Humans ; Freeze Drying ; Capsules ; *Feces/microbiology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Microbial Viability ; RNA, Ribosomal, 16S/genetics ; *Bacteria/genetics/isolation & purification ; }, abstract = {Lyophilised encapsulated faecal microbiota provides a practical and cost-effective treatment option to patients with recurrent Clostridioides difficile infection. This study focused on quality assurance of an enteric-coated capsule formulation of FMT as a medicinal product by evaluating bacterial composition, diversity and viability through manufacturing steps and upon product storage at a range of temperatures. Faecal donations from pre-screened healthy individuals (n = 5) were processed according to a published protocol into one or more treatments; 5 capsules = 1 treatment dose/patient. Culture-independent next-generation 16S rRNA gene sequencing was used to speciate and quantify bacteria using a live-dead cell separation method to discriminate the viable cell load. Species diversity in donor stools aligned with other healthy gut microbiome and remained unchanged through the manufacturing process and after storage at -80 °C for 36 weeks. While diversity indices were consistent, a notable difference was observed between viable and total microbiome, particularly in species richness, which decreased when non-viable or compromised cells were excluded from analysis. Anaerobic species exhibited minimal viability loss despite processing in an aerobic environment. Furthermore, capsules were stable with storage at -20 °C and 2-8 °C, with no significant reduction of total live bacterial load after 24 weeks. In summary, 'live-dead' culture-independent analysis was used to characterise the viable faecal microbiome, which retained a diversity of bacterial species, including anaerobes, through manufacture and after storage in capsules for up to 36 weeks. These data support the comparable effectiveness of lyophilised encapsulated FMT to other formulations and delivery methods.}, } @article {pmid40354842, year = {2025}, author = {Zhang, S and Mao, X and Chang, L and Li, M and Wei, C and Li, H and Shen, X and Niu, K and Zhang, R and Jiang, Y and Lu, X and Song, Y and Zhou, L and Gao, L and Zhao, Z and Niu, L and Yang, Q and Hou, Y and Wu, Y}, title = {Bazi Bushen capsule modulates Akkermansia muciniphila and spermidine metabolism to attenuate brain aging in SAMP8 mice.}, journal = {Journal of ethnopharmacology}, volume = {349}, number = {}, pages = {119944}, doi = {10.1016/j.jep.2025.119944}, pmid = {40354842}, issn = {1872-7573}, mesh = {Animals ; Male ; Mice ; *Drugs, Chinese Herbal/pharmacology ; Gastrointestinal Microbiome/drug effects ; *Aging/drug effects ; *Brain/drug effects/metabolism ; Cognition/drug effects ; Capsules ; Maze Learning/drug effects ; Akkermansia ; }, abstract = {Bazi Bushen Capsule (BZBS), a traditional Chinese medicine formulation composed of multiple bioactive herbal components, has been validated in multicenter randomized double-blind controlled trials for its potent anti-aging properties. Previous studies from our group have demonstrated that BZBS effectively restores gut microbiota homeostasis and attenuates the impairment of intestinal barrier function, thereby ameliorating age-related cognitive decline. However, the specific molecular mechanisms by which BZBS modulates key microbial-metabolite networks to delay brain aging remain poorly understood and warrant further investigation.

AIM OF THE STUDY: This study aims to elucidate the key microbiota-metabolite networks through which BZBS improves cognitive function and delays brain aging in senescence-accelerated mouse-prone 8 (SAMP8) mice.

MATERIALS AND METHODS: Eight-week-old male SAMP8 mice were used as experimental models, randomly divided into Model, BZ-low (0.5 g/kg/d BZBS), BZ-high (1 g/kg/d BZBS), and RAPA (2 mg/kg/d rapamycin) groups. Senescence-accelerated mouse resistant 1 (SAMR1) mice served as the control group. Cognitive function was assessed using the Barnes Maze test and the three-chamber social test. The structural damage and pathological changes in the brain tissue were evaluated through transcranial Doppler, micro-computed tomography, Nissl staining, and Western blot analysis. Next, the intestinal barrier function was detected by hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and immunofluorescence (IF) staining. Characteristic bacteria were identified by 16S rRNA sequencing, and metabolomic profiling was performed using non-targeted metabolomics. Akkermansia muciniphila (Akk) was cultured, and fecal microbiota transplantation (FMT) was employed to evaluate its contribution to intestinal barrier function.

RESULTS: The study revealed that BZBS therapy not only enhances cognitive capabilities but also restores the intestinal barrier function. Akk was identified as a key regulatory agent mediating the therapeutic effects of BZBS. BZBS administration significantly increased the abundance of Akk and modulated its metabolite profile, particularly components associated with spermidine, thereby reinforcing the intestinal barrier and mitigating age-related cognitive decline. Furthermore, this study demonstrated that Akk, administered via fecal microbiota transplantation, alleviated dextran sulfate sodium (DSS)-induced colitis.

CONCLUSION: The results showed that BZBS capsule, a traditional Chinese medicine, may delay brain aging in SAMP8 mice by modulating Akk and its spermidine production.}, } @article {pmid40354071, year = {2025}, author = {Fernandez, E and Wargo, JA and Helmink, BA}, title = {The Microbiome and Cancer: A Translational Science Review.}, journal = {JAMA}, volume = {333}, number = {24}, pages = {2188-2196}, doi = {10.1001/jama.2025.2191}, pmid = {40354071}, issn = {1538-3598}, mesh = {Animals ; Humans ; Anti-Bacterial Agents/therapeutic use/adverse effects ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects/immunology ; Immunotherapy/adverse effects/methods ; *Microbiota/drug effects/immunology ; *Neoplasms/immunology/microbiology/mortality/therapy ; Translational Research, Biomedical ; Translational Science, Biomedical ; }, abstract = {IMPORTANCE: Growing evidence suggests that microbes located within the gastrointestinal tract and other anatomical locations influence the development and progression of diseases such as cancer.

OBSERVATIONS: Clinical and preclinical evidence suggests that microbes in the gastrointestinal tract and other anatomical locations, such as the respiratory tract, may affect carcinogenesis, development of metastases, cancer treatment response, and cancer treatment-related adverse effects. Within tumors of patients with cancer, microbes may affect response to treatment, and therapies that reduce or eliminate these microbes may improve outcomes in patients with cancer. Modulating gastrointestinal tract (gut) microbes through fecal microbiota transplant and other strategies such as dietary intervention (eg, high-fiber diet intervention) has improved outcomes in small studies of patients treated with cancer immunotherapy. In contrast, disruption of the gut microbiota by receipt of broad-spectrum antibiotics prior to treatment with cancer immunotherapy has been associated with poorer overall survival and higher rates of adverse effects in patients treated with immune checkpoint blockade for solid tumors and also with chimeric antigen receptor T-cell therapy for hematologic malignancies.

CONCLUSIONS AND RELEVANCE: Microbes in the gut and other locations in the body may influence the development and progression of cancer and may affect the response to adverse effects from cancer therapy. Future therapies targeting microbes in the gut and other locations in the body could potentially improve outcomes in patients with cancer.}, } @article {pmid40352262, year = {2025}, author = {Bao, M and Wu, R and Li, J and Tang, R and Song, C}, title = {Research summary, possible mechanisms and perspectives of gut microbiota changes causing precocious puberty.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1596654}, pmid = {40352262}, issn = {2296-861X}, abstract = {The increasing global incidence of precocious puberty, linked to environmental, metabolic, and genetic factors, necessitates innovative therapies beyond gonadotropin-releasing hormone (GnRH) analogs. Accumulating evidence implicates gut microbiota dysbiosis as a pivotal regulator of pubertal timing via interactions with hormone metabolism (e.g., estrogen reactivation via β-glucuronidase), neuroendocrine pathways (nitric oxide signaling), and immune-inflammatory responses. This review delineates taxonomic alterations in central precocious puberty (CPP) and obesity-related subtypes, including Streptococcus enrichment and Alistipes depletion, alongside functional shifts in microbial metabolite production. Mechanistic insights highlight microbiota-driven modulation of the hypothalamic-pituitary-gonadal (HPG) axis, leptin/insulin dynamics, and epigenetic regulation. Emerging interventions-probiotics, fecal microbiota transplantation (FMT), and dietary modifications-demonstrate efficacy in preclinical models and early clinical studies for delaying puberty onset and restoring hormonal balance. Translational efforts to validate these strategies are critical for addressing the clinical and psychosocial challenges posed by precocious puberty, positioning gut microbiota modulation as a novel therapeutic frontier in pediatric endocrinology.}, } @article {pmid40350912, year = {2025}, author = {Lu, CY and Yuan, XM and He, LH and Mao, JR and Chen, YG}, title = {[Mechanism of total flavone of Abelmoschus manihot in treating ulcerative colitis and depression via intestinal flora-glycerophospholipid metabolism- macrophage polarization pathway].}, journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica}, volume = {50}, number = {5}, pages = {1286-1297}, doi = {10.19540/j.cnki.cjcmm.20241111.701}, pmid = {40350912}, issn = {1001-5302}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Abelmoschus/chemistry ; *Macrophages/drug effects/immunology/metabolism ; *Colitis, Ulcerative/drug therapy/metabolism/microbiology/genetics/immunology ; *Flavones/administration & dosage ; Male ; *Depression/drug therapy/metabolism/microbiology/genetics ; *Glycerophospholipids/metabolism ; Humans ; *Drugs, Chinese Herbal/administration & dosage ; Mice, Inbred C57BL ; }, abstract = {This study delves into the mechanism of total flavone of Abelmoschus manihot(TFA) in treating ulcerative colitis(UC) and depression via inhibiting M1 polarization of macrophages and reshaping intestinal flora and glycerolphospholipid metabolism. The study established a mouse model of UC and depression induced by chronic restraint stress(CRS) and dextran sulfate sodium(DSS). The fecal microbiota transplantation(FMT) experiment after TFA intervention was conducted. Mice in the FMT donor group were modeled and treated, and fecal samples were taken to prepare the bacterial solution. Mice in the FMT receptor group were treated with antibiotic intervention, and then administered bacterial solution by gavage from mice in the donor group, followed by UC depression modeling. After the experiment, behavioral tests were conducted to evaluate depressive-like behaviors by measuring the levels of 5-hydroxytryptamine(5-HT) and brain-derived neurotrophic factor(BDNF) in the hippocampus of mice. The levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in the brain and colon tissue of mice were also measured, and the polarization status of macrophages was evaluated by measuring the mRNA levels of CD86 and CD206. 16S ribosomal RNA(16S rRNA) sequencing technology was used to analyze changes in the intestinal flora of mice. Wide target lipidomics was used to detect serum lipid metabolite levels in mice after FMT,and correlation analysis was conducted between lipids and differential intestinal flora significantly regulated by TFA. In vitro experiments, representative glycerophospholipid metabolites and glycerophospholipid inhibitors were used to intervene in Raw264.7 macrophages, and the mRNA levels of TNF-α,IL-6,IL-1β,CD86,and CD206 were detected. The results showed that TFA and FMT after intervention could significantly improve depressive-like behavior and intestinal inflammation in mice with UC and depression, significantly downregulate pro-inflammatory cytokines and CD86 mRNA expression in brain and colon tissue, inhibiting M1 polarization of macrophages, and significantly upregulate CD206 mRNA expression, promoting M2 polarization of macrophages. In addition, the high-dose group had a more significant effect. After TFA intervention, FMT significantly corrected the metabolic disorder of glycerophospholipids in mice with UC and depression, and there was a significant correlation between differential intestinal flora and glycerophospholipids. In vitro experiments showed that glycerophospholipid metabolites, especially lysophosphatidylcholine(LPC),significantly upregulated pro-inflammatory cytokines and CD86 mRNA expression, promote M1 polarization of macrophages, while glycerophospholipid inhibitors had the opposite effect. The results indicate that TFA effectively treats depression and UC by correcting intestinal flora dysbiosis and reshaping glycerophospholipid metabolism, thereby inhibiting M1 polarization of macrophages.}, } @article {pmid40350437, year = {2025}, author = {Hsu, CY and Ahmad, I and Maya, RW and Abass, MA and Gupta, J and Singh, A and Joshi, KK and Premkumar, J and Sahoo, S and Khosravi, M}, title = {The potential therapeutic approaches targeting gut health in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a narrative review.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {530}, pmid = {40350437}, issn = {1479-5876}, mesh = {Humans ; *Fatigue Syndrome, Chronic/therapy/microbiology/physiopathology ; *Gastrointestinal Microbiome ; Dysbiosis ; }, abstract = {BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disorder characterized by persistent fatigue and cognitive impairments, with emerging evidence highlighting the role of gut health in its pathophysiology. The main objective of this review was to synthesize qualitative and quantitative data from research examining the gut microbiota composition, inflammatory markers, and therapeutic outcomes of interventions targeting the microbiome in the context of ME/CFS.

METHODS: The data collection involved a detailed search of peer-reviewed English literature from January 1995 to January 2025, focusing on studies related to the microbiome and ME/CFS. This comprehensive search utilized databases such as PubMed, Scopus, and Web of Science, with keywords including "ME/CFS," "Gut-Brain Axis," "Gut Health," "Intestinal Dysbiosis," "Microbiome Dysbiosis," "Pathophysiology," and "Therapeutic Approaches." Where possible, insights from clinical trials and observational studies were included to enrich the findings. A narrative synthesis method was also employed to effectively organize and present these findings.

RESULTS: The study found notable changes in the gut microbiota diversity and composition in ME/CFS patients, contributing to systemic inflammation and worsening cognitive and physical impairments. As a result, various microbiome interventions like probiotics, prebiotics, specific diets, supplements, fecal microbiota transplantation, pharmacological interventions, improved sleep, and moderate exercise training are potential therapeutic strategies that merit further exploration.

CONCLUSIONS: Interventions focusing on the gut-brain axis may help reduce neuropsychiatric symptoms in ME/CFS by utilizing the benefits of the microbiome. Therefore, identifying beneficial microbiome elements and incorporating their assessments into clinical practice can enhance patient care through personalized treatments. Due to the complexity of ME/CFS, which involves genetic, environmental, and microbial factors, a multidisciplinary approach is also necessary. Since current research lacks comprehensive insights into how gut health might aid ME/CFS treatment, standardized diagnostics and longitudinal studies could foster innovative therapies, potentially improving quality of life and symptom management for those affected.}, } @article {pmid40350306, year = {2025}, author = {Liu, C and Gao, Y and Chen, Y and Zhu, L and Rao, F and Huang, Y and Zeng, Y and Cai, R and Wang, F and Cheng, J}, title = {Nephropathy II Decoction Attenuates Renal Fibrosis via Regulating TLR4 and Gut Microbiota Along the Gut-Kidney Axis.}, journal = {Biological & pharmaceutical bulletin}, volume = {48}, number = {5}, pages = {577-594}, doi = {10.1248/bpb.b24-00863}, pmid = {40350306}, issn = {1347-5215}, mesh = {Animals ; *Toll-Like Receptor 4/metabolism/genetics ; *Gastrointestinal Microbiome/drug effects ; Fibrosis ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Kidney/pathology/drug effects/metabolism ; Male ; Myeloid Differentiation Factor 88/metabolism ; Mice ; Mice, Inbred C57BL ; Reperfusion Injury/drug therapy/pathology/metabolism ; Signal Transduction/drug effects ; NF-kappa B/metabolism ; }, abstract = {Nephropathy II Decoction (NED) is a widely used Chinese medicinal formulation for managing chronic kidney disease (CKD). Despite its extensive application, the precise mechanisms underlying its therapeutic effects remain poorly understood. This study aims to elucidate the role of NED in attenuating renal fibrosis and to explore its impact on the gut-kidney axis. The principal constituents of NED were analyzed using ultra-performance LC-tandem mass spectrometry (UPLC-MS/MS). A bilateral renal ischemia-reperfusion injury (bIRI) model was employed to induce fibrosis. RT-qPCR was utilized to assess the expression of mRNA related to the toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) and nuclear factor-κB (NF-κB) signaling pathway. Western blotting analysis was performed to identify changes in renal fibrosis markers, TLR4/MyD88/NF-κB pathway proteins, and the colon proteins ZO-1 and Occludin-1. Serum levels of uremic toxins were quantified using enzyme-linked immunosorbent assay (ELISA), and 16S ribosomal RNA (rRNA) gene sequencing was conducted to explore changes in the gut microbiome of the mice. Our study demonstrated that mice in the NED group exhibited reduced serum creatinine, blood urea nitrogen, and urinary protein levels, alongside improvements in kidney damage and a decrease in renal fibrosis markers. In the bIRI group, TLR4/MyD88/NF-κB protein and mRNA levels, as well as intestinal tight junction proteins and enterogenic uremic toxins, were significantly reduced. NED treatment reversed these changes and modified the gut microbiota. Furthermore, fecal microbial transplantation (FMT) alleviated kidney damage and fibrosis in bIRI mice. In summary, NED ameliorates kidney injury and fibrosis by modulating the gut microbiota and may further attenuate fibrosis through the inhibition of TLR4 expression, thereby influencing the gut-kidney axis.}, } @article {pmid40350047, year = {2025}, author = {Huang, H and Yang, C and Li, S and Zhan, H and Tan, J and Chen, C and Liu, J and Wang, M and Li, H}, title = {Lizhong decoction alleviates experimental ulcerative colitis via regulating gut microbiota-SCFAs-Th17/Treg axis.}, journal = {Journal of ethnopharmacology}, volume = {349}, number = {}, pages = {119958}, doi = {10.1016/j.jep.2025.119958}, pmid = {40350047}, issn = {1872-7573}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis, Ulcerative/drug therapy/immunology/chemically induced/microbiology ; *T-Lymphocytes, Regulatory/drug effects/immunology ; *Th17 Cells/drug effects/immunology ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Dextran Sulfate ; Male ; Mice ; Mice, Inbred C57BL ; *Fatty Acids, Volatile/metabolism ; Disease Models, Animal ; Colon/drug effects/pathology/microbiology ; Fecal Microbiota Transplantation ; }, abstract = {Lizhong decoction (LZD), a Traditional Chinese Medicine formula, is widely utilized to treat gastrointestinal diseases, including ulcerative colitis in China for thousands of years.

AIM OF THE STUDY: To investigate whether the protective effect of LZD on ulcerative colitis is dependent on gut microbiota and T-cell immune homeostasis.

MATERIAL AND METHODS: The preventive effects of LZD on dextran sodium sulfate (DSS)-induced colitis mice were evaluated through the measurement of body weight, disease activity index, colon length and hematoxylin-eosin staining. Flow cytometry was used to detect the ratio of Th17/Treg cells. Pseudo sterile mice and fecal transplantation experiments were used to investigate whether the preventive effect of LZD was dependent on the gut microbiota. The alterations of gut microbiota were identified by the 16S rDNA sequencing. The content of intestinal short-chain fatty acids (SCFAs) was detected by LC-MS/MS analysis. The downstream signal pathways of SCFAs were detected by the immunoblotting.

RESULTS: LZD administration significantly alleviated weight loss and intestinal injury in DSS-induced colitis mice. LZD administration also promotes the balance of Th17/Treg cells. Moreover, LZD administration relies on gut microbiota to alleviate ulcerative colitis and regulate Th17/Treg cell balance. LZD administration significantly improves gut microbial composition in colitis mice, elevating the abundance of SCFAs producing bacterium such as lachnospiraceae_nk4a136_group and Akkermansia. LZD treatment further increases the abundance of SCFAs and promotes activation of free fatty acid activated receptor 2 (FFAR2).

CONCLUSION: LZD administration promotes Th17/Treg cell balance in a gut microbiota-SCFAs dependent manner, which in turn ameliorates ulcerative colitis.}, } @article {pmid40350003, year = {2025}, author = {Nohesara, S and Mostafavi Abdolmaleky, H and Dickerson, F and Pinto-Tomas, AA and Jeste, DV and Thiagalingam, S}, title = {Associations of microbiome pathophysiology with social activity and behavior are mediated by epigenetic modulations: Avenues for designing innovative therapeutic strategies.}, journal = {Neuroscience and biobehavioral reviews}, volume = {174}, number = {}, pages = {106208}, doi = {10.1016/j.neubiorev.2025.106208}, pmid = {40350003}, issn = {1873-7528}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Epigenesis, Genetic/physiology ; *Social Behavior ; Animals ; Probiotics ; }, abstract = {A number of investigations have shown that gut microbiome influences humans' ability to communicate with others, and impairments in social interactions are linked to alterations in gut microbiome composition and diversity, via epigenetic mechanisms. This article reviews the links among gut microbiome, social behavior, and epigenetic shifts relevant to gut microbiome-derived metabolites. First, we discuss how different social determinants of health, such as socioeconomic status, diet, environmental chemicals, migration, ecological conditions, and seasonal changes may influence gut microbiome composition, diversity, and functionality, along with epigenetic alterations and thereby affect social behavior. Next, we consider how gut microbiome-derived metabolites, diet, probiotics, and fecal microbiome transplantation may reduce impairments in social interactions through the adjustment of epigenetic aberrations (e.g., DNA methylation, histone modifications, and microRNAs expression) which may suppress or increase gene expression patterns. Finally, we present the potential benefits and unresolved challenges with the use of gut microbiome-targeted therapeutics in reducing social deficits.}, } @article {pmid40349812, year = {2025}, author = {Quan, T and Zhang, W and Shi, Y and Gao, T}, title = {Melatonin-mediated intestinal microbiota homeostasis improves skin barrier damage involvement of gut-skin axis dysfunction in aging mice.}, journal = {Cellular signalling}, volume = {133}, number = {}, pages = {111859}, doi = {10.1016/j.cellsig.2025.111859}, pmid = {40349812}, issn = {1873-3913}, mesh = {Animals ; *Melatonin/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Mice ; Humans ; *Skin/drug effects/pathology/metabolism ; *Aging ; Lipopolysaccharides/pharmacology ; *Homeostasis/drug effects ; Keratinocytes/metabolism/drug effects ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Male ; beta Catenin/metabolism ; Toll-Like Receptor 4/metabolism ; Skin Aging/drug effects ; Myeloid Differentiation Factor 88/metabolism ; Dysbiosis ; Glycogen Synthase Kinase 3 beta/metabolism ; HaCaT Cells ; }, abstract = {Researches suggested a close connection between the gut microbiome homeostasis and skin health. Melatonin, as a multifunctional molecule, has the potential to regulate intestinal homeostasis and skin function. The study further explored the potential mechanism of melatonin in ameliorating skin barrier damage from the perspective of the association between intestinal microbiota and gut-skin axis in aging mice. We established a natural aging-induced skin barrier damage mouse model with or without melatonin supplementation and fecal microbiota transplantation (FMT) to clarify the crucial role of intestinal microbiota-mediated gut-skin axis in melatonin improving skin barrier damage. Furthermore, lipopolysaccharide (LPS)-treated mice and human keratinocytes cells (HaCaT) explored the modulation mechanism of melatonin. Our results suggested that aging induced skin barrier damage, including skin microbiota disorder and epidermal barrier structure disruption, and intestinal dysbiosis. Similarly, FMT from aging mice and LPS treatment rebuild the aging-like skin barrier damage. Whereas, melatonin or resatorvid (TAK242, the antagonist of LPS) supplementation restored all consequence in aging and LPS-treated mice. In vitro, melatonin restored LPS-induced skin barrier proteins deficiency in HaCaT via decreasing the expression level of TLR4 and MyD88 and increasing the content of p-ERK, p-GSK-3β and β-catenin proteins, while the improving effects was mimicked by pretreatment with a TLR4 antagonist but were blocked by GSK-3β agonists. Our study revealed that melatonin-mediated intestinal microbiota homeostasis suppresses LPS escape to restore the skin barrier function, including skin dysbiosis and epidermal structural disruption via LPS/TLR4/MyD88/ERK/GSK-3β/β-catenin loop, further improving skin aging in mice.}, } @article {pmid40349163, year = {2025}, author = {Huang, M and Huang, M and Liu, L and Yang, F and He, C and Sun, YC and Jiao, YR and Tang, X and Hou, J and Chen, KX and He, WZ and Wei, J and Chen, HL and Li, X and Zeng, C and Lei, GH and Li, CJ}, title = {Gut Microbiota Modulates Obesity-Associated Skeletal Deterioration Through Macrophage Aging and Grancalcin Secretion.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {28}, pages = {e2502634}, pmid = {40349163}, issn = {2198-3844}, support = {2022YFC3601900//National Key Research and Development Program of China/ ; 2022YFC2009604//National Key Research and Development Program of China/ ; 82472521//National Natural Science Foundation of China/ ; 82272560//National Natural Science Foundation of China/ ; 82261160397//National Natural Science Foundation of China/ ; 81922017//National Natural Science Foundation of China/ ; 2023QYJC011//Central South University Research Program of Advanced Interdisciplinary Studies/ ; 2022SK2023//Key Research and Development Program of Hunan Province/ ; 2023RC1027//Science and Technology Innovation Program of Hunan Province/ ; 2022RC1009//Science and Technology Innovation Program of Hunan Province/ ; 2022RC3075//Science and Technology Innovation Program of Hunan Province/ ; 2024JC0004//Major Basic Research Projects in Hunan Province/ ; 2024M763722//China Postdoctoral Science Foundation/ ; 2023JJ30896//Natural Science Foundation of Hunan/ ; 2023JJ40965//Natural Science Foundation of Hunan/ ; 2025JJ60562//Natural Science Foundation of Hunan/ ; }, mesh = {Animals ; *Obesity/metabolism/microbiology/complications ; *Gastrointestinal Microbiome/physiology ; Mice ; *Macrophages/metabolism ; Humans ; Mice, Inbred C57BL ; Male ; *Cellular Senescence ; Female ; }, abstract = {Obesity is associated with skeletal deterioration and increased fracture risk, but the underlying mechanism is unclear. Herein, it is shown that obese gut microbiota promotes skeletal deterioration by inducing bone marrow macrophages (BMMs) senescence and grancalcin (GCA) secretion. Obese mice and those receiving obese fecal microbiota transplants exhibit increased senescent macrophages and elevated GCA expression in the bone marrow. In a study of 40 participants, it is found that obese patients are associated with higher serum GCA levels. It is further revealed that obese gut-microbiota derived lipopolysaccharides (LPS) stimulate GCA expression in senescent BMMs via activating Toll-like receptor 4 pathway. Mice with depletion of the Gca gene are resistant to the negative effects of obesity and LPS on bone. Moreover, neutralizing antibody against GCA mitigates skeletal deterioration in obese mice and LPS-induced chronic inflammation mouse model. The data suggest that the interaction between gut microbiota and the immune system contributes to obesity-associated skeletal deterioration, and targeting senescent macrophages and GCA shows potential of protecting skeletal health in obese population.}, } @article {pmid40348497, year = {2025}, author = {Munk Lauridsen, M and Jonasson, E and Bajaj, JS}, title = {Microbial Approaches to Treat and Prevent Hepatic Encephalopathy.}, journal = {Gastroenterology clinics of North America}, volume = {54}, number = {2}, pages = {429-451}, pmid = {40348497}, issn = {1558-1942}, support = {I01 CX001076/CX/CSRD VA/United States ; I01 CX002472/CX/CSRD VA/United States ; R01 AA029398/AA/NIAAA NIH HHS/United States ; }, mesh = {Humans ; *Hepatic Encephalopathy/prevention & control/therapy/microbiology ; *Gastrointestinal Microbiome ; Probiotics/therapeutic use ; *Fecal Microbiota Transplantation/methods ; Rifaximin/therapeutic use ; Lactulose/therapeutic use ; Gastrointestinal Agents/therapeutic use ; }, abstract = {This review articulates the significance of the gut-liver-brain axis in understanding hepatic encephalopathy (HE), emphasizing the role of gut microbiota in influencing liver and brain health. Key treatments like lactulose, rifaximin, probiotics, and fecal microbiota transplantation are examined for their ability to modulate the gut microbiome, thereby mitigating HE symptoms through reduced neurotoxin production and enhanced gut barrier integrity. The synopsis highlights both established and emerging microbial therapies, presenting them as crucial to the management and future strategies of HE. This comprehensive overview explores current therapeutic approaches alongside promising future interventions, suggesting that personalized microbiome-focused treatments may revolutionize HE management.}, } @article {pmid40348491, year = {2025}, author = {Sartor, RB}, title = {Beyond Random Fecal Microbial Transplants: Next Generation Personalized Approaches to Normalize Dysbiotic Microbiota for Treating IBD.}, journal = {Gastroenterology clinics of North America}, volume = {54}, number = {2}, pages = {333-350}, doi = {10.1016/j.gtc.2024.11.002}, pmid = {40348491}, issn = {1558-1942}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Precision Medicine/methods ; *Gastrointestinal Microbiome ; *Dysbiosis/therapy/microbiology ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Colitis, Ulcerative/therapy/microbiology ; Crohn Disease/therapy/microbiology ; Clostridioides difficile ; Pouchitis/therapy/microbiology ; }, abstract = {This review and commentary outline the strong rationale for normalizing the abnormal microbiota of patients with ulcerative colitis, Crohn's disease, and pouchitis and focus on strategies to improve current variable outcomes of fecal microbial transplant (FMT) in ulcerative colitis. Applying lessons from successful FMT therapy of recurrent Clostridioides difficile and insights from basic scientific understanding of host/microbial interactions provide strategies to enhance clinical outcomes in IBD. We outline promising approaches to develop novel-defined consortia of live biotherapeutic products and combination treatments to improve current results and to optimize and personalize treatment approaches in individual patients and disease subsets.}, } @article {pmid40348489, year = {2025}, author = {Silveira, MAD and Rodrigues, RR and Trinchieri, G}, title = {Intestinal Microbiome Modulation of Therapeutic Efficacy of Cancer Immunotherapy.}, journal = {Gastroenterology clinics of North America}, volume = {54}, number = {2}, pages = {295-315}, pmid = {40348489}, issn = {1558-1942}, support = {Z99 CA999999/ImNIH/Intramural NIH HHS/United States ; ZIA BC011153/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy/methods ; *Neoplasms/therapy/immunology/microbiology ; Fecal Microbiota Transplantation ; Immune Checkpoint Inhibitors/therapeutic use ; }, abstract = {Bacteria are associated with certain cancers and may induce genetic instability and cancer progression. The gut microbiome modulates the response to cancer therapy. Training machine learning models with response associated taxa or bacterial genes predict patients' response to immunotherapies with moderate accuracy. Clinical trials targeting the gut microbiome to improve immunotherapy efficacy have been conducted. While single bacterial strains or small consortia have not be reported yet to be successful, encouraging results have been reported in small single arm and randomized studies using transplant of fecal microbiome from cancer patients who successfully responded to therapy or from healthy volunteers.}, } @article {pmid40348488, year = {2025}, author = {Magier, SJ and Morley, TS and Kelly, CR}, title = {Optimizing Therapeutic Potential of Fecal Transplant in Inflammatory Bowel Disease.}, journal = {Gastroenterology clinics of North America}, volume = {54}, number = {2}, pages = {277-293}, doi = {10.1016/j.gtc.2024.12.002}, pmid = {40348488}, issn = {1558-1942}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Colitis, Ulcerative/therapy/microbiology ; *Crohn Disease/therapy/microbiology ; Pouchitis/therapy ; Remission Induction ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract influenced by genetic, environmental, immune, and microbial factors. Reduced gut microbial diversity and elevated proinflammatory bacteria levels in IBD disrupt mucosal immunity, barrier function, and inflammatory pathways. Fecal microbiota transplantation (FMT) is a potential therapy to restore microbial balance. Studies suggest that FMT may induce remission in mild-to-moderate ulcerative colitis but show limited efficacy in Crohn's disease and pouchitis. Donor microbiota colonization correlates with remission, but varied study designs challenge findings. Further research is required to standardize FMT protocols, optimize donor selection, and ensure long-term safety.}, } @article {pmid40348487, year = {2025}, author = {Ressler, AM and Rao, K and Young, VB}, title = {Current Approaches to Treat and Prevent Recurrence of Clostridioides difficile.}, journal = {Gastroenterology clinics of North America}, volume = {54}, number = {2}, pages = {259-275}, doi = {10.1016/j.gtc.2025.02.005}, pmid = {40348487}, issn = {1558-1942}, mesh = {Humans ; *Clostridium Infections/prevention & control/therapy/microbiology/drug therapy ; *Anti-Bacterial Agents/therapeutic use/adverse effects ; *Clostridioides difficile ; *Gastrointestinal Microbiome/drug effects ; Fecal Microbiota Transplantation ; Recurrence ; Secondary Prevention/methods ; Probiotics/therapeutic use ; }, abstract = {Clostridioides difficile infection (CDI) and recurrent CDI (rCDI) are significant causes of morbidity and mortality. The microbiome plays a significant role in the body's defense against CDI and rCDI. Antibiotics can cause significant injury to the microbiome which leads to an increased risk of CDI and rCDI. Ongoing perturbations of the microbiome perpetuate this risk. Antibiotic treatments for CDI can kill C difficile but also can impact the microbiome. Microbiome therapeutics are effective in restoring the function of the gut microbiota and re-establishing colonization resistance. The field of microbiome therapeutics is evolving with newer, more refined, modalities in development.}, } @article {pmid40348275, year = {2025}, author = {Hassib, L and Kanashiro, A and Pedrazzi, JFC and Vercesi, BF and Higa, S and Arruda, Í and Soares, Y and de Jesus de Souza, A and Barichello, T and Guimarães, FS and Ferreira, FR}, title = {Microbiota-based therapies as novel targets for autism spectrum disorder: A systematic review and meta-analysis.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {139}, number = {}, pages = {111385}, doi = {10.1016/j.pnpbp.2025.111385}, pmid = {40348275}, issn = {1878-4216}, mesh = {Humans ; *Autism Spectrum Disorder/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Prebiotics/administration & dosage ; *Probiotics/therapeutic use/administration & dosage ; Randomized Controlled Trials as Topic/methods ; }, abstract = {BACKGROUND: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by persistent deficits in social interaction and communication. Emerging evidence suggests that alterations in the gut-brain axis play a key role in the pathophysiology of ASD, and that microbiota-targeted interventions may offer therapeutic benefits. However, no clear consensus has been reached regarding the effectiveness of these strategies in ameliorating behavioral characteristics. This systematic review and meta-analysis (PROSPERO registration ID: CRD42023494067) aimed to evaluate the impact of microbiota-based interventions-including synbiotics, prebiotics, single-strain probiotics, probiotic blends, and fecal microbiota transplantation (FMT)-on behavioral outcomes in individuals with ASD, with particular emphasis on social functioning.

RESULTS: Of the 373 records initially identified, 20 studies met the inclusion criteria, comprising 16 randomized controlled trials and 4 open-label studies. The overall effect size indicated a statistically significant improvement in ASD-related behavioral symptoms following microbiota manipulation (Hedges' g = 0.47; 95 % CI: 0.30-0.64; p < 0.001; I[2] = 33.01 %), representing a small but clinically relevant effect. Heterogeneity was classified as moderate. Among the interventions, FMT and probiotic blends yielded the most substantial effects. All major limitations of the current studies were thoroughly addressed and discussed to guide future experimental designs. Additionally, we examined preclinical evidence supporting the involvement of neural, immune, and metabolic pathways in mediating the observed behavioral improvements.

CONCLUSIONS: Our findings support the potential of microbiota-based therapies as a promising and well-tolerated strategy for improving behavioral symptoms in individuals with ASD. FMT and multi-strain probiotic formulations appear particularly effective. Nevertheless, further high-quality randomized controlled trials-especially involving FMT-are urgently needed to validate these results and guide clinical implementation. Thus, these findings provide a critical foundation for future investigations seeking to refine microbiota-based interventions and uncover the underlying mechanisms through which they influence ASD-related behaviors.}, } @article {pmid40348054, year = {2025}, author = {Meher, R}, title = {From 'Aww to Wow': emerging role of transfusion medicine in fecal microbiota transplantation.}, journal = {Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tracli.2025.05.004}, pmid = {40348054}, issn = {1953-8022}, } @article {pmid40341264, year = {2025}, author = {Wang, X and Li, T and Dong, L and Li, Y and Ding, H and Wang, J and Xu, Y and Sun, W and Li, L}, title = {Exploring the lipid-lowering effects of cinnamic acid and cinnamaldehyde from the perspective of the gut microbiota and metabolites.}, journal = {Food & function}, volume = {16}, number = {11}, pages = {4399-4414}, doi = {10.1039/d5fo00384a}, pmid = {40341264}, issn = {2042-650X}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Acrolein/analogs & derivatives/pharmacology/administration & dosage ; Animals ; *Cinnamates/pharmacology/administration & dosage ; Mice ; Male ; Lipid Metabolism/drug effects ; Mice, Inbred C57BL ; Diet, High-Fat/adverse effects ; *Hyperlipidemias/metabolism/drug therapy ; *Hypolipidemic Agents/pharmacology ; Bacteria/classification/drug effects/genetics/isolation & purification ; Liver/metabolism/drug effects ; }, abstract = {The increasing incidence and associated metabolic complications pose major challenges in the treatment of hyperlipidaemia. Cinnamon is a food and medicinal resource associated with lipid metabolism, but the mechanism by which its active components, cinnamic acid (CA) and cinnamaldehyde (CM), alleviate hyperlipidaemia remains unclear. Biochemical, pathological, gut microbiota, and metabolomic analyses were performed to investigate the effects of CA and CM on HFD-fed mice and the underlying mechanisms involved. Supplementation with CA and CM reduced body weight, liver, and adipose tissue accumulation in HFD-induced mice; improved glucose and lipid metabolism; and decreased inflammation and oxidative stress levels, with CM showing superior efficacy. Faecal microbiota transplantation confirmed that the therapeutic effect was closely related to core gut bacteria and metabolites. Specifically, CA and CM inhibited the growth of lipid metabolism-related genera (e.g., Turicibacter and Romboutsia) and metabolites (e.g., PC, LysoPCs, prostaglandin E2, and arachidonic acid) while promoting the growth of beneficial genera (e.g., Oscillospiraceae and Colidextribacter) and metabolites (e.g., linoleic acid, phytosphingosine, and stercobilin). Additionally, Spearman's correlation analysis revealed that serum and hepatic lipids, as well as inflammatory factors, were positively correlated with Erysipelatoclostridium, Turicibacter, Eubacterium fissicatena, Enterorhabdus, cervonoyl ethanolamide, and acetoxystachybotrydial acetate, whereas they were negatively correlated with Lachnospiraceae NK4A136, stercobilin, LysoPE (15:0/0:0), and phytosphingosine. In contrast, hepatic oxidative stress markers exhibited the opposite correlation pattern. In conclusion, CA and CM have the potential to regulate the core gut microbiota and metabolites to improve lipid metabolism and decrease related inflammation and oxidative stress levels.}, } @article {pmid40339798, year = {2025}, author = {Gîlcă-Blanariu, GE and Pakpour, S and Kao, D}, title = {More questions than answers? Predicting faecal microbiota transplantation outcomes for recurrent Clostridioides difficile infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {31}, number = {7}, pages = {1095-1096}, doi = {10.1016/j.cmi.2025.04.036}, pmid = {40339798}, issn = {1469-0691}, } @article {pmid40337926, year = {2025}, author = {Shu, Y and Jiang, H and Gao, X and Hong, P and Wang, Q and Ruan, Y and Wu, H and He, J}, title = {Microcystin-LR Induces Lipid Metabolism Disorder in Pelophylax nigromaculatus Tadpoles via the Gut-Liver Axis.}, journal = {Environmental science & technology}, volume = {59}, number = {19}, pages = {9399-9411}, doi = {10.1021/acs.est.4c12957}, pmid = {40337926}, issn = {1520-5851}, mesh = {Animals ; Larva ; *Microcystins/toxicity ; Liver/drug effects/metabolism ; *Lipid Metabolism/drug effects ; Gastrointestinal Microbiome/drug effects ; Marine Toxins ; Ranidae ; }, abstract = {Disruption of lipid homeostasis in aquatic animals poses serious health risks, including tissue damage and systemic metabolic dysfunction. The precise mechanisms by which microcystin-LR, a potent cyanotoxin, disrupts lipid metabolism in amphibian tadpoles remain unclear. In this study, tadpoles (Pelophylax nigromaculatus) were exposed to MC-LR and fecal microbiota transplantation (FMT) experiments were performed to investigate whether or how MC-LR at environmental concentrations interfered with tadpole lipid metabolism from the perspective of the gut microbiota-gut-liver axis. Following exposure, the liver exhibited significant inflammation, hypertrophy, and fibrosis, accompanied by elevated serum lipid levels. Furthermore, the expression levels of the farnesoid X receptor (FXR), a nuclear receptor, were significantly downregulated. Molecular docking and molecular dynamics simulations indicated a strong and stable binding between FXR and MC-LR. Moreover, MC-LR suppressed liver FXR expression or activity, triggering: (1) upregulation of sterol regulatory element-binding protein 1 (SREBP1)-mediated triglyceride (TG) synthesis, (2) inhibition of free fatty acid (FFA) β-oxidation, and (3) activation of SREBP2-dependent bile acid biosynthesis. Moreover, MC-LR altered the composition of gut microbiota and specific bile acid levels (e.g., taurocholic acid and glycochenodeoxycholic acid) in the gut, thereby interfering with hepatic lipid metabolism, as evidenced by FMT-induced hepatic lipid accumulation in recipient tadpoles. These findings identify FXR as a potentially key molecular target for MC-LR and suggest that changes in bile acid levels of intestinal microbiota metabolism also may be an important pathway driving hepatic lipid dysregulation in amphibians exposed to environmental concentrations of MC-LR.}, } @article {pmid40336226, year = {2025}, author = {Cui, C and Gao, S and Shi, J and Wang, K}, title = {Gut-Liver Axis: The Role of Intestinal Microbiota and Their Metabolites in the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease.}, journal = {Gut and liver}, volume = {19}, number = {4}, pages = {479-507}, pmid = {40336226}, issn = {2005-1212}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Disease Progression ; *Liver/metabolism ; Dysbiosis ; *Fatty Liver/microbiology/metabolism/therapy ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Bile Acids and Salts/metabolism ; *Non-alcoholic Fatty Liver Disease/microbiology ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as one of the most prevalent chronic liver diseases globally, and its pathogenesis is closely linked to the imbalance of intestinal microbiota and their metabolites. This article reviews the mechanisms through which intestinal microbiota influence the progression of MASLD via the gut-liver axis, elaborating on the complex roles of immune cell hyperactivation, impaired intestinal barrier function, and intestinal microbial metabolites such as short-chain fatty acids and bile acids. The imbalance of intestinal microbiota not only directly promotes the development of MASLD but also further exacerbates disease progression through abnormalities in their metabolites. Various novel therapeutic strategies are being actively developed on the basis of gut-liver axis theory, including probiotic/prebiotic/synbiotic treatment, fecal microbiota transplantation, and targeted drug therapy. These strategies aim to precisely regulate microbial homeostasis and improve glucose and lipid metabolism, thereby alleviating hepatic inflammation and fibrosis and optimizing the therapeutic outcomes of patients with MASLD. In the future, as research progresses, we will further uncover the interaction mechanisms between intestinal microbiota and MASLD and continuously explore more effective treatment methods, with the goal of improving the prognosis and quality of life for MASLD patients.}, } @article {pmid40335640, year = {2025}, author = {Kellermayer, R and Nagy-Szakal, D and Ihekweazu, FD and Luna, RA and Versalovic, J}, title = {Mucosal disease activity may predict response to fecal microbiota transplantation in patients with ulcerative colitis.}, journal = {Pediatric research}, volume = {}, number = {}, pages = {}, pmid = {40335640}, issn = {1530-0447}, } @article {pmid40335381, year = {2025}, author = {Vuyk, W and Bobholz, M and Emmen, I and Lail, A and Minor, N and Bhimalli, P and Eickhoff, JC and Ries, HJ and Machkovech, H and Wei, W and Weiler, A and Richardson, A and DePagter, C and VanSleet, G and Bhasin, M and Kamal, S and Wolf, S and Virdi, A and Bradley, T and Gifford, A and Benito, M and Shipe, A and Mohamed, R and Smith, J and Wilson, N and Friedrich, TC and O'Connor, DH and Garonzik-Wang, J}, title = {Longitudinal Assessment of Solid Organ Transplant Recipients With SARS-CoV-2 Infection.}, journal = {Transplantation proceedings}, volume = {57}, number = {5}, pages = {922-930}, doi = {10.1016/j.transproceed.2025.04.004}, pmid = {40335381}, issn = {1873-2623}, mesh = {Humans ; *COVID-19/diagnosis/virology/epidemiology/immunology ; Middle Aged ; *SARS-CoV-2/genetics/isolation & purification ; Male ; *Organ Transplantation/adverse effects ; *Immunocompromised Host ; Female ; Virus Shedding ; *Transplant Recipients ; Prospective Studies ; Adult ; RNA, Viral ; Longitudinal Studies ; Viral Load ; Aged ; Feces/virology ; }, abstract = {BACKGROUND: Compared with immunocompetent individuals, those who are immunocompromised, including solid organ transplant (SOT) recipients, have higher SARS-CoV-2-related morbidity and mortality. We determined the duration of SARS-CoV-2 RNA positivity to evaluate viral persistence in SOT recipients.

METHODS: This study prospectively followed SOT recipients who recently tested positive for SARS-CoV-2. The duration of viral RNA shedding in nasal swabs and stool samples was tracked, and viral genome sequencing was performed where possible. Persistent infection was defined as a positive nucleic acid amplification test (NAAT) for SARS-CoV-2 at 28 days or later after initial infection. This duration was chosen based on the U.S. Centers for Disease Control and Prevention (CDC) recommendation that immunocompromised individuals isolate for at least 20 days [1], compared with 10 days for non-immunocompromised individuals.

RESULTS: Of 30 SOT recipients, 12 (40%) had positive SARS-CoV-2 RNA in nasal swabs or stool (cycle threshold [Ct] < 40) at 28 or more days after the first positive SARS-CoV-2 test. Immunocompromised (IC) subject 015 had high viral loads (Ct < 30) at 28 days, with continued detection for 54 days.

CONCLUSIONS: In 12 of 30 SOT subjects, SARS-CoV-2 RNA was detected at or beyond 28 days post-detection (dpd), despite vaccination and antibody and/or antiviral treatment in most participants. Three subjects tested positive for SARS-CoV-2 RNA past 50 dpd. Viral persistence in the setting of host immune suppression, coupled with exposure to antiviral treatments, raises concern about the selection of unusual viral variants.}, } @article {pmid40335161, year = {2025}, author = {Mela, V and Heras, V and Iesmantaite, M and García-Martín, ML and Bernal, M and Posligua-García, JD and Subiri-Verdugo, A and Martínez-Montoro, JI and Gómez-Pérez, AM and Bandera, B and Moreno-Indias, I and Tinahones, FJ}, title = {Microbiota fasting-related changes ameliorate cognitive decline in obesity and boost ex vivo microglial function through the gut-brain axis.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-335353}, pmid = {40335161}, issn = {1468-3288}, abstract = {BACKGROUND: Obesity-related cognitive decline is linked to gut microbiota dysbiosis, with emerging evidence suggesting that dietary interventions may ameliorate cognitive impairment via gut-brain axis modulation. The role of microglial cells in this process remains underexplored.

OBJECTIVE: To investigate how diet-induced changes in gut microbiota influence cognitive function in individuals with obesity and their microglial activity, and to determine the impact of specific dietary interventions.

DESIGN: This study included 96 participants with obesity who were randomised into three dietary intervention groups: Mediterranean diet (Med), alternate-day fasting (ADF) and ketogenic diet (Keto). Cognitive performance and microbiota composition were assessed pre-intervention and post-intervention. The effects of microbiota-related changes on microglial function were further evaluated in mice models through faecal transplantation and in vitro model with microbiota exosome treatment.

RESULTS: Both the Keto and ADF groups demonstrated significant weight loss, but cognitive performance improved most notably in the ADF group, in association with reduced inflammation. Diet-related microbiota composition was correlated with the cognitive outcomes in the human study. Mice models confirmed that the cognitive benefits of ADF were microbiota-dependent and linked to enhanced microglial phagocytic capacity and reduced inflammation, accompanied by changes in microglia morphology.

CONCLUSION: Fasting-induced modifications in gut microbiota contribute to cognitive improvement in individuals with obesity, with microglial cells playing a crucial mediatory role. Among the interventions, ADF most effectively enhanced microglial function and cognitive performance, suggesting its potential as a therapeutic strategy for obesity-related cognitive decline. Further studies are required to fully elucidate the underlying mechanisms.

TRIAL REGISTRATION NUMBER: NCT04453150.}, } @article {pmid40334428, year = {2025}, author = {Gu, S and Chen, C and Wang, J and Wang, Y and Zhao, L and Xiong, Z and Zhang, H and Deng, T and Pan, Q and Zheng, Y and Li, Y}, title = {Camellia Japonica Radix modulates gut microbiota and 9(S)-HpODE-mediated ferroptosis to alleviate oxidative stress against MASLD.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {143}, number = {}, pages = {156806}, doi = {10.1016/j.phymed.2025.156806}, pmid = {40334428}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Ferroptosis/drug effects ; *Oxidative Stress/drug effects ; *Camellia/chemistry ; Mice ; Male ; Mice, Inbred C57BL ; *Fatty Liver/drug therapy ; Plant Roots/chemistry ; *Plant Extracts/pharmacology ; Humans ; Disease Models, Animal ; }, abstract = {BACKGROUND: Camellia japonica radix (CJR), derived from the root of Camellia japonica L., has the potential to function as an herbal tea substitute for the prevention and intervention of metabolic dysfunction-associated steatotic liver disease (MASLD). It can provide systemic therapeutic benefits, boast a favorable safety profile, facilitate convenient consumption, and support long-term applicability. Despite its potential, research on CJR remains limited.

PURPOSE: The aim of this study aims is to elucidate the therapeutic mechanisms of CJR in MASLD, thereby providing evidence to support its clinical application.

METHODS: The therapeutic effects of CJR were evaluated using a water-supplementation model in MASLD mice. Integrated microbiome, transcriptome, proteome, and metabolome analyses were employed to comprehensively explore the mechanisms involved. A drug-target pull-down assay was performed to identify specific protein targets of small molecule metabolites in vitro. Fecal microbiota transplantation in antibiotic-treated ABX mice was conducted to confirm the critical role of gut microbiota and its metabolites. Furthermore, customized medicated feed supplemented with linoleic acid was used to explore the intervention effect of its metabolite, 9(S)-HpODE, as well as to evaluate its dietary intervention potential.

RESULTS: This present study explicitly elucidates the efficacy of CJR extract in alleviating hepatic inflammation and steatosis in a MASLD model mice, with its pharmacological mechanism associated with gut microbiota, linoleic acid metabolism, and GPX4-mediated ferroptosis. Notably, 9(S)-HpODE was discovered to be a key metabolite of linoleic acid, which could target both KEAP1 and SLC7A11, bidirectionally regulating GPX4-mediated ferroptosis, while acting as a signaling molecule at low doses to induce redox adaptation via oxidative preconditioning, thus ameliorating oxidative stress in MASLD.

CONCLUSION: Our findings indicate that both CJR and linoleic acid exhibit significant potential as dietary interventions for the management of MASLD, offering promising avenues for future research and clinical application.}, } @article {pmid40333159, year = {2025}, author = {Gao, Y and Lou, Y and Hui, Y and Chen, H and Sang, H and Liu, F}, title = {Characterization of the Gut Microbiota in Patients with Psoriasis: A Systematic Review.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {4}, pages = {}, pmid = {40333159}, issn = {2076-0817}, support = {22LCYY-QH10//Jinling Hospital/ ; }, mesh = {Humans ; *Dysbiosis/microbiology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Probiotics/administration & dosage ; *Psoriasis/microbiology/therapy ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Background: Psoriasis is a prevalent and persistent inflammatory disorder with systemic manifestations. Emerging evidence implicates the gut microbiota in regulating inflammatory responses, metabolic pathways, and immune homeostasis. This review synthesizes current evidence on gut microbiota dysbiosis in psoriasis and evaluates the therapeutic potential of probiotics and fecal microbiota transplantation (FMT) in disease management. Method: Following PRISMA guidelines, we systematically reviewed studies investigating gut microbiome profiles in psoriasis through the MEDLINE, EMBASE, and Web of Science databases (January 2015-December 2024). Included studies utilized 16S rRNA gene sequencing or metagenomic analyses for microbial characterization. Results: Comparative analyses revealed distinct gut microbiota patterns in psoriasis patients compared with healthy controls, although specific microbial signatures exhibited inconsistencies across studies. Notably, interventions modulating gut microbiota composition-particularly probiotic supplementation-demonstrated measurable improvements in psoriasis severity scores and inflammatory markers. Conclusions: Gut microbiome modulation represents a promising therapeutic strategy for psoriasis; however, current evidence highlights the need for standardized microbial analysis methodologies and larger longitudinal studies to establish causality. Future research should prioritize the functional characterization of microbiota-host interactions to optimize therapeutic applications.}, } @article {pmid40332367, year = {2025}, author = {Ionescu, VA and Diaconu, CC and Gheorghe, G and Mihai, MM and Diaconu, CC and Bostan, M and Bleotu, C}, title = {Gut Microbiota and Colorectal Cancer: A Balance Between Risk and Protection.}, journal = {International journal of molecular sciences}, volume = {26}, number = {8}, pages = {}, pmid = {40332367}, issn = {1422-0067}, mesh = {Humans ; *Colorectal Neoplasms/microbiology/prevention & control/immunology/etiology ; *Gastrointestinal Microbiome ; Animals ; Risk Factors ; Probiotics ; }, abstract = {The gut microbiome, a complex community of microorganisms residing in the intestinal tract, plays a dual role in colorectal cancer (CRC) development, acting both as a contributing risk factor and as a protective element. This review explores the mechanisms by which gut microbiota contribute to CRC, emphasizing inflammation, oxidative stress, immune evasion, and the production of genotoxins and microbial metabolites. Fusobacterium nucleatum, Escherichia coli (pks+), and Bacteroides fragilis promote tumorigenesis by inducing chronic inflammation, generating reactive oxygen species, and producing virulence factors that damage host DNA. These microorganisms can also evade the antitumor immune response by suppressing cytotoxic T cell activity and increasing regulatory T cell populations. Additionally, microbial-derived metabolites such as secondary bile acids and trimethylamine-N-oxide (TMAO) have been linked to carcinogenic processes. Conversely, protective microbiota, including Lactobacillus, Bifidobacterium, and Faecalibacterium prausnitzii, contribute to intestinal homeostasis by producing short-chain fatty acids (SCFAs) like butyrate, which exhibit anti-inflammatory and anti-carcinogenic properties. These beneficial microbes enhance gut barrier integrity, modulate immune responses, and inhibit tumor cell proliferation. Understanding the dynamic interplay between pathogenic and protective microbiota is essential for developing microbiome-based interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, to prevent or treat CRC. Future research should focus on identifying microbial biomarkers for early CRC detection and exploring personalized microbiome-targeted therapies. A deeper understanding of host-microbiota interactions may lead to innovative strategies for CRC management and improved patient outcomes.}, } @article {pmid40329424, year = {2025}, author = {Ni, Q and Xia, L and Huang, Y and Yuan, X and Gu, W and Chen, Y and Wang, Y and Nian, M and Wu, S and Cai, H and Huang, J}, title = {Gut microbiota dysbiosis orchestrates vitiligo-related oxidative stress through the metabolite hippuric acid.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {112}, pmid = {40329424}, issn = {2049-2618}, support = {82203909//National Natural Science Foundation of China grant/ ; 82100513//National Natural Science Foundation of China grant/ ; GZC20233592//Postdoctoral Fellowship Program of CPSF/ ; 22BJQN003//Youth Talent Support Program of Air Force Medical Center/ ; 21ZT10//Boost Program for Young Doctor of Air Force Medical Center/ ; 2023JH6/100100034//Science and Technology Foundation of Liaoning Province guided by the central government in 2023/ ; }, mesh = {*Vitiligo/microbiology/metabolism/pathology ; *Oxidative Stress ; *Gastrointestinal Microbiome/physiology ; Animals ; *Dysbiosis/microbiology/metabolism ; Mice ; Humans ; *Hippurates/metabolism/blood ; Reactive Oxygen Species/metabolism ; Disease Models, Animal ; Male ; Skin/metabolism/pathology ; Fecal Microbiota Transplantation ; Female ; Melanocytes/metabolism ; Probiotics/administration & dosage ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Vitiligo, a depigmenting autoimmune skin disease characterized by melanocyte dysfunction or death, is known to be associated with an imbalance in gut microbiota. Oxidative stress plays a critical role in the pathogenesis of vitiligo. However, the complex promising interaction between abnormal accumulation of reactive oxygen species (ROS) in the skin and gut microbiota has remained unclear.

RESULTS: Here, we compared transcriptome data of vitiligo lesions and normal skin and identified a high expression of oxidative stress-related genes in vitiligo lesions. We also established a vitiligo mouse model and found that the presence of gut microbiota influenced the expression of ROS-related genes. Depletion of gut microbiota reduced abnormal ROS accumulation and mitochondrial abnormalities in melanocytes, significantly improving depigmentation. Our findings from manipulating gut microbiota through cohousing, fecal microbiota transplantation (FMT), and probiotic supplementation showed that transferring gut microbiota from mice with severe vitiligo-like phenotypes exacerbated skin depigmentation while probiotics inhibited its progression. Targeted metabolomics of fecal, serum, and skin tissues revealed gut microbiota-dependent accumulation of hippuric acid, mediating excessive ROS in the skin. Elevated serum hippuric acid levels were also confirmed in vitiligo patients. Additionally, a microbiota-dependent increase in intestinal permeability in vitiligo mice mediated elevated hippuric acid levels, and we found that hippuric acid could directly bind to ROS-related proteins (NOS2 and MAPK14).

CONCLUSIONS: Our results suggested the important role of gut microbiota in regulating vitiligo phenotypes and oxidative stress. We identified hippuric acid, a gut microbiota-host co-metabolite, as a critical mediator of oxidative stress in vitiligo skin and its binding targets (NOS2 and MAPK14), resulting in oxidative stress. Validation in a small human cohort suggested that hippuric acid could serve as a novel diagnostic biomarker and therapeutic target for vitiligo. These findings provided new insights into how gut microbiota regulates skin oxidative stress in vitiligo and suggested potential treatment strategies for the disease. Video Abstract.}, } @article {pmid40329327, year = {2025}, author = {Ding, L and Qi, K and Zhou, Y and Li, Q and Liu, M and Hu, N and Wang, J and Qiu, J and Deng, X and Xu, L}, title = {Ingestion of Artemisia argyit essential oil combats Salmonella pullorum infections by altering gut microbiota composition in chicks.}, journal = {Veterinary research}, volume = {56}, number = {1}, pages = {98}, pmid = {40329327}, issn = {1297-9716}, support = {2023YFD1800903//National Key Research and Development Program of China/ ; U22A20523//National Natural Science Foundation of China/ ; JJKH20250155KJ//Scientific Research Project of the Education Department of Jilin Province/ ; 2023-JCXK-01//Fundamental Research Funds for the Central Universities/ ; 2024T170330//China Postdoctoral Science Foundation/ ; 2024M751096//China Postdoctoral Science Foundation/ ; GZB20240268//postdoctoral Fellowship Program (Grade B) of China Postdoctoral Science Foundation/ ; }, mesh = {Animals ; *Artemisia/chemistry ; *Gastrointestinal Microbiome/drug effects ; *Chickens ; *Oils, Volatile/pharmacology/administration & dosage ; *Poultry Diseases/microbiology/prevention & control/drug therapy ; *Salmonella Infections, Animal/microbiology/prevention & control/drug therapy ; Fecal Microbiota Transplantation/veterinary ; Animal Feed/analysis ; *Salmonella/drug effects/physiology ; Dietary Supplements/analysis ; *Plant Oils/pharmacology ; Diet/veterinary ; }, abstract = {Pullorum disease, caused by Salmonella pullorum (S. pullorum), is a highly contagious illness affecting the poultry industry. Emerging evidence suggests that Artemisia argyit essential oil can influence the composition of gut microbes in the host, thereby promoting overall health. However, the specific mechanisms by which Artemisia argyit essential oil modulates gut microbiota to combat S. pullorum infection remains unclear. This study explored the effectiveness of various doses of Artemisia argyit essential oil in preventing S. pullorum infection in chicks. Our findings indicate that consuming this essential oil can mitigate the intestinal mucosal barrier damage and excessive inflammatory response caused by S. pullorum, as well as reverse the weight loss seen in infected chicks. Additionally, chicks that received faecal microbiota transplantation (FMT) from the gut microbiota of Artemisia argyit essential oil donors exhibited notable recovery from S. pullorum infections. This suggests that the observed protection may be linked to the modulation of gut microbiota. Furthermore, 16S rRNA sequencing revealed an increased abundance of Lactobacillus reuteri (L. reuteri), which along with the activation of Wnt/β-catenin pathways, played critical roles in the enhanced health of S. pullorum-infected chicks treated with Artemisia argyit essential oil. In summary, these findings highlight that the dietary inclusion of Artemisia argyit essential oil promotes the intestinal enrichment of L. reuteri, offering a promising strategy for the treatment and prevention of pullorum disease in chicks.}, } @article {pmid40329009, year = {2025}, author = {Nobels, A and van Marcke, C and Jordan, BF and Van Hul, M and Cani, PD}, title = {The gut microbiome and cancer: from tumorigenesis to therapy.}, journal = {Nature metabolism}, volume = {7}, number = {5}, pages = {895-917}, pmid = {40329009}, issn = {2522-5812}, support = {T.0032.25//Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research)/ ; EOS: program no. 40007505//Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research)/ ; WELBIO-CR-2022A-02//Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neoplasms/therapy/microbiology/immunology ; *Carcinogenesis ; Animals ; Probiotics/therapeutic use ; Tumor Microenvironment ; Fecal Microbiota Transplantation ; }, abstract = {The gut microbiome has a crucial role in cancer development and therapy through its interactions with the immune system and tumour microenvironment. Although evidence links gut microbiota composition to cancer progression, its precise role in modulating treatment responses remains unclear. In this Review, we summarize current knowledge on the gut microbiome's involvement in cancer, covering its role in tumour initiation and progression, interactions with chemotherapy, radiotherapy and targeted therapies, and its influence on cancer immunotherapy. We discuss the impact of microbial metabolites on immune responses, the relationship between specific bacterial species and treatment outcomes, and potential microbiota-based therapeutic strategies, including dietary interventions, probiotics and faecal microbiota transplantation. Understanding these complex microbiota-immune interactions is critical for optimizing cancer therapies. Future research should focus on defining microbial signatures associated with treatment success and developing targeted microbiome modulation strategies to enhance patient outcomes.}, } @article {pmid40328737, year = {2025}, author = {Hitch, TCA and Masson, JM and Pauvert, C and Bosch, J and Nüchtern, S and Treichel, NS and Baloh, M and Razavi, S and Afrizal, A and Kousetzi, N and Aguirre, AM and Wylensek, D and Coates, AC and Jennings, SAV and Panyot, A and Viehof, A and Schmitz, MA and Stuhrmann, M and Deis, EC and Bisdorf, K and Chiotelli, MD and Lissin, A and Schober, I and Witte, J and Cramer, T and Riedel, T and Wende, M and Winter, KA and Amend, L and Riva, A and Trinh, S and Mitchell, L and Hartman, J and Berry, D and Seitz, J and Bossert, LC and Grognot, M and Allers, T and Strowig, T and Pester, M and Abt, B and Reimer, LC and Overmann, J and Clavel, T}, title = {HiBC: a publicly available collection of bacterial strains isolated from the human gut.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {4203}, pmid = {40328737}, issn = {2041-1723}, support = {513892404//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 445552570//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 395357507//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 403224013//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 460129525//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Plasmids/genetics ; *Bacteria/isolation & purification/classification/genetics ; Phylogeny ; Feces/microbiology ; }, abstract = {Numerous bacteria in the human gut microbiome remain unknown and/or have yet to be cultured. While collections of human gut bacteria have been published, few strains are accessible to the scientific community. We have therefore created a publicly available collection of bacterial strains isolated from the human gut. The Human intestinal Bacteria Collection (HiBC) (https://www.hibc.rwth-aachen.de) contains 340 strains representing 198 species within 29 families and 7 phyla, of which 29 previously unknown species are taxonomically described and named. These included two butyrate-producing species of Faecalibacterium and new dominant species associated with health and inflammatory bowel disease, Ruminococcoides intestinale and Blautia intestinihominis, respectively. Plasmids were prolific within the HiBC isolates, with almost half (46%) of strains containing plasmids, with a maximum of six within a strain. This included a broadly occurring plasmid (pBAC) that exists in three diverse forms across Bacteroidales species. Megaplasmids were identified within two strains, the pMMCAT megaplasmid is globally present within multiple Bacteroidales species. This collection of easily searchable and publicly available gut bacterial isolates will facilitate functional studies of the gut microbiome.}, } @article {pmid40328388, year = {2025}, author = {Wang, J and Yang, L and Liu, L and Ren, J and Jiang, Z and Zhao, X and Jiao, L and Gao, Y and Guo, Y and Yu, T and Li, B and Li, Y and Tong, H}, title = {Pectin from Fructus Mori relieve oxidative stress and regulates gut microbiota in POF mice.}, journal = {International journal of biological macromolecules}, volume = {311}, number = {Pt 4}, pages = {143941}, doi = {10.1016/j.ijbiomac.2025.143941}, pmid = {40328388}, issn = {1879-0003}, mesh = {Animals ; *Pectins/pharmacology/chemistry ; *Gastrointestinal Microbiome/drug effects ; Mice ; Female ; *Oxidative Stress/drug effects ; *Morus/chemistry ; Fruit/chemistry ; Antioxidants/pharmacology ; }, abstract = {Pectin, a complex acidic heteropolysaccharide with diverse biological activities, is widely unilized in cosmetics and food industry. Fructus Mori (F. Mori), an important cultivated fruit, contains abundant pectin. In this study, a pectic polysaccharide (FPA1-1) was extracted from F. Mori through hot-water extraction, ethanol precipitation, and chromatographic purification. Structural analysis revealed that FPA1-1 was a rhamnogalacturonan-I (RG-I)-rich mixed pectin with a branching degree of 48.42 %. In vivo experiments, FPA1-1 (400 mg/kg) effectively shortened the oestrous cycle, reduced follicle stimulating hormone (FSH) level, promoted synthesis and secretion of estradiol hormone (E2) and luteinizing hormone (LH), suppressed serum interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels and improved antioxidant capacity in premature ovarian failure (POF) mice. Moreover, FPA1-1 modulated gut dysbiosis of POF mice by decreasing Firmicutes/ Bacteroidetes ratio and Desulfobacterota abundance at phylum level, enriching Bacteroides, Prevotellaceae, Parabacteroides, Alloprevotella, and Muribaculaceae abundance and inhibiting Desulfovibrionaceae proliferation. FPA1-1 treatment increased short-chain fatty acids (SCFAs) level. Antibiotic cocktail treatment and fecal microbiota transplantation (FMT) experiments confirmed that FPA1-1 ameliorates the ovarian function through altering the gut microbiota composition. These findings provided an experimental basis for further research and applications of F. mori pectin in female ovarian health.}, } @article {pmid40326772, year = {2025}, author = {Chen, Z and Chai, S and Ding, Y and Pang, K and Dong, T and Dai, D and Wang, J and Wang, S and Liu, S}, title = {Gut microbiota modulates lung gene expression and metabolism to aid SD rats in adapting to low-pressure hypoxia.}, journal = {Microbiology spectrum}, volume = {13}, number = {6}, pages = {e0004525}, pmid = {40326772}, issn = {2165-0497}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Rats, Sprague-Dawley ; Rats ; *Lung/metabolism ; *Hypoxia/metabolism ; Fecal Microbiota Transplantation ; Altitude ; Male ; Adaptation, Physiological ; Fatty Acids, Volatile/metabolism ; }, abstract = {UNLABELLED: Hypoxia has long posed a serious threat to the health of both animals and humans, causing respiratory acidosis, metabolic disorders, systemic inflammation, oxidative stress damage, and other issues, thereby endangering life and limiting development in high-altitude areas. Gut microbiota plays a crucial role in life activities and hypoxia adaptation. We transplanted the gut microbiota from small mammals, plateau zokors (Myospalax baileyi), from the Qinghai-Tibetan plateau (3,500 m) to Sprague-Dawley (SD) rats housed in a hypobaric chamber (equivalent to 6,000 m altitude) for 30 days. The results showed that microbiota transplantation significantly reshaped the gut microbiota structure of the rats, notably increasing the abundance of short-chain fatty acid-producing bacteria Lachnospiraceae and Prevotellaceae, alleviating hypoxia and acidosis, reducing pulmonary hypertension and right ventricular hypertrophy, increasing the production of anti-inflammatory substances like indole-3-lactic acid, and reducing the generation of pro-inflammatory substances, such as histamine and uric acid. It also decreased the expression of inflammatory genes like lgE, TNFα, and IFN-γ in the lung. Fecal microbiota transplantation from plateau-specific species to low-altitude SD rats effectively altered metabolism, changed gene expression, decreased pulmonary artery pressure, and enhanced plateau adaptability. This study demonstrates the potential effectiveness of treating hypoxic pulmonary hypertension through microbiota transplantation and offers insights into improving hypoxia adaptation.

IMPORTANCE: We report the beneficial effects of FMT on respiratory capacity, lung metabolism, and lung gene expression in SD rats under hypoxic conditions. We revealed the inhibitory effects of gut microbiota on lung mast cells and histamine expression under hypoxic conditions. The study demonstrated the potential effectiveness of treating HPH through FMT and offers insights into improving hypoxia adaptation.}, } @article {pmid40323507, year = {2025}, author = {Wadan, AS and El-Aziz, MKA and Ellakwa, DE}, title = {The microbiota-gut-brain-axis theory: role of gut microbiota modulators (GMMs) in gastrointestinal, neurological, and mental health disorders.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {40323507}, issn = {1432-1912}, abstract = {The modulation of gut microbiota presents promising therapeutic possibilities for various health conditions, ranging from gastrointestinal infections to neurodegenerative and mental health disorders. Among the available interventions, gut microbiota modulators (GMMs) such as probiotics and prebiotics have demonstrated significant potential in infection prevention and neuroprotection. Despite these encouraging findings, the clinical application of GMMs remains challenging due to safety concerns and inconsistent effectiveness across diverse patient populations. These factors create substantial barriers to the widespread adoption of microbiota-based therapies in clinical practice. To overcome these challenges and fully leverage the therapeutic potential of microbiota modulation, this review explores the feasibility of repurposing GMMs for managing multiple health disorders. A broad spectrum of microbiota-targeted strategies is examined, including dietary modifications, fecal microbiota transplantation, bacteriophage therapy, microbiome engineering, and immune system modulation. A particularly innovative approach involves integrating GMMs with pharmaceutical delivery systems to enhance therapeutic efficacy while mitigating potential adverse effects. This integrative strategy underscores the pivotal role of the gut microbiome in health and disease, supporting the development of precision medicine tailored to individual patient needs. By combining GMMs with targeted delivery mechanisms, this approach not only improves treatment effectiveness but also addresses critical concerns regarding safety and patient variability. Furthermore, this review outlines future research directions within the rapidly evolving field of microbiota modulation, emphasizing the necessity of comprehensive clinical trials and long-term safety evaluations. By critically assessing both the challenges and opportunities associated with microbiota-based interventions, this study provides a strategic framework for translating experimental research into viable clinical applications. A holistic approach to gut microbiota modulation has the potential to redefine treatment paradigms, offering personalized therapeutic strategies for a wide range of disorders and advancing the broader field of precision medicine.}, } @article {pmid40321610, year = {2025}, author = {Dong, Z and Zhang, R and Shen, L and Ji, HF and He, H and Ji, X and Zhao, L}, title = {Gut Microbiota and Immunoglobulin A Nephropathy: Exploration of Dietary Intervention and Treatment Strategies.}, journal = {Food science & nutrition}, volume = {13}, number = {5}, pages = {e70218}, pmid = {40321610}, issn = {2048-7177}, abstract = {Immunoglobulin A nephropathy (IgAN) is a primary glomerular disease characterized by the deposition of IgA. The pathogenesis of it is related to the dysbiosis of gut microbiota. Dysbiosis of gut microbiota influences mucosal immune response and systemic immune system, leading to glycosylation-deficient IgA1 (Gd-IgA1) increasing, which promotes the development of IgAN. Diet plays an important role in regulating gut microbiota and treating IgAN. In this review, we summarize the interplay between gut microbiota and IgAN, and their underlying mechanisms. We also describe the effects of dietary intake on IgAN, as well as the composition of gut microbiota. The progress on IgAN treatment mainly focuses on inhibiting or regulating the immune system. Moreover, therapeutic strategies related to gut microbiota such as dietary intervention, supplement of probiotics and prebiotics, as well as fecal microbiota transplantation (FMT) have shown the possibility of improving IgAN prognosis. Thus, exploration of the gut-kidney axis, the long-term effects of diet and microbiome is necessary to develop more effective treatment strategies.}, } @article {pmid40321299, year = {2025}, author = {Pan, L and Xie, L and Yang, W and Feng, S and Mao, W and Ye, L and Cheng, H and Wu, X and Mao, X}, title = {The role of brain-liver-gut Axis in neurological disorders.}, journal = {Burns & trauma}, volume = {13}, number = {}, pages = {tkaf011}, pmid = {40321299}, issn = {2321-3868}, abstract = {In recent years, with the increasing volume of related research, it has become apparent that the liver and gut play important roles in the pathogenesis of neurological disorders. Considering the interactions among the brain, liver, and gut, the brain-liver-gut axis has been proposed and gradually recognized. In this article, we summarized the complex network of interactions within the brain-liver-gut axis, encompassing the vagus nerve, barrier permeability, immunity and inflammation, the blood-brain barrier, gut microbial metabolites, the gut barrier, neurotoxic metabolites, and beta-amyloid (Aβ) metabolism. We also elaborated on the impact of the brain-liver-gut axis on various neurological disorders. Furthermore, we outline several therapies aimed at modulating the brain-liver-gut axis, including antibiotics, probiotics and prebiotics, fecal microbiota transplantation (FMT), vagus nerve stimulation (VNS), and dietary interventions. The focus is on elucidating possible mechanisms underlying neurological disorders pathogenesis and identifying effective treatments that are based on our understanding of the brain-liver-gut axis.}, } @article {pmid40320851, year = {2025}, author = {Kim, KS and Yang, SY and Jeong, H and Hong, M and Noh, J and Koh, H and Lee, DW}, title = {Development of a Korean Nutrition Model for In Silico Gut Microbiome Analyses Integrated With Nutrigenomics.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e70090}, doi = {10.1002/mnfr.70090}, pmid = {40320851}, issn = {1613-4133}, support = {RS-2021-NR056579//Bio & Medical Technology Development Program of the National Research Foundation (NRF) of Korea/ ; //Ministry of Science and ICT (MSIT)/ ; 20018770//Bioindustrial Technology Development Program of Korea/ ; //Ministry of Trade, Industry and Energy/ ; 2025-12-0026//Yonsei University Research Fund/ ; }, abstract = {The gut microbiome plays a crucial role in human health and disease, with diet serving as a critical determinant of microbial composition and metabolic function. However, most existing nutrition databases are Western-centric, lacking comprehensive dietary information for non-Western populations, including Koreans. This limitation hinders the accuracy of in silico gut microbiome analyses and microbiome-disease associations. We developed the Korean Nutrition Model (KNM) to enhance in silico microbiome analyses by incorporating detailed macronutrient and micronutrient compositions reflective of Korean dietary patterns. KNM was constructed using a decision algorithm that integrates data from the Ministry of Food and Drug Safety and FooDB. Comparative analysis with the European Nutrition Model revealed significant differences in carbohydrate and vitamin compositions, which in turn influenced microbial growth rates and metabolic fluxes in in silico simulations. We further evaluated gut microbiota differences between Korean and European cohorts, including healthy individuals and inflammatory bowel disease patients. Our findings demonstrate that using an appropriate, population-specific nutrition model significantly improves microbiome analyses, reducing the risk of false associations. This study underscores the importance of regionally tailored dietary models and provides a framework for enhancing global dietary models to facilitate precision nutrition and microbiome-based disease interventions.}, } @article {pmid40317768, year = {2025}, author = {Kooij, KL and Andreani, NA and Keller, L and Trinh, S and van der Gun, L and Hak, J and Garner, K and Luijendijk, M and Drost, L and Danner, U and van Elburg, A and Dempfle, A and Seitz, J and Herpertz-Dahlmann, B and Baines, JF and Adan, RAH}, title = {Antibiotic-Induced Microbial Dysbiosis Worsened Outcomes in the Activity-Based Anorexia Model.}, journal = {The International journal of eating disorders}, volume = {58}, number = {8}, pages = {1487-1498}, pmid = {40317768}, issn = {1098-108X}, support = {MIGBAN FKZ: 01EW1906A//ERA_Net/ ; 509492174//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Animals ; *Dysbiosis/chemically induced/microbiology ; Rats, Wistar ; *Gastrointestinal Microbiome/drug effects ; Rats ; *Anti-Bacterial Agents/adverse effects/pharmacology ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; *Anorexia Nervosa/microbiology/therapy ; Humans ; Female ; *Anorexia/microbiology ; Male ; }, abstract = {OBJECTIVE: Anorexia nervosa (AN) is a complex psychiatric disorder characterized by persistent dieting and reduced food intake, leading to significantly low body weight. Dysbiosis in the gut microbiome of patients with AN has been suggested to contribute to the pathogenesis. Here, we used fecal microbiota transplantation (FMT) in the activity-based anorexia (ABA) rat model to investigate the impact of AN-associated gut microbiota on disease-related outcomes.

METHOD: We validated the FMT in 12 Wistar rats by depleting the gut microbiome with antibiotics and transplanting two donors' fecal samples. We then transplanted fecal samples from four patients with AN or four healthy controls in 48 rats just before the ABA model exposure and included an antibiotic-only control group. During ABA, the rats had access to a running wheel and only 1.5 h access to chow for 7 days. We monitored body weight, body temperature, food intake, wheel revolutions, and gut microbiome biodiversity and composition.

RESULTS: The antibiotic treatment significantly depleted the rats' gut microbiome and subsequent transplantation made the rats' microbiome more similar to the donors' microbiome. The antibiotic-only group showed reduced survival, as well as lower body weight and temperature during ABA. Transplanted microbiota from patients with AN and healthy controls improved outcomes in the ABA model.

DISCUSSION: We do not find evidence that the microbiome of patients with AN differentially contributes to anorexia-like phenotypes based upon partial microbiome transplantation. However, the presence of a microbiome impacts the outcome of the ABA model.}, } @article {pmid40316878, year = {2025}, author = {Shirzadi, P and Farokh, P and Osouli Meinagh, S and Izadi-Jorshari, G and Hajikarimloo, B and Mohammadi, G and Parvardeh, S and Nassiri-Asl, M}, title = {The Influence of the Probiotics, Ketogenic Diets, and Gut Microbiota on Epilepsy and Epileptic Models: A Comprehensive Review.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40316878}, issn = {1559-1182}, support = {01-33153//Shahid Beheshti University of Medical Sciences/ ; }, abstract = {About one-third of epilepsies are resistant to antiepileptic drugs; thus, uncovering new pathways in the pathophysiology of epilepsy can reduce the global disease burden. Probiotics are live, non-pathogenic microorganisms that benefit the host by regulating the gut microbiome. This review aims to study the effect of probiotics and ketogenic diets on gut microbiota and their potential as a therapy for epilepsy. We conducted a systematic search of the databases PubMed, Scopus, Embase, and the Web of Science for pertinent studies that have been published. Our search methodology was meticulously structured to be exhaustive, integrating targeted keywords and Boolean operators to guarantee the acquisition of all potentially pertinent articles. Probiotics interact with the gut microbiome, balance its composition, and influence the gut-brain axis. Moreover, they reduce neuroinflammation and oxidative stress. The ketogenic diet (KD) affects gut bacteria, influencing neurotransmitter levels and short-chain fatty acids (SCFAs), which play a role in the gut-brain axis. Studies have shown the positive effects of various probiotics in animal models of epilepsy. They demonstrate improvements in seizure activity, anxiety, and neuroinflammation. In human studies, probiotics reduced seizure frequency and enhanced quality of life in patients with drug-resistant epilepsy. We believe using probiotics or dietary interventions like KD could be a promising therapeutic strategy for managing epilepsy. This could reduce seizure frequency and make life better for patients with epilepsy.}, } @article {pmid40316655, year = {2025}, author = {Neyrinck, AM and Ahmed, H and Leyrolle, Q and Leclercq, S and Amadieu, C and Meuronen, T and Layé, S and Cani, PD and Kärkkäinen, O and Bindels, LB and Hanhineva, K and Delzenne, NM}, title = {Fecal transplantation from humans with obesity to mice drives a selective microbial signature without impacting behavioral and metabolic health.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {15455}, pmid = {40316655}, issn = {2045-2322}, support = {ANR-19-NEUR-0003-03//Agence Nationale de la Recherche/ ; PDR T.0068.19 and PINT-MULTI R.8013.19//FNRS/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Obesity/microbiology/therapy/metabolism ; Humans ; *Gastrointestinal Microbiome ; Mice ; Male ; *Behavior, Animal ; Feces/microbiology ; Mice, Inbred C57BL ; Female ; Metabolomics ; Metabolome ; }, abstract = {Obesity is associated with alterations in the gut microbiome that may contribute to metabolic and mental health disturbances. Fecal microbiota transplantation (FMT) from humans to mice is a model proposed to study human microbiota-associated disorders. In this study, we investigated whether gut microbiota from human donors with obesity could affect behavior and metabolomic profiles of mice. Stools from donors with obesity and from lean donors were inoculated to antibiotic-pretreated mice fed a standard low-fat diet throughout the experiment. Obese-recipient mice exhibited a lower bacterial alpha-diversity and limited changes in specific taxa (e.g., an increase in Eubacterium) but were similar to lean-recipient mice in terms of dietary intake, body weight, fat mass, anxiety/depression-like behavior and glucose homeostasis. Non-targeted LC-MS metabolomic analysis revealed no change in the portal and cava serum samples. However, 1-methylnicotinamide, indole-3-acetic acid (I3A) and methyllysine were increased in the cecal content of obese-recipient compared to lean-recipient mice. Microbial metabolites derived from amino acids were positively correlated with Eubacterium. These results indicate that FMT from donors with obesity to mice fed chow diet (low in lipids) leads to minor but persistent change in intestinal microbial-derived metabolites, without recapitulating the metabolic and behavioral alterations of obesity.}, } @article {pmid40316371, year = {2025}, author = {Werner, M and Vigani, A}, title = {The Microbiome in Critical Illness.}, journal = {The Veterinary clinics of North America. Small animal practice}, volume = {55}, number = {3}, pages = {443-458}, doi = {10.1016/j.cvsm.2025.01.008}, pmid = {40316371}, issn = {1878-1306}, mesh = {Animals ; *Critical Illness/therapy ; Dogs ; *Dog Diseases/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; Probiotics/therapeutic use ; *Cat Diseases/microbiology/therapy ; Cats ; Fecal Microbiota Transplantation/veterinary ; *Gastrointestinal Diseases/veterinary/microbiology/therapy ; }, abstract = {Evidence suggests that the intestinal microbiome may play an important role in the pathogenesis and progression of acute critical illness in humans and other mammals, although evidence in small animal medicine is sparse. Moreover, the intestinal microbiota plays many important metabolic roles (production of short-chain fatty acids, trimethylamine-N-oxide, and normal bile acid metabolism) and is crucial for immunity as well as defense against enteropathogens. The use of probiotics and fecal microbiota transplantation as instruments to modulate the intestinal microbiota seems to be safe and effective in studies on critically ill dogs with acute gastrointestinal diseases.}, } @article {pmid40316177, year = {2025}, author = {Yin, Y and Guan, M and Wu, S and Cui, C and Wang, R and Zhao, X and Yang, X and Qiao, L and Li, Y and Zhang, C}, title = {Young fecal microbiota transplantation improves working memory in aged recipient rats by increasing interleukin-4 and interleukin-17 levels.}, journal = {Neuroscience research}, volume = {216}, number = {}, pages = {104902}, doi = {10.1016/j.neures.2025.04.005}, pmid = {40316177}, issn = {1872-8111}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Memory, Short-Term/physiology ; *Interleukin-4/metabolism ; Rats ; Male ; Gastrointestinal Microbiome/physiology ; *Interleukin-17/metabolism ; *Aging ; Hippocampus/metabolism ; Prefrontal Cortex/metabolism ; }, abstract = {While transplanting the fecal microbiota from young to aged rodents has been extensively studied (that is, young FMT [yFMT]), its mechanism of alleviating working memory decline has not been fully elucidated. In this report, we aimed to investigate the effect of yFMT on the working memory of aged recipient rats performing delayed match-to-position (DMTP) tasks and the associated cellular and molecular mechanisms. The results revealed that yFMT mitigated the decline in DMTP task performance of aged recipients. This improvement was associated with a reshaped gut microbiota and increased levels of brain-derived neurotrophic factor, N-methyl-D-aspartate receptor subunit 1, and synaptophysin, enhancing synaptic formation and transmission. The remodeling of the gut microbiome influenced peripheral circulation and the hippocampus and medial prefrontal cortex by regulating the Th17/Treg ratio and microglial polarization. Ultimately, interleukin-4 and interleukin-17 emerged as potential key molecules driving the beneficial effects of FMT. These observations provide new insights into the gutbrain axis, emphasizing the connection between the gut and brain through the circulation system, and suggest an immunological mechanism that may help reverse age-related declines in the gut microbiota.}, } @article {pmid40316082, year = {2025}, author = {Qiu, MT and Zhou, L and Wang, XY and Li, ZP and Wei, MX and Zeng, ZH and Cheng, J and Xu, GH and Zhu, JX and Yi, LT}, title = {Anti-colitis comparison of polysaccharides and anthocyanins extracted from black wolfberry based on microbiomics, immunofluorescence and multi-cytokines profile analysis.}, journal = {International journal of biological macromolecules}, volume = {310}, number = {Pt 3}, pages = {143700}, doi = {10.1016/j.ijbiomac.2025.143700}, pmid = {40316082}, issn = {1879-0003}, mesh = {*Anthocyanins/pharmacology/chemistry/isolation & purification ; Animals ; *Polysaccharides/pharmacology/chemistry/isolation & purification/therapeutic use ; Gastrointestinal Microbiome/drug effects ; Mice ; *Cytokines/metabolism ; *Lycium/chemistry ; Male ; *Colitis/drug therapy/microbiology/chemically induced/metabolism/pathology ; Disease Models, Animal ; Plant Extracts/pharmacology/chemistry ; Anti-Inflammatory Agents/pharmacology/chemistry ; Dextran Sulfate ; }, abstract = {Black wolfberry (Lycium ruthenicum) is a widely consumed food known for its pharmacological properties, particularly its anti-inflammatory and antioxidant effects. This study investigates the therapeutic potential of black wolfberry polysaccharides (LRP) and anthocyanins (LRA) in treating ulcerative colitis, a chronic inflammatory bowel disease. Using a DSS-induced mouse model of colitis, we administered varying doses of LRP and LRA and evaluated their effects on disease activity, inflammation, gut barrier function, and microbiota composition. LRP demonstrated dose-dependent efficacy, with the 200 mg/kg dose showing the most significant reduction in the disease activity index (DAI), improvement in histopathology, and restoration of tight junction protein expression. In contrast, LRA exhibited an inverted U-shaped response, with the 100 mg/kg dose being the most effective. Additionally, LRP treatment modulated cytokine levels, promoting an anti-inflammatory response, and significantly restored gut microbiota balance by increasing Muribaculaceae and Limosilactobacillus while reducing Bacteroides and Helicobacter. Fecal microbiota transplantation (FMT) experiments further confirmed that the therapeutic effects of LRP are microbiota-dependent. These findings suggest that LRP, a polysaccharide derived from black wolfberry, offers a dietary intervention for colitis through immune modulation and gut microbiota restoration.}, } @article {pmid40315641, year = {2025}, author = {Wei, FH and Xie, WY and Zhao, PS and Ji, ZH and Gao, F and Chen, CZ and Zhang, Z and Gao, W and Yuan, B}, title = {Crataegus pinnatifida polysaccharide alleviates DSS-induced colitis in mice by regulating the intestinal microbiota and enhancing arginine biosynthesis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {142}, number = {}, pages = {156794}, doi = {10.1016/j.phymed.2025.156794}, pmid = {40315641}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Arginine/biosynthesis ; Mice ; *Crataegus/chemistry ; *Polysaccharides/pharmacology ; *Colitis, Ulcerative/drug therapy/chemically induced/microbiology ; Male ; Dextran Sulfate ; Mice, Inbred C57BL ; Colon/drug effects/pathology ; Oxidative Stress/drug effects ; Disease Models, Animal ; Plant Extracts/pharmacology ; }, abstract = {BACKGROUND: The development of effective and safe dietary supplements is essential for both the prevention and management of ulcerative colitis (UC), as its pathogenesis is intricate and difficult to completely resolve. Crataegus pinnatifida, a medicinal food with a long history of use, has broad medicinal value. Recent research has revealed promising insights into the role of polysaccharide derived from Crataegus pinnatifida on modulating short-chain fatty acids (SCFAs) to alleviate UC inflammation. However, the mechanisms by which CPP regulates the intestinal microbiota and key metabolites during the antagonistic phase of UC have yet to be elucidated.

OBJECTIVE: This research elucidated the protective role of CPP in relation to UC, highlighted the mechanisms through which CPP operates, particularly regarding gut microbiota and metabolism, and offered a theoretical foundation for the potential use of CPP as a dietary supplement aimed at preventing UC.

METHODS: The impact of CPP on acute UC induced by 3 % DSS in mice was examined through the evaluation of the disease activity index, measurement of colon length, and observation of body weight changes. Enzyme-linked immunosorbent assay (ELISA) was used to measure inflammatory factor levels in both serum and colon, as well as to assess oxidative stress mediators. The intestinal histological damage, mucus layer damage and the level of tight junction protein were analyzed by histopathological staining and western blot (WB). The impact of gut microbiota on CPP in colitis was evaluated using 16S rRNA sequencing, microbiota depletion experiments, and fecal microbiota transplantation (FMT) studies. The key metabolic pathways and key metabolites affected by CPP in the treatment of UC were analyzed through untargeted metabolomics sequencing, ELISA, and WB assays.

RESULTS: Prophylactic dietary supplementation with Crataegus pinnatifida polysaccharide (CPP) notably reduced the fundamental clinical manifestations of UC induced by DSS, including DAI score, reduced colon length, and weight loss, as well as inflammation and oxidative stress. CPP promoted the expression of Claudin-1, ZO-1 and Occludin and promoted mucin secretion, which contributed to the mitigation of intestinal barrier damage caused by DSS. 16S sequencing results and metabolomics results revealed that CPP intervention upregulated the relative abundance of Lactobacillus, thereby reshaping the intestinal microbiota and activate the arginine biosynthesis pathway. The results of fecal microbiota transplantation and antibiotic clearance experiments indicated that the alleviating effect of CPP on UC was dependent on the intestinal microbiota and this alleviating effect was transferred through fecal microbiota transplantation. Mechanistically, CPP indirectly promoted the expression of the rate-limiting enzyme argininosuccinate synthase 1 (ASS1) in the intestinal Arginine biosynthesis pathway by reshaping the intestinal microbiota, thereby increasing intestinal Arginine level and alleviating the inflammatory response and oxidative stress induced by DSS and intestinal barrier damage.

CONCLUSION: Our research findings demonstrate that CPP is a plant-derived polysaccharide that alleviates UC by modulating the gut microbiota and enhancing arginine biosynthesis.}, } @article {pmid40314722, year = {2025}, author = {Castagnoli, R and Pala, F and Subramanian, P and Oguz, C and Schwarz, B and Lim, AI and Burns, AS and Fontana, E and Bosticardo, M and Corsino, C and Angelova, A and Delmonte, OM and Kenney, H and Riley, D and Smith, G and Ott de Bruin, L and Oikonomou, V and Dos Santos Dias, L and Fink, D and Bohrnsen, E and Kimzey, CD and Marseglia, GL and Alva-Lozada, G and Bergerson, JRE and Brett, A and Brigatti, KW and Dimitrova, D and Dutmer, CM and Freeman, AF and Ale, H and Holland, SM and Licciardi, F and Pasic, S and Poskitt, LE and Potts, DE and Dasso, JF and Sharapova, SO and Strauss, KA and Ward, BR and Yilmaz, M and Kuhns, DB and Lionakis, MS and Daley, SR and Kong, HH and Segre, JA and Villa, A and Pittaluga, S and Walter, JE and Vujkovic-Cvijin, I and Belkaid, Y and Notarangelo, LD}, title = {Immunopathological and microbial signatures of inflammatory bowel disease in partial RAG deficiency.}, journal = {The Journal of experimental medicine}, volume = {222}, number = {8}, pages = {}, pmid = {40314722}, issn = {1540-9538}, support = {U01 DK062413/DK/NIDDK NIH HHS/United States ; HHSN316201300006W/75N93022F00001/HH/HHS/United States ; //National Institute of Allergy and Infectious Diseases/ ; U01DK062413/DK/NIDDK NIH HHS/United States ; DP1HL174182/HL/NHLBI NIH HHS/United States ; 831262//Crohn's & Colitis Foundation Career Development/ ; AI001222/NH/NIH HHS/United States ; DP1 HL174182/HL/NHLBI NIH HHS/United States ; //Fondazione Ghislieri/ ; //Cedars-Sinai Medical Center/ ; }, mesh = {Animals ; *Inflammatory Bowel Diseases/immunology/microbiology/pathology/genetics ; *Homeodomain Proteins/genetics ; Humans ; Mice ; Female ; Male ; Disease Models, Animal ; Gastrointestinal Microbiome ; Bone Marrow Transplantation ; T-Lymphocytes, Regulatory/immunology ; Th17 Cells/immunology ; Mice, Inbred C57BL ; }, abstract = {Partial RAG deficiency (pRD) can manifest with systemic and tissue-specific immune dysregulation, with inflammatory bowel disease (IBD) in 15% of the patients. We aimed at identifying the immunopathological and microbial signatures associated with IBD in patients with pRD and in a mouse model of pRD (Rag1w/w) with spontaneous development of colitis. pRD patients with IBD and Rag1w/w mice showed a systemic and colonic Th1/Th17 inflammatory signature. Restriction of fecal microbial diversity, abundance of pathogenic bacteria, and depletion of microbial species producing short-chain fatty acid were observed, which were associated with impaired induction of lamina propria peripheral Treg cells in Rag1w/w mice. The use of vedolizumab in Rag1w/w mice and of ustekinumab in a pRD patient were ineffective. Antibiotics ameliorated gut inflammation in Rag1w/w mice, but only bone marrow transplantation (BMT) rescued the immunopathological and microbial signatures. Our findings shed new light in the pathophysiology of gut inflammation in pRD and establish a curative role for BMT to resolve the disease phenotype.}, } @article {pmid40314681, year = {2025}, author = {Li, X and Su, K and He, Y and Shao, S and Lan, L and Zhang, Q and Li, L}, title = {Knowledge Mapping of International Microbiota Research: Analyzing Thirty-Year Citation Classics and Exploring Future Expectations.}, journal = {The new microbiologica}, volume = {48}, number = {1}, pages = {46-59}, pmid = {40314681}, issn = {1121-7138}, mesh = {Humans ; *Bibliometrics ; *Biomedical Research ; Gastrointestinal Microbiome ; *Microbiota ; }, abstract = {Microbiota research has rapidly emerged as a pivotal field, with over 250,000 publications and more than ten million citations recorded in the Web of Science Core Collection database by 2024. There were 1682 original microbiota citation classics (each receiving 400 citations or more) identified over the past three decades, totaling 1,559,594 citations and averaging 927 citations per paper. Collaborative efforts in the production of these citation classics involved 87 out of 89 participating countries and 2107 out of 2142 institutions. The USA, various European countries, and China emerged as the leading contributors to this burgeoning research area. Jeffrey I. Gordon, Rob Knight, and Curtis Huttenhower were the prominent figures in microbiota research. Author keywords were analyzed, which revealed a notable shift in research focus from environmental microorganisms to human gut microbiota. Advances such as high-throughput 16S rRNA sequencing and metagenomics expanded the scope of investigations into host-microbiota interactions. Current research interests encompass exploring mechanisms underlying gut-X-axis conditions, including inflammatory bowel disease, obesity, diabetes, colorectal cancer, liver diseases, and neurological disorders. Moreover, environmental exposures have been evidenced to alter gut microbiota and metabolites, contributing a novel research direction. Future research direction is also anticipated to delve further into biosynthetic gene engineering technologies aimed at microbial interventions, including probiotics and fecal microbiota transplantation. This study outlines the evolving landscape of microbiota research and provides valuable insights to inform future investigations within the field.}, } @article {pmid40314129, year = {2025}, author = {Xiao, K and Li, K and Xiao, K and Yang, J and Zhou, L}, title = {Gut Microbiota and Hepatocellular Carcinoma: Metabolic Products and Immunotherapy Modulation.}, journal = {Cancer medicine}, volume = {14}, number = {9}, pages = {e70914}, pmid = {40314129}, issn = {2045-7634}, support = {21MC1930500//Shanghai Clinical Research Center of Traditional Chinese Medicine Oncology, Science and Technology Commission of Shanghai Municipality/ ; ZYYZDXK-2023063//High-Level Traditional Chinese Medicine Key Discipline Construction Project of the National Administration of Traditional Chinese Medicine/ ; //Youth Talent Project of Longhua Hospital, affiliated with Shanghai University of Traditional Chinese Medicine/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/drug effects ; *Carcinoma, Hepatocellular/therapy/immunology/microbiology/metabolism/pathology ; *Liver Neoplasms/therapy/immunology/microbiology/metabolism/pathology ; *Immunotherapy/methods ; Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; }, abstract = {BACKGROUND: The relationship between hepatocellular carcinoma (HCC) and gut microbiota has gained attention for its impact on HCC immunotherapy.

METHODS: Key gut microbial metabolites, including bile acids, toll-like receptor 4, short-chain fatty acids, and bacterial toxins, contribute to HCC progression and influence immune responses through the gut-liver axis. As immune checkpoint inhibitors (ICIs) become common in HCC treatment, modulating the gut microbiota offers new strategies to enhance ICIs efficacy. However, individual differences in microbial composition introduce challenges, with some HCC patients showing resistance to ICIs.

RESULTS: This review summarizes the latest findings on the role of gut microbiota in HCC and explores emerging therapeutic approaches, including fecal microbiota transplantation, probiotics, antibiotics, and natural compounds.

CONCLUSIONS: The focus is on translating these insights into personalized medicine to optimize ICIs responses and improve HCC treatment outcomes.}, } @article {pmid40313405, year = {2025}, author = {Zhao, H and Qiu, X and Wang, S and Wang, Y and Xie, L and Xia, X and Li, W}, title = {Multiple pathways through which the gut microbiota regulates neuronal mitochondria constitute another possible direction for depression.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1578155}, pmid = {40313405}, issn = {1664-302X}, abstract = {As a significant mental health disorder worldwide, the treatment of depression has long faced the challenges of a low treatment rate, significant drug side effects and a high relapse rate. Recent studies have revealed that the gut microbiota and neuronal mitochondrial dysfunction play central roles in the pathogenesis of depression: the gut microbiota influences the course of depression through multiple pathways, including immune regulation, HPA axis modulation and neurotransmitter metabolism. Mitochondrial function serves as a key hub that mediates mood disorders through mechanisms such as defective energy metabolism, impaired neuroplasticity and amplified neuroinflammation. Notably, a bidirectional regulatory network exists between the gut microbiota and mitochondria: the flora metabolite butyrate enhances mitochondrial biosynthesis through activation of the AMPK-PGC1α pathway, whereas reactive oxygen species produced by mitochondria counteract the flora composition by altering the intestinal epithelial microenvironment. In this study, we systematically revealed the potential pathways by which the gut microbiota improves neuronal mitochondrial function by regulating neurotransmitter synthesis, mitochondrial autophagy, and oxidative stress homeostasis and proposed the integration of probiotic supplementation, dietary fiber intervention, and fecal microbial transplantation to remodel the flora-mitochondrial axis, which provides a theoretical basis for the development of novel antidepressant therapies targeting gut-brain interactions.}, } @article {pmid40312419, year = {2025}, author = {Cao, M and Deng, Y and Hao, Q and Yan, H and Wang, QL and Dong, C and Wu, J and He, Y and Huang, LB and Xia, X and Gao, Y and Chen, HN and Zhang, WH and Zhang, YJ and Zhuo, X and Dai, L and Hu, H and Peng, Y and Zhang, F and Liu, Z and Huang, W and Zhang, H and Yang, L and Shu, Y and Zhang, W and Zhang, Y and Xu, H}, title = {Single-cell transcriptomic analysis reveals gut microbiota-immunotherapy synergy through modulating tumor microenvironment.}, journal = {Signal transduction and targeted therapy}, volume = {10}, number = {1}, pages = {140}, pmid = {40312419}, issn = {2059-3635}, support = {82273445//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/immunology/genetics/drug effects ; *Tumor Microenvironment/immunology/genetics/drug effects ; Mice ; *Single-Cell Analysis ; *Immunotherapy ; CD8-Positive T-Lymphocytes/immunology ; Humans ; Gene Expression Profiling ; Transcriptome ; *Neoplasms/immunology/genetics/therapy/microbiology ; *Immune Checkpoint Inhibitors/pharmacology ; Mice, Knockout ; Macrophages/immunology ; }, abstract = {The gut microbiota crucially regulates the efficacy of immune checkpoint inhibitor (ICI) based immunotherapy, but the underlying mechanisms remain unclear at the single-cell resolution. Using single-cell RNA sequencing and subsequent validations, we investigate gut microbiota-ICI synergy by profiling the tumor microenvironment (TME) and elucidating critical cellular interactions in mouse models. Our findings reveal that intact gut microbiota combined with ICIs may synergistically increase the proportions of CD8[+], CD4[+], and γδ T cells, reduce glycolysis metabolism, and reverse exhausted CD8[+] T cells into memory/effector CD8[+] T cells, enhancing antitumor response. This synergistic effect also induces macrophage reprogramming from M2 protumor Spp1[+] tumor-associated macrophages (TAMs) to Cd74[+] TAMs, which act as antigen-presenting cells (APCs). These macrophage subtypes show a negative correlation within tumors, particularly during fecal microbiota transplantation. Depleting Spp1[+] TAMs in Spp1 conditional knockout mice boosts ICI efficacy and T cell infiltration, regardless of gut microbiota status, suggesting a potential upstream role of the gut microbiota and highlighting the crucial negative impact of Spp1[+] TAMs during macrophage reprogramming on immunotherapy outcomes. Mechanistically, we propose a γδ T cell-APC-CD8[+] T cell axis, where gut microbiota and ICIs enhance Cd40lg expression on γδ T cells, activating Cd40 overexpressing APCs (e.g., Cd74[+] TAMs) through CD40-CD40L-related NF-κB signaling and boosting CD8[+] T cell responses via CD86-CD28 interactions. These findings highlight the potential importance of γδ T cells and SPP1-related macrophage reprogramming in activating CD8[+] T cells, as well as the synergistic effect of gut microbiota and ICIs in immunotherapy through modulating the TME.}, } @article {pmid40311999, year = {2025}, author = {Liu, A and Wang, B and Wang, M and Tang, R and Xu, W and Xiao, W}, title = {l-theanine alleviates ulcerative colitis by repairing the intestinal barrier through regulating the gut microbiota and associated short-chain fatty acids.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {202}, number = {}, pages = {115497}, doi = {10.1016/j.fct.2025.115497}, pmid = {40311999}, issn = {1873-6351}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Fatty Acids, Volatile/metabolism ; *Colitis, Ulcerative/drug therapy/metabolism/microbiology ; *Glutamates/pharmacology/therapeutic use ; Mice ; Male ; Mice, Inbred C57BL ; Receptors, G-Protein-Coupled/metabolism/genetics ; Fecal Microbiota Transplantation ; Signal Transduction/drug effects ; *Intestinal Mucosa/drug effects/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; }, abstract = {Ulcerative colitis (UC) is closely related to impaired intestinal barrier function and imbalanced gut microbial communities. l-theanine shows great potential in maintaining intestinal integrity and regulating the gut microbiota and associated short-chain fatty acids (SCFAs). However, whether l-theanine can alleviate UC by repairing the intestinal barrier through these regulatory processes remains unclear. In this study, l-theanine was used to optimize the gut microbiota, and the restorative effect and mechanism of l-theanine in UC by repairing the gut barrier through the gut microbiota and SCFAs were investigated via fecal microbiota transplantation. The findings revealed that l-theanine regulated the gut microbiota structure, increased SCFA contents, and promoted gut barrier repair in UC mice. Moreover, l-theanine upregulated the protein and mRNA expression of G-protein-coupled receptor 43 (GPR43), AKT, and phosphatidylinositide 3-kinase (PI3K). These results indicated that l-theanine alleviates UC by repairing the gut barrier via regulating the gut microbiota and SCFAs through the GPR43/PI3K/AKT signaling pathway activation. This study provides a method of preventing and treating UC via l-theanine as a safe food dietary supplement.}, } @article {pmid40309228, year = {2025}, author = {Li, Y and Wu, YT and Wu, H}, title = {Management of hepatic encephalopathy following transjugular intrahepatic portosystemic shunts: Current strategies and future directions.}, journal = {World journal of gastroenterology}, volume = {31}, number = {15}, pages = {103512}, pmid = {40309228}, issn = {2219-2840}, mesh = {Humans ; *Portasystemic Shunt, Transjugular Intrahepatic/adverse effects ; *Hepatic Encephalopathy/etiology/therapy/prevention & control/diagnosis ; *Hypertension, Portal/surgery/etiology ; *Liver Cirrhosis/complications/surgery ; *Postoperative Complications/therapy/etiology/prevention & control ; Quality of Life ; Stents ; Treatment Outcome ; Biomarkers/blood ; Fecal Microbiota Transplantation ; }, abstract = {Transjugular intrahepatic portosystemic shunts (TIPSs) are generally used for the management of complications of portal hypertension in patients with decompensated cirrhosis. However, hepatic encephalopathy (HE), which impairs neuropsychiatric function and motor control, remains the primary adverse effect of TIPS, limiting its utility. Prompt prevention and treatment of post-TIPS HE are critical, as they are strongly associated with readmission rates and poor quality of life. This review focuses on the main pathophysiological mechanisms underlying post-TIPS HE, explores advanced biomarkers and predictive tools, and discusses current management strategies and future directions to prevent or reverse HE following TIPS. These strategies include preoperative patient assessment, individualized shunt diameter optimization, spontaneous portosystemic shunt embolization during the TIPS procedure, postoperative preventive and therapeutic measures such as nutrition management, medical therapy, fecal microbiota transplantation, and stent reduction.}, } @article {pmid40309194, year = {2025}, author = {Tang, CT and Wu, Y and Tao, Q and Zeng, CY and Chen, YX}, title = {Thalidomide mitigates Crohn's disease colitis by modulating gut microbiota, metabolites, and regulatory T cell immunity.}, journal = {Journal of pharmaceutical analysis}, volume = {15}, number = {4}, pages = {101121}, pmid = {40309194}, issn = {2214-0883}, abstract = {Thalidomide (THA) is renowned for its potent anti-inflammatory properties. This study aimed to elucidate its underlying mechanisms in the context of Crohn's disease (CD) development. Mouse colitis models were established by dextran sulfate sodium (DSS) treatment. Fecal microbiota and metabolites were analyzed by metagenomic sequencing and mass spectrometry, respectively. Antibiotic-treated mice served as models for microbiota depletion and transplantation. The expression of forkhead box P3[+] (FOXP3[+]) regulatory T cells (Tregs) was measured by flow cytometry and immunohistochemical assay in colitis model and patient cohort. THA inhibited colitis in DSS-treated mice by altering the gut microbiota profile, with an increased abundance of probiotics Bacteroides fragilis, while pathogenic bacteria were depleted. In addition, THA increased beneficial metabolites bile acids and significantly restored gut barrier function. Transcriptomic profiling revealed that THA inhibited interleukin-17 (IL-17), IL-1β and cell cycle signaling. Fecal microbiota transplantation from THA-treated mice to microbiota-depleted mice partly recapitulated the effects of THA. Specifically, increased level of gut commensal B. fragilis was observed, correlated with elevated levels of the microbial metabolite 3alpha-hydroxy-7-oxo-5beta-cholanic acid (7-ketolithocholic acid, 7-KA) following THA treatment. This microbial metabolite may stable FOXP3 expression by targeting the receptor FMR1 autosomal homolog 1 (FXR1) to inhibit autophagy. An interaction between FOXP3 and FXR1 was identified, with binding regions localized to the FOXP3 domain (aa238-335) and the FXR1 domain (aa82-222), respectively. Conclusively, THA modulates the gut microbiota and metabolite profiles towards a more beneficial composition, enhances gut barrier function, promotes the differentiation of FOXP3[+] Tregs and curbs pro-inflammatory pathways.}, } @article {pmid40309103, year = {2025}, author = {Cong, X and Liu, X and Zhou, D and Xu, Y and Liu, J and Tong, F}, title = {Characterization and comparison of the fecal bacterial microbiota in Red Back Pine Root Snake (Oligodon formosanus) and Chinese Slug-Eating Snake (Pareas chinensis).}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1575405}, pmid = {40309103}, issn = {1664-302X}, abstract = {INTRODUCTION: The gastrointestinal tracts and oral cavities of animals harbor complex microbial communities that assist hosts in nutrient absorption and immune responses, thereby influencing behavior, development, reproduction, and overall health.

METHODS: We utilized metagenomic sequencing technology to conduct a detailed analysis of the fecal bacterial communities of six Red Back Pine Root Snakes (Oligodon formosanus, XT) and three Chinese Slug-Eating Snakes (Pareas chinensis, Z) individuals. The microbial composition was assessed through taxonomic profiling, alpha diversity analysis, and functional annotation using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database.

RESULTS: The results indicated that Proteobacteria, Bacteroidetes, Firmicutes, Verrucomicrobia, Actinobacteria, and Fusobacteria were the dominant phyla in XT samples, while Z samples additionally contained Patescibacteria. Alpha diversity analysis revealed significant differences in species abundance at the family level, with Z samples exhibiting higher microbial richness than XT. Furthermore, KEGG analysis showed that XT had higher functional gene abundance in pathways related to transcription, translation, environmental adaptation, membrane transport, cellular communities (prokaryotes), motility, and replication/repair compared to Z.

DISCUSSION: This study provides a comparative analysis of their gut microbiomes, offering valuable insights for future research on zoonotic diseases, host-microbe interactions, and ecological, evolutionary, behavioral, and seasonal influences on snake microbiota. These findings contribute to a broader understanding of microbial ecology in reptiles and its implications for conservation and disease dynamics.}, } @article {pmid40308808, year = {2025}, author = {Wei, H and Mai, ZL and Ma, BT and Chang, B}, title = {Creeping fat: A promising radiological predictor in small bowel Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {31}, number = {16}, pages = {105186}, pmid = {40308808}, issn = {2219-2840}, mesh = {Humans ; *Crohn Disease/diagnostic imaging/therapy/pathology ; *Intestine, Small/diagnostic imaging/pathology ; Treatment Outcome ; Fecal Microbiota Transplantation ; Predictive Value of Tests ; Tomography, X-Ray Computed ; Magnetic Resonance Imaging ; *Adipose Tissue/diagnostic imaging/pathology ; Biological Products/therapeutic use ; }, abstract = {In this manuscript, we comment on the article by Hasnaoui et al. Specifically, we delve into the characteristic manifestation of Crohn's disease (CD) known as creeping fat (CF). Our primary focus is to investigate the potential of imaging features of CF in predicting the response of small bowel CD to biologic therapies and fecal microbiota transplantation. We believe that further research should be dedicated to developing methods for quantifying CF in order to provide more accurate predictive tools for the treatment of small bowel CD.}, } @article {pmid40307551, year = {2025}, author = {Kennedy, MS and Freiburger, A and Cooper, M and Beilsmith, K and St George, ML and Kalski, M and Cham, C and Guzzetta, A and Ng, SC and Chan, FK and DeLeon, O and Rubin, D and Henry, CS and Bergelson, J and Chang, EB}, title = {Diet outperforms microbial transplant to drive microbiome recovery in mice.}, journal = {Nature}, volume = {642}, number = {8068}, pages = {747-755}, pmid = {40307551}, issn = {1476-4687}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/physiology ; Mice ; *Dysbiosis/microbiology/chemically induced/therapy ; Male ; *Fecal Microbiota Transplantation ; Anti-Bacterial Agents/pharmacology ; Female ; Salmonella typhimurium/physiology ; *Diet, Western/adverse effects ; Mice, Inbred C57BL ; Feces/microbiology ; Salmonella Infections/microbiology ; Diet, High-Fat/adverse effects ; }, abstract = {A high-fat, low-fibre Western-style diet (WD) induces microbiome dysbiosis characterized by reduced taxonomic diversity and metabolic breadth[1,2], which in turn increases risk for a wide array of metabolic[3-5], immune[6] and systemic pathologies. Recent work has established that WD can impair microbiome resilience to acute perturbations such as antibiotic treatment[7,8], although little is known about the mechanism of impairment and the specific consequences for the host of prolonged post-antibiotic dysbiosis. Here we characterize the trajectory by which the gut microbiome recovers its taxonomic and functional profile after antibiotic treatment in mice on regular chow (RC) or WD, and find that only mice on RC undergo a rapid successional process of recovery. Metabolic modelling indicates that a RC diet promotes the development of syntrophic cross-feeding interactions, whereas in mice on WD, a dominant taxon monopolizes readily available resources without releasing syntrophic byproducts. Intervention experiments reveal that an appropriate dietary resource environment is both necessary and sufficient for rapid and robust microbiome recovery, whereas microbial transplant is neither. Furthermore, prolonged post-antibiotic dysbiosis in mice on WD renders them susceptible to infection by the intestinal pathogen Salmonella enterica serovar Typhimurium. Our data challenge widespread enthusiasm for faecal microbiota transplant (FMT) as a strategy to address dysbiosis, and demonstrate that specific dietary interventions are, at a minimum, an essential prerequisite for effective FMT, and may afford a safer, more natural and less invasive alternative.}, } @article {pmid40307477, year = {2025}, author = {Iyengar, A and Ramadass, B and Venkatesh, S and Mak, RH}, title = {Gut microbiota-targeted therapies in pediatric chronic kidney disease: gaps and opportunities.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {}, number = {}, pages = {}, pmid = {40307477}, issn = {1432-198X}, abstract = {Given the complex relationship between the gut microbiome and chronic kidney disease (CKD), exploring the potential role and scope of microbiota-targeted therapies in pediatric CKD is highly relevant. We aim to provide an overview of gut-targeted therapeutic strategies, including nutritional interventions (fiber, phytochemicals, fermented foods, and traditional Chinese medicines), probiotics, synbiotics, oral absorbents, and fecal microbial transplantation. Enhancing physical activity and preventing constipation are additional strategies that may promote gut microbiome health. In a uremic environment, gut microbiota-targeted therapies could potentially rebalance the gut microbiota, improve gut barrier function, decrease uremic toxin concentrations, enhance the production of short-chain fatty acids (SCFA), and reduce inflammation. While research in adult CKD patients has provided insights into these approaches, there are limited data in children with CKD. This review aims to summarize potential targeted therapies for restoring a balanced gut microbiota, emphasizing the need for studies that evaluate their effects on clinical outcomes in pediatric CKD.}, } @article {pmid40306604, year = {2025}, author = {Lee, SH and Han, C and Shin, C}, title = {IUPHAR review: Microbiota-gut-brain axis and its role in neuropsychiatric disorders.}, journal = {Pharmacological research}, volume = {216}, number = {}, pages = {107749}, doi = {10.1016/j.phrs.2025.107749}, pmid = {40306604}, issn = {1096-1186}, mesh = {Humans ; *Gastrointestinal Microbiome ; Animals ; *Brain/metabolism/microbiology ; *Mental Disorders/microbiology/therapy ; *Brain-Gut Axis ; Probiotics/therapeutic use ; Prebiotics ; }, abstract = {The human gut microbiome, composed of a vast array of microorganisms that have co-evolved with humans, is crucial for the development and function of brain systems. Research has consistently shown bidirectional communication between the gut and the brain through neuronal, endocrine, and immunological, and chemical pathways. Recent neuroscience studies have linked changes in the microbiome and microbial metabolites to various neuropsychiatric disorders such as autism, depression, anxiety, schizophrenia, eating disorders, and neurocognitive disorders. Novel metagenome-wide association studies have confirmed these microbiome variations in large samples and expanded our understanding of the interactions between human genes and the gut microbiome. The causal relationship between gut microbiota and neuropsychiatric disorders is being elucidated through the establishment of large cohort studies incorporating microbiome data and advanced statistical techniques. Ongoing animal and human studies focused on the microbiota-gut-brain axis are promising for developing new prevention and treatment strategies for neuropsychiatric conditions. The scope of these studies has broadened from microbiome-modulating therapies including prebiotics, probiotics, synbiotics and postbiotics to more extensive approaches such as fecal microbiota transplantation. Recent systematic reviews and meta-analyses have strengthened the evidence base for these innovative treatments. Despite extensive research over the past decade, many intriguing aspects still need to be elucidated regarding the role and therapeutic interventions of the microbiota-gut-brain axis in neuropsychiatric disorders.}, } @article {pmid40306274, year = {2025}, author = {Kim, SH and White, Z and Gainullina, A and Kang, S and Kim, J and Dominguez, JR and Choi, Y and Cabrera, I and Plaster, M and Takahama, M and Czepielewski, RS and Yeom, J and Gunzer, M and Hay, N and David, O and Chevrier, N and Sano, T and Kim, KW}, title = {IL-10 sensing by lung interstitial macrophages prevents bacterial dysbiosis-driven pulmonary inflammation and maintains immune homeostasis.}, journal = {Immunity}, volume = {58}, number = {5}, pages = {1306-1326.e7}, pmid = {40306274}, issn = {1097-4180}, support = {P01 HL151327/HL/NHLBI NIH HHS/United States ; R01 DK126753/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Dysbiosis/immunology/microbiology ; *Interleukin-10/metabolism/immunology/genetics ; Homeostasis/immunology ; Mice ; *Pneumonia/immunology/microbiology ; Mice, Knockout ; Mice, Inbred C57BL ; Humans ; Lung/immunology ; Signal Transduction ; *Macrophages, Alveolar/immunology ; Germ-Free Life ; Microbiota/immunology ; }, abstract = {Crosstalk between the immune system and the microbiome is critical for maintaining immune homeostasis. Here, we examined this communication and the impact of immune-suppressive IL-10 signaling on pulmonary homeostasis. We found that IL-10 sensing by interstitial macrophages (IMs) is required to prevent spontaneous lung inflammation. Loss of IL-10 signaling in IMs initiated an inflammatory cascade through the activation of classical monocytes and CD4[+] T cell subsets, leading to chronic lung inflammation with age. Analyses of antibiotic-treated and germ-free mice established that lung inflammation in the animals lacking IL-10 signaling was triggered by commensal bacteria. 16S rRNA sequencing revealed Delftia acidovorans and Rhodococcus erythropolis as potential drivers of lung inflammation. Intranasal administration of these bacteria or transplantation of human fecal microbiota elicited lung inflammation in gnotobiotic Il10-deficient mice. These findings highlight that IL-10 sensing by IMs contributes to pulmonary homeostasis by preventing lung inflammation caused by commensal dysbiosis.}, } @article {pmid40305972, year = {2025}, author = {Jiang, ZM and Fang, ZY and Yang, X and Ji, XX and Zhao, YY and Lin, BY and Weng, ZB and Liu, EH}, title = {Glycyrrhetinic acid ameliorates gastric mucosal injury by modulating gut microbiota and its metabolites via Thbs1/PI3K-Akt/p53 pathway.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {142}, number = {}, pages = {156745}, doi = {10.1016/j.phymed.2025.156745}, pmid = {40305972}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Glycyrrhetinic Acid/pharmacology ; Male ; *Gastric Mucosa/drug effects/injuries/pathology/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Rats, Sprague-Dawley ; Rats ; Dysbiosis/drug therapy ; Tumor Suppressor Protein p53/metabolism ; Signal Transduction/drug effects ; Phosphatidylinositol 3-Kinases/metabolism ; Thrombospondin 1/metabolism ; Ethanol ; Hydrochloric Acid ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Dysbiosis of the gut microbiota is pivotal in the development of gastric mucosa injury (GMI). Glycyrrhetinic acid (GA) is a bioactive triterpenoid compound abundantly present in licorice roots. Although GA's potential in mitigating GMI is recognized, its precise mechanism remains elusive, particularly concerning the role of gut microbiota.

PURPOSE: This study aimed to explore the protective effects and mechanisms of GA in preventing HCl/ethanol-induced GMI in rats.

RESULTS: This study demonstrated the protective effects of GA on gastric mucosa, evidenced by enhanced morphology and structure as revealed through H&E staining. Utilizing fecal microbiota transplantation, GA was found to significantly mitigate oxidative damage, inflammation, and expression of apoptosis-related genes in GMI rats by a gut microbiota-dependent mechanism. 16S rRNA sequencing and metabolomics profiling revealed that GA ameliorated HCl/ethanol-triggered intestinal dysbiosis and imbalances in sphingolipid, arginine, and tryptophan metabolism. By promoting the prevalence of Bifidobacterium longum subsp. infantis (B. infantis) in the gut microbiota, GA improved metabolic disturbances linked to injury. Furthermore, its action mechanism was related to the inhibition of the Thbs1/PI3K-Akt/p53 signaling pathway.

CONCLUSION: The administration of GA improves GMI by mitigating intestinal dysbiosis and fostering colonization of B. infantis. GA offers therapeutic potential for GMI by modulating the Thbs1/PI3K-Akt/p53 pathway, thus alleviating inflammatory responses associated with gut microbiota imbalance.}, } @article {pmid40305678, year = {2025}, author = {Wang, Y and Wang, X and Chen, Z and Zheng, J and Liu, X and Zheng, Y and Zheng, Z and Xu, Z and Zhang, Y and Chen, K and Zhang, Y and Yu, L and Ding, Y}, title = {Akkermansia muciniphila exacerbates acute radiation-induced intestinal injury by depleting mucin and enhancing inflammation.}, journal = {The ISME journal}, volume = {19}, number = {1}, pages = {}, pmid = {40305678}, issn = {1751-7370}, support = {2023A0060//Science and Technology Plan Project of Jiangxi Provincial Administration of Traditional Chinese Medicine/ ; 2023A1515010502//Guangdong Basic and Applied Basic Research Foundation/ ; 2023A1515030044//Guangdong Basic and Applied Basic Research Foundation/ ; 2025A1515010567//Guangdong Basic and Applied Basic Research Foundation/ ; 202206010045//Key Science &Technology Brainstorm Project of Guangzhou/ ; 32300085//National Natural Science Foundation of China/ ; 82273564//National Natural Science Foundation of China/ ; 82473567//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome/radiation effects ; *Mucins/metabolism ; Mice, Inbred C57BL ; Dysbiosis/microbiology ; *Inflammation/microbiology ; Intestinal Mucosa/radiation effects/microbiology/pathology ; Fecal Microbiota Transplantation ; Male ; *Intestines/microbiology/radiation effects/pathology ; Akkermansia ; Verrucomicrobia ; *Radiation Injuries/microbiology ; Disease Models, Animal ; }, abstract = {Dysbiosis of gut microbiota plays a crucial role in acute radiation-induced intestinal injury. However, studies on the influence of gut microbiota on acute radiation-induced intestinal injury are inconsistent. In this study, we established an acute radiation-induced intestinal injury mouse model and performed fecal microbiota transplantation to explore the role of the gut microbiota in acute radiation-induced intestinal injury. We observed a significant increase in Akkermansia muciniphila following irradiation, whereas fecal microbiota transplantation effectively reduced A. muciniphila levels. Contrary to expectations, A. muciniphila supplementation increased acute radiation-induced intestinal injury and mortality. Mechanistically, postradiation A. muciniphila upregulates mucin metabolism genes and consumes mucin, thinning the mucosal barrier and promoting the adhesion and translocation of potential pathogens to epithelial cells, thus exacerbating acute radiation-induced intestinal injury. This enables A. muciniphila to use mucin as an energy source. Additionally, A. muciniphila increases the inflammatory macrophage changes and secretion of inflammatory cytokines, leading to a decrease in epithelial stem cell density and inhibition of goblet cell differentiation, further exacerbating acute radiation-induced intestinal injury. Our findings suggest that in certain intestinal environments, the addition of A. muciniphila may worsen radiation-induced intestinal damage; thus, alternative approaches to reverse the dysbiosis associated with radiotherapy should be explored.}, } @article {pmid40305219, year = {2025}, author = {Alves Costa Silva, C and Almonte, AA and Zitvogel, L}, title = {Oncobiomics: Leveraging Microbiome Translational Research in Immuno-Oncology for Clinical-Practice Changes.}, journal = {Biomolecules}, volume = {15}, number = {4}, pages = {}, pmid = {40305219}, issn = {2218-273X}, mesh = {Humans ; *Neoplasms/immunology/microbiology/therapy/metabolism ; *Translational Research, Biomedical ; *Microbiota ; *Gastrointestinal Microbiome/immunology ; Dysbiosis/microbiology/immunology ; }, abstract = {Growing evidence suggests that cancer should not be viewed solely as a genetic disease but also as the result of functional defects in the metaorganism, including disturbances in the gut microbiota (i.e., gut dysbiosis). The human microbiota plays a critical role in regulating epithelial barrier function in the gut, airways, and skin, along with host metabolism and systemic immune responses against microbes and cancer. Collaborative international networks, such as ONCOBIOME, are essential in advancing research equity and building microbiome resources to identify and validate microbiota-related biomarkers and therapies. In this review, we explore the intricate relationship between the microbiome, metabolism, and cancer immunity, and we propose microbiota-based strategies to improve outcomes for individuals at risk of developing cancer or living with the disease.}, } @article {pmid40304829, year = {2025}, author = {Alum, EU and Uti, DE and Ugwu, OP and Alum, BN and Edeh, FO and Ainebyoona, C}, title = {Unveiling the microbial orchestra: exploring the role of microbiota in cancer development and treatment.}, journal = {Discover oncology}, volume = {16}, number = {1}, pages = {646}, pmid = {40304829}, issn = {2730-6011}, abstract = {The human microbiota comprises a diverse microbial ecosystem that significantly impacts health and disease. Among its components, the gut microbiota plays a crucial role in regulating metabolic, immunologic, and inflammatory responses. Dysbiosis, an imbalance in microbial composition, has been linked to carcinogenesis through mechanisms such as chronic inflammation, metabolic disturbances, epigenetic modifications, and immune system dysregulation. Additionally, dysbiosis influences the efficacy and toxicity of cancer therapies. Given these associations, there is growing interest in leveraging the microbiota as a biomarker for cancer detection and outcome prediction. Notably, distinct microbial signatures have been identified across various cancer types, suggesting their potential as diagnostic markers. Furthermore, modulation of the microbiota presents a promising avenue for improving cancer treatment outcomes through strategies such as antibiotics, prebiotics, probiotics, fecal microbiota transplantation, dietary interventions, small-molecule inhibitors, and phage therapy. To explore these relationships, we conducted a comprehensive literature review using Web of Science, Scopus, PubMed, MEDLINE, Embase, and Google Scholar as our primary online databases, focusing on indexed peer-reviewed articles up to the present year. This review aims to elucidate the role of dysbiosis in cancer development, examine the molecular mechanisms involved, and assess the impact of microbiota on cancer therapies. Additionally, we highlight microbiota-based therapeutic strategies and discuss their potential applications in cancer management. A deeper understanding of the intricate interplay between the microbiota and cancer may pave the way for novel approaches to cancer prevention, early detection, and treatment optimization.}, } @article {pmid40302307, year = {2025}, author = {Hoffmann, DE and Javitt, GH and Kelly, CR and Keller, JJ and Baunwall, SMD and Hvas, CL}, title = {Fecal microbiota transplantation: a tale of two regulatory pathways.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2493901}, pmid = {40302307}, issn = {1949-0984}, mesh = {*Fecal Microbiota Transplantation/history/methods/standards/adverse effects ; Humans ; *Gastrointestinal Microbiome ; United States ; Europe ; }, abstract = {Fecal microbiota transplantation (FMT) is a procedure involving the transfer of intestinal microbiota from a healthy donor to a patient to restore a functional intestinal microbiome. First described in modern science in 1958, the use of FMT has been practiced for decades, but only during the past dozen years have clinical frameworks and legal regulations from competent authorities been developed. Future development of microbiota-derived medical therapies will be shaped by the regulatory frameworks of various jurisdictions. This review examines the historical development and status of FMT regulations in the United States and Europe, with particular attention to their respective approaches to ensuring the safety and quality of the therapeutic product and patient access.}, } @article {pmid40301246, year = {2025}, author = {Liu, X and Cui, J and Tan, X and Yu, Y and Niu, J and Wang, Q}, title = {Short-Chain Fatty Acids Alleviate Perioperative Neurocognitive Disorders Through BDNF/PI3K/Akt Pathway in Middle-Aged Rats.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40301246}, issn = {1559-1182}, support = {246Z7702G//Central Government - Guided Local Science and Technology Development Fund/ ; }, abstract = {Perioperative neurocognitive disorders (PND), characterized by persistent cognitive impairment lasting from days to years, present substantial clinical challenges in elderly surgical populations, profoundly compromising functional independence, quality of life, and long-term prognosis. We aimed to investigate the effects of short-chain fatty acids (SCFAs) treatment on PND via mediating Brain-derived neurotrophic factor (BDNF)/Phosphatidylinositol3-kinase (PI3K)/Protein kinase B (Akt) pathway. Using 16S rDNA sequencing targeting the V3-V4 hypervariable regions, we first demonstrated significant gut microbiota dysbiosis in PND model rats, accompanied by altered SCFAs profiles. Subsequent fecal microbiota transplantation (FMT) experiments established causal relationships between PND-associated microbial alterations and spatial cognitive deficits. Mechanistically, SCFAs supplementation attenuated neuronal damage and restored synaptic plasticity, as evidenced by Nissl staining quantification (reduced chromatolysis), TUNEL assay (decreased apoptosis rate), and immunohistochemical analysis (upregulated NeuN expression). Molecular investigations revealed that SCFAs-mediated cognitive improvement involved BDNF upregulation and subsequent PI3K/Akt pathway activation, ultimately enhancing neuronal survival and synaptic integrity. Notably, PND animals exhibited characteristic neuropathological features including synaptic density reduction (PSD-95 downregulation), neuroinflammation amplification (IL-6 elevation), and apoptosis activation-all significantly reversed by SCFA intervention. Our findings establish a novel gut-brain axis mechanism wherein microbiota-derived SCFAs may exert neuroprotection through BDNF-dependent PI3K/Akt signaling, and offer potential therapeutic strategies for PND management.}, } @article {pmid40301116, year = {2025}, author = {Kamath, S and Bryant, RV and Costello, SP and Day, AS and Forbes, B and Haifer, C and Hold, G and Kelly, CR and Li, A and Pakuwal, E and Stringer, A and Tucker, EC and Wardill, HR and Joyce, P}, title = {Translational strategies for oral delivery of faecal microbiota transplantation.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-335077}, pmid = {40301116}, issn = {1468-3288}, abstract = {Faecal microbiota transplantation (FMT) has emerged as a transformative therapy for Clostridioides difficile infections and shows promise for various GI and systemic diseases. However, the poor patient acceptability and accessibility of 'conventional' FMT, typically administered via colonoscopies or enemas, hinders its widespread clinical adoption, particularly for chronic conditions. Oral administration of FMT (OralFMT) overcomes these limitations, yet faces distinct challenges, including a significant capsule burden, palatability concerns and poor microbial viability during gastric transit. This review provides a comprehensive analysis of emerging strategies that aim to advance OralFMT by: (1) refining processing technologies (eg, lyophilisation) that enable manufacturing of low-volume FMT formulations for reducing capsule burden and (2) developing delivery technologies that improve organoleptic acceptability and safeguard the microbiota for targeted colonic release. These advancements present opportunities for OralFMT to expand its therapeutic scope, beyond C. difficile infections, towards chronic GI conditions requiring frequent dosing regimens. While this review primarily focuses on optimising OralFMT delivery, it is important to contextualise these advancements within the broader shift towards defined microbial consortia. Live biotherapeutic products (LBPs) offer an alternative approach, yet the interplay between OralFMT and LBPs in clinical practice remains unresolved. We postulate that continued innovation in OralFMT and LBPs via a multidisciplinary approach can further increase therapeutic efficacy and scalability by enabling disease site targeting, co-delivery of therapeutic compounds and overcoming colonisation resistance. Realising these goals positions OralFMT as a cornerstone of personalised care across a range of diseases rooted in microbiome health.}, } @article {pmid40300858, year = {2025}, author = {Almonte, AA and Zitvogel, L}, title = {Gut reactions: harnessing microbial metabolism to fuel next-generation cancer immunotherapy.}, journal = {Journal for immunotherapy of cancer}, volume = {13}, number = {4}, pages = {}, pmid = {40300858}, issn = {2051-1426}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy/methods ; *Neoplasms/therapy/immunology ; }, abstract = {Immunotherapies, including immune checkpoint inhibitors and chimeric antigen receptor-T cell therapies, depend heavily on a healthy and diverse gut microbiome for optimal efficacy. Dysbiosis, or an imbalance in gut microbial composition and function, can diminish immunotherapy responses by altering immune cell trafficking and metabolic output. Key microbial metabolites such as short-chain fatty acids and modified bile acids shape host immunity and influence T-cell function, while their disruption can foster an immunosuppressive microenvironment. Emerging strategies to restore a balanced microbiome and boost treatment outcomes include dietary interventions, supplementation with beneficial microbes, and fecal microbiota transplantation. Despite these advances, challenges remain in defining dysbiosis, identifying reliable biomarkers, and tailoring microbiota-centered interventions. Nevertheless, as our understanding evolves, the gut microbiome holds promise as an integral component of personalized cancer immunotherapy.}, } @article {pmid40300731, year = {2025}, author = {Mahmoud, AA and Wang, X and Liao, X and Zhang, S and Ding, T and Ahn, J}, title = {Impact of prophages on gut microbiota and disease associations.}, journal = {Microbial pathogenesis}, volume = {204}, number = {}, pages = {107642}, doi = {10.1016/j.micpath.2025.107642}, pmid = {40300731}, issn = {1096-1208}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Prophages/physiology/genetics ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Phage Therapy ; Inflammatory Bowel Diseases/microbiology/therapy ; Bacteria/virology ; Virus Activation ; Animals ; }, abstract = {The gut microbiota plays an important role in maintaining host health by affecting various physiological functions. Among the diverse microbial communities in the gut, prophages are integral components of bacterial genomes, contributing significantly to bacterial evolution, ecology and pathogenicity. Prophages are capable of switching to lytic cycles in response to various internal and external factors. Factors that induce prophage induction include DNA damage, oxidative stress, nutrient availability, host immune response, quorum sensing, diet, secondary metabolites, antibiotics, and lifestyle changes. Prophage induction could contribute to both gut homeostasis and dysbiosis. Importantly, the connections between prophage induction and disorders such as inflammatory bowel disease, ulcerative colitis, and bacterial vaginosis highlight the dual roles of prophages in both health and disease. Although therapeutic approaches such as phage therapy (PT), fecal microbiota transplants (FMT), and fecal virome transplants (FVT) have gained attention, the concept of dietary prophage induction therapy offers a novel, targeted method to modulate gut microbiota. In spite of recent advances in understanding the role of prophages in gut health, the exact mechanisms by which they influence gut health remain only partially understood. Therefore, further research is needed to elucidate additional molecular mechanisms of prophage induction pathways and to explore their implications for gut microbiota dynamics and disease associations. This review discusses the molecular mechanisms and key factors that trigger prophage induction in the gut. Insights into these processes could lead to innovative therapeutic strategies that utilize prophages to support gut health.}, } @article {pmid40300608, year = {2025}, author = {Wirbel, J and Andermann, TM and Brooks, EF and Evans, L and Groth, A and Dvorak, M and Chakraborty, M and Palushaj, B and Reynolds, GZM and Porter, IE and Al Malki, M and Rezvani, A and Gooptu, M and Elmariah, H and Runaas, L and Fei, T and Martens, MJ and Bolaños-Meade, J and Hamadani, M and Holtan, S and Jenq, R and Peled, JU and Horowitz, MM and Poston, KL and Saber, W and Kean, LS and Perales, MA and Bhatt, AS}, title = {Accurate prediction of absolute prokaryotic abundance from DNA concentration.}, journal = {Cell reports methods}, volume = {5}, number = {5}, pages = {101030}, pmid = {40300608}, issn = {2667-2375}, support = {U10 HL069294/HL/NHLBI NIH HHS/United States ; R01 AI148623/AI/NIAID NIH HHS/United States ; R01 AG081144/AG/NIA NIH HHS/United States ; U19 AG065156/AG/NIA NIH HHS/United States ; P30 AG066515/AG/NIA NIH HHS/United States ; U24 HL138660/HL/NHLBI NIH HHS/United States ; R01 AI143757/AI/NIAID NIH HHS/United States ; T32 HG000044/HG/NHGRI NIH HHS/United States ; R01 AG089169/AG/NIA NIH HHS/United States ; R01 NS115114/NS/NINDS NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; S10 OD026899/OD/NIH HHS/United States ; S10 OD025004/OD/NIH HHS/United States ; R01 NS107513/NS/NINDS NIH HHS/United States ; S10 RR019513/RR/NCRR NIH HHS/United States ; U01 DK140939/DK/NIDDK NIH HHS/United States ; S10 RR026338/RR/NCRR NIH HHS/United States ; K23 AI163365/AI/NIAID NIH HHS/United States ; R21 NS132101/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; *DNA, Bacterial/genetics/analysis ; Machine Learning ; *Prokaryotic Cells ; Male ; Parkinson Disease/microbiology ; }, abstract = {Quantification of the absolute microbial abundance in a human stool sample is crucial for a comprehensive understanding of the microbial ecosystem, but this information is lost upon metagenomic sequencing. While several methods exist to measure absolute microbial abundance, they are technically challenging and costly, presenting an opportunity for machine learning. Here, we observe a strong correlation between DNA concentration and the absolute number of 16S ribosomal RNA copies as measured by digital droplet PCR in clinical stool samples from individuals undergoing hematopoietic cell transplantation (BMT CTN 1801). Based on this correlation and additional measurements, we trained an accurate yet simple machine learning model for the prediction of absolute prokaryotic load, which showed exceptional prediction accuracy on an external cohort that includes people living with Parkinson's disease and healthy controls. We propose that, with further validation, this model has the potential to enable accurate absolute abundance estimation based on readily available sample measurements.}, } @article {pmid40300372, year = {2025}, author = {Liu, Z and Zhang, H and Wang, J and Yao, Y and Wang, X and Liu, Y and Fang, W and Liu, X and Zheng, Y}, title = {Clca1 deficiency exacerbates colitis susceptibility via impairment of mucus barrier integrity and gut microbiota homeostasis.}, journal = {Microbiological research}, volume = {297}, number = {}, pages = {128191}, doi = {10.1016/j.micres.2025.128191}, pmid = {40300372}, issn = {1618-0623}, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; Homeostasis ; *Intestinal Mucosa/microbiology/metabolism/pathology/immunology ; Disease Models, Animal ; Dextran Sulfate ; Mice, Knockout ; *Chloride Channels/deficiency/genetics/metabolism ; *Colitis/microbiology/chemically induced/pathology ; Dysbiosis ; Goblet Cells ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; *Mucus/metabolism ; Disease Susceptibility ; Colitis, Ulcerative/microbiology ; Neutrophils/immunology ; Immunity, Mucosal ; Neutrophil Infiltration ; }, abstract = {The intestinal mucus barrier has emerged as a promising therapeutic target for inflammatory bowel disease. Understanding its regulatory mechanisms is critical for elucidating ulcerative colitis (UC) pathogenesis, improving diagnostics, guiding treatments, and preventing relapse. Chloride Channel Accessory 1 (Clca1), a constituent of the mucus layer, remains understudied in colitis. Here, we investigated Clca1's role in mucosal immunity and intestinal homeostasis using experimental colitis models. Clca1-deficient (Clca1[-/-]) mice displayed compromised mucus layer integrity, reduced neutrophil infiltration, and gut microbiota dysbiosis. Notably, Clca1[-/-] mice exhibited exacerbated colitis severity following dextran sulfate sodium (DSS) challenge, accompanied by a diminished goblet cell populations. Fecal microbiota transplantation (FMT) studies revealed that gut microbiota critically modulates divergent phenotypic outcomes between genotypes. Our findings establish Clca1 as a multifunctional regulator of mucus barrier integrity through mechanisms involving goblet cell maintenance, neutrophil-mediated immunity, and host-microbiota crosstalk. These results advance the understanding of UC pathogenesis and identify Clca1-associated pathways as potential targets for barrier restoration therapies.}, } @article {pmid40299998, year = {2025}, author = {Cao, J and Wang, X and Lei, Y and Jiang, X and Kannan, K and Li, M}, title = {Health Risks of Low-Dose Dietary Exposure to Triphenyl Phosphate and Diphenyl Phosphate in Mice: Insights from the Gut-Liver Axis.}, journal = {Environmental science & technology}, volume = {59}, number = {18}, pages = {8960-8971}, doi = {10.1021/acs.est.4c08270}, pmid = {40299998}, issn = {1520-5851}, mesh = {Animals ; *Liver/drug effects/metabolism ; Mice ; *Organophosphates/toxicity ; Male ; Mice, Inbred C57BL ; *Dietary Exposure ; Gastrointestinal Microbiome/drug effects ; }, abstract = {Aryl phosphate esters have been detected throughout the natural environment and in human blood samples, making it important to determine the health risks associated with exposure to triphenyl phosphate (TPHP) and its metabolite diphenyl phosphate (DPHP). Here, C57BL/6J male mice were exposed to TPHP or DPHP for 12 weeks at estimated daily intake doses of 0.1 and 7 μg/kg bw/day. TPHP intake affected the levels of short-chain fatty acids and bile acids in the gut, enhancing the production of 29 medium- and long-chain fatty acids in the liver by 3.72-fold and significantly increasing hepatic lipid and cholesterol levels. Metabolomic and molecular analysis confirmed that elevated liver cholesterol levels persisted after an 8 week recovery period. Gut microbiota-dependent cholesterol alterations were the toxic end points observed in TPHP-fed mice, as supported by the results of fecal microbiota transplantation. In DPHP-fed mice, serotonergic and glutamatergic synapses were simultaneously altered in the liver and intestine, corresponding to the reduction of five brain neurotransmitters (15.4-60.8%). Decreased liver carbohydrate levels and insulin resistance were observed in the DPHP-fed mice. These results suggest that TPHP and DPHP affect metabolism via different toxic modes, mediated through the gut-liver axis, providing novel insights into the mechanisms of organophosphate-ester-mediated metabolic disruption.}, } @article {pmid40299512, year = {2025}, author = {Eslami, M and Adampour, Z and Fadaee Dowlat, B and Yaghmayee, S and Motallebi Tabaei, F and Oksenych, V and Naderian, R}, title = {A Novel Frontier in Gut-Brain Axis Research: The Transplantation of Fecal Microbiota in Neurodegenerative Disorders.}, journal = {Biomedicines}, volume = {13}, number = {4}, pages = {}, pmid = {40299512}, issn = {2227-9059}, abstract = {The gut-brain axis (GBA) represents a sophisticated bidirectional communication system connecting the central nervous system (CNS) and the gastrointestinal (GI) tract. This interplay occurs primarily through neuronal, immune, and metabolic pathways. Dysbiosis in gut microbiota has been associated with multiple neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). In recent years, fecal microbiota transplantation (FMT) has gained attention as an innovative therapeutic approach, aiming to restore microbial balance in the gut while influencing neuroinflammatory and neurodegenerative pathways. This review explores the mechanisms by which FMT impacts the gut-brain axis. Key areas of focus include its ability to reduce neuroinflammation, strengthen gut barrier integrity, regulate neurotransmitter production, and reinstate microbial diversity. Both preclinical and clinical studies indicate that FMT can alleviate motor and cognitive deficits in PD and AD, lower neuroinflammatory markers in MS, and enhance respiratory and neuromuscular functions in ALS. Despite these findings, several challenges remain, including donor selection complexities, uncertainties about long-term safety, and inconsistencies in clinical outcomes. Innovations such as synthetic microbial communities, engineered probiotics, and AI-driven analysis of the microbiome hold the potential to improve the precision and effectiveness of FMT in managing neurodegenerative conditions. Although FMT presents considerable promise as a therapeutic development, its widespread application for neurodegenerative diseases requires thorough validation through well-designed, large-scale clinical trials. It is essential to establish standardized protocols, refine donor selection processes, and deepen our understanding of the molecular mechanisms behind its efficacy.}, } @article {pmid40299326, year = {2025}, author = {Hauser, G and Benjak Horvat, I and Rajilić-Stojanović, M and Krznarić-Zrnić, I and Kukla, M and Aljinović-Vučić, V and Mikolašević, I}, title = {Intestinal Microbiota Modulation by Fecal Microbiota Transplantation in Nonalcoholic Fatty Liver Disease.}, journal = {Biomedicines}, volume = {13}, number = {4}, pages = {}, pmid = {40299326}, issn = {2227-9059}, abstract = {Numerous factors are involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which are responsible for its development and progression as an independent entity, but also thanks to their simultaneous action. This is explained by the hypothesis of multiple parallel hits. These factors are insulin resistance, lipid metabolism alteration, oxidative stress, endoplasmic reticulum stress, inflammatory cytokine liberation, gut microbiota dysbiosis or gut-liver axis activation. This is a systematic review which has an aim to show the connection between intestinal microbiota and the role of its disbalance in the development of NAFLD. The gut microbiota is made from a wide spectrum of microorganisms that has a systemic impact on human health, with a well-documented role in digestion, energy metabolism, the stimulation of the immune system, synthesis of essential nutrients, etc. It has been shown that dysbiosis is associated with all three stages of chronic liver disease. Thus, the modulation of the gut microbiota has attracted research interest as a novel therapeutic approach for the management of NAFLD patients. The modification of microbiota can be achieved by substantial diet modification and the application of probiotics or prebiotics, while the most radical effects are observed by fecal microbiota transplantation (FMT). Given the results of FMT in the context of metabolic syndrome (MetS) and NAFLD in animal models and scarce pilot studies on humans, FMT seems to be a promising treatment option that could reverse intestinal dysbiosis and thereby influence the course of NAFLD.}, } @article {pmid40298931, year = {2025}, author = {Gao, X and Fu, N and Ben, Q and Bu, X}, title = {A Meta-Analysis of the Effects of Gut Microbiota-Based Interventions on Gastrointestinal and Behavioral Symptoms in Children With Autism Spectrum Disorder.}, journal = {Nutrition reviews}, volume = {}, number = {}, pages = {}, doi = {10.1093/nutrit/nuaf050}, pmid = {40298931}, issn = {1753-4887}, abstract = {CONTEXT: Despite an increasing body of research showing gut microbiota-based interventions can improve gastrointestinal (GI) symptoms and behavioral symptoms in both humans and animals, there are still disagreements about its impact on autism spectrum disorder (ASD) in children.

OBJECTIVE: The goal of this systematic review and meta-analysis was to fully investigate the effects of gut microbiota-based interventions (eg, fecal microbiota transplantation, probiotics, prebiotics) on GI and behavioral symptoms in children with ASD.

DATA SOURCES: The PubMed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, and Scopus databases were searched from inception to August 25, 2024.

DATA EXTRACTION: Data were extracted by 2 reviewers independently, and discrepancies in authors' judgments were resolved by discussion or consulting a third author.

DATA ANALYSIS: The scale score of GI and behavioral symptoms before and after the intervention was extracted from included trials to evaluate the therapeutic effects of gut microbiota-based therapy in children with autism.

RESULTS: A total of 5722 records were identified, of which 13 included in narrative synthesis and 8 studies included a meta-analysis. The nonsignificant overall effect size of gut microbiota-based intervention on GI symptoms (standardized mean difference [SMD] = -0.34 [95% CI, -0.76 to 0.07]; P = .11) and behavioral symptoms (SMD = -0.18 [95% CI, -0.37 to 0.02]; P = .08) was observed. Nevertheless, we observed a significant effect size on behavioral symptoms in the subgroup of the intervention duration (SMD = -0.26 [95% CI, -0.49 to -0.03]; P = .02).

CONCLUSIONS: In children with autism, the proof supporting the validity of gut microbiota-based intervention on GI and behavioral symptoms should be interpreted cautiously. More randomized controlled trials with rigorous methodological quality are required to precisely confirm the curative benefits of gut microbiota-based interventions on GI and behavioral symptoms in children with autism.

PROSPERO registration no. CRD42024583213.}, } @article {pmid40298495, year = {2025}, author = {Cusumano, G and Flores, GA and Venanzoni, R and Angelini, P}, title = {The Impact of Antibiotic Therapy on Intestinal Microbiota: Dysbiosis, Antibiotic Resistance, and Restoration Strategies.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {4}, pages = {}, pmid = {40298495}, issn = {2079-6382}, abstract = {The human gut microbiota-an intricate and dynamic ecosystem-plays a pivotal role in metabolic regulation, immune modulation, and the maintenance of intestinal barrier integrity. Although antibiotic therapy is indispensable for managing bacterial infections, it profoundly disrupts gut microbial communities. Such dysbiosis is typified by diminished diversity and shifts in community structure, especially among beneficial bacterial genera (e.g., Bifidobacterium and Eubacterium), and fosters antibiotic-resistant strains and the horizontal transfer of resistance genes. These alterations compromise colonization resistance, increase intestinal permeability, and amplify susceptibility to opportunistic pathogens like Clostridioides difficile. Beyond gastrointestinal disorders, emerging evidence associates dysbiosis with systemic conditions, including chronic inflammation, metabolic syndrome, and neurodegenerative diseases, underscoring the relevance of the microbiota-gut-brain axis. The recovery of pre-existing gut communities post-antibiotic therapy is highly variable, influenced by drug spectrum, dosage, and treatment duration. Innovative interventions-such as fecal microbiota transplantation (FMT), probiotics, synbiotics, and precision microbiome therapeutics-have shown promise in counteracting dysbiosis and mitigating its adverse effects. These therapies align closely with antibiotic stewardship programs aimed at minimizing unnecessary antibiotic use to preserve microbial diversity and curtail the spread of multidrug-resistant organisms. This review emphasizes the pressing need for microbiota-centered strategies to optimize antibiotic administration, promote long-term health resilience, and alleviate the disease burden associated with antibiotic-induced dysbiosis.}, } @article {pmid40297591, year = {2025}, author = {Pei, X and Liu, L and Han, Y}, title = {Advances in human microbiome and prostate cancer research.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1576679}, pmid = {40297591}, issn = {1664-3224}, mesh = {Humans ; *Prostatic Neoplasms/microbiology/therapy/immunology/metabolism/etiology ; Male ; *Microbiota ; *Gastrointestinal Microbiome ; Tumor Microenvironment/immunology ; Animals ; }, abstract = {Prostate cancer (PCa) is the second most common malignant tumor in men worldwide, and its metastatic and heterogeneous nature makes it significantly more difficult to treat. Recent studies have revealed the critical role of microbiota in PCa occurrence, progression, and treatment. Accumulating evidence from 16S rRNA and metagenomic sequencing suggests the presence of specific microbiota in prostate tissues and macrogenomics techniques: cancerous tissues are enriched with pro-inflammatory genera (e.g., Fusobacterium, Propionibacterium acnes), whereas commensal bacteria (e.g., Pseudomonas) are more common in paracancerous tissues. The microbiota drive tumor progression through activation of the NF-κB/STAT3 pathway to induce chronic inflammation, modulation of the immune microenvironment (e.g., Treg/Th17 imbalance and M2-type macrophage polarization), and metabolite (e.g., LPS, short-chain fatty acids)-mediated hormonal and epigenetic regulation. In terms of clinical translation, urinary microbiota characterization combined with metabolomics analysis may enhance diagnostic specificity, while gut flora modulation (e.g., probiotic interventions or fecal transplants) may improve resistance to androgen deprivation therapy. Current challenges include sequencing accuracy of low-biomass samples, limitations of causal mechanism validation models, and large cohort heterogeneity. In the future, it will be necessary to integrate multi-omics technologies to explore the bidirectional regulation of the "gut-prostate axis" and develop personalized therapeutic strategies targeting microorganisms. In this paper, we systematically review the interactions between microbiota and PCa and their clinical potentials to provide a theoretical basis for precision diagnosis and treatment.}, } @article {pmid40297203, year = {2025}, author = {Nguyen, JDK and Yohannes, KG and Setiady, I and Phillips, EC and Hays, RA and Behm, BW and Warren, CA and Shin, JH}, title = {Factors associated with failure of fecal microbiota transplant for recurrent Clostridioides difficile infection.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848251334517}, pmid = {40297203}, issn = {1756-283X}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) has emerged as a prevalent and recurrent antibiotic-associated infection. Fecal microbiota transplantation (FMT) is the most effective treatment for recurrent CDI (rCDI). Despite high success rates, FMT is ineffective in 5%-20% of cases. Factors associated with failure have not been clearly defined.

OBJECTIVES: In this study, we seek to identify factors predictive of FMT failure.

DESIGN: Retrospective cohort study.

METHODS: A retrospective chart review was conducted on adult patients who were screened at the Complicated C. difficile Clinic at the University of Virginia Health System and received FMT for rCDI between 2013 and 2022. The primary outcome was failure of FMT, defined as either rCDI or all-cause death within 1 year.

RESULTS: In total, 240 patients underwent FMT: 70.4% were female, the median age was 68, and the median episode of CDI was 4. A total of 24.6% experienced failure within 1 year (18.3% had rCDI and 7.1% died). Age 70 or older (odds ratio (OR) = 2.66 (1.29-5.67)), ⩾4 episodes of CDI (OR = 3.13 (1.47-7.09)), and diabetes mellitus (OR = 2.82 (1.25-6.50)) were associated with failure on multivariate analysis.

CONCLUSION: Our study shows that FMT remains an effective treatment for rCDI. We highlight several factors associated with FMT failure, such as older age, ⩾4 episodes of CDI, and diabetes mellitus, and the need for additional research to clearly define causality.}, } @article {pmid40296251, year = {2025}, author = {Zheng, H and Chen, Y and Lu, S and Liu, Z and Ma, Y and Zhang, C and Zhang, Y and Zhang, J and Liu, C and Chu, M and Pei, F and Liu, S and Duan, L}, title = {Mechanosensory Piezo2 regulated by gut microbiota participates in the development of visceral hypersensitivity and intestinal dysmotility.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2497399}, pmid = {40296251}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; Humans ; Mice ; *Irritable Bowel Syndrome/microbiology/physiopathology/metabolism/therapy ; *Ion Channels/metabolism/genetics ; Male ; Female ; Fecal Microbiota Transplantation ; *Gastrointestinal Motility ; Adult ; Middle Aged ; Colon/metabolism ; Mice, Inbred C57BL ; Feces/microbiology ; Fusobacterium/physiology ; Dysbiosis/microbiology ; Disease Models, Animal ; Ganglia, Spinal/metabolism ; Akkermansia ; }, abstract = {The gut microbiota plays a crucial role in the manifestation of intestinal dysfunction associated with irritable bowel syndrome (IBS). The mechanosensory Piezo2 has been implicated in the regulation of intestinal function. However, it remains unclear whether Piezo2 is modulated by the gut microbiota, thus contributing to the development of visceral hypersensitivity and gut dysmotility. The study enrolled patients with diarrhea-predominant IBS (IBS-D) alongside healthy controls (HC). Questionnaires, rectal barostat test, and colonoscopy with mucosal biopsy were conducted. Fecal microbiota transplantation (FMT) was performed using samples from HC or IBS-D patients, and interventions with Akkermansia muciniphila or Fusobacterium varium were carried out on colon- or dorsal root ganglion (DRG)- Piezo2 knockdown pseudo-germ-free mice. Visceral sensitivity and intestinal motility were assessed. Piezo2 levels were detected using western blot and immunofluorescence. Fecal 16S rRNA sequencing and cecum untargeted metabolomics analysis, followed by molecular docking predictions of Piezo2, were also performed. The ratio of Piezo2[+]/5-HT[+] cells was lower in IBS-D patients, positively correlated with visceral sensation and intestinal dysbiosis. The mice that received FMT from IBS-D patients exhibited colonic dysmotility and visceral hypersensitivity, along with elevated Piezo2 protein levels in the colon and DRG. Knockdown of Piezo2 in the colon or DRG ameliorated the FMT-induced colonic dysmotility and visceral hypersensitivity. Fecal 16S rRNA sequencing revealed distinct microbiota composition. Notably, Fusobacterium varium, but not Akkermansia muciniphila, induced gut dysmotility and visceral hypersensitivity, effects that could be alleviated by colon or DRG Piezo2 knockdown. Additionally, Fusobacterium varium lead to increased Piezo2 protein levels, as well as elevated levels of indole-3-acetic acid and indole-3-acrylic acid, which were predicted to bind to Piezo2, causing disturbances. Piezo2 can be regulated by gut microbiota and involved in visceral hypersensitivity and colonic dysmotility, with Fusobacterium varium playing a crucial role.}, } @article {pmid40295906, year = {2025}, author = {Ahmadi, A and Shokoohizadeh, L and Sheikhesmaili, F and Mirzaei, MK and Mohammadi, A and Nikkhoo, B and Khodaei, H and Alikhani, MY and Yousefimashouf, R}, title = {Gut microbiomes and treatment-resistant ulcerative colitis: a case-control study using qPCR.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {254}, pmid = {40295906}, issn = {1471-2180}, mesh = {Humans ; *Colitis, Ulcerative/microbiology/drug therapy ; Case-Control Studies ; *Gastrointestinal Microbiome/genetics ; Male ; Adult ; Female ; Feces/microbiology ; Middle Aged ; Real-Time Polymerase Chain Reaction ; *Bacteria/genetics/classification/isolation & purification ; Young Adult ; }, abstract = {BACKGROUND: The gut microbiome has been identified as a pivotal factor in ulcerative colitis (UC), given its role as the main reservoir of microbes in the body. This community of microorganisms, present in variable concentrations in the digestive tract, makes a wide range of beneficial roles for the host. However, the role of the gut microbiome in patients with refractory UC is still significant, so this study aimed to further investigate the role of these bacteria in patients with refractory UC.

METHODS: This case-control study was conducted on stool samples from four distinct groups: the first group comprised new patients diagnosed with ulcerative colitis (all of them had responded to treatment after follow-up) (N = 24); the second group consisted of patients with treatment-resistant ulcerative colitis (N = 23); the third group included first-degree relatives of group 1 patients (N = 24); and the fourth group consisted of first-degree relatives of group 2 patients (N = 23). The research tools employed in this study included a questionnaire, quantitative real-time PCR (qPCR) test, and culture on stool samples.

RESULT: The mean age of patients in groups 1 and 2 was 45.88 ± 18.51 and 41.30 ± 13.01 years, while the mean age of controls in groups 3 and 4 was 37.29 ± 9.62 and 40.96 ± 13.01 years, respectively. Stool culture results for pathogenic bacteria were negative in all four groups. The of history of consuming dairy products containing probiotics was highest in Group 1, with 22 (91.67%) subjects, while the lowest was observed in Group 3, with 16 (66.67%). The highest history of self-administered antibiotic use was observed in Group 2, with 13 cases (56.52%), while the lowest was noted in Group 3, with 4 cases (16.67%). The findings indicated a statistically significant relationship (P < 0.05) between Groups 2 and 4 with respect to the E. coli and Bifidobacterium ssp. microbial population. Additionally, a significant relationship was identified between the Lactobacillus ssp., Bifidobacterium ssp., and Bacteroides ssp. microbial community between groups 1 and 2 (P < 0.05).

CONCLUSION: The findings of this study demonstrated that several intestinal microbiomes have a substantial impact on the management of ulcerative colitis. The results of this study suggest that by comparing the gut microbiome of treatment-resistant and individuals newly diagnosed with ulcerative colitis, we can gain a better understanding of microbiome differences that may influence treatment outcomes. The results of this study may also lead to the identification of new therapeutic strategies that are based on regulating the gut microbiome. These strategies could include the use of fecal microbiome transplantation (FMT), probiotics, prebiotics, or specific bacteria-based therapies.}, } @article {pmid40295607, year = {2025}, author = {Mohammadi, M and Rahimi, K and Rezaie, A and Tabandeh, MR}, title = {The role of fecal microbiota transplantation on the NLRP3-Caspase 1 pathway and anxiety like behavioral in the ulcerative colitis model in rats.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {14831}, pmid = {40295607}, issn = {2045-2322}, mesh = {Animals ; *Caspase 1/metabolism/genetics ; *Fecal Microbiota Transplantation/methods ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; *Anxiety/therapy/metabolism/etiology ; Rats ; Signal Transduction ; Male ; *Colitis, Ulcerative/therapy/chemically induced/metabolism ; Disease Models, Animal ; Hippocampus/metabolism ; Behavior, Animal ; Colon/metabolism/pathology ; Acetic Acid ; Interleukin-18/metabolism ; }, abstract = {The purpose of this study was to investigate the function of the NLRP3-Caspase 1 signaling pathway in the colon during fecal microbiota transplantation (FMT) in colitis induced by acetic acid. Additionally, the study aimed to determine the impact of FMT on anxiety behaviors by analyzing the function of the NLRP3-Caspase 1 signaling pathway in the hippocampus. A total of twenty-four rats were selected randomly for the study and divided into two groups, a control group, and an acid acetic-induced colitis group. The acid acetic-induced colitis group further consisted of three subgroups: untreated acid acetic-induced colitis group, mesalazine 0.3 gr/kg group, and FMT group. After 6 days, the colon was evaluated for macroscopic and microscopic damage, and the signaling pathway NLRP3-Caspase1-related genes in the colon and hippocampus were analyzed. Additionally, anxiety-related behaviors of the rats were observed. FMT decreased colonic mRNA expression levels of NLRP3, NF-кB, and Caspase1 and pro-inflammatory cytokines (IL-1β and IL-18). Also, FMT reduced the expression of NLRP3, NF-κB, and Caspase1 protein levels as well as pro-inflammatory cytokines IL-1β and IL-18 in the hippocampus, resulting in a reduction of anxiety behaviors in the open field and elevated plus maze tests in the colitis model. FMT may improve acetic acid-induced colitis by regulating the NLRP3-Caspase1 signaling pathway in the colon. It also reduced colitis-induced anxiety behavior by regulating the expression of proteins related to the NLRP3-Caspase 1 pathway in the hippocampus.}, } @article {pmid40295196, year = {2025}, author = {Sun, J and Shi, L and Xu, F and Sun, H and Liu, Y and Sun, J and Zhou, Q}, title = {Naringenin Inhibits Colorectal Cancer associated with a High-Fat Diet through Modulation of Gut Microbiota and IL-6/STAT3 Pathway.}, journal = {Journal of microbiology and biotechnology}, volume = {35}, number = {}, pages = {e2412029}, pmid = {40295196}, issn = {1738-8872}, mesh = {*Flavanones/pharmacology ; *Gastrointestinal Microbiome/drug effects ; *Colorectal Neoplasms/drug therapy/microbiology/prevention & control/etiology/metabolism ; *STAT3 Transcription Factor/metabolism ; *Diet, High-Fat/adverse effects ; Animals ; *Interleukin-6/metabolism ; Mice ; Male ; Signal Transduction/drug effects ; Fecal Microbiota Transplantation ; Humans ; Mice, Inbred C57BL ; Bacteria/drug effects/classification/genetics ; }, abstract = {Colorectal cancer (CRC) is a worldwide health issue. It causes illness and death in millions of people each year. A positive correlation has been observed between the intake of dietary fat and the development of CRC. The composition of gut microbiota exhibits a significant correlation with pathophysiologic processes in intestine. Clinical treatment remains inadequate due to the complex pathogenic mechanisms of CRC triggered by a high-fat diet (HFD). Naringenin, a flavonoid from grapefruit, has anti-cancer activity. Our findings suggest that naringenin enhances gut microbiota diversity by increasing the abundance of beneficial bacterial species while reducing opportunistic pathogenic bacteria. The fecal microbiota transplantation assay (FMT) demonstrated that the anti-HFD-CRC activity of naringenin depended on the gut microbiota. Furthermore, naringenin antagonized the IL-6/STAT3 pathway. These results suggest that naringenin may be a potential treatment for HFD-CRC.}, } @article {pmid40294087, year = {2025}, author = {Duarte, L and Magne, F and Gotteland, M}, title = {Gut microbiota in patients with metabolic, dysfunction-associated steatotic liver disease.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {28}, number = {4}, pages = {307-315}, pmid = {40294087}, issn = {1473-6519}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology/therapy ; *Fatty Liver/microbiology/therapy ; Liver/microbiology/metabolism ; *Non-alcoholic Fatty Liver Disease/microbiology ; Probiotics ; Animals ; }, abstract = {PURPOSE OF REVIEW: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent condition that can progress to fibrosis, steatohepatitis, and hepatocellular carcinoma. This review examines recent advances concerning the role of gut microbiota in MASLD and microbiota-focused interventions to positively impact disease outcome.

RECENT FINDINGS: Dysbiotic microbiota and a compromised gut barrier facilitate the translocation of microbial-associated molecular patterns and harmful metabolites into the portal circulation and liver, where they exacerbate inflammatory and fibrogenic processes. Conversely, other bacterial metabolites have protective effects in the liver. Therefore, microbiota homeostasis is essential for maintaining liver health.

SUMMARY: Levels of harmful bacterial metabolites including ethanol, NH 3 , trimethylamine-L-oxide, 2-oleylglycerol, and litocholic acid are often increased in patients with MASLD. Conversely, short-chain fatty acids, indole derivatives, histidine, and the acids taurodeoxycholic, 3-succinylcholic, and hyodeoxycholic are decreased. The main aim of current interventions/treatments is to reduce harmful metabolites and increase beneficial ones. These interventions include drugs (pemafibrate, metformin, obeticholic acid), natural compounds (silymarin, lupeol, dietary fiber, peptides), exogenous bacteria (probiotics, gut symbionts), special diets (Mediterranean diet, time-restricted feeding), as well as microbiota transplantation, and phage therapy. Most improve gut permeability, liver inflammation, and fibrosis through microbiota regulation, and are promising alternatives for MASLFD management. However, most results come from animal studies, while clinical trials in MASLD patients are lacking. Further research is therefore needed in this area.}, } @article {pmid40292220, year = {2025}, author = {Ma, P and Wang, R and Chen, H and Zheng, J and Yang, W and Meng, B and Liu, Y and Lu, Y and Zhao, J and Gao, H}, title = {Fecal microbiota transplantation alleviates lipopolysaccharide-induced osteoporosis by modulating gut microbiota and long non-coding RNA TUG1 expression.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1535666}, pmid = {40292220}, issn = {2235-2988}, mesh = {Animals ; *RNA, Long Noncoding/genetics/metabolism ; *Gastrointestinal Microbiome/genetics ; *Osteoporosis/therapy/chemically induced/microbiology ; *Fecal Microbiota Transplantation/methods ; *Lipopolysaccharides/adverse effects ; Mice, Inbred C57BL ; Mice ; Disease Models, Animal ; RNA, Ribosomal, 16S/genetics ; Femur/pathology/diagnostic imaging ; Core Binding Factor Alpha 1 Subunit/metabolism ; X-Ray Microtomography ; Male ; }, abstract = {PURPOSE: To study whether fecal microbiota transplantation (FMT) can alleviate lipopolysaccharide (LPS)-induced osteoporosis (OP) by regulating the composition and abundance of gut microbiota and the expression level of long non-coding RNA (lncRNA) TUG1.

METHODS: Twenty C57BL/6 mice were selected. Two mice were randomly designated as fecal donors, while the remaining mice were randomly divided into control group, LPS group, and LPS + FMT group. Each group consisted of 6 mice. The mice in the LPS and LPS + FMT groups were intraperitoneally injected with LPS to establish the OP model, and the mice in the LPS + FMT group were treated with donor feces by gavage. Micro-CT was used to scan the femur specimens of mice, and the bone structural parameters of the control and LPS groups were compared to verify the effectiveness of the OP model. HE staining was used to compare the microstructure of femurs in the 3 groups. 16S rRNA gene sequencing was used to analyze the composition and abundance of gut microbiota in mice. Immunofluorescence staining was used to compare the expression levels of Runt-related transcription factor 2 (RUNX2) in the femur of the 3 groups. Real-time quantitative reverse transcription PCR (qRT-PCR) was used to compare the expression levels of lncRNA TUG1 in the intestines and serum of mice in the 3 groups.

RESULTS: Micro-CT showed that compared with the control group, the mice in the LPS group had more bone loss. The bone mineral density, trabecular number, and trabecular thickness of the control group was higher, and the trabecular separation was smaller. The models were validated effectively. HE staining showed that compared with the control group, the bone trabeculae in the LPS group were thinner and sparse, while that in the LPS + FMT group were dense and clear. The 16s rRNA sequencing showed that the abundance of Bacteroides and Lactobacillus in LPS+FMT group was significantly higher than that in LPS group. Immunofluorescence staining showed that the RUNX2 level in the control group and LPS + FMT group was similar, and both were higher than that in the LPS group. The qRT-PCR results showed that the TUG1 mRNA level in the control group and LPS + FMT group was similar and significantly higher than that in the LPS group.

CONCLUSION: FMT can enhance osteoblast levels and improve bone structure by modulating the abundance of gut microbiota in OP mice (such as increasing Bacteroides and Lactobacillus populations) and promoting the expression of lncRNA TUG1, thereby alleviating LPS-induced OP.}, } @article {pmid40292216, year = {2025}, author = {Bu, F and Chen, K and Chen, S and Jiang, Y}, title = {Gut microbiota and intestinal immunity interaction in ulcerative colitis and its application in treatment.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1565082}, pmid = {40292216}, issn = {2235-2988}, mesh = {Humans ; *Colitis, Ulcerative/immunology/therapy/microbiology ; *Gastrointestinal Microbiome/immunology ; Dysbiosis/immunology ; *Immunity, Mucosal ; Intestinal Mucosa/immunology/microbiology ; Animals ; }, abstract = {Ulcerative colitis (UC) is a chronic, non-specific inflammatory bowel disease characterized by inflammation and injury of the colonic mucosa, exhibiting an increasing global incidence. Although research into UC pathogenesis is ongoing, the precise mechanisms remain to be fully elucidated. Studies indicate that UC development results from a complex interplay of factors, including genetic predisposition, environmental exposures, gut microbial dysbiosis, and immune dysregulation. Specifically, UC pathogenesis involves aberrant immune responses triggered by interactions between the host and gut microbiota. A complex, dynamic relationship exists between the microbial community and the host immune system throughout UC pathogenesis. Accumulating evidence suggests that changes in microbiota composition significantly impact gut immunity. This review will examine the intricate balance between the gut microbiota and mucosal immunity in UC progression and discuss potential therapeutic applications, providing a reference for further clinical treatment of this patient population.}, } @article {pmid40291934, year = {2025}, author = {Mattar, L and Thalib, HI and Alnuwaimi, M and Alsaadi, H and Allouji, HA and Alyafei, J and Alshowiman, L and Alsobyani, N and Hassan, FES}, title = {Challenges of concurrent HIV infection in the course and management of Crohn's disease.}, journal = {Journal of medicine and life}, volume = {18}, number = {3}, pages = {171-178}, pmid = {40291934}, issn = {1844-3117}, mesh = {Humans ; *Crohn Disease/therapy/complications/immunology ; *HIV Infections/complications/immunology ; Disease Progression ; Probiotics/therapeutic use ; Gastrointestinal Microbiome ; }, abstract = {Crohn's disease (CD) is a chronic transmural bowel inflammation with a multifactorial etiology involving genetic predisposition and immune dysregulation in response to environmental triggers. In patients with human immunodeficiency virus (HIV), an already compromised immune system further complicates the progression and management of CD, creating unique therapeutic challenges. Probiotics have recently gained attention as a potential therapeutic option for CD, especially due to their role in modulating the gut microbiota. However, their effectiveness in patients with HIV, especially in enhancing and maintaining remissions, remains underexplored. This review aimed to examine how HIV infection influences the course of inflammatory bowel disease (IBD) and its impact on CD management strategies. A systematic literature search was conducted using Google Scholar, PubMed, Springer, and Web of Science to identify studies on patients with HIV and CD. HIV infection significantly alters the progression and management of CD due to its impact on the immune system. The immunosuppressed state of patients with HIV can complicate both the diagnosis and treatment of CD, often requiring adjustments in therapeutic approaches, necessitating a careful, tailored approach.}, } @article {pmid40289872, year = {2025}, author = {Gao, L and Zhang, Y and Hu, Z and Chen, S and Wang, Q and Zeng, Y and Yin, H and Zhao, J and Zhan, Y and Gao, C and Xin, Y and Chen, B and van der Veen, S and Zhao, M and Fang, D and Lu, Q}, title = {Microbiota-Derived Inosine Suppresses Systemic Autoimmunity via Restriction of B Cell Differentiation and Migration.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {20}, pages = {e2409837}, pmid = {40289872}, issn = {2198-3844}, support = {2022YFC3601800//National Key R&D Program of China/ ; 32141004//Special Program of National Natural Science Foundation of China/ ; 2021-I2M-1-059//CAMS Innovation Fund for Medical Sciences (CIFMS) No/ ; 2024-I2M-ZH-020//CAMS Innovation Fund for Medical Sciences (CIFMS) No/ ; 2020-RC320-003//Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ ; NO.82430102//Key Program of the National Natural Science Foundation of China/ ; 82404154//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Mice ; *B-Lymphocytes/immunology/metabolism ; *Gastrointestinal Microbiome/immunology ; *Inosine/metabolism ; *Lupus Erythematosus, Systemic/immunology/microbiology ; *Cell Differentiation/immunology ; *Autoimmunity/immunology ; Fecal Microbiota Transplantation/methods ; Female ; Cell Movement/immunology ; Disease Models, Animal ; Mice, Inbred C57BL ; Dysbiosis/immunology ; }, abstract = {The role of gut microbiota dysbiosis in systemic lupus erythematosus (SLE) pathogenesis remains elusive. Here, it is shown that fecal microbiota transplantation (FMT) from healthy mice to lupus mice ameliorates lupus-like symptoms. Microbiota reconstitution effectively reduces systemic class switch recombination (CSR) and elevates immunoglobulin heavy chain (IGH) naïve isotype. Microbiota profiling reveals an enrichment of Lactobacillus johnsonii post-FMT, with a significant correlation to purine metabolites. Importantly, the L. johnsonii-derived inosine, an intermediate metabolite in purine metabolism, effectively alleviates lupus pathogenesis in mice. Inosine inhibits B cell differentiation and reduces renal B cell infiltration to protect mice from lupus. At the molecular level, inosine reprograms B cells through the extracellular signal-regulated kinase (ERK)-hypoxia-inducible factor-1alpha (HIF-1α) signaling pathway. Therefore, this study highlights the discovery of a novel microbial metabolite modulating autoimmunity and suggests its potential for innovative microbiome-based therapeutic approaches.}, } @article {pmid40289678, year = {2025}, author = {Xu, Z and Li, L and Cheng, L and Gu, Z and Hong, Y}, title = {Maternal obesity and offspring metabolism: revisiting dietary interventions.}, journal = {Food & function}, volume = {16}, number = {10}, pages = {3751-3773}, doi = {10.1039/d4fo06233g}, pmid = {40289678}, issn = {2042-650X}, mesh = {Humans ; Female ; Pregnancy ; *Pregnancy in Obesity/metabolism/diet therapy ; *Metabolic Diseases/etiology/metabolism/prevention & control ; Animals ; *Prenatal Exposure Delayed Effects/metabolism ; Maternal Nutritional Physiological Phenomena ; Diet ; *Obesity/metabolism ; }, abstract = {Maternal obesity increases the risk of metabolic disorders in offspring. Understanding the mechanisms underlying the transgenerational transmission of metabolic diseases is important for the metabolic health of future generations. More research is needed to elucidate the mechanisms underlying the associated risks and their clinical implications because of the inherently complex nature of transgenerational metabolic disease transmission. Diet is a well-recognized risk factor for the development of obesity and other metabolic diseases, and rational dietary interventions are potential therapeutic strategies for their prevention. Despite extensive research on the physiological effects of diet on health and its associated mechanisms, little work has been devoted to understanding the effects of early-life dietary interventions on the metabolic health of offspring. In addition, existing dietary interventions are insufficient to meet clinical needs. Here, we discuss the literature on the effects of maternal obesity on the metabolic health of offspring, focusing on the mechanisms underlying the transgenerational transmission of metabolic diseases. We revisit current dietary interventions and describe their strengths and weaknesses in ameliorating maternal obesity-induced metabolism-related disorders in offspring. We also propose innovative strategies, such as the use of precision nutrition and fecal microbiota transplantation, which may limit the vicious cycle of intergenerational metabolic disease transmission.}, } @article {pmid40289444, year = {2025}, author = {Grimstad, T and Carlsen, A and Kvaløy, JT and Bolstad, N and Warren, DJ and Aabakken, L and Lundin, KEA and Karlsen, L and Steinsbø, Ø and Omdal, R}, title = {Fatigue in Inflammatory Bowel Disease: No Effect of Serum Concentrations of Infliximab, Adalimumab or Anti-Drug Antibodies During Maintenance Therapy.}, journal = {Scandinavian journal of immunology}, volume = {101}, number = {5}, pages = {e70029}, doi = {10.1111/sji.70029}, pmid = {40289444}, issn = {1365-3083}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Adalimumab/therapeutic use/blood/immunology ; Antibodies/blood ; C-Reactive Protein/metabolism ; *Colitis, Ulcerative/drug therapy ; *Crohn Disease/drug therapy ; Cross-Sectional Studies ; *Fatigue/drug therapy/etiology/blood ; Feces/chemistry ; *Inflammatory Bowel Diseases/drug therapy/complications ; *Infliximab/blood/therapeutic use/immunology ; Leukocyte L1 Antigen Complex/metabolism ; Severity of Illness Index ; }, abstract = {Several studies have shown that infliximab and adalimumab ameliorate fatigue in inflammatory bowel disease. We investigated whether serum levels of these agents above or below a selected threshold influence fatigue severity. In this cross-sectional study, we measured serum concentrations (s-) of infliximab and adalimumab and corresponding anti-drug antibody levels. Therapeutic thresholds were defined as s-infliximab ≥ 5.0 mg/L and s-adalimumab ≥ 7.0 mg/L. Disease activity was assessed using the Harvey-Bradshaw Index for Crohn's disease, Partial Mayo Score for ulcerative colitis, and C-reactive protein (CRP) and faecal calprotectin levels for both conditions. Fatigue was assessed with the Fatigue Visual Analog Scale and Fatigue Severity Scale, and depression was evaluated with the Hospital Anxiety and Depression Scale, Depression subscale. Of 171 included patients (112 with Crohn's disease, 59 with ulcerative colitis), 66 (38.6%) were on infliximab and 105 (61.4%) were on adalimumab. Scores on the two fatigue scales were similar for serum values above versus below therapeutic thresholds for both drugs and did not differ with versus without anti-drug antibodies against either drug. CRP was numerically higher with infliximab levels below versus above the threshold (p = 0.06), whereas both CRP and faecal calprotectin were increased with adalimumab below versus above the threshold (p = 0.022, p = 0.0242). In patients with inflammatory bowel disease on maintenance therapy, s-infliximab and s-adalimumab levels below or above therapeutic thresholds or the presence of anti-drug antibodies did not affect fatigue severity. Trial Registration: ClinicalTrials.gov identifier: NCT02134054.}, } @article {pmid40288637, year = {2025}, author = {La Rosa, F and Guzzardi, MA and Pardo-Tendero, M and Barone, M and Ruocco, C and Conti, G and Panetta, D and Riabitch, D and Bernardi, S and Giorgetti, A and Campani, D and Monleon, D and Nisoli, E and Brigidi, P and Iozzo, P}, title = {Effects of children's microbiota on adipose and intestinal development in sex-matched mice persist into adulthood following a single fecal microbiota transplantation.}, journal = {Molecular metabolism}, volume = {97}, number = {}, pages = {102157}, pmid = {40288637}, issn = {2212-8778}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Female ; Mice ; Male ; *Gastrointestinal Microbiome/physiology ; Mice, Inbred C57BL ; Humans ; Adipose Tissue, Brown/metabolism ; Obesity/metabolism/microbiology ; Adipose Tissue, White/metabolism ; Child ; *Intestines/growth & development/microbiology ; Glucose/metabolism ; }, abstract = {BACKGROUND: The global prevalence of obesity and type 2 diabetes, particularly among children, is rising, yet the long-term impacts of early-life fecal microbiota transplantation (FMT) on metabolic health remain poorly understood.

OBJECTIVES: To investigate how early-life FMT from children to young, sex-matched mice influences metabolic outcomes and adipose tissue function in later, adult life.

METHODS: Germ-free mice were colonized with fecal microbiota from either lean children or children with obesity. The impacts on brown adipose tissue (BAT), white adipose tissue (WAT), glucose metabolism, and gut health were analyzed in male and female mice. Microbial communities and metabolite profiles were characterized using sequencing and metabolomics.

RESULTS: Male mice receiving FMT from obese donors exhibited marked BAT whitening and impaired amino acid and glucose metabolism. In contrast, female recipients developed hyperglycemia, accompanied by gut barrier dysfunction and WAT impairment. Distinct microbial and metabolite profiles were associated with these phenotypes: Collinsella and trimethylamine in females; and Paraprevotella, Collinsella, Lachnospiraceae NK4A136, Bacteroides, Coprobacillus, and multiple metabolites in males. These phenotypic effects persisted despite changes in host environment and diet.

CONCLUSIONS: Early-life FMT induced long-lasting effects on the metabolic landscape, profoundly affecting adipose tissue function and systemic glucose homeostasis in adulthood. Donor dietary habits correlated with the fecal microbial profiles observed in recipient mice. These findings highlight the critical need for identifying and leveraging beneficial exposures during early development to combat obesity and diabetes.}, } @article {pmid40288317, year = {2025}, author = {Banerjee, A and Mal, S and Roy, P and Chatterji, U}, title = {Regulating environmental arsenic-mediated gut-brain toxicity using chitosan-conjugated luteolin gold nanoparticles.}, journal = {Ecotoxicology and environmental safety}, volume = {297}, number = {}, pages = {118250}, doi = {10.1016/j.ecoenv.2025.118250}, pmid = {40288317}, issn = {1090-2414}, mesh = {Animals ; *Arsenic/toxicity ; Mice ; *Gold/chemistry ; *Metal Nanoparticles/chemistry ; *Luteolin/chemistry/pharmacology ; *Gastrointestinal Microbiome/drug effects ; *Chitosan/chemistry ; *Brain/drug effects ; Male ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; }, abstract = {Anxiety and depression are two major contributors to global disease burden. Amongst various causal factors, exposure to even low doses of environmental heavy metals, like arsenic, can induce anxiety and depression-like behaviour in mammals. Ingestion of arsenic, primarily through contaminated drinking water, severely disrupts the gut microbes, thereby inducing structural and functional abnormalities in the brain. Fecal microbiota transplantation (FMT) from arsenic-exposed mice to recipient healthy mice (As-FMT) enriched LPS-secreting Gram-negative bacteria and upregulated the expression of TLR4 in intestinal epithelial cells. Consequently, inflammation, oxidative stress and compromised barrier integrity in the gut facilitated LPS translocation into the bloodstream and promoted systemic inflammation. The secretomes eventually affected the brain by activating microglia, altering neurotransmitter levels and reducing the glucocorticoid receptor (GR) expression, contributing to appearance of pyknotic nuclei in dentate gyrus of hippocampus and emergence of anxiety- and depression-like behaviour. Luteolin, a flavonoid, devoid of any apparent side-effects, yet known for its anti-inflammatory and antioxidant properties, showed potential in alleviating the gut-brain toxic effects. However, its limited solubility and bioavailability pose challenges for its effectiveness, for which chitosan-conjugated luteolin gold nanoparticles (CH-LuAuNPs) were synthesized. Interestingly, where FMT from arsenic-treated mice to healthy mice showed deleterious effects in the transplanted mice, FMT from arsenic-treated mice co-administered with CH-LuAuNP attenuated As-FMT-mediated disruption of the gut-brain axis. This study highlighted the critical contribution of healthy gut microbiota in preserving neurobehavioural physiology, as well as underscored the potential therapeutic benefits of luteolin nanoparticles in ameliorating arsenic-induced gut dysbiosis and consequent mental disorders.}, } @article {pmid40287572, year = {2025}, author = {Zou, T and Tang, X and Wang, H and Shang, X and Liang, X and Ma, X}, title = {Nanocrystalline cellulose-geniposide complex enhances gut-brain axis modulation for depression treatment.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {667}, pmid = {40287572}, issn = {2399-3642}, mesh = {Animals ; *Cellulose/chemistry/pharmacology ; Mice ; *Depression/drug therapy ; *Iridoids/pharmacology/chemistry ; *Nanoparticles/chemistry ; Gastrointestinal Microbiome/drug effects ; *Antidepressive Agents/pharmacology ; Male ; Fecal Microbiota Transplantation ; *Brain/drug effects/metabolism ; Mice, Inbred C57BL ; *Brain-Gut Axis/drug effects ; Disease Models, Animal ; }, abstract = {Depression, a major global health issue, is closely associated with imbalances in gut microbiota and altered intestinal functions. This study investigates the antidepressant potential of a composite of Geniposide (GP) and Nanocrystalline Cellulose (NCC), focusing on its effects on the gut-brain axis. Utilizing network pharmacology, GP was identified as a key compound targeting the BCL2 gene in depression management. Experimental approaches, including a chronic unpredictable mild stress (CUMS) model in mice, cellular assays, and fecal microbiota transplantation (FMT), were used to evaluate the composite's effectiveness. Results indicate that GP activates the adenosine monophosphate-activated protein kinase (AMPK) pathway by upregulating BCL2, enhancing intestinal barrier integrity, and balancing gut flora. These mechanisms contribute to its positive effects on hippocampal function and depressive-like behaviors in mice, suggesting that the GP-NCC composite could be a promising avenue for developing depression therapies that target gut health.}, } @article {pmid40286751, year = {2025}, author = {Ji, H and Dong, Z and Yang, Y and Cui, W and Han, J and Hu, Y and Chen, H and Qiao, C and Li, Q and Li, H and Wu, S}, title = {Neixiao-ruanmai decoction No 2 improves carotid atherosclerosis by modulating gut microbiota and inhibiting TLR4/NF-κB pathway activation.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {142}, number = {}, pages = {156775}, doi = {10.1016/j.phymed.2025.156775}, pmid = {40286751}, issn = {1618-095X}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Toll-Like Receptor 4/metabolism ; *NF-kappa B/metabolism ; Male ; Humans ; *Carotid Artery Diseases/drug therapy ; Signal Transduction/drug effects ; Female ; Middle Aged ; Mice ; Aged ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Carotid atherosclerosis(CAs) plaques are challenging to reverse. Neixiao-Ruanmai Decoction No 2(NXRMT No 2), a Traditional Chinese Medicine (TCM) decoction, has shown potential in treating CAs. However, while preliminary clinical trials have confirmed the efficacy of NXRMT No 2 in improving CAs, the comparative effectiveness of long-term versus short-term treatment courses remains unclear, and the underlying mechanisms of this decoction are not yet fully understood.

METHODS: We conducted clinical trials, animal studies, 16S rRNA sequencing, metabolomics and fecal microbiota transplantation.

RESULT: Clinical research results indicate that NXRMT No 2(24 weeks of treatment) reduced total plaque area by 22.02%, maximum plaque thickness by 7.91%, and maximum plaque area by 21.29%. NXRMT No 2 improves patients'serum inflammatory levels, with a 24-week treatment course demonstrated superior efficacy compared to the 12-week treatment. Animal experiments demonstrated that NXRMT No 2 improved CAs progression, modulated the gut microbiota, inhibited the intestinal Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway and activated the expression of intestinal tight junction proteins.

CONCLUSION: NXRMT No 2 significantly attenuates CAs progression, with its primary mechanism likely related to modulating the gut microbiota to counteract the TLR4/NF-κB pathway and protect the intestinal barrier. This study provides evidence-based support for the use of NXRMT No 2 in treating CAs, offers guidance on optimal treatment duration for patients, and contributes to the development of traditional Chinese medicine formulations that improve CAs by modulating the gut microbiota-a significant advance in the prevention and treatment of CAs.}, } @article {pmid40285477, year = {2025}, author = {Hansen, SH and Maseng, MG and Grännö, O and Vestergaard, MV and Bang, C and Olsen, BC and Lund, C and Olbjørn, C and Løvlund, EE and Vikskjold, FB and Huppertz-Hauss, G and Perminow, G and Yassin, H and Valeur, J and Aass Holten, KI and Henriksen, M and Bengtson, MB and Ricanek, P and Opheim, R and Boyar, R and Torp, R and Frigstad, SO and Aabrekk, TB and Detlie, TE and Kristensen, VA and Strande, V and Hovde, Ø and Asak, Ø and Jess, T and Franke, A and Halfvarsson, J and Høivik, ML and Hov, JR}, title = {Fecal Microbiome Reflects Disease State and Prognosis in Inflammatory Bowel Disease in an Adult Population-Based Inception Cohort.}, journal = {Inflammatory bowel diseases}, volume = {31}, number = {8}, pages = {2066-2080}, doi = {10.1093/ibd/izaf060}, pmid = {40285477}, issn = {1536-4844}, support = {//Pfizer/ ; //Tillotts Pharma/ ; //Dam Foundation/ ; //Norwegian South-Eastern Health Authorities/ ; 2020066//Regional Health Authorities South-Eastern Norway/ ; 327634//Research Council of Norway/ ; //Bio-Me AS/ ; //DFG Excellence Cluster 2167/ ; //DFG Research Unit/ ; DNRF148//National Research Foundation/ ; }, abstract = {INTRODUCTION: We aimed to determine the diagnostic and prognostic potential of baseline microbiome profiling in inflammatory bowel disease (IBD).

METHODS: Participants with ulcerative colitis (UC), Crohn's disease (CD), suspected IBD, and non-IBD symptomatic controls were included in the prospective population-based cohort Inflammatory Bowel Disease in South-Eastern Norway III (third iteration) based on suspicion of IBD. The participants donated fecal samples that were analyzed with 16S rRNA sequencing. Disease course severity was evaluated at the 1-year follow-up. A stringent statistical consensus approach for differential abundance analysis with 3 different tools was applied, together with machine learning modeling.

RESULTS: A total of 1404 individuals were included, where n = 1229 samples from adults were used in the main analyses (n = 658 UC, n = 324 CD, n = 36 IBD-U, n = 67 suspected IBD, and n = 144 non-IBD symptomatic controls). Microbiome profiles were compared with biochemical markers in machine learning models to differentiate IBD from non-IBD symptomatic controls (area under the receiver operating curve [AUC] 0.75-0.79). For UC vs controls, integrating microbiome data with biochemical markers like fecal calprotectin mildly improved classification (AUC 0.83 to 0.86, P < .0001). Extensive differences in microbiome composition between UC and CD were identified, which could be quantified as an index of differentially abundant genera. This index was validated across published datasets from 3 continents. The UC-CD index discriminated between ileal and colonic CD (linear regression, P = .008) and between colonic CD and UC (P = .005), suggesting a location-dependent gradient. Microbiome profiles outperformed biochemical markers in predicting a severe disease course in UC (AUC 0.72 vs 0.65, P < .0001), even in those with a mild disease at baseline (AUC 0.66 vs 0.59, P < .0001).

CONCLUSIONS: Fecal microbiome profiling at baseline held limited potential to diagnose IBD from non-IBD compared with standard-of-care. However, microbiome shows promise for predicting future disease courses in UC.}, } @article {pmid40284630, year = {2025}, author = {Zhang, Y and Wang, L and Peng, L}, title = {The Role of Intestinal Fungi in the Pathogenesis and Treatment of Ulcerative Colitis.}, journal = {Microorganisms}, volume = {13}, number = {4}, pages = {}, pmid = {40284630}, issn = {2076-2607}, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease closely associated with dysbiosis of the gut microbiome, encompassing not only bacterial communities but also fungal populations. Despite the growing recognition of the gut microbiome's role in UC pathogenesis, the contribution of intestinal fungi has only recently garnered significant attention. In this review, we comprehensively examine the characteristics of intestinal fungi in both healthy individuals and UC patients, elucidating their role in disease pathogenesis and their interactions with bacterial communities. Additionally, we explore the impact of intestinal fungi on disease severity and therapeutic responses in UC. Furthermore, we evaluate the therapeutic potential of antifungal agents, probiotics, and fecal microbiota transplantation (FMT) in UC management, emphasizing the critical role of fungi in these treatment modalities. Future research should prioritize elucidating the multifunctional roles of fungi in UC pathogenesis and their implications for treatment strategies. Moreover, the identification of fungal biomarkers associated with FMT efficacy could pave the way for precision medicine approaches in FMT, offering novel insights into personalized therapeutic interventions for UC.}, } @article {pmid40284188, year = {2025}, author = {Bonomo, MG and D'Angelo, S and Picerno, V and Carriero, A and Salzano, G}, title = {Recent Advances in Gut Microbiota in Psoriatic Arthritis.}, journal = {Nutrients}, volume = {17}, number = {8}, pages = {}, pmid = {40284188}, issn = {2072-6643}, mesh = {Humans ; *Arthritis, Psoriatic/microbiology/therapy/immunology ; *Gastrointestinal Microbiome ; Dysbiosis/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by joint inflammation and skin lesions. Recent research has underscored the critical role of gut microbiota-comprising bacteria, fungi, viruses, and archaea-in the pathogenesis and progression of PsA. This narrative review synthesizes the latest findings on the influence of gut microbiota on PsA, focusing on mechanisms such as immune modulation, microbial dysbiosis, the gut-joint axis, and its impact on treatment. Advances in high-throughput sequencing and metagenomics have revealed distinct microbial profiles associated with PsA. Studies show that individuals with PsA have a unique gut microbiota composition, differing significantly from healthy controls. Alterations in the abundance of specific bacterial taxa, including a decrease in beneficial bacteria and an increase in potentially pathogenic microbes, contribute to systemic inflammation by affecting the intestinal barrier and promoting immune responses. This review explores the impact of various factors on gut microbiota composition, including age, hygiene, comorbidities, and medication use. Additionally, it highlights the role of diet, probiotics, and fecal microbiota transplantation as promising strategies to modulate gut microbiota and alleviate PsA symptoms. The gut-skin-joint axis concept illustrates how gut microbiota influences not only gastrointestinal health but also skin and joint inflammation. Understanding the complex interplay between gut microbiota and PsA could lead to novel, microbiome-based therapeutic approaches. These insights offer hope for improved patient outcomes through targeted manipulation of the gut microbiota, enhancing both diagnosis and treatment strategies for PsA.}, } @article {pmid40283508, year = {2025}, author = {Boicean, A and Ichim, C and Sasu, SM and Todor, SB}, title = {Key Insights into Gut Alterations in Metabolic Syndrome.}, journal = {Journal of clinical medicine}, volume = {14}, number = {8}, pages = {}, pmid = {40283508}, issn = {2077-0383}, abstract = {Over time, extensive research has underscored the pivotal role of gut microbiota in the onset and progression of various diseases, with a particular focus on fecal microbiota transplantation (FMT) as a potential therapeutic approach. The practice of transferring fecal matter from a healthy donor to a patient provides valuable insights into how alterations in gut microbiota can impact disease development and how rectifying dysbiosis may offer therapeutic benefits. Re-establishing a balanced symbiotic relationship in the gastrointestinal tract has shown positive results in managing both intestinal and systemic conditions. Currently, one of the most pressing global health issues is metabolic syndrome-a cluster of conditions that includes insulin resistance, lipid imbalances, central obesity and hypertension. In this context, FMT has emerged as a promising strategy for addressing key components of metabolic syndrome, such as improving insulin sensitivity, body weight and lipid profiles. However, further well-structured studies are needed to refine treatment protocols and establish the long-term safety and efficacy of this intervention.}, } @article {pmid40283148, year = {2025}, author = {Marano, G and Rossi, S and Sfratta, G and Traversi, G and Lisci, FM and Anesini, MB and Pola, R and Gasbarrini, A and Gaetani, E and Mazza, M}, title = {Gut Microbiota: A New Challenge in Mood Disorder Research.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {4}, pages = {}, pmid = {40283148}, issn = {2075-1729}, abstract = {The gut microbiome has emerged as a novel and intriguing focus in mood disorder research. Emerging evidence demonstrates the significant role of the gut microbiome in influencing mental health, suggesting a bidirectional communication between the gut and the brain. This review examines the latest findings on the gut-microbiota-brain axis and elucidates how alterations in gut microbiota composition can influence this axis, leading to changes in brain function and behavior. Although dietary interventions, prebiotics, probiotics, and fecal microbiota transplantation have yielded encouraging results, significant advances are needed to establish next-generation approaches that precisely target the neurobiological mechanisms of mood disorders. Future research must focus on developing personalized treatments, facilitated by innovative therapies and technological progress, which account for individual variables such as age, sex, drug history, and lifestyle. Highlighting the potential therapeutic implications of targeting the gut microbiota, this review emphasizes the importance of integrating microbiota research into psychiatric studies to develop more effective and personalized treatment strategies for mood disorders.}, } @article {pmid40282300, year = {2025}, author = {Nemati, MH and Yazdanpanah, E and Kazemi, R and Orooji, N and Dadfar, S and Oksenych, V and Haghmorad, D}, title = {Microbiota-Driven Mechanisms in Multiple Sclerosis: Pathogenesis, Therapeutic Strategies, and Biomarker Potential.}, journal = {Biology}, volume = {14}, number = {4}, pages = {}, pmid = {40282300}, issn = {2079-7737}, abstract = {Multiple sclerosis (MS) is a well-known, chronic autoimmune disorder of the central nervous system (CNS) involving demyelination and neurodegeneration. Research previously conducted in the area of the gut microbiome has highlighted it as a critical contributor to MS pathogenesis. Changes in the commensal microbiota, or dysbiosis, have been shown to affect immune homeostasis, leading to elevated levels of pro-inflammatory cytokines and disruption of the gut-brain axis. In this review, we provide a comprehensive overview of interactions between the gut microbiota and MS, especially focusing on the immunomodulatory actions of microbiota, such as influencing T-cell balance and control of metabolites, e.g., short-chain fatty acids. Various microbial taxa (e.g., Prevotella and Faecalibacterium) were suggested to lay protective roles, whereas Akkermansia muciniphila was associated with disease aggravation. Interventions focusing on microbiota, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary therapies to normalize gut microbial homeostasis, suppress inflammation and are proven to improve clinical benefits in MS patients. Alterations in gut microbiota represent opportunities for identifying biomarkers for early diagnosis, disease progression and treatment response monitoring. Further studies need to be conducted to potentially address the interplay between genetic predispositions, environmental cues, and microbiota composition to get the precise mechanisms of the gut-brain axis in MS. In conclusion, the gut microbiota plays a central role in MS pathogenesis and offers potential for novel therapeutic approaches, providing a promising avenue for improving clinical outcomes in MS management.}, } @article {pmid40281872, year = {2025}, author = {Dipasquale, V and Romano, C}, title = {New Therapeutic Challenges in Pediatric Gastroenterology: A Narrative Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {8}, pages = {}, pmid = {40281872}, issn = {2227-9032}, abstract = {Pediatric gastroenterology is entering a pivotal phase marked by significant challenges and emerging opportunities in treating conditions like celiac disease (CeD), eosinophilic esophagitis (EoE), inflammatory bowel disease (IBD), and autoimmune hepatitis (AIH) pose significant clinical hurdles, but new therapeutic avenues are emerging. Advances in precision medicine, particularly proteomics, are reshaping care by tailoring treatments to individual patient characteristics. For CeD, therapies like gluten-degrading enzymes (latiglutenase, Kuma030) and zonulin inhibitors (larazotide acetate) show promise, though clinical outcomes are inconsistent. Immunotherapy and microbiota modulation, including probiotics and fecal microbiota transplantation (FMT), are also under exploration, with potential benefits in symptom management. Transglutaminase 2 inhibitors like ZED-1227 could help prevent gluten-induced damage. Monoclonal antibodies targeting immune pathways, such as AMG 714 and larazotide acetate, require further validation in pediatric populations. In EoE, biologics like dupilumab, cendakimab, dectrekumab (IL-13 inhibitors), and mepolizumab, reslizumab, and benralizumab (IL-5/IL-5R inhibitors) show varying efficacy, while thymic stromal lymphopoietin (TSLP) inhibitors like tezepelumab are also being investigated. These therapies require more pediatric-specific research to optimize their use. For IBD, biologics like vedolizumab, ustekinumab, and risankizumab, as well as small molecules like tofacitinib, etrasimod, and upadacitinib, are emerging treatments. New medications for individuals with refractory or steroid-dependent AIH have been explored. Personalized therapy, integrating precision medicine, therapeutic drug monitoring, and lifestyle changes, is increasingly guiding pediatric IBD management. This narrative review explores recent breakthroughs in treating CeD, EoE, IBD, and AIH, with a focus on pediatric studies when available, and discusses the growing role of proteomics in advancing personalized gastroenterological care.}, } @article {pmid40280962, year = {2025}, author = {Wissel, EF and Chien, HY and Wei, KH and Lee, YC and Ullah, K and Hsieh, PCH}, title = {Microbial metabolites associated in stool and left ventricle of heart failure patients revealed by meta-analysis.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {14576}, pmid = {40280962}, issn = {2045-2322}, support = {110-2320-B-001-023-MY3//National Science and Technology Council/ ; 110-2320-B-001-023-MY3//National Science and Technology Council/ ; 110-2320-B-001-023-MY3//National Science and Technology Council/ ; 110-2320-B-001-023-MY3//National Science and Technology Council/ ; 110-2320-B-001-023-MY3//National Science and Technology Council/ ; 110-2320-B-001-023-MY3//National Science and Technology Council/ ; NHRI-EX113-11203SI//National Health Research Institutes/ ; NHRI-EX113-11203SI//National Health Research Institutes/ ; NHRI-EX113-11203SI//National Health Research Institutes/ ; NHRI-EX113-11203SI//National Health Research Institutes/ ; NHRI-EX113-11203SI//National Health Research Institutes/ ; NHRI-EX113-11203SI//National Health Research Institutes/ ; }, mesh = {Humans ; *Heart Failure/microbiology/metabolism ; *Feces/microbiology ; *Heart Ventricles/metabolism/microbiology ; Metabolomics/methods ; *Gastrointestinal Microbiome ; Metabolome ; }, abstract = {Heart Failure (HF) impacts approximately 64 million people globally. While overall incidence of HF is relatively stable across countries, the overall number of HF patients is increasing due to aging populations. Many articles examine the microbiome in HF, however, studies from humans have not been analyzed systematically. The aim of this meta-analysis is to bridge this gap by analyzing previously published data on human HF patients with untargeted metabolomics to understand whether microbially-mediated metabolites are consistently important for HF status. A systematic survey of the literature identified 708 articles discussing HF, the microbiome, and metabolomics. Of these, 82 were primary studies of HF patients, 61 studied human adults, 23 included an untargeted metabolomics measure, and 3 studies had data that was usable and publicly accessible. These studies include a GCMS study from stool, NMR of saliva and exhaled breath condensate, and LCMS from left ventricle of HF patients undergoing transplantation and unused donor hearts. Significant differences were observed from PCA between HF and controls for stool and left ventricle, but not saliva or EBC samples. OPLS-DA was conducted for stool and ventricle samples, and further revealed significant group differences. Univariate testing with FDR correction revealed 8 significant microbially-relevant metabolites (p < 0.005 after correction), most notably asparagine from left ventricle and 2-methylbutyryl carnitine from stool. Though there is much discussion of the microbiome in health outcomes in HF, there is limited research from human populations. Some microbial co-metabolites from both stool and heart were significantly associated with HF.}, } @article {pmid40280130, year = {2025}, author = {Wellens, J and Vissers, E and Dumoulin, A and Hoekx, S and Vanderstappen, J and Verbeke, J and Vangoitsenhoven, R and Derrien, M and Verstockt, B and Ferrante, M and Matthys, C and Raes, J and Verbeke, K and Vermeire, S and Sabino, J}, title = {Cooking methods affect advanced glycation end products and lipid profiles: A randomized cross-over study in healthy subjects.}, journal = {Cell reports. Medicine}, volume = {6}, number = {5}, pages = {102091}, pmid = {40280130}, issn = {2666-3791}, mesh = {Humans ; *Glycation End Products, Advanced/blood ; *Cooking/methods ; Cross-Over Studies ; Male ; Female ; Adult ; Healthy Volunteers ; *Lipids/blood ; Middle Aged ; }, abstract = {Thermal treatments used in ultra-processed foods (UPFs) lead to advanced glycation end products (AGEs). UPFs and serum AGEs are associated with cardiometabolic disease. We explore differential cooking methods as a mechanistic link between UPFs and detrimental health outcomes through a randomized cross-over cooking method trial in healthy subjects using identical ingredients and a deep profiling analysis. We show that low-AGE-generating cooking methods such as boiling and steaming decrease serum AGEs, improve lipid profiles, and increase serum protein 4E-BP1. In contrast, high-AGE-generating cooking methods such as grilling and baking increase fecal butyrate. In sum, this suggests that low-AGE-generating cooking methods should be considered in cardiovascular risk prevention. Since current dietary guidelines focus on ingredients, but not cooking methods, our results suggest that culinary techniques should be considered as an important factor in cardiometabolic preventive strategies and future dietary trial design. This study was registered at ClinicalTrials.gov (NCT06547190).}, } @article {pmid40280127, year = {2025}, author = {Cai, W and Haddad, M and Haddad, R and Kesten, I and Hoffman, T and Laan, R and Westfall, S and Defaye, M and Abdullah, NS and Wong, C and Brown, N and Tansley, S and Lister, KC and Hooshmandi, M and Wang, F and Lorenzo, LE and Hovhannisyan, V and Ho-Tieng, D and Kumar, V and Sharif, B and Thurairajah, B and Fan, J and Sahar, T and Clayton, C and Wu, N and Zhang, J and Bar-Yoseph, H and Pitashny, M and Krock, E and Mogil, JS and Prager-Khoutorsky, M and Séguéla, P and Altier, C and King, IL and De Koninck, Y and Brereton, NJB and Gonzalez, E and Shir, Y and Minerbi, A and Khoutorsky, A}, title = {The gut microbiota promotes pain in fibromyalgia.}, journal = {Neuron}, volume = {113}, number = {13}, pages = {2161-2175.e13}, doi = {10.1016/j.neuron.2025.03.032}, pmid = {40280127}, issn = {1097-4199}, mesh = {*Fibromyalgia/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; Humans ; Female ; Animals ; Mice ; *Fecal Microbiota Transplantation/methods ; Middle Aged ; Adult ; Quality of Life ; *Chronic Pain/microbiology ; Mice, Inbred C57BL ; *Pain/microbiology ; }, abstract = {Fibromyalgia is a prevalent syndrome characterized by widespread pain in the absence of evident tissue injury or pathology, making it one of the most mysterious chronic pain conditions. The composition of the gut microbiota in individuals with fibromyalgia differs from that of healthy controls, but its functional role in the syndrome is unknown. Here, we show that fecal microbiota transplantation from fibromyalgia patients, but not from healthy controls, into germ-free mice induces pain and numerous molecular phenotypes that parallel known changes in fibromyalgia patients, including immune activation and metabolomic profile alterations. Replacing the fibromyalgia microbiota with a healthy microbiota substantially alleviated pain in mice. An open-label trial in women with fibromyalgia (Registry MOH_2021-11-04_010374) showed that transplantation of a healthy microbiota is associated with reduced pain and improved quality of life. We conclude that altered gut microbiota has a role in fibromyalgia pain, highlighting it as a promising target for therapeutic interventions.}, } @article {pmid40279964, year = {2025}, author = {Zheng, Z and Du, Y and Jiang, H and Shi, Z and Zhou, H and Jiao, L and Liu, P and Gong, Y}, title = {KAJF alleviated colorectal cancer liver metastasis by reshaping the gut microbiota and inhibiting M2-like macrophage polarization.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {142}, number = {}, pages = {156766}, doi = {10.1016/j.phymed.2025.156766}, pmid = {40279964}, issn = {1618-095X}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Colorectal Neoplasms/pathology/drug therapy ; *Liver Neoplasms/secondary/drug therapy ; Mice ; *Drugs, Chinese Herbal/pharmacology ; *Macrophages/drug effects ; Male ; Macrophage Activation/drug effects ; Fecal Microbiota Transplantation ; Molecular Docking Simulation ; Cell Line, Tumor ; }, abstract = {BACKGROUND: Colorectal cancer liver metastasis (CRLM) represents one of the most severe complications of colorectal cancer (CRC), often associated with unfavorable prognosis. The herbal formulation Kang-Ai-Jing-Fang (KAJF) has been employed clinically against CRC for several decades, although its precise mechanism of action remains elusive.

PURPOSE: This study investigates the anti-metastatic potential of KAJF in CRLM, focusing on its modulatory effects on gut microbiota and inhibition of M2-like macrophage activation.

METHODS: KAJF was administered orally to CRLM model mice established through intrasplenic injection of murine CRC cells. To elucidate the role of gut microbiota reshaped by KAJF, fecal microbiota transplantation (FMT) was utilized to assess its impact on CRLM inhibition. Core targets and active compounds were identified through network pharmacology and molecular docking. To characterize microbiota composition, metabolite profiles, and gene expression variations, 16S rRNA sequencing, untargeted liquid chromatography-mass spectrometry (LC-MS/MS) metabolomics, and transcriptomics analyses were performed.

RESULTS: KAJF demonstrated significant inhibitory effects on CRLM and ameliorated gut microbiota dysbiosis by enhancing the abundance of butyrate-producing bacteria (Lactobacillus, Bacteroides, Bifidobacterium). The therapeutic efficacy of KAJF-induced bacterial alterations in delaying CRLM and promoting butyrate-producing microbiota enrichment was further substantiated by FMT. Network pharmacology identified active ingredients in KAJF, including asperulosidic acid, polyphyllin II, ganoderenic acid B, calycosin, and ganoderic acid C, which exhibit substantial interactions with TLR4, PPARγ, SIRT1, PTGS2, and TNF. Molecular dynamics simulations and surface plasmon resonance (SPR) analysis demonstrated that ganoderic acid C2 exhibits a strong binding affinity for PPARγ. Moreover, KAJF administration led to a marked reduction in F4/80[+] CD206[+] macrophages and their associated cytokines (CCL17, CCL22, IL10, IL4, TGF), accompanied by a decrease in CD4[+] T cells and myeloid-derived suppressor cells (MDSCs), while increasing CD8[+] T cell populations.

CONCLUSIONS: This study demonstrates that KAJF mitigates CRLM, primarily through the regulation of gut microbiota and microbial metabolites, alongside inhibition of M2-like macrophage polarization. By integrating metabolomics, transcriptomics, and network pharmacology, this research elucidates the molecular mechanisms underpinning KAJF's therapeutic effects against CRLM, offering a promising approach for clinical intervention.}, } @article {pmid40279942, year = {2025}, author = {Zhang, S and Qian, Y and Li, N and Zhu, Q and Zhang, S and Wen, P and Xiao, Y and Yan, C and Lin, Z and Zhong, J and Ma, J and Wu, X and Zhuang, G and Zhang, K}, title = {Specific MSI2 deletion maintains intestinal barrier integrity by down-regulating ILC3s-derived IL-17 a in mice with colitis.}, journal = {International immunopharmacology}, volume = {156}, number = {}, pages = {114717}, doi = {10.1016/j.intimp.2025.114717}, pmid = {40279942}, issn = {1878-1705}, mesh = {Animals ; *Interleukin-17/metabolism/immunology/genetics ; Dextran Sulfate ; *Intestinal Mucosa/immunology/pathology/metabolism ; Mice ; Disease Models, Animal ; *RNA-Binding Proteins/genetics ; Down-Regulation ; *Colitis, Ulcerative/immunology/chemically induced/genetics/pathology ; Mice, Inbred C57BL ; *Colon/pathology/immunology ; *Lymphocytes/immunology ; Mice, Knockout ; *Colitis/immunology/chemically induced ; Male ; Immunity, Innate ; }, abstract = {BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease with an unknown cause. Previous studies have shown that Group 3 innate lymphoid cells (ILC3s) are crucial for maintaining intestinal mucosal immune homeostasis by producing key cytokines such as IL-22 and IL-17 A. While the RNA-binding protein Musashi-2 (MSI2) is recognized as essential for promoting intestinal epithelial regeneration post-injury, its impact on immune regulation remains unclear. Therefore, we aim to investigate the protective mechanisms associated with ILC3s-specific MSI2 deletion in a mouse model of ulcerative colitis.

METHODS: Dextran sulfate sodium (DSS) was used to induce a mouse colitis model. Colitis severity was evaluated through weight loss, diarrhea, fecal traits, colon length, and pathological scoring. Transcriptome sequencing was utilized to identify differentially expressed genes in colon tissues. Flow cytometry was employed to measure the quantity and functionality of ILC3s. Western blot was conducted to analyze protein expression, while real-time polymerase chain reaction and enzyme-linked immunosorbent assay were employed to quantify inflammatory factors. Additionally, immunofluorescence, AB-PAS staining, and immunohistochemistry were employed to evaluate the integrity of the intestinal barrier.

RESULTS: Following DSS treatment, colon damage was milder in Msi2[∆Rorc] mice than in Msi2[fl/fl] mice. Transcriptomic analysis revealed the down-regulation of cytokines and pro-inflammatory factors in the colon tissue of Msi2[∆Rorc] mice. Flow cytometry showed that specific deletion of MSI2 reduced the infiltration of ILC3s in the intestinal lamina propria of Msi2[∆Rorc] mice and decreased IL-17 A production. The reduction of IL-17 A-mediated immune responses lessened inflammatory damage to the intestinal barrier, thereby reducing colitis severity.

CONCLUSIONS: Specific deletion of MSI2 alleviates DSS-induced colitis in mice by reducing ILC3s infiltration and IL-17 A secretion in the lamina propria of the colon. This decrease in inflammatory mediators and cell infiltration dampens the inflammatory response in the intestinal mucosa, helping to maintain the integrity of the intestinal barrier in mice with colitis. These findings enhance our understanding of UC pathogenesis and offer novel avenues for clinical diagnosis and treatment.}, } @article {pmid40278398, year = {2025}, author = {Zheng, F and Yang, Y and Lu, G and Tan, JS and Mageswary, U and Zhan, Y and Ayad, ME and Lee, YY and Xie, D}, title = {Metabolomics Insights into Gut Microbiota and Functional Constipation.}, journal = {Metabolites}, volume = {15}, number = {4}, pages = {}, pmid = {40278398}, issn = {2218-1989}, support = {2024ZYD0149//Sichuan Science and Technology Program/ ; TB2024017//Special Research Foundation for the Postdoctoral Program of Sichuan Province/ ; 2024SZY004, 2024SZY016//Key Research and Development Project of Deyang Science and Technology Bureau/ ; 2022067//Chengdu Medical Research Project/ ; 2024JDKPO1117//Sichuan Science and Technology Program/ ; FHS202503//Projects of Deyang People's Hospital/ ; }, abstract = {Background: The composition and metabolic activity of the gut microbiota play a crucial role in various health conditions, including the occurrence and development of chronic constipation. Recent metabolomic advances reveal that gut microbiota-derived metabolites-such as SCFAs, bile acids, neurotransmitters, and microbial gases-play critical roles in regulating intestinal function. Methods: We systematically analyzed the current literature on microbial metabolomics in chronic constipation. This review consolidates findings from high-throughput metabolomic techniques (GC-MS, LC-MS, NMR) comparing metabolic profiles of constipated patients with healthy individuals. It also examines diagnostic improvements and personalized treatments, including fecal microbiota transplantation and neuromodulation, guided by these metabolomic insights. Results: This review shows that reduced SCFA levels impair intestinal motility and promote inflammation. An altered bile acid metabolism-with decreased secondary bile acids like deoxycholic acid-disrupts receptor-mediated signaling, further affecting motility. Additionally, imbalances in amino acid metabolism and neurotransmitter production contribute to neuromuscular dysfunction, while variations in microbial gas production (e.g., methane vs. hydrogen) further modulate gut transit. Conclusions: Integrating metabolomics with gut microbiota research clarifies how specific microbial metabolites regulate gut function. These insights offer promising directions for precision diagnostics and targeted therapies to restore microbial balance and improve intestinal motility.}, } @article {pmid40274530, year = {2025}, author = {Ji, ZH and Xie, WY and Wu, HY and Yuan, B}, title = {Coix Seed Polysaccharide Mitigates Ulcerative Colitis in Mice through the Modulation of Gut Microbiota and Improvement of Intestinal Metabolism Balance.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {18}, pages = {11067-11079}, doi = {10.1021/acs.jafc.5c02458}, pmid = {40274530}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis, Ulcerative/microbiology/metabolism/drug therapy ; Mice ; *Polysaccharides/administration & dosage ; Seeds/chemistry ; Male ; Mice, Inbred C57BL ; *Coix/chemistry ; Humans ; Bacteria/classification/genetics/isolation & purification/drug effects ; Dextran Sulfate/adverse effects ; Disease Models, Animal ; *Intestines/microbiology/drug effects/metabolism ; *Drugs, Chinese Herbal/administration & dosage ; Colon/metabolism/drug effects/microbiology ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a rising incidence globally, whereas existing treatments exhibit significant limitations. Coix seed polysaccharide (CSP), a component of traditional Chinese medicine known for its immunomodulatory and antioxidant properties, has not been thoroughly investigated for its role in UC. In this study, CSP was prepared via water extraction and ethanol precipitation, and its protective effects and mechanisms were evaluated using a dextran sulfate sodium salt (DSS)-induced UC mouse model. The results demonstrated that CSP significantly ameliorated DSS-induced UC symptoms, including weight loss, an elevated Disease Activity Index, colon shortening, increased levels of inflammatory cytokines, and intestinal barrier damage. Moreover, CSP reshaped the DSS-induced gut microbiota dysbiosis by increasing gut microbial diversity and regulating the abundance of specific genera, such as increasing Anaerotruncus. Metabolomic analysis revealed that CSP significantly modulated the levels of 116 metabolites, particularly enhancing the beneficial metabolite 3-hydroxybutyrate. Importantly, the preventive effect of CSP on UC was dependent on the gut microbiota and could be transferred via fecal microbiota transplantation. This study demonstrates that CSP, a microecology-regulating polysaccharide, effectively modulates gut microbiota and alleviates symptoms of UC. These findings support the potential of CSP as a dietary supplement for UC prevention and underscore its value in the development of medicinal foods and functional food applications.}, } @article {pmid40274437, year = {2025}, author = {Chang, Z and Zhu, Y and Wang, P and Du, L and Wu, M and Wang, X and Kong, C and Huang, D and Xie, R and Ji, G and Wang, C and Cheng, L and Yan, X and Wei, Q and Qin, H}, title = {Multi-omic analyses of the development of obesity-related depression linked to the gut microbe Anaerotruncus colihominis and its metabolite glutamate.}, journal = {Science bulletin}, volume = {70}, number = {11}, pages = {1822-1833}, doi = {10.1016/j.scib.2025.04.010}, pmid = {40274437}, issn = {2095-9281}, mesh = {*Gastrointestinal Microbiome/genetics ; Animals ; *Glutamic Acid/metabolism ; *Obesity/microbiology/complications/metabolism ; Mice ; Humans ; *Depression/microbiology/etiology/metabolism ; Male ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Female ; Colon/metabolism ; Feces/microbiology ; Multiomics ; }, abstract = {Emerging evidence implicates gut microbiota in the pathogenesis of obesity-related depression (OD); however, the underlying molecular mechanisms remain inadequately explored. This study compared the microbial and transcriptional profiles between patients with OD and healthy individuals. The results revealed an enrichment of Anaerotruncus colihominis (A. colihominis) and glutamate metabolism-related genes in the OD group. Fecal microbiota transplantation (FMT) from patients with OD induced weight gain, compromised barrier function, and intensified depression-like behaviors in high-fat diet (HFD) mice. Microbial analysis in the mice feces corroborated the clinical findings. Single-cell RNA sequencing highlighted the pivotal role of the Efnb2-Ephb2 interaction in cell communication among colon epithelial and hippocampal neuron subtypes in OD mice. Notably, A. colihominis correlated with glutamate levels in the OD mice and patients. It produced glutamate through a glutamic acid metabolism-related DNA sequence, verified in an engineered Escherichia coli MG1655 strain. Both A. colihominis and glutamate reduced barrier proteins in colon epithelial cells and modulated cognitive proteins in neurons. Finally, A. colihominis treatment induced the Efnb2-Ephb2 interaction, exacerbating depression-like behaviors in germ-free HFD mice. Collectively, these findings reveal that A. colihominis and glutamate are potential intervention targets for OD treatment.}, } @article {pmid40272913, year = {2025}, author = {Bohm, MS and Joseph, SC and Sipe, LM and Kim, M and Leathem, CT and Mims, TS and Willis, NB and Tanveer, UA and Elasy, JH and Grey, EW and Pye, ME and Mustafa, ZT and Harper, BA and McGrath, LG and Daria, D and Landvoigt Schmitt, B and Myers, JA and Pantoja Newman, P and Pence, BD and der Merwe, MV and Davis, MJ and Pierre, JF and Makowski, L}, title = {The gut microbiome enhances breast cancer immunotherapy following bariatric surgery.}, journal = {JCI insight}, volume = {10}, number = {11}, pages = {}, pmid = {40272913}, issn = {2379-3708}, support = {F32 CA250192/CA/NCI NIH HHS/United States ; R37 CA226969/CA/NCI NIH HHS/United States ; S10 OD032329/OD/NIH HHS/United States ; 75N93023D00005/AI/NIAID NIH HHS/United States ; 75N95020D00005/DA/NIDA NIH HHS/United States ; 75N99020D00005/OF/ORFDO NIH HHS/United States ; 75N92020D00005/HL/NHLBI NIH HHS/United States ; R01 CA253329/CA/NCI NIH HHS/United States ; R25 CA203650/CA/NCI NIH HHS/United States ; U01 CA272541/CA/NCI NIH HHS/United States ; 75N93022D00005/AI/NIAID NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome/immunology ; Animals ; *Bariatric Surgery ; Female ; Mice ; *Breast Neoplasms/therapy/immunology/microbiology ; Fecal Microbiota Transplantation ; Humans ; *Immunotherapy/methods ; Natural Killer T-Cells/immunology ; Tumor Microenvironment/immunology ; Amino Acids, Branched-Chain/metabolism ; Obesity/surgery ; Mice, Inbred C57BL ; }, abstract = {Bariatric surgery is associated with improved breast cancer (BC) outcomes, including greater immunotherapy effectiveness in a preclinical BC model. A potential mechanism of bariatric surgery-associated protection is the gut microbiota. Here, we demonstrate the dependency of improved immunotherapy response on the post-bariatric surgery gut microbiome via fecal microbiota transplantation (FMT). Response to αPD-1 immunotherapy was significantly improved following FMT from formerly obese bariatric surgery-treated mice. When stool from post-bariatric surgery patients was transplanted into recipient mice and compared to the patients' presurgery transplants, postsurgery microbes significantly reduced tumor burden and doubled immunotherapy effectiveness. Microbes impact tumor burden through microbially derived metabolites, including branched-chain amino acids (BCAAs). Circulating BCAAs correlated significantly with natural killer T (NKT) cell content in the tumor microenvironment in donor mice after bariatric surgery and FMT recipients of donor cecal content after bariatric surgery compared with obese controls. BCAA supplementation replicated improved αPD-1 effectiveness in 2 BC models, supporting the role of BCAAs in increased immunotherapy effectiveness after bariatric surgery. Ex vivo exposure increased primary NKT cell expression of antitumor cytokines, demonstrating direct activation of NKT cells by BCAAs. Together, the findings suggest that reinvigorating antitumor immunity may depend on bariatric surgery-associated microbially derived metabolites, namely BCAAs.}, } @article {pmid40272874, year = {2025}, author = {Ubsdell, D and Maddox, NL and Sheridan, R}, title = {Management of severe and fulminant Clostridioides difficile infection in adults.}, journal = {Journal of medical microbiology}, volume = {74}, number = {4}, pages = {}, pmid = {40272874}, issn = {1473-5644}, mesh = {Humans ; *Clostridium Infections/therapy/microbiology/drug therapy ; *Clostridioides difficile/drug effects ; *Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; Adult ; Metronidazole/therapeutic use ; }, abstract = {Clostridioides difficile (formerly known as Clostridium difficile) is a significant cause of healthcare-associated infection with symptoms ranging from diarrhoea and abdominal pain to pseudomembranous colitis and toxic megacolon. Severe disease can pose a significant morbidity and mortality risk and is to be considered a medical emergency. The emergence of a new C. difficile ribotype with an estimated mortality rate of 20% (ribotype 995) has prompted a re-review of the evidence and guidelines around managing severe C. difficile infections (CDI). International guidance on the management of CDI varies regarding first-line antibiotic choice. Metronidazole is no longer favoured as first line due to concerns around resistance, and vancomycin and fidaxomicin are now recommended as first line options. Antibiotic therapy should be used in conjunction with good supportive measures and early consideration of surgical management. Faecal microbiota transplant can be utilized in recurrent CDI and may be useful in severe disease. Severe CDI is a significant ongoing threat to public health, and further research into effective management is essential to ensure the best possible outcomes for patients.}, } @article {pmid40272189, year = {2025}, author = {Zhang, L and Wang, H and Zhao, L and Zhang, J and Sun, W and Chu, J and Zhao, H and Yang, C and Yan, S and Chen, X and Xu, D}, title = {Unraveling the interplay between mesenchymal stem cells, gut microbiota, and systemic sclerosis: therapeutic implications.}, journal = {Microbiology spectrum}, volume = {13}, number = {6}, pages = {e0157624}, pmid = {40272189}, issn = {2165-0497}, support = {82171790//National Natural Science Foundation of China/ ; 82201925//National Natural Science Foundation of China/ ; 32000075//National Natural Science Foundation of China/ ; ZR2024QC071//Natural Science Foundation of Shandong Province/ ; ZR2024MH079//Natural Science Foundation of Shandong Province/ ; ZR2022QH203//Natural Science Foundation of Shandong Province/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; *Scleroderma, Systemic/therapy/chemically induced/microbiology/pathology ; Animals ; *Mesenchymal Stem Cells/physiology/metabolism ; Mice ; Humans ; *Mesenchymal Stem Cell Transplantation ; Disease Models, Animal ; Bacteria/classification/genetics/isolation & purification/metabolism ; Bleomycin ; Mice, Inbred C57BL ; Feces/microbiology ; Female ; }, abstract = {UNLABELLED: Systemic sclerosis (SSc) is an autoimmune disease with progressive fibrotic disorders in multiple organs. Mesenchymal stem cells (MSCs) have shown great potential in treating SSc, but the exact regulatory mechanism is not fully understood. In this study, we used human umbilical cord-derived MSCs (hUC-MSCs) to treat SSc mice induced by bleomycin. The gut microbiota composition and predicted functions were analyzed using 2bRAD sequencing of fecal samples from control, SSc, and MSCs-treated mice. Treatment with MSCs improved the bleomycin-induced SSc mice, characterized by significantly reduced collagen deposition and dermal thickness. The gut microbiota of SSc mice exhibited lower species evenness and was clearly separated from the control mice based on beta diversity. MSC treatment led to a significant reduction of conditionally pathogenic bacteria enriched in SSc, including Akkermansia muciniphila and Parasutterella excrementihominis. Conversely, the relative abundance of butyrate-producing bacteria, such as Roseburia, Butyricicoccus porcorum, and Gemmiger formicilis, was notably increased in MSCs-treated SSc mice. Additionally, the functional analysis revealed that MSCs intervention effectively enhanced sulfur metabolism, tryptophan metabolism, citrate cycle, RNA polymerase, and beta-lactam resistance. In summary, the findings in the present study have suggested the close association between gut microbiota and metabolic dysbiosis in mice with SSc. The administration of MSCs has been shown to regulate the disrupted metabolic pathways in SSc mice, thus restoring the normal function of the gut microbiota. This study provides valuable insights into the specific gut microbiota and metabolic pathways involved in the efficacy of MSC treatment, thereby proposing a novel therapeutic strategy for SSc.

IMPORTANCE: Human umbilical cord-derived mesenchymal stem cells (HUC‑MSCs) demonstrate efficacy in alleviating skin thickening and collagen deposition in systemic sclerosis (SSc) mice, which also regulate the gut microbiota composition and function. Specifically, MSC intervention leads to a notable increase in butyrate-producing bacteria, a decrease in Akkermansia muciniphila and Parasutterella excrementihominis, and a reversal of the dysregulated microbial function in SSc mice. These findings underscore the potential significance of gut microbiota in the therapeutic effects of MSCs in SSc.}, } @article {pmid40272147, year = {2025}, author = {Dai, X and Cao, Y and Li, L and Gao, Y-X and Wang, J-X and Liu, Y-J and Ma, T-T and Zheng, J-M and Zhan, P-P and Shen, Z-Y}, title = {Gut microbiome and metabolome profiles in renal allograft rejection from multiomics integration.}, journal = {mSystems}, volume = {10}, number = {5}, pages = {e0162624}, pmid = {40272147}, issn = {2379-5077}, support = {82241219//National Natural Science Foundation of China/ ; 82127808//National Major Science and Technology Projects of China/ ; 81921004//National Natural Science Foundation of China/ ; NKTM2023005//Institute of Transplantation Medicine NanKai University/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Kidney Transplantation/adverse effects ; Female ; *Graft Rejection/metabolism/microbiology/diagnosis ; Male ; *Metabolome ; Adult ; Middle Aged ; Metabolomics/methods ; Feces/microbiology ; Multiomics ; }, abstract = {UNLABELLED: The gut microbiome and metabolome play crucial roles in renal allograft rejection progression. Integrated multiomics analyses may provide a comprehensive understanding of specific underlying mechanisms, which remain elusive. This study aimed to identify new approaches for clinical renal allograft rejection diagnosis and treatment. Thirty-five patients were divided into three groups: the rejection (n = 16), dysfunction (n = 7), and control (n = 12) groups. Metagenomic sequencing and nontargeted metabolomics were used to analyze stool and plasma samples. Significant microbiota, metabolites, and signaling pathways were identified. LASSO regression was used to construct a diagnostic model, and its diagnostic value was assessed via receiver operating characteristic curves. The microbiota composition and the related genes in the rejection group significantly differed from that in the dysfunction and control groups at the phylum, genus, and species levels (P < 0.001). The core species in the rejection group networks were Escherichia coli and Ruminococcus gnavus, while core species in the dysfunction group networks were Faecalibacterium prausnitzii and Bacteroides ovatus. The balance of specific microbial species was associated with kidney function in rejection patients. Spearman analysis revealed that specific differential species like Agathobaculum butyriciproducens and Gemmiger qucibialis were closely linked to the levels of serum 4-pyridoxic acid, 4-acetamidobutanoate, and fecal tryptamine from specific differential pathways. Finally, we constructed four clinical models to distinguish the rejection and dysfunction groups, and the model had excellent diagnostic performance. Altered gut microbiota may contribute to changes in metabolic pathway activity and metabolite abundance in rejection and dysfunction patients, which are strongly correlated with host immunological rejection. The diagnostic model, developed based on the gut microbiota and metabolites, has high clinical value for diagnosing renal rejection.

IMPORTANCE: This study aimed to screen new markers for non-invasive diagnosis by the gut microbiome and metabolome analysis, providing new insights into rejection mechanisms and identifying new approaches for clinical renal allograft rejection diagnosis.}, } @article {pmid40270478, year = {2025}, author = {Schoultz, I and Claesson, MJ and Dominguez-Bello, MG and Fåk Hållenius, F and Konturek, P and Korpela, K and Laursen, MF and Penders, J and Roager, H and Vatanen, T and Öhman, L and Jenmalm, MC}, title = {Gut microbiota development across the lifespan: Disease links and health-promoting interventions.}, journal = {Journal of internal medicine}, volume = {297}, number = {6}, pages = {560-583}, pmid = {40270478}, issn = {1365-2796}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Aging/physiology ; Infant ; Dysbiosis ; Probiotics/therapeutic use ; Prebiotics ; Child ; *Health Promotion ; Fecal Microbiota Transplantation ; Adult ; }, abstract = {The gut microbiota plays a pivotal role in human life and undergoes dynamic changes throughout the human lifespan, from infancy to old age. During our life, the gut microbiota influences health and disease across life stages. This review summarizes the discussions and presentations from the symposium "Gut microbiota development from infancy to old age" held in collaboration with the Journal of Internal Medicine. In early infancy, microbial colonization is shaped by factors such as mode of delivery, antibiotic exposure, and milk-feeding practices, laying the foundation for subsequent increased microbial diversity and maturation. Throughout childhood and adolescence, microbial maturation continues, influencing immune development and metabolic health. In adulthood, the gut microbiota reaches a relatively stable state, influenced by genetics, diet, and lifestyle. Notably, disruptions in gut microbiota composition have been implicated in various inflammatory diseases-including inflammatory bowel disease, Type 1 diabetes, and allergies. Furthermore, emerging evidence suggests a connection between gut dysbiosis and neurodegenerative disorders such as Alzheimer's disease. Understanding the role of the gut microbiota in disease pathogenesis across life stages provides insights into potential therapeutic interventions. Probiotics, prebiotics, and dietary modifications, as well as fecal microbiota transplantation, are being explored as promising strategies to promote a healthy gut microbiota and mitigate disease risks. This review focuses on the gut microbiota's role in infancy, adulthood, and aging, addressing its development, stability, and alterations linked to health and disease across these critical life stages. It outlines future research directions aimed at optimizing the gut microbiota composition to improve health.}, } @article {pmid40265594, year = {2025}, author = {Zhang, D and Zhang, Z and Liao, L and Dong, B and Xiong, X and Qin, X and Fan, X}, title = {Impact of fecal microbiota transplantation on lung function and gut microbiome in an ARDS rat model: A multi-omics analysis including 16S rRNA sequencing, metabolomics, and transcriptomics.}, journal = {International journal of immunopathology and pharmacology}, volume = {39}, number = {}, pages = {3946320251333982}, pmid = {40265594}, issn = {2058-7384}, mesh = {Animals ; *Gastrointestinal Microbiome ; Rats, Sprague-Dawley ; *Fecal Microbiota Transplantation/methods ; *Respiratory Distress Syndrome/therapy/microbiology/metabolism/physiopathology/genetics ; *Lung/metabolism/physiopathology/microbiology ; *RNA, Ribosomal, 16S/genetics ; Metabolomics/methods ; Disease Models, Animal ; Rats ; Male ; *Transcriptome ; Multiomics ; }, abstract = {OBJECTIVE: Acute respiratory distress syndrome (ARDS) is a severe pulmonary condition characterized by inflammation and lung damage, frequently resulting in poor clinical outcomes. Recent studies suggest that the gut-lung axis, mediated by gut microbiota, is critical in ARDS progression. This study investigates the therapeutic potential of fecal microbiota transplantation (FMT) in an ARDS rat model (n = 6).

INTRODUCTION: The pathogenesis of ARDS involves complex interactions between the lungs and gut, with microbiota playing a key role. Understanding the effects of FMT on lung function and gut microbiota may provide new therapeutic strategies for ARDS management.

METHODS: Sprague-Dawley rats were pre-treated with a broad-spectrum antibiotic cocktail to create a germ-free state and subsequently exposed to intranasal lipopolysaccharide to induce ARDS. The rats then received FMT treatment. Lung samples were analyzed using histopathology and transcriptomics. Fecal samples were analyzed using 16S rRNA sequencing and metabolomics.

RESULTS: FMT treatment significantly reduced lung injury and improved pulmonary function, as evidenced by increased partial pressure of arterial oxygen (PaO2) and decreased partial pressure of arterial carbon dioxide (PaCO2). FMT also significantly altered in gut microbiota composition by regulating the gut microbiota composition of Akkermansia and Lactobacillus, restoring the abundance of genera such as Muribaculaceae, Clostridia_UCG-014, Prevotella, and Adlercreutzia, while reducing Romboutsia. FMT restored key metabolic pathways involved in lipid metabolism, amino acid biosynthesis, and immune regulation, including the modulation of immune pathways like mTOR signaling. These alterations contribute to reduced lung injury and improved pulmonary function.

CONCLUSION: These findings indicate that FMT may exert its beneficial effects in ARDS by modulating the gut microbiota and enhancing metabolic and immune responses. However, given that this study remains in the preclinical stage, further validation in clinical studies is necessary before considering clinical application.}, } @article {pmid40263850, year = {2025}, author = {He, G and Zhang, B and Chen, T and Shen, C and Wang, N and Yang, J and Chang, F and Sui, Y and Yin, X and Wang, Y and Wang, S and Li, Y and Zong, J and Luo, Y and Meng, Y and Li, C and Zhou, X}, title = {Effects of chitosan on restoring spermatogenesis in mice: Insights from gut microbiota and multi-omics analysis.}, journal = {Food research international (Ottawa, Ont.)}, volume = {208}, number = {}, pages = {116218}, doi = {10.1016/j.foodres.2025.116218}, pmid = {40263850}, issn = {1873-7145}, mesh = {Animals ; Male ; *Spermatogenesis/drug effects ; *Gastrointestinal Microbiome/drug effects ; *Chitosan/pharmacology ; Mice ; Metabolomics ; Testis/drug effects/metabolism ; Busulfan ; Docosahexaenoic Acids/metabolism ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Prebiotics ; Multiomics ; }, abstract = {Chitosan, is a natural bio-based polymer with known prebiotic properties. However, its potential in the management of spermatogenic disorders remains largely unexplored. By utilizing a busulfan-treated mouse model and integrated multi-omics analysis, this study explored the potential mechanisms through which chitosan improves impaired spermatogenesis. The results showed that chitosan treatment can improve testicular function and significantly reshape the gut microbiota composition in busulfan-treated mice. Metabolomics revealed that docosahexaenoic acid (DHA) transport was significantly dysregulated in busulfan-treated mice, but chitosan reversed this dysfunction by modulating tight junction proteins and fatty acid transporters in the intestine. Fecal microbiota transplantation experiments further highlighted the critical role of gut microbiota in DHA transport and spermatogenesis. Additionally, DHA supplementation alleviated busulfan-induced ferroptosis in testicular tissues. Hence, owing to its prebiotic effects chitosan could serve as a novel therapeutic strategy for improving busulfan-induced spermatogenic disorders by restoring the homeostasis of the gut-testis axis.}, } @article {pmid40263438, year = {2025}, author = {Kumpunya, S and Kawang, K and Pollapong, K and Nilaratanakul, V}, title = {The effects of repeated fecal transplantation and activated charcoal treatment on gut dysbiosis induced by concurrent ceftriaxone administration in mice.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {13908}, pmid = {40263438}, issn = {2045-2322}, support = {RA-MF-52/64//Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University/ ; HEA_FF_68_079_3000_013//Thailand Science Research and Innovation Fund Chulalongkorn University/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Charcoal/pharmacology ; *Dysbiosis/chemically induced/therapy/microbiology ; *Ceftriaxone/adverse effects/administration & dosage ; *Gastrointestinal Microbiome/drug effects ; Mice ; Mice, Inbred C57BL ; *Anti-Bacterial Agents/adverse effects/administration & dosage ; RNA, Ribosomal, 16S/genetics ; Male ; Intestinal Mucosa/pathology/microbiology/drug effects ; }, abstract = {BACKGROUND: Antibiotic treatment contributes to gut microbiota dysbiosis. Previous studies have shown that fecal microbiota transplantation (FMT), fecal filtrate (FF), and activated charcoal (AC) treatments can prevent gut microbiota disturbances caused by antibiotics or Clostridioides difficile infection. However, these treatments have typically been limited to restoring gut microbiota after dysbiosis, and antibiotics must be discontinued beforehand. Here, we investigated the protective effects of these treatments on gut microbiota to prevent dysbiosis during concurrent systemic ceftriaxone administration.

METHODS: C57BL/6 mice that received intraperitoneal ceftriaxone for seven consecutive days were concomitantly treated with AC, FMT, FMT + AC, FF, or FF + AC via oral gavage. Gut microbiomes were analyzed using 16 S rRNA gene sequencing, and intestinal mucosal pathology was evaluated through H&E staining.

RESULTS: Systemic ceftriaxone administration significantly altered gut microbiota diversity and composition but did not affect intestinal mucosal histology. Alpha and beta diversity analyses showed that microbiota diversity decreased in all ceftriaxone-treated groups, with the ceftriaxone + FF + AC group retaining the highest diversity. The ceftriaxone + AC group had higher Enterococcus but lower Muribaculaceae relative abundances than the control (no ceftriaxone), ceftriaxone only, and ceftriaxone + FF + AC groups.

CONCLUSIONS: These results show that fecal filtrate transplantation combined with activated charcoal treatment may help balance gut microbiota diversity and reduce the presence of resistant bacteria during ceftriaxone exposure.}, } @article {pmid40263148, year = {2025}, author = {Chi, Q and Tang, J and Ji, C and Chen, S and Chen, Q and Zeng, M and Cao, J and Sun, S and Herr, DR and Zhang, QG and Wang, Z and Huang, CM}, title = {Profiling electric signals of electrogenic probiotic bacteria using self-attention analysis.}, journal = {Applied microbiology and biotechnology}, volume = {109}, number = {1}, pages = {100}, pmid = {40263148}, issn = {1432-0614}, mesh = {*Probiotics/metabolism ; Animals ; Mice ; *Lactococcus lactis/metabolism/physiology ; Chorioallantoic Membrane/microbiology ; Glucose/metabolism ; *Electricity ; Chickens ; Intestines/microbiology ; }, abstract = {We fabricated a self-assembled electric circuit to detect the electrical signals produced by two electrogenic probiotic bacteria [Leuconostoc mesenteroides (L. mesenteroides) and Lactococcus lactis (L. lactis)] on chicken egg chorioallantoic membranes as well as in the intestine lumen of mice. Inoculation of L. mesenteroides or L. lactis plus glucose onto a ferrozine assay triggered the reduction of ferric ions to ferrous ions and the formation of ferrozine complexes, indicating the bacterial electron production. In the presence of glucose, L. lactis yielded higher electricity, measured by voltage changes, than L. mesenteroides in vitro. The spectra of the electrical signals generated by these two probiotic bacteria were highly distinguishable. We evaluated the importance of these differences with the application of a self-attention mechanism, a deep learning-based module, revealing several unique signals in the electrical spectra of L. mesenteroides as well as L. lactis bacteria. The specific electrical spectrum for each probiotic bacterium provided a dynamic signature for evaluation of the efficacy of various therapies using probiotics, antibiotics, and fecal microbiota transplantation in the future. KEY POINTS: • The electrical signals produced by probiotic bacteria L. mesenteroides and L. lactis on chicken egg chorioallantoic membranes and in the mouse intestine lumen were detectable. • In the presence of glucose, L. lactis yielded higher electricity than L. mesenteroides in vitro. Furthermore, the electrical spectra generated by these two bacteria were different. • The importance of these differences with the application of a self-attention mechanism revealed several unique signals in the electrical spectra.}, } @article {pmid40262063, year = {2025}, author = {Elkrief, A and Routy, B and Derosa, L and Bolte, L and Wargo, JA and McQuade, JL and Zitvogel, L}, title = {Gut Microbiota in Immuno-Oncology: A Practical Guide for Medical Oncologists With a Focus on Antibiotics Stewardship.}, journal = {American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting}, volume = {45}, number = {3}, pages = {e472902}, doi = {10.1200/EDBK-25-472902}, pmid = {40262063}, issn = {1548-8756}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/immunology ; *Antimicrobial Stewardship ; *Neoplasms/microbiology/immunology ; *Anti-Bacterial Agents/therapeutic use ; Immune Checkpoint Inhibitors/therapeutic use ; *Medical Oncology ; Oncologists ; }, abstract = {The gut microbiota has emerged as a critical determinant of immune checkpoint inhibitor (ICI) efficacy, resistance, and toxicity. Retrospective and prospective studies profiling the taxonomic composition of intestinal microbes of patients treated with ICI have revealed specific gut microbial signatures associated with response. By contrast, dysbiosis, which can be caused by chronic inflammatory processes (such as cancer) or comedications, is a risk factor of resistance to ICI. Recent large-scale meta-analyses have confirmed that antibiotic (ATB) use before or during ICI therapy alters the microbiota repertoire and significantly shortens overall survival, even after adjusting for prognostic factors. These results underscore the importance of implementing ATB stewardship recommendations in routine oncology practice. Microbiota-centered interventions are now being explored to treat gut dysbiosis and optimize ICI responses. Early-phase clinical trials evaluating fecal microbiota transplantation (FMT) from ICI responders or healthy donors have shown that this approach is safe and provided preliminary data on potential efficacy to overcome both primary and secondary resistance to ICI in melanoma, non-small cell lung cancer, and renal cell carcinoma. More targeted interventions including live bacterial products including Clostridium butyricum and Akkermansia massiliensis represent novel microbiome-based adjunct therapies. Likewise, dietary interventions, such as high-fiber diets, have shown promise in enhancing ICI activity. In this ASCO Educational Book, we summarize the current state-of-the-evidence of the clinical relevance of the intestinal microbiota in cancer immunotherapy and provide a practical guide for ATB stewardship.}, } @article {pmid40261509, year = {2025}, author = {Mahgoup, EM}, title = {"Gut Microbiota as a Therapeutic Target for Hypertension: Challenges and Insights for Future Clinical Applications" "Gut Microbiota and Hypertension Therapy".}, journal = {Current hypertension reports}, volume = {27}, number = {1}, pages = {14}, pmid = {40261509}, issn = {1534-3111}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Hypertension/therapy/microbiology/physiopathology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Antihypertensive Agents/therapeutic use ; Blood Pressure/physiology ; Dysbiosis ; Prebiotics ; }, abstract = {PURPOSE OF REVIEW: Systemic hypertension is a major risk factor for cardiovascular disease and remains challenging to manage despite the widespread use of antihypertensive medications and lifestyle modifications. This review explores the role of gut microbiota in hypertension development and regulation, highlighting key mechanisms such as inflammation, gut-brain axis modulation, and bioactive metabolite production. We also assess the potential of microbiota-targeted therapies for hypertension management.

RECENT FINDINGS: Emerging evidence indicates that microbial dysbiosis, high-salt diets, and gut-derived metabolites such as short-chain fatty acids (SCFAs) and bile acids significantly influence blood pressure regulation. Preclinical and early clinical studies suggest that interventions targeting gut microbiota, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), and dietary modifications, may help modulate hypertension. However, variability in gut microbiota composition among individuals and limited human trial data pose challenges to translating these findings into clinical practice. While microbiota-based therapies show promise for hypertension management, further research is needed to establish their efficacy and long-term effects. Large-scale, standardized clinical trials are crucial for understanding the therapeutic potential and limitations of gut microbiota interventions. A deeper understanding of the gut-hypertension axis could lead to novel, personalized treatment strategies for hypertension.}, } @article {pmid40260582, year = {2025}, author = {Shaukat, A and Drekonja, DM and Huang, Y and Zhang, JH and Davis-Karim, A and Kyriakides, TC}, title = {Efficacy and Safety of Fecal Microbiota Transplant for Prevention of Recurrent Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaf142}, pmid = {40260582}, issn = {1537-6591}, } @article {pmid40260552, year = {2025}, author = {Davido, B and Kharkhordine, M and Moine, P}, title = {Fecal Microbiota Transplantation in Clostridioides Difficile Infections: Rethinking the Approach by Patient Profile in Light of New Evidence.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaf143}, pmid = {40260552}, issn = {1537-6591}, } @article {pmid40260548, year = {2025}, author = {Khoruts, A and Staley, C}, title = {FMT for Recurrent Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaf138}, pmid = {40260548}, issn = {1537-6591}, } @article {pmid40260536, year = {2025}, author = {Paaske, SE and Baunwall, SMD and Ianiro, G and Iqbal, T and Keller, J and Kupciskas, J and Link, A and Mullish, BH and Vehreshild, MJGT and Dahlerup, JF and Hvas, CL}, title = {Clostridioides difficile: Treating Sustained Antibiotic Responders With Fecal Microbiota Transplantation Does Not Improve Efficacy.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaf141}, pmid = {40260536}, issn = {1537-6591}, support = {//the National Institute of Health Research (NIHR) Imperial Biomedical Research Centre (BRC)/ ; //Imperial College London/ ; //Imperial College Healthcare NHS Trust/ ; MR/Z504002/1/MRC_/Medical Research Council/United Kingdom ; }, } @article {pmid40259408, year = {2025}, author = {Cuisiniere, T and Hajjar, R and Oliero, M and Calvé, A and Fragoso, G and Rendos, HV and Gerkins, C and Taleb, N and Gagnon-Konamna, M and Dagbert, F and Loungnarath, R and Sebajang, H and Schwenter, F and Wassef, R and Ratelle, R and De Broux, É and Richard, C and Santos, MM}, title = {Initial gut microbiota composition is a determining factor in the promotion of colorectal cancer by oral iron supplementation: evidence from a murine model.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {100}, pmid = {40259408}, issn = {2049-2618}, support = {PJT-159775/CAPMC/CIHR/Canada ; RGPIN-2024-05660//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Animals ; *Colorectal Neoplasms/microbiology/pathology/etiology ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Iron/adverse effects/administration & dosage ; Humans ; Disease Models, Animal ; *Dietary Supplements/adverse effects ; Fecal Microbiota Transplantation ; Male ; Female ; Administration, Oral ; Feces/microbiology ; Bacteria/classification/isolation & purification/genetics ; Carcinogenesis/drug effects ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Colorectal cancer (CRC) development is influenced by both iron and gut microbiota composition. While iron supplementation is routinely used to manage anemia in CRC patients, it may also impact gut microbiota and promote tumorigenesis. In this study, we investigated the impact of initial gut microbiota composition on iron-promoted tumorigenesis. We performed fecal microbiota transplantation (FMT) in Apc[Min/+] mice using samples from healthy controls, CRC patients, and mice, followed by exposure to iron sufficient or iron excess diets.

RESULTS: We found that iron supplementation promoted CRC and resulted in distinct gut microbiota changes in Apc[Min/+] mice receiving FMT from CRC patients (FMT-CRC), but not from healthy controls or mice. Oral treatment with identified bacterial strains, namely Faecalibaculum rodentium, Holdemanella biformis, Bifidobacterium pseudolongum, and Alistipes inops, protected FMT-CRC mice against iron-promoted tumorigenesis.

CONCLUSIONS: Our findings suggest that microbiota-targeted interventions may mitigate tumorigenic effects of iron supplementation in anemic patients with CRC.}, } @article {pmid40259351, year = {2025}, author = {Kamlárová, A and Kvaková, M and Ambro, Ľ and Link, R and Bertková, I and Hertelyová, Z and Janíčko, M and Hijová, E and Štofilová, J}, title = {Improvement of the inflammation-damaged intestinal barrier and modulation of the gut microbiota in ulcerative colitis after FMT in the SHIME® model.}, journal = {BMC complementary medicine and therapies}, volume = {25}, number = {1}, pages = {145}, pmid = {40259351}, issn = {2662-7671}, support = {APVV-23-0031//Agentúra na Podporu Výskumu a Vývoja/ ; APVV-23-0031//Agentúra na Podporu Výskumu a Vývoja/ ; APVV-23-0031//Agentúra na Podporu Výskumu a Vývoja/ ; APVV-23-0031//Agentúra na Podporu Výskumu a Vývoja/ ; APVV-23-0031//Agentúra na Podporu Výskumu a Vývoja/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; PROBIO-3 ITMS2014+: 313011T651//Operational Program Integrated Infrastructure (OPII) funded by the ERDF/ ; APVV-16-0176//Agentúra na Podporu Výskumu a Vývoja,Slovakia/ ; APVV-16-0176//Agentúra na Podporu Výskumu a Vývoja,Slovakia/ ; APVV-16-0176//Agentúra na Podporu Výskumu a Vývoja,Slovakia/ ; APVV-16-0176//Agentúra na Podporu Výskumu a Vývoja,Slovakia/ ; APVV-16-0176//Agentúra na Podporu Výskumu a Vývoja,Slovakia/ ; APVV-16-0176//Agentúra na Podporu Výskumu a Vývoja,Slovakia/ ; APVV-16-0176//Agentúra na Podporu Výskumu a Vývoja,Slovakia/ ; APVV-16-0176//Agentúra na Podporu Výskumu a Vývoja,Slovakia/ ; APVV-16-0176//Agentúra na Podporu Výskumu a Vývoja,Slovakia/ ; Drive4SIFood 313011V336//Operational Program Integrated Infrastructure/ ; Drive4SIFood 313011V336//Operational Program Integrated Infrastructure/ ; Drive4SIFood 313011V336//Operational Program Integrated Infrastructure/ ; Drive4SIFood 313011V336//Operational Program Integrated Infrastructure/ ; Drive4SIFood 313011V336//Operational Program Integrated Infrastructure/ ; Drive4SIFood 313011V336//Operational Program Integrated Infrastructure/ ; }, mesh = {*Colitis, Ulcerative/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Caco-2 Cells ; Inflammation ; HT29 Cells ; Male ; Female ; Intestinal Mucosa/microbiology ; Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) seems to be a promising approach in ulcerative colitis (UC) management with the aim of repopulating a patient's dysbiotic microbiota with beneficial bacteria and restore its metabolic activity to its healthy characteristics. Metabolites present after FMT may improve the function and integrity of the intestinal barrier, reduce inflammation, and thus induce remission in an UC patient. In this study we evaluated whether the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) model may be a suitable non-invasive alternative for studying and modifying the dysbiotic microbiota in UC by FMT application.

METHODS: SHIME® model was used to investigate microbial and metabolic changes in the gut microbiota of UC patient induced by FMT application. FMT-modified metabolites from SHIME® were applied to an in vitro model of the intestinal barrier (differentiated Caco-2 and HT-29-MTX-E12 cell lines) compromised by pro-inflammatory cytokines to study the effect of FMT on the intestinal barrier.

RESULTS: Qualitative and quantitative microbial analyses showed that FMT increased the diversity and variability of the microbiota in UC patient associated with a significant increase in total bacteria, Bacteroidota and Lactobacillus, as well as an increase in butyrate levels. In addition, an increase in the relative abundance of some important species such as Faecalibacterium prausnitzii and Bifidobacterium longum was observed, and there was also an enrichment of the microbiota with new species such as Blautia obeum, Roseburia faecis, Bifidobacterium adolescentis, Fusicatenibacter saccharivorans and Eubacterium rectale. Furthermore, microbial metabolites modulated by FMT from the SHIME® model prevented intestinal barrier damage and inhibited interleukin 8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) secretion when cell barriers were pretreated with FMT medium for 24 h. In summary, this study confirmed that a single dose of FMT beneficially modulated the composition and metabolic activity of the UC microbiota in the SHIME® model.

CONCLUSIONS: FMT favorably modulates the gut microbiota of UC patient cultured in the SHIME® model. FMT-modulated SHIME-derived microbial metabolites improve intact and inflamed intestinal barrier properties in vitro. Repeated applications are necessary to maintain the beneficial effect of FMT in SHIME® model.}, } @article {pmid40258046, year = {2025}, author = {Lund, AJ and Metzger, ME and Kramer, VL and Kjemtrup, AM}, title = {Low risk for locally acquired Chagas disease in California: A review of human cases and triatomine submissions, 2013-2023.}, journal = {PLoS neglected tropical diseases}, volume = {19}, number = {4}, pages = {e0013036}, pmid = {40258046}, issn = {1935-2735}, support = {U50 CK000387/CK/NCEZID CDC HHS/United States ; }, mesh = {Animals ; Humans ; California/epidemiology ; *Chagas Disease/epidemiology/transmission/parasitology ; *Insect Vectors/parasitology ; *Triatominae/parasitology ; *Trypanosoma cruzi/isolation & purification/genetics ; }, abstract = {Chagas disease is caused by infection with the protozoan parasite Trypanosoma cruzi, which is carried in the guts of triatomine insects. Transmission typically occurs when infective trypomastigotes in triatomine feces encounter mucous membranes or bite wounds, though it is also possible by food-borne, transplant- and transfusion-mediated, and congenital routes. Most transmission occurs in rural and peri-urban parts of continental Latin America where triatomines often inhabit human dwellings. Triatomines infected with T. cruzi are also present across the southern United States, yet relatively few locally acquired infections have been documented. Rather, most reported cases have plausible exposure in Latin America. In California, the widespread distribution of T. cruzi-infected triatomines suggests a potential risk of local transmission. Here, we summarize triatomine submissions and human case reports made to the California Department of Public Health between 2013 and 2023. Of 226 triatomines tested, 63 (28%) were positive for T. cruzi via PCR; none were linked to any of the 40 human T. cruzi cases reported in the same period. Human cases were assessed for likelihood of local transmission. Country of birth, travel history, and location of primary residence suggested non-local transmission for 31 (78%) cases. Local transmission could not be ruled out for the remaining nine (22%) cases. Information on country of birth and travel history were missing from these case reports and prevented full assessment of local transmission criteria, though most of these patients resided within 400 meters of potential triatomine habitat. Despite the presence of triatomines, T. cruzi, and human cases in California, statewide data indicates the risk for locally acquired Chagas disease is low.}, } @article {pmid40257861, year = {2025}, author = {Hu, M and Zhu, X and Huang, X and Hua, L and Lin, X and Zhang, H and Hu, Y and Tong, T and Li, L and Xuan, B and Zhao, Y and Zhou, Y and Ding, J and Ma, Y and Jiang, Y and Ning, L and Zhang, Y and Wang, Z and Fang, JY and Zhang, Y and Xiao, X and Hong, J and Chen, H and Li, J and Chen, H}, title = {Optimizing anti-PD-1/PD-L1 therapy efficacy and fecal microbiota transplantation donor selection through gut mycobiome-based enterotype.}, journal = {Cell reports}, volume = {44}, number = {5}, pages = {115589}, doi = {10.1016/j.celrep.2025.115589}, pmid = {40257861}, issn = {2211-1247}, mesh = {*Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Humans ; Animals ; *Mycobiome ; Mice ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors/metabolism ; Immunotherapy/methods ; CD8-Positive T-Lymphocytes/immunology ; Female ; *B7-H1 Antigen/antagonists & inhibitors/metabolism ; *Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Male ; Tumor Microenvironment ; Mice, Inbred C57BL ; Butyrates/metabolism ; }, abstract = {Immunotherapy has revolutionized cancer treatment, but response variability remains a challenge. The gut microbiome's role in therapeutic efficacy is well established, but the impact of the gut mycobiome is less understood. Using unsupervised clustering, we identify two gut mycobiome-based enterotypes, favorable type and unfavorable type, characterized by distinct microbial compositions linked to immunotherapy outcomes. Favorable-type enterotypes exhibit higher fungal and bacterial alpha diversity, enriched butyrate-producing bacteria, and metabolic pathways related to butyric acid and sugar/starch metabolism. External validation confirms their predictive value in assessing immunotherapy efficacy. Multi-omics analysis reveals increased CD8[+] T cell infiltration in the tumor microenvironment of favorable-type patients. Fecal microbiota transplantation (FMT) from favorable-type donors enhances anti-PD-1 sensitivity, promotes CD8[+] T cell infiltration, and boosts butyrate production in vivo. These findings highlight the gut mycobiome's role in immunotherapy response and support FMT from favorable-type donors as a potential strategy for improving treatment outcomes and patient stratification.}, } @article {pmid40257672, year = {2025}, author = {Bénard, MV and de Bruijn, CMA and Matamoros, S and Wentink-Bonnema, EMS and Benninga, MA and Ponsioen, CY and Zonneveld, R}, title = {Transient colonization with Blastocystis spp. after transmission via fecal microbiota transplantation.}, journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {44}, number = {7}, pages = {1621-1627}, pmid = {40257672}, issn = {1435-4373}, mesh = {Adolescent ; Female ; Humans ; Male ; Young Adult ; *Blastocystis/isolation & purification/genetics ; *Blastocystis Infections/transmission/parasitology ; *Fecal Microbiota Transplantation/adverse effects ; Feces/parasitology/microbiology ; *Irritable Bowel Syndrome/therapy ; }, abstract = {BACKGROUND: The pathogenicity of Blastocystis spp. is still debated. Guidelines for feces donor screening differ in their advice to screen for Blastocystis spp., but when tested, its presence is a common reason for exclusion. Blastocystis spp. are correlated to increased bacterial alpha-diversity and distinct bacterial groups and therefore its presence may indicate favorable efficacy of fecal microbiota transplantation (FMT). The latest European consensus report no longer advices rejecting feces donors testing positive for Blastocystis spp. Only one paper has been published on human transmission of Blastocystis spp. via frozen FMT.

OBJECTIVE: To investigate the transmission and long-term effects of Blastocystis-positive FMT, prepared with fresh (i.e., unfrozen) feces.

METHODS: In a trial (NCT03074227) on FMT for refractory Irritable Bowel Syndrome (IBS), adolescents (age 16-20 years) received two administrations - at baseline and after 6 weeks - of fresh allogeneic FMT from a Blastocystis-positive donor via nasoduodenal tube. The follow-up was 48 weeks. Blastocystis spp. presence, viability and subtyping were determined using microscopy, culture, PCR and sequencing.

RESULTS: Three recipients received FMT from one donor colonized with Blastocystis subtype 3 (ST3). At baseline, two recipients were negative for Blastocystis spp. and one recipient carried ST2. Culturing revealed viable Blastocystis spp. in fresh donor feces but not in frozen samples. After FMT with fresh feces, the two prior-negative recipients tested positive for the donor's ST3 at 12 weeks, but had lost this subtype by week 24 and 48. The recipient initially colonized with ST2 remained colonized with ST2 and did not acquire ST3. Transient adverse events occurred, but did not differ from patients treated with Blastocystis-negative FMT. No FMT-related serious adverse events emerged.

CONCLUSION: We present the first long-term data on viable Blastocystis spp. transmission via fresh FMT in three cases. Transient colonization with Blastocystis spp. was observed, without serious FMT-related adverse events.}, } @article {pmid40257135, year = {2025}, author = {Deepti, I and Chettri, B and Mehra, A and Pinheiro, AM and Ravi, R}, title = {Faecal microbiota transplantation for recurrent Clostridiodes difficile infection & its global regulatory landscape.}, journal = {The Indian journal of medical research}, volume = {161}, number = {2}, pages = {113-119}, pmid = {40257135}, issn = {0971-5916}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Clostridium Infections/therapy/microbiology ; *Clostridioides difficile/pathogenicity ; Recurrence ; Feces/microbiology ; Gastrointestinal Microbiome ; }, abstract = {For recurrent Clostridioides difficile infection (rCDI), faecal microbiota transplantation (FMT) is a known and useful treatment that involves introducing faeces from a healthy individual into the digestive tract of a diseased person. Clostridioides difficile is a substantial global health burden due to its high death rate in elderly populations and its ability to produce colitis and diarrhoea. Despite being used since millennia, FMT has recently become more well-known and two FMT products, namely Vowst and Rebyota also received FDA approval. Different nations address regulation in different ways. For instance, FMT is regulated as a drug in the US but is classified as a medicinal product in the UK. The regulatory frameworks among various European countries also vary; a working group, citing FMT as a transplant product, has requested for complete regulation. There are other classifications as well; in Australia, FMT is categorised as a biologic by the Therapeutic Goods Administration. Research indicates that FMT is beneficial in various illnesses, apart from CDI, due to its impact on the gut flora. Challenges include insufficient FMT product characterisation, ethical concerns, and limited hospital accessibility. There are still issues with data accessibility, security, and privacy, especially considering FMT's commercialisation. The official FMT recommendation for recurrent CDI is emphasised from the perspective of public health, with the argument that early implementation could limit antibiotic overuse and prevent antibiotic resistance. Initiatives like the Universal Stool Bank concept aim to streamline donor selection and distribution procedures to minimise operational restrictions.}, } @article {pmid40256591, year = {2024}, author = {Abedi, B and Karimian, R and Bahari, Z and Iman, M}, title = {Absorbents therapy, as a conservative option, can improve kidney function in chronic kidney disease.}, journal = {Archives of Razi Institute}, volume = {79}, number = {4}, pages = {695-700}, pmid = {40256591}, issn = {2008-9872}, mesh = {Humans ; *Renal Insufficiency, Chronic/therapy/physiopathology ; *Renal Dialysis/methods ; *Conservative Treatment/methods ; }, abstract = {Chronic kidney disease (CKD), also called chronic kidney failure, is increasingly recognized as a global public health problem in the entire world. It is characterized by slow, progressive, and irreversible loss in kidney physiology. Today, the prevalence of CKD is increasing dramatically. CKD can affect almost every organ system, including the cardiovascular system. Many treatments have been attempted for CKD, such as renal transplantation, hemodialysis (HD), and peritoneal dialysis (PD). At the end stage of CKD, HD is the most widely used therapy throughout the world. However, these options can decrease volume expansion and uremic solute retention and also increase patient survival. Furthermore, there are certain complications associated with the use of these methods. Previous studies have reported that the main side effects are headaches, muscle cramps, abdominal pain, hypotension, hypertension, vomiting, and constipation. Therefore, the investigation for better and more convenient dialysis techniques should continue, as well as the search for a better material to enhance the clearance of nitrogenous waste products from the body. The intestine has a significant effect on the clearance of nitrogenous waste products from the body, making it a potentially appropriate site for CKD management. The potential mechanism of the intestinal dialysis technique is that it can absorb excess fluids, uremic toxins, and electrolytes within the gastrointestinal (GI) tract and exert them in the feces before they can be absorbed into the blood. In the present review, we will focus on different absorbents as a conservative treatment to remove uremic waste metabolites from the GI tract for the improvement of kidney function in CKD.}, } @article {pmid40255763, year = {2025}, author = {Rathore, K and Shukla, N and Naik, S and Sambhav, K and Dange, K and Bhuyan, D and Imranul Haq, QM}, title = {The Bidirectional Relationship Between the Gut Microbiome and Mental Health: A Comprehensive Review.}, journal = {Cureus}, volume = {17}, number = {3}, pages = {e80810}, pmid = {40255763}, issn = {2168-8184}, abstract = {The gut microbiome plays a fundamental role in mental health, influencing mood, cognition, and emotional regulation through the gut-brain axis. This bidirectional communication system connects the gastrointestinal and CNS, facilitated by microbial metabolites, neurotransmitters, and immune interactions. Recent research highlights the association between gut dysbiosis and psychiatric disorders, including anxiety, depression, and stress-related conditions. Key findings indicate that altered microbial diversity, decreased short-chain fatty acid (SCFA) production, and increased neuroinflammation contribute to mental health disturbances. This paper explores the mechanism linking the gut microbiome to brain function, including microbial neurotransmitter synthesis, vagus nerve signaling, and hypothalamic-pituitary-adrenal (HPA) axis modulation. Additionally, it evaluates the potential of microbiome-targeted interventions, such as probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation (FMT), in alleviating psychiatric symptoms. Microbiome sequencing and bioinformatics advances further support the development of personalized microbiome-based mental health interventions. Despite promising evidence, challenges such as inter-individual variability, methodological inconsistencies, and the need for longitudinal studies remain. Future research should focus on standardizing microbiome assessment techniques and optimizing therapeutic applications. Integrating precision psychiatry with microbiome-based diagnostics holds immense potential in transforming mental health treatment.}, } @article {pmid40254304, year = {2025}, author = {Fehily, SR and Wright, EK and Basnayake, C and Wilson-O'Brien, AL and Stanley, A and Marks, EP and Russell, EE and Hamilton, AL and Bryant, RV and Costello, SP and Kamm, MA}, title = {Faecal microbiota transplantation in Crohn's disease: an Australian randomised placebo-controlled trial protocol.}, journal = {BMJ open}, volume = {15}, number = {4}, pages = {e094714}, pmid = {40254304}, issn = {2044-6055}, mesh = {Humans ; *Crohn Disease/therapy ; *Fecal Microbiota Transplantation/methods ; Australia ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Remission Induction ; Adult ; Male ; Gastrointestinal Microbiome ; Female ; Multicenter Studies as Topic ; }, abstract = {INTRODUCTION: The enteric microbiota drives inflammation in Crohn's disease. Yet, there are no placebo controlled trials evaluating the efficacy and safety of faecal microbiota transplantation (FMT) in inducing and maintaining remission in patients with active Crohn's disease. The Microbial Restoration (MIRO) study aims to establish this evidence.

METHODS AND ANALYSIS: At two specialist inflammatory bowel disease centres, 120 enrolled patients will have a 3-week period of diet optimisation (removal of ultra-processed foods) together with a 7-day course of antibiotics (to facilitate subsequent FMT engraftment). Patients will then be stratified to upper gut (for disease proximal to the splenic flexure) or lower gut (distal to the splenic flexure) disease. Patients will then be randomised in a 2:1 ratio to receive anaerobically prepared stool or placebo for 8 weeks either by gastroscopy, or colonoscopy and enemas. Clinical response at 8 weeks (Crohn's Disease Activity Index (CDAI) reduction ≥100 points or to <150 points) is the primary outcome measure. Non-responders to placebo and partial responders to FMT (CDAI decrease <100 but >70) receive FMT for weeks 8-16.Patients achieving clinical response from FMT after 8 or 16 weeks will be randomised in a 1:1 ratio to either a 44-week maintenance phase of FMT or placebo. Patients will receive FMT from one donor throughout the study.The MIRO study will establish whether FMT is an effective and safe therapy to induce and maintain remission in patients with active Crohn's disease.

ETHICS AND DISSEMINATION: Ethical approval has been received by the St Vincent's Hospital Melbourne Human Research Ethics Committee (HREC-A 084/21). The results will be disseminated in peer-reviewed journals and presented at international conferences.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT04970446; Registered on 20 July 2021.}, } @article {pmid40253186, year = {2025}, author = {Hao, Y and Wang, C and Wang, L and Hu, L and Duan, T and Zhang, R and Yang, X and Li, T}, title = {Nondigestible stachyose alleviates cyclophosphamide-induced small intestinal mucosal injury in mice by regulating intestinal exosomal miRNAs, independently of the gut microbiota.}, journal = {Food research international (Ottawa, Ont.)}, volume = {209}, number = {}, pages = {116258}, doi = {10.1016/j.foodres.2025.116258}, pmid = {40253186}, issn = {1873-7145}, mesh = {Animals ; *Cyclophosphamide/adverse effects/toxicity ; *Gastrointestinal Microbiome/drug effects ; *MicroRNAs/metabolism/genetics ; *Intestinal Mucosa/drug effects/pathology/metabolism ; *Oligosaccharides/pharmacology ; Mice ; *Intestine, Small/drug effects/pathology/metabolism ; *Exosomes/metabolism/drug effects/genetics ; Male ; Oxidative Stress/drug effects ; Mice, Inbred C57BL ; Cytokines/metabolism ; Prebiotics ; Permeability ; Germ-Free Life ; Tight Junction Proteins/metabolism ; }, abstract = {Stachyose has traditionally been considered to exert prebiotic effects primarily through its interaction with gut microbiota. However, this study reveals a novel mechanism by which stachyose alleviates cyclophosphamide (CY)-induced small intestinal mucosa disruption by regulating the intestinal exosomal miRNAs, without relying on the gut microbiota. Specifically, stachyose significantly mitigates CY-caused damage to the intestinal permeability, oxidative stress, and the structure of intestinal villi and crypts in pseudo-germ-free (PGF) mice. The immunofluorescence staining and qPCR analyses show that stachyose treatment restores CY-caused abnormal changes on the levels of tight junction proteins including MUC2, Occludin, Claudin-1, and ZO-1, and pro-inflammatory cytokines including TNF-α, IL-1β, and IL-2. Furthermore, by conducting fecal miRNA transplantation experiment, we further demonstrated that, similar to stachyose, stachyose-shaped intestinal miRNAs protect against CY-induced intestinal mucosal damage in PGF mice. In summary, this study provides new scientific evidence for the direct interaction between nondigestible stachyose and the proximal small intestine. It also opens new avenues for further investigation into the systemic nutritional functions of stachyose, particularly the health benefits of stachyose in the upper gastrointestinal tract.}, } @article {pmid40253185, year = {2025}, author = {Yang, H and Zhao, Y and Zhang, R and Zhao, L and Yang, H and Liao, X}, title = {CiLi (Rosa roxburghii Tratt.) polyphenols improve colitis via gut microbiota-lipid mediator-immunity axis.}, journal = {Food research international (Ottawa, Ont.)}, volume = {209}, number = {}, pages = {116257}, doi = {10.1016/j.foodres.2025.116257}, pmid = {40253185}, issn = {1873-7145}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Polyphenols/pharmacology ; *Colitis/drug therapy/chemically induced/microbiology/immunology ; Mice ; Mice, Inbred C57BL ; Oxidative Stress/drug effects ; Dextran Sulfate ; Dysbiosis ; Male ; Lipid Metabolism/drug effects ; Disease Models, Animal ; Colon/drug effects ; Fatty Acids, Volatile ; }, abstract = {Dysbiosis of gut microbiome is one of the most important factors leading to inflammatory bowel disease (IBD). Intake of phytochemicals from fruits and vegetables is an effective way to improve IBD, but how these bioactivators regulate gut microbiota to exert healthy effects remains unclear. Here, we found that pretreatment with CiLi juice, particularly its polyphenol component, alleviated dextran sulfate sodium (DSS)-induced colitis while preserving intestinal barrier integrity. CiLi polyphenols (CL_PP) reduced inflammation and oxidative stress in colon tissue and enriched fecal short-chain fatty acids. Importantly, CL_PP significantly regulated the gut microbiome diversity, increasing beneficial bacteria (e.g., Clostridia_UCG-014, f_Muribaculaceae and Ileibacterium_valens) while decreasing harmful bacteria (Escherichia-Shigella and Romboutsia). Multiomics analysis revealed that CL_PP upregulated bioactive lipid metabolites, particularly those derived from polyunsaturated fatty acids (e.g., resolvin D2, prostaglandin A1, and glycerophosphocholine) related gene expressions (Pltp, Alox15 and Pld4). Additionally, CL-PP downregulated the oxidative stress markers (oxidized glutathione and glutathione peroxidase 3), and immune cell markers (CD8 and CD68). Fecal microbiota transplantation confirmed that the fecal microbiota from CL_PP-treated mice exhibited anti-colitis effects. These effects were diminished in antibiotic-treated mice, underscoring the importance of the gut microbiota in mediating the CL_PP's anti-inflammatory benefits. This study suggests that CL_PP is a potential modulator of gut microbiome dysbiosis for the prevention and treatment of colitis.}, } @article {pmid40253128, year = {2025}, author = {Zuo, G and Li, M and Guo, X and Wang, L and Yao, Y and Huang, JA and Liu, Z and Lin, Y}, title = {Fu brick tea supplementation ameliorates non-alcoholic fatty liver disease and associated endotoxemia via maintaining intestinal homeostasis and remodeling hepatic immune microenvironment.}, journal = {Food research international (Ottawa, Ont.)}, volume = {209}, number = {}, pages = {116207}, doi = {10.1016/j.foodres.2025.116207}, pmid = {40253128}, issn = {1873-7145}, mesh = {*Non-alcoholic Fatty Liver Disease/immunology ; Animals ; *Endotoxemia ; Gastrointestinal Microbiome/drug effects ; Male ; Humans ; Homeostasis/drug effects ; *Tea/chemistry ; *Liver/immunology/drug effects/metabolism ; Rats ; Diet, High-Fat/adverse effects ; Caco-2 Cells ; Dysbiosis ; Rats, Sprague-Dawley ; *Dietary Supplements ; Intestines ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a prevalent disorder of excessive fat accumulation and inflammation in the liver that currently lacks effective therapeutic interventions. Fu brick tea (FBT) has been shown to ameliorate liver damage and modulate gut microbiota dysbiosis in NAFLD, but the potential mechanisms have not been comprehensively elucidated, especailly whether its hepatoprotective effects are determined to depend on the homeostasis of gut microbiota, intestinal barrier function and hepatic immune microenvironment. In this study, our results further demonstrated that FBT not only alleviated NAFLD symptoms and related endotoxemia in high-fat diet (HFD)-fed rats, but also attenuated intestinal barrier dysfunction and associated inflammation, also confirmed in Caco-2 cell experiment. Meanwhile, FBT intervention significantly relieved HFD-induced gut microbiota dysbiosis, characterized by increased diversity and composition, particularly facilitating beneficial microbes, including short chain fatty acids (SCFAs) and bile acids producers, such as Blautia and Fusicatenibacter, and inhibiting Gram-negative bacteria, such as Prevotella_9 and Phascolarctobacterium. Also, the gut microbiota-dependent hepatoprotective effects of FBT were verified by fecal microbiota transplantation (FMT) experiment. Thus, the beneficial moulation of gut microbiota altered by FBT in levels of SCFAs, bile acids and lipopolysaccharides, intestinal barrier function and TLR4/NF-κB pathway contributed to alleviate liver steatosis and inflammation. Additionally, the hepatoprotective effects of FBT was further demonstrated by suppressing Kupffer cell activation and regulating lipid metabolism using an ex vivo model of liver organoid. Therefore, FBT supplementation can maintain intenstinal homeostasis and remodel hepatic immune microenvironment to prevent NAFLD and associated endotoxemia.}, } @article {pmid40252900, year = {2025}, author = {Sahebi, K and Arianejad, M and Azadi, S and Hosseinpour-Soleimani, F and Kazemi, R and Tajbakhsh, A and Negahdaripour, M}, title = {The interplay between gut microbiome, epigenetics, and substance use disorders: from molecular to clinical perspectives.}, journal = {European journal of pharmacology}, volume = {998}, number = {}, pages = {177630}, doi = {10.1016/j.ejphar.2025.177630}, pmid = {40252900}, issn = {1879-0712}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Epigenesis, Genetic ; *Substance-Related Disorders/genetics/microbiology/therapy ; Animals ; Brain/metabolism ; Probiotics/therapeutic use ; }, abstract = {Substance use disorders (SUDs) involve a complex series of central and peripheral pathologies, leading to impairments in cognitive, behavioral, and physiological processes. Emerging evidence indicates a more significant role for the microbiome-gut-brain axis (MGBA) in SUDs than previously recognized. The MGBA is interconnected with various body systems by producing numerous metabolites, most importantly short-chain fatty acids (SCFAs), cytokines, and neurotransmitters. These mediators influence the human body's epigenome and transcriptome. While numerous epigenetic alterations in different brain regions have been reported in SUD models, the intricate relationship between SUDs and the MGBA suggests that the gut microbiome may partially contribute to the underlying mechanisms of SUDs. Promising results have been observed with gut microbiome-directed interventions in patients with SUDs, including prebiotics, probiotics, antibiotics, and fecal microbiota transplantation. Nonetheless, the long-term epigenetic effects of these interventions remain unexplored. Moreover, various confounding factors and study limitations have hindered the identification of molecular mechanisms and clinical applications of gut microbiome interventions in SUDs. In the present review, we will (i) provide a comprehensive discussion on how the gut microbiome influences SUDs, with an emphasis on epigenetic alterations; (ii) discuss the current evidence on the bidirectional relationship of gut microbiome and SUDs, highlighting potential targets for intervention; and (iii) review recent advances in gut microbiome-directed therapies, along with their limitations and future directions.}, } @article {pmid40252828, year = {2025}, author = {Zhao, Y and Zhao, W and Chai, X and Sun, P and Huang, J and Guo, X and Zhang, L and Ren, D and Yi, C and Zhu, X and Zhao, S}, title = {Reshaping the gut microbiota: A novel oppinion of Eucommiae cortex polysaccharide alleviate learning and memory impairments in Alzheimer's disease.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.04.025}, pmid = {40252828}, issn = {2090-1224}, abstract = {BACKGROUND: Alzheimer's disease (AD), which is a chronic neurodegenerative disorder, is marked by the progressive deteriorations in learning and memory capabilities. The microbiota-gut-brain axis has come to be regarded as a crucial element in relation to the pathogenesis as well as the treatment of AD. Eucommiae cortex polysaccharides (EPs), being among the most plentiful substances present in the Eucommiae cortex, show the potential to exert immunomodulatory and neuroprotective function. However, whether EPs are protective against AD and their mechanism of action remain to be investigated OBJECTIVES: We hypothesize that EPs can regulate brain glutamine metabolism through gut microbiota and the butyric acid metabolized by them, improve oxidative stress and autophagy in the brain, and thus alleviate AD.

METHODS: In the present study, we used EPs (0.25 % w/w in food) and fecal microbiota transplantation, as well as butyrate supplementation (0.1 M in water), to intervene in AD mice. Multi-omics were used to determine the mechanism by which EPs improve AD-related learning and memory impairments.

RESULTS: Our results suggest that EPs, functioning as a prebiotic, alleviated learning and memory impairments in AD mice. Mechanistically, EPs are able to reshape the gut microbiota, promote the growth of gut microbiota involved in short-chain fatty acid metabolism, particularly butyrate-producing microbes. The butyrate produced by these microbes improves the brain microenvironment by modulating oxidative stress and autophagy mediated by brain glutamate metabolism, improving learning and memory impairments in AD mice, and inhibiting the formation and deposition of beta-amyloid proteins. Fecal microbiota transplantation (FMT) and butyrate supplementation further confirm this conclusion.

CONCLUSIONS: Our results highlighted that EPs can alleviate learning and memory impairments in AD with a gut microbiota-dependent manner and that butyric acid metabolized by butyric acid-metabolizing bacteria in the gut plays a central role in regulating brain glutamine metabolism to improve brain microenvironmental homeostasis. Meanwhile, the present study provides new insights into the treatment of AD with natural products.}, } @article {pmid40252432, year = {2025}, author = {Wang, R and Gan, C and Gong, B and Huang, J and Lou, Z and Wang, D and Yan, R and Li, G and Xiong, T and Guo, J}, title = {Tongfu Xingshen capsule alleviates stroke-associated pneumonia-induced multiple organ injuries by modulating the gut microbiota and sphingolipid metabolism.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {142}, number = {}, pages = {156756}, doi = {10.1016/j.phymed.2025.156756}, pmid = {40252432}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; *Stroke/complications ; *Sphingolipids/metabolism ; *Pneumonia/drug therapy/etiology ; Disease Models, Animal ; *Multiple Organ Failure/drug therapy/etiology ; Klebsiella pneumoniae ; Cerebral Hemorrhage/complications ; Capsules ; }, abstract = {BACKGROUND: Stroke-associated pneumonia (SAP) represents a major complication and cause of death in patients suffering from intracerebral haemorrhage (ICH). It's urgent to develop more effective therapeutic strategies. Tongfu Xingshen capsule (TFXS) is a traditional Chinese medicine that has been utilised in clinical studies for the treatment of ICH and SAP, but the underlying mechanisms remain to be fully elucidated.

PURPOSE: This study aims to explore the therapeutic effects and mechanisms of TFXS on SAP using an aspiration-induced Klebsiella pneumoniae infection-complicating ICH rat model and an intratracheal injection of lipopolysaccharide (LPS)-induced acute lung injury-complicating ICH rat model.

METHODS: The chemical components of TFXS are characterised using ULPLC-Q Exactive-Orbitrap-MS. The therapeutic effects of TFXS are evaluated through neurological scoring, histopathology analysis, magnetic resonance imaging, immunofluorescence, Alcian blue-nuclear fast red staining, myeloperoxidase activity assessment, leukocyte counting, and ELISA. To investigate the underlying mechanisms, faecal microbiota transplantation, 16S rRNA sequencing, untargeted metabolomics, and Spearman correlation analyses are performed.

RESULTS: A total of 60 compounds are identified in TFXS. Pharmacological analysis reveals that TFXS significantly mitigates neurological deficits, enhances haematoma absorption, attenuates brain damage and neuroinflammation, and improves pneumonia and pulmonary injury by reducing the infiltration of leukocytes and lymphocytes, as well as suppressing the infiltration and overactivation of neutrophils. TFXS also alleviates intestinal lesions and barrier damage by increasing acidic mucins and the expression of the tight junction protein zonula occludens-1 (ZO-1). Mechanistically, TFXS ameliorates pneumonia and pulmonary injury in a gut microbiota-dependent manner. It reverses sphingolipid metabolism disorders and ceramide accumulation by modulating SAP-induced gut microbiota dysbiosis and enhancing the abundance of probiotics, including Lactobacillus, Allobaculum and Enterococcus.

CONCLUSION: TFXS exerts anti-inflammatory and protective effects on the brain, lung, and gut by alleviating gut microbiota dysbiosis and sphingolipid metabolism disorders. These findings highlight TFXS as a promising therapeutic candidate for the treatment of SAP.}, } @article {pmid40252102, year = {2025}, author = {Vassallo, GA and Dionisi, T and De Vita, V and Augello, G and Gasbarrini, A and Pitocco, D and Addolorato, G}, title = {The role of fecal microbiota transplantation in diabetes.}, journal = {Acta diabetologica}, volume = {62}, number = {7}, pages = {977-981}, pmid = {40252102}, issn = {1432-5233}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Diabetes Mellitus, Type 2/therapy/microbiology/immunology ; Gastrointestinal Microbiome ; Animals ; *Diabetes Mellitus, Type 1/therapy/microbiology/immunology ; Dysbiosis/therapy ; }, abstract = {Fecal microbiota transplantation (FMT) has emerged as a potential therapeutic strategy for modulating gut dysbiosis in diabetes mellitus. This review critically evaluates preclinical and clinical evidence on FMT in type 1 (T1D) and type 2 diabetes (T2D). Studies suggest that FMT can restore microbial diversity, improve glycemic control, and modulate immune responses, with varying effects across diabetes subtypes. In T1D, preclinical models demonstrate that FMT influences regulatory T-cell expansion and β-cell preservation, though clinical translation remains limited. In T2D, FMT has shown transient improvements in insulin sensitivity, with sustained effects observed only in patients with specific microbiome signatures. However, heterogeneity in patient responses, donor variability, and methodological limitations complicate its clinical application. This review highlights the interplay between FMT, immune modulation, and microbial metabolism, advocating for phenotype-stratified trials and multi-omics integration to enhance therapeutic precision.}, } @article {pmid40251524, year = {2025}, author = {Pan, Q and Guo, F and Chen, J and Huang, H and Huang, Y and Liao, S and Xiao, Z and Wang, X and You, L and Yang, L and Huang, X and Xiao, H and Liu, HF and Pan, Q}, title = {Exploring the role of gut microbiota modulation in the long-term therapeutic benefits of early MSC transplantation in MRL/lpr mice.}, journal = {Cellular & molecular biology letters}, volume = {30}, number = {1}, pages = {49}, pmid = {40251524}, issn = {1689-1392}, support = {82070757//National Natural Science Foundation of China/ ; 82270770//National Natural Science Foundation of China/ ; 82400841//National Natural Science Foundation of China/ ; 2022B1212030003//Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Noncommunicable Diseases/ ; 2022A1515220028//Guangdong Basic and Applied Basic Research Foundation Enterprise Joint Fund/ ; 2021A05060//Zhanjiang Science and Technology Project (Competitive)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice, Inbred MRL lpr ; *Mesenchymal Stem Cell Transplantation/methods ; *Lupus Erythematosus, Systemic/therapy/microbiology ; Mice ; Fecal Microbiota Transplantation ; Humans ; Mesenchymal Stem Cells/cytology/metabolism ; Female ; Disease Models, Animal ; Receptors, Aryl Hydrocarbon/metabolism ; Cytokines/metabolism ; }, abstract = {BACKGROUND: Systemic lupus erythematosus (SLE), influenced by gut microbiota dysbiosis, is characterized by autoimmune and inflammatory responses. Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation is an effective and safe treatment for refractory or severe SLE; however, the long-term efficacy and mechanisms of early hUC-MSC therapeutic benefits in SLE need further investigation.

METHODS: Here, lupus-prone MRL/MpJ-Fas[lpr] (MRL/lpr) mice were divided into three groups: the control (Ctrl) group received saline injections, while the MSC and MSC-fecal microbiota transplantation (FMT) groups received early hUC-MSC transplants at weeks 6, 8, and 10. The MSC-FMT group also underwent FMT from the Ctrl group between weeks 9 and 13.

RESULTS: Our results showed that early MSC treatment extended therapeutic effects up to 12 weeks, reducing autoantibodies, proinflammatory cytokines, B cells, and improving lupus nephritis. It also modulated the gut microbiota, increasing the abundance of beneficial bacteria, such as Lactobacillus johnsonii and Romboutsia ilealis, which led to higher levels of plasma tryptophan and butyrate metabolites. These metabolites activate the aryl hydrocarbon receptor (AHR), upregulate the Cyp1a1 and Cyp1b1 gene, enhance the zonula occludens 1 (ZO-1) protein, promote intestinal repair, and mitigate SLE progression. Notably, FMT from lupus mice significantly reversed hUC-MSC benefits, suggesting that the modulation of the gut microbiota plays a crucial role in the therapeutic response observed in MRL/lpr mice.

CONCLUSIONS: This research innovatively explores the early therapeutic window for MSCs in SLE, highlighting the partial mechanisms through which hUC-MSCs modulate the gut microbiota-tryptophan-AHR axis, thereby ameliorating SLE symptoms.}, } @article {pmid40250802, year = {2025}, author = {Hirai, J}, title = {Extended-pulsed fidaxomicin therapy for recurrent Clostridioides difficile infection after standard vancomycin and fidaxomicin failure: A case report.}, journal = {Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy}, volume = {31}, number = {6}, pages = {102709}, doi = {10.1016/j.jiac.2025.102709}, pmid = {40250802}, issn = {1437-7780}, mesh = {Humans ; Male ; Aged ; *Fidaxomicin/administration & dosage/therapeutic use ; *Vancomycin/therapeutic use ; *Anti-Bacterial Agents/administration & dosage/therapeutic use ; *Clostridium Infections/drug therapy/microbiology ; *Clostridioides difficile/drug effects/isolation & purification ; Recurrence ; Treatment Failure ; Salvage Therapy/methods ; }, abstract = {Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated diarrhea. Recurrence occurs in up to 60 % of patients following multiple episodes, posing a major clinical challenge. While vancomycin (VCM) and fidaxomicin (FDX) are recommended first-line therapies, treatment failures and recurrences are not uncommon. Extended-pulsed fidaxomicin (EPFX) has been proposed to reduce recurrence, especially in high-risk patients, though the evidence remains limited for those with multiple prior relapses. We report the case of a 66-year-old man with advanced esophageal and gastric cancer who experienced four episodes of recurrent CDI despite standard treatment with VCM and FDX. Given the unavailability of bezlotoxumab (BEZ) in Japan and the limited accessibility of fecal microbiota transplantation (FMT), EPFX was selected as a salvage regimen. After both EPFX and pulse-tapered oral VCM were explained, the patient and physician elected to initiate EPFX, consisting of 200 mg twice daily for five days followed by 200 mg every other day for 20 days. No further recurrences were observed for over four months, and no adverse effects were noted. This case supports the use of EPFX in patients with multiple high-risk features-including advanced age, active malignancy, and prior treatment failures-despite the EXTEND trial's exclusion of patients with ≥3 recurrences. The favorable pharmacokinetic properties of FDX may have contributed to its efficacy. Importantly, the patient's medication, nutritional, and oncologic status remained stable throughout treatment, suggesting that EPFX played a pivotal role in achieving remission. EPFX may offer a viable option for patients with recurrent CDI refractory to standard therapies.}, } @article {pmid40248060, year = {2025}, author = {Liu, HJ and Wu, MC and Gau, SY}, title = {Role of gut microbiota and mesenteric adipose tissue in the pathology of Crohn's disease: Potential therapeutic targets.}, journal = {World journal of gastroenterology}, volume = {31}, number = {13}, pages = {102291}, pmid = {40248060}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/physiology ; *Crohn Disease/microbiology/therapy/pathology/immunology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; *Adipose Tissue/pathology ; Treatment Outcome ; Mesentery/pathology ; Colitis, Ulcerative/microbiology/therapy/immunology/pathology ; Remission Induction ; Animals ; Intestinal Mucosa/microbiology/pathology/immunology ; Dysbiosis/therapy/immunology/microbiology ; }, abstract = {This editorial comments on the article by Wu et al in the World Journal of Gastroenterology. The article explored the relationship between mesenteric adipose tissue, creeping fat, inflammation, and gut microbiota in Crohn's disease (CD). We discussed three key aspects of the interaction between gut microbiota and inflammatory bowel disease (IBD): The physiological functions of the gut microbiota, the potential role of probiotics in IBD treatment; and the effect of fecal microbiota transplantation (FMT) in combating IBD. IBD, comprising CD and ulcerative colitis (UC), is influenced by the gut microbiota. Changes in gut microbiota composition disrupt intestinal function and promote chronic inflammation, but the exact mechanisms remain unclear. Probiotics have demonstrated some efficacy in inducing remission in UC, though their effectiveness in CD is still debated. FMT shows promise in treating IBD, especially UC, by restoring gut microbiota diversity and inducing clinical remission. As for CD, FMT has potential, but more studies are needed to confirm its long-term effectiveness and safety. Dietary approaches may help manage IBD symptoms or disease activity, but patient adherence is crucial. Clinicians and researchers must recognize the importance of the gut microbiota and the need for personalized therapies targeting microbial imbalances.}, } @article {pmid40247656, year = {2025}, author = {Bonazzi, E and De Barba, C and Lorenzon, G and Maniero, D and Bertin, L and Barberio, B and Facciotti, F and Caprioli, F and Scaldaferri, F and Zingone, F and Savarino, EV}, title = {Recent developments in managing luminal microbial ecology in patients with inflammatory bowel disease: from evidence to microbiome-based diagnostic and personalized therapy.}, journal = {Expert review of gastroenterology & hepatology}, volume = {19}, number = {5}, pages = {563-576}, doi = {10.1080/17474124.2025.2495087}, pmid = {40247656}, issn = {1747-4132}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Precision Medicine ; Animals ; Fecal Microbiota Transplantation ; *Colitis, Ulcerative/therapy/microbiology/diagnosis ; *Inflammatory Bowel Diseases/therapy/microbiology/diagnosis ; *Crohn Disease/therapy/microbiology/diagnosis ; }, abstract = {INTRODUCTION: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic condition characterized by abnormal immune responses and intestinal inflammation. Emerging evidence highlights the vital role of gut microbiota in IBD's onset and progression. Recent advances have shaped diagnostic and therapeutic strategies, increasingly focusing on microbiome-based personalized care. Methodology: this review covers studies from 2004 to 2024, reflecting the surge in research on luminal microbial ecology in IBD. Human studies were prioritized, with select animal studies included for mechanistic insights. Only English-language, peer-reviewed articles - clinical trials, systematic reviews, and meta-analyses - were considered. Studies without clinical validation were excluded unless offering essential insights. Searches were conducted using PubMed, Scopus, and Web of Science.

AREAS COVERED: we explore mechanisms for managing IBD-related microbiota, including microbial markers for diagnosis and novel therapies such as fecal microbiota transplantation, metabolite-based treatments, and precision microbiome modulation. Additionally, we review technologies and diagnostic tools used to analyze gut microbiota composition and function in clinical settings. Emerging data supporting personalized therapeutic strategies based on individual microbial profiles are discussed.

EXPERT OPINION: Standardized microbiome research integration into clinical practice will enhance precision in IBD care, signaling a shift toward microbiota-based personalized medicine.}, } @article {pmid40246750, year = {2025}, author = {Gefen, R and Dourado, J and Emile, SH and Wignakumar, A and Rogers, P and Aeschbacher, P and Garoufalia, Z and Horesh, N and Wexner, SD}, title = {Fecal microbiota transplantation for patients with ulcerative colitis: a systematic review and meta-analysis of randomized control trials.}, journal = {Techniques in coloproctology}, volume = {29}, number = {1}, pages = {103}, pmid = {40246750}, issn = {1128-045X}, mesh = {Humans ; *Colitis, Ulcerative/therapy ; *Fecal Microbiota Transplantation/methods/adverse effects ; Randomized Controlled Trials as Topic ; Remission Induction/methods ; Treatment Outcome ; Male ; Female ; Adult ; Middle Aged ; Gastrointestinal Microbiome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been shown to restore gut microbiome composition with an acceptable safety profile. FMT in inflammatory bowel disease, specifically ulcerative colitis (UC), has been investigated. We aimed to assess the efficacy of FMT in inducing UC remission.

METHODS: PubMed, Scopus, Google Scholar, and clinicaltrials.gov were searched for randomized control trials that assessed FMT in inducing UC remission. The primary outcome was combined clinical and endoscopic remission. Secondary outcomes were clinical remission, endoscopic remission, post-treatment overall adverse events, and colitis. Sensitivity analyses, meta-regression, bias assessment, and grading of certainty of evidence were performed.

RESULTS: A total of 14 studies including 600 patients (55.8% male; median age 40.7 years) were assessed. FMT was used in 299 patients and associated with significantly higher odds of combined clinical and endoscopic remission (OR 2.25, 95% CI 1.54, 3.3; p < 0.0001), clinical remission (OR 2.02, 95% CI 1.4, 2.93; p = 0.0002), and endoscopic remission (OR 1.95, 95% CI 1.17, 3.28; p = 0.011). The odds of post-treatment overall adverse events (OR 1.24, 95% CI 0.79, 1.95; p = 0.34) and colitis (OR 0.85, 95% CI 0.52, 1.93; p = 0.512) were similar between groups. Compared with baseline, FMT was more effective when biologics (OR 2.71), steroids (OR 2.27), or methotrexate (OR 3.07) were used as pre-FMT treatment. Oral delivery of FMT (OR 3.15) and pooled donors (OR 3.32) led to higher odds of remission. On meta-regression, pooled donors and methotrexate pre-treatment were associated with an increased likelihood of remission.

CONCLUSIONS: FMT is promising in inducing UC remission. Administration of medical treatments before FMT may help achieve higher remission rates. Current evidence shows that oral delivery of FMT and multidonor FMT may confer better results.}, } @article {pmid40246463, year = {2025}, author = {Xia, S and Yan, C and Cai, G and Xu, Q and Zou, H and Gu, J and Yuan, Y and Liu, Z and Bian, J}, title = {Gut dysbiosis exacerbates inflammatory liver injury induced by environmentally relevant concentrations of nanoplastics via the gut-liver axis.}, journal = {Journal of environmental sciences (China)}, volume = {155}, number = {}, pages = {250-266}, doi = {10.1016/j.jes.2024.11.022}, pmid = {40246463}, issn = {1001-0742}, mesh = {Animals ; *Dysbiosis/chemically induced ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Microplastics/toxicity ; Liver/drug effects ; *Environmental Pollutants/toxicity ; *Chemical and Drug Induced Liver Injury ; Inflammation/chemically induced ; Male ; *Nanoparticles/toxicity ; }, abstract = {As an emerging and potentially threatening pollutant, nanoplastics (NPs) have received considerable global attention. Due to their physical properties and diminutive size, NPs ingestion can more easily cross biological barriers and enter the human and animal body. Despite reports of hepatotoxicity associated with NPs, their impact and potential underlying mechanisms remain elusive. In this study, we investigated the impact of NPs at concentrations found in the environment on the gut flora, intestinal barrier function, liver pyroptosis, and inflammation in mice following 12 weeks of exposure. To further validate the involvement of gut flora in inflammatory liver damage caused by NPs, we utilized antibiotics to remove the intestinal flora and performed fecal microbiota transplantation. We confirmed that NPs exposure altered the gut microbiota composition, with a notable rise in the proportions of Alloprevotella and Ileibacterium while causing a decrease in the relative proportions of Dubosiella. This disruption also affected the gut barrier, increasing lipopolysaccharides in circulation and promoting liver pyroptosis. Importantly, mice receiving fecal transplants from NPs-treated mice showed intestinal barrier damage, liver pyroptosis, and inflammation. However, NPs effects on the intestinal barrier and liver pyroptosis were attenuated by antibiotics depletion of the commensal microbiota. In summary, our current research revealed that extended exposure to environmentally relevant concentrations of NPs resulted in inflammatory damage to the liver. Additionally, we have identified for the first time that imbalances in intestinal flora are crucial in liver pyroptosis induced by NPs.}, } @article {pmid40246176, year = {2025}, author = {Adıgüzel, E and Yılmaz, ŞG and Atabilen, B and Şeref, B}, title = {Microbiome modulation as a novel therapeutic modality for anxiety disorders: A review of clinical trials.}, journal = {Behavioural brain research}, volume = {487}, number = {}, pages = {115595}, doi = {10.1016/j.bbr.2025.115595}, pmid = {40246176}, issn = {1872-7549}, mesh = {Humans ; *Anxiety Disorders/microbiology/physiopathology/therapy ; Clinical Trials as Topic ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Prebiotics/administration & dosage ; Probiotics/administration & dosage ; Synbiotics/administration & dosage ; }, abstract = {Anxiety disorders are one of the major conditions in psychiatry characterized by symptoms such as worry, social and performance fears, unexpected and/or triggered panic attacks, anticipatory anxiety, and avoidance behaviors. Recent developments have drawn attention to the putative involvement of peripheral systems in the control of anxiety, and the gut microbiota has come to light as an emerging peripheral target for anxiety. The relationship between the gut-brain axis, a bidirectional communication network between the central nervous system (CNS) and enteric nervous system (ENS), and anxiety has been the subject of some recent studies. Therefore, this systematic review analyzed clinical trials evaluating the potential of microbiome modulation methods in mitigating and ameliorating anxiety disorders. Clinical studies on probiotic, prebiotic, synbiotic supplements, dietary interventions, and fecal microbiota transplantation in anxiety disorders were screened. All of the studies examined the effects of probiotic intervention. One of these studies compared a prebiotic-rich diet with probiotic supplementation. Longitudinal analyses showed that the probiotic intervention alleviated anxiety. However, most of the controlled studies reported that the probiotic intervention did not make a difference compared to placebo. Thus, the current findings suggest that it is too early to consider the promising role of microbiome modulation in the treatment of anxiety disorders. However, it is obvious that more clinical research is needed to clarify issues such as probiotic strains, prebiotic types, and their doses that may be effective on anxiety disorders.}, } @article {pmid40245946, year = {2025}, author = {Vinit, N and Glenisson, M and Leroy, J and Sarnacki, S and Crétolle, C and Beaudoin, S}, title = {Anatomical Correction and Early Outcomes of One-step Ventral and Dorsal Proctoplasty in Girls with Low Anorectal Malformations.}, journal = {European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2590-5697}, pmid = {40245946}, issn = {1439-359X}, abstract = {Rectoperineal fistula (RPF) and rectovestibular fistula (RVF) are the most common forms of low anorectal malformations (ARMs) in girls, and lead to difficult stooling, thus demanding early surgical correction. This study's aim was to assess early outcomes associated with one-step ventral and dorsal proctoplasty in RPF/RVF.All female infants who consecutively underwent one-step proctoplasty for RPF/RVF at our institution (2012-2022) were retrospectively included. Reviewed data included: age at procedure, congenital anomalies, fistula location, preoperative symptoms, intraoperative findings, operative time, postoperative complications, and bowel functional outcome. Success of the technique, defined as spontaneous bowel movement at last follow-up without anal dilation, was assessed. Secondary outcomes included resolution of preoperative symptoms, and Krickenbeck score and fecal continence in girls older than 3 years at last follow-up. No preoperative bowel preparation was necessary.None of the 77 included girls (median age at surgery: 3.2 months (2.3-7.3)) had prior colostomy. In every case, intraoperative findings included: ventral defect of the external anal sphincter, and abnormal attachment of the bulbospongiosus muscles to the fistula and posterior ledge, thus justifying both ventral and dorsal reconstructions. The median operative time was 34 min (27-38), and the median hospital stay was 2 days (2-3). Limited ventral skin dehiscence was the most common postoperative complication (31%), with limited effect on clinical outcome (one secondary anal stricture). No child required secondary colostomy or revision anoplasty. One child underwent secondary pull-through due to persistent megarectum. Preoperative symptoms resolved in 98% of cases. After a median follow-up of 27.6 months (9.8-48.3), all girls had spontaneous bowel movement and 21% had grade-2 constipation. The technique was successful in 97% of cases (two anal strictures treated with dilations).RPF/RVF in female share abnormal anatomical characteristics. One-step ventral and dorsal proctoplasty allows precise anatomical correction of low ARM in girls.}, } @article {pmid40245774, year = {2025}, author = {Zhang, X and Yin, Y and Chen, Y and Lin, L and Shen, S and Fang, F and Wang, Q}, title = {Gut microbiota contributes to obstructive sleep apnea-induced hypertension by gut-heart axis in mice.}, journal = {International immunopharmacology}, volume = {155}, number = {}, pages = {114667}, doi = {10.1016/j.intimp.2025.114667}, pmid = {40245774}, issn = {1878-1705}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Sleep Apnea, Obstructive/complications/microbiology ; *Hypertension/microbiology/etiology ; Male ; Toll-Like Receptor 4/metabolism ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; *Dysbiosis/microbiology ; Mice ; Humans ; NF-kappa B/metabolism ; Lipopolysaccharides/metabolism ; Signal Transduction ; Blood Pressure ; }, abstract = {BACKGROUND: The gut microbiome has been closely linked to obstructive sleep apnea (OSA)-associated hypertension (HTN). However, its precise role in the pathogenesis of OSA-induced HTN remains unclear.

METHODS: To clarify the causal relationship between gut dysbiosis and OSA-related HTN, C57BL6J mice were randomly assigned to four groups. Each group underwent fecal microbiota transplantation from healthy individuals (control), OSA patients (OSA group), OSA patients with pre-hypertension (OSA-pHTN group), or OSA patients with HTN (OSA-HTN group). The pro-hypertensive effects of the OSA gut microbiota were verified, and the composition and function of the gut microbiota were compared using 16S rDNA gene sequencing. Additionally, the gut microbiota-related lipopolysaccharide (LPS)/ Toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-κB) pathway in aortic tissues was investigated.

RESULTS: Fecal microbiota transplantation induced increased systolic blood pressure and aortic injury in mice from the OSA, OSA-pHTN and OSA-HTN groups, whereas no significant injury was observed in the control group. These three groups exhibited dysbiosis and impaired intestinal barrier function as evidenced by a reduction in Akkermansia and decreased expression of zonula occludens-1 and Occludin proteins. In addition, LPS, TLR4 and phosphorylated NF-κB expression were increased in aortic tissue from the three groups, and immunofluorescence showed a significant upregulation of TLR4 expression in aortic endothelial cells compared to controls.

CONCLUSION: This study demonstrates the pro-hypertensive effects of gut microbiota in OSA, mediated through the gut-derived LPS/TLR4/NF-κB pathway. These findings may guide the development of therapeutic strategies focused on restoring gut microbiome homeostasis.}, } @article {pmid40244948, year = {2025}, author = {Zhou, H and Zhuang, Y and Liang, Y and Chen, H and Qiu, W and Xu, H and Zhou, H}, title = {Curcumin exerts anti-tumor activity in colorectal cancer via gut microbiota-mediated CD8[+] T Cell tumor infiltration and ferroptosis.}, journal = {Food & function}, volume = {16}, number = {9}, pages = {3671-3693}, doi = {10.1039/d4fo04045g}, pmid = {40244948}, issn = {2042-650X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Curcumin/pharmacology/administration & dosage ; Mice ; *Colorectal Neoplasms/drug therapy/immunology/microbiology ; *CD8-Positive T-Lymphocytes/drug effects/immunology ; Humans ; *Ferroptosis/drug effects ; Cell Line, Tumor ; Male ; *Antineoplastic Agents/pharmacology ; Mice, Inbred BALB C ; Apoptosis/drug effects ; }, abstract = {Colorectal cancer (CRC), as a high-incidence malignancy, continues to present significant challenges in prevention, screening, and treatment. Curcumin (Cur) exhibits notable anti-inflammatory and anticancer properties. Despite its poor solubility in water and low bioavailability, high concentrations of Cur are detected in the gastrointestinal tract after oral administration, suggesting that it may directly interact with the gut microbiota and exert regulatory effects. This study aims to explore the mechanisms by which Cur improves CRC by modulating gut microbiota. Firstly, we evaluated the effect of Cur on CRC cell viability in vitro using the MTT assay, and the results showed a significant inhibitory effect on CRC cell growth. The IC50 values for Cur in CT26 and RKO cells were 23.52 μM, 16.11 μM, and 13.62 μM at 24, 48, and 72 hours, respectively, and 26.3 μM, 16.52 μM, and 14.22 μM at 24, 48, and 72 hours, respectively. Cur induced apoptosis and caused G2 phase cell cycle arrest in tumor cells. Subsequently, we established a CRC mouse model. Oral administration of Cur at 15 mg kg[-1] and 30 mg kg[-1] inhibited CRC progression, as evidenced by reduced tumor volume, histological analysis, immunohistochemistry, and an increased number of CD8[+] T cells infiltrating the tumors. Ferroptosis in tumor cells was also observed. Cur partially restored the gut microbiota of CRC mice, altering the abundance and diversity of the gut microbiota and affecting serum metabolite distribution, with significant increases in the abundance of SCFA-producing microbes such as Lactobacillus and Kineothrix. To verify causality, we designed a fecal microbiota transplantation (FMT) experiment. Compared with CRC mice, the fecal microbiota from Cur-treated mice significantly alleviated CRC symptoms, including slowed tumor growth, enhanced CD8[+] T cell tumor infiltration, and induced ferroptosis in tumor cells. Additionally, when gut microbiota was depleted with antibiotics, Cur's antitumor effects disappeared, suggesting that Cur mitigates CRC in a gut microbiota-dependent manner. These findings provide new insights into the mechanisms underlying CRC and propose novel therapeutic interventions, emphasizing the interaction between gut microbiota and immune responses within the tumor immune microenvironment (TIME).}, } @article {pmid40244415, year = {2025}, author = {Nista, EC and Parello, S and Brigida, M and Amadei, G and Saviano, A and De Lucia, SS and Petruzziello, C and Migneco, A and Ojetti, V}, title = {Exploring the Role of Gut Microbiota and Probiotics in Acute Pancreatitis: A Comprehensive Review.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40244415}, issn = {1422-0067}, mesh = {*Probiotics/therapeutic use ; *Gastrointestinal Microbiome ; Humans ; *Pancreatitis/microbiology/therapy ; Fecal Microbiota Transplantation ; Animals ; Acute Disease ; }, abstract = {Acute pancreatitis (AP) is a common and potentially severe gastrointestinal condition characterized by acute inflammation of the pancreas. The pathophysiology of AP is multifactorial and intricate, involving a cascade of events that lead to pancreatic injury and systemic inflammation. The progression of AP is influenced by many factors, including genetic predispositions, environmental triggers, and immune dysregulation. Recent studies showed a critical involvement of the gut microbiota in shaping the immune response and modulating inflammatory processes during AP. This review aims to provide a comprehensive overview of the emerging role of gut microbiota and probiotics in AP. We analyzed the implication of gut microbiota in pathogenesis of AP and the modification during an acute attack. The primary goals of microbiome-based therapies, which include probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and enteral nutrition, are to alter the composition of the gut microbial community and the amount of metabolites derived from the microbiota. By resetting the entire flora or supplementing it with certain beneficial organisms and their byproducts, these therapeutic approaches aim to eradicate harmful microorganisms, reducing inflammation and avoiding bacterial translocation and the potential microbiota-based therapeutic target for AP from nutrition to pre- and probiotic supplementation to fecal transplantation.}, } @article {pmid40244136, year = {2025}, author = {Wu, Z and Yan, S and Zhang, H and Ma, Z and Du, R and Liu, Z and Li, X and Cao, G and Song, Y}, title = {Oral Sheep Milk-Derived Exosome Therapeutics for Cadmium-Induced Inflammatory Bowel Disease.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40244136}, issn = {1422-0067}, support = {No. 2022JBGS0021//Inner Mongolia Autonomous Region "Jiebangguashuai" project of China/ ; No. 2022ZD0401403//The Scientific and Technological Innovation 2030 - major project funding/ ; 10000-23122101/021//2024 Inner Mongolia University "Steed Plan" high-level talent funding/ ; }, mesh = {Animals ; Mice ; *Exosomes/metabolism ; *Cadmium/toxicity ; Gastrointestinal Microbiome ; *Milk/chemistry ; Sheep ; *Inflammatory Bowel Diseases/therapy/chemically induced/etiology/microbiology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Administration, Oral ; }, abstract = {Cadmium (Cd) contamination in plants and soil poses significant risks to livestock, particularly sheep. Cd exposure often leads to severe gastrointestinal diseases in sheep that are difficult to treat. Milk-derived exosomes, particularly those from sheep milk (SM-Exo), have shown potential in treating gastrointestinal disorders, though their efficacy in Cd-induced colitis remains unclear. In this study, we investigated the therapeutic potential of SM-Exo in a Cd-induced colitis model. Hu sheep were exposed to Cd, and their fecal microbiota were collected to prepare bacterial solutions for fecal microbiota transplantation (FMT) in mice. The changes in gut microbiota and gene expression were analyzed through microbiome and transcriptomics. Our results showed that prior to treatment, harmful bacteria (e.g., Bacteroides and Parabacteroides) were increased in FMT mice. SM-Exo treatment increased beneficial bacteria, particularly Lachnoclostridium, and activated the Cyclic Adenosine Monophosphate (cAMP) pathway, upregulating genes like Adcy1, Adcy3, CREB, and Sst. These changes were linked to reduced Cd-induced cell death and alleviation of colonic inflammation. In conclusion, SM-Exo appears to be a promising treatment for Cd-induced colitis, likely through modulation of the gut microbiota and activation of the cAMP pathway.}, } @article {pmid40243936, year = {2025}, author = {Ma, B and Barathan, M and Ng, MH and Law, JX}, title = {Oxidative Stress, Gut Microbiota, and Extracellular Vesicles: Interconnected Pathways and Therapeutic Potentials.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40243936}, issn = {1422-0067}, support = {FF-2024-115/1//National University of Malaysia/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Oxidative Stress ; *Extracellular Vesicles/metabolism ; Animals ; Dysbiosis/metabolism ; Signal Transduction ; Reactive Oxygen Species/metabolism ; Antioxidants ; Probiotics/therapeutic use ; Inflammation ; }, abstract = {Oxidative stress (OS) and gut microbiota are crucial factors influencing human health, each playing a significant role in the development and progression of chronic diseases. This review provides a comprehensive analysis of the complex interplay between these two factors, focusing on how an imbalance between reactive oxygen species (ROS) and antioxidants leads to OS, disrupting cellular homeostasis and contributing to a range of conditions, including metabolic disorders, cardiovascular diseases, neurological diseases, and cancer. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, is essential for regulating immune responses, metabolic pathways, and overall health. Dysbiosis, an imbalance in the gut microbiota composition, is closely associated with chronic inflammation, metabolic dysfunction, and various diseases. This review highlights how the gut microbiota influences and is influenced by OS, complicating the pathophysiology of many conditions. Furthermore, emerging evidence has identified extracellular vesicles (EVs) as critical facilitators of cellular crosstalk between the OS and gut microbiota. EVs also play a crucial role in signaling between the gut microbiota and host tissues, modulating immune responses, inflammation, and metabolic processes. The signaling function of EVs holds promise for the development of targeted therapies aimed at restoring microbial balance and mitigating OS. Personalized therapeutic approaches, including probiotics, antioxidants, and fecal microbiota transplantation-based strategies, can be used to address OS-related diseases and improve health outcomes. Nonetheless, further research is needed to study the molecular mechanisms underlying these interactions and the potential of innovative interventions to offer novel strategies for managing OS-related diseases and enhancing overall human health.}, } @article {pmid40243802, year = {2025}, author = {Xiong, Y and Guo, J and Yu, W and Zeng, D and Song, C and Zhou, L and Anatolyevna, NL and Baranenko, D and Xiao, D and Zhou, Y and Lu, W}, title = {Molecular Mechanism of Microgravity-Induced Intestinal Flora Dysbiosis on the Abnormalities of Liver and Brain Metabolism.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40243802}, issn = {1422-0067}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Liver/metabolism/pathology ; *Brain/metabolism ; *Dysbiosis/metabolism/microbiology/etiology ; Mice ; *Weightlessness/adverse effects ; Male ; Space Flight ; Weightlessness Simulation/adverse effects ; Mice, Inbred C57BL ; Metabolomics/methods ; }, abstract = {Space flight has many adverse effects on the physiological functions of astronauts. Certain similarities have been observed in some physiological processes of rodents and astronauts in space, although there are also differences. These similarities make rodents helpful models for initial investigations into space-induced physiological changes. This study uses a 3D-Clinostat to simulate microgravity and explores the role of microgravity in space flight-induced liver and brain abnormalities by comparing changes in the gut microbiota, serum metabolites, and the function and physiological biochemistry of liver and brain tissues between the simulated microgravity (SMG) group mice and the wild type (WT) group mice. The study, based on hematoxylin-eosin (HE) staining, 16S sequencing technology, and non-targeted metabolomics analysis, shows that the gut tissue morphology of the SMG group mice is abnormal, and the structure of the gut microbiota and the serum metabolite profile are imbalanced. Furthermore, using PICRUST 2 technology, we have predicted the functions of the gut microbiota and serum metabolites, and the results indicate that the liver metabolism and functions (including lipid metabolism, amino acid metabolism, and sugar metabolism, etc.) of the SMG group mice are disrupted, and the brain tissue metabolism and functions (including neurotransmitters and hormone secretion, etc.) are abnormal, suggesting a close relationship between microgravity and liver metabolic dysfunction and brain dysfunction. Additionally, the high similarity in the structure of the gut microbiota and serum metabolite profile between the fecal microbiota transplant (FMT) group mice and the SMG group mice, and the physiological and biochemical differences in liver and brain tissues compared to the WT group mice, suggest that microgravity induces imbalances in the gut microbiota, which in turn triggers abnormalities in liver and brain metabolism and function. Finally, through MetaMapp analysis and Pearson correlation analysis, we found that valeric acid, a metabolite of gut microbiota, is more likely to be the key metabolite that relates to microgravity-induced gut microbiota abnormalities, disorders of amino acid and lipid metabolism, and further induced metabolic or functional disorders in the liver and brain. This study has significant practical application value for deepening the understanding of the adaptability of living organisms in the space environment.}, } @article {pmid40243712, year = {2025}, author = {Murgiano, M and Bartocci, B and Puca, P and di Vincenzo, F and Del Gaudio, A and Papa, A and Cammarota, G and Gasbarrini, A and Scaldaferri, F and Lopetuso, LR}, title = {Gut Microbiota Modulation in IBD: From the Old Paradigm to Revolutionary Tools.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40243712}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/therapy/microbiology ; Fecal Microbiota Transplantation/methods ; Probiotics/therapeutic use ; Animals ; Prebiotics ; }, abstract = {Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders primarily comprising two main conditions: ulcerative colitis and Crohn's disease. The gut microbiota's role in driving inflammation in IBD has garnered significant attention, yet the precise mechanisms through which the microbiota influences IBD pathogenesis remain largely unclear. Given the limited therapeutic options for IBD, alternative microbiota-targeted therapies-including prebiotics, probiotics, postbiotics, and symbiotics-have been proposed. While these approaches have shown promising results, microbiota modulation is still mainly considered an adjunct therapy to conventional treatments, with a demonstrated impact on patients' quality of life. Fecal microbiota transplantation (FMT), already approved for treating Clostridioides difficile infection, represents the first in a series of innovative microbiota-based therapies under investigation. Microbial biotherapeutics are emerging as personalized and cutting-edge tools for IBD management, encompassing next-generation probiotics, bacterial consortia, bacteriophages, engineered probiotics, direct metabolic pathway modulation, and nanotherapeutics. This review explores microbial modulation as a therapeutic strategy for IBDs, highlighting current approaches and examining promising tools under development to better understand their potential clinical applications in managing intestinal inflammatory disorders.}, } @article {pmid40243656, year = {2025}, author = {Li, X and Yang, W and Weng, Y and Zhao, Y and Chen, H and Chen, Y and Qiu, J and Jiang, B and Li, C and Lai, Y}, title = {Scutellarin Alleviates CCl4-Induced Liver Fibrosis by Regulating Intestinal Flora and PI3K/AKT Signaling Axis.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40243656}, issn = {1422-0067}, support = {No. 81360511//National Natural Science Foundation of China/ ; No.KY2319102140//Dali University Research and Development Fund/ ; }, mesh = {Animals ; *Apigenin/pharmacology/chemistry/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; *Glucuronates/pharmacology/chemistry ; *Proto-Oncogene Proteins c-akt/metabolism ; Male ; Rats ; *Phosphatidylinositol 3-Kinases/metabolism ; *Signal Transduction/drug effects ; *Liver Cirrhosis/drug therapy/chemically induced/metabolism/pathology ; Carbon Tetrachloride/toxicity ; Rats, Sprague-Dawley ; Molecular Docking Simulation ; }, abstract = {Liver fibrosis is a pathological manifestation of chronic liver disease developing to the terminal stage, and there is a lack of effective therapeutic drugs in clinical practice. Scutellarin (SCU) is a flavonoid extracted from Erigeron breviscapus (Vaniot.) Hand.-Mazz., which has significant anti-liver-fibrosis efficacy, but its mode of action remains incompletely understood. A liver fibrosis model was built with male Sprague Dawley rats induced with the disease by CCl4 to evaluate the therapeutic effect of drugs. 16S rRNA sequencing and metabolomics were used to analyze the regulatory effects of SCU on intestinal flora and host metabolism; antibiotics were administered to eliminate gut microbiota and fecal microbiota transplantation (FMT) experiments were used to verify the mechanism. The mechanistic basis underlying SCU's hepatic anti-fibrotic effects was screened by network pharmacology combined with transcriptomics, combined with molecular docking, qPCR, and WB verification. The results showed that SCU may play an anti-liver-fibrosis role by correcting the imbalance of gut flora and regulating the linoleic acid and purine metabolic pathways. In addition, SCU can downregulate the levels of proteins and genes related to the PI3K/AKT axis. In summary, SCU alleviates liver fibrosis by reversing intestinal flora imbalance, regulating the metabolic profile, and inhibiting the PI3K/AKT axis.}, } @article {pmid40243472, year = {2025}, author = {Beyoğlu, D and Idle, JR}, title = {The Microbiome and Metabolic Dysfunction-Associated Steatotic Liver Disease.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40243472}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome ; Animals ; Dysbiosis/microbiology ; *Fatty Liver/microbiology/metabolism/therapy ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Liver/microbiology/metabolism/pathology ; Bile Acids and Salts/metabolism ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is a condition wherein excessive fat accumulates in the liver, leading to inflammation and potential liver damage. In this narrative review, we evaluate the tissue microbiota, how they arise and their constituent microbes, and the role of the intestinal and hepatic microbiota in MASLD. The history of bacteriophages (phages) and their occurrence in the microbiota, their part in the potential causation of MASLD, and conversely, "phage therapy" for antibiotic resistance, obesity, and MASLD, are all described. The microbiota metabolism of bile acids and dietary tryptophan and histidine is defined, together with the impacts of their individual metabolites on MASLD pathogenesis. Both periodontitis and intestinal microbiota dysbiosis may cause MASLD, and how individual microorganisms and their metabolites are involved in these processes is discussed. Novel treatment opportunities for MASLD involving the microbiota exist and include fecal microbiota transplantation, probiotics, prebiotics, synbiotics, tryptophan dietary supplements, intermittent fasting, and phages or their holins and endolysins. Although FDA is yet to approve phage therapy in clinical use, there are multiple FDA-approved clinical trials, and this may represent a new horizon for the future treatment of MASLD.}, } @article {pmid40243365, year = {2025}, author = {Ismeurt-Walmsley, C and Giannoni, P and Servant, F and Mekki, L-N and Baranger, K and Rivera, S and Marin, P and Lelouvier, B and Claeysen, S}, title = {The same but different: impact of animal facility sanitary status on a transgenic mouse model of Alzheimer's disease.}, journal = {mBio}, volume = {16}, number = {5}, pages = {e0400124}, pmid = {40243365}, issn = {2150-7511}, support = {Inserm Cross-Cutting program on Microbiota//Institut National de la Santé et de la Recherche Médicale/ ; Recherche & Société(s) 2018 - MICMALZ//Région Occitanie Pyrénées-Méditerranée/ ; Recherche & Société(s) 2018 - MICMALZ//European Regional Development Fund/ ; ANR-15-CE16-0006 (MAD5)//Agence Nationale de la Recherche/ ; CIFRE fellowship//SynAging/ ; Aide Individuelle//Association France Alzheimer/ ; Fin de thèse//Soroptimist International France - Club de Montpellier Metropole/ ; ANR-22-CE36-0003 (DENTALCOG)//Agence Nationale de la Recherche/ ; }, mesh = {Animals ; *Alzheimer Disease/microbiology/pathology ; Disease Models, Animal ; Mice ; *Gastrointestinal Microbiome ; Mice, Transgenic ; *Housing, Animal/standards ; Feces/microbiology ; Fecal Microbiota Transplantation ; Specific Pathogen-Free Organisms ; Dysbiosis/microbiology ; Male ; Female ; }, abstract = {UNLABELLED: The gut-brain axis has emerged as a key player in the regulation of brain function and cognitive health. Gut microbiota dysbiosis has been observed in preclinical models of Alzheimer's disease and patients. Manipulating the composition of the gut microbiota enhances or delays neuropathology and cognitive deficits in mouse models. Accordingly, the health status of the animal facility may strongly influence these outcomes. In the present study, we longitudinally analyzed the fecal microbiota composition and amyloid pathology of 5XFAD mice housed in a specific opportunistic pathogen-free (SOPF) and a conventional facility. The composition of the microbiota of 5XFAD mice after aging in conventional facility showed marked differences compared to WT littermates that were not observed when the mice were bred in SOPF facility. The development of amyloid pathology was also enhanced by conventional housing. We then transplanted fecal microbiota (FMT) from both sources into wild-type (WT) mice and measured memory performance, assessed in the novel object recognition test, in transplanted animals. Mice transplanted with microbiota from conventionally bred 5XFAD mice showed impaired memory performance, whereas FMT from mice housed in SOPF facility did not induce memory deficits in transplanted mice. Finally, 18 weeks of housing SOPF-born animals in a conventional facility resulted in the reappearance of specific microbiota compositions in 5XFAD vs WT mice. In conclusion, these results show a strong impact of housing conditions on microbiota-associated phenotypes and question the relevance of breeding preclinical models in specific pathogen-free (SPF) facilities.

IMPORTANCE: Housing conditions affect the composition of the gut microbiota. Gut microbiota of 6-month-old conventionally bred Alzheimer's mice is dysbiotic. Gut dysbiosis is absent in Alzheimer's mice housed in highly sanitized facilities. Transfer of fecal microbiota from conventionally bred mice affects cognition. Microbiota of mice housed in highly sanitized facilities has no effect on cognition.}, } @article {pmid40243343, year = {2025}, author = {Olesen, RH and Larsen, EB and Rubak, T and Baunwall, SMD and Paaske, SE and Gregersen, M and Foss, CH and Erikstrup, C and Krogh, CB and Ehlers, LH and Hvas, CL}, title = {Cost-Effectiveness of Hospital-at-Home and Fecal Microbiota Transplantation in Treating Older Patients With Clostridioides difficile.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaf104}, pmid = {40243343}, issn = {1537-6591}, support = {NNF22OC0074080//Novo Nordisk Foundation/ ; }, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) primarily affects older patients with comorbid conditions and has a high mortality rate. Fecal microbiota transplantation (FMT) is effective and cost-effective for CDI. In a recent study, we demonstrated the clinical benefits of combining hospital-at-home care with FMT for older patients with CDI, but its cost-effectiveness remains unknown. The current study aimed to evaluate the cost-effectiveness of the intervention in patients aged ≥70 years with CDI, compared with standard treatment.

METHODS: The cost-utility analysis was conducted using data from a randomized clinical trial enrolling 217 patients, assessing the cost-effectiveness of the intervention over 90 days. Resource use was assessed from a healthcare sector perspective. Missing data were handled with proxy replacement and multiple imputation. Sensitivity analyses included probabilistic analysis, complete case analysis, adjustment of key unit prices, and a hospital perspective. A willingness-to-pay threshold was set to €22 994 or $24 863 per quality-adjusted life year (QALY).

RESULTS: In the base case analysis, the intervention was dominant, with mean cost savings of €2556 ($2764) and a mean gain of 0.004 QALY. Although resource use was higher, the intervention resulted in an average reduction of 6 hospital admission days per patient and increased odds of clinical resolution. The results remained robust across different perspectives, the exclusion of patients with missing data, and variations in hospital admission costs.

CONCLUSIONS: In patients aged ≥70 years with CDI, an intervention combining hospital-at-home care and FMT is cost-effective compared with standard treatment. The cost-effectiveness is mainly driven by fewer hospital admission days.}, } @article {pmid40237231, year = {2025}, author = {Saeedi, N and Pourabdolhossein, F and Dadashi, M and Suha, AJ and Janahmadi, M and Behzadi, G and Hosseinmardi, N}, title = {Faecal Microbiota Transplantation Modulates Morphine Addictive-Like Behaviours Through Hippocampal Metaplasticity.}, journal = {Addiction biology}, volume = {30}, number = {4}, pages = {e70034}, pmid = {40237231}, issn = {1369-1600}, support = {//Vice President of Research and Technology of Shahid Beheshti University of Medical Sciences/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Male ; Rats, Wistar ; Rats ; *Morphine/pharmacology ; *Morphine Dependence/therapy/physiopathology ; *Neuronal Plasticity/drug effects/physiology ; *Hippocampus/drug effects/physiopathology ; Substance Withdrawal Syndrome ; Naloxone/pharmacology ; Gastrointestinal Microbiome ; Narcotic Antagonists/pharmacology ; Analgesics, Opioid/pharmacology ; }, abstract = {The microbiota-gut-brain axis has been implicated in the pathology of substance use disorders (SUDs). In light of the brain's capability to reorganize itself in response to intrinsic and extrinsic stimuli, opioid-induced dysbiosis is likely to contribute to addictive behaviour through modulating neuroplasticity. In this study, a faecal microbiota transplantation (FMT) from a saline-donor was performed on morphine-treated rats to evaluate the effects of gut microbiota on morphine-induced metaplasticity and addictive behaviours. Male Wistar rats were treated with subcutaneous injections of 10 mg/kg morphine sulphate every 12 h for 9 days in an effort to induce dependence. The withdrawal syndrome was precipitated by injecting naloxone (1.5 mg/kg, ip) after the final dose of morphine. The tolerance was induced by repeated morphine injections over a period of 7 days (10 mg/kg, once a day, ip). FMT was applied daily through gavage of processed faeces 1 week before and during the morphine treatment. Field potential recordings (i.e., fEPSP) were carried out to assess short-term and long-term synaptic plasticity in the CA1 area of the hippocampus following Schaffer-collateral stimulation. Animals subjected to FMT exhibited significant reductions in naloxone-precipitated withdrawal syndrome (one-way ANOVA, p < 0.05). Tolerance to the analgesic effects of morphine was not affected by FMT (two-way ANOVA, p > 0.05). Following high-frequency stimulation (HFS) to induce long-term potentiation (LTP), a greater fEPSP slope was observed in morphine-treated animals (unpaired t test, p < 0.05). FMT from saline-donor rats diminished morphine-induced augmented LTP (unpaired t test, p < 0.05). These results highlighted the alleviating effects of FMT from saline-donors on morphine-induced metaplasticity and dependence potentially by modulating the dysbiosis of gut microbiota.}, } @article {pmid40237060, year = {2025}, author = {Li, H and Lai, H and Xing, Y and Zou, S and Yang, X}, title = {Microbiota-gut-brain axis: Novel Potential Pathways for Developing Antiepileptogenic Drugs.}, journal = {Current neuropharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/1570159X23666250414094040}, pmid = {40237060}, issn = {1875-6190}, abstract = {The treatment of epilepsy remains imperfect due to a lack of understanding of its pathogenesis. Although antiseizure medications can control most seizures, up to 30% of patients experience uncontrolled seizures, leading to refractory epilepsy. Therefore, elucidating the pathogenesis of epilepsy and exploring new avenues to design antiepileptic drugs may improve epilepsy treatment. Recent studies have identified an imbalance of the gut microbiota (GM) in both patients with epilepsy and various animal models of epilepsy. In response to this phenomenon, an increasing number of studies have focused on controlling seizures by regulating GM homeostasis, utilizing methods such as dietary restrictions, fecal microbiota transplantation, and the use of prebiotics. Surprisingly, these interventions have shown promising antiepileptic effects, suggesting that GM, through the regulatory role of the microbiota-gut-brain axis (gut-brain axis), may emerge as a novel strategy for treating epilepsy. This review aims to discuss the research progress on the relationship between GM and epilepsy, incorporating the latest clinical studies and animal experiments. We will specifically concentrate on the potential key role of the gut-brain axis in epileptogenesis, epilepsy development, and outcomes of epilepsy. Through a detailed analysis of the underlying mechanisms of the gut-brain axis, we aim to provide a more comprehensive perspective on understanding the pathophysiology of epilepsy and lay the groundwork for the development of new antiepileptic drugs in the future.}, } @article {pmid40235083, year = {2025}, author = {Brown, R and Barko, P and Ruiz Romero, JDJ and Williams, DA and Gochenauer, A and Nguyen-Edquilang, J and Suchodolski, JS and Pilla, R and Ganz, H and Lopez-Villalobos, N and Gal, A}, title = {The effect of lyophilised oral faecal microbial transplantation on functional outcomes in dogs with diabetes mellitus.}, journal = {The Journal of small animal practice}, volume = {66}, number = {8}, pages = {567-581}, pmid = {40235083}, issn = {1748-5827}, support = {//University of Illinois at Urbana-Champaign Companion Animal Research Grant Program/ ; }, mesh = {Animals ; Dogs ; *Fecal Microbiota Transplantation/veterinary ; *Dog Diseases/therapy ; Feces/microbiology/chemistry ; Pilot Projects ; Male ; *Diabetes Mellitus/veterinary/therapy ; Female ; Double-Blind Method ; Prospective Studies ; Glucagon-Like Peptide 1/blood ; Fatty Acids, Volatile/analysis ; Blood Glucose ; Bile Acids and Salts/analysis ; }, abstract = {OBJECTIVES: We aimed to determine if oral faecal microbiota transplantation improves indices of glycaemic control, changes the faecal dysbiosis indices, alters faecal short-chain fatty acid and bile acid profiles and increases serum glucagon-like-peptide 1 concentrations in diabetic dogs.

MATERIALS AND METHODS: In this prospective randomised, placebo-controlled, double-blinded pilot study, we recruited nine diabetic dogs (five faecal microbiota transplantation and four placebo) and nine healthy controls.

RESULTS: Compared to healthy dogs, diabetic dogs had altered faecal short-chain fatty acid and bile acid profiles. In the first 30 days, the faecal microbiota transplantation group had a more rapid decline in interstitial glucose; however, the mean interstitial glucose of the faecal microbiota transplantation recipients did not differ from the placebo recipients at the end of the study. Compared with placebo, faecal microbiota transplantation recipients had a decreased 24-hour water intake at day 60 and increased faecal abundance of Faecalibacterium.

CLINICAL SIGNIFICANCE: This study provides a proof of concept for faecal microbiota transplantation in canine diabetes, and its data could inform the design of future large-scale studies. Further investigation is required to determine whether faecal microbiota transplantation would have any role as an adjunctive therapy in canine diabetes and to elucidate the mechanisms by which faecal microbiota transplantation may provide a beneficial clinical effect in canine diabetes.}, } @article {pmid40235010, year = {2025}, author = {Chen, M and Pan, J and Song, Y and Liu, S and Sun, P and Zheng, X}, title = {Effect of inulin supplementation in maternal fecal microbiota transplantation on the early growth of chicks.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {98}, pmid = {40235010}, issn = {2049-2618}, support = {20170204043NY2//key technology research. project of Changchun Key R&D Program, and the Outstanding Talents in Science and Technology Innovation/ ; 32472995//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Inulin/administration & dosage/pharmacology ; *Chickens/growth & development/microbiology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/drug effects ; Female ; Dietary Supplements ; Feces/microbiology ; Prebiotics/administration & dosage ; }, abstract = {BACKGROUND: Fecal microbial transplantation (FMT) is an important technology for treating diarrhea and enteritis. Additionally, FMT has been applied to improve productivity, alter abnormal behavior, relieve stress, and reduce burdens. However, some previous studies have reported that FMT may cause stress in acceptor animals. Inulin, a prebiotic, can promote growth, enhance immunity, and balance the gut microbiota. Currently, there are limited reports on the effects of combining FMT with inulin on early growth performance in chicks.

RESULTS: In this study, a total of 90 1-day-old chicks were randomly divided into the control group (CON), FMT group, and inulin group (INU). The CON group was fed a basic diet, whereas the FMT and INU groups received fecal microbiota transplantation and FMT with inulin treatment, respectively. Compared with the FMT and CON groups, the INU group presented significantly greater average daily gain (ADG) and average daily feed intake (ADFI) values (P < 0.05). However, the organ indices did not significantly change (P > 0.05). The ratio of the villi to crypts in the ileum significantly differed at 21 and 35 days (P < 0.05). In addition, the cecum concentrations of acetic acid and butyric acid significantly increased in the INU group (P < 0.05). In addition, gut inflammation and serum inflammation decreased in the INU group, and immune factors increased after inulin supplementation. (P < 0.05). Firmicutes and Bacteroidetes were the dominant phyla, with more than 90% of all sequences being identified as originating from these two phyla. Inulin supplementation during mother-sourced microbial transplantation significantly increased the abundance of Rikenella, Butyricicoccus, and [Ruminococcus], which contributed positively to the promotion of early intestinal health and facilitated the early growth of chicks.

CONCLUSION: The results of this study suggest that inulin supplementation in maternal fecal microbiota transplantation can effectively promote early growth and probiotic colonization, which favors the health of chicks. Video Abstract.}, } @article {pmid40234859, year = {2025}, author = {Senthilkumar, H and Arumugam, M}, title = {Gut microbiota: a hidden player in polycystic ovary syndrome.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {443}, pmid = {40234859}, issn = {1479-5876}, mesh = {Humans ; *Polycystic Ovary Syndrome/microbiology/physiopathology/therapy ; *Gastrointestinal Microbiome ; Female ; Animals ; Dysbiosis ; }, abstract = {Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects reproductive-aged women worldwide, causing hormonal imbalances and ovarian dysfunction. PCOS affects metabolic health and increases the risk of obesity, insulin resistance, and cardiovascular disease, in addition to infertility. This review delves deeper into the connections of gut microbiota with PCOS pathophysiology, particularly into its impact on hormone metabolism, obesity, inflammation, and insulin resistance by way of short-chain fatty acids, lipopolysaccharides, and gut-brain axis. Studies also show that changes in the metabolic processes and immune responses are seen in changes in the gut microbiota in PCOS subjects, such as changes in the Bacteroidetes and Firmicutes groups. Some bacteria, like Escherichia and Shigella, have been associated with dysbiosis in patients with PCOS, leading to systemic inflammation and changed hormone levels, which further worsen the clinical symptoms. Therapeutic interventions targeting the gut microbiota comprise probiotics, prebiotics, and fecal microbiota transplantation; these have potential to alleviate the symptoms of PCOS. Other precision microbiome-based therapies include postbiotics, and CRISPR-Cas9 genome editing, which are relatively new avenues toward precision treatment. This complex interlink of gut microbiota and PCOS pathophysiology will open the avenues for possible treatments for hormonal imbalances and metabolic problems that characterize these complex disorders. The review here focuses on the requirement of further studies to be able to elucidate the specific pathways relating gut microbiota dysregulation to PCOS and, thus, improve microbiome-based therapies for better clinical outcomes in affected individuals.}, } @article {pmid40234406, year = {2025}, author = {Sui, Y and Zhang, T and Ou, S and Li, G and Liu, L and Lu, T and Zhang, C and Cao, Y and Bai, R and Zhou, H and Zhao, X and Yuan, Y and Wang, G and Chen, H and Kong, R and Sun, B and Li, L}, title = {Statin therapy associated Lactobacillus intestinalis attenuates pancreatic fibrosis through remodeling intestinal homeostasis.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {59}, pmid = {40234406}, issn = {2055-5008}, support = {82270665//National Natural Science Foundation of China/ ; 82270666//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Mice ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Homeostasis/drug effects ; Fibrosis ; Fecal Microbiota Transplantation ; Male ; *Pancreas/pathology/drug effects ; Macrophages/immunology ; Mice, Inbred C57BL ; CD8-Positive T-Lymphocytes/immunology ; *Intestines/microbiology/drug effects ; *Lactobacillus ; Disease Models, Animal ; *Probiotics/administration & dosage ; }, abstract = {Chronic pancreatitis (CP) is characterized by irreversible fibrotic destruction and impaired pancreatic function. CP disrupts lipid metabolism and causes the imbalance of gut microbiota which in turn exacerbates pancreatic fibrosis. Statins alter gut microbiota and exert anti-inflammatory effects, but its role in CP has not been fully elucidated. Here, we found that statins-associated higher abundance of Lactobacillus intestinalis (L.intestinalis) maintained gut homeostasis that restrained bacteria translocation from gut to the pancreas, which eventually aggravated pancreatic fibrosis through inhibiting CD8[+]T cells-dependent immunity. Fecal microbiota transplantation (FMT) or L.intestinalis administration inhibited the infiltration of CD8[+]T cells and macrophages that delayed CP progression. L.intestinalis restrained the recruitment of M1 macrophages and limited the release of Ccl2/7 in the colon, which prevented epithelial damage and epithelial barrier dysfunction through blocking Ccl2/7-Ccr1 signaling. Our findings elucidate that the utilization of statin therapy or supplementation of L.intestinalis can be potential approach for the therapies of CP.}, } @article {pmid40233040, year = {2025}, author = {Pomej, K and Frick, A and Scheiner, B and Balcar, L and Pajancic, L and Klotz, A and Kreuter, A and Lampichler, K and Regnat, K and Zinober, K and Trauner, M and Tamandl, D and Gasche, C and Pinter, M}, title = {Study protocol: Fecal Microbiota Transplant combined with Atezolizumab/Bevacizumab in Patients with Hepatocellular Carcinoma who failed to achieve or maintain objective response to Atezolizumab/Bevacizumab - the FAB-HCC pilot study.}, journal = {PloS one}, volume = {20}, number = {4}, pages = {e0321189}, pmid = {40233040}, issn = {1932-6203}, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration & dosage ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Bevacizumab/therapeutic use/administration & dosage ; *Carcinoma, Hepatocellular/therapy/drug therapy ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; *Liver Neoplasms/therapy/drug therapy ; Pilot Projects ; Clinical Trials, Phase II as Topic ; }, abstract = {BACKGROUND: The gut microbiota is often altered in chronic liver diseases and hepatocellular carcinoma (HCC), and increasing evidence suggests that it may influence response to cancer immunotherapy. Strategies to modulate the gut microbiome (i.e., fecal microbiota transplant (FMT)) may help to improve efficacy of immune checkpoint inhibitors (ICIs) or even overcome resistance to ICIs. Here, we describe the design and rationale of FAB-HCC, a single-center, single-arm, phase II pilot study to assess safety, feasibility, and efficacy of FMT from patients with HCC who responded to PD-(L)1-based immunotherapy or from healthy donors to patients with HCC who failed to achieve or maintain a response to atezolizumab plus bevacizumab.

METHODS: In this single-center, single-arm, phase II pilot study (ClinicalTrials.gov identifier: NCT05750030), we plan to include 12 patients with advanced HCC who failed to achieve or maintain a response to atezolizumab/bevacizumab. Patients will receive a single FMT via colonoscopy from donors with HCC who responded to PD-(L)1-based immunotherapy or from healthy individuals, followed by atezolizumab/bevacizumab every 3 weeks. The primary endpoint is safety, measured by incidence and severity of treatment-related adverse events. The main secondary endpoint is efficacy, as assessed by best radiological response according to RECISTv1.1 and mRECIST. Additional exploratory endpoints include data on the effect of FMT on recipient gut microbiota, as well as metagenomic analysis of stool samples, analyses of circulating immune cells and serum and stool proteomic, metabolomic and lipidomic signatures.

DISCUSSION: The results of this study will help to define the potential of FMT as add-on intervention in the systemic treatment of advanced HCC, with the potential to improve efficacy of immunotherapy or even overcome resistance.

TRIAL REGISTRATION: EudraCT Number: 2022-000234-42 Clinical trial registry & ID: ClinicalTrials.gov identifier: NCT05750030 (Registration date: 16.01.2023).}, } @article {pmid40232107, year = {2025}, author = {Ravizza, T and Volpedo, G and Riva, A and Striano, P and Vezzani, A}, title = {Intestinal microbiome alterations in pediatric epilepsy: Implications for seizures and therapeutic approaches.}, journal = {Epilepsia open}, volume = {}, number = {}, pages = {}, doi = {10.1002/epi4.70037}, pmid = {40232107}, issn = {2470-9239}, support = {PE0000006/DN.1553//National Recovery and Resilience Plan (NRRP)/ ; //AICE-FIRE/ ; }, abstract = {The intestinal microbiome plays a pivotal role in maintaining host health through its involvement in gastrointestinal, immune, and central nervous system (CNS) functions. Recent evidence underscores the bidirectional communication between the microbiota, the gut, and the brain and the impact of this axis on neurological diseases, including epilepsy. In pediatric patients, alterations in gut microbiota composition-called intestinal dysbiosis-have been linked to seizure susceptibility. Preclinical models revealed that gut dysbiosis may exacerbate seizures, while microbiome-targeted therapies, including fecal microbiota transplantation, pre/pro-biotics, and ketogenic diets, show promise in reducing seizures. Focusing on clinical and preclinical studies, this review examines the role of the gut microbiota in pediatric epilepsy with the aim of exploring its implications for seizure control and management of epilepsy. We also discuss mechanisms that may underlie mutual gut-brain communication and emerging therapeutic strategies targeting the gut microbiome as a novel approach to improve outcomes in pediatric epilepsy. PLAIN LANGUAGE SUMMARY: Reciprocal communication between the brain and the gut appears to be dysfunctional in pediatric epilepsy. The composition of bacteria in the intestine -known as microbiota- and the gastrointestinal functions are altered in children with drug-resistant epilepsy and animal models of pediatric epilepsies. Microbiota-targeted interventions, such as ketogenic diets, pre-/post-biotics administration, and fecal microbiota transplantation, improve both gastrointestinal dysfunctions and seizures in pediatric epilepsy. These findings suggest that the gut and its microbiota represent potential therapeutic targets for reducing drug-resistant seizures in pediatric epilepsy.}, } @article {pmid40231893, year = {2025}, author = {Vargas-Castellanos, E and Rincón-Riveros, A}, title = {Microsatellite Instability in the Tumor Microenvironment: The Role of Inflammation and the Microbiome.}, journal = {Cancer medicine}, volume = {14}, number = {8}, pages = {e70603}, pmid = {40231893}, issn = {2045-7634}, support = {C-012-2023//Hospital Universitario Mayor Méderi/ ; }, mesh = {Humans ; *Tumor Microenvironment/immunology/genetics ; *Microsatellite Instability ; *Neoplasms/genetics/microbiology/immunology/pathology ; *Inflammation/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Animals ; Dysbiosis ; Immune Checkpoint Inhibitors/therapeutic use ; }, abstract = {BACKGROUND: Microsatellite instability (MSI) is a hallmark of DNA mismatch repair (MMR) deficiency that leads to genomic instability and increased cancer risk. The tumor microenvironment (TME) significantly influences MSI-driven tumorigenesis, and emerging evidence points to a critical role of the microbiome in shaping this complex interplay.

METHODS: This review comprehensively examines the existing literature on the intricate relationship between MSI, microbiome, and cancer development, with a particular focus on the impact of microbial dysbiosis on the TME.

RESULTS: MSI-high tumors exhibited increased immune cell infiltration owing to the generation of neoantigens. However, immune evasion mechanisms such as PD-1/CTLA-4 upregulation limit the efficacy of immune checkpoint inhibitors (ICIs) in a subset of patients. Pathobionts, such as Fusobacterium nucleatum and Bacteroides fragilis, contribute to MSI through the production of genotoxins, further promoting inflammation and oxidative stress within the TME.

CONCLUSIONS: The microbiome profoundly affects MSI-driven tumorigenesis. Modulation of the gut microbiota through interventions such as fecal microbiota transplantation, probiotics, and dietary changes holds promise for improving ICI response rates. Further research into cancer pharmacomicrobiomics, investigating the interplay between microbial metabolites and anticancer therapies, is crucial for developing personalized treatment strategies.}, } @article {pmid40230225, year = {2025}, author = {Fang, X and Zhang, Y and Huang, X and Miao, R and Zhang, Y and Tian, J}, title = {Gut microbiome research: Revealing the pathological mechanisms and treatment strategies of type 2 diabetes.}, journal = {Diabetes, obesity & metabolism}, volume = {27}, number = {8}, pages = {4051-4068}, doi = {10.1111/dom.16387}, pmid = {40230225}, issn = {1463-1326}, support = {CI2021A01601//Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences/ ; HLCMHPP20230CZ40907//High Level Chinese Medical Hospital Promotion Project/ ; ZZ13-YQ-026//CACMS Outstanding Young Scientific and Technological Talents Program/ ; CI2021B008//Innovation Team Project of Science and Technology Innovation Engineering of China Academy of Chinese Medical Sciences/ ; 82474323//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Diabetes Mellitus, Type 2/microbiology/therapy/metabolism/pathology ; *Gastrointestinal Microbiome/physiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics ; Precision Medicine ; }, abstract = {The high prevalence and disability rate of type 2 diabetes (T2D) caused a huge social burden to the world. Currently, new mechanisms and therapeutic approaches that may affect this disease are being sought. With in-depth research on the pathogenesis of T2D and growing advances in microbiome sequencing technology, the association between T2D and gut microbiota has been confirmed. The gut microbiota participates in the regulation of inflammation, intestinal permeability, short-chain fatty acid metabolism, branched-chain amino acid metabolism and bile acid metabolism, thereby affecting host glucose and lipid metabolism. Interventions focusing on the gut microbiota are gaining traction as a promising approach to T2D management. For example, dietary intervention, prebiotics and probiotics, faecal microbiota transplant and phage therapy. Meticulous experimental design and choice of analytical methods are crucial for obtaining accurate and meaningful results from microbiome studies. How to design gut microbiome research in T2D and choose different machine learning methods for data analysis are extremely critical to achieve personalized precision medicine.}, } @article {pmid40229514, year = {2025}, author = {Du, J and Guan, Y and Zhang, E}, title = {Regulatory role of gut microbiota in immunotherapy of hepatocellular carcinoma.}, journal = {Hepatology international}, volume = {19}, number = {3}, pages = {507-518}, pmid = {40229514}, issn = {1936-0541}, mesh = {Humans ; *Carcinoma, Hepatocellular/therapy/immunology/microbiology ; *Gastrointestinal Microbiome/immunology/drug effects ; *Liver Neoplasms/therapy/immunology/microbiology ; Tumor Microenvironment/immunology ; *Immunotherapy/methods ; Immune Checkpoint Inhibitors/therapeutic use ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; }, abstract = {BACKGROUND: The gut microbiota plays a role in triggering innate immunity and regulating the immune microenvironment (IME) of hepatocellular carcinoma (HCC) by acting on various signaling receptors and transcription factors through its metabolites and related molecules. Furthermore, there is an increasing recognition of the gut microbiota as a potential therapeutic target for HCC, given its ability to modulate the efficacy of immune checkpoint inhibitors (ICIs).

OBJECTIVE: This review will discuss the mechanisms of gut microbiota in modulating immunotherapy of HCC, the predictive value of efficacy, and the therapeutic strategies for modulating the gut microbiota in detail.

METHODS: We conducted a systematic literature search in PubMed, Embase, Scopus, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Chinese databases for articles involving the influence of gut microbiota on HCC immunotherapy.

RESULTS: The mechanisms underlying the effect of gut microbiota on HCC immunotherapy include gut-liver axis, tumor immune microenvironment (TIME), and antibodies. Patients who benefit from ICIs exhibit a higher abundance of gut microbiota. Antibiotics, fecal microbiota transplantation (FMT), probiotics, and prebiotics are effective methods to regulate gut microbiota.

CONCLUSION: The strong connection between the liver and gut will provide numerous opportunities for the development of microbiome-based diagnostics, treatments, or prevention strategies for HCC patients.}, } @article {pmid40229213, year = {2025}, author = {Hoops, SL and Moutsoglou, D and Vaughn, BP and Khoruts, A and Knights, D}, title = {Metagenomic source tracking after microbiota transplant therapy.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2487840}, pmid = {40229213}, issn = {1949-0984}, mesh = {Humans ; *Metagenomics/methods ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/genetics ; Colitis, Ulcerative/therapy/microbiology ; *Bacteria/genetics/classification/isolation & purification ; RNA, Ribosomal, 16S/genetics ; *Metagenome ; Bayes Theorem ; Feces/microbiology ; }, abstract = {Reliable engraftment assessment of donor microbial communities and individual strains is an essential component of characterizing the pharmacokinetics of microbiota transplant therapies (MTTs). Recent methods for measuring donor engraftment use whole-genome sequencing and reference databases or metagenome-assembled genomes (MAGs) to track individual bacterial strains but lack the ability to disambiguate DNA that matches both donor and patient microbiota. Here, we describe a new, cost-efficient analytic pipeline, MAGEnTa, which compares post-MTT samples to a database comprised MAGs derived directly from donor and pre-treatment metagenomic data, without relying on an external database. The pipeline uses Bayesian statistics to determine the likely sources of ambiguous reads that align with both the donor and pre-treatment samples. MAGEnTa recovers engrafted strains with minimal type II error in a simulated dataset and is robust to shallow sequencing depths in a downsampled dataset. Applying MAGEnTa to a dataset from a recent MTT clinical trial for ulcerative colitis, we found the results to be consistent with 16S rRNA gene SourceTracker analysis but with added MAG-level specificity. MAGEnTa is a powerful tool to study community and strain engraftment dynamics in the development of MTT-based treatments that can be integrated into frameworks for functional and taxonomic analysis.}, } @article {pmid40227949, year = {2025}, author = {He, Y and Cai, J and Xie, X and Zhang, X and Qu, L and Liu, J and Cao, Y}, title = {Dimethyl Itaconate Alleviates Escherichia coli-Induced Endometritis Through the Guanosine-CXCL14 Axis via Increasing the Abundance of norank_f_Muribaculaceae.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {21}, pages = {e2414792}, pmid = {40227949}, issn = {2198-3844}, support = {2023YFD1801100//Key Technologies Research and Development Program of Anhui Province/ ; }, mesh = {Female ; Animals ; Mice ; *Succinates/pharmacology ; *Endometritis/microbiology/drug therapy/metabolism ; *Escherichia coli/pathogenicity ; Gastrointestinal Microbiome/drug effects ; *Escherichia coli Infections/drug therapy ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Chemokines, CXC/metabolism ; }, abstract = {Endometritis, a prevalent reproductive system disease with high incidence, leads to reproductive dysfunction in humans and animals, causing huge economic losses. Dimethyl itaconate (DI) has been demonstrated to exert protective effects in multiple inflammatory diseases. Nevertheless, the efficacy of DI in preventing endometritis and the role played by the gut microbiota remain unknown. In this study, it is found that DI ameliorated Escherichia coli (E. coli) induced endometritis in mice. The protective effect is abolished by antibiotic-induced depletion of the gut microbiota, and fecal microbiota transplantation (FMT) from DI-treated mice to recipient mice ameliorated E. coli-induced endometritis. Integrative multiomics reveals that DI promotes the multiplication of norank_f_Muribaculaceae in vivo, and supplementation of Muribaculum intestinale (DSM 28989), which belongs to the norank_f_Muribaculaceae genus, upregulates the level of guanosine in the uterus. Mechanistically, the protective effect of guanosine in endometritis is mediated by activating the expression of CXCL14 in uterine epithelial cells. Moreover, the antibody-neutralizing experiment of CXCL14 eliminated this protective effect. In conclusion, this study elucidates the significant role of the gut microbiota and its metabolites in the protection of DI against endometritis, and provides new evidence for the regulation of distal organ by the gut microbiota.}, } @article {pmid40223320, year = {2025}, author = {Yaghmaei, H and Taromiha, A and Nojoumi, SA and Soltanipur, M and Shahshenas, S and Rezaei, M and Mirhosseini, SM and Hosseini, SM and Siadat, SD}, title = {Role of Gut-Liver Axis in Non-Alcoholic Fatty Liver Disease.}, journal = {Iranian biomedical journal}, volume = {29}, number = {1 & 2}, pages = {1-8}, pmid = {40223320}, issn = {2008-823X}, mesh = {*Non-alcoholic Fatty Liver Disease/microbiology ; Humans ; *Gastrointestinal Microbiome ; Animals ; *Liver/pathology/microbiology/metabolism ; Dysbiosis ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant global health problem, mainly due to the increasing prevalence of obesity and metabolic syndrome. The gut microbiota plays an essential role in the development of NAFLD through the gut-liver axis. Dysbiosis of. the gut microbiota (GM) is associated with the pathogenesis of NAFLD. Dietary choices and other lifestyle factors influence the composition of the GM and contribute to the development of NAFLD. At the phylum level, individuals with NAFLD show an increased level in Actinobacteria and Firmicutes, while Verrucomicrobia, Thermus, Proteobacteria, Lentiphaerae, and Fusobacteria are found to be decreased. Several genera, including Faecalibacterium and Akkermansia, exhibit alterations in NAFLD and are linked to disease progression. Modulating the GM through prebiotics, probiotics, or fecal microbiota transplantation represents a promising therapeutic strategy for NAFLD. This review summarizes the current understanding of GM changes in NAFLD, focusing on findings from both human and animal studies.}, } @article {pmid40221450, year = {2025}, author = {Kim, KS and Noh, J and Kim, BS and Koh, H and Lee, DW}, title = {Refining microbiome diversity analysis by concatenating and integrating dual 16S rRNA amplicon reads.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {57}, pmid = {40221450}, issn = {2055-5008}, support = {RS-2021-NR056579//National Research Foundation of Korea (NRF)/ ; RS-2023-KH141436//Ministry of Health and Welfare (Ministry of Health, Welfare and Family Affairs)/ ; 200118770//Ministry of Trade, Industry and Energy (Ministry of Trade, Industry and Energy, Korea)/ ; }, mesh = {*RNA, Ribosomal, 16S/genetics ; Humans ; *Gastrointestinal Microbiome/genetics ; *Bacteria/classification/genetics/isolation & purification ; *Metagenomics/methods ; Sequence Analysis, DNA/methods ; Metagenome ; Colitis, Ulcerative/microbiology ; DNA, Bacterial/genetics ; Republic of Korea ; Phylogeny ; Feces/microbiology ; Biodiversity ; High-Throughput Nucleotide Sequencing ; }, abstract = {Understanding the role of human gut microbiota in health and disease requires insights into its taxonomic composition and functional capabilities. This study evaluates whether concatenating paired-end reads enhances data output for gut microbiome analysis compared to the merging approach across various regions of the 16S rRNA gene. We assessed this approach in both mock communities and Korean cohorts with or without ulcerative colitis. Our results indicate that using the direct joining method for the V1-V3 or V6-V8 regions improves taxonomic resolution compared to merging paired-end reads (ME) in post-sequencing data. While predicting microbial function based on 16S rRNA sequencing has inherent limitations, integrating sequencing reads from both the V1-V3 and V6-V8 regions enhanced functional predictions. This was confirmed by whole metagenome sequencing (WMS) of Korean cohorts, where our approach improved taxa detection that was lost using the ME method. Thus, we propose that the integrated dual 16S rRNA sequencing technique serves as a valuable tool for microbiome research by bridging the gap between amplicon sequencing and WMS.}, } @article {pmid40220715, year = {2025}, author = {Chen, Y and Chen, Z and Liang, L and Li, J and Meng, L and Yuan, W and Xie, B and Zhang, X and Feng, L and Jia, Y and Fu, Z and Su, P and Tong, Z and Zhong, J and Liu, X}, title = {Multi-kingdom gut microbiota dysbiosis is associated with the development of pulmonary arterial hypertension.}, journal = {EBioMedicine}, volume = {115}, number = {}, pages = {105686}, pmid = {40220715}, issn = {2352-3964}, mesh = {*Dysbiosis/microbiology/complications ; *Gastrointestinal Microbiome ; Animals ; Rats ; Humans ; Fecal Microbiota Transplantation ; Male ; Disease Models, Animal ; *Pulmonary Arterial Hypertension/etiology/microbiology ; Metagenomics/methods ; Female ; Middle Aged ; Bacteria/genetics/classification ; }, abstract = {BACKGROUND: Gut microbiota dysbiosis has been implicated in pulmonary arterial hypertension (PAH). However, the exact roles and underlying mechanisms of multi-kingdom gut microbiota, including bacteria, archaea, and fungi, in PAH remain largely unclear.

METHODS: The shotgun metagenomics was used to analyse multi-kingdom gut microbial communities in patients with idiopathic PAH (IPAH) and healthy controls. Furthermore, fecal microbiota transplantation (FMT) was performed to transfer gut microbiota from IPAH patients or monocrotaline (MCT)-PAH rats to normal rats and from normal rats to MCT-PAH rats.

FINDINGS: Gut microbiota analysis revealed substantial alterations in the bacterial, archaeal, and fungal communities in patients with IPAH compared with healthy controls. Notably, FMT from IPAH patients or MCT-PAH rats induced PAH phenotypes in recipient rats. More intriguingly, FMT from normal rats to MCT-PAH rats significantly ameliorated PAH symptoms; restored gut bacteria, archaea, and fungi composition; and shifted the plasma metabolite profiles of MCT-PAH rats toward those of normal rats. In parallel, RNA-sequencing analysis demonstrated the expression of genes involved in key signalling pathways related to PAH. A panel of multi-kingdom markers exhibited superior diagnostic accuracy compared with single-kingdom panels for IPAH.

INTERPRETATION: Our findings established an association between multi-kingdom gut microbiota dysbiosis and PAH, thereby indicating the therapeutic potential of FMT in PAH. More importantly, apart from gut bacteria, gut archaea and fungi were also significantly associated with PAH pathogenesis, highlighting their indispensable role in PAH.

FUNDING: This work was supported by Noncommunicable Chronic Diseases-National Science and Technology Major Projects No. 2024ZD0531200, No. 2024ZD0531201 (Research on Prevention and Treatment of Cancer, Cardiovascular and Cerebrovascular Diseases, Respiratory Diseases, and Metabolic Diseases), the National Natural Science Foundation of China of China (No. 82170302, 82370432), Financial Budgeting Project of Beijing Institute of Respiratory Medicine (Ysbz2025004, Ysbz2025007), National clinical key speciality construction project Cardiovascular Surgery, Reform and Development Program of Beijing Institute of Respiratory Medicine (Ggyfz202417, Ggyfz202501), Clinical Research Incubation Program of Beijing Chaoyang Hospital Affiliated to Capital Medical University (CYFH202209).}, } @article {pmid40220396, year = {2025}, author = {Kou, G and Yao, S and Ullah, A and Fang, S and Guo, E and Bo, Y}, title = {Polystyrene microplastics impair brown and beige adipocyte function via the gut microbiota-adipose tissue crosstalk in high-fat diet mice.}, journal = {Journal of hazardous materials}, volume = {492}, number = {}, pages = {138225}, doi = {10.1016/j.jhazmat.2025.138225}, pmid = {40220396}, issn = {1873-3336}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Diet, High-Fat ; Mice, Inbred C57BL ; *Microplastics/toxicity ; Male ; Mice ; *Adipocytes, Beige/drug effects/metabolism ; *Polystyrenes/toxicity ; Energy Metabolism/drug effects ; *Adipocytes, Brown/drug effects ; Adipose Tissue, Brown/drug effects/metabolism ; Lipid Metabolism/drug effects ; Thermogenesis/drug effects ; }, abstract = {BACKGROUND: Microplastics (MPs) are pervasive in the environment and food. The potential health hazards of this emerging pollutant have raised significant concerns in recent years. However, the underlying mechanism by which MPs have any impact on brown and beige adipocytes in the context of obesity is yet to be investigated.

METHODS: The C57BL/6 J mice were randomly assigned to the HFD and HFD+MPs group for 12 weeks of exposure to explore the differences in brown and beige adipocyte function. The gut microbiota analysis, fecal microbiota transplantation and metabolomic profiling were carried out to further determine its potential mechanism.

RESULTS: The present work demonstrated that high-fat diet mice accumulate lipids and have reduced energy expenditure after three months of oral administration of MPs. In addition to escalating intestinal dysbiosis, exposing HFD mice to MPs induces thermogenic dysfunction in inguinal white adipose tissue and brown adipose tissue. Following the fecal microbiota transplantation, the accumulation of lipids and dysfunction in energy expenditure within the microbiota of recipient mice further elucidated the inhibitory effect of MPs.

CONCLUSIONS: Our results suggest that MPs induced the thermogenic dysfunction of BAT and iWAT by affecting gut microbiota composition. The present study highlights the mechanisms by which MPs produce thermogenic dysfunction in BAT and iWAT and disruption in the gastrointestinal microbiota.}, } @article {pmid40220293, year = {2025}, author = {Damiani, F and Giuliano, MG and Cornuti, S and Putignano, E and Tognozzi, A and Suckow, V and Kalscheuer, VM and Pizzorusso, T and Tognini, P}, title = {Multi-site investigation of gut microbiota in CDKL5 deficiency disorder mouse models: Targeting dysbiosis to improve neurological outcomes.}, journal = {Cell reports}, volume = {44}, number = {4}, pages = {115546}, pmid = {40220293}, issn = {2211-1247}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Disease Models, Animal ; *Dysbiosis/microbiology ; Mice ; Mice, Knockout ; Microglia/pathology/metabolism ; Fecal Microbiota Transplantation ; *Spasms, Infantile/microbiology ; *Protein Serine-Threonine Kinases/deficiency/genetics ; *Epileptic Syndromes/microbiology ; *Rett Syndrome/microbiology ; Mice, Inbred C57BL ; Male ; Female ; }, abstract = {Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a rare neurodevelopmental disorder often associated with gastrointestinal (GI) issues and subclinical immune dysregulation, suggesting a link to the gut microbiota. We analyze the fecal microbiota composition in two CDKL5 knockout (KO) mouse models at postnatal days (P) 25, 32 (youth), and 70 (adulthood), revealing significant microbial imbalances, particularly during juvenile stages. To investigate the role of the intestinal microbiota in CDD and assess causality, we administer antibiotics, which lead to improved visual cortical responses and reduce hyperactivity. Additionally, microglia morphology changes, indicative of altered surveillance and activation states, are reversed. Strikingly, fecal transplantation from CDKL5 KO to wild-type (WT) recipient mice successfully transfers both visual response deficits and hyperactive behavior. These findings show that gut microbiota alterations contribute to the severity of neurological symptoms in CDD, shedding light on the interplay between microbiota, microglia, and neurodevelopmental outcomes.}, } @article {pmid40219707, year = {2025}, author = {Li, M and Ren, J and Bao, Y and Wei, W and Yu, X and He, X and Gulisima, M and Sheng, L and Zheng, N and Wan, J and Zhou, H and Zhao, L and Li, H}, title = {Aged Gut Microbiota Contributes to Cognitive Impairment and Hippocampal Synapse Loss in Mice.}, journal = {Aging cell}, volume = {24}, number = {7}, pages = {e70064}, pmid = {40219707}, issn = {1474-9726}, support = {21XD1403500//Shanghai Excellent Academic Leaders Program/ ; //"Youth Qi Huang Scholar" by State Administration of TCM/ ; 2021YFE0111800//2021 UK-China Health and Ageing Flagship Challenge/ ; 81871098//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Cognitive Dysfunction/microbiology/pathology ; *Hippocampus/pathology/metabolism ; Mice ; *Synapses/pathology/metabolism ; Humans ; Male ; Indoleacetic Acids/metabolism ; Mice, Inbred C57BL ; Tryptophan/metabolism ; *Aging ; Female ; }, abstract = {Gut microbiota alteration during the aging process serves as a causative factor for aging-related cognitive decline, which is characterized by the early hallmark, hippocampal synaptic loss. However, the impact and mechanistic role of gut microbiota in hippocampal synapse loss during aging remains unclear. Here, we observed that the fecal microbiota of naturally aged mice successfully transferred cognitive impairment and hippocampal synapse loss to young recipients. Multi-omics analysis revealed that aged gut microbiota was characterized with obvious change in Bifidobacterium pseudolongum (B.p) and metabolite of tryptophan, indoleacetic acid (IAA) in the periphery and brain. These features were also reproduced in young recipients that were transplanted with aged gut microbiota. Fecal B.p abundance was reduced in patients with cognitive impairment compared to healthy subjects and showed a positive correlation with cognitive scores. Microbiota transplantation from patients who had fewer B.p abundances yielded worse cognitive behavior in mice than those with higher B.p abundances. Meanwhile, supplementation of B.p was capable of producing IAA and enhancing peripheral and brain IAA bioavailability, as well as improving cognitive behaviors and microglia-mediated synapse loss in 5 × FAD transgenic mice. IAA produced from B.p was shown to prevent microglia engulfment of synapses in an aryl hydrocarbon receptor-dependent manner. This study reveals that aged gut microbiota -induced cognitive decline and microglia-mediated synapse loss that is, at least partially, due to the deficiency in B.p and its metabolite, IAA. It provides a proof-of-concept strategy for preventing neurodegenerative diseases by modulating gut probionts and their tryptophan metabolites.}, } @article {pmid40219669, year = {2025}, author = {Murray, J and Kefayat, A and Finlayson, M and Seenan, JP and Hsu, R and Din, S}, title = {RCPE in association with the American College of Gastroenterology and the Scottish Society of Gastroenterology - Gastroenterology: A global perspective.}, journal = {The journal of the Royal College of Physicians of Edinburgh}, volume = {55}, number = {2}, pages = {132-138}, doi = {10.1177/14782715251332318}, pmid = {40219669}, issn = {2042-8189}, mesh = {Humans ; *Gastroenterology ; Scotland ; Societies, Medical ; Inflammatory Bowel Diseases/therapy ; Gastrointestinal Microbiome ; Congresses as Topic ; }, abstract = {On 6 November 2024, the Royal College of Physicians of Edinburgh (RCPE) hosted its annual gastroenterology symposium, marking the first collaboration with the American College of Gastroenterology (ACG) and the Scottish Society of Gastroenterology (SSG). The event addressed key global challenges in gastroenterology, including obesity, liver disease, inflammatory bowel disease (IBD), the gut microbiome, endoscopy quality and artificial intelligence (AI) applications. Discussions emphasised the growing burden of metabolic dysfunction-associated steatotic liver disease (MASLD), with promising pharmacologic and endoscopic interventions emerging. Advances in microbiome-targeted therapies, including faecal microbiota transplantation (FMT), were explored for recurrent Clostridium difficile infection and IBD. Professor David Rubin delivered the esteemed Sir Stanley Davidson lecture, highlighting the era of disease modification in IBD, emphasising early intervention and personalised treatment strategies. The symposium also addressed the role of AI in improving endoscopic detection rates and optimising resource allocation. This international collaboration underscored the importance of a multidisciplinary approach to tackling global digestive diseases, integrating clinical innovation, policy interventions and technological advancements. The event fostered knowledge exchange among global experts, aiming to advance patient care and improve long-term outcomes in gastroenterology.}, } @article {pmid40218893, year = {2025}, author = {Młynarska, E and Barszcz, E and Budny, E and Gajewska, A and Kopeć, K and Wasiak, J and Rysz, J and Franczyk, B}, title = {The Gut-Brain-Microbiota Connection and Its Role in Autism Spectrum Disorders.}, journal = {Nutrients}, volume = {17}, number = {7}, pages = {}, pmid = {40218893}, issn = {2072-6643}, mesh = {Humans ; *Autism Spectrum Disorder/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/complications/microbiology ; *Brain/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; *Brain-Gut Axis ; }, abstract = {Autism spectrum disorder (ASD) is a group of complex neurodevelopmental conditions with a heterogeneous and multifactorial etiology that is not yet fully understood. Among the various factors that may contribute to ASD development, alterations in the gut microbiota have been increasingly recognized. Microorganisms in the gastrointestinal tract play a crucial role in the gut-brain axis (GBA), affecting nervous system development and behavior. Dysbiosis, or an imbalance in the microbiota, has been linked to both behavioral and gastrointestinal (GI) symptoms in individuals with ASD. The microbiota interacts with the central nervous system through mechanisms such as the production of short-chain fatty acids (SCFAs), the regulation of neurotransmitters, and immune system modulation. Alterations in its composition, including reduced diversity or an overabundance of specific bacterial taxa, have been associated with the severity of ASD symptoms. Dietary modifications, such as gluten-free or antioxidant-rich diets, have shown potential for improving gut health and alleviating behavioral symptoms. Probiotics, with their anti-inflammatory properties, may support neural health and reduce neuroinflammation. Fecal microbiota transplantation (FMT) is being considered, particularly for individuals with persistent GI symptoms. It has shown promising outcomes in enhancing microbial diversity and mitigating GI and behavioral symptoms. However, its limitations should be considered, as discussed in this narrative review. Further research is essential to better understand the long-term effects and safety of these therapies. Emphasizing the importance of patient stratification and phenotype characterization is crucial for developing personalized treatment strategies that account for individual microbiota profiles, genetic predispositions, and coexisting conditions. This approach could lead to more effective interventions for individuals with ASD. Recent findings suggest that gut microbiota may play a key role in innovative therapeutic approaches to ASD management.}, } @article {pmid40216789, year = {2025}, author = {Shekarriz, S and Szamosi, JC and Whelan, FJ and Lau, JT and Libertucci, J and Rossi, L and Fontes, ME and Wolfe, M and Lee, CH and Moayyedi, P and Surette, MG}, title = {Detecting microbial engraftment after FMT using placebo sequencing and culture enriched metagenomics to sort signals from noise.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {3469}, pmid = {40216789}, issn = {2041-1723}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Metagenomics/methods ; *Colitis, Ulcerative/therapy/microbiology ; *Gastrointestinal Microbiome/genetics ; Feces/microbiology ; Male ; Female ; Placebos ; Adult ; Middle Aged ; }, abstract = {Fecal microbiota transplantation (FMT) has shown efficacy for the treatment of ulcerative colitis but with variable response between patients and trials. The mechanisms underlying FMT's therapeutic effects remains poorly understood but is generally assumed to involve engraftment of donor microbiota into the recipient's microbiome. Reports of microbial engraftment following FMT have been inconsistent between studies. Here, we investigate microbial engraftment in a previous randomized controlled trial (NCT01545908), in which FMT was sourced from a single donor, using amplicon-based profiling, shotgun metagenomics, and culture-enriched metagenomics. Placebo samples were included to estimate engraftment noise, and a significant level of false-positive engraftment was observed which confounds the prediction of true engraftment. We show that analyzing engraftment across multiple patients from a single donor enhances the accuracy of detection. We identified a unique set of genes engrafted in responders to FMT which supports strain displacement as the primary mechanism of engraftment in our cohort.}, } @article {pmid40216297, year = {2025}, author = {Tanabe, M and Kunisawa, K and Saito, I and Ojika, H and Saito, K and Nabeshima, T and Mouri, A}, title = {High-Cellulose Diet Ameliorates Cognitive Impairment by Modulating Gut Microbiota and Metabolic Pathways in Mice.}, journal = {The Journal of nutrition}, volume = {155}, number = {6}, pages = {1689-1699}, doi = {10.1016/j.tjnut.2025.04.004}, pmid = {40216297}, issn = {1541-6100}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Male ; *Cognitive Dysfunction/diet therapy/microbiology ; Mice, Inbred C57BL ; Mice ; *Cellulose/administration & dosage/pharmacology ; *Metabolic Networks and Pathways/drug effects ; *Diet ; Dietary Fiber/administration & dosage ; }, abstract = {BACKGROUND: Nutrition is a key factor in cognitive function, and safe dietary interventions are promising to prevent cognitive impairment in pediatric psychiatric disorders. We previously demonstrated that childhood social isolation (SI) stress affects colonic function, leading to cognitive impairment. Cellulose, an insoluble dietary fiber, shows benefits to intestinal health, but its potential impact on cognitive impairment has not been explored.

OBJECTIVES: This study investigated whether a high-cellulose diet ameliorates cognitive impairment induced by SI through modulation of gut microbiota and metabolic pathways.

METHODS: C57BL/6J male mice (3 wk old; n = 10-15/group) were randomly divided into 2 groups: individually housed (SI) group and housed 5 mice per cage (group-housed) group. Each group received either a normal diet (5% cellulose) or a high-cellulose diet (30% cellulose) for 5 wk daily until the end of the behavioral testing. We evaluated behavior abnormalities, gut microbiota composition, and metabolites, and performed 2-way analysis of variance.

RESULTS: Intake of a high-cellulose diet ameliorated cognitive impairment, including decreased time spent in a novel location of SI mice in novel object location test (NOLT; +30%; P < 0.01) with reduction of Iba-1 positive cells, microglia, in the hippocampus (-33%; P < 0.05). The high-cellulose diet indicated a significant difference in gut microbiota clustering plots (P < 0.01) and enhanced the variation in malate-aspartate shuttle pathways in SI mice (P < 0.01). Notably, fecal microbiota transplantation (FMT) from SI mice fed a high-cellulose diet after antibiotic treatment, replicated amelioration of cognitive impairment in NOLT (+46%; P < 0.01). Additionally, the FMT replicated a decrease of Iba-1 positive cells indicating suppressed hippocampal microglial activation (-52%; P < 0.01), and enhanced the variation in malate-aspartate shuttle pathways (P < 0.01).

CONCLUSIONS: These findings suggest that a high-cellulose diet may ameliorate pediatric-specific cognitive impairment through modulation of the gut microbiota and metabolic pathways.}, } @article {pmid40211390, year = {2025}, author = {Wang, Z and Gao, X and Ji, H and Shao, M and Ni, B and Fei, S and Sun, L and Chen, H and Tan, R and Du, M and Gu, M}, title = {Characterization of gut microbiota and metabolites in renal transplant recipients during COVID-19 and prediction of one-year allograft function.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {420}, pmid = {40211390}, issn = {1479-5876}, support = {82170769//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Kidney Transplantation ; *COVID-19/metabolism/microbiology/complications ; *Gastrointestinal Microbiome/physiology ; Female ; Male ; Middle Aged ; Adult ; *Metabolome ; SARS-CoV-2 ; Allografts ; Transplant Recipients ; Feces/microbiology ; Aged ; }, abstract = {BACKGROUND: The gut-lung-kidney axis is pivotal in immune-related kidney diseases, with gut dysbiosis potentially exacerbating the severity of Coronavirus disease 2019 (COVID-19) in recipients of kidney transplant. This study aimed to characterize the gut microbiome and metabolome in renal transplant recipients with COVID-19 pneumonia over a one-year follow-up period.

METHODS: A total of 30 renal transplant recipients were enrolled, comprising 17 with COVID-19 pneumonia, six with mild COVID-19, and seven without COVID-19. Fecal samples were collected at the onset of infection for gut microbiome and metabolome analysis. Generalized Estimating Equations (GEE) model and Latent Class Growth Mixed Model (LCGMM) were employed to dissect the relationships among clinical characteristics, laboratory tests, and gut microbiota and metabolites.

RESULTS: Four microbial phyla (Deferribacteres, TM7, Fusobacteria, and Gemmatimonadetes) and 13 genera were significantly enriched across three recipients groups, correlating with baseline inflammatory response and allograft function. Additionally, 52 differentially expressed metabolites were identified, with seven significantly correlating with eight altered microbiota genera. LCGMM revealed two distinct classes of recipients, with those suffering from COVID-19 pneumonia exhibiting significantly elevated serum creatinine (Scr) trajectories over the one-year period. GEE further identified 12 genera and 181 metabolites closely associated with these trajectories; a multivariable model incorporating gut metabolites of 1-Caffeoylquinic Acid and PMK was found to effectively predict one-year allograft function.

CONCLUSIONS: Our study indicates a possible interaction between the composition of the gut microbiota and metabolites community and COVID-19 in renal transplant recipients, particularly in relation to disease severity and the prediction of one-year allograft function.}, } @article {pmid40211191, year = {2025}, author = {Li, A and Costello, SP and Bryant, RV and Haylock-Jacobs, S and Haifer, C and Lee, C and Yeung, D and Giri, P and Blunt, D and Bowen, JB and Ryan, FJ and Yong, A and Wardill, HR}, title = {A study protocol for a double-blinded, randomised, placebo-controlled trial on the use of encapsulated FMT for reducing the side effects of HSCT: the HSCT-BIOME study.}, journal = {BMC cancer}, volume = {25}, number = {1}, pages = {656}, pmid = {40211191}, issn = {1471-2407}, support = {#2021/81-QA25313//Hospital Research Foundation/ ; 2033529//National Health and Medical Research Council/ ; }, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects/methods ; Double-Blind Method ; *Fecal Microbiota Transplantation/methods/adverse effects ; Gastrointestinal Microbiome ; Adult ; Female ; Male ; *Hematologic Neoplasms/therapy ; Randomized Controlled Trials as Topic ; Middle Aged ; Diarrhea/etiology/prevention & control ; Transplantation, Autologous ; Young Adult ; }, abstract = {BACKGROUND: The composition of the gut microbiota both prior to and after haematopoietic stem cell transplantation (HSCT) is increasingly implicated in the outcomes of HSCT, including infections, poor immune reconstitution and disease relapse. Faecal microbiota transplantation (FMT) offers a potential strategy of supporting the gut microbiota and improve HSCT outcomes. Although FMT has been investigated in HSCT recipients, it has largely been evaluated therapeutically for indications such as infection, or once immunocompetency is regained.

METHODS: Peri-HSCT FMT (i.e. before and after HSCT) will be administered to eligible participants (adults undergoing autologous HSCT for a haematological malignancy) over two courses, with the first delivered immediately prior to conditioning and the second starting when ANC > 0.8. Following an open-label, safety run in (N = 5), peri-HSCT FMT will be evaluated for its efficacy in 51 participants, randomised 2:1 to FMT or placebo. The primary outcome is the proportion of participants who develop severe gastrointestinal toxicity defined by 3 consecutive days of severe diarrhoea (Bristol Stool Chart 6+), at a frequency of 4 + bowel movements/day within 3 weeks of HSCT. Safety is defined as the incidence of treatment-emergent adverse events (TE-AEs). Tolerability is defined as the incidence of TE-AEs and adherence to FMT.

DISCUSSION: The HSCT-BIOME study is a multi-centre, double-blind, randomised placebo-controlled trial designed to determine the tolerability, safety and efficacy of orally-administered encapsulated FMT to promote the stability of the gastrointestinal microenvironment for HSCT recipients. Peri-HSCT delivered FMT is hypothesised to promote microbial composition both before and following HSCT. Thus, the study will determine if administration of FMT post-HSCT during the neutropenic phase will enhance efficacy.

TRIAL REGISTRATION: ACTRN12624001104549. Date of registration: September 19, 2024 (prospectively registered).}, } @article {pmid40210439, year = {2025}, author = {Smith, BJ and Zhao, C and Dubinkina, V and Jin, X and Zahavi, L and Shoer, S and Moltzau-Anderson, J and Segal, E and Pollard, KS}, title = {Accurate estimation of intraspecific microbial gene content variation in metagenomic data with MIDAS v3 and StrainPGC.}, journal = {Genome research}, volume = {35}, number = {5}, pages = {1247-1260}, pmid = {40210439}, issn = {1549-5469}, support = {R01 HL160862/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Metagenomics/methods ; *Gastrointestinal Microbiome/genetics ; *Metagenome ; *Genetic Variation ; *Bacteria/genetics/classification ; }, abstract = {Metagenomics has greatly expanded our understanding of the human gut microbiome by revealing a vast diversity of bacterial species within and across individuals. Even within a single species, different strains can have highly divergent gene content, affecting traits such as antibiotic resistance, metabolism, and virulence. Methods that harness metagenomic data to resolve strain-level differences in functional potential are crucial for understanding the causes and consequences of this intraspecific diversity. The enormous size of pangenome references, strain mixing within samples, and inconsistent sequencing depth present challenges for existing tools that analyze samples one at a time. To address this gap, we updated the MIDAS pangenome profiler, now released as version 3, and developed StrainPGC, an approach to strain-specific gene content estimation that combines strain tracking and correlations across multiple samples. We validate our integrated analysis using a complex synthetic community of strains from the human gut and find that StrainPGC outperforms existing approaches. Analyzing a large, publicly available metagenome collection from inflammatory bowel disease patients and healthy controls, we catalog the functional repertoires of thousands of strains across hundreds of species, capturing extensive diversity missing from reference databases. Finally, we apply StrainPGC to metagenomes from a clinical trial of fecal microbiota transplantation for the treatment of ulcerative colitis. We identify two Escherichia coli strains, from two different donors, that are both frequently transmitted to patients but have notable differences in functional potential. StrainPGC and MIDAS v3 together enable precise, intraspecific pangenomic investigations using large collections of metagenomic data without microbial isolation or de novo assembly.}, } @article {pmid40210198, year = {2025}, author = {Fu, M and Wang, QW and Liu, YR and Chen, SJ}, title = {The role of the three major intestinal barriers in ulcerative colitis in the elderly.}, journal = {Ageing research reviews}, volume = {108}, number = {}, pages = {102752}, doi = {10.1016/j.arr.2025.102752}, pmid = {40210198}, issn = {1872-9649}, mesh = {Humans ; *Colitis, Ulcerative/therapy/microbiology/immunology/physiopathology ; *Intestinal Mucosa/immunology ; *Gastrointestinal Microbiome/physiology ; Aged ; *Aging/pathology ; }, abstract = {With the unprecedented pace of global population aging, there has been a parallel epidemiological shift marked by increasing incidence rates of ulcerative colitis (UC) in geriatric populations, imposing a substantial disease burden on healthcare systems globally. The etiopathogenesis of UC in the elderly remains poorly delineated, while current therapeutic strategies require further optimization to accommodate the unique pathophysiological characteristics of elderly patients. This review systematically elucidates the three barrier dysfunction - encompassing the gut microbiota ecosystem, mucosal epithelial integrity, and immunoregulatory network - that collectively drives UC pathogenesis during biological senescence. We emphasize the therapeutic potential of barrier-targeted interventions, particularly highlighting emerging modalities including fecal microbiota transplantation, intestinal organoid regeneration techniques, mesenchymal stem cell-mediated immunomodulation, and precision-engineered Chimeric Antigen Receptor T-cell therapies. Through this multidimensional analysis, we propose a paradigm-shifting approach to UC management in the elderly, advocating for the development of tailored and evidence-based therapeutic interventions that address the complex interplay between age-related biological changes and intestinal barrier homeostasis in elderly patients.}, } @article {pmid40210031, year = {2025}, author = {Zhao, M and Liu, Z and Geng, Y and Lv, X and Xu, J and Zhao, X and Yu, Z and Zhu, R and Li, M and Han, F and Ma, X and Gu, N}, title = {Role of a low-molecular-weight polysaccharide from Boletus edulis Bull: Fr. in modulating gut microbiota and metabolic disorders.}, journal = {International journal of biological macromolecules}, volume = {309}, number = {Pt 3}, pages = {142789}, doi = {10.1016/j.ijbiomac.2025.142789}, pmid = {40210031}, issn = {1879-0003}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Polysaccharides/pharmacology/chemistry ; Mice ; Male ; *Metabolic Diseases/drug therapy/metabolism/microbiology ; Diet, High-Fat/adverse effects ; Molecular Weight ; Lipid Metabolism/drug effects ; Toll-Like Receptor 4/metabolism ; }, abstract = {This study aimed to investigate the effects of Boletus edulis Bull: Fr. polysaccharide (BEP), extracted using a deep eutectic solvent based on l-lactic acid and glycine, on glucose and lipid metabolism in high-fat diet (HFD)-fed mice. The primary mechanism by which BEP improves symptoms of glucose and lipid imbalances involves the modulation of gut microbiota. Key beneficial bacteria, including S24-7, Lachnospiraceae, [Prevotella], and Lactobacillus, were significantly enriched in the intestines of BEP-treated mice, with abundances 2.48-, 1.62-, 6.33- and 2.60-fold higher, respectively, compared to the HFD group. In contrast, the abundance of harmful bacteria, particularly Desulfovibrio, was reduced by 1.81-fold. These microbial shifts contributed to the alleviation of intestinal mucus layer damage and a 50 % reduction in serum lipopolysaccharide (LPS) levels, a key driver of systemic inflammation, compared to the HFD group. As a result, BEP effectively inhibited LPS-induced activation of the hepatic TLR4/Myd88/MAPK signaling pathway, thereby normalizing the expression of proteins related to glucose and lipid metabolism. A fecal microbiota transplantation study further demonstrated that the gut microbiota changes induced by BEP were central to its anti-metabolic syndrome effects. Overall, BEP may serve as a dietary supplement for preventing and treating diet-induced metabolism disorders by targeting the gut microbiota.}, } @article {pmid40209695, year = {2025}, author = {Yamane, T and Masaoka, T and Ishii, C and Masuoka, H and Suda, W and Kurokawa, S and Kishimoto, T and Mikami, Y and Fukuda, S and Kanai, T}, title = {Factors Contributing to the Efficacy of Fecal Microbiota Transplantation for Diarrhea-Dominant Functional Bowel Disorders.}, journal = {Digestion}, volume = {}, number = {}, pages = {1-11}, doi = {10.1159/000545183}, pmid = {40209695}, issn = {1421-9867}, abstract = {INTRODUCTION: In cases of effective fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), donor feces have been observed to be enriched in Bifidobacterium spp. Moreover, FMT for functional bowel disease can improve psychiatric symptoms. Although intestinal dysbiosis has received attention as one of the pathophysiologies of IBS, the efficacy of FMT for IBS has not yet been established. In this study, we performed a post hoc analysis of the efficacy of FMT, focusing on metabolites in donor feces.

METHODS: FMT was performed in 12 patients, 8 with refractory diarrhea-predominant IBS and 4 with functional diarrhea (FDr), who were refractory to medical therapy. The donors were family members within a second degree of kinship and differed for each transplant. Fecal characteristics were evaluated before and 12 weeks after transplantation using the Bristol stool scale (BS). BS scores of 3-5 at 12 weeks after transplantation were considered to indicate responders, while BS scores of 6 and 7 indicated nonresponders. Metagenomic and metabolomic analyses of all 12 donor fecal samples were performed to compare the responder and nonresponder groups.

RESULTS: Before transplantation, all patients had BS scores of 6-7, but 12 weeks after transplantation, 6 were considered responders and 6 were nonresponders. Metagenomic analysis showed that effective donor feces contained significantly higher levels of Prevotella than did the ineffective donor feces. Metabolomic analysis showed that effective donor feces contained significantly higher levels of propionate and butyrate and significantly lower lactate levels than did ineffective donor feces.

CONCLUSION: Propionate-, butyrate-, or Prevotella-rich donor feces may contribute to successful FMT in patients with diarrhea-dominant functional gastrointestinal disorders.}, } @article {pmid40208412, year = {2025}, author = {Sandu, AM and Chifiriuc, MC and Vrancianu, CO and Cristian, RE and Alistar, CF and Constantin, M and Paun, M and Alistar, A and Popa, LG and Popa, MI and Tantu, AC and Sidoroff, ME and Mihai, MM and Marcu, A and Popescu, G and Tantu, MM}, title = {Healthcare-Associated Infections: The Role of Microbial and Environmental Factors in Infection Control-A Narrative Review.}, journal = {Infectious diseases and therapy}, volume = {14}, number = {5}, pages = {933-971}, pmid = {40208412}, issn = {2193-8229}, support = {CNFIS-FDI-2024-F-0484 INOVEX//University of Bucharest/ ; Pillar III//Ministry of Research, Innovation and Digitalization through the National Recovery and Resilience Plan (PNRR) of Romania/ ; Component C9/Investment no. 8 (I8) - contract CF 68//Ministry of Research, Innovation and Digitalization through the National Recovery and Resilience Plan (PNRR) of Romania/ ; Project No. RO1567-IBB05/2023//Institute of Biology Bucharest of the Romanian Academy/ ; project no. 23020101//The core program within the National Research Development and Innovation Plan, 2022-2027', carried out with the support of the Ministry of Research, Innovation and Digitalization (MCID),/ ; Contract no. 7N from 3 January 2023//The core program within the National Research Development and Innovation Plan, 2022-2027', carried out with the support of the Ministry of Research, Innovation and Digitalization (MCID),/ ; Dezvoltarea cercetării genomice în România - ROGEN" (Development of genomic research in Romania -ROGEN).//ROGEN/ ; }, abstract = {Healthcare-associated infections (HAIs), previously known as nosocomial infections, represent a significant threat to healthcare systems worldwide, prolonging patient hospital stays and the duration of antimicrobial therapy. One of the most serious consequences of HAIs is the increase in the rate of antibiotic resistance (AR) generated by the prolonged, frequent, and sometimes incorrect use of antibiotics, which leads to the selection of resistant bacteria, making treatment difficult and expensive, with direct consequences for the safety of patients and healthcare personnel. Therefore, timely and accurate diagnosis of HAIs is mandatory to develop appropriate infection prevention and control practices (IPC) and new therapeutic strategies. This review aimed to present the prevalence, risk factors, current diagnosis, including artificial intelligence (AI) and machine learning approaches, future perspectives in combating HAIs causative bacteria (phage therapy, microbiome-based interventions, and vaccination), and HAIs surveillance strategies. Also, we discussed the latest findings regarding the relationships of AR with climate change and environmental pollution in the context of the One Health approach. Phage therapy is an emerging option that can offer an alternative to ineffective antibiotic treatments for antibiotic-resistant bacteria causing HAIs. Clinical trials dealing with vaccine development for resistant bacteria have yielded conflicting results. Two promising strategies, fecal microbiota transplantation and probiotic therapy, proved highly effective against recurrent Clostridium difficile infections and have been shown to reduce HAI incidence in hospitalized patients undergoing antibiotic therapy. Artificial intelligence and machine learning systems offer promising predictive capabilities in processing large volumes of clinical, microbiological, and patient data but require robust data integration. Our paper argues that HAIs are still a global challenge, requiring stringent IPC policies, computer vision, and AI-powered tools. Despite promising avenues like integrated One Health approaches, optimized phage therapy, microbiome-based interventions, and targeted vaccine development, several knowledge gaps in clinical efficacy, standardization, and pathogen complexity remain to be answered.}, } @article {pmid40208053, year = {2025}, author = {Xu, K and Motiwala, Z and Corona-Avila, I and Makhanasa, D and Alkahalifeh, L and Khan, MW}, title = {The Gut Microbiome and Its Multifaceted Role in Cancer Metabolism, Initiation, and Progression: Insights and Therapeutic Implications.}, journal = {Technology in cancer research & treatment}, volume = {24}, number = {}, pages = {15330338251331960}, pmid = {40208053}, issn = {1533-0338}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Neoplasms/metabolism/therapy/etiology/pathology/microbiology ; Disease Progression ; Animals ; Dysbiosis/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {This review summarizes the intricate relationship between the microbiome and cancer initiation and development. Microbiome alterations impact metabolic pathways, immune responses, and gene expression, which can accelerate or mitigate cancer progression. We examine how dysbiosis affects tumor growth, metastasis, and treatment resistance. Additionally, we discuss the potential of microbiome-targeted therapies, such as probiotics and fecal microbiota transplants, to modulate cancer metabolism. These interventions offer the possibility of reversing or controlling cancer progression, enhancing the efficacy of traditional treatments like chemotherapy and immunotherapy. Despite promising developments, challenges remain in identifying key microbial species and pathways and validating microbiome-targeted therapies through large-scale clinical trials. Nonetheless, the intersection of microbiome research and cancer initiation and development presents an exciting frontier for innovative therapies. This review offers a fresh perspective on cancer initiation and development by integrating microbiome insights, highlighting the potential for interdisciplinary research to enhance our understanding of cancer progression and treatment strategies.}, } @article {pmid40207935, year = {2025}, author = {Karra, DA and Suchodolski, JS and Newman, SJ and Flouraki, E and Lidbury, JA and Steiner, JM and Xenoulis, PG}, title = {Single Enema Fecal Microbiota Transplantation in Cats With Chronic Enteropathy.}, journal = {Journal of veterinary internal medicine}, volume = {39}, number = {3}, pages = {e70054}, pmid = {40207935}, issn = {1939-1676}, mesh = {Animals ; Cats ; *Cat Diseases/therapy ; *Fecal Microbiota Transplantation/veterinary ; Female ; Male ; *Enema/veterinary ; Chronic Disease ; Prospective Studies ; Dysbiosis/veterinary/therapy ; *Intestinal Diseases/veterinary/therapy ; }, abstract = {BACKGROUND: Chronic enteropathies (CE) are common in cats, and alterations of the intestinal microbiota might be involved in the pathogenesis.

HYPOTHESIS/OBJECTIVES: To evaluate the efficacy of a single enema fecal microbiota transplantation (FMT) in improving intestinal dysbiosis and clinical scores in cats with CE.

ANIMALS: Twenty-eight cats with either chronic inflammatory enteropathy (CIE; n = 19) or small cell gastrointestinal lymphoma (SCGL; n = 9) were prospectively enrolled.

METHODS: Eleven cats were randomly selected to receive a single enema FMT (FMT-group), and 17 cats were used as controls. Clinical activity was determined using the Feline Chronic Enteropathy Activity Index (FCEAI), and intestinal dysbiosis was determined using the feline dysbiosis index (DI) on the day of FMT (T0) and 30 days after FMT (T1).

RESULTS: At T0, 14/28 cats had an abnormal DI > 0. No significant difference was found in the DI from T0 to T1 in the FMT group (mean[SD]: 0.01[2.5] vs. 0.7[2.1]; p = 0.47). No significant difference was found in the DI between the FMT group and the control group at T1 (mean[SD]: -0.7[2.1] vs. 0.8[1.8]; p = 0.92). FCEAI significantly decreased at T1 compared to T0 in the FMT group (median[IQR] 10.0[7.7-11.3] vs. 4.5[4-5]; p = 0.002). No significant difference was found in the FCEAI between the FMT group and the control group at T1 (median[IQR] 4.5[4-5] vs. 4[3-5.75]; p = 0.64).

CONCLUSIONS: In this study, single enema FMT did not lead to a significant improvement in DI or FCEAI in cats with CE compared to controls.}, } @article {pmid40207915, year = {2025}, author = {Moya Uribe, IA and Terauchi, H and Bell, JA and Zanetti, A and Jantre, S and Huebner, M and Arshad, SH and Ewart, SL and Mansfield, LS}, title = {Fecal microbiota transplants (FMT) of three distinct human communities to germ-free mice exacerbated inflammation and decreased lung function in their offspring.}, journal = {mBio}, volume = {16}, number = {5}, pages = {e0376424}, pmid = {40207915}, issn = {2150-7511}, support = {GS100019MAN//University Distinguished Professor Endowment/ ; RN031097-DEHN//Albert C. and Lois E. Dehn Endowment/ ; R21AI121748//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; R21 AI121748/AI/NIAID NIH HHS/United States ; R01 AI091905/AI/NIAID NIH HHS/United States ; R01AI091905//HHS | National Institutes of Health (NIH)/ ; RG072646 Mansfield DFI//Michigan State University Discretionary Funds/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; Mice ; *Gastrointestinal Microbiome ; Mice, Inbred C57BL ; *Lung/physiopathology ; Germ-Free Life ; *Inflammation ; Female ; Male ; Infant ; }, abstract = {UNLABELLED: Despite explosive rise in allergies, little is known about early life gut microbiota effects on postnatal respiratory function. We hypothesized that Enterobacteriaceae-dominant gut microbiota from eczemic infants increases Type 2 inflammation and decreases lung function in transplanted mice, while Bacteroidaceae-dominant gut microbiota from non-eczemic infants is protective. Fecal microbiota transplants (FMT) from eczemic infants "Infant A" and non-eczemic infants "Infant B" were successfully transplanted into germ-free C57BL/6 mice, passing to offspring unchanged. Infant A and B, Adult C-human-derived (positive control), and Mouse (negative control) microbiotas all in C57BL/6 mice were tested for effects on airway function in nonallergic (phosphate-buffered saline [PBS]) and allergic (house dust mite [HDM]) conditions. Baseline lung mechanics in mice with human microbiotas ([HU]microbiota) were significantly impaired compared to Mouse microbiota controls ([MO]microbiota) with or without HDM; respiratory system resistance (Rrs) was increased (P < 0.05-P < 0.01), and respiratory system compliance (Crs) was decreased (P < 0.05-P < 0.01). [HU]Microbiota mice showed a statistically significant impairment compared to [MO]microbiota mice in lung parameters Rrs, Ers, Rn, and G at baseline, and at multiple methacholine (MCh) doses with baseline removed. Impairment manifested as increased small airway resistance and tissue resistance. HDM significantly elevated IL-4, eosinophils, lung inflammation, and mucus cell metaplasia, and decreased macrophages and lung function (P < 0.05) in mice of all microbiotas, yet each [HU]microbiota produced distinct features. Infant B and Adult C mice had elevated basal levels of total IgE compared to [MO]microbiota and Infant A mice (P < 0.05). In [HU]microbiota mice given HDM, only Adult C had elevated IL-5 and IL-13 (P < 0.05), only Adult C and Infant B mice had elevated neutrophils (P < 0.05), and only Infant A had elevated lymphocytes (P < 0.01).

IMPORTANCE: Fecal microbiota transplants (FMT) of three distinct human communities to germ-free mice exacerbated inflammation and decreased lung function in their offspring. Taxa formerly described to induce an allergic response (agonists) and pro-inflammatory taxa were abundant in [HU]microbiotas compared to [MO]microbiota controls, while taxa formerly described to reduce allergic responses (antagonists) and anti-inflammatory taxa were numerous in [MO]microbiotas and low in [HU]microbiotas. Thus, we largely rejected our hypotheses because data supported multiple pro-inflammatory allergy agonists functioning in a community-wide fashion to impair lung function in the absence of antagonistic anti-inflammatory taxa. Structure of [HU]microbiotas played a key role in determining varied allergic responses and resulting lung impairment, yet, strikingly, all mice with [HU]microbiotas had impaired lung function even in the absence of allergens. Using a comparative approach, we showed that composition of gut microbiota can alter innate/immune regulation in the gut-lung axis to increase baseline lung function responses and the risk of allergic sensitization.}, } @article {pmid40207909, year = {2025}, author = {Spiegelhauer, MR and Offersen, SM and Mao, X and Gambino, M and Sandris Nielsen, D and Nguyen, DN and Brunse, A}, title = {Protection against experimental necrotizing enterocolitis by fecal filtrate transfer requires an active donor virome.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2486517}, pmid = {40207909}, issn = {1949-0984}, mesh = {Animals ; *Enterocolitis, Necrotizing/prevention & control/therapy/microbiology/pathology ; Swine ; Gastrointestinal Microbiome ; *Feces/virology ; *Virome/radiation effects ; *Fecal Microbiota Transplantation/methods ; Disease Models, Animal ; Animals, Newborn ; Virus Inactivation/radiation effects ; Ultraviolet Rays ; Clostridium perfringens ; Humans ; Bacteria/classification/genetics/isolation & purification ; }, abstract = {Necrotizing enterocolitis (NEC) remains a frequent catastrophic disease in preterm infants, and fecal filtrate transfer (FFT) has emerged as a promising prophylactic therapy. This study explored the role of virome viability for the protective effect of FFT. Using ultraviolet (UV) irradiation, we established a viral inactivation protocol and administered FFT, UV-inactivated FFT (iFFT) or sterile saline orally to preterm piglets at risk for experimental NEC. The gut pathology and barrier properties were assessed, while the microbiome was explored by 16S rRNA amplicon and metavirome sequencing. Like in prior studies, FFT reduced NEC severity and intestinal inflammation, while these effects were absent in the iFFT group. Unexpectedly, piglets receiving FFT exhibited mild side effects in the form of early-onset diarrhea. The FFT also converged the gut colonization by increased viral heterogeneity and a reduced abundance of pathobionts like Clostridium perfringens and Escherichia. In contrast, the gut microbiome of iFFT recipients diverged from both FFT and the controls. These findings highlight the clear distinction between the ability of active and inactivate viromes to modulate gut microbiota and decrease pathology. The efficacy of FFT may be driven by active bacteriophages, and loss of virome activity could have consequences for the treatment efficacy.}, } @article {pmid40207766, year = {2025}, author = {Kumar, M and Mehan, S and Sharma, T and Kumar, A and Khan, Z and Sharma, AK and Kumar, N and Gupta, GD}, title = {Integrating Gut-Brain Axis: Exploring the Neurogastrointestinal Interactions and Therapeutic Potentials in Autism Spectrum Disorder.}, journal = {Endocrine, metabolic & immune disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715303369166250325110016}, pmid = {40207766}, issn = {2212-3873}, abstract = {This comprehensive review critically examines the gut-brain axis (GBA) and its implications in autism spectrum disorder (ASD). The GBA is a complex, bidirectional communication network that integrates the gastrointestinal tract, the central nervous system, and the gut microbiota. This axis is mediated through various physiological pathways, including the enteric nervous system (ENS), the vagus nerve, immune responses, and metabolic activities of gut microorganisms. ASD, a developmental disorder marked by social impairments and repetitive behaviors, presents with notable neurological irregularities. The review highlights the increased prevalence of gastrointestinal (GI) disturbances in individuals with ASD, suggesting a potential link between GI symptoms and the severity of ASD-related behaviors. This correlation is supported by evidence of altered gut microbiota composition in ASD, indicating significant interactions between the gut environment and neurological health. Moreover, the pathophysiology of ASD is explored with an emphasis on genetic and environmental contributions to neurodevelopmental impairments. Key topics include synaptic dysfunction, the roles of neurotransmitters like GABA and serotonin, and the impact of gut-brain interactions on ASD progression. Specifically, this review addresses how gut microbiota may influence metabolic alterations, immune dysregulation, oxidative stress, mitochondrial function, and neurotransmitter production in ASD. Emerging research on microbiome-based therapies for ASD is discussed, focusing on the potential of probiotics, prebiotics, and faecal microbiota transplantation (FMT) as novel interventions. Ethical considerations in this burgeoning field are also considered, highlighting the necessity for rigorous scientific inquiry and ethical oversight. The review advocates for a multidisciplinary approach to understanding and addressing the complexities of ASD. By integrating insights from genetics, neuroscience, psychology, and gastroenterology, a more comprehensive understanding of the role of GBA in ASD can be achieved. This interdisciplinary perspective is crucial for developing effective, individualized treatments and improving the quality of life for individuals with ASD.}, } @article {pmid40207754, year = {2025}, author = {V S, S and Prasad, C and Panicker, SP}, title = {Exploring the Role of Non-Coding RNAs in the Gut and Skin Microbiome: Implications for Colorectal Cancer and Healthy Longevity.}, journal = {MicroRNA (Shariqah, United Arab Emirates)}, volume = {}, number = {}, pages = {}, doi = {10.2174/0122115366342509250401043719}, pmid = {40207754}, issn = {2211-5374}, abstract = {In the last forty years, cancer mortality rates have risen by more than 40%, with colo-rectal cancer (CRC) ranking as the third most common kind worldwide, significantly affected by dietary factors. Restricted access to sophisticated medical treatment and insufficient comprehen-sion of colorectal cancer's biology contribute to its elevated occurrence. Researchers have recog-nized dysbiosis of the gut microbiome as a critical contributor to the development of colorectal cancer, as it influences the expression of non-coding RNAs (ncRNAs) and subsequent molecular pathways essential for tumor proliferation. Moreover, interactions between gut and skin microbi-ota can impact systemic health and ncRNA regulation, influencing CRC advancement. This study shows how important the gut-skin microbiome axis is in developing colorectal cancer. It suggests that targeting this axis may lead to new treatments, such as changing the microbiome through probiotics, prebiotics, or fecal microbiota transplantation. Nonetheless, we must address obstacles such as population heterogeneity and intricate microbiome-host interactions to facilitate the tran-sition of these medicines into clinical practice. This study seeks to elucidate the roles of dietary treatments, microbiomes, and ncRNAs in the etiology and prevention of colorectal cancer (CRC).}, } @article {pmid40207229, year = {2025}, author = {Chen, S and Yi, M and Yi, X and Zhou, Y and Song, H and Zeng, M}, title = {Unveiling the fungal frontier: mycological insights into inflammatory bowel disease.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1551289}, pmid = {40207229}, issn = {1664-3224}, mesh = {Humans ; *Inflammatory Bowel Diseases/microbiology/therapy/immunology/etiology/metabolism ; *Gastrointestinal Microbiome/immunology ; *Dysbiosis/immunology/microbiology ; *Fungi/immunology ; Animals ; *Mycoses/immunology/microbiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal disease that seriously affects the quality of life of patients around the world. It is characterized by recurrent abdominal pain, diarrhea, and mucous bloody stools. There is an urgent need for more accurate diagnosis and effective treatment of IBD. Accumulated evidence suggests that gut microbiota plays an important role in the occurrence and development of gut inflammation. However, most studies on the role of gut microbiota in IBD have focused on bacteria, while fungal microorganisms have been neglected. Fungal dysbiosis can activate the host protective immune pathway related to the integrity of the epithelial barrier and release a variety of pro-inflammatory cytokines to trigger the inflammatory response. Dectin-1, CARD9, and IL-17 signaling pathways may be immune drivers of fungal dysbacteriosis in the development of IBD. In addition, fungal-bacterial interactions and fungal-derived metabolites also play an important role. Based on this information, we explored new strategies for IBD treatment targeting the intestinal fungal group and its metabolites, such as fungal probiotics, antifungal drugs, diet therapy, and fecal microbiota transplantation (FMT). This review aims to summarize the fungal dysbiosis and pathogenesis of IBD, and provide new insights and directions for further research in this emerging field.}, } @article {pmid40206278, year = {2025}, author = {Cresci, GAM and Liu, Q and Sangwan, N and Liu, D and Grove, D and Shapiro, D and Ali, K and Cazzaniga, B and Prete, LD and Miller, C and Hashimoto, K and Quintini, C}, title = {The Impact of Liver Graft Preservation Method on Longitudinal Gut Microbiome Changes Following Liver Transplant: A Proof-of-concept Study.}, journal = {Journal of clinical and translational hepatology}, volume = {13}, number = {4}, pages = {284-294}, pmid = {40206278}, issn = {2310-8819}, abstract = {BACKGROUND AND AIMS: End-stage liver disease is associated with disruptions in gut microbiota composition and function, which may facilitate gut-to-liver bacterial translocation, impacting liver graft integrity and clinical outcomes following liver transplantation. This study aimed to assess the impact of two liver graft preservation methods on fecal microbiota and changes in fecal and breath organic acids following liver transplantation.

METHODS: This single-center, non-randomized prospective pilot study enrolled liver transplant patients whose grafts were preserved using either static cold storage or ex situ normothermic machine perfusion (NMP). Fresh stool and breath samples were collected immediately before surgery and at postoperative months 3, 6, and 12. Stool microbiota was profiled via 16S rRNA gene sequencing, stool short-chain fatty acids were measured using gas chromatography/-mass spectrometry, and breath volatile organic compounds (VOCs) were analyzed with selected-ion flow-tube mass spectrometry.

RESULTS: Both cohorts experienced a loss of microbiota diversity and dominance by single taxa. The NMP cohort demonstrated enrichment of several beneficial gut taxa, while the static cold storage cohort showed depletion of such taxa. Various gut bacteria were found to correlate with stool short-chain fatty acids (e.g., lactic acid, butyric acid) and several VOCs.

CONCLUSIONS: Fecal microbiota alterations associated with end-stage liver disease do not fully normalize to a healthy control profile following liver transplantation. However, notable differences in microbiota composition and function were observed between liver graft preservation methods. Future research with larger randomized cohorts is needed to explore whether the NMP-associated shift in gut microbiota impacts clinical outcomes and if breath VOCs could serve as biomarkers of the clinical trajectory in liver transplant patients.}, } @article {pmid40204291, year = {2025}, author = {Li, S and Li, J and Chen, K and Wang, J and Wang, L and Feng, C and Wang, K and Xu, Y and Gao, Y and Yan, X and Zhao, Q and Li, B and Qiu, Y}, title = {Chronic Arsenic Exposure Causes Alzheimer's Disease Characteristic Effects and the Intervention of Fecal Microbiota Transplantation in Rats.}, journal = {Journal of applied toxicology : JAT}, volume = {45}, number = {8}, pages = {1476-1486}, doi = {10.1002/jat.4782}, pmid = {40204291}, issn = {1099-1263}, support = {202203021211246//Shanxi Natural Science Foundation of China/ ; 20240017//Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Alzheimer Disease/chemically induced/therapy ; *Gastrointestinal Microbiome/drug effects ; *Arsenic/toxicity ; Female ; Rats ; Male ; Rats, Sprague-Dawley ; tau Proteins/metabolism ; Pregnancy ; Hippocampus/drug effects/metabolism ; Amyloid beta-Peptides/metabolism ; Feces/microbiology ; }, abstract = {Arsenic exposure and intestinal microbiota disorders may be related with Alzheimer's disease (AD), but the mechanism has not been elucidated. This study conducted chronic arsenic exposure from rat's maternal body to adult offspring to investigate the mechanisms of the characteristic effects of chronic arsenic exposure on AD, and further explored the intervention effect of fecal microbiota transplantation (FMT) on arsenic-mediated neurotoxicity. Transmission electron microscopy, HE staining, and related indicators were measured in the control group, the exposed group, and the FMT intervention group. Western blot was used to determine microtubule-associated proteins Tau and p-Tau396, intestinal-brain barrier-related proteins Claudin-1 and Occludin, ELISA was used to detect the content of Aβ1-42, and 16S rRNA sequencing was used to detect the intestinal flora of feces. Results showed that chronic arsenic exposure could lead to neurobehavioral defects in rats, increase the expression levels of Tau, p-Tau396, and Aβ1-42 in hippocampus (p < 0.05), increase the abundance of Clostridium _ UCG-014, decrease the abundance of Roseburia, and decrease the expression levels of Claudin-1 and Occludin in colon and hippocampus (p < 0.05). After FMT intervention, the expression levels of Tau and p-Tau396 were decreased (p < 0.05), and the abundance of Roseburia was increased. In summary, chronic arsenic exposure caused intestinal flora disorder by changing the abundance of inflammation-related flora, thereby destroying the gut-brain barrier and causing AD characteristic effects in rats. Although the bacterial specific genus was improved and the expression of AD-related proteins was reduced after transplantation, it could not alleviate the neurobehavioral defects and neurotoxicity caused by arsenic exposure.}, } @article {pmid40203217, year = {2025}, author = {Randolph, NK and Salerno, M and Klein, H and Diaz-Campos, D and van Balen, JC and Winston, JA}, title = {Preparation of Fecal Microbiota Transplantation Products for Companion Animals.}, journal = {PloS one}, volume = {20}, number = {4}, pages = {e0319161}, pmid = {40203217}, issn = {1932-6203}, support = {T35 OD010977/OD/NIH HHS/United States ; }, mesh = {Animals ; Dogs ; Cats ; *Fecal Microbiota Transplantation/methods/veterinary ; *Feces/microbiology ; *Pets/microbiology ; Microbial Viability ; }, abstract = {Fecal microbiota transplantation (FMT) is increasingly utilized in small animal medicine for the treatment of a variety of gastrointestinal and non-gastrointestinal disorders. Despite proven clinical efficacy, there is no detailed protocol available for the preparation and storage of FMT products for veterinarians in a variety of clinical settings. Herein, the effect of processing technique on the microbial community structure was assessed with amplicon sequence analysis. Microbial viability was assessed with standard culture techniques using selective media. Given the fastidious nature of many intestinal microbes, colony forming units are considered surrogate viable microbes, representing a portion of potentially viable microbes. FMT products from four screened canine fecal donors and six screened feline fecal donors were processed aerobically according to a double centrifugation protocol adapted from the human medical literature. Fresh feces from an additional three screened canine fecal donors were used to evaluate the effect of cryopreservative, centrifugation, and short-term storage on microbial community structure and in vitro surrogate bacterial viability. Finally, fresh feces from a third group of three screened canine and three screened feline fecal donors were used to evaluate the long-term in vitro surrogate bacterial viability of three frozen and lyophilized FMT products. Microbiota analysis revealed that each canine fecal donor has a unique microbial profile. Processing of canine and feline feces for FMT does not significantly alter the overall microbial community structure. The addition of cryopreservatives and lyopreservatives significantly improved long-term viability, up to 6 months, for frozen and lyophilized FMT products compared to unprocessed raw feces with no cryopreservative. These results prove the practicality of this approach for FMT preparation in veterinary medicine and provide a detailed protocol for researchers and companion animal practitioners. Future in vivo research is needed to evaluate how the preparation and microbial viability of FMT impacts the recipient's microbial community and clinical outcomes across multiple disease phenotypes.}, } @article {pmid40202719, year = {2025}, author = {Huang, Z and Liu, C and Zhao, X and Guo, Y}, title = {The effect of elevated levels of the gut metabolite TMAO on glucose metabolism after sleeve gastrectomy.}, journal = {Archives of physiology and biochemistry}, volume = {131}, number = {4}, pages = {691-700}, doi = {10.1080/13813455.2025.2489721}, pmid = {40202719}, issn = {1744-4160}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Gastrectomy ; *Methylamines/metabolism/blood ; Mice ; Male ; Liver/metabolism ; *Glucose/metabolism ; Mice, Inbred C57BL ; *Obesity/metabolism/surgery/microbiology ; Forkhead Box Protein O1/metabolism/genetics ; Glycogen/metabolism ; Oxygenases ; }, abstract = {PURPOSE: Bariatric surgery can effectively alleviate obesity and diabetes by regulation of the gut microbiota. This study aimed to investigate the change in the gut microbiota metabolite TMAO and to explore its effect on glucose metabolism after sleeve gastrectomy (SG).

MATERIALS AND METHODS: Diet-induced obesity mouse models were established, and the mice were randomly divided into four groups: an SG group, a sham-operated group pair-fed with the SG group (PF), a sham-operated group fed ad libitum (AL), and a lean control group (C). At 10 weeks post-surgery, the changes in glycogen content of liver, gut microbiota and the level of FMO3 in the liver were evaluated, and their correlation with TMAO production was analysed. The expression levels of the TMAO/PERK/FOXO1 pathway and the gluconeogenic genes G6PC and PCK1 were measured.

RESULTS: At 10 weeks post-surgery, hepatocyte glycogen levels were restored, and serum TMA and TMAO levels were significantly increased. Faecal metagenomic sequencing results showed that the abundances of Ruminococcaceae and Lachnospiraceae, which were positively correlated with TMAO production, were significantly increased after surgery. While the changes in FMO3, the key enzyme producing TMAO in the liver was found decreased significantly after SG. The expression levels of the TMAO/PERK/FOXO1 pathway and the gluconeogenic genes G6PC and PCK1 were measured. Inconsistent with the changing trend of TMAO, the expression of PERK, FOXO1, PCK, and G6PC significantly decreased after SG.

CONCLUSIONS: SG can significantly reduce obesity and restore glucose metabolism. After surgery, TMAO metabolites increased in a microbiota-dependent manner.}, } @article {pmid40202676, year = {2025}, author = {Sharma, S and Tiwari, N and Tanwar, SS}, title = {The current findings on the gut-liver axis and the molecular basis of NAFLD/NASH associated with gut microbiome dysbiosis.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {40202676}, issn = {1432-1912}, abstract = {Recent research has highlighted the complex relationship between gut microbiota, metabolic pathways, and nonalcoholic fatty liver disease (NAFLD) progression. Gut dysbiosis, commonly observed in NAFLD patients, impairs intestinal permeability, leading to the translocation of bacterial products like lipopolysaccharides, short-chain fatty acids, and ethanol to the liver. These microbiome-associated mechanisms contribute to intestinal and hepatic inflammation, potentially advancing NAFLD to NASH. Dietary habits, particularly those rich in saturated fats and fructose, can modify the microbiome composition, leading to dysbiosis and fatty liver development. Metabolomic approaches have identified unique profiles in NASH patients, with specific metabolites like ethanol linked to disease progression. While bariatric surgery has shown promise in preventing NAFLD progression, the role of gut microbiome and metabolites in this improvement remains to be proven. Understanding these microbiome-related pathways may provide new diagnostic and therapeutic targets for NAFLD and NASH. A comprehensive review of current literature was conducted using multiple medical research databases, including PubMed, Scopus, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov, ScienceDirect, Medline, ProQuest, and Google Scholar. The review focused on studies that examine the relationship between gut microbiota composition, metabolic pathways, and NAFLD progression. Key areas of interest included microbial dysbiosis, endotoxin production, and the influence of diet on gut microbiota. The analysis revealed that gut dysbiosis contributes to NAFLD through several mechanisms, diet significantly influences gut microbiota composition, which in turn affects liver function through the gut-liver axis. High-fat diets can lead to dysbiosis, altering microbial metabolic activities and promoting liver inflammation. Specifically, gut microbiota-mediated generation of saturated fatty acids, such as palmitic acid, can activate liver macrophages and increase TNF-α expression, contributing to NASH development. Different dietary components, including cholesterol, fiber, fat, and carbohydrates, can modulate the gut microbiome and influence NAFLD progression. This gut-liver axis plays a crucial role in maintaining immune homeostasis, with the liver responding to gut-derived bacteria by activating innate and adaptive immune responses. Microbial metabolites, such as bile acids, tryptophan catabolites, and branched-chain amino acids, regulate adipose tissue and intestinal homeostasis, contributing to NASH pathogenesis. Additionally, the microbiome of NASH patients shows an elevated capacity for alcohol production, suggesting similarities between alcoholic steatohepatitis and NASH. These findings indicate that targeting the gut microbiota may be a promising approach for NASH treatment and prevention. Recent research highlights the potential of targeting gut microbiota for managing nonalcoholic fatty liver disease (NAFLD). The gut-liver axis plays a crucial role in NAFLD pathophysiology, with dysbiosis contributing to disease progression. Various therapeutic approaches aimed at modulating gut microbiota have shown promise, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and dietary interventions. Probiotics have demonstrated efficacy in human randomized controlled trials, while other interventions require further investigation in clinical settings. These microbiota-targeted therapies may improve NAFLD outcomes through multiple mechanisms, such as reducing inflammation and enhancing metabolic function. Although lifestyle modifications remain the primary recommendation for NAFLD management, microbiota-focused interventions offer a promising alternative for patients struggling to achieve weight loss targets.}, } @article {pmid40201970, year = {2025}, author = {Chen, Y and Zeng, Y and Zhang, Y and Chen, J and Qian, Y and Huang, J and Chen, G and Xia, G and Wang, C and Feng, A and Nie, X}, title = {Differential gut microbiota and inflammatory cytokines contribute to IgA vasculitis.}, journal = {Clinical and experimental rheumatology}, volume = {43}, number = {4}, pages = {563-574}, doi = {10.55563/clinexprheumatol/ff61t7}, pmid = {40201970}, issn = {0392-856X}, mesh = {*Gastrointestinal Microbiome/immunology ; Humans ; Animals ; Male ; Female ; Child ; *Immunoglobulin A/immunology/blood ; *Cytokines/blood/immunology ; *Dysbiosis/immunology ; *IgA Vasculitis/microbiology/immunology/blood/diagnosis ; Case-Control Studies ; Mice ; *Inflammation Mediators/blood ; Disease Models, Animal ; *Bacteria/immunology/genetics ; Adolescent ; Child, Preschool ; Fecal Microbiota Transplantation ; }, abstract = {OBJECTIVES: Immunoglobulin A vasculitis (IgAV) is the most common form of vasculitis in childhood. Emerging evidence indicates that gut microbiota plays a key role in the pathogenesis of IgAV. However, the factors linking gut microbiota to the onset and progression of IgAV are poorly understood. We aimed to demonstrate that the presence of a specific dysbiosis in patients with IgAV contributes to the onset of IgAV.

METHODS: We transplanted gut microbiota from human donors with IgAV or healthy controls (HCs). The changes in gut microbiota and serum indexes of the recipient mice were detected, and the IgAV-associated bacteria were determined by integrating the results from the mouse sequence data analysis with the human sequence results.

RESULTS: 55 amplicon sequence variants (ASVs) specific to IgAV children were detected in the recipient IgAV microbiota (rIMb) mice, and 35 ASVs specific to healthy children were detected in the recipient healthy microbiota (rHMb) mice. Gut microbiota in rIMb mice differs from that in rHMb mice. Alcaligenaceae could discriminate rIMb from rHMb mice, while its abundance was decreased in rIMb compared to rHMb (p<0.05). In children with IgAV, the abundance of Burkholderiaceae (Alcaligenaceae accounted for 99.7%) at the family level was significantly lower compared to HCs, which can be used to distinguish children with IgAV from HCs, and the constructed receiver operating characteristic (ROC) curve had an area under the curve (AUC) value of 0.766. In addition, the rIMb group had a markedly higher interleukin (IL)-17A and IL-21 level than those in the rHMb group. The Spearman correlation analysis indicated significant correlations between the relative levels of these pro-inflammatory cytokines, IgA and alterations of gut microbiota.

CONCLUSIONS: IgAV is characterised by disturbances of gut microbiota composition and an imbalance in inflammatory cytokines. The manipulation of gut microbiota could be a possible way to prevent and manage IgAV.}, } @article {pmid40201831, year = {2025}, author = {Dewey, CW}, title = {Poop for thought: Can fecal microbiome transplantation improve cognitive function in aging dogs?.}, journal = {Open veterinary journal}, volume = {15}, number = {2}, pages = {556-564}, pmid = {40201831}, issn = {2218-6050}, mesh = {Dogs ; Animals ; *Fecal Microbiota Transplantation/veterinary ; *Dog Diseases/therapy/microbiology ; Dysbiosis/therapy/veterinary ; Gastrointestinal Microbiome ; *Aging ; *Cognitive Dysfunction/therapy ; Cognition ; *Alzheimer Disease/therapy/veterinary ; Humans ; }, abstract = {Canine cognitive dysfunction (CCD) is the dog version of human Alzheimer's disease (AD), and it has strikingly similar pathological features to those of this neurodegenerative disorder. The gastrointestinal system is in constant communication with the brain via several conduits collectively termed the gut-brain axis. The microbial population of the gut, referred to as the microbiota, has a profound effect on the interactions that occur along this communication route. Recent evidence suggests that dysbiosis, an abnormal gastrointestinal microbial population, is linked to cognitive impairment in rodent AD models and human AD. There is also evidence from rodent AD models that correcting dysbiosis by transferring fecal material from healthy donors to the gastrointestinal tracts of cognitively impaired recipients [fecal microbiome transplantation (FMT)] reverses AD-associated brain pathology and improves cognitive function. Although limited, some clinical reports have described the improvement of cognitive function with FMT in human AD. The goals of this review article are to provide an overview of the mechanisms involved in dysbiosis- associated cognitive decline and the role of FMT in therapy for such decline. The potential role of FMT in CCD is also discussed.}, } @article {pmid40201444, year = {2025}, author = {Liu, Y and Li, X and Chen, Y and Yao, Q and Zhou, J and Wang, X and Meng, Q and Ji, J and Yu, Z and Chen, X}, title = {Fecal microbiota transplantation: application scenarios, efficacy prediction, and factors impacting donor-recipient interplay.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1556827}, pmid = {40201444}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) represents a therapeutic approach that directly regulates the gut microbiota of recipients, normalizes its composition and reaping therapeutic rewards. Currently, in addition to its general application in treating Clostridium difficile (C. difficile) infection (CDI), FMT treatment has also been extended to the fields of other gastrointestinal diseases, infections, gut-liver or gut-brain axis disorders, metabolic diseases and cancer, etc. Prior to FMT, rigorous donor screening is essential to reduce the occurrence of adverse events. In addition, it is imperative to evaluate whether the recipient can safely and effectively undergo FMT treatment. However, the efficacy of FMT is influenced by the complex interactions between the gut microbiota of donor and recipient, the degree of donor microbiota engraftment is not necessarily positively related with the success rate of FMT. Furthermore, an increasing number of novel factors affecting FMT outcomes are being identified in recent clinical trials and animal experiments, broadening our understanding of FMT treatment. This article provides a comprehensive review of the application scenarios of FMT, the factors influencing the safety and efficacy of FMT from the aspects of both the donors and the recipients, and summarizes how these emerging novel regulatory factors can be combined to predict the clinical outcomes of patients undergoing FMT.}, } @article {pmid40200137, year = {2025}, author = {Wang, X and Geng, Q and Jiang, H and Yue, J and Qi, C and Qin, L}, title = {Fecal microbiota transplantation enhanced the effect of chemoimmunotherapy by restoring intestinal microbiota in LLC tumor-bearing mice.}, journal = {BMC immunology}, volume = {26}, number = {1}, pages = {30}, pmid = {40200137}, issn = {1471-2172}, support = {CJ20220086//Changzhou 8th Batch of Science and Technology Project (Applied Basic Research)/ ; CMCC202201//Clinical Research Project of Changzhou Medical Center, Nanjing Medical University/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; *Fecal Microbiota Transplantation/methods ; Mice ; *Carcinoma, Lewis Lung/therapy/immunology/microbiology ; Mice, Inbred C57BL ; *Immunotherapy/methods ; RNA, Ribosomal, 16S/genetics ; Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology ; }, abstract = {OBJECTIVE: To assess the effect of half-dose chemotherapy (HDC) and standard-dose chemotherapy (SDC) on the intestinal microbiota and to investigate whether fecal microbiota transplantation (FMT) can restore the intestinal microecology to enhance the efficacy of chemoimmunotherapy containing an anti-PD- 1 antibody (PD1).

METHODS: Lewis lung cancer (LLC) tumor-bearing mice were divided into six groups, including Control, HDC, SDC, SDC + FMT, SDC + PD1, and SDC + PD1 + FMT. After the treatment, analyses were conducted on intestinal microbiota using 16S rRNA sequencing, immune cells through flow cytometry, cytokines and chemokines via polymerase chain reaction (PCR), and programmed death-ligand 1 (PD-L1) expression in tumor tissues by immunohistochemistry.

RESULTS: Alpha and beta diversity of intestinal flora were not significantly different between HDC and SDC groups, nor was there a significant difference in the abundance of the top 10 species at the phylum, class, order, family, genus, or species levels. FMT increased both alpha and beta diversity and led to an increase in the abundance of Ruminococcus_callidus and Alistipes_finegoldii at the species level in mice receiving SDC + FMT. Besides, tumor growth was significantly slowed in SDC + PD1 + FMT compared to SDC + PD1 group, accompanied by an up-regulated Bacteroidetes/Firmicutes ratio, down-regulated abundance of Proteobacteria species (including Pseudolabrys, Comamonas, Alcaligenaceae, Xanthobacteraceae and Comamonadaceae), as well as Faecalicoccus of Firmicutes, the increased number of cDC1 cells, cDC2 cells, CD4[+] T cells and CD8[+] T cells in the peripheral blood, and IFN-γ[+]CD8[+] T cells, IFN-γ, granzyme B, TNF-α, CXCL9 and CXCL10 in intestinal tissues.

CONCLUSIONS: There were no significant differences between HDC and SDC in their effects on the intestinal microbiota. FMT exhibited a beneficial impact on gut microbiota and improved the efficacy of chemoimmunotherapy, possibly associated with the increase of immune cells and the modulation of related cytokines and chemokines.}, } @article {pmid40199985, year = {2025}, author = {Vecchiato, CG and Sabetti, MC and Sung, CH and Sportelli, F and Delsante, C and Pinna, C and Alonzo, M and Erba, D and Suchodolski, JS and Pilla, R and Pietra, M and Biagi, G and Procoli, F}, title = {Effect of faecal microbial transplantation on clinical outcome, faecal microbiota and metabolome in dogs with chronic enteropathy refractory to diet.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {11957}, pmid = {40199985}, issn = {2045-2322}, mesh = {Animals ; Dogs ; *Fecal Microbiota Transplantation/methods ; *Metabolome ; Male ; Female ; *Feces/microbiology ; *Dog Diseases/therapy/microbiology/metabolism ; Treatment Outcome ; Gastrointestinal Microbiome ; *Intestinal Diseases/therapy/veterinary/microbiology ; Chronic Disease ; Diet ; Bile Acids and Salts/metabolism ; Dysbiosis/therapy ; }, abstract = {Chronic enteropathy (CE) is a common complaint in canine gastroenterology. Recently, faecal microbiota transplantation (FMT) gained attention as a treatment strategy. However, the efficacy and long-term impact of FMT is still unclear. Clinical index (CIBDAI), faecal microbiota and metabolome were monitored in 20 CE dogs refractory to diet before (T0) and 3 months (T3) after FMT. Further data were retrospectively collected up to 1-year after FMT. Significant improvements were observed in CIBDAI, Dysbiosis Index (DI), and primary (PBAs) and secondary (SBAs) faecal bile acids and propionate one month (T1) after FMT (CIBDAI (median and range): T0 5 (1-9) vs. T1 1 (0-5), p < 0.0001; DI (median and range): T0 -0.1 (-5.6 to 3.8) vs. T1 -2.1 (-5.7 to 4.7), p < 0.05; PBAs decreased by 57%, SBAa increased by 41%; propionate increased by 20%). According to CIBDAI, 17 dogs clinically improved up to T3, and 10 dogs remained clinically stable up to one year after FMT. Alpha- and beta-diversity of the faecal microbiota of CE dogs did not differ, neither before nor after FMT, from that of 17 healthy controls. The results highlight that CE dogs refractory to diet with mild clinical signs and dysbiosis may benefit long-term from treatment with FMT.}, } @article {pmid40199868, year = {2025}, author = {Liu, C and Zheng, X and Ji, J and Zhu, X and Liu, X and Liu, H and Guo, L and Ye, K and Zhang, S and Xu, YJ and Sun, X and Zhou, W and Wong, HLX and Tian, Y and Qian, H}, title = {The carotenoid torularhodin alleviates NAFLD by promoting Akkermanisa muniniphila-mediated adenosylcobalamin metabolism.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {3338}, pmid = {40199868}, issn = {2041-1723}, mesh = {Animals ; *Carotenoids/pharmacology ; Male ; *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism/microbiology ; Mice ; Humans ; Gastrointestinal Microbiome/drug effects ; Mice, Inbred C57BL ; *Akkermansia/metabolism/drug effects ; Liver/metabolism/drug effects/pathology ; Disease Models, Animal ; *Vitamin B 12/metabolism/analogs & derivatives ; Colon/metabolism/drug effects ; }, abstract = {Torularhodin, a unique carotenoid, confers beneficial effects on nonalcoholic fatty liver disease (NAFLD). However, the precise mechanism underlying its therapeutic effects remains unknown. Here, we report that torularhodin alleviates NAFLD in male mice by modulating the gut microbiota. Additionally, transplanting fecal microbiota from torularhodin-treated mice to germ-free mice also improves NAFLD. Mechanistically, torularhodin specifically enriches the abundance of Akkermansia muciniphila, which alleviates NAFLD by promoting the synthesis of adenosylcobalamin. Utilizing a human gastrointestinal system and a colonic organoid model, we further demonstrate that adenosylcobalamin confers protective effects against NAFLD through reducing ceramides, a well-known liver damaging compound, and this effect is mediated by inhibition of the hypoxia-inducible factor 2α pathway. Notably, we construct electrospun microsphere-encapsulated torularhodin, which facilitates the slow release of torularhodin in the colon. Together, our findings indicate the therapeutic potential of microbial utilization of carotenoids, such as torularhodin, for treating NAFLD.}, } @article {pmid40198765, year = {2025}, author = {Saha, S and Rehman, L and Rehman, A and Darbaniyan, F and Weber, DM and Becnel, M and Gaballa, M and Thomas, SK and Lee, HC and Chang, CC and Arora, R and Menges, M and Corallo, S and Davila, ML and Locke, FL and Tanner, MR and Neelapu, SS and Shpall, EJ and Flowers, CR and Orlowski, RZ and Jenq, RR and Jain, MD and Peterson, C and Hansen, DK and Saini, NY and Patel, KK}, title = {Longitudinal analysis of gut microbiome and metabolome correlates of response and toxicity with idecabtagene vicleucel.}, journal = {Blood advances}, volume = {9}, number = {14}, pages = {3429-3440}, pmid = {40198765}, issn = {2473-9537}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Metabolome ; *Immunotherapy, Adoptive/adverse effects/methods ; Male ; Female ; Middle Aged ; Aged ; Longitudinal Studies ; Feces/microbiology ; Receptors, Chimeric Antigen ; }, abstract = {Increasing evidence suggests that the gut microbiome may influence the responses and toxicities associated with chimeric antigen receptor T-cell (CAR-T) therapy. We conducted whole-genome shotgun sequencing on stool samples (N = 117) collected at various times from patients with multiple myeloma (n = 33) who underwent idecabtagene vicleucel (ide-cel) anti-B-cell maturation antigen CAR-T therapy. We observed a significant decrease in bacterial diversity after ide-cel infusion, along with significant differences in the bacterial composition linked to therapy response and toxicities. Specifically, we found significant enrichment of Flavonifractor plautii, Bacteroides thetaiotaomicron, Blautia fecis, and Dysosmobacter species in ide-cel responders. A notable finding was the link of major microbiome disruption, defined as the presence of dominant specific taxa (>35% prevalence), and increased facultative pathobionts, like Enterococcus, with ide-cel toxicities, especially cytokine release syndrome (CRS). Patients with genus dominance in baseline samples had a higher incidence of grade 2 or higher CRS at 46.2% than those without genus dominance (11.1%; P = .043). In addition, network analysis and mass spectrometric assessment of stool metabolites revealed important associations and pathways, such as F plautii being linked to increased indole metabolites and pathways in responders. Our findings uncovered novel microbiome associations between ide-cel responses and toxicities that may be useful for developing modalities to improve CAR-T outcomes.}, } @article {pmid40198451, year = {2025}, author = {Duo, R and Wang, Y and Ma, Q and Wang, X and Zhang, Y and Shen, H}, title = {MTX-induced gastrointestinal reactions in RA: Prevotella enrichment, gut dysbiosis, and PI3K/Akt/Ras/AMPK pathways.}, journal = {Clinical rheumatology}, volume = {44}, number = {6}, pages = {2163-2177}, pmid = {40198451}, issn = {1434-9949}, support = {No. CY2023-MS-A13//CuiYing Technology Project of Lanzhou University/ ; No. 2023-4-27//Science and Technology Planning Project of Lanzhou/ ; No. 2018-3-49//Science and Technology Planning Project of Lanzhou/ ; No. CYXZ2022-13//Cuiying Scientific Training Program for Undergraduates of The Second Hospital & Clinical Medical School/ ; 25JRRA617//Natural Science Foundation of Gansu Province/ ; 2025B-020//Gansu Province Higher Education Institution Teachers' Innovation Fund Project/ ; }, mesh = {*Arthritis, Rheumatoid/drug therapy/microbiology ; Male ; *Gastrointestinal Microbiome/drug effects ; *Dysbiosis/microbiology ; Female ; Humans ; Animals ; *Methotrexate/adverse effects/therapeutic use ; Middle Aged ; *Prevotella ; Mice ; Prospective Studies ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Adult ; Signal Transduction ; *Antirheumatic Agents/adverse effects/therapeutic use ; AMP-Activated Protein Kinases/metabolism ; Aged ; Fecal Microbiota Transplantation ; }, abstract = {OBJECTIVES: To investigate the role of gut microbiota in methotrexate (MTX)-induced gastrointestinal reactions (MRGR) in patients with rheumatoid arthritis (RA).

METHODS: As a prospective, single-center, convenience sampling study, stool samples were obtained from 28 RA patients (male: female = 10:18) at Lanzhou University Second Hospital who were undergoing MTX treatment for analysis of their gut microbiota using 16S rRNA gene sequencing. Clinical disease activity (CDAI) and MRGR were assessed after two months of MTX therapy. All data collection periods exceeded one year. Intestinal germ-free mice, generated through antibiotic treatment, received fecal microbiota transplantation (FMT) from the patients, followed by varying doses of MTX to observe MRGR. Intestinal transcriptomics and markers related to intestinal barrier function were subsequently examined.

RESULTS: Females (84.6%) and high disease activity (CDAI scores, 39.6 ± 11.2 vs 26.3 ± 9.2) were prone to have MRGR in RA patients. Patients with MRGR (PT-GR) showed lower gut microbial diversity versus non-MRGR (PT-noGR). Prevotella abundance, positively correlated with CDAI and MRGR (p < 0.05), was elevated in PT-GR. Administering 10 mg/kg MTX to mice caused intestinal damage. FMT-GR-MTX mice exhibited weight loss (95.2%), morphological deterioration (86.4%), and reduced tight junction proteins (Claudin-1:72.4%; ZO-1:81.2%). Transcriptomics linked upregulated Gβγ/CREB/Atp4b to PI3K/Akt/Ras pathways and downregulated PFK2/PP2 to AMPK signaling in MRGR.

CONCLUSION: Our study identified notable gut microbiota alterations in RA patients prone to MRGR, with changes in intestinal gene expression and reduced intestinal barrier function potentially contributing to MRGR. These findings suggest potential strategies to mitigate MRGR in RA patients undergoing MTX treatment. Key Points • The RA-related MRGR is correlated with the intestinal microbiota. • Females, low gut diversity, and Prevotella enrichment are MRGR risks in RA. • Upregulated DEGs in MRGR linked to PI3K/Akt, Ras pathways. • Downregulated DEGs in MRGR focus on the AMPK pathway.}, } @article {pmid40198007, year = {2025}, author = {Attauabi, M and Madsen, GR and Holm, JP and Bendtsen, F and Møller, S and Seidelin, JB and Burisch, J}, title = {Incidence of Osteoporosis and Osteopenia in Newly Diagnosed Inflammatory Bowel Disease: A Population-Based Cohort Study.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izaf063}, pmid = {40198007}, issn = {1536-4844}, support = {//Novo Nordisk Fonden/ ; 101095470//EU Horizon Europe Program/ ; }, abstract = {BACKGROUND: Individuals with Crohn's disease (CD) and ulcerative colitis (UC) are at risk of developing osteoporosis. In Denmark, osteoporosis has been observed in 12.0% of postmenopausal women and 2.6% in men aged ≥ 50 years in the general population. We aimed to conduct a population-based analysis determining bone mineral density (BMD) at diagnosis of UC and CD.

METHODS: All adult patients diagnosed with UC or CD between May 2021 and May 2023 in an area covering 20% (1.2 million inhabitants) of the Danish population were invited for dual-energy X-ray absorptiometry at inflammatory bowel disease (IBD) diagnosis.

RESULTS: In total, 209 and 141 patients with UC and CD, respectively, were included. Among postmenopausal women (age ≥ 52 years) with UC, 15/42 (35.7%) had osteoporosis and 17/42 (40.5%) had osteopenia, while rates among patients with CD were 6/21 (28.6%, P = .57) and 8/21 (38.1%, P = .86), respectively. Among males aged ≥ 50 years, the rates were 5/38 (13.2%) and 17/38 (44.7%) in UC, respectively, and 3/24 (12.5%, P = 1.00) and 12/24 (50.0%, P = .69) in CD, respectively. Among younger patients, BMD below the expected range for age was observed in 3/69 (4.3%) and 3/60 (5.0%) of females and males with UC, and in 1/42 (2.4%) and 8/54 (14.8%) with CD, respectively. No nutritional or inflammatory marker, including C-reactive protein, fecal calprotectin, Mayo Endoscopic Score, or Simple Endoscopic Score for CD correlated with the T-score.

CONCLUSIONS: This population-based study demonstrated high rates of osteoporosis among postmenopausal women and males aged ≥ 50 years at IBD diagnosis, highlighting the need for systematic evaluation in these patients.}, } @article {pmid40197991, year = {2025}, author = {Malard, F and Thepot, S and Cluzeau, T and Carré, M and Lebon, D and Bories, P and Legrand, O and Schwarz, M and Loschi, M and Meunier, M and Joris, M and Gasc, C and Jouve, J and Levast, B and Plantamura, E and Prestat, E and Sabourin, A and Gaugler, B and Dore, J and Récher, C and Mohty, M}, title = {Gut microbiota restoration with oral pooled fecal microbiotherapy after intensive chemotherapy: the phase 1b CIMON trial.}, journal = {Blood advances}, volume = {9}, number = {15}, pages = {3739-3749}, pmid = {40197991}, issn = {2473-9537}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Male ; Middle Aged ; Female ; Adult ; *Fecal Microbiota Transplantation/methods ; Aged ; *Leukemia, Myeloid, Acute/therapy/drug therapy/microbiology ; Administration, Oral ; Feces/microbiology ; Treatment Outcome ; }, abstract = {Intensive induction chemotherapy (IC) combined with broad-spectrum antibiotics for acute myeloid leukemia (AML) leads to gut microbiota dysbiosis, promoting pathological conditions and an increased incidence of complications, possibly limiting eligibility to allogeneic hematopoietic cell transplantation (alloHCT). The purpose of this dose-ranging phase 1 study (CIMON) was to evaluate the first-in-man use of MaaT033, a pooled, allogeneic, lyophilized, and standardized fecal microbiotherapeutic product, formulated as a delayed-release capsule for oral administration. Primary objectives of the study were to evaluate the maximum tolerable dose of MaaT033 in 21 patients with AML having undergone IC and antibiotics. Secondary objectives were to assess MaaT033 safety, its efficacy in restoring the patients' gut microbiome using shotgun sequencing to evaluate the recommended dose regimen, and patient compliance. MaaT033 was shown to be safe and effective for gut microbiota restoration in patients with AML receiving IC and antibiotics, with an excellent gut microbiota reconstruction based on diversity indices at the species level and restoration of microbial communities close to the composition of the drug product. The maximum tolerable dose of MaaT033 was not determined because the interim results suggested adequate efficacy as measured by engraftment at lower doses (3 capsules per day). Moreover, inflammatory markers (C-reactive protein, interleukin-6) decrease with treatment, whereas short-chain fatty acids increase over time. A randomized, placebo-controlled phase 2b trial, in recipients of alloHCT patients is ongoing. This trial was registered at www.clinicaltrials.gov as #NCT04150393.}, } @article {pmid40196486, year = {2025}, author = {Shealy, NG and Baltagulov, M and de Brito, C and McGovern, A and Castro, P and Schrimpe-Rutledge, AC and Malekshahi, C and Condreanu, SG and Sherrod, SD and Jana, S and Jones, K and Ribeiro, TM and McLean, JA and Beiting, DP and Byndloss, MX}, title = {Short-term alterations in dietary amino acids override host genetic susceptibility and reveal mechanisms of Salmonella Typhimurium small intestine colonization.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40196486}, issn = {2692-8205}, support = {R01 AI168302/AI/NIAID NIH HHS/United States ; R01 DK131104/DK/NIDDK NIH HHS/United States ; T32 ES007028/ES/NIEHS NIH HHS/United States ; }, abstract = {In addition to individual genetics, environmental factors (e.g., dietary changes) may influence host susceptibility to gastrointestinal infection through unknown mechanisms. Herein, we developed a model in which CBA/J mice, a genetically resistant strain that tolerates intestinal colonization by the enteric pathogen Salmonella Typhimurium (S. Tm), rapidly succumb to infection after exposure to a diet rich in L-amino acids (AA). In mice, S. Tm-gastroenteritis is restricted to the large intestine (cecum), limiting their use to understand S. Tm small intestine (ileum) colonization, a feature of human Salmonellosis. Surprisingly, CBA mice fed AA diet developed ileitis with enhanced S. Tm ileal colonization. Using germ-free mice and ileal-fecal slurry transplant, we found diet-mediated S. Tm ileal expansion to be microbiota-dependent. Mechanistically, S. Tm relied on Fructosyl-asparagine utilization to expand in the ileum during infection. We demonstrate how AA diet overrides host genetics by altering the gut microbiota's ability to prevent S. Tm ileal colonization.}, } @article {pmid40195995, year = {2025}, author = {Ayayee, P and Custer, G and Clayton, JB and Price, J and Ramer-Tait, A and Larsen, T}, title = {Assessing gut microbial provisioning of essential amino acids to host in a murine model with reconstituted gut microbiomes.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {40195995}, issn = {2693-5015}, support = {K01 OD030514/OD/NIH HHS/United States ; P20 GM103427/GM/NIGMS NIH HHS/United States ; P30 CA036727/CA/NCI NIH HHS/United States ; }, abstract = {Gut microbial essential amino acid (EAA) provisioning to mammalian hosts remains a critical yet poorly understood aspect of host-microbe nutritional interactions, with significant implications for human and animal health. To investigate microbial EAA contributions in mice with reconstituted gut microbiomes, we analyzed stable carbon isotopes ([13]C) of six EAAs across multiple organs. Germ-free (GF) mice fed a high-protein diet (18%) were compared to conventionalized (CVZ) mice fed a low-protein diet (10%) following fecal microbiota transplantation 30 days prior and a 20-day dietary intervention. We found no evidence for microbial EAA contributions to host tissues, with [13]C-EAA fingerprinting revealing nearly identical patterns between GF and CVZ organs. Both groups maintained their expected microbiome statuses, with CVZ gut microbiota dominated by Firmicutes and Bacteroidetes phyla. These findings raise important questions about the functional capacities of reconstituted gut microbiomes. Future studies should investigate longer adaptation periods, varied dietary protein levels, and complementary analytical techniques to better understand the context-dependent nature of microbial EAA provisioning in mammalian hosts.}, } @article {pmid40195644, year = {2025}, author = {Barrios Steed, D and Koundakjian, D and Harris, AD and Rosato, AE and Konstantinidis, KT and Woodworth, MH}, title = {Leveraging strain competition to address antimicrobial resistance with microbiota therapies.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2488046}, pmid = {40195644}, issn = {1949-0984}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; R38 AI174306/AI/NIAID NIH HHS/United States ; U54 CK000601/CK/NCEZID CDC HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Anti-Bacterial Agents/pharmacology ; *Bacteria/drug effects/genetics/growth & development ; Fecal Microbiota Transplantation ; *Drug Resistance, Bacterial ; Animals ; Probiotics ; }, abstract = {The enteric microbiota is an established reservoir for multidrug-resistant organisms that present urgent clinical and public health threats. Observational data and small interventional studies suggest that microbiome interventions, such as fecal microbiota products and characterized live biotherapeutic bacterial strains, could be an effective antibiotic-sparing prevention approach to address these threats. However, bacterial colonization is a complex ecological phenomenon that remains understudied in the context of the human gut. Antibiotic resistance is one among many adaptative strategies that impact long-term colonization. Here we review and synthesize evidence of how bacterial competition and differential fitness in the context of the gut present opportunities to improve mechanistic understanding of colonization resistance, therapeutic development, patient care, and ultimately public health.}, } @article {pmid40192235, year = {2025}, author = {Jiao, Y and Ren, J and Xie, S and Yuan, N and Shen, J and Yin, H and Wang, J and Guo, H and Cao, J and Wang, X and Wu, D and Zhou, Z and Qi, X}, title = {Raffinose-metabolizing bacteria impair radiation-associated hematopoietic recovery via the bile acid/FXR/NF-κB signaling pathway.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2488105}, pmid = {40192235}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/radiation effects ; *Bile Acids and Salts/metabolism ; Mice ; *NF-kappa B/metabolism/genetics ; Signal Transduction/radiation effects ; *Raffinose/metabolism ; Mice, Inbred C57BL ; Whole-Body Irradiation/adverse effects ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; Fecal Microbiota Transplantation ; Male ; *Acute Radiation Syndrome/microbiology/metabolism ; *Hematopoiesis/radiation effects ; *Bacteria/metabolism/genetics/classification/isolation & purification ; Dysbiosis/microbiology ; }, abstract = {Radiation-associated hematopoietic recovery (RAHR) is critical for mitigating lethal complications of acute radiation syndrome (ARS), yet therapeutic strategies remain limited. Through integrated multi-omics analysis of a total body irradiation (TBI) mouse model, we identify Bacteroides acidifaciens-dominated gut microbiota as key mediators of RAHR impairment. 16S ribosomal rRNA sequencing revealed TBI-induced dysbiosis characterized by Bacteroidaceae enrichment, while functional metagenomics identified raffinose metabolism as the most significantly perturbed pathway. Notably, raffinose supplementation (10% w/v) recapitulated radiation-induced microbiota shifts and delayed bone marrow recovery. Fecal microbiota transplantation (FMT) revealed a causative role for raffinose-metabolizing microbiota, particularly Bacteroides acidifaciens, in delaying RAHR progression. Mechanistically, B. acidifaciens-mediated bile acid deconjugation activated FXR, subsequently suppressing NF-κB-dependent hematopoietic recovery. Therapeutic FXR inhibition via ursodeoxycholic acid (UDCA) had been shown to be a viable method for rescuing RAHR. Our results delineated a microbiome-bile acid-FXR axis as a master regulator of post-irradiation hematopoiesis. Targeting B. acidifaciens or its metabolic derivatives could represent a translatable strategy to mitigate radiation-induced hematopoietic injury.}, } @article {pmid40192143, year = {2025}, author = {Feuerstadt, P and Allegretti, J and Khanna, S}, title = {Treatment of Clostridioides difficile : The Times They Are Changing.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ajg.0000000000003445}, pmid = {40192143}, issn = {1572-0241}, } @article {pmid40192074, year = {2025}, author = {Geng, L and Yang, X and Sun, J and Ran, X and Zhou, D and Ye, M and Wen, L and Wang, R and Chen, M}, title = {Gut Microbiota Modulation by Inulin Improves Metabolism and Ovarian Function in Polycystic Ovary Syndrome.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {20}, pages = {e2412558}, pmid = {40192074}, issn = {2198-3844}, support = {23Y11909600//Science and Technology Commission of Shanghai Municipality/ ; 1365//Talent reservoir program of Shanghai First Maternity and Infant Hospital/ ; 81871213//National Natural Science Foundation of China/ ; 81671468//National Natural Science Foundation of China/ ; SHDC2020CR4080//Shanghai Municipal Hospital Development Center/ ; 2021ScienceandTechnology02-37//Shanghai Collaborative Innovation Center for Chronic Disease Prevention and Health Services/ ; }, mesh = {*Polycystic Ovary Syndrome/metabolism/microbiology/drug therapy ; Female ; *Gastrointestinal Microbiome/drug effects/physiology ; Animals ; *Inulin/pharmacology ; Mice ; Fecal Microbiota Transplantation/methods ; Humans ; *Ovary/metabolism/drug effects ; Disease Models, Animal ; Fatty Acids, Volatile/metabolism ; }, abstract = {The management of metabolic disorder associated with polycystic ovary syndrome (PCOS) has been suggested as an effective approach to improve PCOS which is highly involved with gut microbiota, while the underlying mechanism is unclear. Here, we investigated the role of inulin, a gut microbiota regulator, in the alleviation of PCOS. Our findings showed that inulin treatment significantly improved hyperandrogenism and glucolipid metabolism in both PCOS cohort and mice. Consistent with the cohort, inulin increased the abundance of microbial co-abundance group (CAG) 12 in PCOS mice, including Bifidobacterium species and other short-chain fatty acids (SCFAs)-producers. We further verified the enhancement of SCFAs biosynthesis capacity and fecal SCFAs content by inulin. Moreover, inulin decreased lipopolysaccharide-binding protein (LBP) and ameliorated ovarian inflammation in PCOS mice, whereas intraperitoneal lipopolysaccharide (LPS) administration reversed the protective effects of inulin. Furthermore, fecal microbiota transplantation (FMT) from inulin-treated patients with PCOS enhanced insulin sensitivity, improved lipid accumulation and thermogenesis, reduced hyperandrogenism and ovarian inflammatory response in antibiotic-treated mice. Collectively, these findings revealed that gut microbiota mediates the beneficial effects of inulin on metabolic disorder and ovarian dysfunction in PCOS. Therefore, modulating gut microbiota represents a promising therapeutic strategy for PCOS.}, } @article {pmid40191185, year = {2025}, author = {Chen, L and Ruan, G and Zhao, X and Yi, A and Xiao, Z and Tian, Y and Cheng, Y and Chen, D and Wei, Y}, title = {Pseudomonas aeruginosa enhances anti-PD-1 efficacy in colorectal cancer by activating cytotoxic CD8[+] T cells.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1553757}, pmid = {40191185}, issn = {1664-3224}, mesh = {Animals ; *Colorectal Neoplasms/immunology/therapy/microbiology ; *Pseudomonas aeruginosa/immunology ; Mice ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology ; *Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Gastrointestinal Microbiome/immunology ; Humans ; *CD8-Positive T-Lymphocytes/immunology ; Fecal Microbiota Transplantation ; Female ; Lymphocyte Activation/immunology ; *T-Lymphocytes, Cytotoxic/immunology ; Cell Line, Tumor ; Male ; }, abstract = {BACKGROUND: Immune checkpoint therapy for colorectal cancer (CRC) has been found to be unsatisfactory for clinical treatment. Fecal microbiota transplantation (FMT) has been shown to remodel the intestinal flora, which may improve the therapeutic effect of αPD-1. Further exploration of key genera that can sensitize cells to αPD-1 for CRC treatment and preliminary exploration of immunological mechanisms may provide effective guidance for the clinical treatment of CRC.

METHODS: In this study, 16S rRNA gene sequencing was analyzed in the fecal flora of both responders and no-responders to αPD-1 treatment, and the therapeutic effect was experimentally verified.

RESULTS: Pseudomonas aeruginosa was found to be highly abundant in the fecal flora of treated mice, and Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) in combination with αPD-1 was effective in the treatment of CRC through the induction of CD8[+] T-cell immunological effects.

CONCLUSION: The clinical drug PA-MSHA can be used in combination with αPD-1 for the treatment of CRC as a potential clinical therapeutic option.}, } @article {pmid40190259, year = {2025}, author = {Nagayama, M and Gogokhia, L and Longman, RS}, title = {Precision microbiota therapy for IBD: premise and promise.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2489067}, pmid = {40190259}, issn = {1949-0984}, support = {R01 AT013241/AT/NCCIH NIH HHS/United States ; R01 DK128257/DK/NIDDK NIH HHS/United States ; T32 DK116970/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/methods ; *Inflammatory Bowel Diseases/therapy/microbiology ; Animals ; *Precision Medicine/methods ; }, abstract = {Inflammatory Bowel Disease (IBD) is a spectrum of chronic inflammatory diseases of the intestine that includes subtypes of ulcerative colitis (UC) and Crohn's Disease (CD) and currently has no cure. While IBD results from a complex interplay between genetic, environmental, and immunological factors, sequencing advances over the last 10-15 years revealed signature changes in gut microbiota that contribute to the pathogenesis of IBD. These findings highlight IBD as a disease target for microbiome-based therapies, with the potential to treat the underlying microbial pathogenesis and provide adjuvant therapy to the emerging spectrum of advanced therapies for IBD. Building on the success of fecal microbiota transplantation (FMT) for Clostridioides difficile infection, therapies targeting gut microbiota have emerged as promising approaches for treating IBD; however, unique aspects of IBD pathogenesis highlight the need for more precision in the approach to microbiome therapeutics that leverage aspects of recipient and donor selection, diet and xenobiotics, and strain-specific interactions to enhance the efficacy and safety of IBD therapy. This review focuses on both pre-clinical and clinical studies that support the premise for microbial therapeutics for IBD and aims to provide a framework for the development of precision microbiome therapeutics to optimize clinical outcomes for patients with IBD.}, } @article {pmid40189556, year = {2025}, author = {Zhang, Y and Si, L and Shu, X and Qiu, C and Wan, X and Li, H and Ma, S and Jin, X and Wei, Z and Hu, H}, title = {Gut microbiota contributes to protection against porcine deltacoronavirus infection in piglets by modulating intestinal barrier and microbiome.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {93}, pmid = {40189556}, issn = {2049-2618}, mesh = {Animals ; Swine ; *Gastrointestinal Microbiome ; *Deltacoronavirus/physiology ; *Swine Diseases/microbiology/virology/prevention & control ; *Coronavirus Infections/veterinary/microbiology/virology ; Fecal Microbiota Transplantation ; *Intestinal Mucosa/microbiology ; Feces/microbiology ; Diarrhea ; Intestines/microbiology/virology ; }, abstract = {BACKGROUND: Gut microbiota plays a critical role in counteracting enteric viral infection. Our previous study demonstrated that infection of porcine deltacoronavirus (PDCoV) disturbs gut microbiota and causes intestinal damage and inflammation in piglets. However, the influence of gut microbiota on PDCoV infection remains unclear.

RESULTS: Firstly, the relationship between gut microbiota and disease severity of PDCoV infection was evaluated using 8-day-old and 90-day-old pigs. The composition of gut microbiota was significantly altered in 8-day-old piglets after PDCoV infection, leading to severe diarrhea and intestinal damage. In contrast, PDCoV infection barely affected the 90-day-old pigs. Moreover, the diversity (richness and evenness) of microbiota in 90-day-old pigs was much higher compared to the 8-day-old piglets, suggesting the gut microbiota is possibly associated with the severity of PDCoV infection. Subsequently, transplanting the fecal microbiota from the 90-day-old pigs to the 3-day-old piglets alleviated clinical signs of PDCoV infection, modulated the diversity and composition of gut microbiota, and maintained the physical and chemical barrier of intestines. Additionally, metabolomic analysis revealed that the fecal microbiota transplantation (FMT) treatment upregulated the swine intestinal arginine biosynthesis, FMT significantly inhibited the inflammatory response in piglet intestine by modulating the TLR4/MyD88/NF-κB signaling pathway.

CONCLUSIONS: PDCoV infection altered the structure and composition of the gut microbiota in neonatal pigs. FMT treatment mitigated the clinical signs of PDCoV infection in the piglets by modulating the gut microbiota composition and intestinal barrier, downregulating the inflammatory response. The preventive effect of FMT provides novel targets for the development of therapeutics against enteropathogenic coronaviruses. Video Abstract.}, } @article {pmid40189555, year = {2025}, author = {Zhou, J and Lu, P and He, H and Zhang, R and Yang, D and Liu, Q and Liu, Q and Liu, M and Zhang, G}, title = {The metabolites of gut microbiota: their role in ferroptosis in inflammatory bowel disease.}, journal = {European journal of medical research}, volume = {30}, number = {1}, pages = {248}, pmid = {40189555}, issn = {2047-783X}, support = {No.82474662//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Ferroptosis ; *Gastrointestinal Microbiome/physiology ; *Inflammatory Bowel Diseases/microbiology/metabolism/therapy/pathology ; Oxidative Stress ; Animals ; Fatty Acids, Volatile/metabolism ; Bile Acids and Salts/metabolism ; }, abstract = {Inflammatory bowel disease (IBD) includes chronic inflammatory conditions, such as Crohn's disease and ulcerative colitis, characterized by impaired function of the intestinal mucosal epithelial barrier. In recent years, ferroptosis, a novel form of cell death, has been confirmed to be involved in the pathological process of IBD and is related to various pathological changes, such as oxidative stress and inflammation. Recent studies have further revealed the complex interactions between the microbiome and ferroptosis, indicating that ferroptosis is an important target for the regulation of IBD by the gut microbiota and its metabolites. This article reviews the significant roles of gut microbial metabolites, such as short-chain fatty acids, tryptophan, and bile acids, in ferroptosis in IBD. These metabolites participate in the regulation of ferroptosis by influencing the intestinal microenvironment, modulating immune responses, and altering oxidative stress levels, thereby exerting an impact on the pathological development of IBD. Treatments based on the gut microbiota for IBD are gradually becoming a research hotspot. Finally, we discuss the potential of current therapeutic approaches, including antibiotics, probiotics, prebiotics, and fecal microbiota transplantation, in modulating the gut microbiota, affecting ferroptosis, and improving IBD symptoms. With a deeper understanding of the interaction mechanisms between the gut microbiota and ferroptosis, it is expected that more precise and effective treatment strategies for IBD will be developed in the future.}, } @article {pmid40189523, year = {2025}, author = {Yu, X and Chen, Y and Lei, L and Li, P and Lin, D and Shen, Y and Hou, C and Chen, J and Fan, Y and Jin, Y and Lu, H and Wu, D and Xu, Y}, title = {Mendelian randomization analysis of blood metabolites and immune cell mediators in relation to GVHD and relapse.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {201}, pmid = {40189523}, issn = {1741-7015}, support = {QNXM2024010//Suzhou Science and Education Strengthening Health Youth ProjectSuzhou Science and Education Strengthening Health Youth Project/ ; MQ2024022//Medical research project of Jiangsu Provincial Health Commission/ ; BXQN2023032//Boxi cultivation program project of the First Affiliated Hospital of Suzhou University/ ; KYCX23_3270//Postgraduate Research & Practice Innovation Program of Jiangsu Province/ ; SKJY2021049//Suzhou Science and Technology Program Project/ ; SKY2022043//Suzhou Science and Technology Program Project/ ; SLT201911//Suzhou Science and Technology Program Project/ ; 82100231//National Natural Science Foundation of China/ ; 82020108003//National Natural Science Foundation of China/ ; 82070187//National Natural Science Foundation of China/ ; CXZX202201//Jiangsu Provincial Medical Innovation Center/ ; 2022YFC2502700//National Key Research and Development Program/ ; }, mesh = {*Graft vs Host Disease/genetics/blood/immunology ; Humans ; *Mendelian Randomization Analysis ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Recurrence ; Genome-Wide Association Study ; Male ; Female ; }, abstract = {BACKGROUND: Graft-versus-host disease (GVHD) and relapse are major complications following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Metabolites play crucial roles in immune regulation, but their causal relationships with GVHD and relapse remain unclear.

METHODS: We utilized genetic variants from genome-wide association studies (GWAS) of 309 known metabolites as instrumental variables to evaluate their causal effects on acute GVHD (aGVHD), gut GVHD, chronic GVHD (cGVHD), and relapse in different populations. Multiple causal inference methods, heterogeneity assessments, and pleiotropy tests were conducted to ensure result robustness. Multivariable MR analysis was performed to adjust for potential confounders, and validation MR analysis further confirmed key findings. Mediation MR analysis was employed to explore indirect causal pathways.

RESULTS: After correction for multiple testing, we identified elevated pyridoxate and proline levels as protective factors against grade 3-4 aGVHD (aGVHD3) and relapse, respectively. Conversely, glycochenodeoxycholate increased the risk of aGVHD3, whereas 1-stearoylglycerophosphoethanolamine had a protective effect. The robustness and stability of these findings were confirmed by multiple causal inference approaches, heterogeneity, and horizontal pleiotropy analyses. Multivariable MR analysis further excluded potential confounding pleiotropic effects. Validation MR analyses supported the causal roles of pyridoxate and 1-stearoylglycerophosphoethanolamine, while mediation MR revealed that pyridoxate influences GVHD directly and indirectly via CD39[ +] Tregs. Pathway analyses highlighted critical biochemical alterations, including disruptions in bile acid metabolism and the regulatory roles of vitamin B6 derivatives. Finally, clinical metabolic analyses, including direct fecal metabolite measurements, confirmed the protective role of pyridoxate against aGVHD.

CONCLUSIONS: Our findings provide novel insights into the metabolic mechanisms underlying GVHD and relapse after allo-HSCT. Identified metabolites, particularly pyridoxate, may serve as potential therapeutic targets for GVHD prevention and management.}, } @article {pmid40189067, year = {2025}, author = {Jiang, ST and Wang, MQ and Gao, L and Zhang, QC and Tang, C and Dong, YF}, title = {Adjusting the composition of gut microbiota prevents the development of post-stroke depression by regulating the gut-brain axis in mice.}, journal = {Journal of affective disorders}, volume = {381}, number = {}, pages = {242-259}, doi = {10.1016/j.jad.2025.03.195}, pmid = {40189067}, issn = {1573-2517}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/physiology ; Mice ; Male ; *Fecal Microbiota Transplantation ; *Depression/prevention & control/etiology/microbiology ; *Brain/metabolism ; *Stroke/complications/psychology ; Disease Models, Animal ; *Brain-Gut Axis/physiology/drug effects ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; Fluoxetine/pharmacology ; Mice, Inbred C57BL ; }, abstract = {Disturbances in gut microbiota contribute to an imbalanced gut-brain axis, which is critical for post-stroke depression (PSD), while the underlying mechanisms remain unclear. The objective of this study was to examine the effects of modifying gut microbiota through antibiotic treatment (ABX) and fecal microbiota transplantation (FMT) on the progression of PSD. The PSD model was established by occluding the middle cerebral artery (MCAO), followed by a four-week isolated housing and restraint stress initiated three days after MCAO. For ABX, the PSD mice received antibiotic water for four weeks. While another group of PSD mice underwent FMT or fluoxetine (FLX) for four weeks. At day 35 post-MCAO, behavioral tests were conducted. Results indicated ABX and FMT significantly altered the composition of intestinal flora caused by PSD, all the treatments markedly attenuated anxiety- and depressive-like behaviors and inflammation in the gut and brain. ABX obviously alleviated PSD-induced disorder of intestinal barrier, decreased mRNA levels of TNF-α, IL-1β and IL-6, and decreased CD4[+] cells in the colon. While FMT significantly decreased CD8[+] cells and increased the goblet cells in colon. Furthermore, both ABX and FMT could reduce activated microglia and pro-inflammatory cytokines in the brain, alleviate decreased Nissl's bodies in the hippocampus, and reverse the decreases in 5-HT, Glu and DA in the striatum caused by PSD. Unlike ABX, FMT was similar to FLX. These findings suggest homeostasis of gut microbiota is indispensable for the development of PSD; adjusting the gut microbiota significantly improves PSD with enhanced functions of gut-brain axis.}, } @article {pmid40188410, year = {2025}, author = {Oyovwi, MO and Ben-Azu, B and Babawale, KH}, title = {Therapeutic potential of microbiome modulation in reproductive cancers.}, journal = {Medical oncology (Northwood, London, England)}, volume = {42}, number = {5}, pages = {152}, pmid = {40188410}, issn = {1559-131X}, mesh = {Humans ; *Microbiota ; Probiotics/therapeutic use ; Female ; Dysbiosis/microbiology/therapy ; *Genital Neoplasms, Female/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; Animals ; Gastrointestinal Microbiome ; }, abstract = {The human microbiome, a complex ecosystem of microbial communities, plays a crucial role in physiological processes, and emerging research indicates a potential link between it and reproductive cancers. This connection highlights the significance of understanding the microbiome's influence on cancer development and treatment. A comprehensive review of current literature was conducted, focusing on studies that investigate the relationship between microbiome composition, reproductive cancer progression, and potential therapeutic approaches to modulate the microbiome. Evidence suggests that imbalances in the microbiome, known as dysbiosis, may contribute to the development and progression of reproductive cancers. Specific microbial populations have been associated with inflammatory responses, immune modulation, and even resistance to conventional therapies. Interventions such as probiotics, dietary modifications, and fecal microbiota transplantation have shown promise in restoring healthy microbiome function and improving cancer outcomes in pre-clinical models, with pilot studies in humans indicating potential benefits. This review explores the therapeutic potential of microbiome modulation in the management of reproductive cancers, discussing the mechanisms involved and the evidence supporting microbiome-targeted therapies. Future research is warranted to unravel the complex interactions between the microbiome and reproductive cancer pathophysiology, paving the way for innovative approaches.}, } @article {pmid40187666, year = {2025}, author = {Moreno-Sabater, A and Sintes, R and Truong, S and Lemoine, K and Camou, O and Kapel, N and Magne, D and Joly, AC and Quelven-Bertin, I and Alric, L and Hennequin, C and Sokol, H and , }, title = {Assessment of Dientamoeba fragilis interhuman transmission by fecal microbiota transplantation.}, journal = {International journal of antimicrobial agents}, volume = {66}, number = {2}, pages = {107504}, doi = {10.1016/j.ijantimicag.2025.107504}, pmid = {40187666}, issn = {1872-7913}, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects ; Retrospective Studies ; Male ; *Dientamoeba/isolation & purification ; Female ; Middle Aged ; Feces/parasitology/microbiology ; Aged ; *Clostridium Infections/therapy ; Adult ; *Dientamoebiasis/transmission ; Treatment Outcome ; Clostridioides difficile ; }, abstract = {Fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) requires careful selection of stool donors to avoid transmitting pathogens. Dientamoeba fragilis detection remains an exclusion criterion based on its uncertain pathogenicity. The aim of this study was to assess D. fragilis interhuman transmission by FMT and its impact on the clinical success of rCDI. A retrospective study was conducted in rCDI patients from the COSMIC cohort undergoing FMT to investigate the potential transfer of D. fragilis from donor to recipient. The impact of FMT involving D. fragilis was also evaluated in regard to the clinical outcomes of rCDI and adverse effects. This protist was found to be present in 15 of 86 healthy donors screened (18.7%) who voluntarily took part in an FMT program. Examination of D. fragilis presence in stool samples from 17 patients both before and after FMT with D. fragilis-positive donations revealed no evidence of interhuman transmission through this process. Analysis of clinical outcomes and adverse events in 124 rCDI patients who underwent FMT (with 45 receiving D. fragilis-positive donations) showed no significant differences in success rates between patients receiving positive or negative D. fragilis transplants (95.5% and 93.6%, respectively). No significant variances were observed in other side effects analyzed. These findings underscore the safety of using fecal transplant from D. fragilis-positive donors in the FMT process. D. fragilis should be removed from the donor screening, which will represent a major improvement in the donor selection process from financial and practical standpoints.}, } @article {pmid40187461, year = {2025}, author = {Yang, J and Ren, H and Cao, J and Fu, J and Wang, J and Su, Z and Lu, S and Sheng, K and Wang, Y}, title = {Gut commensal Lachnospiraceae bacteria contribute to anti-colitis effects of Lactiplantibacillus plantarum exopolysaccharides.}, journal = {International journal of biological macromolecules}, volume = {309}, number = {Pt 1}, pages = {142815}, doi = {10.1016/j.ijbiomac.2025.142815}, pmid = {40187461}, issn = {1879-0003}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis/microbiology/drug therapy/pathology/metabolism/therapy ; Mice ; *Lactobacillus plantarum/chemistry ; *Probiotics/pharmacology ; *Polysaccharides, Bacterial/pharmacology ; Fecal Microbiota Transplantation ; *Clostridiales ; Mice, Inbred C57BL ; Male ; }, abstract = {The probiotic Lactiplantibacillus plantarum (L. plantarum) could ameliorate colitis. Alterations in the composition of gut microbiota (GM) have been proved in cases of colitis. The exopolysaccharides from L. plantarum HMPM2111 (LPE) could be effective in colitis through altering the composition of the GM. These effects were linked to inhibiting intestinal inflammation, regulating the TXNIP/NLRP3 inflammasome axis, and attenuating colonic barrier dysfunction. The combination of fecal microbiota transplantation (FMT) and antibiotic inducement showed that gut bacteria susceptible to vancomycin were inversely associated with colitis features and were necessary for the anti-inflammatory effects of LPE. The elevated abundances of gut commensal Lachnospiraceae bacteria were associated with the restoration of colitis treated by LPE. Metabolomics analysis showed that colitis mice treated with LPE had higher levels of propionate and tryptophan metabolites generated from gut bacteria. The administration of these metabolites protected colitis and resulted in a reduction in inflammatory responses. The outcomes of our investigation emerge the significance of the GM in controlling the protective implications of LPE against colitis. Lachnospiraceae bacteria, together with downstream metabolites, contribute substantially to protection. This work elucidates the essential function of the GM-metabolite axis in producing comprehensive protection versus colitis and identifies prospective treatment targets.}, } @article {pmid40187430, year = {2025}, author = {Cai, M and Xue, SS and Zhou, CH and Feng, YC and Liu, JZ and Liu, R and Wang, P and Wang, HN and Peng, ZW}, title = {Effects of fecal microbiota transplantation from patients with generalized anxiety on anxiety-like behaviors: The role of the gut-microbiota-endocannabinoid-brain Axis.}, journal = {Journal of affective disorders}, volume = {381}, number = {}, pages = {131-149}, doi = {10.1016/j.jad.2025.04.018}, pmid = {40187430}, issn = {1573-2517}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Mice ; *Endocannabinoids/metabolism ; Male ; *Anxiety Disorders/therapy/microbiology/metabolism ; Humans ; *Brain/metabolism ; Amidohydrolases/metabolism/genetics ; Receptor, Cannabinoid, CB1/metabolism/genetics ; Mice, Knockout ; *Anxiety ; Mice, Inbred C57BL ; Monoacylglycerol Lipases/genetics/metabolism ; Disease Models, Animal ; Generalized Anxiety Disorder ; }, abstract = {BACKGROUND: Intestinal dysbacteriosis is frequently implicated in generalized anxiety disorder (GAD). However, the molecular mechanisms and functional changes of the gut-brain axis in GAD remain largely unexplored.

METHODS: We investigated anxiety-like behaviors, gut microbiota changes, brain region-specific endocannabinoid (eCB) system alterations, including the expression of cannabinoid type 1 (CB1R), monoacylglycerol lipase (MAGL), and fatty acid amide hydrolase (FAAH) in the hippocampus (Hip), prefrontal cortex (PFC), and amygdala (Amy), as well as plasma medium- and long-chain fatty acids (MLCFAs) in a mouse model of chronic restraint stress (CRS) and antibiotic-treated mice receiving fecal microbiota transplantation from GAD patients (FMT-GAD). Additionally, we assessed the impact of FMT-GAD on anxiety-like behavior in systemic CB1R/FAAH/MAGL knockout mice.

RESULTS: CRS induced anxiety-like behaviors, suppressed eCB signaling in the brain, and altered the gut microbiota and plasma MLCFA composition in mice. FMT-GAD-treated mice exhibited anxiety-like behaviors, increased FAAH expression in the Hip and Amy, and MAGL expression in the Hip, while reducing CB1R expression in the Hip. FMT-GAD was associated with decreased plasma polyunsaturated fatty acids (PUFAs) and reduced microbiome function for fatty acid biosynthesis. Notably, FMT-GAD intensified anxiety-like behaviors in CB1R-KO mice but failed to induce anxiety-like behaviors in MAGL-KO and FAAH-KO mice.

CONCLUSIONS: This study demonstrates that the interplay between the gut microbiota and the eCB system modulates GAD-related anxiety-like behaviors.}, } @article {pmid40185558, year = {2025}, author = {Shin, JH and Jackson-Akers, JY and Hoang, SC and Behm, BW and Warren, CA}, title = {Fulminant Clostridioides difficile Infection: A Journey into the Unknown!.}, journal = {The Medical clinics of North America}, volume = {109}, number = {3}, pages = {721-734}, doi = {10.1016/j.mcna.2025.01.001}, pmid = {40185558}, issn = {1557-9859}, support = {R01 AI145322/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Clostridium Infections/diagnosis/therapy ; *Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile/isolation & purification ; Colectomy ; Fecal Microbiota Transplantation ; Ileostomy ; Immunoglobulins, Intravenous/therapeutic use ; }, abstract = {Clostridioides difficile is 1 of the 5 urgent antibiotic resistance threats in the United States as reported by the Centers for Disease Control and Prevention. Fulminant C difficile infection (CDI), characterized by hallmarks of critical illness such as hypotension, shock, or megacolon, has been difficult to define and treat. In this article, we describe the diagnostic criteria for fulminant CDI, clinical factors and inflammatory markers. We review the currently recommended treatment modalities including antibiotics and surgical interventions, colectomy, and diverting loop ileostomy. We also included treatment approaches that are still investigational such as intestinal microbiota transplant, tigecycline, and intravenous immunoglobulin.}, } @article {pmid40185194, year = {2025}, author = {Docherty, J}, title = {Therapeutic potential of faecal microbiota transplantation for alcohol use disorder, a narrative synthesis.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {138}, number = {}, pages = {111354}, doi = {10.1016/j.pnpbp.2025.111354}, pmid = {40185194}, issn = {1878-4216}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome/physiology ; *Alcoholism/therapy ; Animals ; Brain-Gut Axis/physiology ; }, abstract = {BACKGROUND: Faecal microbiota transplantation is proposed as an alternative therapy to treat alcohol use disorder and has completed a Phase 1 clinical trial, with a Phase 2 clinical trial underway. Alcohol, a modifiable risk factor for noncommunicable diseases, resulted in approximately 3 million global deaths (5 %) in 2016 according to the World Health Organization.

AIMS: A narrative synthesis examines the effects of alcohol and faecal microbiota transplantation on gut microbiota and how gut microbiota impacts the gut-brain axis, leading to certain behavioural symptoms of alcohol use disorder. These behavioural symptoms are alcohol craving and relapse in humans; and preference for alcohol, anxiety and depression in rodents.

SEARCH METHODS AND RESULTS: Electronic databases PubMed, Embase, and Scopus were searched in January 2024 using the terms: faecal microbiota trans* AND alcohol AND microbio*. Ten studies out of 964 met the inclusion criteria of published primary studies with faecal microbiota transplantation as an intervention to study the gut-brain axis in alcohol use disorder.

RESULTS: The gut microbiota is altered in alcohol use disorder, which can be modified with faecal microbiota transplantation. Behavioural symptoms such as alcohol craving and relapse are associated with inflammation due to a loss of intestinal barrier function. Beneficial microbiota produce short-chain fatty acids that maintain intestinal barrier function and reduce inflammation. Studies also reported anxiety and depression-like behaviours, in addition to a preference for alcohol in alcohol-naïve rodents after faecal microbiota transplantation from patients with alcohol use disorder.

CONCLUSIONS: Faecal microbiota transplantation may moderate the behavioural symptoms of alcohol use disorder by altering gut microbiota, affecting intestinal permeability and inflammation, however, specific gut microbiota composition and long-term treatment outcomes require further clinical studies.}, } @article {pmid40185172, year = {2025}, author = {Liu, C and Fan, P and Dai, J and Ding, Z and Yi, Y and Zhan, X and Wang, CC and Liang, R}, title = {Integrated microbiome and metabolome analysis reveals that zishen qingre lishi huayu recipe regulates gut microbiota and butyrate metabolism to ameliorate polycystic ovary syndrome.}, journal = {Microbial pathogenesis}, volume = {204}, number = {}, pages = {107533}, doi = {10.1016/j.micpath.2025.107533}, pmid = {40185172}, issn = {1096-1208}, mesh = {*Polycystic Ovary Syndrome/drug therapy/microbiology/metabolism ; *Gastrointestinal Microbiome/drug effects ; Female ; *Butyrates/metabolism ; Animals ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Mice ; *Metabolome/drug effects ; Humans ; Metabolomics ; Feces/microbiology ; Fecal Microbiota Transplantation ; Adult ; RNA, Ribosomal, 16S/genetics ; Disease Models, Animal ; Testosterone/blood ; Bacteria/classification/genetics/metabolism/isolation & purification ; }, abstract = {BACKGROUND: Polycystic ovary syndrome (PCOS) is a metabolic disorder disease strongly associated with gut microbiota (GM). Zishen Qingre Lishi Huayu recipe (ZQLHR), a traditional Chinese medicinal compound, has patented and shown therapeutic effects in treating PCOS in clinical trials without clear pharmacological mechanisms. This study aimed to disclose the potential therapeutic mechanism of ZQLHR on PCOS.

METHODS: We firstly confirmed the therapeutic effects of ZQLHR treatment in PCOS patients. 16 S rRNA sequencing, untargeted metabolomics, fecal microbiota transplantation (FMT), high performance liquid chromatography (HPLC) and Person's correlation analysis were conducted to elucidate the potential therapeutic mechanism.

RESULTS: These results showed that PCOS symptoms in ZQLHR patients were significantly ameliorated. ZQLHR could increase the levels of butyrate-producing Lachnospira and Faecalibacterium and decrease the abundance of Escherichia-Shigella. Untargeted metabolomics showed that ZQLHR significantly improved host metabolic function, particularly butyrate metabolism and citrate cycle (TCA cycle) metabolism. The combined Faecalibacterium and butyrate metabolism datasets were correlated. Stool samples from ZQLHR patients could ameliorate ovarian architecture, significantly reduce testosterone (T), estradiol (E2) and luteinizing hormone (LH) levels and increased follicle-stimulating hormone (FSH) levels and increase the content of butyric acid in PCOS mice (P < 0.01). Moreover, the correlation analysis showed that some biochemical parameters (T, E2, LH levels and FSH) and butyric acid were correlated.

CONCLUSION: We firstly depicted that ZQLHR could alleviate the series of symptom in women with PCOS by regulating gut microbiota and butyrate metabolism. This study provides a scientific basis and new ideas for the therapy of PCOS.}, } @article {pmid40184763, year = {2025}, author = {Huang, M and Zhang, Y and Chen, Z and Yu, X and Luo, S and Peng, X and Li, X}, title = {Gut microbiota reshapes the TNBC immune microenvironment: Emerging immunotherapeutic strategies.}, journal = {Pharmacological research}, volume = {215}, number = {}, pages = {107726}, doi = {10.1016/j.phrs.2025.107726}, pmid = {40184763}, issn = {1096-1186}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Tumor Microenvironment/immunology ; Animals ; *Immunotherapy/methods ; *Triple Negative Breast Neoplasms/immunology/therapy/microbiology ; Female ; Probiotics/therapeutic use ; Prebiotics/administration & dosage ; Fecal Microbiota Transplantation ; }, abstract = {Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options and poor prognosis. The gut microbiota, a diverse community of microorganisms in the gastrointestinal tract, plays a crucial role in regulating immune responses through the gut-immune axis. Recent studies have highlighted its significant impact on TNBC progression and the efficacy of immunotherapies. This review examines the interactions between gut microbiota and the immune system in TNBC, focusing on key immune cells and pathways involved in tumor immunity. It also explores microbiota modulation strategies, including probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation, as potential methods to enhance immunotherapeutic outcomes. Understanding these mechanisms offers promising avenues for improving treatment efficacy and patient prognosis in TNBC.}, } @article {pmid40184501, year = {2025}, author = {de Schrijver, S and Vanhulle, E and Ingenbleek, A and Alexakis, L and Johannesen, CK and Broberg, EK and Harvala, H and Fischer, TK and Benschop, KSM and , }, title = {Epidemiological and Clinical Insights into Enterovirus Circulation in Europe, 2018-2023: A Multicenter Retrospective Surveillance Study.}, journal = {The Journal of infectious diseases}, volume = {232}, number = {1}, pages = {e104-e115}, pmid = {40184501}, issn = {1537-6613}, support = {//French National Public Health Network/ ; //Santé Publique France/ ; PI18CIII/00017//Instituto de Salud Carlos III/ ; PI22CIII/00035//Instituto de Salud Carlos III/ ; //Clinical Virology Network/ ; TYH2024104//HUS Diagnostic Center/ ; //European Centre for Disease Prevention and Control/ ; }, mesh = {Humans ; *Enterovirus Infections/epidemiology/virology ; Europe/epidemiology ; Retrospective Studies ; Child, Preschool ; Infant ; *Enterovirus/classification/isolation & purification ; Child ; Adolescent ; Male ; Female ; Adult ; Infant, Newborn ; Middle Aged ; Young Adult ; Epidemiological Monitoring ; COVID-19/epidemiology ; Aged ; Seasons ; }, abstract = {BACKGROUND: Enteroviruses (EV) cause yearly outbreaks with severe infections, particularly in young children. This study investigates EV circulation, age, and clinical presentations in Europe from 2018 to 2023.

METHODS: Aggregated data were requested from the European Centre for Disease Prevention and Control National Focal Points for Surveillance and European Non-Polio Enterovirus Network. Data included detection month, specimen type, age group, and clinical presentation for the 10 most commonly reported EV types per year.

RESULTS: Twenty-eight institutions (16 countries) reported 563 654 EV tests during the study period with 33 265 (5.9%) EV positive. Forty-two types were identified (n = 11 605 cases) with echovirus 30 (E30), coxsackievirus A6 (CVA6), EV-D68, E9, E11, CVB5, E18, CVB4, EV-A71, and E6 most frequently reported. E30 declined after 2018/2019, while CVA6, CVB5, E9, E11, and EV-D68 were prevalent both before and after the coronavirus disease 2019 (COVID-19) pandemic, and CVB4 and E18 were prevalent after the pandemic. A shift in seasons (summer to fall) and specimen positivity (feces to respiratory) was observed. Neurological signs predominated among EV-A71, CVB4, CVB5, E6, E9, E11, E18, and E30 (30%-72%). CVB4, CVB5, E9, E11, and E18 were frequently reported among neonates (18%-32%). CVA6 was frequently associated with hand, foot and mouth disease, and EV-D68 with respiratory infections. Paralysis was reported among 22 infections, associated with 10 nonpolio types.

CONCLUSIONS: This study emphasizes the widespread circulation and severity of EV infections in Europe, as well as the (re)emergence of specific types postpandemic. Our findings highlight the need for continuous EV surveillance to monitor variation in circulation, age, and clinical presentations, including paralysis among nonpolio EV infections.}, } @article {pmid40183701, year = {2025}, author = {Peng, W and Jin, Z and Liu, J and Zhang, Q and Liu, W}, title = {Tangeretin modulates gut microbiota metabolism and macrophage immunity following fecal microbiota transplantation in obesity.}, journal = {Journal of food science}, volume = {90}, number = {4}, pages = {e70171}, doi = {10.1111/1750-3841.70171}, pmid = {40183701}, issn = {1750-3841}, support = {//National Natural Science Foundation of China (81670481)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Obesity/therapy/immunology/microbiology/metabolism/drug therapy ; Male ; Mice, Inbred C57BL ; Mice ; *Fecal Microbiota Transplantation ; *Macrophages/immunology/drug effects ; *Flavones/pharmacology ; Diet, High-Fat/adverse effects ; Adipose Tissue/metabolism ; }, abstract = {Obesity, characterized by excessive body fat, is a leading preventable cause of death globally and represents one of the most critical public health challenges of the 21st century. This study aimed to investigate the action of tangeretin on gut microbiota metabolism and inflammation in high-fat diet (HFD)-induced obese mice. A model of obesity was established using 6-week-old male C57BL/6J mice fed with HFD, which were then used for the treatment with tangeretin (20 mg/kg/mice/day) or antibiotic (Abx). The results showed that the tangeretin intervention alleviated fat deposition and disorder of cellular structural integrity in the model group. The obese mice showed a significant increase in the levels of lipid (glycerol, triglyceride, and total cholesterol), inflammatory factors (IL-6 and TNF-α), and F4/80 expression in both serum and adipose tissues. Following tangeretin treatment, the levels of lipid, inflammatory factors, and the ratio of F4/80 + CD206 + macrophages were decreased in both serum and adipose tissue. 16S rRNA sequencing and LC-MS/MS analysis revealed that tangeretin decreased obesity in HFD-induced obese mice by interacting with gut microbiota, particularly influencing Parabacteroides, Blautia, and Parasutterella, and amino acids such as threonine, isoleucine, leucine, phenylalanine, arginine, glutamine, L-tryptophan, and tyrosine. Abx-mediated clearance of gut microbiota blocked the HFD-induced obesity and abrogated the therapeutic effects of tangeretin in obese mice. Fecal microbiota transplantation (FMT) proved that clearing gut microbiota with Abx blocked the beneficial effects of FMT[HFD+Tangeretin] intervention. These findings suggested that tangeretin improved HFD-induced obesity by regulating lipid metabolism and modulating F4/80 macrophage activation via gut microbiota.}, } @article {pmid40182777, year = {2025}, author = {Zhou, S and Zhou, X and Zhang, P and Zhang, W and Huang, J and Jia, X and He, X and Sun, X and Su, H}, title = {The gut microbiota-inflammation-HFpEF axis: deciphering the role of gut microbiota dysregulation in the pathogenesis and management of HFpEF.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1537576}, pmid = {40182777}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Heart Failure/microbiology/therapy/physiopathology/etiology ; *Inflammation/microbiology ; *Dysbiosis ; Animals ; Stroke Volume ; }, abstract = {Heart failure with preserved left ventricular ejection fraction (HFpEF) is a disease that affects multiple organs throughout the body, accounting for over 50% of heart failure cases. HFpEF has a significant impact on individuals' life expectancy and quality of life, but the exact pathogenesis remains unclear. Emerging evidence implicates low-grade systemic inflammation as a crucial role in the onset and progression of HFpEF. Gut microbiota dysregulation and associated metabolites alteration, including short-chain fatty acids, trimethylamine N-oxides, amino acids, and bile acids can exacerbate chronic systemic inflammatory responses and potentially contribute to HFpEF. In light of these findings, we propose the hypothesis of a "gut microbiota-inflammation-HFpEF axis", positing that the interplay within this axis could be a crucial factor in the development and progression of HFpEF. This review focuses on the role of gut microbiota dysregulation-induced inflammation in HFpEF's etiology. It explores the potential mechanisms linking dysregulation of the gut microbiota to cardiac dysfunction and evaluates the therapeutic potential of restoring gut microbiota balance in mitigating HFpEF severity. The objective is to offer novel insights and strategies for the management of HFpEF.}, } @article {pmid40182189, year = {2025}, author = {Burdette, RA and Whitt, CC and Behm, BW and Warren, CA}, title = {Avoiding Premature Antibiotic Use in Recurrent Clostridioides difficile Infection After Fecal Microbiota Transplant.}, journal = {ACG case reports journal}, volume = {12}, number = {4}, pages = {e01660}, pmid = {40182189}, issn = {2326-3253}, abstract = {Recurrent Clostridioides difficile infection (rCDI) remains a major clinical challenge, often requiring fecal microbiota transplantation (FMT) after conventional treatment fails. An 86-year-old woman with rCDI underwent FMT after failing multiple antibiotic therapies. Shortly after FMT, she experienced diarrhea and abdominal pain, alongside positive C. difficile stool tests. Antibiotics were withheld because of clinical improvement, and she achieved complete resolution of symptoms without further treatment. This case demonstrates the potential benefit of withholding antibiotics in rCDI patients soon after FMT to allow sufficient time for donor microbiota engraftment and underscores the need for further research to optimize post-FMT management.}, } @article {pmid40180421, year = {2025}, author = {Clavijo-Salomon, MA and Trinchieri, G}, title = {Unlocking the power of the microbiome for successful cancer immunotherapy.}, journal = {Journal for immunotherapy of cancer}, volume = {13}, number = {4}, pages = {}, pmid = {40180421}, issn = {2051-1426}, mesh = {Humans ; *Immunotherapy/methods ; *Neoplasms/therapy/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Fecal Microbiota Transplantation/methods ; *Microbiota ; }, abstract = {In recent years, evidence has shown that the gut microbiome significantly influences responses to immunotherapy. This has sparked interest in targeting it to improve therapy outcomes and predictions of response and toxicity. Research has demonstrated that dysbiosis, often resulting from antibiotic use, can diminish the effectiveness of immune checkpoint inhibitors, and this lack of efficacy could be linked to systemic inflammation. Certain bacterial species have been identified as having beneficial and harmful effects on immunotherapy in the clinic. While a clear consensus has yet to emerge on the optimal species for therapeutic use, introducing a new microbiome into immunotherapy-refractory patients may boost their chances of responding to further treatment attempts. State-of-the-art interventions targeting the microbiome-such as fecal microbiota transplantation-are being assessed clinically for their safety and potential to enhance treatment outcomes, with promising results. Additionally, the microbiome has been leveraged for its power to predict clinical outcomes using machine learning, and surprisingly, its predictive capability is comparable to that of other described multi-biomarker clinical scores. Here, we discuss developing knowledge concerning the microbiome's significance in cancer immunotherapy and outline future strategies for maximizing its potential in immuno-oncology.}, } @article {pmid40177494, year = {2025}, author = {Liu, J and Li, F and Yang, L and Luo, S and Deng, Y}, title = {Gut microbiota and its metabolites regulate insulin resistance: traditional Chinese medicine insights for T2DM.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1554189}, pmid = {40177494}, issn = {1664-302X}, abstract = {The gut microbiota is closely associated with the onset and development of type 2 diabetes mellitus (T2DM), characterized by insulin resistance (IR) and chronic low-grade inflammation. However, despite the widespread use of first-line antidiabetic drugs, IR in diabetes and its complications continue to rise. The gut microbiota and its metabolic products may promote the development of T2DM by exacerbating IR. Therefore, regulating the gut microbiota has become a promising therapeutic strategy, with particular attention given to probiotics, prebiotics, synbiotics, and fecal microbiota transplantation. This review first examines the relationship between gut microbiota and IR in T2DM, summarizing the research progress of microbiota-based therapies in modulating IR. We then delve into how gut microbiota-related metabolic products contribute to IR. Finally, we summarize the research findings on the role of traditional Chinese medicine in regulating the gut microbiota and its metabolic products to improve IR. In conclusion, the gut microbiota and its metabolic products play a crucial role in the pathophysiological process of T2DM by modulating IR, offering new insights into potential therapeutic strategies for T2DM.}, } @article {pmid40177417, year = {2025}, author = {Wu, Y and Chen, X and Wu, Q and Wang, Q}, title = {Research progress on fecal microbiota transplantation in tumor prevention and treatment.}, journal = {Open life sciences}, volume = {20}, number = {1}, pages = {20220954}, pmid = {40177417}, issn = {2391-5412}, abstract = {The application of fecal microbiota transplantation (FMT) as a therapeutic strategy to directly modify the makeup of the gut microbiota has made significant progress in the last few decades. The gut microbiota, a sizable microbial community present in the human gut, is essential for digestion, immunomodulation, and nutrition absorption. Alternatively, a growing body of research indicates that gut microbiota is a key contributor to cancer, and intratumoral bacteria are considered to be crucial "accomplices" in the development and metastasis of malignancies. The exceptional clinical effectiveness of FMT in treating melanoma patients has been adequately established in earlier research, which has created new avenues for the diagnosis and treatment of cancer and sparked an increasing interest in the treatment and prevention of other cancers. However, further research on the function and mechanisms of the gut microbiota is required to properly comprehend the impact and role of these organisms in tumor regulation. In this article, we present a detailed account of the influence of FMT on the entire course of cancer patients' illness and treatment, from tumor development, metastasis, and invasion, to the impact and application of treatment and prognosis, as well as address the associated mechanisms.}, } @article {pmid40176987, year = {2025}, author = {Yarahmadi, A and Najafiyan, H and Yousefi, MH and Khosravi, E and Shabani, E and Afkhami, H and Aghaei, SS}, title = {Beyond antibiotics: exploring multifaceted approaches to combat bacterial resistance in the modern era: a comprehensive review.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1493915}, pmid = {40176987}, issn = {2235-2988}, mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use/pharmacology ; *Drug Resistance, Bacterial ; *Bacterial Infections/therapy/microbiology/drug therapy ; Animals ; *Bacteria/drug effects ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Antimicrobial Peptides/therapeutic use ; }, abstract = {Antibiotics represent one of the most significant medical breakthroughs of the twentieth century, playing a critical role in combating bacterial infections. However, the rapid emergence of antibiotic resistance has become a major global health crisis, significantly complicating treatment protocols. This paper provides a narrative review of the current state of antibiotic resistance, synthesizing findings from primary research and comprehensive review articles to examine the various mechanisms bacteria employ to counteract antibiotics. One of the primary sources of antibiotic resistance is the improper use of antibiotics in the livestock industry. The emergence of drug-resistant microorganisms from human activities and industrial livestock production has presented significant environmental and public health concerns. Today, resistant nosocomial infections occur following long-term hospitalization of patients, causing the death of many people, so there is an urgent need for alternative treatments. In response to this crisis, non-antibiotic therapeutic strategies have been proposed, including bacteriophages, probiotics, postbiotics, synbiotics, fecal microbiota transplantation (FMT), nanoparticles (NPs), antimicrobial peptides (AMPs), antibodies, traditional medicines, and the toxin-antitoxin (TA) system. While these approaches offer innovative solutions for addressing bacterial infections and preserving the efficacy of antimicrobial therapies, challenges such as safety, cost-effectiveness, regulatory hurdles, and large-scale implementation remain. This review examines the potential and limitations of these strategies, offering a balanced perspective on their role in managing bacterial infections and mitigating the broader impact of antibiotic resistance.}, } @article {pmid40176137, year = {2025}, author = {Sommer, F and Bernardes, JP and Best, L and Sommer, N and Hamm, J and Messner, B and López-Agudelo, VA and Fazio, A and Marinos, G and Kadibalban, AS and Ito, G and Falk-Paulsen, M and Kaleta, C and Rosenstiel, P}, title = {Life-long microbiome rejuvenation improves intestinal barrier function and inflammaging in mice.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {91}, pmid = {40176137}, issn = {2049-2618}, support = {SO1141/10-1//Deutsche Forschungsgemeinschaft/ ; CRC1182//Deutsche Forschungsgemeinschaft/ ; miTARGET//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; RNA, Ribosomal, 16S/genetics ; *Fecal Microbiota Transplantation ; *Aging/physiology ; Feces/microbiology ; *Bacteria/classification/genetics/isolation & purification ; Male ; *Intestinal Mucosa/microbiology/metabolism ; *Inflammation/microbiology ; Mice, Inbred C57BL ; *Rejuvenation ; Permeability ; *Intestines/microbiology ; Metagenomics ; Intestinal Barrier Function ; }, abstract = {BACKGROUND: Alterations in the composition and function of the intestinal microbiota have been observed in organismal aging across a broad spectrum of animal phyla. Recent findings, which have been derived mostly in simple animal models, have even established a causal relationship between age-related microbial shifts and lifespan, suggesting microbiota-directed interventions as a potential tool to decelerate aging processes. To test whether a life-long microbiome rejuvenation strategy could delay or even prevent aging in non-ruminant mammals, we performed recurrent fecal microbial transfer (FMT) in mice throughout life. Transfer material was either derived from 8-week-old mice (young microbiome, yMB) or from animals of the same age as the recipients (isochronic microbiome, iMB) as control. Motor coordination and strength were analyzed by rotarod and grip strength tests, intestinal barrier function by serum LAL assay, transcriptional responses by single-cell RNA sequencing, and fecal microbial community properties by 16S rRNA gene profiling and metagenomics.

RESULTS: Colonization with yMB improved coordination and intestinal permeability compared to iMB. yMB encoded fewer pro-inflammatory factors and altered metabolic pathways favoring oxidative phosphorylation. Ecological interactions among bacteria in yMB were more antagonistic than in iMB implying more stable microbiome communities. Single-cell RNA sequencing analysis of intestinal mucosa revealed a salient shift of cellular phenotypes in the yMB group with markedly increased ATP synthesis and mitochondrial pathways as well as a decrease of age-dependent mesenchymal hallmark transcripts in enterocytes and TA cells, but reduced inflammatory signaling in macrophages.

CONCLUSIONS: Taken together, we demonstrate that life-long and repeated transfer of microbiota material from young mice improved age-related processes including coordinative ability (rotarod), intestinal permeability, and both metabolic and inflammatory profiles mainly of macrophages but also of other immune cells. Video Abstract.}, } @article {pmid40175647, year = {2025}, author = {Ahn, JS and Kim, S and Han, EJ and Hong, ST and Chung, HJ}, title = {Increasing spatial working memory in mice with Akkermansia muciniphila.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {546}, pmid = {40175647}, issn = {2399-3642}, support = {C512230//Korea Basic Science Institute (KBSI)/ ; RS-2023-00224099//National Research Foundation of Korea (NRF)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; *Fecal Microbiota Transplantation ; *Memory, Short-Term/physiology ; Male ; *Spatial Memory/physiology ; Akkermansia ; Humans ; Verrucomicrobia ; Feces/microbiology ; Brain-Derived Neurotrophic Factor/metabolism ; }, abstract = {Recent research has shown the gut microbiome's impact on memory, yet limitations hinder the identification of specific microbes linked to cognitive function. We measured spatial working memory in individual mice before and after fecal microbiota transplantation (FMT) to develop a targeted analysis that identifies memory-associated strains while minimizing host genetic effects. Transplantation of human fecal into C57BL/6 mice yielded varied outcomes: some mice showed significant improvements while others had negligible changes, indicating that these changes are due to differences in FMT colonization. Metagenomic analysis, stratified by memory performance, revealed a positive correlation between the abundance of Akkermansia muciniphila and improved memory. Moreover, administering two A. muciniphila strains, GMB 0476 and GMB 2066, to wild-type mice elevated spatial working memory via BDNF activation. Our findings indicate that specific gut microbes, particularly A. muciniphila, may modulate memory and represent potential targets for therapeutic intervention in cognitive enhancement.}, } @article {pmid40175389, year = {2025}, author = {Braga, JD and Yang, Y and Nagao, T and Kato, N and Yanaka, N and Nishio, K and Okada, M and Kuroda, M and Yamaguchi, S and Kumrungsee, T}, title = {Fructooligosaccharides and Aspergillus enzymes increase brain GABA and homocarnosine by modulating microbiota in adolescent mice.}, journal = {NPJ science of food}, volume = {9}, number = {1}, pages = {48}, pmid = {40175389}, issn = {2396-8370}, abstract = {Recent research suggests that dietary prebiotics, probiotics, or healthy fecal-microbiota transplantation attenuate gut microbiota dysbiosis and ameliorate neurological disorders, in which gut-microbiota-derived γ-aminobutyric acid (GABA) has gained much attention as one of key mediators in the gut-brain axis. Although it is widely accepted that prebiotics and probiotics induce gut and brain GABA production via modulating gut microbiota, only evidence of probiotics has been solidly demonstrated while this evidence of prebiotics is scarce. Here, we demonstrated that prebiotic fructo-oligosaccharides and Aspergillus-derived enzymes elevated gut and brain GABA concentrations by modulating gut microbiota. Interestingly, we found that the prebiotic and enzymes increased a brain-specific dipeptide, homocarnosine. Gut GABA levels were found correlated with brain GABA/homocarnosine levels. Parabateroides, Akkermansia, Muribaculum, Hungatella, Marvinbryantia, Flavonifractor, and Incertae_sedis exhibited a positive correlation with gut GABA and brain GABA/homocarnosine levels, while Blautia, Unclassified_Lachnospiraceae, Colidextribacter, Acetatifactor, Roseburia, Unclassified_Oscillospiraceae, Romboutsia, and Eubacterium_coprostanoligenes exhibited a negative correlation with those levels.}, } @article {pmid40174272, year = {2025}, author = {Abavisani, M and Tafti, P and Khoshroo, N and Ebadpour, N and Khoshrou, A and Kesharwani, P and Sahebkar, A}, title = {The heart of the matter: How gut microbiota-targeted interventions influence cardiovascular diseases.}, journal = {Pathology, research and practice}, volume = {269}, number = {}, pages = {155931}, doi = {10.1016/j.prp.2025.155931}, pmid = {40174272}, issn = {1618-0631}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Cardiovascular Diseases/microbiology/therapy/prevention & control ; *Dysbiosis/microbiology/complications ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics ; Animals ; }, abstract = {The human body is habitat to a wide spectrum of microbial populations known as microbiota, which play an important role in overall health. The considerable research has mostly focused on the gut microbiota due to its potential to impact numerous physiological functions and its correlation with a variety of disorders, such as cardiovascular diseases (CVDs). Imbalances in the gut microbiota, known as dysbiosis, have been linked to the development and progression of CVDs through various processes, including the generation of metabolites like trimethylamine-N-oxide and short-chain fatty acids. Studies have also looked at the idea of using therapeutic interventions, like changing your diet, taking probiotics or prebiotics, or even fecal microbiota transplantation (FMT), to change the gut microbiota's make-up and how it works in order to prevent or treat CVDs. Exploring the cause-and-effect connection between the gut microbiota and CVDs offers a hopeful path for creating innovative microbiome-centered strategies to prevent and cure CVDs. This review presents an in-depth review of the correlation between the gut microbiota and CVDs, as well as potential therapeutic approaches for manipulating the gut microbiota to enhance cardiovascular health.}, } @article {pmid40171188, year = {2025}, author = {Li, C and Cheng, D and Ren, H and Zhang, T}, title = {Unraveling the gut microbiota's role in PCOS: a new frontier in metabolic health.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1529703}, pmid = {40171188}, issn = {1664-2392}, mesh = {Humans ; *Polycystic Ovary Syndrome/microbiology/metabolism ; *Gastrointestinal Microbiome/physiology ; Female ; *Dysbiosis/microbiology/metabolism ; Energy Metabolism ; }, abstract = {Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting reproductive-age women, characterized primarily by hyperandrogenism, ovulatory dysfunction, and metabolic abnormalities. In recent years, the gut microbiota has garnered widespread attention for its potential role as a key regulator of host metabolism in the pathogenesis of PCOS. Studies have shown that PCOS patients exhibit dysbiosis in their gut microbiota, characterized by reduced microbial diversity, an imbalance in the ratio of Firmicutes to Bacteroidetes, changes in the abundance of specific taxa, and abnormal levels of metabolic products. These alterations may exacerbate metabolic dysfunction in PCOS through multiple mechanisms, including influencing host energy metabolism, disrupting lipid and bile acid metabolism, and inducing chronic inflammation. Addressing gut dysbiosis through the modulation of patients' microbiomes-such the use of, prebiotics, fecal microbiota transplantation, and optimizing diet lifestyle-may offer strategies for improving metabolic abnormalities and alleviating clinical symptoms in PCOS. Additionally, the gut microbiome promises as a potential marker, aiding in the precise diagnosis and personalization of PCOS. Although our current understanding of how the gut microbiota influences PCOS is still limited, research is needed to explore the causal relationships and mechanisms involved, providing a more reliable theoretical basis for clinical. This review aims summarize the research progress on the relationship between gut microbiota and PCOS, and to suggest future directions to promote the development of prevention and treatment strategies for PCOS.}, } @article {pmid40171160, year = {2025}, author = {Chen, F and Zhang, H and Wei, Q and Tang, J and Yin, L and Ban, Y and Zhou, Q}, title = {Disrupted gut microbiota promotes the progression of chronic kidney disease in 5/6 nephrectomy mice by Bacillus pumilus gavage.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1548767}, pmid = {40171160}, issn = {2235-2988}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Renal Insufficiency, Chronic/microbiology/pathology ; Mice ; Disease Models, Animal ; Probiotics/administration & dosage ; Disease Progression ; RNA, Ribosomal, 16S/genetics ; Nephrectomy ; *Bacillus pumilus/physiology ; Feces/microbiology ; Kidney/pathology ; Male ; Mice, Inbred C57BL ; Dysbiosis ; Metabolomics ; }, abstract = {BACKGROUND: Our previous study identified differences in the gut microbiota between patients with chronic kidney disease (CKD) and healthy individuals. We observed that antibiotic-treated mice exhibited symptoms similar to those of patients with CKD after receiving a gut microbiota transplant from patients with CKD. Bacillus pumilus (B. pumilus), an alien microorganism to both human and mouse gut microbiota, possesses antibiotic properties that can alter the microbial community structure. Therefore, this study aimed to explore how changes in the gut microbiota structure induced by the oral gavage of B. pumilus affect the progression of CKD. We sought to identify the gut microbes and metabolic pathways associated with CKD to lay the groundwork for future clinical probiotic applications in patients with CKD.

METHODS: We constructed sham-operated and 5/6 nephrectomy mice as the sham control (SC) and CKD models, respectively. CKD models were divided into a control group (CG) and an intervention group (IG). After 16 weeks of normal feeding, the IG were treated with B. pumilus by oral gavage, while SC and CG were treated with PBS once daily, 5 days per week, for 7 weeks. Fecal samples were collected for 16s rRNA sequencing and metabolomic analysis, kidneys were harvested for histological examination, and the colon was used for RT-PCR analysis.

RESULTS: B. pumilus intervention exacerbated gut microbial homeostasis in CKD mice and increased serum creatinine and urea nitrogen levels, further aggravating kidney damage. 16s rRNA and metabolomic analysis revealed that Parvibacter and Enterorhabdus were probiotics related to kidney function, while Odoribacter was associated with kidney injury. Metabolomic analysis showed that glycerophospholipid and lysine metabolism were upregulated in CKD model mice, correlating with kidney damage.

CONCLUSION: This study shows that changes in the gut microbiota can affect the kidneys through gut metabolism, confirming that the lack of probiotics and the proliferation of harmful bacteria leading to gut microbiota dysbiosis are drivers of CKD progression. Our findings provide a basis for clinical interventions using gut microbes and offer a reference for targeted probiotic therapy.}, } @article {pmid40170570, year = {2025}, author = {Yao, N and Liu, Y and Zhang, ZY and Tian, M and Xie, WJ and Zhao, H and Yang, H and Rodewald, LE and Wen, N and Yin, ZD and Wang, FZ and Wang, Q and Xu, JW}, title = {Excretion and clearance of Sabin-like type 3 poliovirus in a child diagnosed with severe combined immunodeficiency.}, journal = {Human vaccines & immunotherapeutics}, volume = {21}, number = {1}, pages = {2484882}, pmid = {40170570}, issn = {2164-554X}, mesh = {Humans ; *Poliovirus/isolation & purification ; *Severe Combined Immunodeficiency/complications/therapy ; *Poliomyelitis/virology/epidemiology ; *Virus Shedding ; Hematopoietic Stem Cell Transplantation/adverse effects ; Child, Preschool ; Female ; Feces/virology ; Pilot Projects ; Infant ; Poliovirus Vaccine, Oral/adverse effects/administration & dosage ; Male ; Child ; Homeodomain Proteins ; }, abstract = {Children with primary immunodeficiency disorder (PID) are at higher risk of developing vaccine-associated paralytic poliomyelitis (VAPP) or vaccine-derived polioviruses (VDPV) infection when inadvertently expose to poliovirus vaccine, oral (OPV). A pilot study was initiated to describe the epidemiology of immunodeficiency-associated VDPV (iVDPV) and to estimate the risk of iVDPV shedding among individuals with PID. Children under 18 years of age newly diagnosed with PID were recruited for investigation and tested for poliovirus excretion. Children with poliovirus-positive stool samples had regular follow-up testing for poliovirus excretion and determination of clinical prognosis. A patient with severe combined immunodeficiency (SCID) with compound heterozygous mutations in the RAG1 gene was found to be excreting Sabin-like type 3 (SL3) poliovirus. Excretion stopped six weeks after hematopoietic stem-cell transplantation (HSCT). Graft versus host disease (GVHD) and poor graft function (PGF) occurred after HSCT, resulting in failure of hematopoiesis and immune system reconstitution. Given deficient innate and adaptive immunity, immune-mediated destruction of gastrointestinal (GI) tract caused by GVHD and inflammatory diarrheal illness of the girl may have contributed to her clearance of SL3 poliovirus. Intermittent surveillance of immune system parameters for iVDPV excreters receiving HSCT should be included in the PID surveillance program for further understanding poliovirus clearance mechanisms.}, } @article {pmid40170504, year = {2025}, author = {Zheng, Y and Chen, J and Zhang, Y and Guan, H and Deng, S and Chang, D and Wang, Y and Lu, J and Zhou, X and Xie, Q and Song, J and Huang, M}, title = {Gut Microbiota and Bile Acid Metabolism in the Mechanism of Ginsenoside Re Against Nonalcoholic Fatty Liver Disease.}, journal = {Phytotherapy research : PTR}, volume = {39}, number = {5}, pages = {2339-2356}, doi = {10.1002/ptr.8474}, pmid = {40170504}, issn = {1099-1573}, support = {2022YFC3501205//National Key Research and Development Program of China Stem Cell and Translational Research/ ; 2021FX02//Collaborative Innovation Platform Project of Fuxiaquan National Innovation Demonstration Zone/ ; 82274080//National Natural Science Foundation of China Projects/ ; //Research Support Program Fellowship, Western Sydney University/ ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism/microbiology ; *Bile Acids and Salts/metabolism ; *Ginsenosides/pharmacology ; Male ; Mice, Inbred C57BL ; Mice ; Diet, High-Fat/adverse effects ; Liver/drug effects/pathology/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {Gut microbiota and bile acid metabolism play crucial roles in the progression of nonalcoholic fatty liver disease (NAFLD). Early evidence demonstrates that Ginsenoside Re (Re) possesses pharmacological effects on NAFLD, but its mechanisms of action are not well understood. This study aimed to investigate the hepatic protective effects of Re in NAFLD and elucidate relevant mechanisms. The effects of Re treatments (10, 20, or 40 mg/kg) against high-fat diet-induced NAFLD were initially tested on male C57BL/6 mice. Then, a separate mouse group received Re with or without antibiotics to confirm the regulatory role of microbiota in the effect of Re. Finally, another group of mice received fecal microbiota transplantation (FMT) from the initial experiment of NAFLD mice to further investigate the mechanistic role of gut microbiota. Re significantly improved liver function by reducing hepatic lipid accumulation, injury and hepatocyte steatosis, and inflammation. The liver protection was mediated by the regulation of gut microbiota as evidenced by restored intestinal barrier integrity, normalized Firmicutes/Bacteroidota ratio, enhanced abundances of Adlercreutzia equolifaciens , and reduced Faecalibaculum rodentium. Following that, Re reduced total and primary bile acids and downregulated bile acid synthesis genes and proteins such as farnesoid X receptor and cytochrome P450 family 7 subfamily A member 1. The co-administration of antibiotic cocktail counteracted the effect of Re against NAFLD. Further, the results obtained from the FMT animal study confirmed that Re's liver protective effects were at least partly driven by the regulation of gut microbiota. Re modulated bile salt hydrolase-related microbial genera to alter bile acid synthesis pathways, thereby inhibiting NAFLD progression.}, } @article {pmid40168721, year = {2025}, author = {Shi, Y and Jiang, M and Zhu, W and Chang, K and Cheng, X and Bao, H and Peng, Z and Hu, Y and Li, C and Fang, F and Song, J and Jian, C and Chen, J and Shu, X}, title = {Cyclosporine combined with dexamethasone regulates hepatic Abca1 and PPARα expression and lipid metabolism via butyrate derived from the gut microbiota.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {186}, number = {}, pages = {118017}, doi = {10.1016/j.biopha.2025.118017}, pmid = {40168721}, issn = {1950-6007}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Cyclosporine/pharmacology/administration & dosage ; *Dexamethasone/pharmacology/administration & dosage ; *Lipid Metabolism/drug effects ; *Butyrates/metabolism ; *PPAR alpha/metabolism/genetics ; *Liver/metabolism/drug effects ; Mice ; *ATP Binding Cassette Transporter 1/metabolism/genetics ; Male ; Macaca mulatta ; Immunosuppressive Agents/pharmacology ; Dysbiosis ; }, abstract = {Immunosuppression often leads to drastic metabolic, hormonal, and physiological disorders. Changes in the gut microbiota are believed to be one of the factors contributing to these disorders, but the association remains uncertain. Clinical studies can be complicated by confounding variables, such as diet and other drivers of heterogeneity in human microbiomes. In this study, we identified pronounced gut microbiome signatures in rhesus macaques (RMs) with immunosuppression-induced lipid metabolism disorders following cyclosporine combined with dexamethasone. Furthermore, we observed similar changes in the gut microbiota of mice with immunosuppression-induced lipid metabolism disorders, which were associated with short-chain fatty acid metabolism. ELISA showed that immunosuppression significantly reduced the levels of butyric acid in both feces and serum of mice. Spearman correlation analysis identified a significant correlation between serum butyric acid levels and gut microbial dysbiosis induced by immunosuppression, particularly in relation to f_Lachnospiraceae, g_unidentified_Ruminococcaceae, and s_Clostridium leptum. Additionally, mice transplanted with gut microbiota from immunosuppressed mice exhibited hepatic lipid metabolism disorders, and RNA sequencing revealed significant downregulation of ABC transporters and PPARα in the liver, which was closely associated with lipid transport and metabolism, particularly Abca1. Moreover, butyric acid supplementation alleviated hepatic lipid metabolism disorders and upregulated the expression of Abca1 and PPARα in mice transplanted with immunosuppression-induced gut microbiota. Thus, we propose that the combination of cyclosporine and dexamethasone regulates the expression of hepatic Abca1 and PPARα by modulating the gut microbiota and its derived butyrate, particularly Lachnospiraceae and Clostridium leptum, further regulating hepatic lipid metabolism.}, } @article {pmid40168084, year = {2025}, author = {Ishikawa, D and Watanabe, H and Nomura, K and Zhang, X and Maruyama, T and Odakura, R and Koma, M and Shibuya, T and Osada, T and Fukuda, S and Nakahara, T and Terauchi, J and Nagahara, A and Yamada, T}, title = {Patient-donor similarity and donor-derived species contribute to the outcome of fecal microbiota transplantation for ulcerative colitis.}, journal = {Journal of Crohn's & colitis}, volume = {19}, number = {4}, pages = {}, doi = {10.1093/ecco-jcc/jjaf054}, pmid = {40168084}, issn = {1876-4479}, support = {JP16K09328//Japan Society for the Promotion of Science/ ; //Kyowa Kirin Co., Ltd./ ; //Kyowa Hakko Bio Co., Ltd./ ; //Kirin Holdings Co., Ltd./ ; //Metagen Therapeutics Inc./ ; JP21ae0121038//Japan Agency for Medical Research and Development/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Colitis, Ulcerative/therapy/microbiology ; Male ; Female ; Middle Aged ; Adult ; Feces/microbiology ; Anti-Bacterial Agents/therapeutic use ; Gastrointestinal Microbiome ; Treatment Outcome ; Tissue Donors ; Severity of Illness Index ; *Donor Selection ; }, abstract = {BACKGROUND AND AIMS: Clinical applications of fecal microbiota transplantation (FMT) for treating ulcerative colitis (UC) have shown promising results. However, whether the beneficial effects of FMT are due to the transfer and colonization of donor-derived species in patients remains unclear. Here, we investigated the factors affecting the efficacy of the administration of triple antibiotics (A-FMT) and the criteria for appropriate donor and patient-donor matching.

METHODS: Ninety-seven patients with active UC who were enrolled between March 2014 and October 2019 underwent FMT. The clinical features were assessed based on a reduction in Lichtiger's clinical activity index 4 weeks after A-FMT, with long-term responders (LTR) defined as those with no increase or intensification within 12 months after A-FMT. Microbiome analysis was performed on 147 fecal samples (pre-A-FMT, post-A-FMT, and donor) from 49 patient-donor combinations that were assigned using the one-patient-to-one-donor strategy.

RESULTS: Of the 97 patients, 61 achieved a clinical response, and of those, 35 were classified as having clinical remission. The efficacy of A-FMT was affected by UC severity and previous administration of steroids (P = .027), immunosuppressants (P = .049), and biologics (P = .029). Effective donors were rich in taxa such as Bacteroidota, which are lost in UC, and the abundances of "patient-origin" and "new-amplicon sequence variant" taxa were significantly lower in Responders compared to Nonresponders (Remission; P = .03, LTR; P = .05). "Donor-derived" amplicon sequence variant sequences, Oscillospiraceae UCG-002 and Alistipes, were significantly enriched in Responders (P < .05). Our results showed that the taxonomic composition of patients and the similarity of Bacteroides and butyric-acid-producing bacteria in the patient-donor microbiota significantly influenced A-FMT efficacy (P < .05).

CONCLUSIONS: This study provides important insights for developing patient-tailored FMT-based therapies for UC.}, } @article {pmid40167852, year = {2025}, author = {Xiang, M and Wu, S and Liu, M and Zhang, B and Xia, X and Tan, W and Xiang, S}, title = {Iota-carrageenan oligosaccharide ameliorates DSS-induced colitis in mice by mediating gut microbiota dysbiosis and modulating SCFAs-PI3K-AKT pathway.}, journal = {Inflammopharmacology}, volume = {33}, number = {6}, pages = {3443-3460}, pmid = {40167852}, issn = {1568-5608}, support = {NO.2024AFD252//the Natural Science Foundation of Hubei Province/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis/drug therapy/chemically induced/metabolism/microbiology ; Mice ; Male ; Mice, Inbred C57BL ; *Oligosaccharides/pharmacology ; *Dysbiosis/drug therapy/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Fatty Acids, Volatile/metabolism ; *Carrageenan/pharmacology ; Dextran Sulfate ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/drug effects ; Disease Models, Animal ; Fecal Microbiota Transplantation/methods ; Cytokines/metabolism ; }, abstract = {Iota-carrageenan oligosaccharides (iCOs), derived from marine red algae, are traditionally used as antithrombotic and anti-inflammatory agents in folk medicinal practice. Despite the prevailing emphasis on these aspects in their applications, the potential of iCOs as a prebiotic agent for gut health and its subsequent impact on intestinal disorders such as colitis remains largely unexplored. A DSS-induced colitis model was employed in C57BL/6 male mice to analyze the gut microbiota via 16S rRNA sequencing. Fecal microbiota transplantation (FMT) was used to assess the therapeutic effects of iCOs on colitis. RNA sequencing (RNA-Seq) identified pathways and genes affected by iCOs. ELISA measured inflammatory cytokines, while western blot and RT-qPCR evaluated protein and gene expressions, respectively. The iCOs increased beneficial bacteria, such as Lactobacillus, Bifidobacterium, and Akkermansia. They enhanced short-chain fatty acid production and upregulated GPR41, GPR43, and GPR109A mRNA, influencing cytokine secretion. The iCOs reduced mRNA of SPHK1, BDKRB1, LCN2, and so on, potentially through PI3K-Akt pathway inhibition, and promoted tight junction protein expression. Our findings highlight the novel therapeutic potential of iCOs in colitis, indicating a multifaceted approach to treatment that includes gut microbiota modulation, intestinal barrier restoration, and the suppression of inflammatory responses.}, } @article {pmid40166981, year = {2025}, author = {Huang, M and Ji, Q and Huang, H and Wang, X and Wang, L}, title = {Gut microbiota in hepatocellular carcinoma immunotherapy: immune microenvironment remodeling and gut microbiota modification.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2486519}, pmid = {40166981}, issn = {1949-0984}, mesh = {Humans ; Animals ; *Gastrointestinal Microbiome ; *Liver Neoplasms/immunology/microbiology/pathology/therapy ; *Carcinoma, Hepatocellular/immunology/microbiology/pathology/therapy ; Tumor Microenvironment ; *Immunotherapy ; Dysbiosis ; Lymphocytes/immunology ; Immune System ; Treatment Outcome ; }, abstract = {Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with limited treatment options at advanced stages. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, plays a pivotal role in regulating immune responses through the gut-liver axis. Emerging evidence underscores its impact on HCC progression and the efficacy of immunotherapy. This review explores the intricate interactions between gut microbiota and the immune system in HCC, with a focus on key immune cells and pathways involved in tumor immunity. Additionally, it highlights strategies for modulating the gut microbiota - such as fecal microbiota transplantation, dietary interventions, and probiotics - as potential approaches to enhancing immunotherapy outcomes. A deeper understanding of these mechanisms could pave the way for novel therapeutic strategies aimed at improving patient prognosis.}, } @article {pmid40166958, year = {2025}, author = {Zhang, Z and Zhu, T and Li, Y and Yu, B and Tao, H and Zhao, H and Cui, B}, title = {Butyrate Regulates Intestinal DNA Virome and Lipopolysaccharide Levels to Prevent High-Fat Diet-Related Liver Damage in Rats.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {14}, pages = {8277-8289}, doi = {10.1021/acs.jafc.4c07966}, pmid = {40166958}, issn = {1520-5118}, mesh = {Animals ; Diet, High-Fat/adverse effects ; *Lipopolysaccharides/metabolism ; Rats ; Gastrointestinal Microbiome/drug effects ; Male ; *Non-alcoholic Fatty Liver Disease/metabolism/microbiology/etiology/virology/prevention & control/drug therapy ; *Butyrates/administration & dosage/metabolism ; Humans ; Rats, Sprague-Dawley ; *Virome/drug effects ; Liver/metabolism/drug effects/injuries ; *Intestines/virology/microbiology/drug effects ; *Bacteriophages/genetics/metabolism ; Bacteria/metabolism/genetics/virology/isolation & purification ; Hep G2 Cells ; }, abstract = {As the adsorption receptor of bacteriophage tail protein, bacterial lipopolysaccharide (LPS) is a main culprit responsible for nonalcoholic fatty liver disease (NAFLD) caused by high-fat diets. However, few studies have focused on how the interaction between intestinal bacteriophages and bacterial LPS affects the development and progression of NAFLD. Herein, we determined that excessive fat intake significantly increases the levels of endogenous LPS, while the administration of beneficial metabolites of the intestinal microbiota (specifically butyrate) alleviated hepatic injury in rats. The beneficial mechanism of butyrate was attributed to the reprogramming of the structure of the intestinal DNA virome (primarily, phageome). Butyrate possesses the potential to augment bacteriophagic microbial diversity, thereby potentially facilitating interactions between intestinal bacteriophages and bacterial LPS (in the case of homologous phage), further improving mitochondrial dysfunction and reactive oxygen species production, which, in turn, lowered HepG2 cell damage. Likewise, fecal phage transplantation further confirmed that intestinal phages from rats that received butyrate could effectively interact with bacterial LPS to reduce liver damage in rats. Taken together, modifying the intestinal phageome is a promising treatment option for high-fat diet-related NAFLD.}, } @article {pmid40166696, year = {2025}, author = {Halvorsen, N and Hassan, C and Correale, L and Pilonis, N and Helsingen, LM and Spadaccini, M and Repici, A and Foroutan, F and Olav Vandvik, P and Sultan, S and Løberg, M and Kalager, M and Mori, Y and Bretthauer, M}, title = {Benefits, burden, and harms of computer aided polyp detection with artificial intelligence in colorectal cancer screening: microsimulation modelling study.}, journal = {BMJ medicine}, volume = {4}, number = {1}, pages = {e001446}, pmid = {40166696}, issn = {2754-0413}, abstract = {OBJECTIVE: To estimate the benefits, burden, and harms of implementing computer aided detection (CADe) of polyps in colonoscopy of population based screening programmes for colorectal cancer.

DESIGN: Microsimulation modelling study.

SETTING: Cost effectiveness working package in the OperA (optimising colorectal cancer prevention through personalised treatment with artificial intelligence) project. A parallel guideline committee panel (BMJ Rapid recommendation) was consulted in defining the screening interventions and selection of outcome measures.

POPULATION: Four cohorts of 100 000 European individuals aged 60-69 years.

INTERVENTION: The intervention was one screening of colonoscopy and a screening of colonoscopy after faecal immunochemical test every other year with CADe. The comparison group had the same screening every other year without CADe.

MAIN OUTCOME MEASURES: Benefits (colorectal cancer incidence and death), burden (surveillance colonoscopies), and harms (colonoscopy related adverse events) over 10 years were measured. The certainty in each outcome was assessed by use of the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

RESULTS: For 100 000 individuals participating in colonoscopy screening, 824 (0.82%) were diagnosed with colorectal cancer within 10 years without CADe versus 713 (0.71%) with CADe (risk difference -0.11% (95% CI -0.43% to 0.21%)). For faecal immunochemical test screening colonoscopy, the risk was 5.82% (n=5820) without CADe versus 5.77% (n=5770) with CADe (difference -0.05% (-0.33% to 0.15%)). The risk of surveillance colonoscopy increased from 26.45% (n=26 453) to 32.82% (n=32 819) (difference 6.37% (5.8% to 6.9%)) for colonoscopy screening and from 52.26% (n=52 263) to 53.08% (n=53 082) (difference 0.82% (0.38% to 1.26%)) for faecal immunochemical test screening colonoscopy. No significant differences were noted in adverse events related to the colonoscopy between CADe and no CADe. The model estimates were sensitive to the assumed effects of screening on colorectal cancer risk and of CADe on adenoma detection rates. All outcomes were graded as low certainty.

CONCLUSION: With low certainty of evidence, adoption of CADe in population based screening provides small and uncertain clinical meaningful benefit, no incremental harms, and increased surveillance burden after screening.}, } @article {pmid40165964, year = {2025}, author = {Ding, W and Cheng, Y and Liu, X and Zhu, Z and Wu, L and Gao, J and Lei, W and Li, Y and Zhou, X and Wu, J and Gao, Y and Ling, Z and Jiang, R}, title = {Harnessing the human gut microbiota: an emerging frontier in combatting multidrug-resistant bacteria.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1563450}, pmid = {40165964}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Drug Resistance, Multiple, Bacterial ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Probiotics/therapeutic use ; *Bacterial Infections/microbiology/therapy ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Prebiotics ; Animals ; *Bacteria/drug effects ; }, abstract = {Antimicrobial resistance (AMR) has become a major and escalating global health threat, undermining the effectiveness of current antibiotic and antimicrobial therapies. The rise of multidrug-resistant bacteria has led to increasingly difficult-to-treat infections, resulting in higher morbidity, mortality, and healthcare costs. Tackling this crisis requires the development of novel antimicrobial agents, optimization of current therapeutic strategies, and global initiatives in infection surveillance and control. Recent studies highlight the crucial role of the human gut microbiota in defending against AMR pathogens. A balanced microbiota protects the body through mechanisms such as colonization resistance, positioning it as a key ally in the fight against AMR. In contrast, gut dysbiosis disrupts this defense, thereby facilitating the persistence, colonization, and dissemination of resistant pathogens. This review will explore how gut microbiota influence drug-resistant bacterial infections, its involvement in various types of AMR-related infections, and the potential for novel microbiota-targeted therapies, such as fecal microbiota transplantation, prebiotics, probiotics, phage therapy. Elucidating the interactions between gut microbiota and AMR pathogens will provide critical insights for developing novel therapeutic strategies to prevent and treat AMR infections. While previous reviews have focused on the general impact of the microbiota on human health, this review will specifically look at the latest research on the interactions between the gut microbiota and the evolution and spread of AMR, highlighting potential therapeutic strategies.}, } @article {pmid40165428, year = {2025}, author = {Wang, L and Shao, L and Gao, YC and Liu, J and Li, XD and Zhou, J and Li, SF and Song, YL and Liu, B and Zhang, W and Huang, WH}, title = {Panax notoginseng Saponins Alleviate Inflammatory Bowel Disease via Alteration of Gut Microbiota-Bile Acid Metabolism.}, journal = {The American journal of Chinese medicine}, volume = {53}, number = {2}, pages = {567-596}, doi = {10.1142/S0192415X25500223}, pmid = {40165428}, issn = {1793-6853}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Saponins/pharmacology/isolation & purification/therapeutic use/administration & dosage ; *Panax notoginseng/chemistry ; *Bile Acids and Salts/metabolism ; *Inflammatory Bowel Diseases/drug therapy/metabolism/microbiology ; Animals ; Th17 Cells/immunology ; T-Lymphocytes, Regulatory/immunology ; Male ; *Phytotherapy ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Humans ; }, abstract = {Bile acid metabolism mediated by gut microbiota is significantly related to immunity regulation that plays an important role in the development and treatment of inflammatory bowel disease (IBD). Our previous study has demonstrated that Panax notoginseng saponins (PNS) alleviate colitis due to the regulation of T helper 17/Regulatory T cells (Th17/Treg) balance via gut microbiota. However, the effects and mechanism of PNS on colitis pertinent to bile acid metabolism mediated by gut microbiota remain elusive. This study aims to investigate the anti-colitis mechanism of PNS by regulating the Th17/Treg balance pertinent to gut microbiota-bile acid metabolism. Results showed that PNS significantly decreased the relative abundance of Allobaculum, Dubosiella, Muribaculum, and Alistipes, and up-regulated the relative contents of conjugated bile acids, such as TCA and TCDCA. Fecal microbiota transplantation (FMT) showed that the gut microbiota remodeled by PNS had a regulatory effect on bile acid metabolism, and up-regulated the relative contents of TCA and TCDCA, which alleviated IBD and promoted Treg cell expression in vivo and in vitro. Taken together, PNS could reshape the profiling of gut microbiota to generate more TCA and TCDCA, which improve the balance of Th17/Treg to exert anti-IBD effects.}, } @article {pmid40164697, year = {2025}, author = {Jia, L and Ke, Y and Zhao, S and Liu, J and Luo, X and Cao, J and Liu, Y and Guo, Q and Chen, WH and Chen, F and , and Wang, J and Wu, H and Ding, J and Zhao, XM}, title = {Metagenomic analysis characterizes stage-specific gut microbiota in Alzheimer's disease.}, journal = {Molecular psychiatry}, volume = {30}, number = {9}, pages = {3951-3962}, pmid = {40164697}, issn = {1476-5578}, mesh = {*Gastrointestinal Microbiome/genetics/physiology ; *Alzheimer Disease/microbiology/genetics/metabolism ; Humans ; Metagenomics/methods ; Male ; Female ; Mice ; Animals ; Aged ; Feces/microbiology ; Dysbiosis/microbiology/genetics ; Disease Progression ; Cohort Studies ; Fecal Microbiota Transplantation/methods ; Metagenome/genetics ; Brain/metabolism ; Middle Aged ; Cognitive Dysfunction/microbiology ; }, abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a decade-long preclinical pathological period that can be divided into several stages. Emerging evidence has revealed that the microbiota-gut-brain axis plays an important role in AD pathology. However, the role of gut microbiota in different AD stages has not been well characterized. In this study, we performed fecal shotgun metagenomic analysis on a Chinese cohort with 476 participants across five stages of AD pathology to characterize stage-specific alterations in gut microbiota and evaluate their diagnostic potential. We discovered extensive gut dysbiosis that is associated with neuroinflammation and neurotransmitter dysregulation, with over 10% of microbial species and gene families showing significant alterations during AD progression. Furthermore, we demonstrated that microbial gene families exhibited strong diagnostic capabilities, evidenced by an average AUC of 0.80 in cross-validation and 0.75 in independent external validation. In the optimal model, the most discriminant gene families are primarily involved in the metabolism of carbohydrates, amino acids, energy, glycan and vitamins. We found that stage-specific microbial gene families in AD pathology could be validated by an in vitro gut simulator and were associated with specific genera. We also observed that the gut microbiota could affect the progression of cognitive decline in 5xFAD mice through fecal microbiota transplantation, which could be used for early intervention of AD. Our multi-stage large cohort metagenomic analysis demonstrates that alterations in gut microbiota occur from the very early stages of AD pathology, offering important etiological and diagnostic insights.}, } @article {pmid40163879, year = {2025}, author = {Cintosun, A and Jamal, I and Samnani, S and Song, YN and Bretthauer, M}, title = {Gastroenterology/Hepatology: What You May Have Missed in 2024.}, journal = {Annals of internal medicine}, volume = {178}, number = {5_Supplement}, pages = {S39-S53}, doi = {10.7326/ANNALS-25-00959}, pmid = {40163879}, issn = {1539-3704}, mesh = {Humans ; *Gastroenterology/trends ; *Colorectal Neoplasms/diagnosis ; Early Detection of Cancer ; Proton Pump Inhibitors/therapeutic use ; Colonoscopy ; }, abstract = {This article highlights selected major advances in gastroenterology and hepatology from 2024 that are relevant for internal medicine specialists. In colorectal cancer (CRC) screening, new developments include a head-to-head comparison of different fecal immunochemical tests and a new blood-based DNA screening test, benefits and harms of artificial intelligence-assisted colonoscopy, and adenoma detection rate improvement and risk for cancer. Treatment options for metabolic dysfunction-associated steatotic liver disease now include resmetirom, a recently approved drug for treatment of patients with moderate-to-severe fibrosis, and liver transplantation may now be an option in patients with unresectable colorectal liver metastases. Also featured are new data on the efficacy of indomethacin and pancreatic stent placement for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography and news on the efficacy and safety of zastaprazan, a new potassium-competitive acid blocker for reflux esophagitis. Finally, a recent randomized trial is highlighted that has dispelled concerns about potential harms of proton-pump inhibitors for stress ulcer prophylaxis in patients receiving invasive mechanical ventilation.}, } @article {pmid40162905, year = {2025}, author = {Sigtryggsson, AT and Helgason, KO and Bjarnason, A and Gottfredsson, M}, title = {[Clostridioides difficile infections at Landspítali University Hospital 2017-2022].}, journal = {Laeknabladid}, volume = {111}, number = {4}, pages = {158-165}, doi = {10.17992/lbl.2025.04.834}, pmid = {40162905}, issn = {1670-4959}, mesh = {Humans ; Female ; Male ; *Hospitals, University ; Iceland/epidemiology ; Incidence ; Middle Aged ; Aged ; Risk Factors ; *Clostridium Infections/epidemiology/therapy/diagnosis/microbiology/mortality ; Adult ; Anti-Bacterial Agents/therapeutic use ; Time Factors ; *Clostridioides difficile/pathogenicity/drug effects/isolation & purification ; *Cross Infection/epidemiology/microbiology/therapy/diagnosis/mortality ; Aged, 80 and over ; Recurrence ; Treatment Outcome ; Community-Acquired Infections/epidemiology/microbiology/therapy/diagnosis/mortality ; Retrospective Studies ; Young Adult ; }, abstract = {OBJECTIVE: To investigate the epidemiology, severity, treatment, and prognosis of patients with C. difficile infections (CDI) diagnosed at Landspítali University Hospital from 2017-2022.

MATERIALS AND METHODS: The study population consisted of adult patients at Landspítali with double-positive (PCR + ELISA) diagnostic tests. If the same patient had two or more positive samples within a 28-day period, they were considered to reflect the same infection, and the latter samples were excluded.

RESULTS: Overall, 358 CDI were identified in 301 patients. The majority of cases were diagnosed in women (59.5%). The incidence of healthcare-associated CDI was 3.23 infections/10.000 in-hospital days (range 2.65 - 3.26). Incidence of community-associated CDI was 0.57 infections/10.000 inhabitants of the Reykjavik metropolitan area. Incidence was positively correlated with increasing age and remained similar throughout the study period. The recurrence rate during the study period was 15.3% with a mean follow-up period of 1.6 person-years. At least 85.5% of patients had taken antibiotics within a month before diagnosis, most commonly from the penicillin class (57.8%), followed by cephalosporins (51.5%). More than half (54.7%) of patients had taken proton pump inhibitors preceding diagnosis. Metronidazole was the most common initial treatment (63.0%). Of these, 29.4% of cases required further treatment within 28 days of treatment start. Fecal microbiota transplantation was performed in 13 cases. The 30-day all-cause mortality rate was 7.3%.

CONCLUSIONS: The incidence of CDI at Landspítali has remained stable and comparable to what has been reported in Europe during the same period. Most patients had one or more risk factors present. Most received antibiotics as treatment, most commonly metronidazole. The results of this study indicate that incidence and clinical presentation of CDI in Iceland are stable, whilst novel treatment options look promising.}, } @article {pmid40161742, year = {2025}, author = {Wong, MK and Armstrong, E and Heirali, AA and Schneeberger, PHH and Chen, H and Cochrane, K and Sherriff, K and Allen-Vercoe, E and Siu, LL and Spreafico, A and Coburn, B}, title = {Assessment of ecological fidelity of human microbiome-associated mice in observational studies and an interventional trial.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40161742}, issn = {2692-8205}, support = {UM1 CA186644/CA/NCI NIH HHS/United States ; }, abstract = {Composition and function of the gut microbiome is associated with diverse health conditions and treatment responses. Human microbiota-associated (HMA) mouse models are used to establish causal links for these associations but have important limitations. We assessed the fidelity of HMA mouse models to recapitulate ecological responses to a microbial consortium using stools collected from a human clinical trial. HMA mice were generated using different routes of consortium exposure and their ecological features were compared to human donors by metagenomic sequencing. HMA mice were more similar in gut composition to other mice than their respective human donors, with taxa including Akkermansia muciniphila and Bacteroides species enriched in mouse recipients. A limited repertoire of microbes was able to engraft into HMA mice regardless of route of consortium exposure. In publicly available HMA mouse datasets from four distinct health conditions, we confirmed our observation that a taxonomically restricted set of microbes reproducibly engrafts in HMA mice and observed that stool microbiome composition of HMA mice were more like other mice than their human donor. Our data suggest that HMA mice are limited models to assess the ecological impact of microbial consortia, with ecological effects in HMA mice being more strongly associated with host species than donor stool ecology or ecological responses to treatment in humans. Comparisons to published studies suggest this may be due to comparatively large host-species effects that overwhelm ecological effects of treatment in humans that HMA models aim to recapitulate.}, } @article {pmid40161578, year = {2025}, author = {Zhong, XS and Lopez, KM and Krishnachaitanya, SS and Liu, M and Xiao, Y and Ou, R and Nagy, HI and Kochkarian, T and Powell, DW and Fujise, K and Li, Q}, title = {Fecal microbiota transplantation mitigates cardiac remodeling and functional impairment in mice with chronic colitis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.03.13.643179}, pmid = {40161578}, issn = {2692-8205}, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with significant extraintestinal manifestations, including cardiovascular derangements. However, the molecular mechanisms underlying the cardiac remodeling and dysfunction remain unclear.

METHODS: We investigated the effects of chronic colitis on the heart using two mouse models: DSS-induced colitis and Il10 [-/-] spontaneous colitis. Echocardiography was employed to assess heart function and molecular characterization was performed using bulk RNA-sequencing, RT-qPCR, and western blot.

RESULTS: Both models exhibited significant cardiac impairment, including reduced ejection fraction and fractional shortening as well as increased collagen deposition, inflammation, and myofibril reorganization. Molecular analyses revealed upregulation of fibrosis markers (i.e. COL1A1, COL3A1, Fibronectin) and β-catenin reactivation, indicating a pro-fibrotic cardiac environment. Each model yielded common upregulation of eicosanoid-associated and inflammatory genes (Cyp2e1 , Map3k6 , Pck1 , Cfd), and model-specific alterations in pathways regulating cAMP- and cGMP-signaling, arachidonic and linoleic acid metabolism, Cushing syndrome-related genes, and immune cell responses. DSS colitis caused differential regulation of 232 cardiac genes, while Il10 [-/-] colitis yielded 105 dysregulated genes, revealing distinct molecular pathways driving cardiac dysfunction. Importantly, therapeutic fecal microbiota transplantation (FMT) restored heart function in both models, characterized by reduced fibrosis markers and downregulated pro-inflammatory genes (Lbp and Cdkn1a in Il10 [-/-] mice and Fos in DSS mice), while also mitigating intestinal inflammation. Post-FMT cardiac RNA-sequencing revealed significant gene expression changes, with three altered genes in DSS mice and 67 genes in Il10 [-/-] mice. Notably, Il10 [-/-] mice showed relatively less cardiac recovery following FMT, highlighting IL-10's cardioprotective and anti-inflammatory contribution.

CONCLUSIONS: Our findings elucidate novel insights into colitis-induced cardiac remodeling and dysfunction and suggest that FMT mitigates cardiac dysfunction by attenuating systemic inflammation and correcting gut dysbiosis. This study underscores the need for further evaluation of gut-heart interactions and microbiome-based therapies to improve cardiovascular health in IBD patients.}, } @article {pmid40161500, year = {2025}, author = {Dai, W and Chen, X and Zhou, H and Liu, N and Jin, M and Guo, Z}, title = {Microbiota modulation for infectious complications following allogeneic hematopoietic stem cell transplantation in pediatric hematological malignancies.}, journal = {Frontiers in pediatrics}, volume = {13}, number = {}, pages = {1509612}, pmid = {40161500}, issn = {2296-2360}, abstract = {The intervention of microbiota modulation in the treatment of infection complications after allogeneic hematopoietic stem cell transplantation in pediatric patients with hematological malignancies has shown potential benefits. Through the use of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), these interventions modulate the gut microbiota and enhance immune function to prevent and treat infections. They have been shown to reduce the incidence of diarrhea and intestinal infections, mitigate the issue of antibiotic resistance, and promote the recovery of gut microbiota. Future research is needed to further assess the safety and efficacy of these interventions and to establish standardized treatment protocols.}, } @article {pmid40160347, year = {2025}, author = {Tucker, EC and Angelica, B and Mathias, RM and Edwards, L and Bryant, RV and Costello, SP}, title = {Outcomes of Fecal Microbiota Transplantation for Clostridioides difficile Infection in South Australia.}, journal = {Open forum infectious diseases}, volume = {12}, number = {4}, pages = {ofaf149}, pmid = {40160347}, issn = {2328-8957}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) sourced from a bank of prescreened anaerobically processed frozen donor stool has been available in South Australia since 2013. This study aimed to evaluate the real-world clinical and safety outcomes of FMT for recurrent, refractory, and/or severe or fulminant Clostridioides difficile infection (CDI) facilitated via this centralized facility.

METHODS: Donor screening test data were prospectively collected on all donors who passed prescreening evaluations between April 2013 and August 2023. The South Australian FMT for CDI database prospectively recorded outcomes for consecutive patients who underwent FMT for CDI from August 2013 to May 2023 in South Australia.

RESULTS: An overall 98 potential donors passed prescreening assessments and underwent laboratory screening tests: 32 (33%) had tests that failed, 5 (5%) had incomplete screening, and 61 (62%) passed. Detection of an extended-spectrum β-lactamase-producing organism (9/65, 14%) was the common reason for ineligibility following completion of screening tests. In total 220 cases of CDI were recorded, and follow-up data were available in 216. Primary cure occurred in 84% of cases (182/216): 88% (132/150) for recurrent CDI, 76% (50/66) for refractory CDI, 85% (51/60) for severe disease, and 65% (17/26) for fulminant disease. Repeat FMT was delivered in 23 of 34 cases (68%), with secondary cure in 74% (17/23 cases). Serious adverse events were observed in 6 patients overall (3%). No deaths were directly attributable to FMT.

CONCLUSIONS: FMT was safe and efficacious for management of recurrent and refractory CDI over a 10-year period in a real-world prospective Australian cohort. Further studies to optimize the use of FMT for severe and fulminant CDI are warranted.}, } @article {pmid40160324, year = {2025}, author = {Cao, Z and Gao, T and Bajinka, O and Zhang, Y and Yuan, X}, title = {Fecal microbiota transplantation-current perspective on human health.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1523870}, pmid = {40160324}, issn = {2296-858X}, abstract = {Recently, microbiome medicine has attracted the attention of researchers. While this rapidly growing medical approach for various diseases and disorders is changing the paradigm, it is imperative to weigh both its benefits and the associated risk factors. For instance, manipulation of the gut microbiota (GM) has positive effects on metabolic and neurodegenerative diseases. Notably, fecal microbiota transplantation (FMT), a complex method, has shown promise; however, many doubt its feasibility without adverse effects on human health. Given the number of human clinical trials investigating FMT for the treatment of various disorders, this review summarizes recent findings on its impact on human health. This review summarizes the metabolic responses associated with FMT and their reversal effects on gastrointestinal infections, behavioral changes, and immune responses. Additionally, this review discusses the role of FMT in antimicrobial resistance and its co-supplementation effects on human health, safety, potential risks, limitations, prospects, and recommendations. Although this review does not cover all the studies in the database, the searched terms for FMT and human health in clinical trials are sufficient to provide a summary of the current perspective.}, } @article {pmid40158522, year = {2025}, author = {Bretthauer, M and Kalager, M}, title = {First head-to-head trial of colonoscopy versus faecal testing for colorectal cancer screening.}, journal = {Lancet (London, England)}, volume = {405}, number = {10486}, pages = {1204-1206}, doi = {10.1016/S0140-6736(25)00288-0}, pmid = {40158522}, issn = {1474-547X}, } @article {pmid40157463, year = {2025}, author = {Han, Y and Zhang, Y and Chen, J and Jiang, S and Zheng, Y and Xu, Y and Li, Y and Kong, J and Yu, X and Du, H}, title = {Iron overload exacerbates metabolic dysfunction-associated steatohepatitis via the microbiota-gut-liver axis through lipopolysaccharide-mediated Akr1b8 activation.}, journal = {Free radical biology & medicine}, volume = {233}, number = {}, pages = {196-208}, doi = {10.1016/j.freeradbiomed.2025.03.039}, pmid = {40157463}, issn = {1873-4596}, mesh = {Animals ; *Iron Overload/metabolism/complications/pathology/genetics/microbiology ; *Gastrointestinal Microbiome ; *Lipopolysaccharides/metabolism ; Mice ; Liver/metabolism/pathology ; Mice, Knockout ; *Aldo-Keto Reductases/metabolism/genetics ; Male ; Mice, Inbred C57BL ; *Fatty Liver/pathology/metabolism/microbiology ; Hemochromatosis Protein/genetics ; Iron/metabolism ; Disease Models, Animal ; Methionine/deficiency ; Lipid Metabolism ; }, abstract = {Iron homeostatic is closely linked to the development of metabolic dysfunction-associated steatohepatitis (MASH). However, the underlying mechanisms remain poorly understood. HFE knockout (KO) mice were used to generate mild iron-overload models. MASH was induced by feeding mice a methionine- and choline-deficient (MCD) diet for 4 weeks. Iron overload significantly exacerbated the pathologies of MCD-induced MASH, including liver injury, hepatic lipid accumulation, inflammation, and fibrosis. Additionally, iron overload reshaped the composition of gut microbiota, and fecal microbiota transplantation assay proved that gut microbiota from iron-overload mice contributed to hepatic lipid accumulation in control mice. Furthermore, iron overload-induced dysbacteriosis altered the metabolite profiles, reducing short-chain fatty acid levels and increasing lipopolysaccharide (LPS) levels. Notably, elevated LPS levels upregulated the expression of aldo-keto reductase family 1 member B8 (Akr1b8), which accelerated lipid accumulation and inflammation in hepatocytes. Above results indicated that iron overload promoted MASH progression through the microbiota-gut-liver axis, mediated by LPS-induced activation of Akr1b8. These findings highlight the critical role of iron homeostasis and gut microbiota in MASH pathogenesis.}, } @article {pmid40157004, year = {2025}, author = {Rahimi, A and Baghernejadan, Z and Hazrati, A and Malekpour, K and Samimi, LN and Najafi, A and Falak, R and Khorramdelazad, H}, title = {Combination therapy with immune checkpoint inhibitors in colorectal cancer: Challenges, resistance mechanisms, and the role of microbiota.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {186}, number = {}, pages = {118014}, doi = {10.1016/j.biopha.2025.118014}, pmid = {40157004}, issn = {1950-6007}, mesh = {Humans ; Animals ; Drug Combinations ; *Immune Checkpoint Inhibitors/therapeutic use ; *Microbiota ; *Colorectal Neoplasms/drug therapy ; *Drug Resistance, Neoplasm ; Tumor Microenvironment/drug effects ; Clinical Trials as Topic ; }, abstract = {Colorectal cancer (CRC) is still one of the leading causes of cancer deaths worldwide. Even though there has been progress in cancer immunotherapy, the results of applying immune checkpoint inhibitors (ICIs) have been unsatisfactory, especially in microsatellite stable (MSS) CRC. Single-agent ICIs that target programmed cell death-1 (PD-1)/ PD-L1, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T cell Ig- and mucin-domain-containing molecule-3 (TIM-3), and lymphocyte activation gene (LAG)-3 have emerged as having specific benefits. However, many primary and secondary resistance mechanisms are available in the tumor microenvironment (TME) that prevent it from happening. Combination strategies, such as the use of anti-PD-1 and anti-CTLA-4, can be effective in overcoming these resistance pathways, but toxicities remain a significant concern. Moreover, ICIs have been integrated with various treatment modalities, including chemotherapy, radiotherapy, antibiotics, virotherapy, polyadenosine diphosphate-ribose polymerase (PARP) inhibitors, and heat shock protein 90 (HSP90) inhibitors. The outcomes observed in both preclinical and clinical settings have been encouraging. Interestingly, manipulating gut microbiota via fecal microbiota transplantation (FMT) has been identified as a new strategy to increase the efficacy of immunotherapy in CRC patients. Therefore, integrating ICIs with other treatment approaches holds promise in enhancing the prognosis of CRC patients. This review focuses on the unmet need for new biomarkers to select patients for combination therapies and the ongoing work to overcome resistance and immune checkpoint blockade.}, } @article {pmid40156349, year = {2025}, author = {Karataş, M and Bloemen, M and Cuypers, L and Wollants, E and Van Ranst, M and Matthijnssens, J}, title = {14 years of rotavirus A surveillance: unusual dominance of equine-like G3P[8] genotype with DS-1-like genotype constellation after the pandemic, Belgium, 2009 to 2023.}, journal = {Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin}, volume = {30}, number = {12}, pages = {}, pmid = {40156349}, issn = {1560-7917}, mesh = {Humans ; *Rotavirus/genetics/isolation & purification/classification ; *Rotavirus Infections/epidemiology/virology ; Belgium/epidemiology ; Genotype ; Feces/virology ; Child, Preschool ; *Gastroenteritis/epidemiology/virology ; Infant ; *COVID-19/epidemiology ; Male ; Female ; Pandemics ; Capsid Proteins/genetics ; SARS-CoV-2 ; Child ; Rotavirus Vaccines ; Antigens, Viral/genetics ; }, abstract = {IntroductionDespite vaccine availability, rotavirus persists as a leading cause of gastroenteritis in children younger than 5 years.AimWe aimed to evaluate temporal changes in rotavirus epidemiology in Belgium between 2009 and 2023, including the period of the COVID-19 pandemic.MethodsWe collected 8,024 rotavirus-positive stool samples throughout Belgium. For 6,352 samples, we determined the G and/or P genotypes through sequencing of the genes encoding the outer capsid proteins VP7 and VP4.ResultsBefore the COVID-19pandemic, we received on average 622 samples per rotavirus epidemiological year, which decreased to 114 and 111 samples during the two pandemic rotavirus epidemiological years, followed by a peak of 1,048 samples in the first post-pandemic year. Notably, the proportion of cases in the age group 2-5-years increased from 20.3% before to 33% after the pandemic (p < 0.001). Over the 14-year study period, the most common genotypes were G2P[4], G3P[8] and G9P[8]. Post-pandemic data show an unusually strong dominance of the equine-like G3P[8] genotype which carried a DS-1-like genotype constellation in the period 2021 to 2023. Additionally, vaccinated individuals were significantly overrepresented among patients infected with the equine-like VP7 carrying G3P[8] rotavirus compared with other genotypes, including typical human VP7 G3P[8].ConclusionDespite the presence of typical yearly genotype fluctuations, several epidemiological changes were associated with the COVID-19 pandemic, including the unusual dominance of an emerging rotavirus strain against which current vaccines may be less effective. It is essential to closely monitor this strain to determine if the phenomenon is temporary.}, } @article {pmid40155609, year = {2025}, author = {Rodriguez, J and Cordaillat-Simmons, M and Pot, B and Druart, C}, title = {The regulatory framework for microbiome-based therapies: insights into European regulatory developments.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {53}, pmid = {40155609}, issn = {2055-5008}, mesh = {Humans ; *Microbiota ; Europe ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; *Biological Therapy/methods ; }, abstract = {The emergence of a broad spectrum of microbiome-based therapies has triggered changes in European regulatory frameworks. The first part of the review describes these innovative therapies. The second part provides an overview of the current framework and key changes introduced by the Regulation on substances of human origin (SoHO) for the development of microbiome-based therapies, highlighting the need of microbiome regulatory science to unlock the full potential of microbiome-based therapies.}, } @article {pmid40154780, year = {2025}, author = {Lin, SM and Le, PH and Chen, CL and Yeh, YM and Liao, HL and Chiu, CH}, title = {Faecal microbiota transplantation to decolonize vancomycin-resistant Enterococcus: A pilot study to evaluate safety and clinical outcome.}, journal = {Journal of global antimicrobial resistance}, volume = {43}, number = {}, pages = {1-6}, doi = {10.1016/j.jgar.2025.03.011}, pmid = {40154780}, issn = {2213-7173}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; Pilot Projects ; *Vancomycin-Resistant Enterococci ; Male ; Female ; Middle Aged ; Feces/microbiology ; Aged ; Prospective Studies ; Treatment Outcome ; *Gram-Positive Bacterial Infections/therapy/microbiology ; Adult ; Feasibility Studies ; Gastrointestinal Microbiome ; }, abstract = {OBJECTIVES: Faecal microbiota transplantation (FMT) has shown promise as a treatment for recurrent or refractory Clostridioides difficile infections. This study aimed to evaluate the decolonization effects of FMT on vancomycin-resistant Enterococcus (VRE).

METHODS: This feasibility trial prospectively recruited patients with more than three recurrent VRE infections. FMT was performed by infusing faecal microbiota solutions from healthy, unrelated donors into the participants' guts via colonoscopy. Faecal microbiota profiles before and after FMT were analysed.

RESULTS: Three of the six patients (50%) experienced VRE decolonization after FMT, lasting over 6 months. Baseline analysis revealed that patients who achieved decolonization had greater microbial diversity compared to those with persistent VRE colonization. Throughout the study, there were no adverse events observed in the patients after FMT. Elevated alpha diversity persisted in responders, while non-responders showed no significant changes. In responders, the abundance of genera within the phylum Firmicutes (Bacillota), including Anaerostipes, Blautia, Faecalibacterium, and Ruminococcus, and the genus Collinsella within the phylum Actinobacteriota increased steadily through 180 days post-FMT.

CONCLUSIONS: FMT may leverage bacterial strain competition to facilitate decolonization of drug-resistant organisms, with successful VRE decolonization potentially linked to increased abundance of phyla Firmicutes and Actinobacteriota over 6 months.}, } @article {pmid40154488, year = {2025}, author = {Martin, D and Bonneau, M and Orfila, L and Horeau, M and Hazon, M and Demay, R and Lecommandeur, E and Boumpoutou, R and Guillotel, A and Guillemot, P and Croyal, M and Cressard, P and Cressard, C and Cuzol, A and Monbet, V and Derbré, F}, title = {Atypical gut microbial ecosystem from athletes with very high exercise capacity improves insulin sensitivity and muscle glycogen store in mice.}, journal = {Cell reports}, volume = {44}, number = {4}, pages = {115448}, doi = {10.1016/j.celrep.2025.115448}, pmid = {40154488}, issn = {2211-1247}, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; Humans ; *Glycogen/metabolism ; Mice ; *Insulin Resistance/physiology ; *Athletes ; Male ; Fecal Microbiota Transplantation ; *Muscle, Skeletal/metabolism ; *Exercise/physiology ; Adult ; Mice, Inbred C57BL ; Female ; Young Adult ; Feces/microbiology ; }, abstract = {Although the gut microbiota is known to act as a bridge between dietary nutrients and the body's energy needs, the interactions between the gut microbiota, host energy metabolism, and exercise capacity remain uncertain. Here, we characterized the gut microbiota ecosystem in a cohort of healthy normo-weight humans with highly heterogeneous aerobic exercise capacities and closely related body composition and food habits. While our data support the idea that the bacterial ecosystem appears to be modestly altered between individuals with low-to-high exercise capacities and close food habits, we report that gut bacterial α diversity, density, and functional richness are significantly reduced in athletes with very high exercise capacity. By using fecal microbiota transplantation, we report that the engraftment of gut microbiota from athletes with very high exercise capacity improves insulin sensitivity and muscle glycogen stores into transplanted mice, which highlights promising therapeutic perspectives in fecal transplantation from human donors selected based on exercise capacity traits.}, } @article {pmid40153399, year = {2025}, author = {Gabarre, P and Palacios, R and Perez, K and Seksik, P and Bonnard, B and Loens, C and Lefranc, C and de Barros, JP and Anjou, L and Tamzali, Y and Zahr, N and Jaisser, F and Tourret, J}, title = {Immunosuppressive drugs and diet interact to modify the gut microbiota and cardiovascular risk factors, and to trigger diabetes.}, journal = {PloS one}, volume = {20}, number = {3}, pages = {e0320438}, pmid = {40153399}, issn = {1932-6203}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Male ; *Diet, High-Fat/adverse effects ; Mice ; *Immunosuppressive Agents/adverse effects/pharmacology ; *Cardiovascular Diseases/etiology ; Heart Disease Risk Factors ; Mice, Inbred C57BL ; Insulin Resistance ; Feces/microbiology ; Blood Glucose/metabolism ; Prednisone/adverse effects/pharmacology ; Risk Factors ; }, abstract = {BACKGROUND: Kidney transplant recipients are prescribed an immunosuppressive therapy (IST) and some of them follow a high fat diet (HFD) despite medical recommendations. Both are frequently associated with gut microbiota changes and metabolic disorders. We aimed at precisely identifying the effect of the IST and the HFD on metabolic parameters and the gut microbiota in mice, and at establishing correlations between the latters.

METHODS: 8-week-old male mice were treated with IST (a combination of prednisone, mycophenolate mofetil and tacrolimus) or not and were fed HFD or standard chow. Metabolic parameters were measured, and the gut microbiota was explored by the quantification of specific bacterial groups by qPCR and by 16S rDNA sequencing.

RESULTS: The HFD increased insulinemia and decreased the fecal proportion of Bacteroidetes and of Bacteroides. The IST increased systolic blood pressure and the fecal proportion of Escherichia coli. The HFD and the IST administered together resulted in an additive effect on glucose intolerance, high fasting blood glucose, homeostasis model assessment of insulin resistance (HOMA-IR), percentage of fat mass, blood triglyceride, blood cholesterol, and endotoxemia. On the opposite, the HFD and the IST had antagonistic effects on body weight, the proportion of Firmicutes, the Firmicutes/Bacteroidetes ratio, and the proportion of Clostridium leptum, Bifidobacterium, and Lactobacillus in the feces. Finally, we found that the correlations between gut bacterial communities and metabolic consequences of the HFD were altered by the IST.

CONCLUSION: The IST and the HFD have specific consequences on the gut microbiota and metabolism. We hypothesize that the metabolic consequences are at least partially mediated by IST/HFD-induced dysbiosis.}, } @article {pmid40151642, year = {2025}, author = {Cai, X and Cho, JY and Chen, L and Liu, Y and Ji, F and Salgado, K and Ge, S and Yang, D and Yu, H and Shao, J and Futreal, PA and Sepesi, B and Gibbons, D and Chen, Y and Wang, G and Cheng, C and Wu, M and Zhang, J and Hsiao, A and Xia, T}, title = {Enriched pathways in gut microbiome predict response to immune checkpoint inhibitor treatment across demographic regions and various cancer types.}, journal = {iScience}, volume = {28}, number = {4}, pages = {112162}, pmid = {40151642}, issn = {2589-0042}, abstract = {Understanding the effect of gut microbiota function on immune checkpoint inhibitor (ICI) responses is urgently needed. Here, we integrated 821 fecal metagenomes from 12 datasets to identify differentially abundant genes and construct random forest models to predict ICI response. Gene markers demonstrated excellent predictive performance, with an average area under the curve (AUC) of 0.810. Pathway analyses revealed that quorum sensing (QS), ABC transporters, flagellar assembly, and amino acid biosynthesis pathways were enriched between responders (R) and non-responders (NRs) across 12 datasets. Furthermore, luxS, manA, fliC, and trpB exhibited consistent changes between R and NR across 12 datasets. Follow-up microbiota transplant experiments showed that inter-species signaling by different QS autoinducer-2 (AI-2) molecules (synthesized by luxS) can act on overall community function to promote the colonization of Akkermansia muciniphila, which is associated with superior ICI responses. Together, our data highlight the role of gut microbiota function in modulating the microbiome and antitumor immunity.}, } @article {pmid40150325, year = {2025}, author = {Wang, K and Suo, Y and Shen, D and Shi, Y and Jin, X and Li, Y and Li, C}, title = {Improvement in Heat Stress-Induced Damage to Sperm Quality Following Fecal Microbiota Transplantation from L-Arginine-Treated Mice.}, journal = {Animals : an open access journal from MDPI}, volume = {15}, number = {6}, pages = {}, pmid = {40150325}, issn = {2076-2615}, support = {32372935//National Natural Science Foundation of China/ ; }, abstract = {Heat stress has become a significant concern in animal husbandry, as it adversely affects reproductive performance, particularly sperm quality, through mechanisms that are not fully understood. This study aimed to investigate the protective effects of L-arginine against heat stress-induced sperm damage and explore its potential mechanisms through the modulation of the intestinal microbiota. This study consisted of two experiments. First, in a heat-stressed mouse model, L-arginine was administered to evaluate its effects on the reproductive health of heat-stressed mice. In the second experiment, by transplanting L-arginine-induced changes in the gut microbiota into heat-stressed mice, the protective effects of the microbiota on the sperm of heat-stressed mice were assessed. The findings revealed a significant amelioration of decreased sperm quality and testicular injury induced by heat stress. Post heat stress, mice supplemented with L-arginine presented an increase in seminal vesicle gland weight and index, partial alleviation of testicular tissue morphology, and a substantial increase in testosterone concentration (p < 0.05). Additionally, L-arginine upregulated the expression of testosterone synthesis genes and the mRNA levels of sperm generation-related genes, including 3β-HSD, Stra8, WT1, and Gdnf (p < 0.05). Concurrently, L-arginine-induced microbial communities mitigated heat stress-induced decreases in sperm quality and testicular injury, coupled with increases in the mRNA expression levels of Cyp17a1, 17β-HSD, Plzf, and Gdnf (p < 0.05). Furthermore, there was a reduction in the expression of proinflammatory factors, namely, NFκB, MyD88, TNF-α, and TGF-β3 (p < 0.05). In conclusion, L-arginine may influence the ratio of beneficial bacteria to harmful bacteria in the intestinal microbiota, thereby reducing inflammation caused by heat stress, maintaining intestinal health, and influencing the microenvironment for spermatogenesis.}, } @article {pmid40149692, year = {2025}, author = {Sivakumar, N and Krishnamoorthy, A and Ryali, H and Arasaradnam, RP}, title = {Gut Microbial Targets in Inflammatory Bowel Disease: Current Position and Future Developments.}, journal = {Biomedicines}, volume = {13}, number = {3}, pages = {}, pmid = {40149692}, issn = {2227-9059}, abstract = {Inflammatory bowel disease (IBD) is a debilitating condition in which surgery is often seen as a last resort. However, this is associated with morbidity and, in some cases, mortality. There are emerging therapies that seek to better modulate the immune response of hosts with IBD. Aims: The main aim of this study is to focus on novel therapies and techniques studied in the last year that are non-surgical treatments of IBD. Methods: We looked at all the research between March 2024 and February 2025 detailing treatment in IBD and focused on the gut microbiome and gene therapy. Results: Novel therapies are gaining traction in safety and popularity. The results from some animal studies show promise and, with FDA approval, some probiotic therapies show optimistic research potential for future human trials. Conclusions: The research into the diagnostics and novel therapies available on the horizon for humans is very promising. Animal studies have shown potentially transferrable and safe therapies that can target specific sites of inflammation. Modulating the inflammatory response is a powerful therapy with what is shown to be a reasonably safe profile to build further research on.}, } @article {pmid40149377, year = {2025}, author = {Zhang, B and Mohd Sahardi, NFN and Di, W and Long, X and Shafiee, MN}, title = {The Gut-Endometrium Axis: Exploring the Role of Microbiome in the Pathogenesis and Treatment of Endometrial Cancer-A Narrative Review.}, journal = {Cancers}, volume = {17}, number = {6}, pages = {}, pmid = {40149377}, issn = {2072-6694}, abstract = {Background/Objectives: Endometrial cancer (EC) is a prevalent gynecological malignancy with an increasing incidence, particularly in developed countries. Recent research has demonstrated the significant involvement of gut and endometrial microbiomes in the pathogenesis and progression of EC. This review provides a comprehensive overview of the existing knowledge on the interactions between these microbial communities and their influence on EC. Methodology: A literature review was conducted using electronic databases including Google Scholar, Scopus, and PUBMED, covering the period from 2017 to 2024. The following keywords were used for the literature search: (1) gut microbiome and endometrial cancer, (2) endometrium microbiome and endometrial cancer, and (3) endometrial cancer and microbial dysbiosis. The selected articles were chosen based on inclusion and exclusion criteria. Scale for Assessment of Narrative Review Articles (SANRA) was used for evaluating and assessing the quality of articles. Results: The gut microbiome modulates systemic inflammation, immune responses, and estrogen metabolism, all of which are crucial factors in EC development. Dysbiosis is an imbalance in the composition of microbes that can cause chronic inflammation and hormonal imbalances, which can contribute to the EC. Similarly, the endometrial microbiome, while less extensively studied, has been implicated in EC through mechanisms involving local immune modulation and the production of harmful metabolites. Probiotics, prebiotics, fecal microbiota transplantation (FMT), and personalized microbiota-based therapies can be used as clinical interventions for EC management. This review emphasizes the need for further research to explore the gut-endometrium axis and its potential for innovative therapeutic approaches. Understanding these complex interactions will become a novel strategy to prevent and treat EC, ultimately enhancing patient outcomes.}, } @article {pmid40149075, year = {2025}, author = {Kenneth, MJ and Wu, CC and Fang, CY and Hsu, TK and Lin, IC and Huang, SW and Chiu, YC and Hsu, BM}, title = {Exploring the Impact of Chemotherapy on the Emergence of Antibiotic Resistance in the Gut Microbiota of Colorectal Cancer Patients.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {3}, pages = {}, pmid = {40149075}, issn = {2079-6382}, support = {R0010//This research was supported by Cheng Hsin General Hospital, Dalin Tzu Chi Hospital, Asia University Hospital, and Ditmanson Medical Foundation Chiayi Christian Hospital-National Chung Cheng University Joint Research Program/ ; }, abstract = {With nearly half of colorectal cancer (CRC) patients diagnosed at advanced stages where surgery alone is insufficient, chemotherapy remains a cornerstone for this cancer treatment. To prevent infections and improve outcomes, antibiotics are often co-administered. However, chemotherapeutic interactions with the gut microbiota cause significant non-selective toxicity, affecting not only tumor and normal epithelial cells but also the gut microbiota. This toxicity triggers the bacterial SOS response and loss of microbial diversity, leading to bacterial mutations and dysbiosis. Consequently, pathogenic overgrowth and systemic infections increase, necessitating broad-spectrum antibiotics intervention. This review underscores how prolonged antibiotic use during chemotherapy, combined with chemotherapy-induced bacterial mutations, creates selective pressures that drive de novo antimicrobial resistance (AMR), allowing resistant bacteria to dominate the gut. This compromises the treatment efficacy and elevates the mortality risk. Restoring gut microbial diversity may mitigate chemotherapy-induced toxicity and improve therapeutic outcomes, and emerging strategies, such as fecal microbiota transplantation (FMT), probiotics, and prebiotics, show considerable promise. Given the global threat posed by antibiotic resistance to cancer treatment, prioritizing antimicrobial stewardship is essential for optimizing antibiotic use and preventing resistance in CRC patients undergoing chemotherapy. Future research should aim to minimize chemotherapy's impact on the gut microbiota and develop targeted interventions to restore microbial diversity affected during chemotherapy.}, } @article {pmid40147837, year = {2025}, author = {Foroutan, F and Vandvik, PO and Helsingen, LM and Kalager, M and Rutter, M and Selby, K and Pilonis, ND and Anderson, JC and McKinnon, A and Fuchs, JM and Quinlan, C and Buskermolen, M and Senore, C and Wang, P and Sung, JJY and Haug, U and Bjerkelund, S and Triantafyllou, K and Shung, DL and Halvorsen, N and McGinn, T and Hafver, TL and Reinthaler, V and Guyatt, G and Agoritsas, T and Sultan, S}, title = {Computer aided detection and diagnosis of polyps in adult patients undergoing colonoscopy: a living clinical practice guideline.}, journal = {BMJ (Clinical research ed.)}, volume = {388}, number = {}, pages = {e082656}, doi = {10.1136/bmj-2024-082656}, pmid = {40147837}, issn = {1756-1833}, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Artificial Intelligence ; *Colonic Polyps/diagnosis ; *Colonoscopy/methods/standards ; *Colorectal Neoplasms/diagnosis/prevention & control ; *Diagnosis, Computer-Assisted/methods/standards ; Early Detection of Cancer/methods ; Practice Guidelines as Topic ; }, abstract = {CLINICAL QUESTION: In adult patients undergoing colonoscopy for any indication (screening, surveillance, follow-up of positive faecal immunochemical testing, or gastrointestinal symptoms such as blood in the stools) what are the benefits and harms of computer-aided detection (CADe)?

CONTEXT AND CURRENT PRACTICE: Colorectal cancer (CRC), the third most common cancer and the second leading cause of cancer-related death globally, typically arises from adenomatous polyps. Detection and removal of polyps during colonoscopy can reduce the risk of cancer. CADe systems use artificial intelligence (AI) to assist endoscopists by analysing real-time colonoscopy images to detect potential polyps. Despite their increasing use in clinical practice, guideline recommendations that carefully balance all patient-important outcomes remain unavailable. In this first iteration of a living guideline, we address the use of CADe at the level of an individual patient.

EVIDENCE: Evidence for this recommendation is drawn from a living systematic review of 44 randomised controlled trials (RCTs) involving more than 30 000 participants and a companion microsimulation study simulating 10 year follow-up for 100 000 individuals aged 60-69 years to assess the impact of CADe on patient-important outcomes. While no direct evidence was found for critical outcomes of colorectal cancer incidence and post-colonoscopy cancer incidence, low certainty data from the trials indicate that CADe may increase positive endoscopy findings. The microsimulation modelling, however, suggests little to no effect on CRC incidence, CRC-related mortality, or colonoscopy-related complications (perforation and bleeding) over the 10 year follow-up period, although low certainty evidence indicates CADe may increase the number of colonoscopies performed per patient. A review of values and preferences identified that patients value mortality reduction and quality of care but worry about increased anxiety, overdiagnosis, and more frequent surveillance.

RECOMMENDATION: For adults who have agreed to undergo colonoscopy, we suggest against the routine use of CADe (weak recommendation).

An international panel, including three patient partners, 11 healthcare providers, and seven methodologists, deemed by MAGIC and The BMJ to have no relevant competing interests, developed this recommendation. For this guideline the panel took an individual patient approach. The panel started by defining the clinical question in PICO format, and prioritised outcomes including CRC incidence and mortality. Based on the linked systematic review and microsimulation study, the panel sought to balance the benefits, harms, and burdens of CADe and assumed patient preferences when making this recommendation UNDERSTANDING THE RECOMMENDATION: The guideline panel found the benefits of CADe on critical outcomes, such as CRC incidence and post-colonoscopy cancer incidence, over a 10 year follow up period to be highly uncertain. Low certainty evidence suggests little to no impact on CRC-related mortality, while the potential burdens-including more frequent surveillance colonoscopies-are likely to affect many patients. Given the small and uncertain benefits and the likelihood of burdens, the panel issued a weak recommendation against routine CADe use.The panel acknowledges the anticipated variability in values and preferences among patients and clinicians when considering these uncertain benefits and potential burdens. In healthcare settings where CADe is available, individual decision making may be appropriate.

UPDATES: This is the first iteration of a living practice guideline. The panel will update this living guideline if ongoing evidence surveillance identifies new CADe trial data that substantially alters our conclusions about CRC incidence, mortality, or burdens, or studies that increase our certainty in values and preferences of individual patients. Updates will provide recommendations on the use of CADe from a healthcare systems perspective (including resource use, acceptability, feasibility, and equity), as well as the combined use of CADe and computer aided diagnosis (CADx). Users can access the latest guideline version and supporting evidence on MAGICapp, with updates periodically published in The BMJ.}, } @article {pmid40147263, year = {2025}, author = {Ye, X and An, X and Zhang, T and Kong, Y and Jia, S and Wu, J}, title = {CGA protects against experimental colitis by modulating host purine metabolism through the gut microbiota.}, journal = {International immunopharmacology}, volume = {153}, number = {}, pages = {114547}, doi = {10.1016/j.intimp.2025.114547}, pmid = {40147263}, issn = {1878-1705}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis/chemically induced/drug therapy/microbiology/metabolism ; *Purines/metabolism ; Dextran Sulfate ; *Chlorogenic Acid/therapeutic use/pharmacology ; Mice ; Disease Models, Animal ; Male ; Mice, Inbred C57BL ; Colon/pathology/drug effects/microbiology ; Fecal Microbiota Transplantation ; Cytokines/metabolism ; Dysbiosis/drug therapy ; Humans ; Intestinal Mucosa/drug effects/pathology ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; Fatty Acids, Volatile/metabolism ; RNA, Ribosomal, 16S/genetics ; }, abstract = {OBJECTIVE: Alterations in the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Chlorogenic acid (CGA), a product of the esterification of caffeic acid and quinic acid, is one of the most abundant polyphenols in the human diet and has potential beneficial effects on gut function. However, the underlying mechanisms remain unclear. In this study, the pharmacological effects of CGA on colitis and the potential underlying mechanisms were investigated.

METHODS: A mouse model of colitis was induced via the use of 4 % dextran sulfate sodium (DSS), and the mice were treated with 200 mg/kg CGA. Body weight, colon length, colon tissue pathology, and plasma and colon inflammatory cytokine levels were assessed. RNA sequencing was used to detect changes in gene expression in mouse colon tissues, and 16S rRNA sequencing was used to analyze the composition and structure of the gut microbiota. Fecal metabolomic analysis was performed, and fecal microbiota transplantation (FMT) was used to evaluate the contribution of the gut microbiota.

RESULTS: CGA significantly alleviated DSS-induced colitis, alleviating intestinal mucosal barrier damage and gut microbiota dysbiosis. It significantly enriched bacteria that produce short-chain fatty acids (SCFAs). CGA inhibited the accumulation of purine metabolites derived from the microbiota and suppressed immune-related signaling cascades, exerting immunomodulatory effects. Furthermore, the gut microbiota of CGA-treated mice alleviated DSS-induced colitis through FMT.

CONCLUSION: CGA alleviates colitis in a gut microbiota-dependent manner, potentially providing a new strategy for the treatment of IBD.}, } @article {pmid40143866, year = {2025}, author = {Zhou, M and Niu, B and Ma, J and Ge, Y and Han, Y and Wu, W and Yue, C}, title = {Intervention and research progress of gut microbiota-immune-nervous system in autism spectrum disorders among students.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1535455}, pmid = {40143866}, issn = {1664-302X}, abstract = {Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by difficulties in social interaction and communication, repetitive and stereotyped behaviors, restricted interests, and sensory abnormalities. Its etiology is influenced by both genetic and environmental factors, with no definitive cause identified and no specific pharmacological treatments available, posing a significant burden on patients' families and society. In recent years, research has discovered that gut microbiota dysbiosis plays a crucial role in the pathogenesis of ASD. The gut microbiota can influence brain function and behavior through the gut-brain axis via the nervous system, immune system, and metabolic pathways. On the one hand, specific gut microbes such as Clostridium and Prevotella species are found to be abnormal in ASD patients, and their metabolic products, like short-chain fatty acids, serotonin, and GABA, are also involved in the pathological process of ASD. On the other hand, ASD patients exhibit immune system dysfunction, with gut immune cells and related cytokines affecting neural activities in the brain. Currently, intervention methods targeting the gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation, have shown some potential in improving ASD symptoms. However, more studies are needed to explore their long-term effects and optimal treatment protocols. This paper reviews the mechanisms and interrelationships among gut microbiota, immune system, and nervous system in ASD and discusses the challenges and future directions of existing research, aiming to provide new insights for the prevention and treatment of ASD.}, } @article {pmid40143713, year = {2025}, author = {Zhang, F and Kamm, MA and Wu, X and Kao, D and Borody, TJ and Chen, LA and He, X and Fischer, M and Wong, SH and Ng, SC and Cui, B and Chan, FK and Nie, Y and Sood, A and Li, J and Sun, Y and Dai, I and Chen, Q and Lv, M and Zhang, Z and Ianiro, G and Yang, Y and Kelly, CR}, title = {Preferred Reporting Items for Microbiotherapy (PRIM) Guidelines Across Medical Disciplines: An International Delphi Consensus.}, journal = {Journal of gastroenterology and hepatology}, volume = {40}, number = {6}, pages = {1364-1373}, pmid = {40143713}, issn = {1440-1746}, support = {2021YFA0717004//Ministry of Science and Technology of China, National Key Program/ ; 82170563//National Natural Science Fundation of China/ ; 2020-3HIM//Nanjing Medical University Fan Daiming Research Funds for Holistic Integrative Medicine/ ; }, mesh = {Humans ; *Delphi Technique ; *Dysbiosis/therapy ; Consensus ; *Practice Guidelines as Topic ; *Checklist ; Fecal Microbiota Transplantation ; Internationality ; }, abstract = {Microbiotherapy has opened new avenues for managing dysbiosis-related diseases. However, many studies did not cover all the necessary reporting items for microbiotherapy making the interpretation of results, safety assessment, technology extension, and even the transparency of legitimacy difficult. This project consisted of 2 phases. First, we proposed an initial preferred reporting items for microbiotherapy (PRIM) checklist and applied it to oncology studies from 2011 to 2023 according to Meta-Analyses guideline. Only 39.3% (n = 64) of these studies (n = 163) met all PRIM checklist items. The culture-based microbiotherapy (CMT) studies had higher score than non-culture-based (NMT) ones (p = 0.018). In the second phase, the expert panel consisting of 22 specialists from eight countries across Asia, Australia, Europe, and North America refined and finalized the PRIM guidelines (named as PRIM 2024) through Delphi consensus. The PRIM 2024 guidelines conclude 10 statements and 18 points on diagnosis, delivery route, source, classification, preparation, dosage, state, concomitant treatment, efficacy, and safety. The panel defined less than 80% of all PRIM points (14 points) as low-quality reports. These guidelines are recommended for reporting on microbiotherapy in clinical studies and reports on compassionate use, including but not limited to fecal microbiota transplantation, phage therapy, probiotics, and synbiotics. These consistent and transparent reporting items can help researchers and practitioners better evaluate, compare, implement research findings in microbiotherapy.}, } @article {pmid40142532, year = {2025}, author = {Niu, Q and Yang, K and Zhou, Z and Huang, Q and Wang, J}, title = {Intergenerational Transmission of Gut Microbiome from Infected and Non-Infected Salmonella pullorum Hens.}, journal = {Microorganisms}, volume = {13}, number = {3}, pages = {}, pmid = {40142532}, issn = {2076-2607}, support = {2022-02-08-00-12-F01184//Shanghai Agriculture Applied Technology Development Program,China/ ; }, abstract = {Pullorum disease (PD) is one of the common infectious diseases in the poultry industry in the world. Our previous study showed that gut bacterial structure has a significant difference between positive and negative hens. However, the gut bacterial basis of intergenerational transmission of PD continues to elude a scientific explanation. The present study carried out fecal microbiota transplantation (FMT) in chicks of a negative group, then fecal samples of the chicks in the control team (CT), Salmonella pullorum (S. pullorum)-negative transplantation team (PN) and S. pullorum-positive transplantation team (PP) were separately collected to be analyzed for microbial structure and prediction functions. Microbial diversity results revealed that there was a large difference in the gut microbiota of these three groups. Prevotella and Parasutterella with higher abundance in PN (p < 0.05) were transplanted from gut bacteria of S. pullorum-negative hens. Furthermore, the differences of the most major microbial functions (top 100) were similar in hens and chicks, including a pentose phosphate pathway and oxidative phosphorylation. The data provided a reference for exploring the intergenerational transmission and genetic mechanisms of gut microbiota associated with S. pullorum in poultry, as well as a theoretical basis for improving intestinal health through the rational regulation of microbiota-host interactions.}, } @article {pmid40142480, year = {2025}, author = {Shaheen, M and McDougall, C and Chan, L and Franz, R and Wong, K and Giebelhaus, RT and Nguyen, G and Nam, SL and de la Mata, AP and Yeo, S and Harynuk, JJ and Pakpour, S and Xu, H and Kao, D}, title = {Impact of Fecal Microbiota Transplant Formulations, Storage Conditions, and Duration on Bacterial Viability, Functionality, and Clinical Outcomes in Patients with Recurrent Clostridioides difficile Infection.}, journal = {Microorganisms}, volume = {13}, number = {3}, pages = {}, pmid = {40142480}, issn = {2076-2607}, abstract = {Fecal microbiota transplantation (FMT) is the most effective therapy for preventing recurrent Clostridioides difficile infection (rCDI). However, the impact of FMT formulations and storage conditions on bacterial viability, community structure, functionality, and clinical efficacy remains under-investigated. We studied the effect of different storage conditions on the bacterial viability (live/dead staining and cell sorting), community structure (16S rDNA analysis), and metabolic functionality (fermentation) of frozen and lyophilized FMT formulations. The clinical success rates of rCDI patients were correlated retrospectively with FMT formulations, storage durations, and host factors using the Edmonton FMT program database. Bacterial viability remained at 10-20% across various storage conditions and formulations and was comparable to that of fresh FMT. Live and dead bacterial fractions in both frozen and lyophilized FMT preparations exhibited distinct community structures. Storage durations, but not temperatures, negatively affected bacterial diversity. More short-chain fatty acids were found in the metabolomic profiling of in vitro fermentation products using lyophilized than frozen FMT. Clinical success rates in 537 rCDI patients receiving a single dose of FMT were not significantly different among the three formulations. However, longer storage durations and advanced recipient age negatively impacted clinical efficacy. Together, our findings suggest that FMT formulations and storage durations should be considered when establishing guidelines for product shelf life for optimal treatment outcomes.}, } @article {pmid40142449, year = {2025}, author = {Kume, M and Din, J and Zegarra-Ruiz, DF}, title = {Dysregulated Intestinal Host-Microbe Interactions in Systemic Lupus Erythematosus: Insights from Patients and Mouse Models.}, journal = {Microorganisms}, volume = {13}, number = {3}, pages = {}, pmid = {40142449}, issn = {2076-2607}, abstract = {Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation that affects multiple organs, with its prevalence varying by ethnicity. Intestinal dysbiosis has been observed in both SLE patients and murine models. Additionally, intestinal barrier impairment is thought to contribute to the ability of pathobionts to evade and breach immune defenses, resulting in antigen cross-reactivity, microbial translocation, subsequent immune activation, and, ultimately, multiple organ failure. Since the detailed mechanisms underlying these processes are difficult to examine using human samples, murine models are crucial. Various SLE murine models, including genetically modified spontaneous and inducible murine models, offer insights into pathobionts and how they dysregulate systemic immune systems. Furthermore, since microbial metabolites modulate systemic immune responses, bacteria and their metabolites can be targeted for treatment. Based on human and mouse research insights, this review examines how lupus pathobionts trigger intestinal and systemic immune dysregulation. Therapeutic approaches, such as fecal microbiota transplantation and dietary adjustments, show potential as cost-effective and safe methods for preventing and treating SLE. Understanding the complex interactions between the microbiota, host factors, and immune dysregulation is essential for developing novel, personalized therapies to tackle this multifaceted disease.}, } @article {pmid40141109, year = {2025}, author = {Ye, Y and Abulizi, A and Zhang, Y and Lu, F and An, Y and Ren, C and Zhang, H and Wang, Y and Lin, D and Lu, D and Li, M and Yang, B}, title = {Ganoderic Acid Ameliorates Ulcerative Colitis by Improving Intestinal Barrier Function via Gut Microbiota Modulation.}, journal = {International journal of molecular sciences}, volume = {26}, number = {6}, pages = {}, pmid = {40141109}, issn = {1422-0067}, support = {82273999//National Natural Science Foundation of China grants/ ; 81974083//National Natural Science Foundation of China grants/ ; 7212151//Beijing Natural Science Foundation grant/ ; 2022-JKCS-15//The grant from the non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Colitis, Ulcerative/drug therapy/microbiology/metabolism/pathology/chemically induced ; Mice ; *Triterpenes/pharmacology/therapeutic use ; *Intestinal Mucosa/drug effects/metabolism ; Disease Models, Animal ; Dextran Sulfate ; Humans ; Male ; Claudin-1/metabolism ; Fecal Microbiota Transplantation ; Zonula Occludens-1 Protein/metabolism ; Occludin/metabolism ; Mice, Inbred C57BL ; Caco-2 Cells ; Colon/drug effects/pathology/metabolism ; Intestinal Barrier Function ; }, abstract = {Ulcerative colitis (UC) is a chronic and recurrent gastrointestinal disease that affects millions of humans worldwide and imposes a huge social and economic burden. It is necessary to find safe and efficient drugs for preventing and treating UC. The aim of this study was to determine whether ganoderic acid (GA), the main bioactive components of Ganoderma lucidum, has preventive and therapeutic effect on UC in a dextran sulfate sodium (DSS)-induced UC mouse model. Our experimental results showed that GA significantly ameliorated the body weight loss and disease activity index (DAI) of UC mice. GA significantly restored 11% of the colon length and 69% of the spleen index compared to UC mice. GA significantly decreased the intestinal inflammatory response and improved the barrier function of the intestine by upregulating the tight junction proteins Zonula occludens-1 (ZO-1), occludin and claudin-1. A co-housing experiment showed that gut microbiota accounted for the therapeutic activity of GA on UC, which was confirmed by fecal microbiota transplantation from GA-treated mice to the UC mice. Furthermore, 16S rDNA high-throughput sequencing of fecal bacteria showed that GA significantly enriched the abundance of Lactobacillus, Oscillospira, Odoribacter and Ruminococcus, which were positively correlated with colon length. Furthermore, this study found the functional metabolites, including Indole-3-acetaldehyde (IAAld), Glutamine (Gln) and Glutathione (GSH), reduced barrier damage in the Caco-2 cell model. In conclusion, this study suggests that GA could ameliorate UC by improving intestinal barrier function via modulating gut microbiota and associated metabolites.}, } @article {pmid40141007, year = {2025}, author = {Wang, Y and Chen, Y and Xiao, Z and Shi, Y and Fu, C and Cao, Y}, title = {Fecal microbiota transplantation modulates myeloid-derived suppressor cells and attenuates renal fibrosis in a murine model.}, journal = {Renal failure}, volume = {47}, number = {1}, pages = {2480749}, pmid = {40141007}, issn = {1525-6049}, mesh = {Animals ; *Myeloid-Derived Suppressor Cells/immunology ; Fibrosis ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; *Fecal Microbiota Transplantation ; Male ; *Kidney/pathology ; *Renal Insufficiency, Chronic/therapy/pathology/immunology ; Cytokines/metabolism ; Ureteral Obstruction/complications ; Gastrointestinal Microbiome ; }, abstract = {BACKGROUND: Renal fibrosis is a hallmark of progressive chronic kidney disease (CKD), with emerging evidence linking gut microbiota dysbiosis to disease progression. Myeloid-derived suppressor cells (MDSCs) have demonstrated renoprotective effects, yet the impact of fecal microbiota transplantation (FMT) on MDSC-mediated modulation of renal fibrosis remains unclear.

METHODS: C57BL/6J mice underwent unilateral ureteral obstruction (UUO) to induce renal fibrosis, followed by FMT administration via gavage. Flow cytometry was used to quantify granulocytic (G-MDSCs) and monocytic (M-MDSCs) MDSC populations in peripheral blood, kidney, and spleen. To elucidate the role of MDSCs in FMT-mediated effects, MDSCs were depleted or adoptively transferred in vivo. Renal fibrosis severity and inflammatory cytokine expression were subsequently analyzed.

RESULTS: FMT altered MDSC distribution, increasing M-MDSC accumulation in the blood and kidney. This was associated with downregulation of proinflammatory cytokines and attenuation of renal fibrosis. Adoptive MDSC transfer similarly produced anti-inflammatory and antifibrotic effects, reinforcing their therapeutic role in FMT-mediated renal protection.

CONCLUSIONS: FMT enhances M-MDSC-mediated immunomodulation, reducing inflammation and renal fibrosis in UUO-induced CKD. These findings suggest a potential therapeutic strategy targeting the gut-kidney axis in CKD management.}, } @article {pmid40140901, year = {2025}, author = {Wu, Y and Cheng, R and Lin, H and Li, L and Jia, Y and Philips, A and Zuo, T and Zhang, H}, title = {Gut virome and its implications in the pathogenesis and therapeutics of inflammatory bowel disease.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {183}, pmid = {40140901}, issn = {1741-7015}, support = {2023YFS0279//Sichuan Science and Technology Program/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Virome ; *Inflammatory Bowel Diseases/virology/therapy/microbiology ; }, abstract = {Inflammatory bowel disease (IBD) refers to chronic, recurrent inflammatory intestinal disorders, primarily including Crohn's disease (CD) and Ulcerative colitis (UC). Numerous studies have elucidated the importance of the gut microbiome in IBD. Recently, numerous studies have focused on the gut virome, an intriguing and enigmatic aspect of the gut microbiome. Alterations in the composition of phages, eukaryotic viruses, and human endogenous retroviruses that occur in IBD suggest potential involvement of the gut virome in IBD. Nevertheless, the mechanisms by which it maintains intestinal homeostasis and interacts with diseases are only beginning to be understood. Here, we thoroughly reviewed the composition of the gut virome in both healthy individuals and IBD patients, emphasizing the key viruses implicated in the onset and progression of IBD. Furthermore, the complex connections between the gut virome and the intestinal barrier, immunity, and gut microbiome were dissected to advance the interpretation of IBD pathogenesis. The updated discussion of the evidence regarding the gut virome will advance our knowledge in gut virome and chronic gastrointestinal diseases. Targeting the gut virome is a promising avenue for IBD treatment in future.}, } @article {pmid40138872, year = {2025}, author = {Liang, T and Jiang, T and Liang, Z and Li, L and Chen, Y and Chen, T and Yang, L and Zhang, N and Dong, B and Xie, X and Gu, B and Wu, Q}, title = {Gut microbiota-driven BCAA biosynthesis via Staphylococcus aureus -expressed acetolactate synthase impairs glycemic control in type 2 diabetes in South China.}, journal = {Microbiological research}, volume = {296}, number = {}, pages = {128145}, doi = {10.1016/j.micres.2025.128145}, pmid = {40138872}, issn = {1618-0623}, mesh = {*Diabetes Mellitus, Type 2/microbiology/metabolism ; *Gastrointestinal Microbiome/physiology ; *Staphylococcus aureus/enzymology/genetics/metabolism ; *Amino Acids, Branched-Chain/biosynthesis ; *Acetolactate Synthase/metabolism/genetics ; Humans ; Animals ; Mice ; China ; Male ; Insulin Resistance ; Female ; Middle Aged ; *Glycemic Control ; Blood Glucose ; Feces/microbiology ; Staphylococcal Infections/microbiology ; Metagenomics ; Prediabetic State/microbiology ; Metabolomics ; Insulin ; }, abstract = {An increase in branched-chain amino acid (BCAA) levels can result in insulin resistance at different stages of type 2 diabetes (T2D), however, the causes of this increase are unclear. We performed metagenomics and metabolomics profiling in patients with prediabetes (PDM), newly diagnosed diabetes (NDDM), and post-medication type 2 diabetes (P2DM) to investigate whether altered gut microbes and metabolites could explain the specific clinical characteristics of different disease stages of T2D. Here we identify acetolactate synthase (ALS) a BCAA biosynthesis enzyme in Staphylococcus aureus as a cause of T2D insulin resistance. Compared with healthy peoples, patients with PDM, NDDM, and P2DM groups, especially in P2DM group, have increased faecal numbers of S. aureus. We also demonstrated that insulin administration may be a risk factor for S. aureus infection in T2D. The presence of ALS-positive S. aureus correlated with the levels of BCAAs and was associated with an increased fasting blood glucose (FBG) and insulin resistance. Humanized microbiota transplantation experiment indicated that ALS contributes to disordered insulin resistance mediated by S. aureus. We also found that S. aureus phage can reduced the FBG levels and insulin resistance in db/db mice. The ALS-positive S. aureus are associated with insulin resistance in T2D, opening a new therapeutic avenue for the prevention or treatment of diabetes.}, } @article {pmid40137411, year = {2025}, author = {Mougiou, D and Gioula, G and Skoura, L and Anastassopoulou, C and Kachrimanidou, M}, title = {Insights into the Interaction Between Clostridioides difficile and the Gut Microbiome.}, journal = {Journal of personalized medicine}, volume = {15}, number = {3}, pages = {}, pmid = {40137411}, issn = {2075-4426}, abstract = {Clostridioides difficile (C. difficile) is a significant healthcare-associated pathogen that is predominantly caused by antibiotic-induced microbiota disturbance. Antibiotics decrease microbial diversity, resulting in C. difficile colonization and infection. Clostridium difficile infection (CDI) manifests through toxins A and B, causing diarrhea and colitis. Antibiotic usage, old age, and hospitalization are significant risk factors. A healthy gut microbiota, which is dominated by Firmicutes and Bacteroidetes, provides colonization resistance to C. difficile due to competition for nutrients, creating inhibitory substances and stimulating the immune response. Antibiotic-induced dysbiosis decreases resistance, allowing C. difficile spores to transform into vegetative forms. Patients with CDI have decreased gut microbiota diversity, with a decrease in beneficial bacteria, including Bacteroidetes, Prevotella, and Bifidobacterium, and a rise in harmful bacteria like Clostridioides and Lactobacillus. This disparity worsens the infection's symptoms and complicates therapy. Fecal Microbiota Transplantation (FMT) has emerged as a potential therapy for recurrent CDI by restoring gut microbiota diversity and function. Comprehending the connection between gut microbiota and CDI pathogenesis is critical for establishing effective preventive and treatment plans. Maintaining a healthy gut microbiota through careful antibiotic use and therapeutic options such as FMT can help in the management and prevention of CDI.}, } @article {pmid40136508, year = {2025}, author = {Zalila-Kolsi, I and Dhieb, D and Osman, HA and Mekideche, H}, title = {The Gut Microbiota and Colorectal Cancer: Understanding the Link and Exploring Therapeutic Interventions.}, journal = {Biology}, volume = {14}, number = {3}, pages = {}, pmid = {40136508}, issn = {2079-7737}, abstract = {CRC remains a significant public health challenge due to its high prevalence and mortality rates. Emerging evidence highlights the critical role of the gut microbiota in both the pathogenesis of CRC and the efficacy of treatment strategies, including chemotherapy and immunotherapy. Dysbiosis, characterized by imbalances in microbial communities, has been implicated in CRC progression and therapeutic outcomes. This review examines the intricate relationship between gut microbiota composition and CRC, emphasizing the potential for microbial profiles to serve as biomarkers for early detection and prognosis. Various interventions, such as prebiotics, probiotics, postbiotics, fecal microbiota transplantation, and dietary modifications, aim to restore microbiota balance and shift dysbiosis toward eubiosis, thereby improving health outcomes. Additionally, the integration of microbial profiling into clinical practice could enhance diagnostic capabilities and personalize treatment strategies, advancing the field of oncology. The study of intratumoral microbiota offers new diagnostic and prognostic tools that, combined with artificial intelligence algorithms, could predict treatment responses and assess the risk of adverse effects. Given the growing understanding of the gut microbiome-cancer axis, developing microbiota-oriented strategies for CRC prevention and treatment holds promise for improving patient care and clinical outcomes.}, } @article {pmid40134274, year = {2025}, author = {Flores-Treviño, S and Bocanegra-Ibarias, P and Salas-Treviño, D and Ramírez-Elizondo, MT and Pérez-Alba, E and Camacho-Ortiz, A}, title = {Microbiota transplantation and administration of live biotherapeutic products for the treatment of dysbiosis-associated diseases.}, journal = {Expert opinion on biological therapy}, volume = {25}, number = {5}, pages = {1-14}, doi = {10.1080/14712598.2025.2484303}, pmid = {40134274}, issn = {1744-7682}, mesh = {Humans ; *Dysbiosis/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; *Biological Products/therapeutic use/administration & dosage ; *Microbiota ; Female ; Clostridium Infections/therapy/microbiology ; Animals ; Vaginosis, Bacterial/therapy/microbiology ; Vagina/microbiology ; *Biological Therapy/methods ; }, abstract = {INTRODUCTION: The microbiota composition in humans varies according to the anatomical site and is crucial for maintaining homeostasis and an overall healthy state. Several gastrointestinal, vaginal, respiratory, and skin diseases are associated with dysbiosis. Alternative therapies such as microbiota transplantation can help restore microbiota normal composition and can be implemented to treat clinically relevant diseases.

AREAS COVERED: Current microbiota transplantation therapies conducted in clinical trials were included in this review (after searching on MEDLINE database from years 2017 to 2025) such as fecal microbiota transplantation (FMT) against recurrent Clostridioides difficile infection (rCDI) and vaginal microbiota transplantation (VMT) against bacterial vaginosis. Washed microbiota transplantation (WMT) and live biotherapeutic products (LBPs) were also reviewed.

EXPERT OPINION: In microbiota-based transplantation therapy, selecting optimal donors is a limitation. A stool or a vaginal microbiota bank should be implemented to overcome the time-consuming and expensive process of donor recruitment. Microbiota-based LBPs are also promising treatment alternatives for rCDI and other dysbiosis-associated diseases. Specific LBPs could be engineered out of donor fluids-derived strains to achieve the selection of specific beneficial microorganisms for the treatment of specific dysbiosis-associated diseases. Personalized microbiota-based treatments are promising solutions for dysbiosis-associated diseases, which remains an important necessity in clinical practice.}, } @article {pmid40134246, year = {2025}, author = {Gao, Q and Bai, M and Qi, T and Zhai, J and Song, Y and Zhang, W and Liang, G}, title = {Changes in Vitamin D and Gut Microbiota in Pediatric Hematopoietic Stem Cell Transplantation Patients with Bloodstream Infections.}, journal = {International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition}, volume = {95}, number = {1}, pages = {26126}, doi = {10.31083/IJVNR26126}, pmid = {40134246}, issn = {0300-9831}, support = {2022QN07//Aerospace Center Hospital Youth Innovation Fund/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Male ; Female ; Case-Control Studies ; *Vitamin D/blood/analogs & derivatives ; Child ; Prospective Studies ; Child, Preschool ; Feces/microbiology ; Adolescent ; *Bacteremia/microbiology/blood ; Infant ; }, abstract = {BACKGROUND: Vitamin D (VD) and gut microbiota (GM) are important variables in pediatric hematopoietic stem cell transplantation (HSCT) recipients with bloodstream infections (BSI). Both VD and GM play significant roles in immune regulation and in maintaining intestinal barrier function.

METHODS: This prospective case-control study included 48 consecutive pediatric patients who underwent HSCT, as well as 20 healthy children from the community. Plasma samples were collected pre- and post-HSCT, together with post-HSCT fecal samples. Serum 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) were measured using chemiluminescence and enzyme linked immunosorbent assay, respectively. GM was analyzed by 16S rDNA next generation sequencing.

RESULTS: The incidence of BSI in pediatric HSCT recipients was 33.3% (16/48). No significant differences in serum 25(OH)D or 1,25(OH)2D3 levels were observed between the BSI and non-BSI groups either before or after transplantation, or with the healthy control group. The α-diversity of GM in BSI and non-BSI patients was significantly lower than in healthy subjects. Proteobacteria were significantly more abundant in BSI patients than in non-BSI patients (p = 0.0434) or healthy controls (p = 0.0193). Pediatric HSCT patients showed significantly higher levels of Staphylococcus (p < 0.001), Pseudomonas (p < 0.001), Enterococcus (p < 0.001), Clostridium innocuum (p = 0.0175) and Enterobacter (p = 0.0394) compared to the controls, whereas the levels of Firmicutes (p = 0.009), Actinobacteria (p < 0.001), Bifidobacterium (p < 0.001) and Faecalibacterium (p < 0.001) were significantly lower. β-diversity analysis revealed significant population differences between the three groups.

CONCLUSIONS: These results indicate there is no practical value in monitoring VD in HSCT patients. During HSCT and BSI, the GM experiences a loss of probiotics and an increase in potential pathogens.}, } @article {pmid40133348, year = {2025}, author = {Jing, Y and Wang, Q and Bai, F and Li, Z and Li, Y and Liu, W and Yan, Y and Zhang, S and Gao, C and Yu, Y}, title = {Age-related alterations in gut homeostasis are microbiota dependent.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {51}, pmid = {40133348}, issn = {2055-5008}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Homeostasis ; Mice ; *Aging ; Fecal Microbiota Transplantation ; Gene Expression Profiling ; Mice, Inbred C57BL ; Male ; Transcriptome ; *Bacteria/classification/genetics/isolation & purification ; Colon/microbiology ; Computational Biology ; }, abstract = {Accumulating data suggest that remodeling aged gut microbiota improves aging-related imbalance in intestinal homeostasis. However, evidence in favor of the beneficial effect of remodeling gut microbiota on intestinal stress and immune responses during aging is scarce. The current study revealed that old mice presented impaired gut barrier integrity. Transcriptome sequencing coupled with bioinformatics analysis revealed that aging altered gene expression profiles of the colon and mesenteric lymph nodes, which are involved mainly in stress and immune responses, respectively. Notably, gut microbiota was closely related to the differentially expressed genes. Microbiota depletion in old mice ameliorated gut barrier integrity and partially reversed the inflammatory factors upregulated in aging mice. Furthermore, fecal microbiota transplantation from young mice to old mice resulted in a significant improvement in intestinal barrier integrity and immune homeostasis. These findings highlight the potential of microbiota-targeted interventions on aging-related physiological processes and call for further investigation.}, } @article {pmid40133336, year = {2025}, author = {Tillett, BJ and Dwiyanto, J and Secombe, KR and George, T and Zhang, V and Anderson, D and Duggan, E and Giri, R and Loo, D and Stoll, T and Morrison, M and Begun, J and Hill, MM and Gurzov, EN and Bell, KJ and Saad, S and Barlow, CK and Creek, DJ and Chong, CW and Mariño, E and Hamilton-Williams, EE}, title = {SCFA biotherapy delays diabetes in humanized gnotobiotic mice by remodeling mucosal homeostasis and metabolome.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2893}, pmid = {40133336}, issn = {2041-1723}, support = {2-SRA-2019-703-M-B, 201308399//Juvenile Diabetes Research Foundation Australia (JDRF Australia)/ ; 2002917, 2028813//Department of Health | National Health and Medical Research Council (NHMRC)/ ; }, mesh = {Animals ; Humans ; *Metabolome ; Gastrointestinal Microbiome/drug effects ; Mice ; *Fatty Acids, Volatile/metabolism ; Homeostasis ; *Diabetes Mellitus, Type 1/metabolism/therapy/immunology/microbiology ; Female ; Male ; Adult ; Germ-Free Life ; *Intestinal Mucosa/metabolism/immunology ; Fecal Microbiota Transplantation ; Mice, Inbred NOD ; Metabolomics ; Immunity, Mucosal ; }, abstract = {Type 1 diabetes (T1D) is linked to an altered gut microbiota characterized by reduced short-chain fatty acid (SCFA) production. Oral delivery of a SCFA-yielding biotherapy in adults with T1D was followed by increased SCFAs, altered gut microbiota and immunoregulation, as well as delaying diabetes in preclinical models. Here, we show that SCFA-biotherapy in humans is accompanied by remodeling of the gut proteome and mucosal immune homeostasis. Metabolomics showed arginine, glutamate, nucleotide and tryptophan metabolism were enriched following the SCFA-biotherapy, and found metabolites that correlated with glycemic control. Fecal microbiota transfer demonstrated that the microbiota of SCFA-responders delayed diabetes progression in humanized gnotobiotic mice. The protected mice increased similar metabolite pathways to the humans including producing aryl-hydrocarbon receptor ligands and reducing inflammatory mucosal immunity and increasing IgA production in the gut. These data demonstrate that a potent SCFA immunomodulator promotes multiple beneficial pathways and supports targeting the microbiota as an approach against T1D. Trial registration: Australia New Zealand Clinical Trials Registry ACTRN12618001391268.}, } @article {pmid40131972, year = {2025}, author = {Duan, JQ and Sun, YF and Wang, X and Liu, HY and Chang, ZP and Shao, YY and Liu, JJ and Hou, RG}, title = {Shaoyao-Gancao decoction improves dyslipidemia in rats with polycystic ovary syndrome by reshaping the gut microbiota and regulating the bile acid/FXR pathway.}, journal = {Journal of Asian natural products research}, volume = {}, number = {}, pages = {1-14}, doi = {10.1080/10286020.2025.2482072}, pmid = {40131972}, issn = {1477-2213}, abstract = {This study aims to investigate the potential mechanism of Shaoyao-Gancao Decoction (SGD) in treating polycystic ovary syndrome (PCOS). Our results suggested that SGD effectively regulated estrous cycles, reduced body weight and serum lipid levels in PCOS rats. Additionally, SGD administration significantly remodeled the structure of gut microbiota, especially the BA-related bacteria. The mRNA expressions of BAs metabolism pathway-related genes were significantly changed by SGD treatment. Furthermore, transplantation of fecal microbiota from SGD rats verified these results. In conclusion, SGD could ameliorate dyslipidemia in PCOS rats by remodeling the structure of the gut microbiome and regulating the bile acid/FXR pathway.}, } @article {pmid40131871, year = {2025}, author = {Kellingray, L and Savva, GM and Garcia-Gutierrez, E and Snell, J and Romano, S and Yara, DA and Altera, A and de Oliveira Martins, L and Hutchins, C and Baker, D and Hayhoe, A and Hacon, C and Elumogo, N and Narbad, A and Sayavedra, L}, title = {Temporal dynamics of SARS-CoV-2 shedding in feces and saliva: a longitudinal study in Norfolk, United Kingdom during the 2021-2022 COVID-19 waves.}, journal = {Microbiology spectrum}, volume = {13}, number = {5}, pages = {e0319524}, pmid = {40131871}, issn = {2165-0497}, abstract = {UNLABELLED: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was originally described as a respiratory illness; however, it is now known that the infection can spread to the gastrointestinal tract, leading to shedding in feces potentially being a source of infection through wastewater. We aimed to assess the prevalence and persistence of SARS-CoV-2 in fecal and saliva samples for up to 7 weeks post-detection in a cohort of 98 participants from Norfolk, United Kingdom using RT-qPCR. Secondary goals included sequencing the viral isolates present in fecal samples and comparing the genetic sequence with isolates in the saliva of the same participant. Furthermore, we sought to identify factors associated with the presence of detectable virus in feces or saliva after a positive SARS-CoV-2 test. Saliva remained SARS-CoV-2-positive for longer periods compared to fecal samples, with all positive fecal samples occurring within 4 weeks of the initial positive test. Detectable virus in fecal samples was positively associated with the number of symptoms experienced by the individuals. Based on the genome sequencing and taxonomic classification of the virus, one donor had a distinct strain in feces compared to saliva on the same collection date, which suggests that different isolates could dominate different tissues. Our results underscore the importance of considering multiple biological samples, such as feces, in the detection and characterization of SARS-CoV-2, particularly in clinical procedures involving patient fecal material transplant. Such insights could contribute to enhancing the safety protocols surrounding the handling of patient samples and aid in devising effective strategies for mitigating the spread of coronavirus disease.

IMPORTANCE: This study provides critical insights into the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding in fecal and saliva samples, demonstrating that while viral RNA is detectable shortly after diagnosis, its prevalence declines rapidly over the course of infection. Detection was more common among individuals with more concurrent symptoms, emphasizing the potential influence of symptom burden on viral persistence. By analyzing a United Kingdom-based cohort, this study fills a significant gap in the literature, which has largely focused on Asian and North American populations, offering a geographically unique perspective on viral shedding dynamics. Our findings contribute to a globally relevant understanding of SARS-CoV-2 shedding by revealing differences in shedding durations compared to studies from other regions. These differences highlight the need for geographically diverse research to account for variations in genetic background, immune response, and healthcare practices.}, } @article {pmid40130013, year = {2024}, author = {Wang, IC and Buffington, SA and Salas, R}, title = {Microbiota-Gut-Brain Axis in Psychiatry: Focus on Depressive Disorders.}, journal = {Current epidemiology reports}, volume = {11}, number = {4}, pages = {222-232}, pmid = {40130013}, issn = {2196-2995}, support = {I01 CX001937/CX/CSRD VA/United States ; R01 HD109095/HD/NICHD NIH HHS/United States ; R01 HD109780/HD/NICHD NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: Gut microbiota contribute to several physiological processes in the host. The composition of the gut microbiome is associated with different neurological and neurodevelopmental diseases. In psychiatric disease, stress may be a major factor leading to gut microbiota alterations. Depressive disorders are the most prevalent mental health issues worldwide and patients often report gastrointestinal symptoms. Accordingly, evidence of gut microbial alterations in depressive disorders has been growing. Here we review current literature revealing links between the gut microbiome and brain function in the context of depression.

RECENT FINDINGS: The gut-brain axis could impact the behavioral manifestation of depression and the underlying neuropathology via multiple routes: the HPA axis, immune function, the enteric nervous system, and the vagus nerve. Furthermore, we explore possible therapeutic interventions including fecal microbiota transplant or probiotic supplementation in alleviating depressive symptoms.

SUMMARY: Understanding the mechanisms by which bidirectional communication along the gut-brain axis can be dysregulated in patients with depression could lead to the development of personalized, microbiome-targeted therapies for the treatment of this disorder.}, } @article {pmid40128912, year = {2025}, author = {Feng, Y and Chen, W and Chen, J and Sun, F and Kong, F and Li, L and Zhao, Y and Wu, S and Li, Z and Du, Y and Kong, X}, title = {Dietary emulsifier carboxymethylcellulose-induced gut dysbiosis and SCFA reduction aggravate acute pancreatitis through classical monocyte activation.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {83}, pmid = {40128912}, issn = {2049-2618}, support = {82172572//National Natural Science Foundation of China/ ; 82170659//National Natural Science Foundation of China/ ; 82072760//National Natural Science Foundation of China/ ; 2019YFC1315900//National Key R&D Program of China/ ; }, mesh = {Animals ; *Dysbiosis/chemically induced/microbiology ; *Carboxymethylcellulose Sodium/adverse effects ; *Gastrointestinal Microbiome/drug effects ; Mice ; Mice, Inbred C57BL ; *Fatty Acids, Volatile/metabolism ; *Pancreatitis/microbiology/chemically induced/pathology ; *Monocytes/immunology/drug effects/metabolism ; Male ; Humans ; Fecal Microbiota Transplantation ; Feces/microbiology/chemistry ; Butyrates ; RNA, Ribosomal, 16S/genetics ; Akkermansia ; Disease Models, Animal ; Verrucomicrobia ; }, abstract = {OBJECTIVE: Carboxymethylcellulose (CMC), one of the most common emulsifiers used in the food industry, has been reported to promote chronic inflammatory diseases, but its impact on acute inflammatory diseases, e.g., acute pancreatitis (AP), remains unclear. This study investigates the detrimental effects of CMC on AP and the potential for mitigation through Akkermansia muciniphila or butyrate supplementation.

DESIGN: C57BL/6 mice were given pure water or CMC solution (1%) for 4 weeks and then subjected to caerulein-induced AP. The pancreas, colon, and blood were sampled for molecular and immune parameters associated with AP severity. Gut microbiota composition was assessed using 16S rRNA gene amplicon sequencing. Fecal microbiota transplantation (FMT) was used to illustrate gut microbiota's role in mediating the effects of CMC on host mice. Additional investigations included single-cell RNA sequencing, monocytes-specific C/EBPδ knockdown, LPS blocking, fecal short-chain fatty acids (SCFAs) quantification, and Akkermansia muciniphila or butyrate supplementation. Finally, the gut microbiota of AP patients with different severity was analyzed.

RESULTS: CMC exacerbated AP with gut dysbiosis. FMT from CMC-fed mice transferred such adverse effects to recipient mice, while single-cell analysis showed an increase in classical monocytes in blood. LPS-stimulated C/EBPδ, caused by an impaired gut barrier, drives monocytes towards classical phenotype. LPS antagonist (eritoran), Akkermansia muciniphila or butyrate supplementation ameliorates CMC-induced AP exacerbation. Fecal Akkermansia muciniphila abundance was negatively correlated with AP severity in patients.

CONCLUSIONS: This study reveals the detrimental impact of CMC on AP due to gut dysbiosis, with Akkermansia muciniphila or butyrate offering potential therapeutic avenues for counteracting CMC-induced AP exacerbation. Video Abstract.}, } @article {pmid40127764, year = {2025}, author = {Verbiest, A and Andersen, JHM and Hvistendahl, MK and Tóth, J and Vandermeulen, G and De Meyere, L and Joly, F and Verbeke, K and Jeppesen, PB and Vanuytsel, T}, title = {Transferability of metabolic balance studies in short bowel syndrome.}, journal = {Clinical nutrition ESPEN}, volume = {67}, number = {}, pages = {377-386}, doi = {10.1016/j.clnesp.2025.03.029}, pmid = {40127764}, issn = {2405-4577}, mesh = {Humans ; *Short Bowel Syndrome/metabolism/physiopathology ; Intestinal Absorption ; Male ; Electrolytes ; Female ; Energy Metabolism ; Adult ; Nutrients ; Middle Aged ; Feces/chemistry ; }, abstract = {BACKGROUND: Metabolic balance studies (MBS) are the gold standard method to assess the intestinal absorptive function in patients with short bowel syndrome (SBS). During a full MBS, patients are admitted to the hospital to collect duplicates of all ingested foods and drinks, as well as their fecal and urinary output, typically over a 72-h period. These collections are further processed to assess absorption of energy, macronutrients (nitrogen, fat and carbohydrate) and electrolytes (sodium, potassium, calcium and magnesium). Full MBS require dedicated laboratory personnel, equipment, knowledge and experience, which explains why they are currently only performed in one center.

AIM: We aimed to explore the transferability of full MBS in patients with SBS from the reference center to a clinical center that was new to and unexperienced in MBS.

METHODS: A collaboration between the centers was initiated to transfer knowledge on how to perform MBS collections, how to process and how to analyze energy, macronutrient and electrolyte content in the collected samples. At practical level, transferability included successful MBS collecting and processing. At analytical level, transferability included the lyophilization of homogenized samples at both centers. The powder that was created at the reference center was measured at both centers to assess the transferability of the analytical methods; while the site-specific powder was measured at the corresponding center to determine full process transferability. The intraclass correlation coefficient (ICC) was calculated to define the absolute agreement between both centers.

RESULTS: A total of 21 MBS were performed in 7 patients with SBS at the new center. A total of 189 samples were collected, equally distributed among combined meals and drinks (n = 63), fecal output (n = 63) and urinary output (n = 63). Meals and drinks samples and fecal output samples were processed in the new center and lyophilized at both centers, with a perfect reliability for dry matter between the centers (ICC = 1). At the level of method transferability, there was an excellent absolute agreement between centers for energy and nitrogen analyses (ICC>0.9). For fat, the mean coefficients of variation (cv) between centers for fecal output (6.3 %) and meals and drinks (12.0 %) were higher, but ICC showed excellent (0.957) to good (0.787) agreement, respectively. Carbohydrate results differed more between the centers (mean cv of 17.5 % for fecal output and 16.4 % for meals and drinks), translating into a moderate (meals and drinks, ICC = 0.654) to good (fecal output, ICC = 0.812) reliability. Similar results and degrees of agreement as obtained for the method transferability were observed with the site-specific powder.

CONCLUSION: Our study showed the feasibility of a full MBS transferability to a new unexperienced center with promising agreement of the results obtained between both centers. Our findings aim to inspire other specialized intestinal failure centers to adopt the full MBS methodology for both clinical practice and research purposes.}, } @article {pmid40123400, year = {2025}, author = {Tian, HL and Wang, L and Ma, CL and Yang, B and Li, L and Ye, C and Zhao, D and Lin, ZL and Cui, JQ and Liu, YK and Zhu, WY and Zhou, SL and Li, N and Chen, QY}, title = {[Fecal microbiota transplantation for the treatment of intestinal disorders: An analysis of treatment of 15 000 patients].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {3}, pages = {296-303}, doi = {10.3760/cma.j.cn441530-20250114-00025}, pmid = {40123400}, issn = {1671-0274}, support = {82100698//National Natural Science Foundation of China/ ; 2021SYPDRC045//the Climb Plan of Tenth People's Hospital of Tongji University/ ; 202240177//Shanghai Health Commission's Surface Project/ ; }, mesh = {Humans ; Retrospective Studies ; Female ; Male ; *Fecal Microbiota Transplantation/methods ; Middle Aged ; *Intestinal Diseases/therapy ; Adult ; Treatment Outcome ; Dysbiosis/therapy ; Irritable Bowel Syndrome/therapy ; Aged ; Diarrhea/therapy ; }, abstract = {Objective: To examine the long-term efficacy and complications of fecal microbiota transplantation (FMT) for the treatment of diseases related to intestinal dysbiosis. Methods: This was a retrospective descriptive study. Relevant data were collected from the records of 15 000 patients who had undergone FMT and been followed up for more than 3 months during the period from May 2017 to September 2024. The patient cohort comprised 3746 male and 11 254 female patients aged (45.3±12.2) years. The inclusion criterion was meeting the indications for FMT. Application of this criterion yielded 8258 patients with constipation, 684 with Clostridium difficile infection, 1730 with chronic diarrhea, 510 with inflammatory bowel disease, 432 with radiation enteritis, 1940 with irritable bowel syndrome, 365 with autism, 870 with postoperative gastrointestinal dysfunction, and 211 with neurodegenerative diseases. The three routes of delivering FMT comprised infusion of an enterobacterial solution through a nasoenteric tube into the jejunum for 6 consecutive days (upper gastrointestinal FMT group, 11 125 patients), oral intake of enterobacterial capsules for 6 consecutive days (oral capsule FMT, 3597 patients), and a single injection of a bacterial solution into the colon via colonoscopy (lower gastrointestinal FMT group, 278 patients). Other treatments were discontinued during the treatment and follow-up period and administration of other medications was not recommended unless absolutely necessary. The primary outcomes were the efficacy of FMT after 3, 12 and 36 months of treatment, and improvement in chronic constipation, C. difficile infection, chronic diarrhea, inflammatory bowel disease, radiation enteritis, irritable bowel syndrome, post-surgery gastrointestinal dysfunction, and autism. Other outcomes included the occurrence of short-term (within 2 weeks after treatment) and long-term (within 36 months after treatment) adverse reactions. Results: At 3, 12 and 36 months after treatment, the overall rates of effectiveness of treatment were 71.8% (10 763/15 000), 64.4% (7600/11 808) and 58.8% (3659/6218), respectively. Specifically, the rates of clinical improvement were 70.3% (5805/8258), 62.6% (3970/6345), and 56.5% (1894/3352), respectively, for constipation; 85.8% (587/684), 72.3% (408/564), and 67.3% (218/324), respectively, for C.difficile infection; 81.0% (1401/1730), 78.1% (1198/1534), and 72.3% (633/876), respectively, for chronic diarrhea; 64.3% (328/510), 52.3% (249/476), and 46.6 % (97/208), respectively, for inflammatory bowel disease; 77.3% (334/432), 65.4% (212/324), and 53.6% (82/153), respectively, for radiculitis; 70.6% (1370/1940), 64.5% (939/1456), and 60.4% (475/786), respectively, for irritable bowel syndrome; 75.3% (275/365), 70.0% (201/287), and 63.6% (112/176), respectively, for autism; 65.3% (568/870), 54.3% (355/654), and 46.5% (114/245), respectively, for post-surgical gastrointestinal dysfunction; and 45.0% (95/211), 40.5% (68/168), and 34.7% (34/98), respectively, for neurodegenerative diseases. At 3, 12, and 36 months post-treatment, clinical improvement rates were 77.1% (8580/11 125), 67.1% (6437/9595), and 62.1% (3196/5145), respectively, in the upper gastrointestinal route group; and 57.3% (2062/3597), 53.6% (1115/2081), and 45.0% (453/1006), respectively, in the oral capsule group; and 43.5% (121/278) , 36.4% (48/132) and 14.9% (10/67), respectively, in the lower gastrointestinal route group. No serious adverse reactions occurred during treatment or follow-up. The most common adverse reactions in the upper gastrointestinal route group, oral capsule group, and lower gastrointestinal route group were respiratory discomfort (20.4%, 2269/11 125), nausea and vomiting on swallowing the capsule (7.6%, 273/3597), and diarrhea (47.5%, 132/278), respectively; these symptoms resolved at the end of treatment. At 36 months of follow-up, 19 patients reported exacerbation of symptoms of pre-existing diseases and there had been 16 deaths that were not directly related to FMT. Additionally, no systemic diseases had developed after FMT. Conclusion: FMT for the treatment of intestinal dysfunction associated with disorders of the intestinal flora and related extraintestinal diseases is effective and not associated with serious adverse events.}, } @article {pmid40123399, year = {2025}, author = {Li, L and Wang, L and Guo, GG and Fan, YH and Shi, JG and Yuan, XG and Dong, XS and Liu, L and Li, N and Chen, QY}, title = {[Evaluation of the efficacy and safety of multi-center fecal microbiota transplantation for treatment of functional constipation: A retrospective real-world study].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {3}, pages = {288-295}, doi = {10.3760/cma.j.cn441530-20250102-00001}, pmid = {40123399}, issn = {1671-0274}, support = {82470701//National Natural Science Foundation of China/ ; YJXYS-C-003//Research Physician Training Program of Shanghai 10th People's Hospital/ ; 20234Y0079//Scientific Research Project of Shanghai Municipal Health Commission/ ; }, mesh = {Humans ; *Constipation/therapy ; Retrospective Studies ; *Fecal Microbiota Transplantation/adverse effects ; Female ; Male ; Middle Aged ; Treatment Outcome ; Adult ; Aged ; Quality of Life ; Feces/microbiology ; }, abstract = {Objective: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for treating functional constipation, analyze the incidence of, and factors that influence, adverse events, and provide scientific evidence for optimizing FMT treatment. Methods: This retrospective, multicenter, single-arm, pre-post real-world study included 1529 patients with functional constipation from four clinical centers. Eligibility criteria comprised meeting the diagnostic criteria for functional constipation, having undergone at least one FMT treatment, complete pre- and post-treatment data available, and age ≥18 years. Patients who had received other interventions affecting gut function within 1 month before treatment and those with severe organic diseases or immune deficiencies were excluded. Applying the above criteria yielded 1529 eligible patients with functional constipation from four medical centers (1405 from the Shanghai Tenth People's Hospital Affiliated to Tongji University, 20 from the Central Hospital of Wuhan, 67 from the Shanxi Bethune Hospital and 37 from the Longgang District People's Hospital of Shenzhen). The study cohort comprised 746 male (48.8%) and 783 female patients (51.2%) of mean age (51.4 ± 17.4) years, mean body mass index (26.4 ± 4.9) kg/m[2], and mean duration of disease (15.0 ± 8.3) years. The primary outcomes were the incidence, types, and severity of adverse reactions during treatment, and their impact on patients' quality of life. Secondary outcomes included: (1) the efficacy of FMT in treating constipation. This was assessed based on changes in Patient Assessment of Constipation Symptoms (PAC-SYM) scores, where higher score indicates worse symptom. (2) Subjective satisfaction, evaluated through questionnaires or rating scales, reflecting patients' acceptance of and satisfaction with the treatment, with scores ranging from 1 to 5, where higher scores indicated greater satisfaction. Paired t-tests and Wilcoxon signed-rank tests were used to evaluate changes in symptom scores and biochemical indicators before and after treatment. Logistic regression was performed to analyze factors influencing adverse events, and subgroup analyses to explored differences in efficacy between patient groups. Results: In this cohort of 1529 patients with functional constipation, adverse reactions were primarily mild to moderate (1048/1529,68.5%). They comprised fever in 54 patients (3.5%), dizziness or fatigue in 218 (14.3%), throat discomfort in 806 (52.7%), nausea and vomiting in 166 (10.9%), and abdominal distension or pain in 415 (27.1%). According to multivariate logistic regression analysis, PAC-SYM scores were associated with the rate of adverse reactions, higher scores indicating a lower risk (OR = 0.958, 95% CI: 0.923-0.993, P=0.021). Among the 1529 patients, 274 (17.9%) underwent two or more treatment courses. After one treatment course, the patients' PAC-SYM scores decreased from (37.7 ± 3.2) pre-treatment to (23.7 ± 8.6) (mean difference 14.0 ± 9.1). PAC-SYM scores decreased by (20.7 ± 7.7) after two courses of FMT, and by (19.4 ± 6.3) after three courses. After treatment, 50.7%(775/1529) of patients reported satisfaction scores of ≥4. Adverse reactions impacted satisfaction; specifically, dizziness/fatigue, throat discomfort, and abdominal distension/pain were significantly associated with satisfaction (all P < 0.05). Conclusions: FMT achieved good relief of symptoms of functional constipation and multiple treatment courses have a cumulative effect. Adverse reactions, mainly dizziness/fatigue, throat discomfort, and abdominal distension/pain, had significant negative impacts on patient satisfaction.}, } @article {pmid40123398, year = {2025}, author = {Xu, Y and Ye, C and Li, N and Chen, QY}, title = {[Challenges and progress in in the clinical application of fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {3}, pages = {266-273}, doi = {10.3760/cma.j.cn441530-20241224-00420}, pmid = {40123398}, issn = {1671-0274}, support = {82470701, 82401727//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; }, abstract = {With the deepening understanding of the role of gut microbiota in human health and disease, fecal microbiota transplantation has gained widespread attention as an emerging therapeutic approach in recent years. This technique involves the transplantation of microbial communities from the feces of healthy donors into patients to reconstruct or improve the gut microbiota structure, thereby achieving therapeutic goals. Fecal microbiota transplantation has become an effective method for treating recurrent or refractory Clostridium difficile infections and has shown good therapeutic effects and safety in clinical trials for various gastrointestinal diseases, including inflammatory bowel disease, irritable bowel syndrome, slow transit constipation, and chronic diarrhea. Moreover, its application has been extended to research in metabolic diseases and neurological disorders, which are not directly related to the gut. However, the clinical efficacy of fecal microbiota transplantation still needs improvement, and there are many challenges regarding specific application strategies that remain to be addressed. This article discusses the current progress and challenges of fecal microbiota transplantation strategies and reviews cutting-edge interventional methods such as small intestine microbiota intervention and bacteriophage therapy, aiming to provide reference for further research in fecal microbiota transplantation.}, } @article {pmid40123397, year = {2025}, author = {Jin, YF and Wen, WJ and Zuo, T}, title = {[Phages in human health and gut microbiota transplantation therapy].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {3}, pages = {261-265}, doi = {10.3760/cma.j.cn441530-20241130-00387}, pmid = {40123397}, issn = {1671-0274}, support = {82172323, 32100134//National Natural Science Foundation of China/ ; 2024A1515010533//Guangdong Provincial Natural Science Foundation/ ; 202206010014//Guangzhou Key R&D program/ ; 2022JBGS03//Seed Fund from the Sixth Affiliated Hospital of Sun Yat-sen University and Sun Yat-sen University/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; *Bacteriophages/physiology ; }, abstract = {Phages, prokaryotic viruses widely present in the human, are a crucial component of the gut microbiome. They play a significant role in human health and the development of diseases. Emerging evidence indicates that phages can interact with bacteria to affect their abundance, metabolism, and antibiotic resistance, thereby influencing the balance of the gut microbiota. In addition, phages also contribute to the gut immune response, and can become dysregulated in a range of immune-related diseases. Gut phages also carry important roles in fecal microbiota transplantation (FMT) for disease treatment. Phages can target specific bacterial members and communities, thereby reduce the risk of bacterial infections or the presence of bacteria, and maintain the stability of the gut microbiome. However, gut phageome research is still in its infancy and additional basic and clinical researches are required to evaluate its species composition, mechanisms of pathogenicity or protection, as well as its efficacy and safety.}, } @article {pmid40123396, year = {2025}, author = {Wang, XJ and Zhao, D and Qin, YH and Yu, LT and Cao, Z and Liu, WH and Yang, B and Li, N and Chen, QY and Qin, HL}, title = {[How close is fecal microbiota transplantation to moving to precision medicine?].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {3}, pages = {254-260}, doi = {10.3760/cma.j.cn441530-20241220-00415}, pmid = {40123396}, issn = {1671-0274}, support = {82300753, 82330093, 82470701//National Natural Science Foundation of China/ ; 2024YFA1307101//National Key R&D Program/ ; }, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Precision Medicine ; *Gastrointestinal Microbiome ; Feces/microbiology ; }, abstract = {Fecal microbiota transplantation (FMT) has the potential to rebuild the intestinal microbiome of patients, which can influence the disease course, alleviate symptoms, or even cure the disease. It is seen as a promising breakthrough for treating major chronic diseases that are difficult to manage. Currently, FMT therapy has been clinically studied for over 80 diseases and has led to significant breakthroughs. However, there are still four main challenges: (1) identifying the effective characteristics of donor microbiota and ensuring precise matching between donors and recipients; (2) understanding the pathways and molecular mechanisms by which key FMT bacteria and metabolites improve disease outcomes; (3) studying strain interactions and colonization mechanisms to restore intestinal microbiota balance; and (4) refining the precision of microbiome and functional microbiota transplantation. To address these clinical challenges, this article reviews the latest research both domestically and internationally, outlines the response patterns of FMT therapy, examines the reasons behind FMT failure, and explores future directions for the development of FMT. The aim is to accelerate the scientific and precise advancement of FMT technology in China.}, } @article {pmid40123393, year = {2025}, author = {, and , and , }, title = {[Consensus of Chinese experts on gut microbiota and fecal microbiota transplantation in inflammatory bowel disease (2025 edition)].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {3}, pages = {225-235}, doi = {10.3760/cma.j.cn441530-20241224-00422}, pmid = {40123393}, issn = {1671-0274}, support = {2022YFC2010101//Ministry of Science and Technology Major Research and Development Program/ ; 2022YFA1304100//Ministry of Science and Technology Major Research and Development Program Subproject/ ; 82470701, 81700480, 82300753//National Natural Science Foundation of China/ ; 076478684Q/2023-00154//Shanghai Municipal Health Commission Key Project/ ; ZJ2022-ZD-005//Shanghai Zhangjiang National Independent Innovation Demonstration Zone Special Development Fund Major Project/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Gastrointestinal Microbiome ; Consensus ; China ; }, abstract = {In recent years, significant progress has been made in the clinical and basic research on fecal microbiota transplantation (FMT) for the treatment of inflammatory bowel disease (IBD). With the continuous application of new microbiota-based diagnostic and therapeutic concepts in clinical practice, it is imperative to standardize the diagnostic and therapeutic processes of FMT for IBD and provide consensus recommendations based on the latest evidence from evidence-based medicine for clinical practitioners. Organized by the Chinese Society for Parenteral and Enteral Nutrition of the Chinese Medical Association, the Gut Microbiota and FMT Committee of the Chinese Society for Human Health Sciences, and the Gut Microbiota Committee of the Shanghai Preventive Medicine Association, and with reference to the latest international consensus and relevant research advancements, this consensus integrates the clinical practice experience of domestic experts to establish the "Consensus of Chinese experts on gut microbiota and fecal microbiota transplantation in inflammatory bowel disease (2025 edition)". This consensus provides 29 recommendations focusing on the selection of FMT indications, gut microbiota analysis, donor selection and quality control for IBD transplantation, considerations during the transplantation period, selection of transplantation routes and dosages, management of FMT-related complications, and future research directions, aiming to offer standardized guidance for the clinical application of FMT in the treatment of IBD.}, } @article {pmid40122676, year = {2025}, author = {González-Correa, C and Moleón, J and Miñano, S and Robles-Vera, I and de la Visitación, N and Guerra-Hernández, E and Toral, M and Jiménez, R and Duarte, J and Romero, M}, title = {Protective Effect of Dietary Fiber on Blood Pressure and Vascular Dysfunction Through Regulation of Sympathetic Tone and Immune Response in Genetic Hypertension.}, journal = {Phytotherapy research : PTR}, volume = {39}, number = {4}, pages = {1858-1875}, doi = {10.1002/ptr.8484}, pmid = {40122676}, issn = {1099-1573}, support = {B-CTS-046-UGR18//Junta de Andalucía and European Regional Development Fund (ERDF)/ ; CTS 164//Junta de Andalucía and European Regional Development Fund (ERDF)/ ; P20_00193//Junta de Andalucía and European Regional Development Fund (ERDF)/ ; MCIN/AEI/10.13039/501100011033//Ministry of Science and Innovation- State Research Agency of Spain (MSI-SRA)/ ; PID2020-116347RB-I00//Ministry of Science and Innovation- State Research Agency of Spain (MSI-SRA)/ ; FJC2021-048099-I//Ministerio de Economia y Competitividad (MINECO)/ ; FPU18/02561//Ministerio de Economia y Competitividad (MINECO)/ ; FPU22/00397//Ministerio de Economia y Competitividad (MINECO)/ ; }, mesh = {Animals ; Rats, Inbred SHR ; *Hypertension/immunology/genetics/prevention & control ; Male ; Rats, Inbred WKY ; *Dietary Fiber/pharmacology ; *Blood Pressure/drug effects ; Gastrointestinal Microbiome/drug effects ; Rats ; Oxidative Stress/drug effects ; Fecal Microbiota Transplantation ; *Sympathetic Nervous System/drug effects ; Fatty Acids, Volatile/metabolism ; T-Lymphocytes, Regulatory ; }, abstract = {The mechanisms underlying the antihypertensive effect of dietary fibers remain poorly understood. This study investigates whether dietary fiber supplementation can prevent cardiovascular damage and high blood pressure in a genetic model of neurogenic hypertension. Six-week-old male spontaneously hypertensive rats (SHR) and their respective normotensive control, Wistar Kyoto rats (WKY), were divided into four groups: Untreated WKY, untreated SHR, SHR treated with resistant starch (SHR + RS), and SHR treated with inulin-type fructans (SHR + ITF) for 12 weeks. Additionally, a faecal microbiota transplantation (FMT) experiment was conducted, transferring faecal content from treated SHR donors to recipient SHRs. A diet rich in RS fiber reduced vascular oxidative stress, inflammation, and high blood pressure. These protective effects were associated with a reshaped gut microbiota, leading to increased short-chain fatty acid production, reduced endotoxemia, decreased sympathetic activity, and a restored balance between Th17 and Treg lymphocytes in mesenteric lymph nodes and aorta. Elevated plasma levels of acetate and butyrate in the SHR + RS group correlated with increased expression of aortic GPR41, GRP43 and PPARδ. Conversely, ITF treatment failed to prevent hypertension or endothelial dysfunction in SHR. FMT from the SHR + RS group to recipient SHR partially replicated these beneficial effects. This study highlights the antihypertensive benefits of dietary insoluble RS fiber, which are attributed to enhanced short-chain fatty acids production in the gut. This leads to improved gut permeability, reduced sympathetic tone, and diminished vascular T-cell accumulation. Therefore, dietary interventions with RS fiber may offer promising therapeutic strategies for preventing hypertension.}, } @article {pmid40122597, year = {2025}, author = {Su, R and Wen, W and Jin, Y and Cao, Z and Feng, Z and Chen, J and Lu, Y and Zhou, G and Dong, C and Gao, S and Li, X and Zhang, H and Chao, K and Lan, P and Wu, X and Philips, A and Li, K and Gao, X and Zhang, F and Zuo, T}, title = {Dietary whey protein protects against Crohn's disease by orchestrating cross-kingdom interaction between the gut phageome and bacteriome.}, journal = {Gut}, volume = {74}, number = {8}, pages = {1246-1260}, doi = {10.1136/gutjnl-2024-334516}, pmid = {40122597}, issn = {1468-3288}, mesh = {*Crohn Disease/microbiology/prevention & control ; *Gastrointestinal Microbiome/drug effects/physiology ; Humans ; Animals ; Mice ; *Whey Proteins/pharmacology/administration & dosage ; Female ; Male ; Adult ; *Bacteriophages ; *Diet ; Disease Models, Animal ; Middle Aged ; Intestinal Mucosa/microbiology ; }, abstract = {BACKGROUND: The gut microbiome and diet are important factors in the pathogenesis and management of Crohn's disease (CD). However, the role of the gut phageome under dietary influences is unknown.

OBJECTIVE: We aim to explore the effect of diet on the gut phageome-bacteriome interaction linking to CD protection.

DESIGN: We recruited CD patients and healthy subjects (n=140) and conducted a multiomics investigation, including paired ileal mucosa phageome and bacteriome profiling, dietary survey and phenome interrogation. We screened for the effect of diet on the gut phageome and bacteriome, as well as its epidemiological association with CD risks. The underlying mechanisms were explored in target phage-bacteria monocultures and cocultures in vitro and in two mouse models in vivo.

RESULTS: On dietary screening in humans, whey protein (WP) consumption was found to profoundly impact the gut phageome and bacteriome (more pronounced on the phageome) and was associated with a lower CD risk. Indeed, the WP reshaped gut phageome can causally attenuate intestinal inflammation, as shown by faecal phageome versus bacteriome transplantation from WP-consuming versus WP-non-consuming mice to recipient mice. Mechanistically, WP induced phage (a newly isolated phage AkkZT003P herein) lysis of the mucin-foraging bacterium Akkermansia muciniphila, which unleashed the symbiotic bacterium Streptococcus thermophilus to counteract intestinal inflammation.

CONCLUSION: Our study charted the importance of cross-kingdom interaction between gut phage and bacteria in mediating the dietary effect on CD protection. Importantly, we uncovered a beneficial dietary WP, a keystone phage AkkZT003P, and a probiotic S. thermophilus that can be used in CD management in the future.}, } @article {pmid40120791, year = {2025}, author = {Xu, DQ and Geng, JX and Gao, ZK and Fan, CY and Zhang, BW and Han, X and He, LQ and Dai, L and Gao, S and Yang, Z and Zhang, Y and Arshad, M and Fu, Y and Mu, XQ}, title = {To explore the potential combined treatment strategy for colorectal cancer: Inhibition of cancer stem cells and enhancement of intestinal immune microenvironment.}, journal = {European journal of pharmacology}, volume = {998}, number = {}, pages = {177533}, doi = {10.1016/j.ejphar.2025.177533}, pmid = {40120791}, issn = {1879-0712}, mesh = {Animals ; *Colorectal Neoplasms/therapy/immunology/pathology/microbiology/chemically induced ; *Neoplastic Stem Cells/drug effects/pathology/immunology ; Gastrointestinal Microbiome/drug effects/immunology ; *Tumor Microenvironment/drug effects/immunology ; Mice ; *Fecal Microbiota Transplantation ; *Pyrans/pharmacology/therapeutic use ; Male ; Mice, Inbred C57BL ; Combined Modality Therapy ; Cell Proliferation/drug effects ; Cytokines/metabolism ; Disease Models, Animal ; Dextran Sulfate ; *Intestines/immunology ; Polyether Polyketides ; }, abstract = {BACKGROUND: The antibiotic salinomycin, a well-known cancer stem cell inhibitor, may impact the diversity of the intestinal microbiota in colorectal cancer (CRC) mice, which plays a pivotal role in shaping the immune system. This study explores the anti-cancer effects and mechanisms of combining salinomycin and fecal microbiota transplantation (FMT) in treating CRC.

METHODS: FMT was given via enema, while salinomycin was injected intraperitoneally into the CRC mouse model induced by azoxymethane/dextran sodium sulfate.

RESULTS: In CRC mice, a large number of LGR5-labeled cancer stem cells and severe disturbances in the intestinal microbiota were observed. Interestingly, salinomycin inhibited the proliferation of cancer stem cells without exacerbating the microbial disorder as expected. In comparison to salinomycin treatment, the combination of salinomycin and FMT significantly improved pathological damage and restored intestinal microbial diversity, which is responsible for shaping the anti-cancer immune microenvironment. The supplementation of FMT significantly increased the levels of propionic acid and butyric acid while also promoting the infiltration of CD8[+] T cells and Ly6G[+] neutrophils, as well as reducing F4/80[+] macrophage recruitment. Notably, cytokines that were not impacted by salinomycin exhibited robust reactions to alterations in the gut microbiota. These included pro-inflammatory factors (IL6, IL12b, IL17, and IL22), chemokine-like protein OPN, and immunosuppressive factor PD-L1.

CONCLUSIONS: Salinomycin plays the role of "eliminating pathogenic qi," targeting cancer stem cells; FMT plays the role of "strengthening vital qi," reversing the intestinal microbiota disorder and enhancing anti-cancer immunity. They have a synergistic effect on the development of CRC.}, } @article {pmid40120542, year = {2025}, author = {Luo, F and Yang, J and Song, Z and Zhao, Y and Wang, P and Liu, K and Mou, X and Liu, W and Li, W}, title = {Renshen Zhuye decoction ameliorates high-fat diet-induced obesity and insulin resistance by modulating gut microbiota and metabolic homeostasis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {141}, number = {}, pages = {156655}, doi = {10.1016/j.phymed.2025.156655}, pmid = {40120542}, issn = {1618-095X}, mesh = {Animals ; *Insulin Resistance ; *Gastrointestinal Microbiome/drug effects ; Diet, High-Fat/adverse effects ; *Drugs, Chinese Herbal/pharmacology ; *Obesity/drug therapy/metabolism ; Male ; Homeostasis/drug effects ; Mice ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Lipid Metabolism/drug effects ; Energy Metabolism/drug effects ; }, abstract = {BACKGROUND: Obesity, characterized by excessive adipose tissue accumulation, has become a global health challenge with rapidly increasing prevalence. It contributes significantly to metabolic disorders including insulin resistance (IR). Renshen-zhuye decoction (RZD), a traditional Chinese medicine formula historically used for diabetes, shows potential for improving metabolic parameters, but its effects and mechanisms in obesity and insulin resistance remain unclear.

PURPOSE: This study aimed to evaluate the therapeutic benefits of RZD on obesity and insulin resistance, and to elucidate the underlying mechanisms through which it improves glucose and lipid metabolism.

METHODS: The role of RZD was evaluated in a high-fat diet (HFD) mouse model. The formula was characterized using UPLC-MS. Comprehensive analyses including histopathological staining, immunofluorescence, biochemical assays, 16S rRNA gene sequencing of gut microbiota, and non-targeted metabolomic analysis were performed. To validate the role of gut microbiota, we employed antibiotic treatment (ABX) to deplete intestinal flora and conducted fecal microbiota transplantation (FMT) experiments.

RESULTS: RZD treatment dose-dependently alleviated HFD-induced dyslipidemia and insulin resistance, improving glucose tolerance, insulin sensitivity, and energy expenditure. Gut microbiota analysis revealed that RZD significantly modulated the composition of intestinal flora and their metabolic profiles. Additionally, RZD reduced intestinal and systemic inflammation by enhancing intestinal barrier integrity, particularly through increased expression of tight junction proteins such as Occludin. Importantly, the beneficial effects of RZD on weight management and glucose homeostasis were antagonized by antibiotic intervention, while FMT experiments confirmed that these improvements were mediated through gut microbiota modulation.

CONCLUSION: This study provides new insights into RZD's modulatory effects on gut microbiota and subsequent improvements in obesity-related metabolic parameters. RZD alleviates HFD-induced obesity and insulin resistance in mice by modulating gut microbiota composition and function, which subsequently improves intestinal barrier integrity, reduces inflammation, and enhances metabolic homeostasis.}, } @article {pmid40120240, year = {2025}, author = {Gao, C and Chen, Y and Zhang, Z and Xu, D and Liu, X and Wang, D and Shi, L and Wang, X and Chen, H and Hao, E}, title = {LAYING RATE WAS CORRELATED WITH MICROBIAL Fecal microbiota transplantation improves the laying performance by changing the gut microbiota composition in late laying period.}, journal = {Poultry science}, volume = {104}, number = {5}, pages = {105064}, pmid = {40120240}, issn = {1525-3171}, mesh = {Animals ; *Chickens/physiology/microbiology ; *Gastrointestinal Microbiome ; Female ; *Fecal Microbiota Transplantation/veterinary ; *Reproduction ; *Oviposition ; Age Factors ; }, abstract = {This research investigated the differences and succession patterns of microbes in different ages, the performance of laying hens, and the effect of Fecal Microbiota Transplantation (FMT) on aged laying hens. First, based on the different laying rates and age, we divided the laying hens into four groups: 75-week-old high-yield (OH, laying rate (LR) > 90%), 75-week-old low-yield (OL, LR < 60%), 75-week-old non-laying hens (OZ, LR = 0%) and 35-week-old high-yield (YH, LR > 90%) with 5 replicates in each group and 6 chickens in each replicate. The microbial metabolic patterns between different ages and laying rates were determined using 16S rDNA technology. Then, to verify the results of microbiome research, we utilized FMT technology to transplant the gut microbiota from OH to OZ (OZFMT-OH), thereby revealing the connection between gut microbes and production performance. The results showed that high-yielding hens (YH and OH groups) had higher levels of Superoxide dismutase (SOD) and Immunoglobulin A (IgA) compared to OL and OZ groups. The Villus height to Crypt depth ratio(V/C) was significantly higher in the YH group than in 75-week-old hens (P < 0.05). Alpha diversity indicated higher microbial diversity in the YH group compared to older hens (P < 0.05), with YH hens harboring more Megamonas, OH hens more Bacteroides, and OL and OZ groups showing higher levels of harmful bacteria. The villus height, V/C, mucosal layer thickness, cup cell number acetic acid level, and LR in the OZFMT-OH group were significantly higher than those in the OZ group (P < 0.05), while the IL-2 level, crypt depth and cecal intestinal wall thickness were significantly lower than those in OZ group (P < 0.05). FMT also changed the morphological structure of grade follicles and small yellow follicles, improved the microbe composition of cecum and increased Bacteroides abundance. In the late laying period, if the intestinal flora cannot maintain the dynamic balance and carry out timely replacement, the production performance may be decreased, and the increase of Bacteroides abundance in the intestinal tract can improve the intestinal health and production performance of laying hens in the late laying period.}, } @article {pmid40118401, year = {2025}, author = {Zhang, J and Zhou, J and He, Z and Xia, Z and Liu, H and Wu, Y and Chen, S and Wu, B and Li, H}, title = {Salidroside attenuates NASH through regulating bile acid-FXR/TGR5 signaling pathway via targeting gut microbiota.}, journal = {International journal of biological macromolecules}, volume = {307}, number = {Pt 4}, pages = {142276}, doi = {10.1016/j.ijbiomac.2025.142276}, pmid = {40118401}, issn = {1879-0003}, mesh = {Animals ; *Glucosides/pharmacology ; *Gastrointestinal Microbiome/drug effects ; *Phenols/pharmacology ; *Bile Acids and Salts/metabolism ; *Non-alcoholic Fatty Liver Disease/metabolism/drug therapy/microbiology/pathology ; *Signal Transduction/drug effects ; Mice ; *Receptors, G-Protein-Coupled/metabolism ; Male ; *Receptors, Cytoplasmic and Nuclear/metabolism ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Disease Models, Animal ; }, abstract = {Nonalcoholic steatohepatitis (NASH) is a significant threat to human health. Our previous study revealed that salidroside attenuated NASH and regulated the gut microbiota. However, whether the therapeutic effect of salidroside depends on gut microbiota remains to be determined. Therefore, we conducted further experiments to elucidate the essential functions of gut microbiota-associated metabolic pathways in the anti-NASH effects of salidroside. Our results showed that salidroside effectively alleviated lipid accumulation and inflammatory injury in NASH mice. 16S rRNA sequencing revealed that salidroside increased the abundance of Bacteroides. Mice receiving fecal microbiota transplantation (FMT) from salidroside-treated also presented less hepatic steatosis and higher abundance of Bacteroides. Antibiotics eliminated the effects of salidroside on hepatic steatosis and the gut microbiota. Mechanistically, salidroside and FMT from salidroside-treated altered the bile acid (BA) profile by decreasing the levels of conjugated BAs and tauro-α/β-muricholic acid and activated downstream farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). Furthermore, we found that inhibitors of bile salt hydrolase (BSH) and FXR/TGR5 abolished the effects of salidroside and reduced downstream carnitine palmitoyltransferase 1α and lipoprotein lipase expression. These data demonstrate that salidroside attenuated NASH via gut microbiota-BA-FXR/TGR5 signaling pathway and reveal the underlying mechanism of salidroside on NASH.}, } @article {pmid40118127, year = {2025}, author = {Wu, S and Qiao, L and Liu, H and Li, YL and Wang, R and Yin, Y and Li, E and Wang, L and Guan, X and Yin, L and Liu, Q and Peng, X and Zhang, Y and Yang, Z and Zuo, L and Zhang, C}, title = {Age related gut microbiota regulates energy-related metabolism to influence natural aging phenotypes in the heart.}, journal = {Experimental gerontology}, volume = {203}, number = {}, pages = {112734}, doi = {10.1016/j.exger.2025.112734}, pmid = {40118127}, issn = {1873-6815}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Aging/metabolism/physiology ; Male ; Fecal Microbiota Transplantation ; *Energy Metabolism/physiology ; Rats ; *Myocardium/metabolism ; Positron Emission Tomography Computed Tomography ; *Heart/physiology ; Oxidative Stress ; Phenotype ; Autophagy ; Rats, Sprague-Dawley ; RNA, Ribosomal, 16S ; }, abstract = {As the population ages, problems pertaining to health and life expectancy due to the aging heart have become increasingly prominent. The gut microbiota has become a potential therapeutic target in several diseases, including cardiovascular diseases. Current studies on the roles of the gut microbiota in the cardiovascular system have focused mainly on cardiovascular diseases; therefore, the effects of the gut microbiota on the natural aging of myocardial tissue remain unclear. The present study aimed to explore the roles and mechanisms of the gut microbiota and related metabolites in the natural aging of the heart. Animal models of fecal microbiota transplantation (FMT) were established in elderly and young rats. 16S rRNA sequencing revealed that the gut microbiota of the recipients shifted toward the profile of the donors, with concomitant cardiac structure and diastolic function changes detected via ultrasound and positron emission tomography-computed tomography (PET-CT). A group of significantly enriched myocardial metabolites detected by LC/MS were involved in the fatty acid β-oxidation process. Together with altered glucose uptake, as revealed by PET-CT, changes in ATP content and mitochondrial structure further verified a metabolic difference related to energy among rats transplanted with the gut microbiota from donors of different ages. This study demonstrated that gut microbes may participate in the physiological aging process of the rat heart by regulating oxidative stress and autophagy. The gut microbiota has been shown to be involved in the natural aging of the heart at multiple levels, from the organ level to the metabolically plastic myocardiocytes and associated molecules.}, } @article {pmid40116713, year = {2025}, author = {Chinna Meyyappan, A and Sgarbossa, C and Bromley, H and Forth, E and Müller, DJ and Vazquez, G and Cabrera, C and Milev, R}, title = {The Safety and Efficacy of Microbial Ecosystem Therapeutic-2 in People With Major Depression - A Phase 2, Double-Blind, Placebo-Controlled Study: Clinical Results: Innocuité et efficacité du traitement de l'écosystème microbien (met-2) dans la dépression majeure - une étude de phase 2 à double insu contrölée par placebo : résultats cliniques.}, journal = {Canadian journal of psychiatry. Revue canadienne de psychiatrie}, volume = {}, number = {}, pages = {7067437251328270}, pmid = {40116713}, issn = {1497-0015}, abstract = {ObjectivesThis study examines the safety and efficacy of a fecal transplant alternative, Microbial Ecosystem Therapeutic-2 (MET-2), in improving symptoms of depression. The primary objective of this study is to assess changes in depressive symptoms before, during, and after administration of MET-2 in comparison to placebo. Mood-related symptoms such as anxiety and anhedonia, gastrointestinal symptoms, and safety of the therapeutic were also assessed using both self-report and clinician-rated measures.MethodsTwenty-nine participants (n = 29) experiencing a major depressive episode were recruited from the Kingston and Toronto areas. Participants orally consumed MET-2, an encapsulated microbial therapeutic containing 40 different strains of bacteria, or placebo alternative, once daily for 6 weeks with a 2-week follow-up. Participants underwent a series of clinical assessments used to measure mood, anxiety, and gastrointestinal symptoms.ResultsThere was a significant improvement in depressive symptomology over time as determined by Montgomery-Åsberg Depression Rating Scale scores (p < 0.0001); however there was no significant difference between placebo and MET-2 groups (p = 0.338). No serious adverse events were reported. The findings of this study are the first to provide evidence for the role of oral microbial therapeutics, such as MET-2, as treatment for symptoms of depression.ConclusionsThough there are positive trends suggesting a greater improvement in depressive symptomology among the MET-2 group compared to the placebo group, a larger sample size is needed for more conclusive results. Clinicaltrials.gov NCT04602715.}, } @article {pmid40116683, year = {2025}, author = {Prati, D and Caprioli, F and Stea, L and Berzuini, A and Pizzotti, D and Petrillo, E and Coluccio, E and Erba, E and Lamorte, G and Ferrari, F and Cariani, L and Amoroso, C and Preti, AC and Bandera, A and Callegaro, A and Castaldi, S and Cardillo, M and Vecchi, M and Valenti, L and De Angelis, V}, title = {A "movement" worth making: why and how Transfusion Services can play a role in Fecal Microbiota Transplant programs.}, journal = {Blood transfusion = Trasfusione del sangue}, volume = {23}, number = {3}, pages = {275-282}, pmid = {40116683}, issn = {2385-2070}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Clostridium Infections/therapy ; *Clostridioides difficile ; Donor Selection ; *Blood Transfusion ; *Transfusion Medicine/methods ; }, abstract = {Fecal Microbiota Transplantation (FMT) is an innovative therapy with growing applications, particularly for recurrent Clostridioides difficile infections (rCDI). However, the broader use of FMT is challenged by the complexities of donor recruitment, the necessity of stringent screening protocols, and the need for maintaining high-quality stool biobanks. This paper explores the integration of FMT programs within transfusion medicine departments, taking advantage of their expertise in donor management and biological material processing. Despite the complexities of donor screening, including a low eligibility rate, the collaboration between transfusion services and other hospital departments demonstrates a viable model for expanding FMT access. Additionally, the recent EU regulations on substances of human origin (SoHO) offer a framework for standardizing and scaling stool banking, enhancing the safety and efficacy of FMT procedures.}, } @article {pmid40116376, year = {2025}, author = {Yang, Y and Zhang, Y and Zhang, W and Lu, K and Wang, L and Liu, Y and Du, L and Yang, J and Guan, L and Ma, H}, title = {Flammulina velutipes residue Polysaccharide Alleviates Immunosuppression and Intestinal Injury by Modulating Gut Microbiota and Associated Metabolites.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {13}, pages = {7788-7806}, doi = {10.1021/acs.jafc.4c12105}, pmid = {40116376}, issn = {1520-5118}, mesh = {Animals ; *Flammulina/chemistry ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Polysaccharides/administration & dosage ; *Intestines/drug effects/injuries/immunology/microbiology ; Bacteria/genetics/isolation & purification/classification/drug effects/metabolism ; Male ; Humans ; Cyclophosphamide/adverse effects ; Mice, Inbred C57BL ; Immunosuppression Therapy ; }, abstract = {This study elucidated the mechanisms underlying the immunoregulatory and gut-microbiota-modulating effects of Flammulina velutipes residue polysaccharide (FVRP) using cyclophosphamide (CTX)-induced mouse models. FVRP supplementation alleviated CTX-induced intestinal damage and boosted antioxidant enzyme activity and cytokine secretion. Additionally, FVRP enhanced the diversity and total species richness of the gut microbiota, promoting the proliferation of beneficial bacteria (e.g., Prevotellaceae), while reducing the abundance of CTX-derived bacteria (Lachnospiraceae and Rikenellaceae). FVRP facilitates the accumulation of short-chain fatty acids. Untargeted metabolomic analyses of cecal content revealed that FVRP treatment notably restored the levels of 32 endogenous metabolites altered by CTX. Based on a pseudosterility mice model, fecal microbiota transplantation (FMT), and fecal filtrate transplantation (FFT), gut microbiota and associated metabolites were demonstrated to play a crucial role in the immunomodulatory and protective effects of FVRP against intestinal injury. In conclusion, FVRP exhibits significant potential as an immune enhancer and natural therapeutic agent for alleviating intestinal inflammatory conditions.}, } @article {pmid40115610, year = {2025}, author = {Waterman, A and Doumas, SA and Fischer, M and Mattar, M and Charbel, S and Jennings, J and Doman, DB}, title = {Uncovering the Hidden Link Between the Aberrant Intestinal Microbiome and Fibromyalgia.}, journal = {Gastroenterology & hepatology}, volume = {21}, number = {2}, pages = {111-121}, pmid = {40115610}, issn = {1554-7914}, abstract = {Fibromyalgia is a multifaceted syndrome primarily characterized by chronic widespread pain and fatigue. Despite its significant prevalence and incidence, the mechanisms mediating the disease pathogenesis have remained poorly understood; however, increasing evidence suggests a potentially central role of intestinal dysbiosis. Researchers have been examining possible diagnostic biomarkers, such as Helicobacter pylori infection, urine metabolite profiles, and cytokine levels, which reflect these microbiome changes. Additionally, evaluation of therapeutic interventions targeting the gut microbiome, including probiotics, fecal microbiota transplantation, and antibiotics for specific infections, has highlighted their potential in alleviating fibromyalgia symptoms. This article delves into the emerging role of the gut microbiome in fibromyalgia pathogenesis, illustrating how alterations in gut bacterial composition and diversity are implicated in the pathophysiology of the disease through the gut-brain axis, and sets a direction for future research to enhance diagnostic accuracy and therapeutic efficacy of this complex condition.}, } @article {pmid40111698, year = {2025}, author = {Vernon, JJ}, title = {Modulation of the Human Microbiome: Probiotics, Prebiotics, and Microbial Transplants.}, journal = {Advances in experimental medicine and biology}, volume = {1472}, number = {}, pages = {277-294}, pmid = {40111698}, issn = {0065-2598}, mesh = {Humans ; *Probiotics/therapeutic use/administration & dosage ; *Prebiotics/administration & dosage ; *Microbiota/physiology ; *Mouth/microbiology ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; }, abstract = {The balance between health and disease is intrinsically linked to the interactions between microbial communities and the host. This complex environment of antagonism and synergy involves both prokaryotic and eukaryotic cells, whose collaborative metabolic pathways and immunomodulatory elements influence system homeostasis. As with the gut and other niches, the oral microbiome has the capacity to affect distal host sites. The ability to manipulate this environment holds the potential to impact local and systemic disease.With the increasing threat of antimicrobial resistance, novel approaches to reduce the burden of disease are essential. The use of probiotics and prebiotics is one such strategy. Probiotics introduce non-pathogenic bacteria into the environment to compete with pathogens for nutrients and attachment sites, or to produce metabolites that counteract disease aetiologies. Prebiotic compounds enhance the growth of health-associated organisms, offering additional benefits, whilst a conjunctive approach with probiotics potentially holds even greater promise. Though widely studied in the gastrointestinal context, their potential for treating oral diseases, such as dental caries and periodontitis, is less understood. Additionally, the use of microbial transplantations has demonstrated efficacy in other areas, reducing systemic inflammation and recolonising with commensal bacteria. Here we evaluate their use in the oral context and their modulatory impact on overall health.In this chapter, we discuss how pro- and prebiotic strategies seek to modulate both the oral and gut environments to promote oral health and prevent disease. We assess novel approaches for utilising health-associated microorganisms to combat oral disorders, either administered locally in the mouth or imparting influence through immune modulation via the oral-gut axis. By examining available clinical trial data, we aim to further understand the intricacies involved in this discipline. Furthermore, we consider the challenges facing the research community, including optimal candidate organism/compound selection and colonisation retention, as well as considerations for future research.}, } @article {pmid40110391, year = {2025}, author = {Zhu, B and Gu, Z and Hu, H and Huang, J and Zeng, Z and Liang, H and Yuan, Z and Huang, S and Qiu, Y and Sun, XD and Liu, Y}, title = {Altered Gut Microbiota Contributes to Acute-Respiratory-Distress-Syndrome-Related Depression through Microglial Neuroinflammation.}, journal = {Research (Washington, D.C.)}, volume = {8}, number = {}, pages = {0636}, pmid = {40110391}, issn = {2639-5274}, abstract = {Acute respiratory distress syndrome (ARDS) survivors often suffer from long-term psychiatric disorders such as depression, but the underlying mechanisms remain unclear. Here, we found marked alterations in the composition of gut microbiota in both ARDS patients and mouse models. We investigated the role of one of the dramatically changed bacteria-Akkermansia muciniphila (AKK), whose abundance was negatively correlated with depression phenotypes in both ARDS patients and ARDS mouse models. Specifically, while fecal transplantation from ARDS patients into naive mice led to depressive-like behaviors, microglial activation, and intestinal barrier destruction, colonization of AKK or oral administration of its metabolite-propionic acid-alleviated these deficits in ARDS mice. Mechanistically, AKK and propionic acid decreased microglial activation and neuronal inflammation through inhibiting the Toll-like receptor 4/nuclear factor κB signaling pathway. Together, these results reveal a microbiota-dependent mechanism for ARDS-related depression and provide insight for developing a novel preventative strategy for ARDS-related psychiatric symptoms.}, } @article {pmid40110192, year = {2025}, author = {Zhang, C and Wang, Y and Cheng, L and Cao, X and Liu, C}, title = {Gut microbiota in colorectal cancer: a review of its influence on tumor immune surveillance and therapeutic response.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1557959}, pmid = {40110192}, issn = {2234-943X}, abstract = {Colorectal cancer (CRC) poses a significant global health burden, with gut microbiota emerging as a crucial modulator of CRC pathogenesis and therapeutic outcomes. This review synthesizes current evidence on the influence of gut microbiota on tumor immune surveillance and responses to immunotherapies and chemotherapy in CRC. We highlight the role of specific microbial taxa in promoting or inhibiting tumor growth and the potential of microbiota-based biomarkers for predicting treatment efficacy. The review also discusses the implications of microbiota modulation strategies, including diet, probiotics, and fecal microbiota transplantation, for personalized CRC management. By critically evaluating the literature, we aim to provide a comprehensive understanding of the gut microbiota's dual role in CRC and to inform future research directions in this field.}, } @article {pmid40110027, year = {2025}, author = {Cai, S and Li, Z and Bai, J and Ding, Y and Liu, R and Fang, L and Hou, D and Zhang, S and Wang, X and Wang, Y and Jiang, Y and Xiang, Y and Wu, W and He, Y and Zhang, Y and Ren, X}, title = {Optimized oxygen therapy improves sleep deprivation-induced cardiac dysfunction through gut microbiota.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1522431}, pmid = {40110027}, issn = {2235-2988}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/physiology ; Mice ; Fecal Microbiota Transplantation ; *Sleep Deprivation/complications ; RNA, Ribosomal, 16S/genetics ; Disease Models, Animal ; *Oxygen/therapeutic use ; Male ; Mice, Inbred C57BL ; *Heart Diseases/therapy/etiology ; Fibrosis ; }, abstract = {Adequate sleep is of paramount importance for relieving stress and restoring mental vigor. However, the adverse physiological and pathological responses resulting from sleep insufficiency or sleep deprivation (SD) are becoming increasingly prevalent. Currently, the impact of sleep deficiency on gut microbiota and microbiota-associated human diseases, especially cardiac diseases, remains controversial. Here, we employed the following methods: constructed an experimental sleep-deprivation model in mice; conducted 16S rRNA sequencing to investigate the changes in gut microbiota; through fecal microbiota transplantation (FMT) experiments, transplanted fecal microbiota from sleep-deprived mice to other mice; established an environment with a 30% oxygen concentration to explore the therapeutic effects of oxygen therapy on gut microbiota-associated cardiac fibrosis and dysfunction; and utilized transcriptome data to study the underlying mechanisms of oxygen therapy. The results revealed that: sleep-deprived mice exhibited weakness, depression-like behaviors, and dysfunction in multiple organs. Pathogenic cardiac hypertrophy and fibrosis occurred in sleep-deprived mice, accompanied by poor ejection fraction and fractional shortening. 16S rRNA sequencing indicated that sleep deprivation induced pathogenic effects on gut microbiota, and similar phenomena were also observed in mice that received fecal microbiota from sleep-deprived mice in the FMT experiments. The environment with a 30% oxygen concentration effectively alleviated the pathological impacts on cardiac function. Transcriptome data showed that oxygen therapy targeted several hypoxia-dependent pathways and inhibited the production of cardiac collagen. In conclusion, these results demonstrate the significance of sufficient sleep for gut microbiota and may represent a potential therapeutic strategy, where the oxygen environment exerts a protective effect on insomniacs through gut microbiota.}, } @article {pmid40108157, year = {2025}, author = {Huang, R and Shen, ZY and Huang, D and Zhao, SH and Dan, LX and Wu, P and Tang, QZ and Ma, ZG}, title = {Microbiota-indole-3-propionic acid-heart axis mediates the protection of leflunomide against αPD1-induced cardiotoxicity in mice.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2651}, pmid = {40108157}, issn = {2041-1723}, support = {82070410; 82270248//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; *Leflunomide/pharmacology/therapeutic use ; Mice ; *Cardiotoxicity/prevention & control/etiology/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Indoles/pharmacology/metabolism ; Myocytes, Cardiac/drug effects/metabolism ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Mice, Inbred C57BL ; *Heart/drug effects ; *Propionates/metabolism/pharmacology ; Male ; Receptors, Aryl Hydrocarbon/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Fecal Microbiota Transplantation ; Immune Checkpoint Inhibitors/adverse effects ; }, abstract = {Anti-programmed death 1 (αPD1) immune checkpoint blockade is used in combination for cancer treatment but associated with cardiovascular toxicity. Leflunomide (Lef) can suppress the growth of several tumor and mitigate cardiac remodeling in mice. However, the role of Lef in αPD1-induced cardiotoxicity remains unclear. Here, we report that Lef treatment inhibits αPD1-related cardiotoxicity without compromising the efficacy of αPD1-mediated immunotherapy. Lef changes community structure of gut microbiota in αPD1-treated melanoma-bearing mice. Moreover, mice receiving microbiota transplants from Lef+αPD1-treated melanoma-bearing mice have better cardiac function compared to mice receiving transplants from αPD1-treated mice. Mechanistically, we analyze metabolomics and identify indole-3-propionic acid (IPA), which protects cardiac dysfunction in αPD1-treated mice. IPA can directly bind to the aryl hydrocarbon receptor and promote phosphoinositide 3-kinase expression, thus curtailing the cardiomyocyte response to immune injury. Our findings reveal that Lef mitigates αPD1-induced cardiac toxicity in melanoma-bearing mice through modulation of the microbiota-IPA-heart axis.}, } @article {pmid40107339, year = {2025}, author = {Xue, M and Deng, Q and Deng, L and Xun, T and Huang, T and Zhao, J and Wei, S and Zhao, C and Chen, X and Zhou, Y and Liang, Y and Yang, X}, title = {Alterations of gut microbiota for the onset and treatment of psoriasis: A systematic review.}, journal = {European journal of pharmacology}, volume = {998}, number = {}, pages = {177521}, doi = {10.1016/j.ejphar.2025.177521}, pmid = {40107339}, issn = {1879-0712}, mesh = {Humans ; *Psoriasis/microbiology/therapy/immunology ; *Gastrointestinal Microbiome/drug effects ; Probiotics/therapeutic use/administration & dosage ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; Animals ; Skin/microbiology/drug effects/immunology ; }, abstract = {Psoriasis is a chronic, recurrent and systemic inflammatory skin disease which is mediated by immunoreaction. Its pathogenesis is multifactorial, and the exact driving factor remains unclear. Recent studies showed that gut microbiota, which maintain immune homeostasis of our bodies, is closely related with occurrence, development and prognosis of psoriasis. The intestinal microbial abundance and diversity in patients with psoriasis have changed significantly, including intestinal microbiota disorders and reduced production of short chain fatty acids (SCFAs), abnormalities in Firmicutes/Bacteroidetes (F/B), etc. Besides, the intestinal microbiota of psoriasis patients has also changed after treatment of systemic drugs, biologics and small molecule chemical drugs, suggesting that the intestinal microbiota may be a potential response-to-treatment biomarker for evaluating treatment effectiveness. Oral probiotics and prebiotics administration as well as fecal microbial transplantation were also reported to benefit well in psoriasis patients. Additionally, we also discussed the microbial changes from the skin and other organs, which regulated both the onset and treatment of psoriasis together with gut microbiota. Herein, we reviewed recent studies on the psoriasis-related microbiota in an attempt to confidently identify the "core" microbiota of psoriatic patients, understand how microbiota influence psoriasis through the gut-skin axis, and explore potential therapeutic strategies for psoriasis.}, } @article {pmid40104324, year = {2025}, author = {Gu, C and Sha, G and Zeng, B and Cao, H and Cao, Y and Tang, D}, title = {Therapeutic potential of fecal microbiota transplantation in colorectal cancer based on gut microbiota regulation: from pathogenesis to efficacy.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848251327167}, pmid = {40104324}, issn = {1756-283X}, abstract = {Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide, with its progression intricately linked to gut microbiota dysbiosis. Disruptions in microbial homeostasis contribute to tumor initiation, immune suppression, and inflammation, establishing the microbiota as a key therapeutic target. Fecal microbiota transplantation (FMT) has emerged as a transformative approach to restore microbial balance, enhance immune responses, and reshape the tumor microenvironment. This review explores the mechanisms underlying FMT's therapeutic potential, evaluates its advantages over other microbiota-based interventions, and addresses challenges such as donor selection, safety concerns, and treatment standardization. Looking forward, the integration of FMT into personalized CRC therapies requires robust clinical trials and the identification of predictive biomarkers to optimize its efficacy and safety.}, } @article {pmid40104059, year = {2025}, author = {Sharma, P and Jain, T and Sorgen, A and Iyer, S and Tarique, M and Roy, P and Kurtom, S and Sethi, V and Bava, EP and Gutierrez-Garcia, AK and Vaish, U and Suresh, DS and Sahay, P and Edwards, D and Afghani, J and Putluri, S and Reddy, KRK and Amara, CS and Kamal, AHM and Fodor, A and Dudeja, V}, title = {Smoking-induced gut microbial dysbiosis mediates cancer progression through modulation of anti-tumor immune response.}, journal = {iScience}, volume = {28}, number = {3}, pages = {112002}, pmid = {40104059}, issn = {2589-0042}, support = {S10 OD032296/OD/NIH HHS/United States ; }, abstract = {Cigarette smoke exposure (CSE) increases the risk for a plethora of cancers. Recent evidence indicates that the gut microbiome can influence cancer progression by immune system modulation. Since CSE alters the gut microbiome, we hypothesized that the gut microbiome serves as a causative link between smoking and cancer growth. Through a combination of syngeneic animal models and fecal microbiota transplantation studies, we established an essential role for smoke-induced dysbiosis in cancer growth. 16s rRNA sequencing and liquid chromatography-mass spectrometry indicated a unique CSE-associated microbial and metabolomic signature. Immunophenotyping of tumor specimens and experiments in Rag1-KO and CD8-KO demonstrated that smoke-induced tumor growth requires functional adaptive immunity. Finally, utilizing gut microbial ablation strategies with broad- and narrow-spectrum antibiotics, we demonstrated the reversal of phenotypic effects of CSE. Our study provides evidence for gut microbiome as an actionable target to mitigate CSE-induced tumor promotion.}, } @article {pmid40103733, year = {2025}, author = {Hirsch, W and Fischer, M and Khoruts, A and Allegretti, JR and Kelly, CR and Vaughn, B}, title = {Risk Factors for Antibiotic Exposure Post-Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection: A Prospective Multicenter Observational Study.}, journal = {Open forum infectious diseases}, volume = {12}, number = {3}, pages = {ofaf130}, pmid = {40103733}, issn = {2328-8957}, abstract = {BACKGROUND: Recurrent Clostridioides difficile infection (CDI) is primarily driven by antibiotic-induced disruption of the indigenous intestinal microbiota. Restoration of microbiota through fecal microbiota transplantation (FMT) is effective in preventing subsequent CDI, although this effect is attenuated with additional antibiotic exposure. The aim of this study was to identify the risk factors for recurrent antibiotic administration after FMT.

METHODS: This is a prospective cohort of patients who were administered FMT for recurrent CDI from 1 July 2019 through 23 November 2023 across 6 institutions in the United States. Providers collected de-identified data at the time of FMT administration and in the months post-FMT administration.

RESULTS: The analysis included 448 patients. Risk factors for non-CDI antibiotic administration within 2 months of FMT included immunocompromised status (odds ratio [OR], 2.2 [95% confidence interval {CI}, 1.1-4.4]; P = .02), >3 non-CDI antibiotic courses pre-FMT (OR, 3.1 [95% CI, 1.4-6.8]; P = .006), and prior hospitalization for CDI (OR, 2.0 [95% CI, 1.1-3.8]; P = .02). The most common indications for non-CDI antibiotic administration post-FMT were urinary tract infections, respiratory infections, and procedure prophylaxis.

CONCLUSIONS: Non-CDI antibiotic exposure significantly increases the risk of CDI recurrence post-FMT. Risk factors for non-CDI antibiotic administration within 2 months of FMT include immunocompromised status, multiple prior non-CDI antibiotics, and prior hospitalization for CDI. These individuals may benefit from additional or modified recurrent CDI prevention strategies.}, } @article {pmid40099491, year = {2025}, author = {Deng, Z and Mei, S and Ouyang, Z and Wang, R and Wang, L and Zou, B and Dai, J and Mao, K and Li, Q and Guo, Q and Yi, C and Meng, F and Xie, M and Zhang, X and Wang, R and Deng, T and Wang, Z and Li, X and Wang, Q and Liu, B and Tian, X}, title = {Dysregulation of gut microbiota stimulates NETs-driven HCC intrahepatic metastasis: therapeutic implications of healthy faecal microbiota transplantation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2476561}, pmid = {40099491}, issn = {1949-0984}, mesh = {*Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; *Liver Neoplasms/therapy/pathology/microbiology ; Humans ; Animals ; *Carcinoma, Hepatocellular/therapy/pathology/microbiology ; Mice ; *Extracellular Traps/metabolism ; Male ; Female ; Bacteria/classification/isolation & purification/genetics ; Disease Models, Animal ; Neoplasm Metastasis ; Neutrophils/immunology ; Middle Aged ; }, abstract = {The stringent regulation of intrahepatic metastases is essential for improving survival outcomes in patients with hepatocellular carcinoma (HCC). This study investigated the impact of gut microbiota on intrahepatic metastasis of HCC and evaluated the therapeutic potential of healthy fecal microbiota transplantation (FMT). Dysregulation of the gut microbiota, characterized by a significant reduction in the abundance of beneficial bacteria, such as Anaerotruncus colihominis and Dysosmobacter welbionis, was observed in patients with intrahepatic metastatic HCC. A human flora-associated (HFA) intrahepatic metastatic HCC mouse model was successfully established through consecutive 4 weeks of human-mouse FMT. Dysregulation of gut microbiota promoted intrahepatic metastasis in the mouse model, primarily by enhancing neutrophil-mediated inflammatory responses and lead to excessive formation of neutrophil extracellular traps (NETs). Consequently, it promoted tumor vascular growth and tissue necrosis, resulting in intrahepatic metastasis of HCC. Notably, FMT from healthy donors mitigated these pathological processes. This study elucidated the role and mechanism of dysregulated gut microbiota in promoting intrahepatic metastasis of HCC. Healthy FMT emerges as a promising novel therapeutic strategy for preventing and treating intrahepatic metastasis of HCC.}, } @article {pmid40098090, year = {2025}, author = {Xiao, P and Li, Y and Li, X and Ge, T and Li, D and Xu, Q and Ruan, Y and Xiao, F and Xiao, Y and Zhang, T}, title = {Long-term safety of fecal microbiota transplantation in Chinese children from 2013 to 2023: a single-center retrospective study.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {152}, pmid = {40098090}, issn = {1471-2180}, mesh = {Humans ; Male ; Retrospective Studies ; Female ; *Fecal Microbiota Transplantation/adverse effects/methods ; Child ; Child, Preschool ; China ; Infant ; Adolescent ; Gastrointestinal Microbiome ; Treatment Outcome ; East Asian People ; }, abstract = {BACKGROUND: The gut microbiome plays a vital role in influencing various health conditions. Fecal Microbiota Transplantation (FMT) has emerged as a rapid, safe, and effective method for modifying the microbiome. However, there is a lack of long-term safety data regarding FMT in children. This study presents the largest single-center analysis of the long-term safety outcomes of FMT in pediatric patients in China, featuring a substantial sample size and an extended follow-up period to thoroughly examine its safety in children.

METHODS: A retrospective study was conducted on 813 patients who underwent FMT treatments at our hospital from December 2013 to December 2023. All FMT procedures adhered to standardized protocols. The safety of these treatments was retrospectively assessed, focusing on adverse events (AEs) and serious adverse events (SAEs). AEs associated with FMT were categorized as short-term (within 48 h post-FMT) and long-term (within 3 months). Various potential influencing factors for AEs, including sex, age, route of administration, disease type, and consanguineous donor, were examined as independent variables. Significant independent factors and their associated risk ratios with 95% confidence intervals (CI) were determined through multivariate logistic regression analysis. A p-value of less than 0.05 was considered statistically significant.

RESULTS: A total of 813 patients underwent FMT, with a median age of 93 months (range 4-215) and 68.0% being males. The average follow-up time was 32.3 months (range 1-122). All short-term AEs resolved within 48 h, with an overall occurrence rate of 5.8% (47/813). The most common short-term AEs included vomiting (2.0%), abdominal pain (1.6%), diarrhea (0.9%), fever (0.7%), dysphoria (0.4%), and nausea (0.4%). Multivariable analysis revealed that patients with inflammatory bowel disease (IBD) (OR: 3.98, 95% CI: 1.78-8.92, P = 0.001) and those who received FMT via capsules (OR: 0.09, 95% CI: 0.03-0.27, P = 0.000) were independent risk factors for FMT-related AEs. All 813 patients were followed up for at least 1 month, with 78.8% followed for more than 12 months. No long-term AEs occurred during the longest follow-up period of 122 months.

CONCLUSIONS: FMT is a promising treatment option that appears to be safe and well tolerated. This study stands out for its substantial sample size, making it's the largest reported series in pediatrics, as well as for having the longest follow-up period for FMT in this population.

CLINICAL TRIAL NUMBER: Not applicable.}, } @article {pmid40098052, year = {2025}, author = {Oami, T and Shimazui, T and Yumoto, T and Otani, S and Hayashi, Y and Coopersmith, CM}, title = {Gut integrity in intensive care: alterations in host permeability and the microbiome as potential therapeutic targets.}, journal = {Journal of intensive care}, volume = {13}, number = {1}, pages = {16}, pmid = {40098052}, issn = {2052-0492}, support = {R35 GM148217/GM/NIGMS NIH HHS/United States ; GM148217//Foundation for the National Institutes of Health/ ; }, abstract = {BACKGROUND: The gut has long been hypothesized to be the "motor" of critical illness, propagating inflammation and playing a key role in multiple organ dysfunction. However, the exact mechanisms through which impaired gut integrity potentially contribute to worsened clinical outcome remain to be elucidated. Critical elements of gut dysregulation including intestinal hyperpermeability and a perturbed microbiome are now recognized as potential therapeutic targets in critical care.

MAIN BODY: The gut is a finely tuned ecosystem comprising ~ 40 trillion microorganisms, a single cell layer intestinal epithelia that separates the host from the microbiome and its products, and the mucosal immune system that actively communicates in a bidirectional manner. Under basal conditions, these elements cooperate to maintain a finely balanced homeostasis benefitting both the host and its internal microbial community. Tight junctions between adjacent epithelial cells selectively transport essential molecules while preventing translocation of pathogens. However, critical illness disrupts gut barrier function leading to increased gut permeability, epithelial apoptosis, and immune activation. This disruption is further exacerbated by a shift in the microbiome toward a "pathobiome" dominated by pathogenic microbes with increased expression of virulence factors, which intensifies systemic inflammation and accelerates organ dysfunction. Research has highlighted several potential therapeutic targets to restore gut integrity in the host, including the regulation of epithelial cell function, modulation of tight junction proteins, and inhibition of epithelial apoptosis. Additionally, microbiome-targeted therapies, such as prebiotics, probiotics, fecal microbiota transplantation, and selective decontamination of the digestive tract have also been extensively investigated to promote restoration of gut homeostasis in critically ill patients. Future research is needed to validate the potential efficacy of these interventions in clinical settings and to determine if the gut can be targeted in an individualized fashion.

CONCLUSION: Increased gut permeability and a disrupted microbiome are common in critical illness, potentially driving dysregulated systemic inflammation and organ dysfunction. Therapeutic strategies to modulate gut permeability and restore the composition of microbiome hold promise as novel treatments for critically ill patients.}, } @article {pmid40097405, year = {2025}, author = {Li, L and Li, T and Liang, X and Zhu, L and Fang, Y and Dong, L and Zheng, Y and Xu, X and Li, M and Cai, T and Zhao, F and Xin, M and Shao, M and Guan, Y and Liu, M and Li, F and Zhang, C and Wang, Q and Sun, W and Zheng, Y}, title = {A decrease in Flavonifractor plautii and its product, phytosphingosine, predisposes individuals with phlegm-dampness constitution to metabolic disorders.}, journal = {Cell discovery}, volume = {11}, number = {1}, pages = {25}, pmid = {40097405}, issn = {2056-5968}, support = {2023T160729//China Postdoctoral Science Foundation/ ; }, abstract = {According to traditional Chinese medicine (TCM) constitutional theory, individuals with phlegm-dampness constitution (PDC) are at increased risk for metabolic disorders. Previous studies have indicated that PDC individuals exhibit gene expression changes associated with metabolic disorders, even individuals with normal metabolic indices. However, the biological mechanisms underlying these changes remain unclear. The gut microbiota has recently emerged as a promising avenue for elucidating TCM principles. Here, we revealed that individuals with PDC have distinct gut microbiota and serum metabolite profiles. A decrease in phytosphingosine was associated with increased PDC scores and metabolic disorder severity. Subsequent experiments demonstrated that Flavonifractor plautii can biosynthesize phytosphingosine, which was also negatively correlated with the PDC score. Interestingly, both F. plautii and phytosphingosine levels decreased in PDC subjects with normal metabolic indices. Fecal transplantation from these individuals accelerated the development of metabolic disorders in mice. However, supplementation with F. plautii and phytosphingosine ameliorated metabolic disorders by increasing phytosphingosine levels in the gut‒hepatic axis. Mechanistic investigations confirmed that phytosphingosine can directly bind to hepatic peroxisome proliferator-activated receptor α (PPARα) and activate its nuclear transcription activity, thereby regulating downstream gene expression related to glucose‒lipid metabolism. Our research indicates that the decrease in F. plautii and its product, phytosphingosine, contributes to gene expression changes related to metabolic disorders in PDC individuals and increases their susceptibility to metabolic disorders. These findings suggest that diagnosing PDC may be beneficial for identifying at-risk populations among apparently healthy individuals, thereby advancing the broader field of metabolic disorder prevention and TCM integration.}, } @article {pmid40096354, year = {2025}, author = {Dongre, DS and Saha, UB and Saroj, SD}, title = {Exploring the role of gut microbiota in antibiotic resistance and prevention.}, journal = {Annals of medicine}, volume = {57}, number = {1}, pages = {2478317}, pmid = {40096354}, issn = {1365-2060}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/physiology ; *Anti-Bacterial Agents/therapeutic use/pharmacology ; *Dysbiosis/microbiology/prevention & control ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation/methods ; *Drug Resistance, Multiple, Bacterial/genetics ; Prebiotics ; *Drug Resistance, Microbial ; }, abstract = {BACKGROUND/INTRODUCTION: Antimicrobial resistance (AMR) and the evolution of multiple drug-resistant (MDR) bacteria is of grave public health concern. To combat the pandemic of AMR, it is necessary to focus on novel alternatives for drug development. Within the host, the interaction of the pathogen with the microbiome plays a pivotal role in determining the outcome of pathogenesis. Therefore, microbiome-pathogen interaction is one of the potential targets to be explored for novel antimicrobials.

MAIN BODY: This review focuses on how the gut microbiome has evolved as a significant component of the resistome as a source of antibiotic resistance genes (ARGs). Antibiotics alter the composition of the native microbiota of the host by favouring resistant bacteria that can manifest as opportunistic infections. Furthermore, gut dysbiosis has also been linked to low-dosage antibiotic ingestion or subtherapeutic antibiotic treatment (STAT) from food and the environment.

DISCUSSION: Colonization by MDR bacteria is potentially acquired and maintained in the gut microbiota. Therefore, it is pivotal to understand microbial diversity and its role in adapting pathogens to AMR. Implementing several strategies to prevent or treat dysbiosis is necessary, including faecal microbiota transplantation, probiotics and prebiotics, phage therapy, drug delivery models, and antimicrobial stewardship regulation.}, } @article {pmid40095949, year = {2025}, author = {Newsome, RC and McGriff, C and Gharaibeh, RZ and Jobin, C}, title = {Preparation and Maintenance of Bioexclusion IsoPositive Cage Experiment for Human Fecal Transplantation into Germ-Free Mice.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {216}, pages = {}, doi = {10.3791/68029}, pmid = {40095949}, issn = {1940-087X}, mesh = {Animals ; Mice ; Humans ; *Fecal Microbiota Transplantation/methods ; *Germ-Free Life ; *Housing, Animal ; *Feces/microbiology ; Female ; }, abstract = {Germ-free mice are an important investigation tool for understanding the contribution of microorganisms in host health and disease, enabling assessment of the specific role of individuals, defined or complex groups of microorganisms in host response. Traditionally bred and reared in flexible-film or semi-rigid isolators, germ-free mouse husbandry and experimental manipulation are costly and require numerous trained staff and a large space footprint in animal housing facilities. The IsoPositive caging system allows for experimental manipulation of germ-free mice in individual, hermetically-sealed, positive-pressure isolator cages (isocages), reducing cost and enabling greater flexibility in experimental manipulations. Here, a protocol is described for transferring germ-free mice from breeding isolators to isocages and subsequent fecal transfer from human donor stool into mice to create stable long-term gut "humanized" mice for future studies. The materials and preparation needed for the utilization of the isocage system are described, including the use of chlorine-dioxide sterilant chemical sterilant to clean cages, supplies, equipment, and personal protective equipment. The methods for confirming the germ-free status of transferred mice and how to determine contamination in the caging system are discussed. The procedure for husbandry, including bedding, food, and water supply, is further discussed. The protocol for human fecal slurry preparation and gavage into germ-free mice to create gut "humanized" mice, along with stool collection to monitor the microbial community composition of these mice, are described. An experiment illustrates that two weeks post-human fecal transplant allows for stable colonization of donor microbiota in the murine hosts, enabling subsequent experimental usage. Furthermore, the collection of humanized mouse feces in viability preservation media, enabling use in further functional experiments, is described. Overall, these methods allow for the safe and effective establishment of humanized mouse communities in experimental gnotobiotic cages for further manipulation.}, } @article {pmid40094148, year = {2025}, author = {Wang, X and Wang, WY and Yu, XL and Chen, JW and Yang, JS and Wang, MK}, title = {Comprehensive review of Clostridium difficile infection: Epidemiology, diagnosis, prevention, and treatment.}, journal = {World journal of gastrointestinal pharmacology and therapeutics}, volume = {16}, number = {1}, pages = {100560}, pmid = {40094148}, issn = {2150-5349}, abstract = {In recent years, nosocomial infections caused by Clostridium difficile (C. difficile) have risen, becoming a leading cause of hospital-acquired diarrhea. The global prevalence of C. difficile infection (CDI) varies across regions and populations. The diagnosis relies primarily on laboratory testing, including toxin, glutamate dehydrogenase, and nucleic acid amplification tests. Treatment strategies for CDI include antimicrobial therapy (e.g., metronidazole, vancomycin, and fidamycin), fecal transplantation, and immunotherapy (e.g., belotozumab), depending on the patient's specificity and severity. This paper reviews recent research on CDI's epidemiological characteristics, risk factors, diagnosis, treatment, and prevention, aiming to support hospitals and public health initiatives in implementing effective detection, prevention, and treatment strategies.}, } @article {pmid40091757, year = {2025}, author = {Le, PH and Chen, CL and Kuo, CJ and Yeh, PJ and Chen, CC and Chen, YC and Chiu, CT and Cheng, HT and Tsou, YK and Pan, YB and Chiu, CH}, title = {Impact of Clostridioides difficile Infection on Clinical Outcomes in Hospitalized IBD Patients and the Role of Fecal Microbiota Transplantation: A Retrospective Cohort Study.}, journal = {The Kaohsiung journal of medical sciences}, volume = {41}, number = {5}, pages = {e70002}, pmid = {40091757}, issn = {2410-8650}, support = {MOHW113-TDU-B-212-114010//Ministry of Health and Welfare (Taiwan)/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; Retrospective Studies ; *Clostridium Infections/therapy/microbiology/complications ; *Inflammatory Bowel Diseases/therapy/microbiology/complications ; Middle Aged ; Adult ; *Clostridioides difficile/pathogenicity ; Hospitalization ; Treatment Outcome ; Anti-Bacterial Agents/therapeutic use ; Risk Factors ; Aged ; }, abstract = {Clostridioides difficile infection (CDI) worsens the prognosis of patients with inflammatory bowel disease (IBD). This retrospective cohort study aimed to evaluate the risk factors, clinical manifestations, and outcomes of CDI in hospitalized patients with IBD, including those with toxin A/B results between April 2007 and April 2021. Patients were classified into the CDI and control groups. Patients with IBD and recurrent or refractory CDI underwent fecal microbiota transplantation (FMT). A total of 144 inpatients with IBD-45 in the CDI group and 99 in the control group-were analyzed. The incidence of CDI in inpatients with IBD was 31%. The Risk factors for CDI included longer IBD duration, biological therapy failure, and biological use. More patients in the CDI group presented with abdominal pain (77.8% vs. 55.6%, p = 0.011). In the antibiotic treatment-only group, the symptom improvement rate was 60.7% (17/28), the microbiological cure rate was 89.3% (25/28), and the overall success rate was 71.4% (20/28). After antibiotic treatment and FMT, 71.4% (10/14) of the patients tested negative for CDI, and 64.3% (9/14) had improved clinical symptoms. CDI led to more hospitalizations (median two times [range 0-12] vs. median one time [range 0-19], p = 0.008), a lower steroid-free remission rate (46.7% vs. 67.7%, p = 0.017), and higher Mayo scores (median 5 points [range 2-12] vs. median 3 points [range 0-12]). Patients who received FMT had fewer hospitalizations and fewer IBD-related complications during follow-up than those who received antibiotics alone. FMT should be considered in patients with IBD with refractory or recurrent CDI to improve clinical outcomes.}, } @article {pmid40091072, year = {2025}, author = {Liu, Y and Liu, J and Ren, R and Xin, Z and Luo, Y and Chen, Y and Huang, C and Liu, Y and Yang, T and Wang, X}, title = {Short-term and long-term high-fat diet promote metabolic disorder through reprogramming mRNA m[6]A in white adipose tissue by gut microbiota.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {75}, pmid = {40091072}, issn = {2049-2618}, support = {32330098//National Natural Science Foundation of China/ ; 2022R52023//Science and technology innovation leading talent project of Zhejiang Province/ ; 2023YFD1301303//National Key Research and Development Program of China/ ; }, mesh = {*Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Animals ; Mice ; *Adipose Tissue, White/metabolism ; Male ; *RNA, Messenger/genetics/metabolism ; *Metabolic Diseases/microbiology/metabolism/etiology/genetics ; Mice, Inbred C57BL ; Endogenous Retroviruses/genetics ; Fecal Microbiota Transplantation ; Histone-Lysine N-Methyltransferase/metabolism/genetics ; Long Interspersed Nucleotide Elements ; DNA Transposable Elements ; Epigenesis, Genetic ; }, abstract = {BACKGROUND: Although short-term high-fat diet (S-HFD) and long-term high-fat diet (L-HFD) induce metabolic disorder, the underlying epigenetic mechanism is still unclear.

RESULTS: Here, we found that both 4 days of S-HFD and 10 weeks of L-HFD increased mRNA m[6]A level in epididymal white adipose tissue (eWAT) and impaired metabolic health. Interestingly, S-HFD activated transposable elements (TEs), especially endogenous retroviruses (ERVs) in eWAT, while L-HFD activated long interspersed elements (LINEs). Subsequently, we demonstrated that both S-HFD and L-HFD increased m[6]A level of Ehmt2 and decreased EHMT2 protein expression and H3K9me2 level, accounting for activation of ERVs and LINEs. Overexpression of EHMT2 in eWAT or inhibition of ERVs and LINEs by antiviral therapy improved metabolic health under HFD feeding. Notably, we found that both short-term and long-term HFD feeding increased Fimicutes/Bacteroidota ratio and decreased the gut microbiome health index. Fecal microbiota transplantation (FMT) experiments demonstrated that gut microbiota from S-HFD and L-HFD was responsible for increased m[6]A level in eWAT, resulting in glucose intolerance and insulin insensitivity. Furthermore, we identified that both S-HFD and L-HFD increased the abundance of the gut microbial metabolite homogentisic acid (HGA), and HGA level was positively correlated with unclassified_f__Lachnospiraceae which was both increased in S-HFD and L-HFD feeding mice. Administration of HGA increased the m[6]A level of Ehmt2 and decreased the EHMT2 protein expression and H3K9me2 level in eWAT, leading to metabolic disorder in mice.

CONCLUSIONS: Together, this study reveals a novel mechanism that S-HFD and L-HFD induce metabolism disorder through gut microbiota-HGA-m[6]A-Ehmt2-ERV/LINE signaling. These findings may provide a novel insight for prevention and treatment of metabolism disorder upon short-term or long-term dietary fat intake. Video Abstract.}, } @article {pmid40089059, year = {2025}, author = {Fan, J and Wu, Y and Wang, X and Ullah, H and Ling, Z and Liu, P and Wang, Y and Feng, P and Ji, J and Li, X}, title = {The probiotic enhances donor microbiota stability and improves the efficacy of fecal microbiota transplantation for treating colitis.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.03.017}, pmid = {40089059}, issn = {2090-1224}, abstract = {INTRODUCTION: The stability and metabolic functionality of donor microbiota are critical determinants of fecal microbiota transplantation (FMT) efficacy in inflammatory bowel disease (IBD). While probiotics show potential to enhance microbiota resilience, their role in optimizing donor microbiota for FMT remains underexplored.

OBJECTIVES: This study investigated whether pretreatment of donor microbiota with L. plantarum GR-4 could improve FMT outcomes in a DSS-induced colitis model by modulating microbial stability, metabolic activity, and host-microbiome interactions.

METHODS: Donor mice received L. plantarum GR-4 for 3 weeks to generate modified FMT (MFMT). DSS-colitis mice were treated with MFMT, conventional FMT, or 5-aminosalicylic acid (5-ASA). Multi-omics analyses and functional assays (stress resistance, engraftment efficiency) were used to evaluate therapeutic mechanisms.

RESULTS: GR-4 pretreatment conferred three key advantages to donor microbiota: Ecological stabilization: 1. GR-4-driven acidification (pH 3.97 vs. 4.59 for LGG, p < 0.0001) enriched butyrogenic Butyricicoccus (73 % butyrate increase, p < 0.05) and improved stress resistance to bile acids/gastric conditions (1.25 × survival vs. FMT). 2. Metabolic reprogramming: GR-4 metabolized 25.3 % of tryptophan (vs. 10.3 % for LGG) to generate immunomodulatory indoles (ILA, IAA), activating aryl hydrocarbon receptor (AHR) signaling and upregulating anti-inflammatory IL-10/IL-22. 3. Bile acid remodeling: MFMT restored sulfolithocholic acid and β-MCA levels, outperforming FMT in resolving DSS-induced dysregulation. MFMT achieved an 83 % remission rate (vs. 50 % for FMT), enhanced gut barrier integrity, and reversed colitis-associated metabolic dysregulation (e.g., elevated spermidine, 7-sulfocholic acid). Probiotic preconditioning improved donor engraftment by 1.25 × and enriched success-associated taxa (Sporobacter, Butyricimonas), while suppressing pathogens (Clostridium papyrosolvens).

CONCLUSIONS: L. plantarum GR-4 optimizes donor microbiota via pH-driven niche engineering, immunometabolic reprogramming, and bile acid modulation, addressing key limitations of conventional FMT. The multi-targeted efficacy of MFMT, evidenced by superior remission rates and metabolic restoration, establishes this approach as a translatable strategy for IBD therapy. This study establishes probiotic-enhanced FMT as a paradigm for precision microbiome interventions.}, } @article {pmid40088964, year = {2025}, author = {Hajjeh, O and Rajab, I and Bdair, M and Saife, S and Zahran, A and Nazzal, I and AbuZahra, MI and Jallad, H and Abukhalil, MM and Hallak, M and Al-Said, OS and Al-Braik, R and Sawaftah, Z and Milhem, F and Almur, O and Saife, S and Aburemaileh, M and Abuhilal, A}, title = {Enteric nervous system dysfunction as a driver of central nervous system disorders: The Forgotten brain in neurological disease.}, journal = {Neuroscience}, volume = {572}, number = {}, pages = {232-247}, doi = {10.1016/j.neuroscience.2025.03.015}, pmid = {40088964}, issn = {1873-7544}, mesh = {Humans ; *Enteric Nervous System/physiopathology ; Animals ; Gastrointestinal Microbiome/physiology ; *Central Nervous System Diseases/physiopathology/therapy ; *Brain/physiopathology ; Brain-Gut Axis/physiology ; }, abstract = {The Enteric Nervous System (ENS), often called the "second brain," is a complex network of neurons and glial cells within the gastrointestinal (GI) tract. It functions autonomously while maintaining close communication with the central nervous system (CNS) via the gut-brain axis (GBA). ENS dysfunction plays a crucial role in neurodegenerative and neurodevelopmental disorders, including Parkinson's disease, Alzheimer's disease, and autism spectrum disorder. Disruptions such as altered neurotransmission, gut microbiota imbalance, and neuroinflammation contribute to disease pathogenesis. The GBA enables bidirectional communication through the vagus nerve, gut hormones, immune signaling, and microbial metabolites, linking gut health to neurological function. ENS dysregulation is implicated in conditions like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), influencing systemic and CNS pathology through neuroinflammation and impaired barrier integrity. This review highlights emerging therapeutic strategies targeting ENS dysfunction, including prebiotics, probiotics, fecal microbiota transplantation (FMT), and vagus nerve stimulation, which offer novel ways to modulate gut-brain interactions. Unlike previous perspectives that view the ENS as a passive disease marker, this review repositions it as an active driver of neurological disorders. By integrating advances in ENS biomarkers, therapeutic targets, and GBA modulation, this article presents a paradigm shift-emphasizing ENS dysfunction as a fundamental mechanism in neurodegeneration and neurodevelopmental disorders. This perspective paves the way for innovative diagnostics, personalized gut-targeted therapies, and a deeper understanding of the ENS's role in brain health and disease.}, } @article {pmid40087204, year = {2025}, author = {Lin, D and Howard, A and Raihane, AS and Di Napoli, M and Cáceres, E and Ortiz, M and Davis, J and Abdelrahman, AN and Divani, AA}, title = {Traumatic Brain Injury and Gut Microbiome: The Role of the Gut-Brain Axis in Neurodegenerative Processes.}, journal = {Current neurology and neuroscience reports}, volume = {25}, number = {1}, pages = {23}, pmid = {40087204}, issn = {1534-6293}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Brain Injuries, Traumatic/complications/microbiology/physiopathology/metabolism ; *Neurodegenerative Diseases/metabolism/microbiology/physiopathology/etiology ; Animals ; *Brain/metabolism/physiopathology ; Dysbiosis ; *Brain-Gut Axis/physiology ; }, abstract = {PURPOSE OF REVIEW: A deeper understanding of the communication network between the gut microbiome and the central nervous system, termed the gut-brain axis (GBA), has revealed new potential targets for intervention to prevent the development of neurodegenerative disease associated with tramatic brain injury (TBI). This review aims to comprehensively examine the role of GBA post-traumatic brain injury (TBI).

RECENT FINDINGS: The GBA functions through neural, metabolic, immune, and endocrine systems, creating bidirectional signaling pathways that modulate brain and gastrointestinal (GI) tract physiology. TBI perturbs these signaling pathways, producing pathophysiological feedback loops in the GBA leading to dysbiosis (i.e., a perturbed gut microbiome, impaired brain-blood barrier, impaired intestinal epithelial barrier (i.e., "leaky gut"), and a maladaptive, systemic inflammatory response. Damage to the CNS associated with TBI leads to GI dysmotility, which promotes small intestinal bacterial overgrowth (SIBO). SIBO has been associated with the early stages of neurodegenerative conditions such as Parkinson's and Alzheimer's disease. Many of the bacteria associated with this overgrowth promote inflammation and, in rodent models, have been shown to compromise the structural integrity of the intestinal mucosal barrier, causing malabsorption of essential nutrients and further exacerbating dysbiosis. TBI-induced pathophysiology is strongly associated with an increased risk of neurodegenerative diseases, including Parkinson's and Alzheimer's diseases, which represents a significant public health burden and challenge for patients and their families. A healthy gut microbiome has been shown to promote improved recovery from TBI and prevent the development of neurodegenerative disease, as well as other chronic complications. The role of the gut microbiome in brain health post-TBI demonstrates the potential for microbiome-targeted interventions to mitigate TBI-associated comorbidities. Promising new evidence on prebiotics, probiotics, diet, and fecal microbiota transplantation may lead to new therapeutic options for improving the quality of life for patients with TBI. Still, many of these preliminary findings must be explored further in clinical settings. This review covers the current understanding of the GBA in the setting of TBI and how the gut microbiome may provide a novel therapeutic target for treatment in this patient population.}, } @article {pmid40084003, year = {2025}, author = {Oliwa-Libumska, K and Jaworska-Czerwinska, A and Mallek-Grabowska, M and Wlodarski, R and Zuratynski, P and Kozlowski, B}, title = {Fecal microbiota transplantation in a patient hospitalized in the intensive care unit - Case report.}, journal = {Heliyon}, volume = {11}, number = {4}, pages = {e42793}, pmid = {40084003}, issn = {2405-8440}, abstract = {Clostridioides difficile infections are difficult and serious problem occurring in patients staying in intensive care units. In recent years, the number and severity of these infections, as well as the mortality rate, have been increasing, posing a serious epidemiological problem. This is caused, among other factors, by stressors, artificial nutrition, and sepsis, which lead to disturbances in the patients' microbiome. Basic method of treatment is antibiotic therapy, however some patients experience recurrences of the infection. Fecal Microbiota Transplantation (FMT) is one of the alternative methods used in treating recurring infections of Clostridioides difficile etiology (Clostridioides Difficile Infection, CDI). The presented case refers to a patient with severe pseudomembranous enterocolitis who underwent FMT twice. This report highlights the role of FMT in the treatment of severe Clostridioides difficile infections in critically ill patients.}, } @article {pmid40083791, year = {2025}, author = {, }, title = {Erratum: Integrative analysis of intestinal flora and untargeted metabolomics in attention-deficit/hyperactivity disorder.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1576969}, doi = {10.3389/fmicb.2025.1576969}, pmid = {40083791}, issn = {1664-302X}, abstract = {[This corrects the article DOI: 10.3389/fmicb.2025.1452423.].}, } @article {pmid40083245, year = {2025}, author = {Özdirik, B and Berger, H and Tonetti, FR and Cabré, N and Treichel, N and Clavel, T and Tacke, F and Sigal, M and Schnabl, B}, title = {Faecal Cytolysin is Associated With Worse Survival in Patients With Primary Sclerosing Cholangitis.}, journal = {Liver international : official journal of the International Association for the Study of the Liver}, volume = {45}, number = {4}, pages = {e16181}, doi = {10.1111/liv.16181}, pmid = {40083245}, issn = {1478-3231}, support = {OE821/1-1;Ta434/8-1;CRC1382Project-ID403224013//Deutsche Forschungsgemeinschaft/ ; R01AA24726;R37AA020703;U01AA026939;P30DK120515//National Institutes of Healthy (NIH)/ ; BX004594//Biomedical Laboratory Research & Development Service of the VA Office of Research and Development/ ; }, mesh = {Humans ; *Cholangitis, Sclerosing/mortality/microbiology ; Male ; Female ; Middle Aged ; *Feces/microbiology/chemistry ; Adult ; RNA, Ribosomal, 16S/genetics ; *Enterococcus faecalis/isolation & purification/genetics ; Case-Control Studies ; *Perforin/analysis/genetics ; Inflammatory Bowel Diseases/microbiology ; Gastrointestinal Microbiome ; Liver Transplantation ; Aged ; Virulence Factors/genetics ; }, abstract = {BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is an immune-related cholangiopathy without treatment options beyond liver transplantation. The gut-liver axis, especially the role of gut microbes, has emerged as a crucial pathway contributing to PSC pathogenesis. Recent research has revealed Enterococcus (E.) faecalis and its virulence factor cytolysin to increase mortality risk in patients with alcohol-associated hepatitis. Thus, we studied the role of enterococci, particularly E. faecalis and its virulence factor genes cytolysin and gelatinase, in faecal samples from patients with PSC.

METHODS: To assess the relevance of Enterococcus species, we performed 16S rRNA gene amplicon analysis in faecal samples from 60 patients with PSC. We validated our findings by qPCR of faecal microbial DNA in an extended cohort of 105 patients with PSC, 104 patients with inflammatory bowel disease (IBD) and 68 healthy subjects.

RESULTS: High-throughput 16S rRNA amplicon analysis revealed an increased relative abundance of enterococci in PSC patients compared with healthy controls and IBD patients, respectively, (p < 0.0001). PSC patients with high enterococci abundance had a decreased probability of transplant-free survival (p = 0.028). E. faecalis and its virulence factors cytolysin and gelatinase were more abundant in patients with PSC. Higher faecal cytolysin was associated with lower overall survival (p = 0.04), while survival was independent of gelatinase levels.

CONCLUSION: Our data highlight the association of E. faecalis and faecal cytolysin with lower survival in patients with PSC. These data should prompt further research into the pathogenic role of cytolysin-positive E. faecalis, and to explore its role as a potential therapeutic target.}, } @article {pmid40082770, year = {2025}, author = {Jahn, B and Bundo, M and Arvandi, M and Schaffner, M and Todorovic, J and Sroczynski, G and Knudsen, A and Fischer, T and Schiller-Fruehwirth, I and Öfner, D and Renner, F and Jonas, M and Kuchin, I and Kruse, J and Santamaria, J and Ferlitsch, M and Siebert, U}, title = {One in three adenomas could be missed by white-light colonoscopy - findings from a systematic review and meta-analysis.}, journal = {BMC gastroenterology}, volume = {25}, number = {1}, pages = {170}, pmid = {40082770}, issn = {1471-230X}, mesh = {Humans ; *Colonoscopy/methods ; *Adenoma/pathology/diagnosis/diagnostic imaging ; *Colorectal Neoplasms/diagnosis/pathology ; *Missed Diagnosis/statistics & numerical data ; Early Detection of Cancer/methods ; }, abstract = {BACKGROUND: White light (conventional) colonoscopy (WLC) is widely used for colorectal cancer screening, diagnosis and surveillance but endoscopists may fail to detect adenomas. Our goal was to assess and synthesize overall and subgroup-specific adenoma miss rates (AMR) of WLC in daily practice.

METHODS: We conducted a systematic review in MEDLINE, EMBASE, Cochrane Library, and grey literature on studies evaluating diagnostic WLC accuracy in tandem studies with novel-colonoscopic technologies (NCT) in subjects undergoing screening, diagnostic or surveillance colonoscopy. Information on study design, AMR overall and specific for adenoma size, histology, location, morphology and further outcomes were extracted and reported in standardized evidence tables. Study quality was assessed using the QUADAS-2 tool. Random-effects meta-analyses and meta-regression were performed to estimate pooled estimates for AMR with 95% confidence intervals (95% CI) and to explain heterogeneity.

RESULTS: Out of 5,963 identified studies, we included sixteen studies with 4,101 individuals in our meta-analysis. One in three adenomas (34%; 95% CI: 30-38%) was missed by WLC in daily practice individuals. Subgroup analyses showed significant AMR differences by size (36%, adenomas 1-5 mm; 27%, adenomas 6-9 mm; 12%, adenomas ≥ 10 mm), histology (non-advanced: 42%, advanced: 21%), morphology (flat: 50%, polypoid: 27%), but not by location (distal: 36%, proximal: 36%).

CONCLUSIONS: Based on our meta-analysis, one in three adenomas could be missed by WLC. This may significantly contribute to interval cancers. Our results should be considered in health technology assessment when interpreting sensitivity of fecal occult blood or other screening tests derived from studies using WLC as "gold standard".}, } @article {pmid40082445, year = {2025}, author = {Manns, MP and Bergquist, A and Karlsen, TH and Levy, C and Muir, AJ and Ponsioen, C and Trauner, M and Wong, G and Younossi, ZM}, title = {Primary sclerosing cholangitis.}, journal = {Nature reviews. Disease primers}, volume = {11}, number = {1}, pages = {17}, pmid = {40082445}, issn = {2056-676X}, mesh = {Humans ; *Cholangitis, Sclerosing/diagnosis/physiopathology/therapy/complications/epidemiology ; Ursodeoxycholic Acid/therapeutic use ; Liver Transplantation/methods ; }, abstract = {Primary sclerosing cholangitis (PSC) is a chronic biliary inflammation associated with periductular fibrosis of the intrahepatic and extrahepatic bile ducts leading to strictures, bacterial cholangitis, decompensated liver disease and need for liver transplantation. This rare focal liver disease affects all races and ages, with a predominance of young males. There is an up to 88% association with inflammatory bowel disease. Although the aetiology is unknown and the pathophysiology is poorly understood, PSC is regarded as an autoimmune liver disease based on a strong immunogenetic background. Further, the associated risk for various malignancies, particularly cholangiocellular carcinoma, is also poorly understood. No medical therapy has been approved so far nor has been shown to improve transplant-free survival. However, ursodeoxycholic acid is widely used since it improves the biochemical parameters of cholestasis and is safe at low doses. MRI of the biliary tract is the primary imaging technology for diagnosis. Endoscopic interventions of the bile ducts should be limited to clinically relevant strictures for balloon dilatation, biopsy and brush cytology. End-stage liver disease with decompensation is an indication for liver transplantation with recurrent PSC in up to 38% of patients. Several novel therapeutic strategies are in various stages of development, including apical sodium-dependent bile acid transporter and ileal bile acid transporter inhibitors, integrin inhibitors, peroxisome proliferator-activated receptor agonists, CCL24 blockers, recombinant FGF19, CCR2/CCR5 inhibitors, farnesoid X receptor bile acid receptor agonists, and nor-ursodeoxycholic acid. Manipulation of the gut microbiome includes faecal microbiota transplantation. This article summarizes present knowledge and defines unmet medical needs to improve quality of life and survival.}, } @article {pmid40081233, year = {2025}, author = {Yang, S and Pan, H and Wang, T and Zhou, X and Fan, L and Xiao, H and Zhou, Z and Xiao, Y and Shi, D}, title = {Bacillus paralicheniformis-mediated gut microbiota promotes M2 macrophage polarization by inhibiting P38 MAPK signaling to alleviate necrotizing enterocolitis and apoptosis in mice.}, journal = {Microbiological research}, volume = {296}, number = {}, pages = {128136}, doi = {10.1016/j.micres.2025.128136}, pmid = {40081233}, issn = {1618-0623}, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; *Enterocolitis, Necrotizing/microbiology/therapy ; *Apoptosis ; *Bacillus/physiology ; *p38 Mitogen-Activated Protein Kinases/metabolism ; Probiotics ; Fecal Microbiota Transplantation ; *Macrophages/immunology/metabolism ; Disease Models, Animal ; Dysbiosis/microbiology/therapy ; Clostridium perfringens ; Clostridium Infections/microbiology/therapy ; Mice, Inbred C57BL ; Male ; MAP Kinase Signaling System ; Signal Transduction ; Indoleacetic Acids/metabolism ; }, abstract = {Clostridial necrotizing enterocolitis is a severe gastrointestinal disease induced by Clostridium, strongly associated with intestinal dysbiosis. Fecal microbiota transplantation (FMT) has proven effective in treating gastrointestinal diseases by remodeling intestinal microbial homeostasis. However, it remains unclear whether FMT from donors with beneficial microbiota can improve the recipient's intestinal function more efficiently. This study found that probiotic Bacillus paralicheniformis SN-6-mediated gut microbiota effectively prevent Clostridial necrotizing enteritis and explored the underlying molecular mechanisms. Data demonstrated that SN-6 altered gut microbiota composition, ameliorated Clostridium perfringens-induced intestinal microbiota dysbiosis and metabolic reprogramming, particularly enhancing tryptophan metabolism. This led to a marked reduction in intestinal barrier damage and inflammation. FMT from SN-6-treated mice reduced jejunal inflammation in Clostridium perfringens-infected mice, strengthened jejunal barrier and enriched beneficial bacteria, such as Lactobacillus, Blautia, Akkermansia. Furthermore, 3-indoleacetic acid (IAA), a metabolite enriched by SN-6, activated aryl hydrocarbon receptor (AhR), suppressed the P38 mitogen-activated protein kinase (P38 MAPK) signaling, and drove macrophage polarization from M0 to M2-type, thereby reducing apoptosis and excessive inflammation. This study highlights Bacillus paralicheniformis SN-6 as a key modulator of intestinal immunomodulation via the gut microbiota-IAA-AhR-P38 MAPK axis, offering a potential therapeutic target for preventing and controlling clostridial necrotizing enteritis.}, } @article {pmid40079755, year = {2025}, author = {Menozzi, E and Schapira, AHV and Borghammer, P}, title = {The Gut-Brain Axis in Parkinson disease: Emerging Concepts and Therapeutic Implications.}, journal = {Movement disorders clinical practice}, volume = {12}, number = {7}, pages = {904-916}, pmid = {40079755}, issn = {2330-1619}, support = {ASAP-000420//Aligning Science Across Parkinson's/ ; MR/T046007/1//EU Joint Programme - Neurodegenerative Disease Research/ ; }, mesh = {Humans ; *Parkinson Disease/therapy/physiopathology ; *Gastrointestinal Microbiome/physiology ; *Brain/physiopathology ; *Brain-Gut Axis/physiology ; *Gastrointestinal Tract/physiopathology ; Animals ; }, abstract = {BACKGROUND: The gut-brain axis, i.e. the bidirectional communication system between the gut and the brain, has become of central importance in Parkinson disease (PD) research over the past 20 years.

AIMS: We aimed to describe the milestones of the gut-brain axis research in PD and the development of theories proposing the involvement of the gastrointestinal tract in PD pathogenesis.

METHODS: We searched PubMed using the terms 'gut-brain axis' AND 'Parkinson disease', and selected relevant articles to provide the foundation for reconstructing an historical overview of the gut-brain axis research in PD.

RESULTS: Mounting evidence from preclinical, clinical and post-mortem studies suggests that a subgroup of PD patients present with a range of prodromal symptoms (e.g., autonomic dysfunction, rapid eye movement sleep behaviour disorder) which reflect initial accumulation and later spread of pathological α-synuclein rostrally from the gastrointestinal tract ("body-first" PD). Through neural connections along the gut-brain axis, pathological α-synuclein may spread to the brain, producing clinically manifest disease. Recently, two mechanisms involving the gut-brain axis have attracted increasing attention for their role in PD pathogenesis and progression, namely the perturbation of the composition of the microorganisms living in the gut (the gut microbiome), and the dysfunction of enteroendocrine cells.

CONCLUSION: Treatments targeting the gut-brain axis, especially the gut microbiome and the enteroendocrine cells pathway, could potentially slow disease progression or even prevent disease onset. Among these, pre/probiotics, faecal microbiota transplantation, and glucagon-like peptide-1 receptor agonists, have entered advanced stages of clinical trials in humans and shown potential symptomatic and disease-modifying effects.}, } @article {pmid40078367, year = {2025}, author = {Ullah, H and Arbab, S and Chang, C and Bibi, S and Muhammad, N and Rehman, SU and Suleman, and Ullah, I and Hassan, IU and Tian, Y and Li, K}, title = {Gut microbiota therapy in gastrointestinal diseases.}, journal = {Frontiers in cell and developmental biology}, volume = {13}, number = {}, pages = {1514636}, pmid = {40078367}, issn = {2296-634X}, abstract = {The human gut microbiota, consisting of trillions of microorganisms, plays a crucial role in gastrointestinal (GI) health and disease. Dysbiosis, an imbalance in microbial composition, has been linked to a range of GI disorders, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, and colorectal cancer. These conditions are influenced by the interactions between the gut microbiota, the host immune system, and the gut-brain axis. Recent research has highlighted the potential for microbiome-based therapeutic strategies, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary modifications, to restore microbial balance and alleviate disease symptoms. This review examines the role of gut microbiota in the pathogenesis of common gastrointestinal diseases and explores emerging therapeutic approaches aimed at modulating the microbiome. We discuss the scientific foundations of these interventions, their clinical effectiveness, and the challenges in their implementation. The review underscores the therapeutic potential of microbiome-targeted treatments as a novel approach to managing GI disorders, offering personalized and alternative options to conventional therapies. As research in this field continues to evolve, microbiome-based interventions hold promise for improving the treatment and prevention of gastrointestinal diseases.}, } @article {pmid40077957, year = {2025}, author = {Ma, Z and Wen, X and Zhang, Y and Ai, Z and Zhao, X and Dong, N and Dou, X and Shan, A}, title = {Thymol Alleviates Colitis by Modulating Intestinal Barrier Damage, Gut Microbiota, and Amino Acid Metabolic Pathways.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {12}, pages = {7211-7227}, doi = {10.1021/acs.jafc.4c10406}, pmid = {40077957}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Colitis/microbiology/drug therapy/metabolism/genetics ; *Thymol/administration & dosage ; *Amino Acids/metabolism ; Male ; Mice, Inbred C57BL ; *Intestinal Mucosa/metabolism/drug effects/microbiology ; Humans ; Bacteria/genetics/classification/isolation & purification/metabolism/drug effects ; Metabolic Networks and Pathways/drug effects ; Colon/metabolism/drug effects/microbiology ; Dextran Sulfate/adverse effects ; Cytokines/genetics/metabolism ; }, abstract = {Thymol (THY) is a phenolic monoterpene compound that has garnered attention due to its various biological properties, including antioxidant, anti-inflammatory, and immune-regulatory effects. The purpose of this study was to determine the therapeutic and protective effects of THY in colitic mice, with a particular focus on the mechanisms involving gut microbiota. The results showed that early intervention with THY (40 and 80 mg/kg) not only alleviated the clinical symptoms and colonic damage in mice with dextran sodium sulfate (DSS)-induced colitis but also suppressed the colonic production of inflammatory cytokines (IL-1β, IL-6, and IL-18) and enhanced the expression of mucins (MUC1 and MUC2) and trefoil factor family 3 (TFF3), thereby improving the integrity of the intestinal epithelial barrier. In addition, THY altered the composition of the gut microbiota in colitis mice by increasing the abundance of Bacteroides and reducing the abundance of Proteobacteria. Fecal microbial transplantation (FMT) results demonstrated that FM from THY donor mice significantly improved symptoms of inflammatory bowel disease (IBD), confirming the crucial role of the gut microbiota. Metagenomic and untargeted metabolomic studies found that the characteristic microbiota of THY is Prevotellaceae, and THY significantly upregulated the amino acid metabolic pathways related to arginine and proline metabolism, arginine biosynthesis, and glycerophospholipid metabolism. In summary, THY holds significant potential as a functional additive to enhance host intestinal activity.}, } @article {pmid40077671, year = {2025}, author = {Gao, Y and Borjihan, Q and Zhang, W and Li, L and Wang, D and Bai, L and Zhu, S and Chen, Y}, title = {Complex Probiotics Ameliorate Fecal Microbiota Transplantation-Induced IBS in Mice via Gut Microbiota and Metabolite Modulation.}, journal = {Nutrients}, volume = {17}, number = {5}, pages = {}, pmid = {40077671}, issn = {2072-6643}, support = {2022-Science and Technology Xing Meng-Quality improvement-02//the Science and Technology Xing Meng action focus project of Inner Mongolia Autonomous Region/ ; }, mesh = {Animals ; *Probiotics/pharmacology ; *Gastrointestinal Microbiome/drug effects ; *Fecal Microbiota Transplantation/adverse effects ; *Irritable Bowel Syndrome/therapy/microbiology/etiology/metabolism ; Mice ; Disease Models, Animal ; Feces/microbiology/chemistry ; Male ; Mice, Inbred C57BL ; Serotonin/metabolism ; Serotonin Plasma Membrane Transport Proteins/metabolism ; Tryptophan/metabolism ; Metabolomics ; Dysbiosis ; Metagenomics ; }, abstract = {Background/Objectives: Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder. Emerging evidence implicates gut microbiota dysbiosis in IBS pathogenesis, and probiotic interventions targeting microbial modulation hold therapeutic promise. Methods: this study used fecal microbiota transplantation to establish a mouse model of IBS before evaluating the effects of the complex probiotic by using metagenomics and targeted metabolomics to explore the potential mechanism. Results: After 14 days, the probiotic relieved constipation, reduced inflammation and intestinal permeability, lowered 5-HT levels and increased serotonin transporter (SERT) expression in tissues. Metagenomic analysis showed a reduced inflammation-related species abundance. It also decreased fecal butyric acid, acetic acid and tryptophan levels in IBS mice. Conclusions: The probiotic complex effectively alleviated IBS symptoms in mice by modulating gut microbiota and fecal metabolites, providing insights for future IBS research and treatment.}, } @article {pmid40076864, year = {2025}, author = {Hatamnejad, MR and Medzikovic, L and Dehghanitafti, A and Rahman, B and Vadgama, A and Eghbali, M}, title = {Role of Gut Microbial Metabolites in Ischemic and Non-Ischemic Heart Failure.}, journal = {International journal of molecular sciences}, volume = {26}, number = {5}, pages = {}, pmid = {40076864}, issn = {1422-0067}, support = {R01 HL174472/HL/NHLBI NIH HHS/United States ; R01HL147586/NH/NIH HHS/United States ; R01HL159865/NH/NIH HHS/United States ; 24CDA1263497//American Heart Association/ ; R01 HL162124/HL/NHLBI NIH HHS/United States ; R01HL162124/NH/NIH HHS/United States ; R01 HL147586/HL/NHLBI NIH HHS/United States ; R01 HL159865/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Heart Failure/metabolism/microbiology/etiology ; Animals ; *Myocardial Ischemia/metabolism/microbiology ; Methylamines/metabolism ; Signal Transduction ; Hydrogen Sulfide/metabolism ; }, abstract = {The effect of the gut microbiota extends beyond their habitant place from the gastrointestinal tract to distant organs, including the cardiovascular system. Research interest in the relationship between the heart and the gut microbiota has recently been emerging. The gut microbiota secretes metabolites, including Trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), bile acids (BAs), indole propionic acid (IPA), hydrogen sulfide (H2S), and phenylacetylglutamine (PAGln). In this review, we explore the accumulating evidence on the role of these secreted microbiota metabolites in the pathophysiology of ischemic and non-ischemic heart failure (HF) by summarizing current knowledge from clinical studies and experimental models. Elevated TMAO contributes to non-ischemic HF through TGF-ß/Smad signaling-mediated myocardial hypertrophy and fibrosis, impairments of mitochondrial energy production, DNA methylation pattern change, and intracellular calcium transport. Also, high-level TMAO can promote ischemic HF via inflammation, histone methylation-mediated vascular fibrosis, platelet hyperactivity, and thrombosis, as well as cholesterol accumulation and the activation of MAPK signaling. Reduced SCFAs upregulate Egr-1 protein, T-cell myocardial infiltration, and HDAC 5 and 6 activities, leading to non-ischemic HF, while reactive oxygen species production and the hyperactivation of caveolin-ACE axis result in ischemic HF. An altered BAs level worsens contractility, opens mitochondrial permeability transition pores inducing apoptosis, and enhances cholesterol accumulation, eventually exacerbating ischemic and non-ischemic HF. IPA, through the inhibition of nicotinamide N-methyl transferase expression and increased nicotinamide, NAD+/NADH, and SIRT3 levels, can ameliorate non-ischemic HF; meanwhile, H2S by suppressing Nox4 expression and mitochondrial ROS production by stimulating the PI3K/AKT pathway can also protect against non-ischemic HF. Furthermore, PAGln can affect sarcomere shortening ability and myocyte contraction. This emerging field of research opens new avenues for HF therapies by restoring gut microbiota through dietary interventions, prebiotics, probiotics, or fecal microbiota transplantation and as such normalizing circulating levels of TMAO, SCFA, BAs, IPA, H2S, and PAGln.}, } @article {pmid40076603, year = {2025}, author = {Wang, K and Hu, Y and Wu, Y and Xu, J and Zhao, Y and Yang, J and Li, X}, title = {The Therapeutic Potential of Gut-Microbiota-Derived Metabolite 4-Phenylbutyric Acid in Escherichia coli-Induced Colitis.}, journal = {International journal of molecular sciences}, volume = {26}, number = {5}, pages = {}, pmid = {40076603}, issn = {1422-0067}, support = {32360904//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Escherichia coli/pathogenicity ; *Phenylbutyrates/pharmacology/therapeutic use/metabolism ; Mice ; *Colitis/microbiology/therapy/drug therapy/metabolism ; *Escherichia coli Infections/microbiology ; Fecal Microbiota Transplantation ; Cattle ; Disease Models, Animal ; Cytokines/metabolism ; Male ; NF-kappa B/metabolism ; }, abstract = {Pathogenic Escherichia coli (E. coli) is a widely distributed pathogen that can cause varying degrees of zoonotic diseases, and infected animals often experience intestinal inflammation accompanied by diarrhea and dysbiosis. Previously, for the first time, we isolated Escherichia coli primarily of type B2 from a large-scale dairy farm in Yunnan, China. The 16s rRNA sequencing showed significant differences in the gut microbiota of calves infected with B2 E. coli, with higher abundance of harmful bacteria and lower abundance of beneficial bacteria compared with healthy calves. The metabolomics indicated that the concentrations of oxoadipic acid, 16-oxopalmitate, oerillyl alcohol, palmitoleic acid, and 4-phenylbutyrate (4-PBA) were significantly higher in the healthy group than in the infected group. The mouse model was established to assess the regulatory effect of 4-PBA on E. coli-induced colitis. Both oral administration of 4-PBA and fecal microbiota transplantation (FMT) had strong resistance to E. coli infection, improved survival rate and body weight, reduced intestinal tissue damage, decreased the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), and restrained TLR4/MyD88/NF-κB pathway. Our study demonstrated that 4-PBA could relieve E. coli-induced colitis by improving gut microbiota structure and inhibiting the expression of pro-inflammatory cytokines through the TLR4/MyD88/NF-κB pathway. The present finding reveals the therapeutic potential of the gut-microbiota-derived metabolite 4-PBA for the treatment of colitis caused by E. coli.}, } @article {pmid40075967, year = {2025}, author = {Luo, S and Huang, X and Chen, S and Li, J and Wu, H and He, Y and Zhou, L and Liu, B and Feng, J}, title = {The Gut Microbiota of the Greater Horseshoe Bat Confers Rapidly Corresponding Immune Cells in Mice.}, journal = {Animals : an open access journal from MDPI}, volume = {15}, number = {5}, pages = {}, pmid = {40075967}, issn = {2076-2615}, support = {202311439011//College Students' Innovative Entrepreneurial Training Plan Program/ ; }, abstract = {BACKGROUND: Emerging infectious diseases threaten human and animal health, with most pathogens originating from wildlife. Bats are natural hosts for many infectious agents. Previous studies have demonstrated that changes in some specific genes in bats may contribute to resistance to viral infections, but they have mostly overlooked the immune function of the bat gut microbiota.

AIMS: In this study, we used fecal transplants to transfer the gut microbiota from the Greater Horseshoe Bat (Rhinolophus ferrumequinum) into mice treated with antibiotics. The gut microbiota changes in mice were detected using 16S rRNA high-throughput sequencing technology. Flow cytometry was used to detect changes in associated immune cells in the spleen and mesenteric lymph nodes of the mice.

RESULTS: The results showed that the gut microbiota of mice showed characteristics of some bat gut microbiota. The Greater Horseshoe Bat's gut microbiota changed some immune cells' composition in the spleen and mesenteric lymph nodes of mice and also conferred a faster and higher proportion of natural killer cell activation.

CONCLUSION: This result provides new evidence for the regulatory immune function of bat gut microbiota and contributes to a deeper insight into the unique immune system of bats.}, } @article {pmid40075266, year = {2025}, author = {Cao, H and Xu, J and Wang, H and Yi, W and Yang, D and Yang, J and Sun, J and Wang, Y and Zhang, F and Yan, J and Li, D}, title = {Fecal microbiota transplantation mitigates postdieting weight regain in mice by modulating the gut-liver axis.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {135}, pmid = {40075266}, issn = {1471-2180}, support = {2023YFF1104305//National Key Research and Development Program of China/ ; 2022YFF1100601//National Key Research and Development Program of China/ ; K2023004//Key Research project of Health Commission of Jiangsu Province/ ; M2021055//Key Research project of Health Commission of Jiangsu Province/ ; Y2021001//Wuxi Science and Technology Bureau, "Taihu Light" Science and Technology Research program/ ; K20221026//Wuxi Science and Technology Bureau, "Taihu Light" Science and Technology Research program/ ; CXTD2021003//Key discipline construction program of Wuxi Commission of Health/ ; KX-23-B050//Soft Science Project of Wuxi Science and Technology Association/ ; KX-23-C196//Soft Science Project of Wuxi Science and Technology Association/ ; YJZ202305//Medical research projects in research-oriented hospitals of Affiliated Hospital of Jiangnan University/ ; HB2023062//"Shuangbai Talents" research program of Wuxi Commission of Health/ ; HB2023063//"Shuangbai Talents" research program of Wuxi Commission of Health/ ; HB2023061//"Shuangbai Talents" research program of Wuxi Commission of Health/ ; LCYJ202347//Clinical Research and translational medicine research program of Affiliated Hospital of Jiangnan University/ ; LCYJ202310//Clinical Research and translational medicine research program of Affiliated Hospital of Jiangnan University/ ; LCYJ202322//Clinical Research and translational medicine research program of Affiliated Hospital of Jiangnan University/ ; LCYJ202303//Clinical Research and translational medicine research program of Affiliated Hospital of Jiangnan University/ ; BK20210468//Natural Science Foundation of Jiangsu Province/ ; BK20210060//Natural Science Foundation of Jiangsu Province/ ; 82370809//National Natural Science Foundation of China/ ; 32101033//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation ; Mice ; *Gastrointestinal Microbiome ; *Weight Gain ; *Liver/metabolism ; Male ; Mice, Inbred C57BL ; Bacteria/classification/genetics/isolation & purification ; Dysbiosis/therapy ; Lipid Metabolism ; Fatty Acids, Volatile/blood ; }, abstract = {BACKGROUND: Dysbiosis of the microbiome is strongly associated with weight rebound after dieting. However, the interactions between the host and microbiome and their relevance to the pathogenesis of post-diet weight rebound remain unclear.

PURPOSE: This study aimed to evaluate the effects of fecal microbiota transplantation (FMT) on post-diet weight regain and to investigate the underlying mechanisms by which FMT inhibits weight regain.

METHODS: FMT was administered once daily to mice for 5 weeks. Gas chromatography tandem mass spectrometry was employed to analyze short-chain fatty acid levels in serum, ultrahigh-performance liquid chromatography tandem mass spectrometry was utilized for analyzing hepatic lipid metabolites, and shotgun metagenomic sequencing was applied to examine the intestinal microbiome.

RESULTS: FMT reduced weight regain and prevented lipid accumulation in both liver and adipose tissue while also improving glucose intolerance in mice. Furthermore, FMT increased the abundance of Enterorhabdus caecimuris and decreased the abundances of Burkholderiales, Sutterellaceae, Turicimonas muris, Bacteroides stercorirosoris, and Acetivibrio ethanolgignens within the gut microbiota. Additionally, elevated propionic acid levels and significant alterations in hepatic lipid metabolites were observed following FMT administration.

CONCLUSIONS: Our findings demonstrate that FMT effectively mitigates post-diet weight regain and associated complications. These effects are mediated through interactions between the gut microbiota and the liver via the gut-propionic acid-liver axis.

CLINICAL TRIAL NUMBER: Not applicable.}, } @article {pmid40074992, year = {2025}, author = {Bakhshandi, AK and Minasazi, A and Yeganeh, O and Behi, M}, title = {Therapeutic potential of microbiota modulation in psoriasis: current evidence and future directions.}, journal = {Archives of dermatological research}, volume = {317}, number = {1}, pages = {561}, pmid = {40074992}, issn = {1432-069X}, mesh = {Humans ; *Psoriasis/therapy/immunology/microbiology ; *Fecal Microbiota Transplantation/methods/trends ; *Gastrointestinal Microbiome/immunology ; Probiotics/therapeutic use ; *Dysbiosis/therapy/immunology/microbiology ; Skin/immunology/microbiology/pathology ; Quality of Life ; }, abstract = {The human microbiota plays a significant role in health and the development of autoimmune diseases by maintaining gut-skin homeostasis through diverse microbial communities. Dysbiosis, or imbalance in these communities, is increasingly recognized as a contributing factor in the pathogenesis of autoimmune and inflammatory diseases, including psoriasis. Psoriasis is characterized by immune dysregulation, leading to red and scaly plaques that significantly reduce patients' quality of life. Current evidence highlights the gut microbiota's critical role in driving immune responses and chronic inflammation associated with psoriasis. Therapeutic strategies aimed at restoring microbial balance, such as probiotics, have demonstrated promise in reducing disease severity. Additionally, fecal microbiota transplantation (FMT) has emerged as a novel intervention, with early studies suggesting its potential to alleviate symptoms by correcting gut dysbiosis. These approaches underscore the importance of microbiota-targeted therapies in addressing the systemic nature of psoriasis and pave the way for advancements in personalized treatment strategies.}, } @article {pmid40074633, year = {2025}, author = {Le, PH and Yeh, YM and Chen, YC and Chen, CL and Tsou, YK and Chen, CC and Chiu, CT and Chiu, CH}, title = {Fecal microbiota transplantation for vancomycin-resistant Clostridium innocuum infection in inflammatory bowel disease: A pilot study evaluating safety and clinical and microbiota outcome.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jmii.2025.03.004}, pmid = {40074633}, issn = {1995-9133}, abstract = {BACKGROUND: Clostridium innocuum is a vancomycin-resistant pathobiome associated with poor clinical outcomes in inflammatory bowel disease (IBD). In ulcerative colitis (UC), it correlates with reduced remission rates, while in Crohn's disease (CD), it is linked to creeping fat formation and intestinal strictures. Notably, some patients experience refractory or recurrent C. innocuemailum infections despite metronidazole treatment. This study evaluates the safety and efficacy of single-dose fecal microbiota transplantation (FMT) in IBD patients with refractory or recurrent C. innocuum infections.

METHODS: We conducted a feasibility pilot study involving seven IBD patients (3 CD, 4 UC) with refractory (n = 5) or recurrent (n = 2) C. innocuum infections following metronidazole treatment. Patients underwent single-dose FMT and were monitored for six months.

RESULTS: No adverse events were recorded. All participants demonstrated improved disease activity post-FMT, as assessed by the Crohn's Disease Activity Index and Mayo Score. However, a mild increase in symptom severity was noted at six months. Follow-up cultures showed persistent C. innocuum infection in one patient and asymptomatic recurrence in another at three months. Alpha diversity of the gut microbiome increased post-FMT, and Bray-Curtis dissimilarity analysis revealed a microbiota composition more similar to that of the donor.

CONCLUSION: Single-dose FMT appears to be a safe and feasible therapeutic approach for refractory or recurrent C. innocuum infections in IBD patients, with potential benefits in disease activity and microbiome restoration. Further studies are warranted to optimize long-term outcomes.}, } @article {pmid40072575, year = {2025}, author = {Habeeb, TAAM and Chiaretti, M and Kryvoruchko, IA and Pesce, A and Kechagias, A and Elias, AA and Adam, AAM and Gadallah, MA and Ali Ahmed, SM and Khyrallh, A and Alsayed, MH and Tharwat Kamel Awad, E and Elshafey, MH and Abo Alsaad, MI and Ali, AK and Elbelkasi, H and Abou Zaid, MA and Youssef, HAA and Al-Zamek, MMF and Fiad, A and Elshahidy, TM and Elballat, MR and El Taher, AK and Mohamed, MMM and AboZeid, AK and Mansour, MI and Yassin, MA and Arafa, AS and Lotfy, M and Mousa, B and Atef, B and Naguib, SM and Heggy, IA and Elnemr, M and Zaitoun, MA and AbdAllah, ES and Moussa, MS and Hamed, AEM and Elsayed, RS}, title = {Mucosal advancement flap versus ligation of the inter-sphincteric fistula tract for management of trans-sphincteric perianal fistulas in the elderly: a retrospective study.}, journal = {International journal of colorectal disease}, volume = {40}, number = {1}, pages = {61}, pmid = {40072575}, issn = {1432-1262}, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Anal Canal/surgery ; Fecal Incontinence/etiology ; Ligation ; Postoperative Complications/etiology ; *Rectal Fistula/surgery ; Recurrence ; Retrospective Studies ; Risk Factors ; *Surgical Flaps ; Treatment Outcome ; }, abstract = {PURPOSE: There is no consensus on the standard approach for trans-sphincteric perianal fistulas (TPAF) in the elderly population. The most commonly used sphincter-saving procedures are ligation of the inter-sphincteric fistula tract (LIFT) and mucosal advancement flap (MAF). We aimed to evaluate the incidence and risk factors for recurrence and incontinence in elderly patients with TPAF using both approaches.

METHODS: This retrospective study included 257 patients who underwent LIFT (136 patients) or MAF (121 patients) for de novo and cryptoglandular TPAF between July 2018 and July 2021. Recurrent fistulas were clinically and radiologically detected using MRI. Postoperative incontinence was evaluated using the Wexner score and anorectal manometry. Logistic regression analysis was used to detect the risks of recurrence and incontinence.

RESULTS: The median ages of the patients were 68 (64, 74) and 68 (65, 74) years in the LIFT and MAF groups, respectively. Higher recurrence rates were observed after LIFT (17 (12.5%)) than after MAF (13 (10.7%)), but the difference was not statistically significant (P = 0.662). Postoperative incontinence was observed in 18 patients (13.2%) and seven patients (5.8%) in the LIFT and MAF groups, respectively (P = 0.044). The predictors for fistula recurrence were smoking (OR, 75.52; 95% CI, 1.02 to 5611.35; P = 0.049), length of tract (OR, 17.3; 95% CI, 1.49 to 201.13; P = 0.023), and CD classification (OR, 7.08; 95% CI, 1.51 to 33.14; P = 0.013). A low Charlson comorbidity index score (≤ 5) (OR, 0.68; 95% CI, 0.47 to 0.99; P = 0.046) and high postoperative mean squeeze anal pressure (OR, 0.97; 95% CI, 0.95 to 0.99; P = 0.001) were significant factors associated with reduced risk of incontinence. In particular, LIFT was associated with a significantly higher risk of incontinence than MAF (OR, 2.089; 95% CI, 1.006 to 4.33; P = 0.04).

CONCLUSIONS: The healing rates of MAF and LIFT procedures did not differ significantly; however, continence was significantly better after MAF. MAF should be added to the guidelines as a good option for the treatment of TPAF in elderly patients.

TRIAL REGISTRATION: The study was registered as a clinical trial www.

CLINICALTRIALS: gov (NCT06616662).}, } @article {pmid40072345, year = {2025}, author = {Chen, M and Song, Y and Pan, J and Liu, S and Zheng, X}, title = {Effects of faecal microbiota transplantation supplemented with inulin on early immunity and immune organ histomorphology in chickens.}, journal = {British poultry science}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/00071668.2025.2458581}, pmid = {40072345}, issn = {1466-1799}, abstract = {1. Faecal microbiota transplantation (FMT) is a technique that promotes gut microbiota diversity and abundance by transplantation of faeces into a recipient's gastrointestinal tract via multiple routes.2. Inulin, a plant polysaccharide, is a natural functional dietary fibre found in a variety of plants, including vegetables and fruits. Inulin can inhibit pathogenic bacterial growth by lowering pH, promote mineral absorption and improve intestinal barrier integrity.3. In this study 90 one-day-old chicks were randomly into three groups; control (CON) group was fed a basic diet; FMT group fed two diets containing 40 ml faecal microbial suspension; and INU group fed a diet containing 1.5% inulin and 40 ml faecal microbial suspension.4. Administering the FMT mixed with inulin effectively reduced blood levels of IL-1β, IL-4 and IL-6, promoted the growth of thymus, bursa of Fabricius and spleen. In addition, it enhanced intestinal barrier function, increased intestinal goblet cells and Paneth cells production, promoted probiotic colonisation and butyrate formation and reduced intestinal inflammation.5. In summary, inulin mixed with FMT promoted the growth of the bursa of Fabricius, thymus and spleen as well as facilitated early growth of chick by promoting intestinal health, reducing inflammation and boosting chick immunity.}, } @article {pmid40072088, year = {2025}, author = {Świdnicka-Siergiejko, A and Daniluk, J and Miniewska, K and Daniluk, U and Guzińska-Ustymowicz, K and Pryczynicz, A and Dąbrowska, M and Rusak, M and Ciborowski, M and Dąbrowski, A}, title = {Inflammatory Stimuli and Fecal Microbiota Transplantation Accelerate Pancreatic Carcinogenesis in Transgenic Mice, Accompanied by Changes in the Microbiota Composition.}, journal = {Cells}, volume = {14}, number = {5}, pages = {}, pmid = {40072088}, issn = {2073-4409}, support = {No NCN 2017/27/B/NZ5/02904//National Science Center/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/adverse effects ; Mice, Transgenic ; Mice ; *Pancreatic Neoplasms/microbiology/pathology ; *Carcinogenesis/pathology ; *Inflammation/pathology/microbiology ; *Gastrointestinal Microbiome ; *Carcinoma, Pancreatic Ductal/microbiology/pathology ; Feces/microbiology ; Proto-Oncogene Proteins p21(ras)/genetics ; Male ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; Female ; }, abstract = {An association between gut microbiota and the development of pancreatic ductal adenocarcinoma (PDAC) has been previously described. To better understand the bacterial microbiota changes accompanying PDAC promotion and progression stimulated by inflammation and fecal microbiota transplantation (FMT), we investigated stool and pancreatic microbiota by 16s RNA-based metagenomic analysis in mice with inducible acinar transgenic expressions of KrasG12D, and age- and sex-matched control mice that were exposed to inflammatory stimuli and fecal microbiota obtained from mice with PDAC. Time- and inflammatory-dependent stool and pancreatic bacterial composition alterations and stool alpha microbiota diversity reduction were observed only in mice with a Kras mutation that developed advanced pancreatic changes. Stool Actinobacteriota abundance and pancreatic Actinobacteriota and Bifidobacterium abundances increased. In contrast, stool abundance of Firmicutes, Verrucomicrobiota, Spirochaetota, Desulfobacterota, Butyricicoccus, Roseburia, Lachnospiraceae A2, Lachnospiraceae unclassified, and Oscillospiraceae unclassified decreased, and pancreatic detection of Alloprevotella and Oscillospiraceae uncultured was not observed. Furthermore, FMT accelerated tumorigenesis, gradually decreased the stool alpha diversity, and changed the pancreatic and stool microbial composition in mice with a Kras mutation. Specifically, the abundance of Actinobacteriota, Bifidobacterium and Faecalibaculum increased, while the abundance of genera such as Lachnospiraceace A2 and ASF356, Desulfovibrionaceace uncultured, and Roseburia has decreased. In conclusion, pancreatic carcinogenesis in the presence of an oncogenic Kras mutation stimulated by chronic inflammation and FMT dynamically changes the stool and pancreas microbiota. In particular, a decrease in stool microbiota diversity and abundance of bacteria known to be involved in short-fatty acids production were observed. PDAC mouse model can be used for further research on microbiota-PDAC interactions and towards more personalized and effective cancer therapies.}, } @article {pmid40071861, year = {2025}, author = {Organski, AC and Rajwa, B and Reddivari, A and Jorgensen, JS and Cross, TL}, title = {Gut microbiome-driven regulation of sex hormone homeostasis: a potential neuroendocrine connection.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2476562}, pmid = {40071861}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Male ; Female ; Mice ; *Homeostasis ; *Gonadal Steroid Hormones/metabolism/blood ; Fecal Microbiota Transplantation ; Germ-Free Life ; Mice, Inbred C57BL ; Hypothalamo-Hypophyseal System/metabolism/physiology ; Testosterone/metabolism/blood ; Feces/microbiology ; Testis ; }, abstract = {The gut microbiome is known to have a bidirectional relationship with sex hormone homeostasis; however, its role in mediating interactions between the primary regulatory axes of sex hormones and their productions is yet to be fully understood. We utilized both conventionally raised and gnotobiotic mouse models to investigate the regulatory role of the gut microbiome on the hypothalamic-pituitary-gonadal (HPG) axis. Male and female conventionally raised mice underwent surgical modifications as follows: (1) hormonally intact controls; (2) gonadectomized males and females; (3) gonadectomized males and females supplemented with testosterone and estrogen, respectively. Fecal samples from these mice were used to colonize sex-matched, intact, germ-free recipient mice through fecal microbiota transplant (FMT). Serum gonadotropins, gonadal sex hormones, cecal microbiota, and the serum global metabolome were assessed. FMT recipients of gonadectomized-associated microbiota showed lower circulating gonadotropin levels than recipients of intact-associated microbiota, opposite to that of FMT donors. FMT recipients of gonadectomized-associated microbiota also had greater testicular weights compared to recipients of intact-associated microbiota. The gut microbiota composition of recipient mice differed significantly based on the FMT received, with the male microbiota having a more concerted impact in response to changes in the HPG axis. Network analyses showed that multiple metabolically unrelated pathways may be involved in driving differences in serum metabolites due to sex and microbiome received in the recipient mice. In sum, our findings indicate that the gut microbiome responds to the HPG axis and subsequently modulates its feedback mechanisms. A deeper understanding of interactions between the gut microbiota and the neuroendocrine-gonadal system may contribute to the development of therapies for sexually dimorphic diseases.}, } @article {pmid40070843, year = {2025}, author = {Ren, S and Zhang, Y and Wang, X and Su, J and Wang, X and Yuan, Z and He, X and Guo, S and Chen, Y and Deng, S and Wu, X and Li, M and Du, F and Zhao, Y and Shen, J and Hu, W and Li, X and Xiao, Z}, title = {Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1526967}, pmid = {40070843}, issn = {1664-3224}, mesh = {Humans ; *Carcinoma, Hepatocellular/therapy/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; *Liver Neoplasms/therapy/immunology/microbiology ; *Immunotherapy/methods ; Tumor Microenvironment/immunology ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; }, abstract = {The gut microbiota, a complex microbial ecosystem closely connected to the liver via the portal vein, has emerged as a critical regulator of liver health and disease. Numerous studies have underscored its role in the onset and progression of liver disorders, including alcoholic liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). This review provides a comprehensive overview of current insights into the influence of the gut microbiota on HCC progression, particularly its effects on immune cells within the HCC tumor microenvironment (TME). Furthermore, we explore the potential of gut microbiota-targeted interventions, such as antibiotics, probiotics, prebiotics, and fecal microbiota transplantation (FMT), to modulate the immune response and improve outcomes of immunotherapy in HCC. By synthesizing insights from recent studies, this review aims to highlight microbiota-based strategies that may enhance immunotherapy outcomes, advancing personalized approaches in HCC treatment.}, } @article {pmid40069438, year = {2025}, author = {Park, M and Jung, J and Lee, JA and Lee, E and Lee, H and Eom, HS and Park, HJ}, title = {Understanding gut Microbiome changes in Korean children, adolescents, and young adults with hematologic malignancies.}, journal = {Annals of hematology}, volume = {104}, number = {5}, pages = {2947-2961}, pmid = {40069438}, issn = {1432-0584}, support = {2011500-1//National Cancer Center, Korea/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Adolescent ; Child ; Male ; Female ; *Hematologic Neoplasms/therapy/microbiology/epidemiology ; Young Adult ; Republic of Korea/epidemiology ; Hematopoietic Stem Cell Transplantation ; Feces/microbiology ; Adult ; }, abstract = {We investigated whether changes in the gut microbiome composition are associated with infections and immunologic complications during the treatment of Korean children, adolescents, and young adults (AYAs) with hematologic malignancies. We analyzed stool samples from 26 patients and 10 healthy siblings using 16 S rRNA gene sequencing. At diagnosis, patients exhibited a lower abundance of Lachnospiraceae and a higher abundance of Enterococcaceae than their healthy siblings. Both the Chao1 and Shannon diversity indices declined from diagnosis to the end of induction chemotherapy. Patients with fever during induction had a lower baseline microbial diversity and higher Ruminococcus g4 abundance than those without fever. The use of either meropenem or piperacillin/tazobactam during induction was correlated with reduced richness and altered composition of the gut microbiome after induction. The Chao index and beta diversity of stool samples significantly differed before conditioning when compared with those of healthy siblings. During allogeneic hematopoietic stem cell transplantation, both the Chao1 and Shannon diversity indices significantly decreased on day 14 but recovered by day 60. Our study highlights the role of gut microbiome diversity and compositional structure in influencing treatment outcomes in children and AYA with hematologic malignancies, providing the information required to improve the gut microbiome configuration and treatment outcomes.}, } @article {pmid40068791, year = {2025}, author = {Huang, H and Zhao, T and Ma, W}, title = {Omega-3 polyunsaturated fatty acids attenuate cognitive impairment via the gut-brain axis in diabetes-associated cognitive dysfunction rats.}, journal = {Brain, behavior, and immunity}, volume = {127}, number = {}, pages = {147-169}, doi = {10.1016/j.bbi.2025.03.015}, pmid = {40068791}, issn = {1090-2139}, mesh = {Animals ; *Fatty Acids, Omega-3/pharmacology/metabolism ; *Gastrointestinal Microbiome/drug effects/physiology ; Rats ; *Cognitive Dysfunction/metabolism/etiology/drug therapy ; Male ; Diabetes Mellitus, Experimental/metabolism/complications ; Brain/metabolism/drug effects ; Fecal Microbiota Transplantation/methods ; Diabetes Mellitus, Type 2/metabolism/complications ; *Brain-Gut Axis/drug effects ; Rats, Sprague-Dawley ; Blood Glucose/metabolism ; Cytokines/metabolism ; }, abstract = {Diabetes-related cognitive dysfunction (DACD) is a comorbidity of type 2 diabetes that has a negative effect on patients' quality of life. Research has indicated that disruption of the gut microbiota (GM) may be linked to dementia with altered cognitive performance. Conversely, omega-3 polyunsaturated fatty acids (n-3 PUFAs) may reverse DACD. The present study aimed to assess the effects of an n-3 PUFA intervention and fecal microbiota transplantation (FMT) on high-fat and streptozotocin-induced DACD model rats. In DACD rats, n-3 PUFA treatment restored fasting blood glucose (FBG) levels and cognitive function, increased the expression of anti-inflammatory cytokines and downregulated the expression of proinflammatory cytokines in the cortex and colon. Additionally, the expression of the postsynaptic density protein-95 mRNA and protein varied with n-3 PUFA treatment. Treatment with n-3 PUFAs also increased the expression of tight junction proteins. Beneficial and short-chain fatty acid-producing bacteria were more abundant when rats were exposed to n-3 PUFAs. After FMT from the rats with DACD symptoms that were improved by the n-3 PUFA dietary intervention into another batch of DACD rats, we observed recovery in recipient DACD rats. These results indicated that the alleviation of DACD symptoms by n-3 PUFAs was attributed to gut microbiota remodeling.}, } @article {pmid40066068, year = {2025}, author = {Ganesan, R and Thirumurugan, D and Vinayagam, S and Kim, DJ and Suk, KT and Iyer, M and Yadav, MK and HariKrishnaReddy, D and Parkash, J and Wander, A and Vellingiri, B}, title = {A critical review of microbiome-derived metabolic functions and translational research in liver diseases.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1488874}, pmid = {40066068}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; *Translational Research, Biomedical ; *Liver Diseases/microbiology/therapy/metabolism ; Animals ; Probiotics/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Liver/pathology ; }, abstract = {Significant changes in gut microbial composition are associated with chronic liver disease. Using preclinical models, it has been demonstrated that ethanol/alcohol-induced liver disease is transmissible through fecal microbiota transplantation (FMT). So, the survival rate of people with severe alcoholic hepatitis got better, which suggests that changes in the makeup and function of gut microbiota play a role in metabolic liver disease. The leaky intestinal barrier plays a major role in influencing metabolic-related liver disease development through the gut microbiota. As a result, viable bacteria and microbial products can be transported to the liver, causing inflammation, contributing to hepatocyte death, and causing the fibrotic response. As metabolic-related liver disease starts and gets worse, gut dysbiosis is linked to changes in the immune system, the bile acid composition, and the metabolic function of the microbiota in the gut. Metabolic-related liver disease, as well as its self-perpetuation, will be demonstrated using data from preclinical and human studies. Further, we summarize how untargeted treatment approaches affect the gut microbiota in metabolic-related liver disease, including dietary changes, probiotics, antibiotics, and FMT. It discusses how targeted therapies can improve liver disease in various areas. These approaches may improve metabolic-related liver disease treatment options.}, } @article {pmid40064933, year = {2025}, author = {Madill-Thomsen, KS and Venner, JM and Parsons, DE and Famulski, KS and Thiesen, AL and Hoque, S and Kroeker, KI and Wong, K and Peerani, F and Dieleman, LA and Hoentjen, F and Baumgart, DC and Halloran, PF and Halloran, BP}, title = {Relating the molecular phenotype of ulcerative colitis to the clinical course.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {8342}, pmid = {40064933}, issn = {2045-2322}, mesh = {Humans ; *Colitis, Ulcerative/genetics/pathology/metabolism/diagnosis ; Male ; Female ; Adult ; Middle Aged ; Leukocyte L1 Antigen Complex/genetics/metabolism ; Phenotype ; Disease Progression ; Prospective Studies ; Biopsy ; Immunity, Innate/genetics ; Gene Expression Profiling ; }, abstract = {The expanding portfolio of targeted therapies for ulcerative colitis (UC) suggests that a more precise approach to defining disease activity will aid clinical decision-making. This prospective study used genome-wide microarrays to characterize gene expression in biopsies from the most inflamed colon segments from patients with UC and analyzed associations between molecular changes and short-term outcomes while on standard-of-care treatment. We analyzed 141 biopsies-128 biopsies from 112 UC patients and 13 biopsies from eight inflammatory bowel disease unclassified (IBDU) patients. Endoscopic disease was associated with expression of innate immunity transcripts, e.g. complement factor B (CFB); inflammasome genes (ZBP1 and PIM2); calprotectin (S100A8 and S100A9); and inflammation-, injury-, and innate immunity-associated pathway analysis terms. A cross-validated molecular machine learning classifier trained on the endoscopic Mayo subscore predicted the endoscopic Mayo subscore with area-under-the-curve of 0.85. A molecular calprotectin transcript score showed strong associations with fecal calprotectin and the endoscopic Mayo subscore. Logistic regression models showed that molecular features (e.g. molecular classifier and molecular calprotectin scores) improved the prediction of disease progression over conventional, clinical features alone (e.g. total Mayo score, fecal calprotectin, physician global assessment). The molecular features of UC showed strong correlations with disease activity and permitted development of machine-learning predictive disease classifiers that can be applied to expanded testing in diverse cohorts.}, } @article {pmid40063530, year = {2025}, author = {Serbanescu, M and Lee, S and Li, F and Boppana, SH and Elebasy, M and White, JR and Mintz, CD}, title = {Effects of Perioperative Exposure on the Microbiome and Outcomes From an Immune Challenge in C57Bl/6 Adult Mice.}, journal = {Anesthesia and analgesia}, volume = {}, number = {}, pages = {}, pmid = {40063530}, issn = {1526-7598}, support = {R01 GM137213/GM/NIGMS NIH HHS/United States ; T32 GM008600/GM/NIGMS NIH HHS/United States ; T32 GM075774/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Previous work suggests that the gut microbiome can be disrupted by antibiotics, anesthetics, opiates, supplemental oxygen, or nutritional deprivation-all of which are common and potentially modifiable perioperative interventions that nearly all patients are exposed to in the setting of surgery. Gut microbial dysbiosis has been postulated to be a risk factor for poor surgical outcomes, but how perioperative care-independent of the surgical intervention-impacts the gut microbiome, and the potential consequences of this impact have not been directly investigated.

METHODS: We developed a perioperative exposure model (PEM) in C57Bl/6 mice to emulate the most common elements of perioperative medicine other than surgery, which included 12 hours of nutritional deprivation, 4 hours of volatile general anesthetic, 7 hours of supplemental oxygen, surgical antibiotics (cefazolin), and opioid pain medication (buprenorphine). Gut microbial dynamics and inferred metabolic changes were longitudinally assessed before-and at 3 time points after-PEM by 16S rRNA amplicon sequencing. We then used fecal microbial transplant in secondary abiotic mice to test if, compared to preexposure microbiota, day 3 post-PEM microbial communities affect the clinical response to immune challenge in an endotoxemia model.

RESULTS: We observed transient changes in microbiota structure and function after the PEM, including reduced biodiversity, loss of diverse commensals associated with health (including Lactobacillus, Roseburia, and Ruminococcus), and changes in microbiota-mediated amino acid metabolic pathways. Mice engrafted with day 3 post-PEM microbial communities demonstrated markedly reduced survival after endotoxemia compared to those bearing preexposure communities (7-day survival of ~20% vs ~70%, P = .0002).

CONCLUSIONS: These findings provide the first clear evidence that the combined effects of common perioperative factors, independent of surgery, cause gut microbial dysbiosis and alter the host response to inflammation in the postoperative period.}, } @article {pmid40062406, year = {2025}, author = {Moutsoglou, D and Ramakrishnan, P and Vaughn, BP}, title = {Microbiota transplant therapy in inflammatory bowel disease: advances and mechanistic insights.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2477255}, pmid = {40062406}, issn = {1949-0984}, mesh = {Humans ; *Inflammatory Bowel Diseases/therapy/microbiology/immunology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Treatment Outcome ; Animals ; }, abstract = {Microbiota transplant therapy is an emerging therapy for inflammatory bowel disease, but factors influencing its efficacy and mechanism remain poorly understood. In this narrative review, we outline key elements affecting therapeutic outcomes, including donor factors (such as age and patient relationship), recipient factors, control selection, and elements impacting engraftment and its correlation with clinical response. We also examine potential mechanisms through inflammatory bowel disease trials, focusing on the interplay between the microbiota, host, and immune system. Finally, we briefly explore potential future directions for microbiota transplant therapy and promising emerging treatments.}, } @article {pmid40061173, year = {2025}, author = {Borah, P and Gautam, V and Kumar, V and Saikia, B and Naithani, R}, title = {Fecal Microbiota Transplantation for Refractory Clostridioides difficile Infection Post Haploidentical Transplant for Pediatric Acute Myeloid Leukemia.}, journal = {Blood cell therapy}, volume = {8}, number = {1}, pages = {170-172}, pmid = {40061173}, issn = {2432-7026}, abstract = {BACKGROUND: Clostridioides difficile (C. difficile) infections are common in immunosuppressed patients. Sometimes these are difficult to treat in post-bone marrow transplant situations.

METHODS: A 2-year-old child with relapsed acute myeloid leukemia underwent a haploidentical bone marrow transplant. He developed 30-40 episodes/day of loose watery stools on day +19. The stool was positive for C. difficile infection. He failed oral vancomycin and metronidazole therapy. He received a fecal microbiota transplant (FMT) on day +43. The donor was the same sister who donated hematopoietic stem cells.

RESULTS: Three days later (day +46), stool frequency reduced from 22-24/day to 12-14/day. Color normalized to yellow and consistency improved from watery to semisolid without blood. He was discharged from the hospital 10 days after FMT on oral vancomycin and nasogastric feeding. Stool tested for C. difficile 16 days after FMT was negative and oral vancomycin was stopped.

CONCLUSION: Fecal microbiota transplant could be a useful modality in children with severe C. difficile infection post-bone marrow transplant.}, } @article {pmid40060755, year = {2025}, author = {Yi, D and Li, T and Xiao, Y and Zhang, X and Hao, Q and Zhang, F and Qiu, T and Yang, G and Sun, X and Dong, Y and Wang, N}, title = {Fecal microbiota transplantation for the treatment of intestinal and extra-intestinal diseases: Mechanism basis, clinical application, and potential prospect.}, journal = {Bioengineering & translational medicine}, volume = {10}, number = {2}, pages = {e10728}, pmid = {40060755}, issn = {2380-6761}, abstract = {To review the theoretical basis and therapeutic effects of fecal microbiota transplantation (FMT) in various diseases in animal experiments and clinical studies, as well as the limitations and current standards of FMT application. PubMed and Web of Science databases were searched for articles published only in English between 1975 and 2023 on reliable results of animal experiments and clinical treatment of FMT. The properties of the gut microbiota and its interactions with the host metabolism are critical to human health, and microbiome disturbance is closely associated with human intestinal and extra-intestinal diseases. Therefore, therapeutic tools targeting on the modulation of gut microbiota have attracted increasing attention, among which FMT represents the most widely studied intervention strategy. This review gathered and summarized application of FMT in intestinal diseases, metabolic diseases, hypertension, cancer, nervous system diseases and arthritis, and elaborated the beneficial effects that can be achieved by altering the microbiota with FMT and the mechanisms of action. In addition, the potential risks and side effects of FMT approach are discussed, as well as current efforts to standardize the development of FMT. Through a systemic review of the outcome and mechanism of FMT in the treatment of intestinal diseases and extra-intestinal diseases, we aimed to provide a theoretical basis for the construction of an optimized FMT framework, so as to better exert its application prospects.}, } @article {pmid40060387, year = {2025}, author = {Kim, M and Wang, J and Pilley, SE and Lu, RJ and Xu, A and Kim, Y and Liu, M and Fu, X and Booth, SL and Mullen, PJ and Benayoun, BA}, title = {Estropausal gut microbiota transplant improves measures of ovarian function in adult mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40060387}, issn = {2692-8205}, support = {P30 CA014089/CA/NCI NIH HHS/United States ; R24 HD102061/HD/NICHD NIH HHS/United States ; T32 AG052374/AG/NIA NIH HHS/United States ; }, abstract = {Decline in ovarian function with age not only affects fertility but is also linked to a higher risk of age-related diseases in women (e.g. osteoporosis, dementia). Intriguingly, earlier menopause is linked to shorter lifespan; however, the underlying molecular mechanisms of ovarian aging are not well understood. Recent evidence suggests the gut microbiota may influence ovarian health. In this study, we characterized ovarian aging associated microbial profiles in mice and investigated the effect of the gut microbiome from young and estropausal female mice on ovarian health through fecal microbiota transplantation. We demonstrate that the ovarian transcriptome can be broadly remodeled after heterochronic microbiota transplantation, with a reduction in inflammation-related gene expression and trends consistent with transcriptional rejuvenation. Consistently, these mice exhibited enhanced ovarian health and increased fertility. Using metagenomics-based causal mediation analyses and serum untargeted metabolomics, we identified candidate microbial species and metabolites that may contribute to the observed effects of fecal microbiota transplantation. Our findings reveal a direct link between the gut microbiota and ovarian health.}, } @article {pmid40058319, year = {2025}, author = {Zhang, W and Yi, C and Song, Z and Yu, B and Jiang, X and Guo, L and Huang, S and Xia, T and Huang, F and Yan, Y and Li, H and Dai, Y}, title = {Reshaping the gut microbiota: Tangliping decoction and its core blood-absorbed component quercetin improve diabetic cognitive impairment.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {140}, number = {}, pages = {156560}, doi = {10.1016/j.phymed.2025.156560}, pmid = {40058319}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Cognitive Dysfunction/drug therapy/etiology/microbiology ; *Drugs, Chinese Herbal/pharmacology ; Mice ; *Quercetin/pharmacology ; *Diabetes Mellitus, Type 2/complications ; Male ; Diabetes Mellitus, Experimental/complications ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S ; Maze Learning/drug effects ; }, abstract = {BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cognitive decline, which can result in diabetic cognitive impairment (DCI). Recent studies have indicated that gut microbiota plays a significant role in the development of DCI. Tangliping Decoction (TLP), a traditional Chinese medicine compound, contains various active ingredients that have been shown to regulate the microecology of gut microbiota and potentially improve DCI. However, it remains unclear whether TLP can improve DCI by modulating gut microbiota, as well as which specific component is primarily responsible for these effects.

PURPOSE: Assess the impact of TLP on alleviating DCI and investigate the contribution of quercetin (QR), the core blood-absorbed component of TLP, in this process. and investigate the underlying mechanisms through which TLP and QR enhance DCI by modulating gut microbiota composition.

STUDY DESIGN AND METHODS: Initially, experiments such as morris water maze (MWM), morphological analysis, and 16S ribosomal RNA (16S rRNA) gene amplicon sequencing from DCI mice, were performed to validate the pharmacological efficacy of TLP in mitigating DCI. The results indicated that TLP possesses the capacity to modulate the composition and quantity of gut microbiota and safeguard the integrity of the gut barrier and brain barrier. Secondly, high performance liquid chromatography coupled with high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) combined with network pharmacology methods were used to screen for blood-absorbed components, suggesting that QR may be a potential core blood-absorbed component of TLP in the treatment of DCI. Subsequently, the pharmacological efficacy of QR in ameliorating DCI was confirmed, and the characteristics of gut microbiota as well as the permeability of the gut and brain barrier, were assessed. Finally, fecal microbiota transplantation (FMT) experiments were conducted, wherein fecal matter from TLP and QR-treated mice (donor mice) was transplanted into pseudo-sterile DCI mice with antibiotic-induced depletion of gut microbiota. This approach aimed to elucidate the specific mechanisms by which TLP and QR improve DCI through the modulation of the structure, composition, and abundance of gut microbiota.

RESULTS: TLP and QR have the potential to enhance learning and memory capabilities in DCI mice, as well as reduce homeostasis model assessment insulin resistance (HOMA-IR) and restore homeostasis model assessment-β function (HOMA- β), leading to increased fasting insulin (FIN) levels and decreased fasting blood glucose (FBG) levels. Simultaneously, the administration of FMT from donor mice to pseudo-sterile DCI mice has been shown to alter the composition and abundance of gut microbiota, leading to amelioration of pathological damage in the colon and hippocampal tissues. Ultimately, FMT utilizing fecal suspensions from donor mice treated with TLP and QR improved cognitive function in pseudo-sterile DCI mice, restore gut microbiota dysbiosis, and maintained the integrity of the gut and brain barriers.

CONCLUSION: The results of this study indicate that TLP and its core component, QR, which is absorbed into the bloodstream, improve DCI through a gut microbiota-dependent mechanism, providing further evidence for gut microbiota as a therapeutic target for DCI treatment.}, } @article {pmid40058316, year = {2025}, author = {Tang, X and Huang, L and Ma, W and Huang, M and Zeng, Z and Yu, Y and Qin, N and Zhou, F and Li, F and Gong, S and Yang, H}, title = {Intestinal 8 gingerol attenuates TBI-induced neuroinflammation by inhibiting microglia NLRP3 inflammasome activation in a PINK1/Parkin-dependent manner.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {140}, number = {}, pages = {156580}, doi = {10.1016/j.phymed.2025.156580}, pmid = {40058316}, issn = {1618-095X}, mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Microglia/drug effects/metabolism ; *Catechols/pharmacology ; *Inflammasomes/metabolism/drug effects ; *Brain Injuries, Traumatic/drug therapy/complications/metabolism ; *Fatty Alcohols/pharmacology ; Male ; Ubiquitin-Protein Ligases/metabolism ; Rats ; Rats, Sprague-Dawley ; Gastrointestinal Microbiome/drug effects ; Protein Kinases/metabolism ; Mice ; Fecal Microbiota Transplantation ; *Neuroinflammatory Diseases/drug therapy/etiology ; Dysbiosis ; }, abstract = {BACKGROUND: traumatic brain injury (TBI) is irreversible brain damage, leading to inflammation and cognitive dysfunction. Microglia involved in the inflammatory response after TBI. The gut microbiota, known as the body's "second brain," regulates neurogenesis and immune responses, but its precise role in regulating TBI remains unclear.

PURPOSE: to investigate the effect of gut microbiota and metabolites disorder on TBI injury.

STUDY DESIGN: 16SrRNA and metabolomics compared gut microbiota and metabolites in sham group and TBI group, then proved that the differential metabolite 8-gingerol (8G) alleviated the microglia neuroinflammatory response after TBI.

METHODS: fecal microbiota transplantation explored the role of dysbiosis in TBI. LC/MS detected the content of 8-gingerol in cecum, blood, and brain. HE, Nissl, Tunel staining and mNSS score evaluated brain injury. Western blot and immunofluorescence detected the expression of inflammasome-related proteins and mitophagy-related proteins in brain tissue and BV2 cells. RNA sequencing analyzed the molecular mechanism of 8-gingerol.

RESULT: rats transplanted with TBI feces had worse brain injury and neurological deficits than those with normal feces. 16SrRNA and metabolomics found that TBI caused dysbiosis and decreased 8-gingerol level, leading to severe neuroinflammation. Mechanistically, 8-gingerol inhibited NLRP3 inflammasome by promoting PINK1-Parkin mediated mitophagy in microglia. Inhibition of Parkin, through either small interfering RNA or the inhibitor 3MA reversed the inhibitory effect of 8-gingerol on NLRP3 by blocking mitophagy. BV2 cells transcriptome showed that 8-gingerol significantly increased the expression of autophagy factor Wipi1, and small interfering RNA of Wipi1 abolished the effect of 8-gingerol on promoting mitophagy and the inhibitory effect on NLRP3.

CONCLUSION: our findings shed light on the pivotal role of gut microbes in TBI, and identify 8 gingerol as an important anti-inflammatory compound during TBI.}, } @article {pmid40058066, year = {2025}, author = {Mu, X and Feng, L and Wang, Q and Li, H and Zhou, H and Yi, W and Sun, Y}, title = {Decreased gut microbiome-derived indole-3-propionic acid mediates the exacerbation of myocardial ischemia/reperfusion injury following depression via the brain-gut-heart axis.}, journal = {Redox biology}, volume = {81}, number = {}, pages = {103580}, pmid = {40058066}, issn = {2213-2317}, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; *Myocardial Reperfusion Injury/metabolism/etiology/pathology ; *Indoles/metabolism ; *Depression/complications/metabolism ; Male ; Disease Models, Animal ; Brain/metabolism ; Fecal Microbiota Transplantation ; *Brain-Gut Axis ; }, abstract = {Despite the increasing recognition of the interplay between depression and cardiovascular disease (CVD), the precise mechanisms by which depression contributes to the pathogenesis of cardiovascular disease remain inadequately understood. The involvement of gut microbiota and their metabolites to health and disease susceptibility has been gaining increasing attention. In this study, it was found that depression exacerbated cardiac injury, impaired cardiac function (EF%: P < 0.01; FS%: P < 0.05), hindered long-term survival (P < 0.01), and intensified adverse cardiac remodeling (WGA: P < 0.01; MASSON: P < 0.0001) after myocardial ischemia/reperfusion (MI/R) in mice. Then we found that mice receiving microbiota transplants from chronic social defeat stress (CSDS) mice exhibited worse cardiac function (EF%: P < 0.01; FS%: P < 0.01) than those receiving microbiota transplants from non-CSDS mice after MI/R injury. Moreover, impaired tryptophan metabolism due to alterations in gut microbiota composition and structure was observed in the CSDS mice. Mechanistically, we analyzed the metabolomics of fecal and serum samples from CSDS mice and identified indole-3-propionic acid (IPA) as a protective agent for cardiomyocytes against ferroptosis after MI/R via NRF2/System xc-/GPX4 axis, played a role in mediating the detrimental influence of depression on MI/R. Our findings provide new insights into the role of the gut microbiota and IPA in depression and CVD, forming the basis of intervention strategies aimed at mitigating the deterioration of cardiac function following MI/R in patients experiencing depression.}, } @article {pmid40055837, year = {2025}, author = {Alexandra, P and Noémie, P and Solène, SB and Jean-Benoit, H and Riche, VP and Odile, C and Michel, G and Guy, V and Hamy, A and Mehdi, O and Yannick, T and Jeremie H, L and Amar, A and Emeric, A and Jean-Michel, B and Bridoux, V and Dumont, F and June, F and Alexandra, J and Meurette, G and Duchalais, E}, title = {Evaluation of pelvic floor rehabilitation in the prevention of low anterior resection syndrome: Study protocol of the CONTICARE trial.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {27}, number = {3}, pages = {e70045}, doi = {10.1111/codi.70045}, pmid = {40055837}, issn = {1463-1318}, support = {//French Ministry of Health (PHRCI 2016 - API16/N/055)/ ; }, mesh = {Humans ; *Pelvic Floor/physiopathology ; *Postoperative Complications/prevention & control/etiology ; *Rectal Neoplasms/surgery ; Quality of Life ; Fecal Incontinence/prevention & control/etiology ; Female ; Syndrome ; *Proctectomy/adverse effects/rehabilitation ; Biofeedback, Psychology/methods ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; Middle Aged ; Male ; Adult ; Anal Canal/surgery ; Treatment Outcome ; *Exercise Therapy/methods ; Aged ; Organ Sparing Treatments/adverse effects ; Low Anterior Resection Syndrome ; }, abstract = {AIM: Bowel dysfunction following sphincter-preserving rectal resection for cancer, commonly referred to as low anterior resection syndrome (LARS), significantly impacts patients' quality of life. Preventing this condition is essential for healthcare teams. Postoperative pelvic floor rehabilitation, including anal biofeedback therapy, has shown potential in alleviating established LARS symptoms. This trial aims to evaluate the effectiveness of pelvic floor rehabilitation prior to bowel continuity restoration in preventing LARS in patients undergoing sphincter-preserving rectal resection for cancer.

METHODS: CONTICARE is a national multicentre randomized trial. Patients who have undergone total mesorectal excision with sphincter preservation and a defunctioning stoma (n = 174; 87 per arm) will be randomly assigned to either the rehabilitation or control group before stoma closure. The rehabilitation group will receive systematic pelvic floor rehabilitation, comprising four sessions before and six sessions after stoma closure, following a standardized approach. The control group will receive standard follow-up care, which includes symptom-based therapy after ileostomy closure. The primary outcome measure will be the severity of LARS, assessed using the dedicated LARS score at 6 months. Comparisons of faecal incontinence symptoms, quality of life and complications related to biofeedback therapy will also be evaluated at 6 weeks, 6 months and 1 year between the two groups.

CONCLUSION: Pelvic floor rehabilitation has the potential to enhance symptom management and quality of life for patients following rectal resection by preventing LARS. The combination of anal exercises and biofeedback therapy, which has been extensively studied without reported adverse effects, suggests that the anticipated benefits outweigh any potential risks.

CLINICAL TRIAL REGISTRATION: Registration number NCT03876561, first published on 15 March 2019.

CLINICALTRIALS: gov.}, } @article {pmid40054499, year = {2025}, author = {Luan, WW and Gu, HW and Qiu, D and Ding, X and Liu, PM and Hashimoto, K and Yang, JJ and Wang, XM}, title = {Repeated administration of esketamine ameliorates mechanical allodynia in mice with chemotherapy-induced peripheral neuropathy: A role of gut microbiota and metabolites.}, journal = {Neurochemistry international}, volume = {185}, number = {}, pages = {105961}, doi = {10.1016/j.neuint.2025.105961}, pmid = {40054499}, issn = {1872-9754}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/physiology ; Mice ; *Ketamine/administration & dosage/pharmacology ; *Hyperalgesia/drug therapy/metabolism/chemically induced ; Oxaliplatin/toxicity ; Male ; *Peripheral Nervous System Diseases/chemically induced/drug therapy/metabolism ; *Antineoplastic Agents/toxicity ; Mice, Inbred C57BL ; }, abstract = {Chemotherapy-induced peripheral neuropathy (CIPN) severely diminishes the quality of life for cancer survivors, yet effective treatments remain scarce. Esketamine, a commonly used anesthetic, has demonstrated neuroprotective effects by restoring gut microbiome dysbiosis. In this study, we investigated the impact of esketamine on nociceptive sensitivity in a mouse model of CIPN and explored the potential involvement of the gut microbiome. In mice treated with oxaliplatin, repeated esketamine doses (in contrast to a single dose) significantly improved the paw withdrawal threshold (PWT). Western blot and qPCR analyses further revealed that repeated esketamine administration markedly reduced microglial activation and neuroinflammation in the dorsal root ganglion (DRG), underscoring its potent anti-inflammatory properties. Moreover, fecal 16S rRNA analysis indicated that esketamine partially restored the abnormal gut microbiota composition (β-diversity). Plasma metabolome analysis showed that repeated esketamine treatment significantly lowered the elevated levels of 6H-indolo[2,3-b]quinoline and restored the reduced levels of (3-exo)-3-[3-methyl-5-(1-methylethyl)-4H-1,2,4-triazol-4-yl]-8-azabicyclo[3.2.1]octane observed in oxaliplatin-treated mice. In addition, fecal microbiota transplantation from esketamine-treated CIPN mice notably improved both the diminished PWT and DRG neuroinflammation in oxaliplatin-treated mice. Collectively, these findings suggest that repeated esketamine administration may alleviate mechanical allodynia in CIPN mice by modulating neuroinflammation, gut microbiota, and associated metabolites.}, } @article {pmid40053245, year = {2025}, author = {Lukic, I and Ivkovic, S and Glavonic, E and Adzic, M and Mitic, M}, title = {Long-lasting Depressive Behavior of Adolescent Chronically Stressed Mice is Mediated by Gut Microbiota Dysbiosis.}, journal = {Molecular neurobiology}, volume = {62}, number = {7}, pages = {8868-8886}, pmid = {40053245}, issn = {1559-1182}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology/complications ; *Depression/microbiology/complications ; *Stress, Psychological/microbiology/complications ; Male ; Mice ; *Behavior, Animal ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Anxiety/microbiology ; Chronic Disease ; }, abstract = {Depression is one of the most common mental disorders worldwide, and its prevalence sharply rises during adolescence. Adolescence is a particularly sensitive period to the effects of environmental stressors, which can cause persistent depressive behavior extending into adulthood. However, the studies assessing if changes in gut microbiota could be one of the mediators of long-term effects of adolescent stress are scarce. In the present study, we examined enduring effects of adolescent chronic unpredictable stress (CUS) on mice behavior along with alterations in their gut microbiome, by using 16 s rRNA gene sequencing and fecal microbiota transplantation (FMT). CUS mice, as well as naïve mice receiving FMT from stressed animals, showed long-lasting anxiety and depressive-like behavior extending into adulthood. The microbiota dysbiosis in adolescence was characterized by higher abundance of Alloprevotella and lower abundance of Paraprevotella, Parasutterella, Parabacteroides, and undefined genus Rikenellaceae_RC9_gut_group. On the contrary, microbiota dysbiosis in adulthood was characterized by higher abundance of Bacteroides, Enterorhabdus, Marvinbriantia, and Parabacteroides and lower abundance of Akkermansia, Odoribacter, and Rikenella. In particular, depressive-like behavior in adolescence was negatively correlated with Paraprevotella, while depressive-like behavior in adulthood was negatively correlated with Rikenella abundance, in both CUS and FMT mice. Therefore, the transfer of microbiota from mice stressed in adolescence is able to induce long-lasting depressive-like behavior in naïve mice, clearly showing the importance of gut microbiota dysbiosis in adolescence in shaping enduring depressive behavior. Moreover, our results indicate that changes in specific but different bacteria are related to depressive behavior in adolescence and in adulthood.}, } @article {pmid40051947, year = {2025}, author = {Bhalla, A and Shahi, A and Maity, M and Safa, F and Srividya, V and Clementina, R and Anugu, GR and Younas, S}, title = {Inflammatory Bowel Disease in Children: Current Diagnosis and Treatment Strategies.}, journal = {Cureus}, volume = {17}, number = {2}, pages = {e78462}, pmid = {40051947}, issn = {2168-8184}, abstract = {Pediatric inflammatory bowel disease (PIBD), including Crohn's disease and ulcerative colitis, has emerged as a significant global health challenge with rising incidence rates. Unlike adult inflammatory bowel disease, PIBD presents complexities, including growth impairment, nutritional deficiencies, and psychosocial challenges that necessitate tailored management strategies. This article reviews current diagnostic and emerging treatment strategies to highlight the evolution from traditional therapies such as aminosalicylates, corticosteroids, and immunomodulators to advanced biologic agents like infliximab and adalimumab. Emerging biological therapies, including vedolizumab and ustekinumab, show promise, while novel small molecule therapies such as Janus kinase (JAK) inhibitors are under investigation for potential use in the pediatric population. Supportive treatments, including exclusive enteral nutrition, modified diets, and probiotics, play a critical role in comprehensive disease management. Stem cell therapy and fecal microbiota transplant represent innovative approaches still under clinical evaluation. The review underscores the significance of holistic care, incorporating mind-body interventions and psychosocial support to improve patient quality of life. Key challenges persist, such as infection risks associated with long-term biological therapy use, gaps in pediatric-specific guidelines, and the limited inclusion of children in clinical trials. Future recommendations emphasize the importance of structured transition programs bridging pediatric and adult care, regular updates to clinical guidelines, and the integration of precision medicine to personalize treatment plans. Continued research and collaboration are essential for advancing the understanding and management of PIBD, ensuring that pediatric patients benefit from the most effective, evidence-based care available.}, } @article {pmid40050917, year = {2025}, author = {Zou, B and Liu, S and Dong, C and Shen, H and Lv, Y and He, J and Li, X and Ruan, M and Huang, Z and Shu, S}, title = {Fecal microbiota transplantation restores gut microbiota diversity in children with active Crohn's disease: a prospective trial.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {288}, pmid = {40050917}, issn = {1479-5876}, mesh = {Humans ; *Crohn Disease/therapy/microbiology ; Child ; Male ; *Fecal Microbiota Transplantation/adverse effects ; Prospective Studies ; Female ; *Gastrointestinal Microbiome ; Adolescent ; Treatment Outcome ; Feces/microbiology ; Biomarkers/metabolism ; }, abstract = {BACKGROUND: Clinical data on oral fecal microbiota transplantation (FMT), a promising therapy for Crohn's disease (CD), are limited. Herein, we determined the short-term safety and feasibility of FMT for pediatric patients with active CD.

METHODS: In this open-label, parallel-group, single-center prospective trial, patients with active CD were treated with oral FMT capsules combined with partial enteral nutrition (PEN) (80%). The control group comprised pediatric patients with active CD treated with PEN (80%) and immunosuppressants. Thirty-three patients (11.6 ± 1.82 years)-17 in the capsule and 16 in the control groups-were analyzed. Data regarding the adverse events, clinical reactions, intestinal microbiome composition, and biomarker parameters were collected and compared post-treatment.

RESULTS: At week 10, the clinical and endoscopic remission rates did not differ between the two groups. By week 10, the mean fecal calprotectin level, C-reactive protein level, erythrocyte sedimentation rate, simple endoscopic score for CD, and pediatric CD activity index decreased significantly in the capsule group (all P < 0.05). The main adverse event was mild-to-moderate constipation. Core functional genera, Agathobacter, Akkermansia, Roseburia, Blautia, Subdoligranulum, and Faecalibacterium, were lacking pre-treatment. Post-treatment, the implantation rates of these core functional genera increased significantly, which positively correlated with the anti-inflammatory factor, interleukin (IL)-10, and negatively correlated with the pro-inflammatory factor, IL-6. The combination of these six functional genera distinguished healthy children from those with CD (area under the curve = 0.96).

CONCLUSIONS: Oral FMT capsules combined with PEN (80%) could be an effective therapy for children with active CD. The six core functional genera identified here may be candidate biomarkers for identifying children with CD.

TRIAL REGISTRATION: ClinicalTrials.gov, retrospectively registered, ID# NCT05321758, NCT05321745, date of registration: 2022-04-04.}, } @article {pmid40049043, year = {2025}, author = {Huang, JN and Gao, CC and Ren, HY and Wen, B and Wang, ZN and Gao, JZ and Chen, ZZ}, title = {Multi-omics association pattern between gut microbiota and host metabolism of a filter-feeding fish in situ exposed to microplastics.}, journal = {Environment international}, volume = {197}, number = {}, pages = {109360}, doi = {10.1016/j.envint.2025.109360}, pmid = {40049043}, issn = {1873-6750}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Carps/microbiology/metabolism ; *Water Pollutants, Chemical/toxicity ; *Microplastics/toxicity ; Multiomics ; }, abstract = {Microplastics (MPs) are widespread in water environments and can affect gut microbiota and host metabolism of fish, but whether changes in host metabolism under MPs are mediated by gut microbiota remains unclear. Here, silver carp, a filter-feeding fish with important ecological functions, was in-situ exposure to environmentally relevant MPs. Multi-omics analysis and fecal microbiota transplantation were used to reveal the metabolic responses of carp along gut-liver-muscle axis. After three months of in situ exposure to MPs, community structure of gut microbiota of carp was reshaped, and five dominate phyla were significantly changed, including increased Cyanobacteria, Chloroflexi and Planctomycetota but decreased Firmicutes and Fusobacteriota. Weighted gene co-expression network analysis was further performed between these phyla and liver transcription spectrum, showing that the hub gene module contained up-regulated hppD, maiA and plg and activated ubiquinone and other terpenoid-quinone biosynthesis and phenylalanine metabolism. By fecal microbiota transplantation, the key gene module associated with core microbiota phyla of carp was verified in germ-free zebrafish. Interestingly, up-regulated hppD, maiA and plg and enriched phenylalanine metabolism were also observed in this module. Subsequently, metabolome performed in carp liver also shared activated phenylalanine metabolism, including increased trans-cinnamic acid and L-tyrosine. Furthermore, high-associated mapping showed that the differentially expressed metabolites (gamma-aminobutyric acid, ornithine and L-serine) related to amino acid metabolism in carp muscle were significantly accompanied with increased L-tyrosine in its liver. Overall, MPs exposure could change gut microbiome of silver carp and alter host metabolism especially amino acid metabolism along the gut-liver-muscle axis.}, } @article {pmid40047909, year = {2025}, author = {Heinze, T and Heimke, M and Stelzner, S and Wedel, T}, title = {[Surgical anatomy of the anorectum].}, journal = {Chirurgie (Heidelberg, Germany)}, volume = {96}, number = {5}, pages = {431-444}, pmid = {40047909}, issn = {2731-698X}, mesh = {Humans ; *Anal Canal/anatomy & histology/surgery/blood supply/innervation ; *Rectum/anatomy & histology/surgery/blood supply/innervation ; }, abstract = {The anorectum corresponds to the last segment of the gastrointestinal tract and is responsible for mediating fecal continence and controlled defecation. An understanding of the complex topographic anatomy is an indispensable prerequisite for the surgical treatment of benign and malignant diseases in the anorectal region. The detailed description of perirectal fascia, anorectal blood supply and lymph vessel drainage, pelvic autonomic nerves and components of the anal canal and anal sphincter complex has significantly contributed to improvement of the oncological and functional surgical outcome. In this article the state of knowledge relating to the anorectal anatomy is outlined providing a practical basis for rectal and proctological surgical procedures.}, } @article {pmid40046764, year = {2025}, author = {Hou, PF and Yao, Y and Wu, Y and Yu, HT and Qin, Y and Yi, L and Mi, MT}, title = {Fecal microbiota transplantation improves hepatic steatosis induced by HFD in a mouse model associated with liver ILC1 regulation and indole-3-carbinol level.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1500293}, pmid = {40046764}, issn = {2296-861X}, abstract = {BACKGROUND: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased worldwide. In recent years, fecal microbiota transplantation (FMT) has become an important promising method for the treatment of MASLD. However, the mechanism remains unclear.

METHODS: The animal model with C57BL/6 male mice induced by high-fat diet (HFD) for 12 weeks has been introduced. Fecal microbiota and indole-3-carbinol (I3C) was given by oral gavage.

RESULTS: Our study demonstrated that a 6-week healthy gut microbiota transplantation tended to ameliorate hepatic steatosis and reverse the decreased liver ILC1 induced by HFD. Interestingly, there was also a negative correlation between liver ILC1 and liver TG, TC level. Furthermore, the protective effect was associated with the elevated levels of serum indole-3-carbinol (I3C). Also, a I3C administration for 6 weeks improved liver steatosis and increased the frequency of liver ILC1 induced by HFD through aryl hydrocarbon receptor (AhR) activation. Moreover, I3C binds to the residues of ALA349, PHE348, LEU309, TYR316, PHE318 on AhR through hydrogen bonds, Π bonds, hydrophobic bonds which was proved by molecular docking.

CONCLUSION: To conclude, our data demonstrated that FMT improved liver steatosis induced by HFD associated with liver ILC1 regulation and indole-3-carbinol level. The study highlighted the potential treatment value of FMT and microbiota-derived I3C in the MASLD treatment and regulation of liver ILC1 function.}, } @article {pmid40046008, year = {2024}, author = {Zeng, Z and Feng, M and He, F and Zhang, E and Li, X and Cao, Z}, title = {Gut microbiota mediates the pro-pyroptosis effect of xierezhuyubuxu decoction in hepatocellular carcinoma.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1481111}, pmid = {40046008}, issn = {1664-302X}, abstract = {INTRODUCTION: Xierezhuyubuxu decoction (XRZYBXD) is prepared by adding and reducing the Dahuang Zhechong Pill, which is a traditional Chinese medicinal formula in "The Synopsis of Prescriptions of the Golden Chamber". XRZYBXD has previously been reported to have good efficacy in treating Hepatocellular carcinoma (HCC) in clinical and basic research. However, its underlying mechanism in treating HCC has not been fully elucidated. The aim of the study is to investigate the pro-pyroptosis effect of XRZYBXD in HCC and the role of gut microbiota in this process.

METHODS: Firstly, we executed comprehensive analyses of XRZYBXD on pyroptosis, intestinal flora, microbial metabolites and intestinal barrier function using TUNEL, IHC, ELISA, WB, Q-PCR, 16S rRNA sequencing, and untargeted metabolomics in a H22 tumor-bearing mice model. Further, through rescue experiment of antibiotics-induced microbiota depletion and fecal microbial transplantation (FMT) experiment, the mechanism of XRZYBXD promoting pyroptosis of HCC by improving intestinal flora was verified.

RESULTS: We found that XRZYBXD medium and high dose significantly inhibited the growth of tumor and induced pyroptosis of hepatoma cells. They also modified intestinal ecological disorders by expansion of the abundance of beneficial bacteria (such as Akkermansia muciniphila and Parabacteroides distasonis) and reduction of the abundance of harmful bacteria (such as Barnesiella intestinihominis). Accordingly, microbiota metabolites and intestinal barrier function were also significantly improved by XRZYBXD.

DISCUSSION: Further, elimination of gut microbiota by antibiotics weakened the efficacy of XRZYBXD, and FMT with feces from the XRZYBXD high dose group achieved similar therapeutic efficacy as XRZYBXD. In brief, XRZYBXD promote pyroptosis of hepatoma cells via adjusting intestinal dysbiosis.}, } @article {pmid40045660, year = {2025}, author = {Hu, J and Xu, F and Zhu, L and Cui, Y and Au, R and Li, Y and Tong, Y and Shen, H}, title = {Angelica dahurica Polysaccharides Ameliorate Colitis by Reducing the Restriction of Gut Microbiota-Derived Imidazole Propionate on PPAR-γ Signaling Activation.}, journal = {Phytotherapy research : PTR}, volume = {39}, number = {5}, pages = {2072-2090}, pmid = {40045660}, issn = {1099-1573}, support = {82205023//National Natural Science Foundation of China/ ; 82274483//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *PPAR gamma/metabolism ; *Angelica/chemistry ; *Colitis/drug therapy/chemically induced/microbiology ; Mice ; *Polysaccharides/pharmacology/chemistry ; Dextran Sulfate ; Signal Transduction/drug effects ; Male ; Mice, Inbred C57BL ; *Imidazoles/metabolism ; Fecal Microbiota Transplantation ; Propionates/metabolism ; Plant Roots/chemistry ; Anti-Bacterial Agents/pharmacology ; }, abstract = {Angelica dahurica radix (ADR), the root of the botanical family Apiaceae (genus Angelica, species Angelica dahurica (Hoffm.)), has been used to treat colitis in clinical practice. The immunomodulatory effects of ADR are attributed to its polysaccharides (RP). However, its mechanism of action has not been elucidated. In this study, RP's structure was determined through nuclear magnetic resonance analysis. Dextran sulfate sodium-induced colitis in mice was utilized to assess the therapeutic efficacy of RP, while experiments involving fecal microbiota transplantation (FMT) and antibiotic treatment were performed to investigate the contribution of gut microbiota to RP's protective function. Non-targeted metabolomics was utilized to identify potential targets for elucidating the underlying mechanisms. RP is likely composed of (→4)-α-D-Glcp-(1→ and →4)-α-D-Galp-(1→). It effectively alleviated DSS-induced colitis by restoring the balance of the gut microbial community, a finding validated through FMT and antibiotic intervention experiments. Imidazole propionate (ImP) emerged as a potential target for RP's efficacy in treating colitis, which inhibits the activation of peroxisome proliferator-activated receptor gamma (PPAR-γ). Our findings suggest that RP may confer protection against colitis by activating the PPAR-γ signaling pathway through alleviating the constraint imposed by ImP.}, } @article {pmid40044736, year = {2025}, author = {Song, Y and Li, N and Jiang, S and Wang, K and Lv, G and Fan, Z and Du, X and Gao, W and Lei, L and Wang, Z and Liu, G and Li, X}, title = {Microbiota-derived H2S induces c-kit[+] cDC1 autophagic cell death and liver inflammation in metabolic dysfunction-associated steatohepatitis.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2222}, pmid = {40044736}, issn = {2041-1723}, support = {U24A20454//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32473104//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; Mice ; Humans ; *Gastrointestinal Microbiome/physiology ; *Autophagy/drug effects ; Male ; Liver/pathology/metabolism ; *Proto-Oncogene Proteins c-kit/metabolism/genetics ; Disease Models, Animal ; Mice, Inbred C57BL ; *Fatty Liver/microbiology/metabolism/pathology ; Inflammation ; Diet, Western/adverse effects ; Dysbiosis/microbiology ; Mice, Knockout ; Female ; }, abstract = {Immune dysregulation-induced inflammation serves as a driving force in the progression of metabolic dysfunction-associated steatohepatitis (MASH), while the underlying cellular and molecular mechanisms remain largely uncharted. A Western diet (WD) is employed to construct mouse models of metabolic dysfunction associated steatotic liver disease (MASLD) or MASH. Mass cytometry identifies a c-kit[+] cDC1 subset whose frequency is reduced in the livers of mice and patients with MASH compared with healthy controls. Adoptive cell transfer of c-kit[+] cDC1 protects the progression of MASH. Moreover, analysis of gut microbe sequence shows that WD-fed mice and MASLD/MASH patients exhibit gut microbiota dysbiosis, with an elevated abundance of H2S-producing Desulfovibrio_sp. Transplanting of MASH-derived fecal flora, Desulfovibrio_sp., or injecting H2S intraperitoneally into MASLD mice decreases the c-kit[+]cDC1 population and exacerbates liver inflammation. Mechanistically, H2S induces autophagic cell death of cDC1 in a c-kit-dependent manner in cDC-specific c-kit[-/-] and Atg5[-/-] mice. We thus uncover that microbiota-derived H2S triggers the autophagic cell death of c-kit[+] cDC1 and ignites the liver inflammatory cascade in MASH.}, } @article {pmid40042965, year = {2025}, author = {Sun, W and Jia, J and Liu, G and Liang, S and Huang, Y and Xin, M and Chang, Z and Liu, X and Ma, C and Song, X and He, F and Song, Y and Wu, M}, title = {Polysaccharides Extracted from Old Stalks of Asparagus officinalis L. Improve Nonalcoholic Fatty Liver by Increasing the Gut Butyric Acid Content and Improving Gut Barrier Function.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {11}, pages = {6632-6645}, doi = {10.1021/acs.jafc.4c07078}, pmid = {40042965}, issn = {1520-5118}, mesh = {Animals ; Gastrointestinal Microbiome/drug effects ; *Non-alcoholic Fatty Liver Disease/drug therapy/microbiology/metabolism/genetics ; Mice ; *Polysaccharides/administration & dosage/isolation & purification/chemistry ; *Asparagus Plant/chemistry ; Male ; Mice, Inbred C57BL ; *Plant Extracts/administration & dosage/isolation & purification/chemistry ; *Butyric Acid/metabolism/analysis ; Humans ; Liver/metabolism/drug effects ; NF-kappa B/genetics/metabolism ; Bacteria/isolation & purification/classification/genetics/metabolism ; Toll-Like Receptor 4/genetics/metabolism ; }, abstract = {Nonalcoholic fatty liver disease (NAFLD) ranks among the most prevalent chronic liver diseases worldwide, yet effective treatments remain scarce. Old stalks of Asparagus officinalis L. are rich in polysaccharides. The anti-NAFLD mechanism of polysaccharides from old stalks of A. officinalis (AP) requires further study. Here, we studied the effects of AP on NAFLD mice and its impact on the gut microbiota. AP intervention reduces blood lipids and liver lipids and reduces liver injury and inflammation in mice with NAFLD. Moreover, AP intervention changed gut microbiota composition and increased the abundances of butyric acid-producing bacteria, thereby increasing plasma concentration of butyric acid. Furthermore, AP intervention regulated the AMPK/SREBPs signaling pathway, thereby affecting hepatic lipid synthesis. Additionally, AP intervention improved gut barrier function and reduced plasma LPS levels, which subsequently inhibited the LPS/TLR4/NF-κB signaling pathway, thereby alleviating inflammation in NAFLD model mice. Importantly, fecal microbiota transplant (FMT) outcomes demonstrated that AP-induced changes in the gut microbiota impact the AMPK/SREBPs and LPS/TLR4/NF-κB pathways. These data suggest that AP intervention ameliorates NAFLD by regulating the gut microbiota. These research provides a scientific foundation for the use of the stalks of A. officinalis in the treatment of NAFLD.}, } @article {pmid40041456, year = {2025}, author = {Farah, A and Paul, P and Khan, AS and Sarkar, A and Laws, S and Chaari, A}, title = {Targeting gut microbiota dysbiosis in inflammatory bowel disease: a systematic review of current evidence.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1435030}, pmid = {40041456}, issn = {2296-858X}, abstract = {INTRODUCTION: The dysbiosis of the gut microbiota has been identified as a central factor in the pathogenesis of inflammatory bowel disease (IBD), a chronic condition characterized by frequent recurrence and various adverse effects of traditional therapies. While treatments targeting the gut microbiota show promise, their efficacy in IBD management still requires extensive evaluation. Our systematic review analyzes recent studies to elucidate the advancements and challenges in treating IBD using microbial-based therapies.

METHODS: Through a comprehensive systematic review spanning key scientific databases-PubMed, Embase, Cochrane, Web of Science, Scopus, and Google Scholar-we scrutinized the impact of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) on individuals with IBD. Our detailed analysis covered study and participant demographics, along with seven key outcome measures: disease activity index, inflammatory markers, serum cytokines, microbiome composition, adverse effects, and the rates of remission and relapse.

RESULTS: From 6,080 initial search hits, we included 71 studies that assessed various interventions compared to placebo or standard medical therapy. Although there was notable variation in clinical results while assessing different outcomes, overall, probiotics, prebiotics, and synbiotics enhanced the success rates in inducing remission among IBD patients. Furthermore, we noted significant reductions in levels of pro-inflammatory markers and cytokines. Additionally, the requirement for steroids, hospitalization, and poor outcomes in endoscopic and histological scores were significantly reduced in individuals undergoing FMT.

CONCLUSION: Our investigation highlights the potential of targeting gut microbiota dysbiosis with microbial-based therapies in patients with IBD. We recommend conducting larger, placebo-controlled randomized trials with extended follow-up periods to thoroughly assess these treatments' clinical efficacy and safety before widespread recommendations for clinical application.}, } @article {pmid40040709, year = {2025}, author = {Liu, X and Yang, K and Jia, Y and Yeertai, Y and Wu, C and Wang, X and Jia, Q and Gu, Z and Cong, J and Ling, J}, title = {Chaihushugan powder regulates the gut microbiota to alleviate mitochondrial oxidative stress in the gastric tissues of rats with functional dyspepsia.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1549554}, pmid = {40040709}, issn = {1664-3224}, mesh = {Animals ; *Oxidative Stress/drug effects ; *Gastrointestinal Microbiome/drug effects ; Rats ; *Dyspepsia/drug therapy/metabolism/microbiology ; Male ; *Mitochondria/metabolism/drug effects ; Disease Models, Animal ; Powders ; Fecal Microbiota Transplantation ; Rats, Sprague-Dawley ; *Drugs, Chinese Herbal/pharmacology ; *Gastric Mucosa/metabolism/drug effects ; Gastrointestinal Motility/drug effects ; }, abstract = {INTRODUCTION: Functional dyspepsia (FD) is a prevalent functional gastrointestinal disorder associated with oxidative stress (OS) and dysbiosis. Chaihushugan powder (CHSGP) demonstrates efficacy in treating FD; however, the underlying therapeutic mechanism is not yet elucidated. This study aims to investigate the effects of CHSGP on OS and gut microbiota (GM) in FD rats, with a particular emphasis on the role of GM as a potential target for the antioxidant properties of CHSGP.

METHODS: The FD rat model was established with a modified tail-clamp stimulation and the administration of the CHSGP decoction at a dosage of 9.6 g/kg via gavage for a duration of 4 weeks. The GM was depleted by the administration of a cocktail of metronidazole (200 mg/kg), ampicillin (200 mg/kg), neomycin sulfate (200 mg/kg), and vancomycin (100 mg/kg). Fecal microbiota transplantation (FMT) was performed with CHSGP-treated fecal supernatant at a dosage of 10 mL/kg. The gastrointestinal motility was measured using the rates of gastric emptying and small intestine propulsion. Hematoxylin and eosin staining was employed to elucidate the pathological changes, while the transmission electron microscope was used to examine the microstructures of the interstitial cells of Cajal (ICC). Chemiluminescence, colorimetric assay, immunofluorescence co-staining, and western blot assay were employed to identify the OS-related markers (ROS, SOD, NOX4, PRDX1, and TRX2). Sequencing of fecal microbiota was performed utilizing 16S rDNA.

RESULTS: The CHSGP decoction promoted gastrointestinal motility, protected the microstructure of ICC, and reduced OS in FD rats. The GM composition was also regulated by CHSGP. However, these effects disappeared after microbiota depletion. Fortunately, the FMT therapy reinstated them.

CONCLUSION: Chaihushugan powder decoction might regulate the GM to alleviate mitochondrial OS in the gastric tissues of FD rats.}, } @article {pmid40040609, year = {2025}, author = {Liu, FQ and An, ZY and Cui, LJ and Xiao, MY and Wu, YJ and Li, W and Zhang, BS and Yu, L and Feng, J and Liu, ZG and Feng, R and Jiang, ZX and Huang, RB and Jing, HM and Ren, JH and Zhu, XY and Cheng, YF and Li, YH and Zhou, HB and Gao, D and Liu, Y and Yu, F and Wang, X and Qiao, JL and Hu, DH and Wang, LL and Zang, MT and Chen, Q and Qu, QY and Zhou, JY and Li, ML and Chen, YX and Huang, QS and Fu, HX and Li, YY and Wang, QF and Huang, XJ and Zhang, XH and , }, title = {Correlation Between Fecal Microbiota and Corticosteroid Responsiveness in Primary Immune Thrombocytopenia: an Exploratory Study.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {22}, pages = {e2410417}, pmid = {40040609}, issn = {2198-3844}, support = {2023YFC2507803//Key Technologies Research and Development Program/ ; 82300149//National Natural Science Foundation of China/ ; 82130008//National Natural Science Foundation of China/ ; 82230004//National Natural Science Foundation of China/ ; 82350004//National Natural Science Foundation of China/ ; 82430006//National Natural Science Foundation of China/ ; 2024M761208//China Postdoctoral Science Foundation/ ; 2023ZB182//Department of Human Resources and Social Security of Jiangsu Province/ ; 2022-1-4082//Capital Health Research and Development of Special Fund/ ; 7242154//Natural Science Foundation of Beijing Municipality/ ; 7232188//Natural Science Foundation of Beijing Municipality/ ; 71003Y3035//Peking University Medicine/ ; }, mesh = {Humans ; *Purpura, Thrombocytopenic, Idiopathic/drug therapy/microbiology ; *Gastrointestinal Microbiome/drug effects/genetics ; Male ; Female ; *Feces/microbiology ; Middle Aged ; *Adrenal Cortex Hormones/therapeutic use ; Adult ; Aged ; Support Vector Machine ; Metagenomics ; Machine Learning ; }, abstract = {Corticosteroids (CSs) are the initial therapy for immune thrombocytopenia (ITP); however, their efficacy is not adequately predicted. As a novel biomarker, the composition of the gut microbiota is non-invasively tested and altered in patients with ITP. This study aims to develop a predictive model that leverages gut microbiome data to predict the CS response in patients with ITP within the initial four weeks of treatment. Metagenomic sequencing is performed on fecal samples from 212 patients with ITP, 152 of whom underwent CS treatment and follow-up. Predictive models are trained using six machine-learning algorithms, integrating clinical indices and gut microbiome data. The support vector machine (SVM) algorithm-based model has the highest accuracy (AUC = 0.80). This model utilized a comprehensive feature set that combined clinical data (including sex, age, duration, platelet count, and bleeding scales) with selected microbial species (including Bacteroides ovatus, Bacteroides xylanisolvens, and Parabacteroides gordonii), alpha diversities, KEGG pathways, and microbial modules. This study will provide new ideas for the prediction of clinical CS efficacy, enabling informed decision-making regarding the initiation of CS or personalized treatment in patients with ITP.}, } @article {pmid40038211, year = {2025}, author = {Malik, S and Naqvi, SAA and Shadali, AH and Khan, H and Christof, M and Niu, C and Schwartz, DA and Adler, DG}, title = {Fecal Microbiota Transplantation (FMT) and Clinical Outcomes Among Inflammatory Bowel Disease (IBD) Patients: An Umbrella Review.}, journal = {Digestive diseases and sciences}, volume = {70}, number = {5}, pages = {1873-1896}, pmid = {40038211}, issn = {1573-2568}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Inflammatory Bowel Diseases/therapy ; Treatment Outcome ; Remission Induction ; *Colitis, Ulcerative/therapy ; Meta-Analysis as Topic ; }, abstract = {BACKGROUND AND AIMS: Recent systematic reviews and meta-analyses (SRMAs) have shown inconsistent effectiveness of FMT among patients with IBD. This study aimed to appraise the evidence for clinically relevant outcomes with FMT in patients with IBD using published SRMAs.

METHODS: We searched major databases from inception through Nov 2023 to identify SRMAs assessing the effectiveness of FMT in patients with IBD. Primary outcomes included clinical remission, clinical response, endoscopic remission/response, a composite endpoint, and adverse effects. We included SRMAs investigating FMT's effect in patients with IBD using RCTs and observational studies data. Methodological quality and evidence certainty were assessed using AMSTAR 2 and GRADE.

RESULTS: Out of 106 citations, 16 SRMAs were included with varying study sizes (2 to 60 primary studies) and participants (112 to 1169 per SRMA). Five SRMAs assessed FMT in IBD, while 11 focused on Ulcerative Colitis (UC). Seven SRMAs included RCTs only, and nine included both RCTs and observational studies. Methodological quality was critically low in 9 SRMAs (56%) and low in 7 studies (44%). FMT showed clinical remission benefit in all 16 SRMAs, with varying certainty: 3 high, 4 moderate, 4 low, and 5 very low. Endoscopic remission/response was reported in 5 meta-analyses on UC, with 1 high, 3 moderate, and 1 very low certainty. Combined clinical remission and endoscopic response were reported in 3 SRMAs on UC, with 1 low and 2 moderate certainty. Adverse events were reported in 6 SRMAs, with 1 high, 3 moderate, 1 low, and 1 very low certainty.

CONCLUSION: Current evidence shows potential benefits of FMT in IBD, particularly UC, supported by significant associations in 16 meta-analyses. However, poor methodological quality and variability in evidence certainty call for high-quality RCTs to strengthen the evidence.}, } @article {pmid40037667, year = {2025}, author = {Wei, Y and Qin, L and Wu, X and Li, D and Qian, D and Jiang, H and Geng, Q}, title = {Faecal microbiota transplantation combined with platinum-based doublet chemotherapy and tislelizumab as first-line treatment for driver-gene negative advanced non-small cell lung cancer (NSCLC): study protocol for a prospective, multicentre, single-arm exploratory trial.}, journal = {BMJ open}, volume = {15}, number = {3}, pages = {e094366}, pmid = {40037667}, issn = {2044-6055}, mesh = {Humans ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Carcinoma, Non-Small-Cell Lung/therapy/genetics ; Combined Modality Therapy ; *Fecal Microbiota Transplantation/methods ; *Lung Neoplasms/therapy/genetics ; Multicenter Studies as Topic ; Prospective Studies ; Antibodies, Monoclonal, Humanized ; }, abstract = {INTRODUCTION: The standard first-line treatment for driver-gene negative advanced non-small cell lung cancer (NSCLC) is chemotherapy combined with immunotherapy. However, owing to the immune microenvironment imbalance and immune status impairment caused by repeated chemotherapy, as well as the primary or secondary resistance to immune checkpoint inhibitors, the efficacy of immunotherapy combined with chemotherapy remains unsatisfactory. Recent studies have shown that faecal microbiota transplantation (FMT) can modulate the intestinal microflora, influence the tumour immune microenvironment and even enhance the efficacy of immunotherapy. Hence, we conduct such a prospective, exploratory study to evaluate the efficacy and safety of integrating FMT with standard first-line treatment in patients with driver-gene negative advanced NSCLC.

METHODS AND ANALYSIS: FMT-JSNO-02 (NCT06403111) is a prospective, multicentre, single-arm exploratory study. It is planned to include 62 cases of previously untreated driver-gene negative, Eastern Cooperative Oncology Group Performance Status 0-1, programmed death ligand 1<50% advanced NSCLC patients, who will be given FMT by orally ingested stool capsules on the basis of standard first-line treatment of chemotherapy combined with immunotherapy. The primary endpoint of this study is the 12-month progression-free survival rate.

ETHICS AND DISSEMINATION: The study was approved by the ethics committee of the Second People's Hospital of Changzhou (number [2024] YLJSA005) and is being conducted in accordance with the principles of the Declaration of Helsinki. The results of this study will be disseminated through publication in a peer-reviewed journal and presentation at scientific conferences.

TRIAL REGISTRATION NUMBER: NCT06403111. Date of registration: 7 May 2024, the first version protocol.}, } @article {pmid40037430, year = {2025}, author = {Gao, J and He, Y and Shi, F and Hou, F and Wu, X and Yi, Y and Zhang, Y and Gong, Q}, title = {Activation of Sirt6 by icariside Ⅱ alleviates depressive behaviors in mice with poststroke depression by modulating microbiota-gut-brain axis.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.03.002}, pmid = {40037430}, issn = {2090-1224}, abstract = {BACKGROUND: Sirt6-mediated gut microbiota plays a vital role in poststroke depression (PSD). Icariside Ⅱ (ICS Ⅱ) is a naturally-occurring neuroprotectant with Sirt6 induction potency. However, it is unknown whether ICS Ⅱ protects against PSD through modulation of gut microbiota.

OBJECTIVE: This study aimed to reveal the effect and potential mechanisms of ICS Ⅱ on PSD, and the role of the microbiota-gut-brain axis was investigated.

METHODS: Using middle cerebral artery occlusion (MCAO) and chronic unpredictable mild stress (CUMS) to establish post-stroke depression (PSD) mice, we assessed anti-depressant effects of ICS Ⅱ via behavioral tests, immunohistochemistry, and western blot. Transcriptome profiling, molecular docking, and surface plasmon resonance were used to identify key targets. 16S rDNA genomic-derived taxonomic profiling and fecal microbiota transplantation (FMT) were conducted to figure out the mechanistic role of the gut microbiota and short-chain fatty acids (SCFAs).

RESULTS: ICS Ⅱ ameliorated depressive-like behaviors in PSD mice as evidenced by sucrose preference test, forced swimming test and tail suspension test. ICS Ⅱ restored mitochondrial function, reduced oxidative damage and pro-inflammatory cytokines both in brain and intestine through regulation of Sirt6/NF-κB pathway. ICS Ⅱ significantly increased the abundance of gut microbiota (such asAkkermansia and Ligilactobacillus), enhanced SCFAs concentrations, repaired intestinal barrier integrity and upreglated the tight junction protein expression. FMT from ICS II-treated mice replicated these benefits, confirming gut microbiota's role. Mechanistically, ICS Ⅱ directly bound to Sirt6 and enhanced its activity. However, ICS Ⅱ-mediated neuroprotection was neutralized in PSD mice or hydrogen peroxide-induced enteric glial cells when Sirt6 was absent.

CONCLUSION: Our findings expand the pharmacological properties of ICS II by demonstrating its ability to ameliorate PSD through modulation of the microbiota-gut-brain axis. ICS Ⅱ, as a novel Sirt6 activator, could be translated into an alternative microbiota-targeted avenue for coping with PSD.}, } @article {pmid40037353, year = {2025}, author = {Tian, S and Kim, MS and Zhao, J and Heber, K and Hao, F and Koslicki, D and Tian, S and Singh, V and Patterson, AD and Bisanz, JE}, title = {A designed synthetic microbiota provides insight to community function in Clostridioides difficile resistance.}, journal = {Cell host & microbe}, volume = {33}, number = {3}, pages = {373-387.e9}, pmid = {40037353}, issn = {1934-6069}, support = {R00 AI147165/AI/NIAID NIH HHS/United States ; R35 GM151045/GM/NIGMS NIH HHS/United States ; T32 DK120509/DK/NIDDK NIH HHS/United States ; U01 DK119702/DK/NIDDK NIH HHS/United States ; }, mesh = {*Clostridioides difficile/drug effects/physiology ; Animals ; Humans ; *Fecal Microbiota Transplantation/methods ; Mice ; *Gastrointestinal Microbiome/physiology ; Feces/microbiology ; *Clostridium Infections/microbiology/therapy ; Anti-Bacterial Agents/pharmacology ; Disease Models, Animal ; Bile Acids and Salts/metabolism ; }, abstract = {Clostridioides difficile, a major cause of antibiotic-associated diarrhea, is suppressed by the gut microbiome, but the precise mechanisms are not fully described. Through a meta-analysis of 12 human studies, we designed a synthetic fecal microbiota transplant (sFMT1) by reconstructing microbial networks negatively associated with C. difficile colonization. This lab-built 37-strain consortium formed a functional community suppressing C. difficile in vitro and in animal models. Using sFMT1 as a tractable model system, we find that bile acid 7α-dehydroxylation is not a determinant of sFMT1 efficacy while one strain performing Stickland fermentation-a pathway of competitive nutrient utilization-is both necessary and sufficient for the suppression of C. difficile, replicating the efficacy of a human fecal transplant in a gnotobiotic mouse model. Our data illustrate the significance of nutrient competition in suppression of C. difficile and a generalizable approach to interrogating complex community function through robust methods to leverage publicly available sequencing data.}, } @article {pmid40036939, year = {2025}, author = {Mallick, K and Khodve, G and Ruwatia, R and Banerjee, S}, title = {Gut microbes: Therapeutic Target for neuropsychiatric disorders.}, journal = {Journal of psychiatric research}, volume = {184}, number = {}, pages = {27-38}, doi = {10.1016/j.jpsychires.2025.02.031}, pmid = {40036939}, issn = {1879-1379}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/therapy/microbiology ; *Mental Disorders/microbiology/therapy ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation ; Animals ; Prebiotics ; }, abstract = {Neuropsychiatric diseases encompass a range of mental and neurological disorders that have a significant and far-reaching effect on an individual's quality of life. These conditions affect not only the mental status but also the physical well-being of individuals, which leads to weakened immune systems and other diseases. Emerging research underscores a significant connection between the gut microbiome and neuropsychiatric diseases, suggesting that microbial communities within the gastrointestinal tract may influence brain function and mental health. Gut dysbiosis is caused by various factors, including stress, diet, inappropriate usage of antibiotics, infections, and so on, all of which can disrupt numerous pathways, resulting in abnormal neurotransmitter signaling, inflammation, and impaired brain function. Similarly, various neuropsychiatric diseases can disrupt the specific microbiome in the gut, leading to gut dysbiosis, often impairing memory and cognitive function. The growing evidence supporting the role of gut dysbiosis in neuropsychiatric disorders has opened up new avenues for therapeutic interventions. Modulating the gut microbiome through strategies such as probiotics, prebiotics, or fecal microbiota transplantation has shown promising results in various studies of neuropsychiatric disorders. However, further research is needed to fully elucidate the mechanisms involved in gut dysbiosis-associated brain changes to develop effective and personalized treatment strategies for neuropsychiatric diseases.}, } @article {pmid40035163, year = {2025}, author = {Longhitano, A and Roder, C and Blackmore, T and Campbell, A and May, M and Athan, E}, title = {Australasian Society of Infectious Diseases updated guidelines for the management of Clostridioides difficile infection in adults and children in Australia and New Zealand.}, journal = {Internal medicine journal}, volume = {55}, number = {3}, pages = {503-513}, doi = {10.1111/imj.16638}, pmid = {40035163}, issn = {1445-5994}, mesh = {Adult ; Child ; Humans ; *Anti-Bacterial Agents/therapeutic use ; Australia/epidemiology ; *Clostridioides difficile ; *Clostridium Infections/epidemiology/therapy/diagnosis/drug therapy ; *Disease Management ; Fecal Microbiota Transplantation/methods ; Fidaxomicin/therapeutic use ; Metronidazole/therapeutic use/administration & dosage ; New Zealand/epidemiology ; Societies, Medical/standards ; Vancomycin/therapeutic use ; }, abstract = {Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality within the Australian population. Treatment recommendations for CDI pose challenges at both community and hospital-based levels due to the recurrent, refractory and potentially severe nature of the disease. Since the last published Australasian guidelines in 2016, new therapeutic options are available, prompting a necessary update to management recommendations. On behalf of the Australasian Society of Infectious Diseases, we present the updated guidelines for the management of CDI in adults and children exploring the changes to treatment recommendations - including the replacement of oral metronidazole with vancomycin for initial CDI and the emerging role for fidaxomicin and faecal-microbiota transplant.}, } @article {pmid40033229, year = {2025}, author = {Sóti, Á and Nagy, G and Győri, Z and Vass, T and Hetzman, L and Fenyves, BG and Varga, C}, title = {Tension pneumothorax from large bowel herniation and perforation as a late presentation of traumatic diaphragmatic hernia during pregnancy: a case report.}, journal = {International journal of emergency medicine}, volume = {18}, number = {1}, pages = {40}, pmid = {40033229}, issn = {1865-1372}, abstract = {BACKGROUND: Diaphragmatic hernias can be congenital or acquired, with trauma being the primary cause of the latter. Both types may have delayed presentations, with abdominal organs protruding into the thoracic cavity, causing symptoms of varying severity. Pregnancy can sometimes precipitate the condition. Tension pneumothorax resulting from bowel perforation into the thorax is exceptionally rare, with only a few cases reported. To the best of the authors knowledge, this is the third documented case of a late-presenting trauma-related diaphragmatic hernia during pregnancy, complicated by tension pneumothorax.

CASE PRESENTATION: A 30-year-old woman, 29 weeks pregnant, was referred to Semmelweis University emergency department with moderate dyspnea. Initial investigation revealed tension pneumothorax. Chest tube placement released air, pus, and feces. Computer tomography identified a diaphragmatic hernia with bowel incarceration and perforation as the underlying cause. The patient underwent a delayed cesarean section and surgical repair, with a good outcome. A history of thoracic trauma eight years prior was later revealed.

CONCLUSION: Evaluating pregnant patients with shortness of breath in the emergency department is challenging. Identifying a history of thoracic or abdominal trauma is crucial, as this can raise the suspicion of diaphragmatic hernia, which can present with a wide range of symptoms. Spontaneous tension pneumothorax in pregnant women is extremely rare and requires cautious management. A multidisciplinary approach is crucial for the successful treatment of maternal diaphragmatic hernia.}, } @article {pmid40027572, year = {2025}, author = {Zhang, JG and Wang, YW and Wang, QY and Wen, B}, title = {Clinical features and risk factors for combined Klebsiella pneumoniae infection in patients with liver cirrhosis.}, journal = {World journal of hepatology}, volume = {17}, number = {2}, pages = {103648}, pmid = {40027572}, issn = {1948-5182}, abstract = {This article discusses the findings presented by Zhang et al. They analyzed the risk factors and clinical characteristics associated with Klebsiella pneumoniae infection in patients with liver cirrhosis treated at a hospital in Beijing. In this article, we focus on the connection between chronic kidney disease and the intestinal microbiota, and propose microbiota transplantation as a potential treatment for this patient group. We also examine an intriguing phenomenon related to hepatic encephalopathy, and provide insights into the future research.}, } @article {pmid40027490, year = {2025}, author = {Xie, C and Cheng, J and Chen, P and Yan, X and Luo, C and Qu, H and Shu, D and Ji, J}, title = {Integrating gut and IgA-coated microbiota to identify Blautia as a probiotic for enhancing feed efficiency in chickens.}, journal = {iMeta}, volume = {4}, number = {1}, pages = {e264}, pmid = {40027490}, issn = {2770-596X}, abstract = {This study explores the role of IgA-coated bacteria in improving feed efficiency in chickens, offering a novel perspective for probiotic screening. Chickens with high feed efficiency were found to have a greater abundance of Gram-positive bacteria, while low feed efficiency chickens exhibited higher levels of Gram-negative bacteria and potential pathogens. Through fecal microbiota transplantation (FMT) and integrating analysis of cecal and IgA-coated microbiota, we precisely identified Blautia as a key genus linked to improved feed efficiency. Further validation demonstrated that Blautia coccoides, a representative species of this genus, enhances feed efficiency and activates B cells to produce Immunoglobulin A (IgA), both in vivo and in vitro. Our findings provide new insights into the potential of IgA-coated bacteria as functional probiotics, offering a promising strategy for enhancing feed efficiency in animal production.}, } @article {pmid40027485, year = {2025}, author = {Liu, Y and Li, H and Sun, T and Sun, G and Jiang, B and Liu, M and Wang, Q and Li, T and Cao, J and Zhao, L and Xiao, F and Zhao, F and Cui, H}, title = {Gut microbiome and metabolome characteristics of patients with cholesterol gallstones suggest the preventive potential of prebiotics.}, journal = {iMeta}, volume = {4}, number = {1}, pages = {e70000}, pmid = {40027485}, issn = {2770-596X}, abstract = {Cholesterol gallstones (CGS) still lack effective noninvasive treatment. The etiology of experimentally proven cholesterol stones remains underexplored. This cross-sectional study aims to comprehensively evaluate potential biomarkers in patients with gallstones and assess the effects of microbiome-targeted interventions in mice. Microbiome taxonomic profiling was conducted on 191 samples via V3-V4 16S rRNA sequencing. Next, 60 samples (30 age- and sex-matched CGS patients and 30 controls) were selected for metagenomic sequencing and fecal metabolite profiling via liquid chromatography-mass spectrometry. Microbiome and metabolite characterizations were performed to identify potential biomarkers for CGS. Eight-week-old male C57BL/6J mice were given a lithogenic diet for 8 weeks to promote gallstone development. The causal relationship was examined through monocolonization in antibiotics-treated mice. The effects of short-chain fatty acids such as sodium butyrate, sodium acetate (NaA), sodium propionate, and fructooligosaccharides (FOS) on lithogenic diet-induced gallstones were investigated in mice. Gut microbiota and metabolites exhibited distinct characteristics, and selected biomarkers demonstrated good diagnostic performance in distinguishing CGS patients from healthy controls. Multi-omics data indicated associations between CGS and pathways involving butanoate and propanoate metabolism, fatty acid biosynthesis and degradation pathways, taurine and hypotaurine metabolism, and glyoxylate and dicarboxylate metabolism. The incidence of gallstones was significantly higher in the Clostridium glycyrrhizinilyticum group compared to the control group in mice. The grade of experimental gallstones in control mice was significantly higher than in mice treated with NaA and FOS. FOS could completely inhibit the formation of gallstones in mice. This study characterized gut microbiome and metabolome alterations in CGS. C. glycyrrhizinilyticum contributed to gallstone formation in mice. Supplementing with FOS could serve as a potential approach for managing CGS by altering the composition and functionality of gut microbiota.}, } @article {pmid40027479, year = {2025}, author = {Shi, Y and Chen, Z and Fang, T and Chen, X and Deng, Y and Qin, H and Lian, M and Shen, J and Zong, Y and Chu, H and Hoebinger, C and Guo, H and Yuan, Z and Zheng, J and Zhou, Y and Pan, Y and Mendes, BG and Lang, S and Hendrikx, T and Zeng, S and Cao, H and Yang, L and Chen, L and Chen, P and Dai, L and Wang, H and Yin, S and Zhu, S and Ma, X and Schnabl, B and Chen, H and Duan, Y}, title = {Gut microbiota in treating inflammatory digestive diseases: Current challenges and therapeutic opportunities.}, journal = {iMeta}, volume = {4}, number = {1}, pages = {e265}, pmid = {40027479}, issn = {2770-596X}, support = {P30 DK120515/DK/NIDDK NIH HHS/United States ; P50 AA011999/AA/NIAAA NIH HHS/United States ; }, abstract = {Accumulating evidence indicates that the gut microbiota is intricately involved in the initiation and progression of human diseases, forming a multidirectional regulatory axis centered on intestinal microbiota. This article illustrates the challenges in exploring the role of the gut microbiota in inflammatory digestive diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD) and inflammatory bowel disease (IBD), and summarizes the existing microbiome-focused treatment strategies (probiotics, prebiotics, symbiotics, fecal microbiota transplantation, and bacteriophages therapy), emerging technologies (gut microbiome-on-a-chip and artificial intelligence), as well as possible future research directions. Taken together, these therapeutic strategies and technologies present both opportunities and challenges, which require researchers and clinicians to test the rationality and feasibility of various therapeutic modalities in continuous practice.}, } @article {pmid40026419, year = {2025}, author = {Marizzoni, M and Tournier, BB and Chevalier, C and Saleri, S and Lathuilière, A and Ceyzériat, K and Paquis, A and Park, R and Troesch, E and Cattaneo, A and Millet, P and Frisoni, GB}, title = {Stools from a human APOEe2 donor reduces amyloid and tau pathology and increases neuroinflammation in a 3xTg AD mouse model.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1539067}, pmid = {40026419}, issn = {1663-4365}, abstract = {BACKGROUND: The mechanisms underlying the protective effect of the e2 variant of the APOE gene (APOEe2) against Alzheimer's disease (AD) have not been elucidated. We altered the microbiota of 3xTgAD mice by fecal microbiota transplantation from a human APOEe2 donor (e2-FMT) and tested the effect of microbiota perturbations on brain AD pathology.

METHODS: FMT of bacteria isolated from stools of untreated 3xTgAD mice (M-FMT) or e2-FMT were transplanted in 15-month-old 3xTgAD mice. FMT was done alone or in combination with antibiotic and proton-pump inhibitor following the Microbiota Transfer Therapy protocol (MTT). The effect of donor (M or e2) and transplantation protocol (FMT or MTT) on hippocampal amyloid, tau pathology and neuroinflammation were assessed at the end of the treatment.

RESULTS: e2-FMT reduced amyloid, and tau pathology as well as increased neuroinflammation as compared with M-FMT. MTT was associated with reduced number of Aβ40+ plaques and tau pathology. Low levels of amyloid were associated with high levels of pro-inflammatory molecules in e2-FMT mice. These associations were partially attenuated by MTT.

CONCLUSION: Bacteria from a human APOEe2 donor reduced AD pathology and increased neuroinflammation in mice suggesting that the gut microbiota may be a mediator of the protective effect of APOEe2.}, } @article {pmid40025650, year = {2025}, author = {Qi, C and Li, Z and Tu, H and Sun, F and Guo, W and Di, C and He, R and Ze, X and Zhang, L and Gao, R and Hu, P and Yang, W and Li, K and Liu, J and Pan, X and Jin, Z and Sun, J}, title = {2'-FL and cross-feeding bifidobacteria reshaped the gut microbiota of infants with atopic dermatitis ex vivo and prevented dermatitis in mice post-microbiota transplantation through retinol metabolism activation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2474148}, pmid = {40025650}, issn = {1949-0984}, mesh = {Animals ; *Dermatitis, Atopic/prevention & control/microbiology/therapy/metabolism ; *Gastrointestinal Microbiome/drug effects ; Mice ; Humans ; *Trisaccharides/metabolism/administration & dosage ; Infant ; *Vitamin A/metabolism ; Milk, Human/microbiology/chemistry ; Fatty Acids, Volatile/metabolism ; *Bifidobacterium/metabolism ; Probiotics/administration & dosage ; Disease Models, Animal ; Female ; Fecal Microbiota Transplantation ; Male ; }, abstract = {2'-Fucosyllactose (2'-FL), a predominant human milk oligosaccharide, plays a crucial role in the development of the infant gut microbiota and immune system. However, the microbiota of infants with atopic dermatitis (AD) often has difficulty utilizing 2'-FL. Here, we found that strains from human milk, Bifidobacterium bifidum FN120 and Bifidobacterium longum subsp. longum FN103, utilized 2'-FL for growth by cross-feeding. Through an ex vivo continuous fermentation system, we found that 2'-FL and cross-feeding bifidobacteria synergistically enhanced the production of short-chain fatty acids (SCFAs), particularly acetate and propionate, while reshaping the gut microbiota in infants with AD. The reshaped microbiota was then transplanted into oxazolone-induced mice. We observed that AD symptoms in mice were effectively prevented, with significant changes in the ileum microbiota and increased intestinal SCFA levels. RNA sequencing analysis of Peyer's patches in the small intestine revealed activation of the retinol metabolic pathway. Nontargeted metabolomics analysis revealed a significant increase in plasma retinoate levels, which correlated markedly with AD-related markers. Collectively, our study demonstrated that supplementation with cross-feeding bifidobacteria and 2'-FL reshaped the gut microbiota, activated retinol metabolic pathways, promoted immune tolerance, and thereby prevented AD. Our findings provide novel insights into the therapeutic potential of combining prebiotics and probiotics to modulate the gut - skin axis and support immune tolerance in early life, offering a promising strategy for infantile AD management and prevention.}, } @article {pmid40025585, year = {2025}, author = {Guo, H and Jiang, H and Liu, H}, title = {Case report of clostridium difficile infection after rectal resection with ileostomy.}, journal = {World journal of surgical oncology}, volume = {23}, number = {1}, pages = {70}, pmid = {40025585}, issn = {1477-7819}, mesh = {Humans ; Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile/isolation & purification ; *Clostridium Infections/etiology/therapy/microbiology ; Fecal Microbiota Transplantation/methods ; *Ileostomy/adverse effects ; *Postoperative Complications/microbiology/therapy ; Prognosis ; *Rectal Neoplasms/surgery/pathology ; }, abstract = {Colorectal cancer is the third most common cancer worldwide, with high incidence and mortality rates. Surgical resection is the primary treatment for rectal cancer. To reduce the occurrence and severity of postoperative complications such as anastomotic leakage, prophylactic ileostomy is often performed concurrently. However, following ileostomy creation, there is a disruption in intestinal ecology, making patients susceptible to clostridium difficile infection. clostridium difficile is a Gram-positive anaerobic spore-forming bacterium that is resistant to most antibiotics due to spore formation, leading to high recurrence rates and treatment failure. Additionally, in the early stages of clostridium difficile infection, increased ileostomy output can be challenging to differentiate from normal postoperative conditions, potentially resulting in missed diagnosis, delayed treatment, and increased healthcare burden.This case report describes a case of high out-put ileostomy caused by clostridium difficile infection following rectal resection with ileostomy, which was successfully treated by fecal microbiota transplantation, providing evidence-based medicine for clinical practice.}, } @article {pmid40024791, year = {2025}, author = {Kushima, H and Ishii, H}, title = {Cryptococcosis.}, journal = {Medical mycology journal}, volume = {66}, number = {1}, pages = {27-31}, doi = {10.3314/mmj.25.001}, pmid = {40024791}, issn = {2186-165X}, mesh = {Humans ; *Cryptococcosis/epidemiology/diagnosis/drug therapy/microbiology ; Cryptococcus neoformans ; Antifungal Agents/therapeutic use ; Animals ; Immunocompromised Host ; Antigens, Fungal/blood ; }, abstract = {Approximately one million new cases of cryptococcosis develop each year worldwide, resulting in approximately 600,000 deaths. Most cases occurred in HIV patients from African countries south of the Sahara Desert. In light of this situation, in 2022, the World Health Organization presented a list of priority fungal pathogens to guide research, development, and public health action, with Cryptococcus neoformans as the most important critical fungus. In contrast, a recent retrospective study in developed countries showed that 90% of cases with cryptococcosis were non-HIV patients, including immunocompetent individuals. Underlying diseases of non-HIV immunocompromised patients include cancer and solid organ transplantation. High serum titers cryptococcal antigens independently predicted the risk of central nervous system involvement. Even if the patient is asymptomatic, high antigen levels are considered a possibility of cryptococcal meningitis, and a spinal fluid examination may be recommended. The absence of a history of contact with pigeons should not be used as a basis for denying cryptococcosis because C. neoformans is often detected in old and dried feces of chickens other than pigeons. Donor-derived cryptococcosis is a unique feature of cryptococcosis in solid organ transplant recipients. Pre-transplant screening tests for cryptococcosis, pre-transplant treatment for the donor, and prophylactic antifungal therapy for the recipient may be useful. Defense against cryptococcal infection is regulated by various mechanisms, including Th1, Th2, and Th17 immune responses. Molecularly targeted medicines that target specific cytokines or surface antigen molecules have been widely used with excellent clinical efficacy for the treatment of various diseases. Since cryptococcosis has been recently reported to develop during the use of certain medicines, such as ibrutinib and eculizumab, clinicians need to be mindful that the number of similar cases may increase in the future.}, } @article {pmid40024538, year = {2025}, author = {Sliti, A and Kim, RH and Lee, D and Shin, JH}, title = {Whole genome sequencing and In silico analysis of the safety and probiotic features of Lacticaseibacillus paracasei FMT2 isolated from fecal microbiota transplantation (FMT) capsules.}, journal = {Microbial pathogenesis}, volume = {202}, number = {}, pages = {107405}, doi = {10.1016/j.micpath.2025.107405}, pmid = {40024538}, issn = {1096-1208}, mesh = {*Probiotics/adverse effects ; *Whole Genome Sequencing ; Genome, Bacterial ; *Fecal Microbiota Transplantation ; Humans ; *Lacticaseibacillus paracasei/genetics/isolation & purification/classification ; Phylogeny ; Computer Simulation ; Virulence Factors/genetics ; Feces/microbiology ; Capsules ; Plasmids/genetics ; Prophages/genetics ; Multigene Family ; Gastrointestinal Microbiome ; Clustered Regularly Interspaced Short Palindromic Repeats ; }, abstract = {Lacticaseibacillus paracasei is widely used as a probiotic supplement and food additive in the medicinal and food industries. However, its application requires careful evaluation of safety traits associated with probiotic pathogenesis, including the transfer of antibiotic-resistance genes, the presence of virulence and pathogenicity factors, and the potential disruptions of the gut microbiome and immune system. In this study, we conducted whole genome sequencing (WGS) of L. paracasei FMT2 isolated from fecal microbiota transplantation (FMT) capsules and performed genome annotation to assess its probiotic and safety attributes. Our comparative genomic analysis assessed this novel strain's genetic attributes and functional diversity and unraveled its evolutionary relationships with other L. paracasei strains. The assembly yielded three contigs: one corresponding to the chromosome and two corresponding to plasmids. Genome annotation revealed the presence of 2838 DNA-coding sequences (CDS), 78 ribosomal RNAs (rRNAs), 60 transfer RNAs (tRNAs), three non-coding RNAs (ncRNAs), and 126 pseudogenes. The strain lacked antibiotic resistance genes and pathogenicity factors. Two intact prophages, one Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) region, and three antimicrobial peptide gene clusters were identified, highlighting the genomic stability and antimicrobial potential of the strain. Furthermore, genes linked to probiotic functions, such as mucosal colonization, stress resistance, and biofilm formation, were characterized. The pan-genome analysis identified 3358 orthologous clusters, including 1775 single-copy clusters, across all L. paracasei strains. Notably, L. paracasei FMT2 contained many unique singleton genes, potentially contributing to its distinctive probiotic properties. Our findings confirm the potential of L. paracasei FMT2 for food and therapeutic applications based on its probiotic profile and safety.}, } @article {pmid40024260, year = {2025}, author = {Karmisholt Grosen, A and Mikkelsen, S and Aas Hindhede, L and Ellegaard Paaske, S and Dahl Baunwall, SM and Mejlby Hansen, M and Frederik Dahlerup, J and Steen Mortensen, M and Rask Licht, T and Kjærgaard Boldsen, J and Tornvig Erikstrup, L and Lodberg Hvas, C and Erikstrup, C}, title = {Effects of clinical donor characteristics on the success of faecal microbiota transplantation for patients in Denmark with Clostridioides difficile infection: a single-centre, prospective cohort study.}, journal = {The Lancet. Microbe}, volume = {6}, number = {5}, pages = {101034}, doi = {10.1016/j.lanmic.2024.101034}, pmid = {40024260}, issn = {2666-5247}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; *Clostridium Infections/therapy/microbiology ; Denmark ; Prospective Studies ; Middle Aged ; Clostridioides difficile ; Aged ; Feces/microbiology ; Adult ; Treatment Outcome ; Donor Selection ; *Tissue Donors ; Diarrhea/therapy/microbiology ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an effective treatment for patients with recurrent Clostridioides difficile infection, but donor selection can influence its clinical success. We aimed to investigate the effect of clinical donor characteristics on FMT outcomes in patients with C difficile infection.

METHODS: In this single-centre, prospective cohort study, we included all donors who fulfilled the national criteria for faeces donation and delivered donations to the Centre for Faecal Microbiota Transplantation, Aarhus University Hospital, Denmark, between May 2, 2016, and Oct 31, 2023, and corresponding recipients treated with one-dose FMT for primary or recurrent C difficile infection. In mixed-effects models, we evaluated the effect of donor sex, age, BMI, smoking status, donation stool consistency, total donation weight, antibiotic use, Helicobacter pylori carriage, birth mode, donor-recipient sex concordance, and the alpha diversity of faeces donations on FMT outcomes in recipients. The primary outcome was the resolution of diarrhoea associated with C difficile infection in patients 8 weeks after FMT.

FINDINGS: Among 145 blood donors who also donated faeces, 115 (79·3%) were men and 30 (20·7%) were women. 90 (62·1%) provided faeces for 1351 evaluable FMTs in 952 patients with C difficile infection. 1037 (76·8%) FMTs were administered through oral capsules, 151 (11·2%) via colonoscopy, and 163 FMTs (12·1%) via nasojejunal tube. Antibiotic use 3-12 months before donation decreased the effectiveness of FMT (odds ratio 0·55 [95% CI 0·33-0·91]; p=0·019). Compared with donations with a Bristol Stool Form Scale (BSFS) score of 3, donations with a score of 4 (odds ratio 1·38 [95% CI 1·04-1·83]; p=0·024) and 5 or above (2·89 [1·33-6·26]; p=0·0072) showed improved FMT effectiveness. Donor sex, BMI, smoking status, H pylori carriage, birth mode, total donation weight, and donor-recipient sex concordance did not affect FMT outcomes.

INTERPRETATION: Expanding current donor selection criteria to avoid antibiotic use in the 12 months preceding donation and including donations with a BSFS score of 5 might improve FMT outcomes for patients with C difficile infection. Our findings call for the revision of current clinical donor screening practices, and future studies could further optimise the criteria for selecting optimal faeces donors.

FUNDING: Innovation Fund Denmark.}, } @article {pmid40023843, year = {2025}, author = {Golomb, SM and Guldner, IH and Aleksandrovic, E and Fross, SR and Liu, X and Diao, L and Liang, K and Wu, J and Wang, Q and Lopez, JA and Zhang, S}, title = {Temporal dynamics of immune cell transcriptomics in brain metastasis progression influenced by gut microbiome dysbiosis.}, journal = {Cell reports}, volume = {44}, number = {3}, pages = {115356}, pmid = {40023843}, issn = {2211-1247}, support = {R01 CA222405/CA/NCI NIH HHS/United States ; R21 CA263798/CA/NCI NIH HHS/United States ; R01 CA194697/CA/NCI NIH HHS/United States ; R01 CA255064/CA/NCI NIH HHS/United States ; F31 CA261046/CA/NCI NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome/drug effects/immunology ; Animals ; *Dysbiosis/immunology/microbiology/genetics ; *Brain Neoplasms/secondary/immunology/genetics/pathology/microbiology ; Mice ; Disease Progression ; Microglia/immunology/metabolism ; *Transcriptome/genetics ; Mice, Inbred C57BL ; T-Lymphocytes/immunology/metabolism ; Humans ; Female ; }, abstract = {Interactions between metastatic cancer cells and the brain microenvironment regulate brain metastasis (BrMet) progression. Central nervous system (CNS)-native and peripheral immune cells influence the BrMet immune landscape, but the dynamics and factors modulating this microenvironment remain unclear. As the gut microbiome impacts CNS and peripheral immune activity, we investigated its role in regulating immune response dynamics throughout BrMet stages. Antibiotic-induced (ABX) gut dysbiosis significantly increased BrMet burden versus controls but was equalized with fecal matter transplantation, highlighting microbiome diversity as a regulator of BrMet. Single-cell sequencing revealed a highly dynamic immune landscape during BrMet progression in both conditions. However, the timing of the monocyte inflammatory response was altered. Microglia displayed an elevated activation signature in late-stage metastasis in ABX-treated mice. T cell and microglia perturbation revealed involvement of these cell types in modulating BrMet under gut dysbiosis. These data indicate profound effects on immune response dynamics imposed by gut dysbiosis across BrMet progression.}, } @article {pmid40023320, year = {2025}, author = {Petracco, G and Faimann, I and Reichmann, F}, title = {Inflammatory bowel disease and neuropsychiatric disorders: Mechanisms and emerging therapeutics targeting the microbiota-gut-brain axis.}, journal = {Pharmacology & therapeutics}, volume = {269}, number = {}, pages = {108831}, doi = {10.1016/j.pharmthera.2025.108831}, pmid = {40023320}, issn = {1879-016X}, mesh = {Humans ; *Gastrointestinal Microbiome ; Animals ; *Inflammatory Bowel Diseases/therapy/microbiology/psychology/physiopathology/complications ; *Mental Disorders/therapy/microbiology ; *Brain/metabolism/physiopathology ; Fecal Microbiota Transplantation/methods ; *Brain-Gut Axis ; }, abstract = {Crohn's disease (CD) and ulcerative colitis (UC) are the two major entities of inflammatory bowel disease (IBD). These disorders are known for their relapsing disease course and severe gastrointestinal symptoms including pain, diarrhoea and bloody stool. Accumulating evidence suggests that IBD is not only restricted to the gastrointestinal tract and that disease processes are able to reach distant organs including the brain. In fact, up to 35 % of IBD patients also suffer from neuropsychiatric disorders such as generalized anxiety disorder and major depressive disorder. Emerging research in this area indicates that in many cases these neuropsychiatric disorders are a secondary condition as a consequence of the disturbed communication between the gut and the brain via the microbiota-gut-brain axis. In this review, we summarise the current knowledge on IBD-associated neuropsychiatric disorders. We examine the role of different pathways of the microbiota-gut-brain axis in the development of CNS disorders highlighting altered neural, immunological, humoral and microbial communication. Finally, we discuss emerging therapies targeting the microbiota-gut-brain axis to alleviate IBD and neuropsychiatric symptoms including faecal microbiota transplantation, psychobiotics, microbial metabolites and vagus nerve stimulation.}, } @article {pmid40022204, year = {2025}, author = {Debray, R and Dickson, CC and Webb, SE and Archie, EA and Tung, J}, title = {Shared environments complicate the use of strain-resolved metagenomics to infer microbiome transmission.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {59}, pmid = {40022204}, issn = {2049-2618}, support = {P2C HD065563/HD/NICHD NIH HHS/United States ; R01AG071684/NH/NIH HHS/United States ; R61AG078470//National Science Foundation/ ; R01 AG071684/AG/NIA NIH HHS/United States ; R61 AG078470/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Bacteria/classification/genetics/isolation & purification ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome/genetics ; Metagenome/genetics ; *Metagenomics/standards ; Papio/microbiology ; *Social Behavior ; *Environmental Microbiology ; Female ; Diet ; Rain ; }, abstract = {BACKGROUND: In humans and other social animals, social partners have more similar microbiomes than expected by chance, suggesting that social contact transfers microorganisms. Yet, social microbiome transmission can be difficult to identify based on compositional data alone. To overcome this challenge, recent studies have used information about microbial strain sharing (i.e., the shared presence of highly similar microbial sequences) to infer transmission. However, the degree to which strain sharing is influenced by shared traits and environments among social partners, rather than transmission per se, is not well understood.

RESULTS: Here, we first use a fecal microbiota transplant dataset to show that strain sharing can recapitulate true transmission networks under ideal settings when donor-recipient pairs are unambiguous and recipients are sampled shortly after transmission. In contrast, in gut metagenomes from a wild baboon population, we find that demographic and environmental factors can override signals of strain sharing among social partners.

CONCLUSIONS: We conclude that strain-level analyses provide useful information about microbiome similarity, but other facets of study design, especially longitudinal sampling and careful consideration of host characteristics, are essential for inferring the underlying mechanisms of strain sharing and resolving true social transmission network. Video Abstract.}, } @article {pmid40020386, year = {2025}, author = {Zhang, W and Qi, X and Han, M and Jia, Q and Li, X and Yin, W and Wang, Y and Wu, H and Shao, H and Peng, C and Su, C and Sai, L}, title = {Activation of Sirt1 by acetate alleviates silicofibrosis: Contribution of the gut microbiota.}, journal = {Ecotoxicology and environmental safety}, volume = {292}, number = {}, pages = {117969}, doi = {10.1016/j.ecoenv.2025.117969}, pmid = {40020386}, issn = {1090-2414}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Silicosis/microbiology ; *Sirtuin 1/metabolism ; Rats ; Male ; Fecal Microbiota Transplantation ; *Acetates/pharmacology ; Rats, Sprague-Dawley ; Bifidobacterium ; Lung/pathology/metabolism ; Dysbiosis ; }, abstract = {Silicosis is a prevalent occupational disease marked by progressive pulmonary fibrosis. Despite its significant health burden, the pathogenesis of silicosis remains unclear, and no specific therapeutic drugs are available. In this study, we developed a novel intervention strategy targeting gut microbiota and investigated its underlying mechanisms. Using 16S rRNA gene sequencing, we observed significant gut microbiota dysbiosis in silicosis rats at different times (1-8 weeks), notably characterized by altered relative abundance of Ruminococcus and Lactobacillus. Fecal microbiota transplantation altered the gut microbiota structure of silicosis rats, alleviated silica-induced lung histopathological injury, with LEfSe analysis identifying Bifidobacterium as a potential biomarker. Treatment with Bifidobacterium reduced the level of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and fibrosis markers (collagen III, α-SMA and vimentin) in the lungs of silicosis rats, accompanied with increased serum acetic acid levels. Acetate, a major metabolite of Bifidobacterium, demonstrated similar protective effects against silicosis in this study, suggesting its role as a key mediator of Bifidobacterium action in the lungs. Both Bifidobacterium and acetate significantly upregulated Sirt1 in intestinal and lung tissues, while Sirt1 inhibition diminished their benefits to silicosis. As a widely studied histone deacetylase, Sirt1 was proven to be markedly reduced in the lungs of silicosis rats in this study. EX-527, a potent Sirt1 inhibitor, could worsen silicosis damage by upregulating the level of TGF-β1 and the degree of Smad2/3 acetylation. Our study highlights the efficacy of postbiotics, such as Bifidobacterium and acetate, and identifies Sirt1 as a promising target for silicosis treatment.}, } @article {pmid40019272, year = {2025}, author = {Peng, C and Lei, P and Qi, H and Zhu, Q and Huang, C and Fu, J and Zhao, C}, title = {Effect of fecal microbiota transplantation on diabetic wound healing through the IL-17A-mTOR-HIF1α signaling axis.}, journal = {Applied and environmental microbiology}, volume = {91}, number = {3}, pages = {e0201924}, pmid = {40019272}, issn = {1098-5336}, support = {2021-ZJ-752//Qinghai Provincial Department of Science and Technology ()/ ; }, mesh = {Animals ; *Wound Healing ; *Fecal Microbiota Transplantation ; Mice ; *TOR Serine-Threonine Kinases/metabolism/genetics ; *Interleukin-17/metabolism/genetics ; Humans ; Signal Transduction ; *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; *Diabetes Mellitus, Experimental/therapy ; Male ; Keratinocytes ; Mice, Inbred C57BL ; Gastrointestinal Microbiome ; }, abstract = {UNLABELLED: Diabetes is the third most common chronic disorder worldwide. Diabetic wounds are a severe complication that is costly and often results in non-traumatic lower limb amputation. Recent investigations have demonstrated that the gut microbiota as a "virtual organ" can regulate metabolic diseases like diabetes. Fecal microbiota transplantation (FMT) is an innovative therapeutic approach for promoting wound healing, but its function remains incompletely defined. A diabetes model was established by supplying mice with a high-fat diet and performing an intraperitoneal injection of streptozotocin. Diabetic wounds were then created, followed by bacterial transplantation. The relevant indexes of wound healing were evaluated to verify the promoting effect of FMT on the diabetic wounds. Human skin keratinocytes were also cultured, and cell scratch experiments were conducted to further investigate the underlying mechanism. The FMT regulated the levels of specific bacteria in the diabetic mice and helped restore the balance of intestinal microbes. This transplantation also enhanced wound healing in the diabetic mice by augmenting the closure rate, accelerating re-epithelialization, and boosting collagen deposition in skin wounds. Furthermore, FMT promoted the production of IL-17A, which significantly enhanced the growth and movement of human keratinocytes. Inhibiting molecules related to the IL-17A-mTOR-HIF1α signaling axis were shown to hinder wound re-epithelialization.This study clarifies the function of the IL-17A-mTOR-HIF1α signaling axis in the utilization of FMT in diabetic wound healing, providing a new therapeutic method and target for promoting the healing of diabetic wounds.

IMPORTANCE: The Intestinal microbiota, as the organ with the largest number of microorganisms in the body, plays a crucial role in the physiological functions of the human body. Normal microbiota can be involved in various functions such as energy absorption, metabolism, and immunity of the body, and microbiota imbalance is related to many diseases such as obesity and diabetes. Diabetes, as one of the world's three major chronic diseases, is a significant health issue that troubles more than a billion people globally. Diabetic wounds are a problem that all diabetic patients must confront when undergoing surgery, and it is an important cause of non-traumatic amputations. Exploring the role of intestinal microorganisms in the wound-healing process of diabetic mice can offer the possibility of using microorganisms as a therapeutic means to intervene in clinically related diseases.}, } @article {pmid40015179, year = {2025}, author = {Patra, D and Dev, G and Hand, TW and Overacre-Delgoffe, A}, title = {Friends close, enemies closer: the complex role of the microbiome in antitumor immunity.}, journal = {Current opinion in immunology}, volume = {93}, number = {}, pages = {102537}, doi = {10.1016/j.coi.2025.102537}, pmid = {40015179}, issn = {1879-0372}, mesh = {Humans ; *Neoplasms/immunology/therapy/microbiology ; *Immunotherapy/methods ; Animals ; *Microbiota/immunology ; Tumor Microenvironment/immunology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/immunology ; }, abstract = {Immunotherapy has achieved remarkable advances in cancer treatment by harnessing the immune system to combat tumors, yet its effectiveness remains inconsistent across patients and tumor types. The microbiota, a diverse assemblage of microorganisms residing at host barrier surfaces, is pivotal in shaping immune responses. This review explores the direct and indirect mechanisms via which the microbiota modulates antitumor immune responses both locally within the tumor microenvironment and systemically by affecting distant tumors. We discuss recent findings linking microbiota-derived metabolites and microbiota-derived antigens with antitumor immunity and immunotherapy response. Additionally, we discuss recent advances in microbiome-based therapies, including fecal microbiota transplantation. We propose the use and development of new analytical techniques to further characterize the complex functions and interactions between the microbiome and immune system. To conclude, we outline recommendations for future research and therapeutic approaches to leverage the microbiome to improve current immunotherapies.}, } @article {pmid40015156, year = {2025}, author = {Tang, L and Li, J and Luan, M and Qin, M and Zhong, C and Zhang, Y and Xie, Y and Shi, M and Qiu, L and Yu, J}, title = {Edgeworthia gardneri (Wall.) Meisn protects against HFD-induced murine atherosclerosis through improving gut microbiota-mediated intestinal barrier integrity.}, journal = {Atherosclerosis}, volume = {403}, number = {}, pages = {119132}, doi = {10.1016/j.atherosclerosis.2025.119132}, pmid = {40015156}, issn = {1879-1484}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Atherosclerosis/prevention & control/microbiology/pathology/metabolism ; *Diet, High-Fat ; Disease Models, Animal ; Male ; Mice, Knockout, ApoE ; Mice, Inbred C57BL ; Plaque, Atherosclerotic ; *Intestinal Mucosa/metabolism/microbiology/drug effects ; Fecal Microbiota Transplantation ; Mice ; *Aortic Diseases/pathology/prevention & control/microbiology/metabolism/genetics ; Aorta/pathology/drug effects/metabolism ; *Plant Extracts/pharmacology ; Tight Junctions/metabolism/drug effects ; Permeability ; Apolipoproteins E/genetics/deficiency ; }, abstract = {BACKGROUND: Gut microbiota plays a crucial role in the development and progression of atherosclerosis. Edgeworthia gardneri (Wall.) Meisn, a member of the Thymelaeaceae family and the Edgeworthia genus, has been previously shown in our studies to attenuate atherogenesis when administered orally as an ethanolic extract (EEEG). However, the interaction between EEEG and gut microbiota, and the mechanism by which gut microbiota exerts anti-atherosclerotic effects, remains unclear.

AIMS: This study aims to determine whether the anti-atherosclerotic properties of EEEG are associated with gut microbiota remodeling.

METHOD: Atherosclerosis was induced in ApoE[-/-] mice using a high-fat diet (HFD). The mice were treated with EEEG or Lactobacillus plantarum for 16 weeks. The composition of gut microbiota was analyzed through 16S rDNA sequencing. To assess whether the anti-atherosclerotic effects of EEEG depend on the gut microbiota, HFD-fed mice were treated with a cocktail of antibiotics or underwent fecal microbiota transplantation (FMT). Simultaneously, plaque areas in the aortic roots and whole aortas of apolipoprotein E deficient (ApoE[-/-]) mice were evaluated using oil red O staining and hematoxylin-eosin staining. Serum levels of LPS, fluorescein isothiocyanate-dextran, and expression levels of tight junction proteins were measured to identify the effects of EEEG on gut barrier dysfunction in HFD-fed ApoE[-/-] mice.

RESULTS: The results revealed that EEEG treatment significantly reduced atherosclerotic lesions by ameliorating lipid accumulation and preserving gut barrier integrity. The protective effects were abrogated by antibiotics administration, concomitant with an increase in gut barrier permeability by decreasing expression of tight junction proteins. The microbial analysis indicated an augmented abundance of Lactobacillus, Turicibacter, Faecalibacterium, Akkermansia, and Desulfovibrio following EEEG treatment. Meanwhile, transplantation of fecal microbiota from EEEG-treated mice exerted the anti-atherosclerotic effect in the high-fat diet (HFD)-fed ApoE[-/-] recipient mice, accompanied by improvement of gut barrier integrity through upregulation of tight junction protein expression. Furthermore, exogenous supplementation of Lactobacillus plantarum mitigated AS in ApoE[-/-] mice and improved the gut epithelial barrier function by increasing the expression level of Zo-1.

CONCLUSION: These results suggest that the anti-atherosclerotic efficacy of EEEG is attributed to the preservation of gut barrier integrity mediated by gut microbiota. EEEG and its enriched Lactobacillus plantarum may be promising adjuncts for AS management.

IMPORTANCE: Atherosclerosis (AS) is the primary pathological basis of cardiovascular disease (CVD). The gut microbiota is known to play an important role in the development and progression of atherosclerosis. In the clinical management of AS, pharmacological classes such as antioxidants, lipid-lowering drugs, and antiplatelet agents are commonly utilized. Despite their ability to decelerate the progression of AS, complications and adverse reactions still limit their application. Edgeworthia gardneri (Wall.) Meisn, a member of the Thymelaeaceae family and Edgeworthia Meisn genus, has been shown in previous studies to attenuate atherogenesis when orally administered as an ethanolic extract (EEEG). However, the interaction between EEEG and the gut microbiota, as well as the mechanism by which the gut microbiota exerts its anti-atherosclerotic effects, remain unclear. The significance of our research lies in identifying the mechanism behind the anti-atherosclerotic effect of Edgeworthia gardneri. The expected results will provide an important scientific basis for the clinical development and application of Edgeworthia gardneri in the prevention and treatment of AS.}, } @article {pmid40013938, year = {2025}, author = {Hou, S and Yu, J and Li, Y and Zhao, D and Zhang, Z}, title = {Advances in Fecal Microbiota Transplantation for Gut Dysbiosis-Related Diseases.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {13}, pages = {e2413197}, pmid = {40013938}, issn = {2198-3844}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Dysbiosis/therapy/microbiology ; *Gastrointestinal Microbiome/physiology ; }, abstract = {This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.}, } @article {pmid40012737, year = {2025}, author = {Yassin, LK and Nakhal, MM and Alderei, A and Almehairbi, A and Mydeen, AB and Akour, A and Hamad, MIK}, title = {Exploring the microbiota-gut-brain axis: impact on brain structure and function.}, journal = {Frontiers in neuroanatomy}, volume = {19}, number = {}, pages = {1504065}, pmid = {40012737}, issn = {1662-5129}, abstract = {The microbiota-gut-brain axis (MGBA) plays a significant role in the maintenance of brain structure and function. The MGBA serves as a conduit between the CNS and the ENS, facilitating communication between the emotional and cognitive centers of the brain via diverse pathways. In the initial stages of this review, we will examine the way how MGBA affects neurogenesis, neuronal dendritic morphology, axonal myelination, microglia structure, brain blood barrier (BBB) structure and permeability, and synaptic structure. Furthermore, we will review the potential mechanistic pathways of neuroplasticity through MGBA influence. The short-chain fatty acids (SCFAs) play a pivotal role in the MGBA, where they can modify the BBB. We will therefore discuss how SCFAs can influence microglia, neuronal, and astrocyte function, as well as their role in brain disorders such as Alzheimer's disease (AD), and Parkinson's disease (PD). Subsequently, we will examine the technical strategies employed to study MGBA interactions, including using germ-free (GF) animals, probiotics, fecal microbiota transplantation (FMT), and antibiotics-induced dysbiosis. Finally, we will examine how particular bacterial strains can affect brain structure and function. By gaining a deeper understanding of the MGBA, it may be possible to facilitate research into microbial-based pharmacological interventions and therapeutic strategies for neurological diseases.}, } @article {pmid40011318, year = {2025}, author = {Sedeek, SA and Farowski, F and Youssafi, S and Tsakmaklis, A and Brodesser, S and El-Attar, MM and Abdelmalek, MO and Vehreschild, MJGT}, title = {In vitro validation concept for lyophilized fecal microbiota products with a focus on bacterial viability.}, journal = {World journal of microbiology & biotechnology}, volume = {41}, number = {3}, pages = {83}, pmid = {40011318}, issn = {1573-0972}, mesh = {Freeze Drying ; Humans ; *Feces/microbiology ; *Microbial Viability ; RNA, Ribosomal, 16S/genetics ; Bile Acids and Salts/analysis ; *Bacteria/genetics/isolation & purification/classification/growth & development ; *Fecal Microbiota Transplantation/methods ; Clostridium Infections/therapy/microbiology ; Germany ; }, abstract = {Fecal microbiota transplantation (FMT) effectively treats recurrent Clostridioides difficile infection (rCDI), typically administered as a fresh or frozen stool suspension through colonoscopy, nasojejunal tube, or oral capsules. Lyophilized fecal microbiota (LFM) are an alternative to frozen FM products. We aimed to assess whether lyophilization affects bacterial viability and metabolite levels and to develop LFM capsules for clinical use in Germany. Fecal donations from pre-screened volunteers were aliquoted and analyzed through microbial cell counting, bacterial culture, 16S rRNA gene amplicon sequencing, and bile acid assays. Results showed higher counts of viable bacterial cells and cultured anaerobes in unprocessed stool compared to freshly processed stool (p = 0.012 and p < 0.001, respectively). No significant difference in viable bacterial counts was found between freshly processed (day 0), lyophilized (day 3) and frozen FM (day 3) (p = 0.15), nor between freshly processed (day 0), lyophilized (days 30 and 90) and frozen FM (day 30) (p = 0.07). lyophilization did not significantly impact bile acid and 16S rRNA profiling. Encapsulation of lyophilized powder required fewer capsules (10-14) than frozen capsules (30). LFM products are a practical, viable alternative to frozen and fresh FM products, potentially improving storage and patient acceptance.}, } @article {pmid40011195, year = {2025}, author = {Li, T and Chen, J and Xu, Y and Ji, W and Yang, S and Wang, X}, title = {Hawthorn Pectin Alleviates DSS-Induced Colitis in Mice by Ameliorating Intestinal Barrier Function and Modulating Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {10}, pages = {5872-5885}, doi = {10.1021/acs.jafc.4c07965}, pmid = {40011195}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Pectins/administration & dosage ; Dextran Sulfate/adverse effects ; Mice ; Male ; *Crataegus/chemistry ; Colon/drug effects/metabolism/microbiology ; Humans ; *Colitis, Ulcerative/microbiology/drug therapy/chemically induced/metabolism/genetics ; *Intestinal Mucosa/metabolism/drug effects/microbiology ; Mice, Inbred C57BL ; Bacteria/classification/isolation & purification/genetics/drug effects ; *Plant Extracts/administration & dosage ; Tumor Necrosis Factor-alpha/genetics/immunology ; Interleukin-6/genetics/immunology ; Interleukin-1beta/genetics/immunology ; *Colitis/microbiology/chemically induced/drug therapy ; Occludin/genetics/metabolism ; Zonula Occludens-1 Protein/genetics/metabolism ; Intestinal Barrier Function ; }, abstract = {Pectin, as a kind of soluble dietary fiber in hawthorns, exhibits a wide range of biological activities. Nevertheless, its role and mechanism in ulcerative colitis (UC) remain unclear. In this study, the effect of hawthorn pectin (HP) against dextran sulfate sodium (DSS)-induced UC in mice and its underlying mechanism were evaluated. HP dramatically alleviated the pathological symptoms related to colitis in mice, displaying an increase in body weight and colon length and inhibition in colon damage. Importantly, HP inhibited the serum levels of inflammation-related factors including tumor necrosis factor-α, IL-1β, and IL-6 as well as decreased the number of F4/80-positive macrophages in the colon. Moreover, the expression levels of ZO-1 and occludin proteins related to intestinal permeability were increased. A significant decrease in a dose-dependent manner at the gut bacterial genus level (such as Alistipes, Colidextribacter, and Blautia) was observed after HP treatment. HP improved the metabolic pathways of gut microbiota and increased the concentrations of short-chain fatty acids in cecal contents of UC mice. Intriguingly, fecal microbiota transplantation intervention with an HP-derived microbiome notably increased the length and relieved histopathological changes of colon in UC mice. Conclusively, our study provided valuable insights into the potential of HP as a prebiotic for maintaining intestinal health and confirmed that HP could ameliorate UC in a gut microbiota-dependent manner.}, } @article {pmid40010549, year = {2025}, author = {Wei, J and Chen, A and Huang, D and Teng, C and Cai, D and Wu, X and Wang, T and Hu, W and Huang, Z and Wang, P and Guan, X and Zheng, X and Chen, X}, title = {Gut microbiome-derived lipopolysaccharides aggravate cognitive impairment via TLR4-mediated inflammatory signaling in neonatal rats following hypoxic-ischemic brain damage.}, journal = {Brain, behavior, and immunity}, volume = {127}, number = {}, pages = {4-24}, doi = {10.1016/j.bbi.2025.02.029}, pmid = {40010549}, issn = {1090-2139}, mesh = {Animals ; *Toll-Like Receptor 4/metabolism ; *Gastrointestinal Microbiome/physiology ; *Lipopolysaccharides/metabolism ; *Cognitive Dysfunction/metabolism/microbiology ; Rats ; *Hypoxia-Ischemia, Brain/metabolism/complications/microbiology ; Animals, Newborn ; Inflammation/metabolism ; Signal Transduction ; Dysbiosis/metabolism ; Rats, Sprague-Dawley ; Male ; Hippocampus/metabolism ; Disease Models, Animal ; }, abstract = {Hypoxic-ischemic brain damage (HIBD) is a leading cause of infant mortality and neurological disabilities in children. Recent evidence indicates that gut microbiota significantly contributes to the development of inflammation and cognitive impairments following brain injury. However, the mechanisms by which gut microbiota influence inflammation and cognitive function in the neonates after HIBD are not well understood. This study established a neonatal rat model of HIBD by the classic Rice-Vannucci technique to investigate gut dysbiosis following hypoxic-ischemic (HI) insult and to elucidate the causal relationship between gut dysbiosis and cognitive impairments. Our results demonstrated that HI insult resulted in significant gut microbial dysbiosis, characterized by an expansion of Enterobacteriaceae. This dysbiosis was associated with intestinal barrier damage, lipopolysaccharides (LPS) leakage, and systemic inflammation. Conversely, administration of aminoguanidine (AG) to inhibit Enterobacteriaceae overgrowth restored intestinal barrier integrity and reduced systemic inflammation. Importantly, AG treatment effectively suppressed microglial activation, neuronal damage, and cognitive impairments in the neonatal rats subjected to HI insult. Additionally, RNA sequencing analysis revealed that differentially expressed genes in both colonic and hippocampal tissues were primarily associated with inflammation and neuronal apoptosis after HI insult. Further mechanistic exploration revealed that AG treatment mitigated intestinal LPS leakage, thereby reducing the activation of the TLR4/MyD88/NF-κB signaling pathway and production of the downstream inflammatory cytokines in both the colon and hippocampus. Notably, fecal microbiota transplantation (FMT) from the HIBD rats to the antibiotic cocktail-treated recipient rats resulted in microglial activation, neuronal damage, and cognitive impairments in the recipients. However, these adverse effects were effectively mitigated in the recipient rats that received FMT from the AG-treated donors, as well as in those undergoing hippocampal TLR4 knockdown. In conclusion, our findings indicate that LPS derived from gut Enterobacteriaceae overgrowth plays a critical role in the TLR4-mediated inflammatory signaling, providing a novel microbiota-based therapeutic approach for cognitive impairments following neonatal HIBD.}, } @article {pmid40008452, year = {2025}, author = {Chen, A and Teng, C and Wei, J and Wu, X and Zhang, H and Chen, P and Cai, D and Qian, H and Zhu, H and Zheng, X and Chen, X}, title = {Gut microbial dysbiosis exacerbates long-term cognitive impairments by promoting intestinal dysfunction and neuroinflammation following neonatal hypoxia-ischemia.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2471015}, pmid = {40008452}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology/complications ; Rats ; *Cognitive Dysfunction/microbiology/etiology ; *Hypoxia-Ischemia, Brain/complications/microbiology ; Animals, Newborn ; Fecal Microbiota Transplantation ; Toll-Like Receptor 4/genetics/metabolism ; Male ; Lipopolysaccharides/blood ; *Neuroinflammatory Diseases/microbiology/etiology ; Rats, Sprague-Dawley ; Disease Models, Animal ; Dexamethasone ; Intestines/microbiology/physiopathology ; }, abstract = {Neonatal hypoxic-ischemic brain damage (HIBD) is considered as a major cause of long-term cognitive impairments in newborns. It has been demonstrated that gut microbiota is closely associated with the prognosis of various neurological disorders. However, the role of microbiota-gut-brain axis on cognitive function following neonatal HIBD remains elusive. In this experiment, the correlation analysis supported the involvement of gut microbial changes following hypoxic-ischemic (HI) insult in the development of long-term cognitive impairments. Subsequent experiment revealed the involvement of the intestinal dysfunction in the hippocampal neuroinflammation and synaptic injury. In causal relationship validation experiments, fecal microbiota transplantation (FMT) from cognitively normal rats could restore gut microbial composition, improve intestinal dysfunction, reduce the serum levels of lipopolysaccharides (LPS) and inflammatory mediators, and alleviate neuroinflammation, synaptic damage and cognitive impairments in neonatal HIBD recipient rats. Conversely, the FMT from neonatal HIBD rats could induce above adverse pathological changes in the normal recipient rats. Moreover, oral administration of anti-inflammatory agent dexamethasone (DEX) exhibited the potential to alleviate these detrimental effects in neonatal HIBD rats, with the efficacy being partly reliant on gut microbiota. Further experiment on the potential molecular mechanisms using RNA sequencing indicated a significant increase in the toll-like receptor 4 (TLR4) gene in the intestinal tissues of neonatal HIBD rats. Additionally, the interventions such as TLR4 inhibitor TLR4-IN-C34 administration, FMT, and oral DEX were demonstrated to modulate intestinal function by inhibiting the LPS/TLR4 signaling pathway, thereby exerting neuroprotective effects. Collectively, these findings underscore the contribution of gut microbial dysbiosis post HI insult in activating the LPS/TLR4 signaling pathway, triggering intestinal inflammation and dysfunction, exacerbating systemic inflammation, and consequently worsening synaptic and cognitive impairments in neonatal HIBD rats. Hence, rectifying gut microbial dysbiosis or regulating intestinal function may represent a promising strategy for alleviating long-term cognitive impairments in neonates affected by HIBD.}, } @article {pmid40008084, year = {2025}, author = {Zheng, J and Huang, Y and Zhang, L and Liu, T and Zou, Y and He, L and Guo, S}, title = {Role of the Gut-Lung Microbiome Axis in Airway Inflammation in OVA-Challenged Mice and the Effect of Azithromycin.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {2661-2676}, pmid = {40008084}, issn = {1178-7031}, abstract = {OBJECTIVE: This study aimed to investigate the role of the gut-lung microbiome axis in airway inflammation in asthma and to evaluate the effect of azithromycin on this axis, with a focus on the potential mechanism by which azithromycin reduces allergic airway inflammation.

METHODS: Haematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining were used to assess pathological changes in the lung tissues of asthmatic mice. Leukocyte cell types in bronchoalveolar lavage fluid (BALF) samples were quantified following Wright-Giemsa staining. Total IgE, OVA-specific IgE, IL-4, IL-6, and IL-17A levels in BALF and total IgE in serum were measured by ELISA. The respiratory and gut microbiota were analysed using 16S rRNA gene sequencing and subsequent taxonomic analysis.

RESULTS: OVA-challenged asthmatic mice with gut microbiota dysbiosis exhibited alterations in the respiratory microbiota, resulting in further aggravation of airway inflammation. Following faecal microbiota transplantation (FMT) to restore gut microbiota, respiratory microbiota dysbiosis was partially improved, and airway inflammation was significantly alleviated. Furthermore, azithromycin reduced airway inflammation in asthmatic mice, particularly non-eosinophilic inflammation, for which low-dose azithromycin combined with budesonide proved more effective. Azithromycin significantly enhanced the diversity and microbial composition of the gut microbiota and also affected the respiratory microbiota. At the phylum level, azithromycin decreased the abundance of Proteobacteria in the gut microbiota. At the genus level, azithromycin reduced the abundance of Pseudomonas in the respiratory microbiota.

CONCLUSION: The gut-lung microbiome axis plays a crucial role in airway inflammation in asthma. Azithromycin may reduce airway inflammation in asthma through modulation of the gut-lung microbiome axis.}, } @article {pmid40007342, year = {2025}, author = {Wang, L and Zhang, Z and Chen, X and Wang, Z and Song, X and Geng, Z and Zhang, X and Wang, Y and Li, J and Hu, J and Zuo, L}, title = {Sakuranetin ameliorates experimental colitis in a gut microbiota-dependent manner.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {139}, number = {}, pages = {156540}, doi = {10.1016/j.phymed.2025.156540}, pmid = {40007342}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis/drug therapy/chemically induced/microbiology ; Mice ; Dextran Sulfate ; Fatty Acids, Volatile/metabolism ; Dysbiosis/drug therapy ; Male ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Feces/chemistry/microbiology ; Disease Models, Animal ; Colon/drug effects/pathology ; Intestinal Mucosa/drug effects ; *Anti-Inflammatory Agents/pharmacology ; }, abstract = {BACKGROUND: The progression of inflammatory bowel disease (IBD) is closely connected with intestinal flora dysbiosis. Sakuranetin (SAK) is a natural compound with anti-inflammatory and antibiosis activities. We investigated the properties and mechanisms of SAK on IBD-like colitis.

METHODS: Mice with dextran sulfate sodium (DSS)-induced colitis were accomplished to assess the effects of SAK on colitis, as well as intestinal mucosal immune imbalance and intestinal barrier dysfunction. 16S rDNA was used to characterize the intestinal flora, and the short-chain fatty acid (SCFA) content in faeces was calculated using GS‒MS. Faecal microbiota transplantation (FMT) and a pseudosterile model (antibiotic cocktail, ABX) were used to evaluate whether the effects of SAK on colitis were dependent on the gut flora. Pathohistological and biochemical tests were used to estimate the safety of SAK.

RESULTS: SAK significantly ameliorated DSS-induced colitis in mice, verified by decreased weight loss, less colon shortening, and lower disease activity, histology and colonoscopy scores. Moreover, SAK alleviated gut dysbiosis and elevated the abundance of SCFA-producing bacteria in DSS-treated mice. Meanwhile, SAK increased faecal SCFA levels and activated GPR41/43 signalling. SAK also improved Treg/Th17 homeostasis and intestinal barrier function. In addition, ABX and FMT experiments confirmed that the ability of SAK to alleviate colitis was mediated through the gut flora. Finally, a safety experiment revealed that SAK had no significant adverse effects on major organ or liver/kidney function.

CONCLUSIONS: SAK may improve the intestinal immune balance and barrier function by regulating intestinal flora dysbiosis and increasing SCFA production, thereby protecting against colitis.}, } @article {pmid40007058, year = {2025}, author = {Ge, P and Guo, Y and Che, B and Jin, H and Chen, L and Chen, Z and Tang, K}, title = {Modulation of NLRP3 Inflammasome Activation by QYHT Decoction: Implications for the Treatment of Erectile Dysfunction in Hyperuricemia.}, journal = {American journal of men's health}, volume = {19}, number = {1}, pages = {15579883251318307}, pmid = {40007058}, issn = {1557-9891}, mesh = {Male ; Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/drug effects/metabolism ; Rats ; *Erectile Dysfunction/drug therapy/etiology/therapy ; *Inflammasomes/drug effects/metabolism ; Humans ; *Hyperuricemia/complications ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Gastrointestinal Microbiome/drug effects ; Middle Aged ; Oxidative Stress/drug effects ; Rats, Sprague-Dawley ; Fecal Microbiota Transplantation ; Disease Models, Animal ; }, abstract = {Hyperuricemia (HUA) causes vascular endothelial dysfunction and oxidative stress, and simultaneously activates the NLRP3 inflammasome, leading to inflammatory reactions and erectile dysfunction (ED). This study aimed to investigate the effects of QYHT (Quyuhuatanerxian decoction) decoction on the NLRP3 inflammasome and explore its potential in treating HUA-induced ED. This study employed four treatment methods: (a) treating HUA-induced ED patients with QYHT and analyzing changes in gut microbiota abundance and fecal metabolites through 16S sequencing; (b) establishing an HUA-induced ED rat model, treating with different doses of QYHT, and examining changes in serum metabolites; (c) conducting fecal microbiota transplantation (FMT) therapy; evaluating erectile function, oxidative stress, inflammatory response, and NLRP3 inflammasome activation levels; and (d) exploring key monomeric compounds and potential targets in QYHT through network pharmacology and molecular docking. The treatment with QYHT and FMT increased testosterone levels, reduced oxidative stress and inflammatory marker levels, and inhibited the expressions of NLRP3-related factors. QYHT affected the gut microbiota structure and metabolite levels. The key components were linoleoyl acetate and mandanol, and the target was JAK2. QYHT decoction regulates the distribution of gut microbiota, improves amino acid metabolism, and effectively inhibits the activation of NLRP3 inflammasomes. This, in turn, enhances erectile function and reduces oxidative stress and inflammatory response levels, leading to successful treatment of HUA-induced ED.}, } @article {pmid40005809, year = {2025}, author = {Parodi, E and Novi, M and Bottino, P and La Porta, E and Merlotti, G and Castello, LM and Gotta, F and Rocchetti, A and Quaglia, M}, title = {The Complex Role of Gut Microbiota in Systemic Lupus Erythematosus and Lupus Nephritis: From Pathogenetic Factor to Therapeutic Target.}, journal = {Microorganisms}, volume = {13}, number = {2}, pages = {}, pmid = {40005809}, issn = {2076-2607}, abstract = {The role of gut microbiota (GM) and intestinal dysbiosis in triggering the onset and/or modulating the severity and progression of lupus nephritis (LN) has been the object of intense research over the last few years. Some alterations at the phyla level, such as the abundance of Proteobacteria and reduction in Firmicutes/Bacteroidetes (F/B) ratio and in α-diversity have been consistently reported in systemic lupus erythematosus (SLE), whereas a more specific role has been ascribed to some species (Bacteroides thetaiotaomicron and Ruminococcus gnavus) in LN. Underlying mechanisms include microbial translocation through a "leaky gut" and subsequent molecular mimicry, immune dysregulation (alteration of IFNγ levels and of balance between Treg and Th17 subsets), and epigenetic interactions. Levels of bacterial metabolites, such as butyrate and other short-chain fatty acids (SCFAs), appear to play a key role in modulating LN. Beyond bacterial components of GM, virome and mycobiome are also increasingly recognized as important players in the modulation of an immune response. On the other hand, microbiota-based therapy appears promising and includes diet, prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT). The modulation of microbiota could correct critical alterations, such as F/B ratio and Treg/Th17 imbalance, and blunt production of autoantibodies and renal damage. Despite current limits, GM is emerging as a powerful environmental factor that could be harnessed to interfere with key mechanisms leading to SLE, preventing flares and organ damage, including LN. The aim of this review is to provide a state-of-the-art analysis of the role of GM in triggering and modulating SLE and LN on the one hand, while exploring possible therapeutic manipulation of GM to control the disease on the other hand.}, } @article {pmid40005733, year = {2025}, author = {Romano, FS and Lallo, MA and Romano, RS and Isidoro, LPS and Cardoso, MR and Sodré, LC and Melchert, A and Guimarães-Okamoto, PTC and Pappalardo, MCF and Amaral, AR and Vendramini, THA}, title = {Fecal Microbiota Transplantation as a Treatment for Granulomatous Colitis in a French Bulldog: A Case Report.}, journal = {Microorganisms}, volume = {13}, number = {2}, pages = {}, pmid = {40005733}, issn = {2076-2607}, abstract = {Granulomatous colitis, or ulcerative colitis, is an infectious and inflammatory disease that primarily affects the colon and occasionally extends to the ileum, particularly in young Boxer and French Bulldogs. Unlike typical chronic colitis in small animals, the early onset of the disease suggests a genetic predisposition. The condition is characterized by the overgrowth of Escherichia coli, specifically the enteroinvasive variant, which displaces beneficial gut bacteria, contributing to its infectious nature. Secondary dysbiosis and chronic-active inflammation involving histiocytes and other leukocytic infiltrates are prominent features. Clinical manifestations include chronic diarrhea with blood and mucus, frequent tenesmus, and pain, with variable degrees of weight loss depending on disease severity. The final diagnosis is based on clinical history (chronic diarrhea with hematochezia), macroscopic findings from colonoscopy (edema, ulcers, and wall hyperplasia), histopathology (presence of histiocytes), and Escherichia coli growth in culture from a colon fragment. Treatment is guided by colon antibiograms, which often require prolonged antibiotic therapy. Fecal microbiota transplantation (FMT) has emerged as a potential treatment, either as a primary intervention or adjunctive therapy, for conditions such as acute enteritis (e.g., canine parvovirus), dysbiosis, and chronic enteropathies. However, its application to modulate the microbiota and reduce inflammation in granulomatous colitis, potentially leading to longer intervals between relapses, remains an area of ongoing investigation. This is a case report of a French Bulldog diagnosed with ulcerative colitis accompanied by dysbiosis and refractory to standard treatments but sensitive and partially responsive to amikacin. The patient achieved control and sustained improvement in fecal scoring following fecal transplantation. This approach prevented the need for additional antibiotic therapy, ensuring clinical amelioration alongside microbiome restoration.}, } @article {pmid40005617, year = {2025}, author = {Kaltsas, A and Giannakodimos, I and Markou, E and Adamos, K and Stavropoulos, M and Kratiras, Z and Zachariou, A and Dimitriadis, F and Sofikitis, N and Chrisofos, M}, title = {The Role of Gut Microbiota Dysbiosis in Erectile Dysfunction: From Pathophysiology to Treatment Strategies.}, journal = {Microorganisms}, volume = {13}, number = {2}, pages = {}, pmid = {40005617}, issn = {2076-2607}, abstract = {Erectile dysfunction (ED) is a prevalent male sexual disorder characterized by the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance. While its etiology is multifactorial, encompassing vascular, neurological, hormonal, and psychological components, emerging evidence suggests a significant role for gut microbiota dysbiosis in its development. The gut microbiota influences various metabolic, inflammatory, and neuropsychological processes critical to erectile function. Dysbiosis can lead to systemic inflammation, endothelial dysfunction, hormonal imbalances, and altered neurotransmitter production, all of which are key factors in ED pathogenesis. This narrative review synthesizes current research on the association between gut microbiota alterations and ED, highlighting specific bacterial taxa implicated in ED through mechanisms involving inflammation, metabolic disturbances, and hormonal regulation. This review explores potential mechanisms linking gut microbiota and ED, including pro-inflammatory cytokines, gut barrier integrity disruption, metabolic disorders, psychological factors via the gut-brain axis, and hormonal regulation. Furthermore, the gut microbiota offers promising avenues for developing non-invasive biomarkers and therapeutic interventions such as probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation. Future research should focus on longitudinal studies, mechanistic explorations, and clinical trials to validate these findings and translate them into clinical practice. Understanding the interplay between the gut microbiota and erectile function could unveil novel diagnostic biomarkers and pave the way for innovative treatments targeting the microbiota, ultimately improving men's sexual and overall health.}, } @article {pmid40005608, year = {2025}, author = {Pasta, A and Formisano, E and Calabrese, F and Marabotto, E and Furnari, M and Bodini, G and Torres, MCP and Pisciotta, L and Giannini, EG and Zentilin, P}, title = {From Dysbiosis to Hepatic Inflammation: A Narrative Review on the Diet-Microbiota-Liver Axis in Steatotic Liver Disease.}, journal = {Microorganisms}, volume = {13}, number = {2}, pages = {}, pmid = {40005608}, issn = {2076-2607}, abstract = {The gut microbiota has emerged as a critical player in metabolic and liver health, with its influence extending to the pathogenesis and progression of steatotic liver diseases. This review delves into the gut-liver axis, a dynamic communication network linking the gut microbiome and liver through metabolic, immunological, and inflammatory pathways. Dysbiosis, characterized by altered microbial composition, contributes significantly to the development of hepatic steatosis, inflammation, and fibrosis via mechanisms such as gut barrier dysfunction, microbial metabolite production, and systemic inflammation. Dietary patterns, including the Mediterranean diet, are highlighted for their role in modulating the gut microbiota, improving gut-liver axis integrity, and attenuating liver injury. Additionally, emerging microbiota-based interventions, such as fecal microbiota transplantation and bacteriophage therapy, show promise as therapeutic strategies for steatotic liver disease. However, challenges such as population heterogeneity, methodological variability, and knowledge gaps hinder the translational application of current findings. Addressing these barriers through standardized approaches and integrative research will pave the way for microbiota-targeted therapies to mitigate the global burden of steatotic liver disease.}, } @article {pmid40005065, year = {2025}, author = {Noureldein, MH and Rumora, AE and Teener, SJ and Rigan, DM and Hayes, JM and Mendelson, FE and Carter, AD and Rubin, WG and Savelieff, MG and Feldman, EL}, title = {Dietary Fatty Acid Composition Alters Gut Microbiome in Mice with Obesity-Induced Peripheral Neuropathy.}, journal = {Nutrients}, volume = {17}, number = {4}, pages = {}, pmid = {40005065}, issn = {2072-6643}, support = {1R01DK130913-00A1/NH/NIH HHS/United States ; U24 DK076169/DK/NIDDK NIH HHS/United States ; 1R00DK119366-00A1/NH/NIH HHS/United States ; U24 DK115255/DK/NIDDK NIH HHS/United States ; P30DK020572//Michigan Diabetes Research Center/ ; not applicable//Richard and Jane Manoogian Foundation/ ; not applicable//Dr. John H. Doran Neuropathy Research Initiative/ ; not applicable//Taubman Foundation/ ; P30 DK020572/DK/NIDDK NIH HHS/United States ; not applicable//Nathan and Rose Milstein Research Fund/ ; P30 DK063608/DK/NIDDK NIH HHS/United States ; not applicable//Sinai Medical Staff Foundation/ ; 1K99AG081390-00A1/NH/NIH HHS/United States ; 1R01DK076169-00A1/NH/NIH HHS/United States ; 1R01DK115255-00A1/NH/NIH HHS/United States ; K99 AG081390/AG/NIA NIH HHS/United States ; 1P30DK063608-00A20/NH/NIH HHS/United States ; R01 DK130913/DK/NIDDK NIH HHS/United States ; not applicable//NeuroNetwork for Emerging Therapies/ ; R00 DK119366/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Obesity/complications/microbiology ; Mice ; Diet, High-Fat/adverse effects ; *Peripheral Nervous System Diseases/etiology/microbiology ; *Fatty Acids/administration & dosage ; Male ; Mice, Inbred C57BL ; *Dietary Fats/administration & dosage ; Fecal Microbiota Transplantation ; Fatty Acids, Monounsaturated/administration & dosage ; Disease Models, Animal ; }, abstract = {BACKGROUND: Peripheral neuropathy (PN), a complication of diabetes and obesity, progresses through a complex pathophysiology. Lifestyle interventions to manage systemic metabolism are recommended to prevent or slow PN, given the multifactorial risks of diabetes and obesity. A high-fat diet rich in saturated fatty acids (SFAs) induces PN, which a diet rich in monounsaturated fatty acids (MUFAs) rescues, independent of weight loss, suggesting factors beyond systemic metabolism impact nerve health. Interest has grown in gut microbiome mechanisms in PN, which is characterized by a distinct microbiota signature that correlates with sciatic nerve lipidome.

METHODS: Herein, we postulated that SFA- versus MUFA-rich diet would impact gut microbiome composition and correlate with PN development. To assess causality, we performed fecal microbiota transplantation (FMT) from donor mice fed SFA- versus MUFA-rich diet to lean recipient mice and assessed metabolic and PN phenotypes.

RESULTS: We found that the SFA-rich diet altered the microbiome community structure, which the MUFA-rich diet partially reversed. PN metrics correlated with several microbial families, some containing genera with feasible mechanisms of action for microbiome-mediated effects on PN. SFA and MUFA FMT did not impact metabolic phenotypes in recipient mice although SFA FMT marginally induced motor PN.

CONCLUSIONS: The involvement of diet-mediated changes in the microbiome on PN and gut-nerve axis may warrant further study.}, } @article {pmid40004205, year = {2025}, author = {Blanquet, L and Serra, D and Marrinhas, C and Almeida, A}, title = {Exploring Gut Microbiota-Targeted Therapies for Canine Idiopathic Epilepsy.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, pmid = {40004205}, issn = {1422-0067}, mesh = {Animals ; Dogs ; *Gastrointestinal Microbiome/drug effects ; *Epilepsy/veterinary/microbiology/therapy ; *Dog Diseases/therapy/microbiology ; Dysbiosis/microbiology ; }, abstract = {Epilepsy stands out as one of the most prevalent chronic neurological conditions affecting companion animals. Recent research has increasingly focused on exploring the role of gut microbiota in influencing neurological conditions, like epilepsy. This influence stems from the bidirectional communication pathways between gut bacteria and the brain, which involve metabolic, neural, immunological, and endocrine mechanisms. In fact, a balanced and stable gut microbiota is essential to maintaining normal gut physiology and ensuring appropriate signaling along the gut-brain axis. Conversely, dysbiosis can have detrimental effects on gut physiology and may contribute to the development or exacerbation of neurological conditions, including epilepsy. Considering these findings, this review article aims to deepen the understanding of the mechanisms underlying the microbiota-gut-brain connection in the context of canine idiopathic epilepsy. Moreover, this review presents recent data on innovative gut-related therapeutic strategies for canine idiopathic epilepsy treatment.}, } @article {pmid40004161, year = {2025}, author = {Wang, Z and Ma, X and Shi, W and Zhu, W and Feng, X and Xin, H and Zhang, Y and Cong, B and Li, Y}, title = {The Gut Microbiota Metabolite Butyrate Modulates Acute Stress-Induced Ferroptosis in the Prefrontal Cortex via the Gut-Brain Axis.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, pmid = {40004161}, issn = {1422-0067}, support = {82072109//National Natural Science Foundation of China/ ; 82130055//National Natural Science Foundation of China/ ; 82293651//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Prefrontal Cortex/metabolism/pathology/drug effects ; Mice ; *Ferroptosis/drug effects ; Male ; *Stress, Psychological/metabolism/microbiology ; Depression/metabolism/microbiology ; *Butyrates/metabolism/pharmacology ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; *Brain-Gut Axis ; Disease Models, Animal ; Neurons/metabolism ; }, abstract = {Stress has been implicated in the onset of mental disorders such as depression, with the prefrontal cortex (PFC) playing a crucial role. However, the underlying mechanisms remain to be fully elucidated. Metabolites secreted by intestinal flora can enter the bloodstream and exert regulatory effects on the body. Consequently, this study aims to investigate the molecular mechanisms by which gut flora influences ferroptosis in PFC neurons, thereby affecting depression-like behavioral changes in mice subjected to acute stress. Initially, we established a mouse model of acute restraint stress (3-day duration) and verified that stress-induced ferroptosis of PFC neurons contributed to depression-like behavioral alterations in mice, as evidenced by morphological, behavioral, and molecular biology assessments. Subsequently, through fecal microbiota transplantation (FMT) experiments, we established a significant correlation between gut microbiota and ferroptosis of PFC neurons in acute stress-exposed mice. 16S rDNA sequencing identified butyric acid-producing bacteria, specifically g_Butyricimonas and its primary metabolite, butyric acid, as critical regulators of ferroptosis in PFC neurons in acutely stressed mice. Furthermore, the intervention of butyrate demonstrated its potential to ameliorate damage to the intestinal and blood-brain barriers in these mice. This intervention also mitigated depression-like behaviors induced by ferroptosis of PFC neurons by alleviating systemic inflammatory responses. The findings of this study indicate that acute stress-induced ferroptosis of PFC neurons plays a critical role in depression-like behavioral changes in mice. Additionally, the gut microbiota metabolite butyrate can modulate ferroptosis and depression-like behavioral changes through the gut-brain axis.}, } @article {pmid40004115, year = {2025}, author = {Zhang, J and Wei, J and Lai, W and Sun, J and Bai, Y and Cao, H and Guo, J and Su, Z}, title = {Focus on Glucagon-like Peptide-1 Target: Drugs Approved or Designed to Treat Obesity.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, pmid = {40004115}, issn = {1422-0067}, mesh = {Humans ; *Obesity/drug therapy/metabolism ; *Glucagon-Like Peptide 1/metabolism ; *Anti-Obesity Agents/therapeutic use/pharmacology ; Animals ; Glucagon-Like Peptide-1 Receptor Agonists ; Glucagon-Like Peptide-1 Receptor/metabolism ; }, abstract = {Obesity is closely related to metabolic diseases, which brings a heavy burden to the health care system. It is urgent to formulate and implement effective treatment strategies. Glucagon-like peptide-1 (GLP-1) is a protein with seven transmembrane domains connected by type B and G proteins, which is widely distributed and expressed in many organs and tissues. GLP-1 analogues can reduce weight, lower blood pressure, and improve blood lipids. Obesity, diabetes, cardiovascular diseases, and other diseases have caused scientists' research and development boom. Among them, GLP-1R agonist drugs have developed rapidly in weight-loss drugs. In this paper, based on the target of GLP-1, the mechanism of action of GLP-1 in obesity treatment was deeply studied, and the drugs approved and designed for obesity treatment based on GLP-1 target were elaborated in detail. Innovatively put forward and summarized the double and triple GLP-1 targeted drugs in the treatment of obesity with better effects and less toxic and side effects, and this can make full use of multi-target methods to treat other diseases in the future. Finally, it is pointed out that intestinal flora and microorganisms have many benefits in the treatment of obesity, and fecal bacteria transplantation may be a potential treatment for obesity with less harm to the body. This article provides some promising methods to treat obesity, which have strong practical value.}, } @article {pmid40003979, year = {2025}, author = {Flynn, CK and Adams, JB and Krajmalnik-Brown, R and Khoruts, A and Sadowsky, MJ and Nirmalkar, K and Takyi, E and Whiteley, P}, title = {Review of Elevated Para-Cresol in Autism and Possible Impact on Symptoms.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, pmid = {40003979}, issn = {1422-0067}, support = {N/A//Zoowalk for Autism Research/ ; }, mesh = {*Cresols/metabolism/urine ; Humans ; Animals ; Gastrointestinal Microbiome ; *Autistic Disorder/metabolism ; *Autism Spectrum Disorder/metabolism ; Sulfuric Acid Esters/metabolism/urine ; Brain/metabolism ; Mice ; Renal Insufficiency, Chronic/metabolism ; }, abstract = {Para-cresol (p-cresol), and its primary human metabolite p-cresol sulfate (pCS), are among the most studied gut-derived metabolites relevant to autism spectrum disorder (ASD). P-cresol is produced by bacterial modification of phenylalanine or tyrosine and is one of many potentially deleterious metabolites produced by the gut microbiota. Seventeen studies have observed p-cresol and/or p-cresol sulfate as being higher in the urine of children with autism spectrum disorder (ASD) vs. controls. P-cresol has harmful effects on the body, including within the gut, brain, kidneys, liver, immune system, and mitochondria. Some of these effects may contribute to autism and comorbid symptoms. In the gut, p-cresol acts as an antibiotic, altering the gut microbiome to favor the bacteria that produce it. In the mitochondria, p-cresol disrupts ATP production and increases oxidative stress, which is also common in autism. In the brain, p-cresol impairs neuronal development. P-cresol inactivates dopamine beta-hydroxylase, which converts dopamine to noradrenaline. P-cresol sulfate impairs kidney function and is linked to chronic kidney disease (CKD), which is more common in ASD adults. P-cresol also interferes with immune function. Three animal studies have demonstrated that p-cresol causes autism-related symptoms in mice, and that mice can be recovered by the administration of fecal microbiota transplant from healthy mice. Similarly, it was found that microbiota transplant therapy treatment in children with ASD significantly reduced p-cresol sulfate levels to normal and led to significant improvements in gastrointestinal (GI) and ASD symptoms. In summary, p-cresol and pCS likely contribute to ASD core symptoms in a substantial subset of children with ASD.}, } @article {pmid40003971, year = {2025}, author = {Yu, F and Zhu, C and Wu, W}, title = {Senile Osteoarthritis Regulated by the Gut Microbiota: From Mechanisms to Treatments.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, pmid = {40003971}, issn = {1422-0067}, support = {11DZ2261100//Shanghai Key Laboratory of Human Performance/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Osteoarthritis/therapy/microbiology/etiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; Aging ; Animals ; Medicine, Chinese Traditional ; }, abstract = {Osteoarthritis (OA) is a chronic, progressive degenerative joint disease that affects the entire synovial joint, leading to the progressive degeneration of articular cartilage. It seriously affects the quality of life and global disability of patients. OA is affected by a variety of factors; the most significant risk factor for OA is age. As individuals age, the risk and severity of OA increase due to the exacerbation of cartilage degeneration and wear and tear. In recent years, research has indicated that the gut microbiota may play a significant role in the aging and OA processes. It is anticipated that regulating the gut microbiota may offer novel approaches to the treatment of OA. The objective of this paper is to examine the relationship between the gut microbiota and senile OA, to investigate the potential mechanisms involved. This review also summarizes the therapeutic strategies related to gut flora in OA management, such as prebiotics and probiotics, diet, exercise, traditional Chinese medicine (TCM) modification, and fecal microbiota transplantation (FMT), highlighting the potential clinical value of gut flora and elucidating the current challenges. The foundation for future research directions is established through the summarization of current research progress.}, } @article {pmid40003268, year = {2025}, author = {Todor, SB and Ichim, C}, title = {Microbiome Modulation in Pediatric Leukemia: Impact on Graft-Versus-Host Disease and Treatment Outcomes: A Narrative Review.}, journal = {Children (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {40003268}, issn = {2227-9067}, abstract = {The gut microbiome significantly influences the outcomes of pediatric leukemia, particularly in patients undergoing hematopoietic stem cell transplantation (HSCT). Dysbiosis, caused by chemotherapy, antibiotics, and immune system changes, contributes to complications such as graft-versus-host disease (GVHD), gastrointestinal issues, and infections. Various microbiome-related interventions, including prebiotics, probiotics, postbiotics, and fecal microbiota transplantation (FMT), have shown potential in mitigating these complications. Specific microbial signatures have been linked to GVHD risk, and interventions like inulin, Lactobacillus, and SCFAs (short-chain fatty acids), particularly butyrate, may help modulate the immune system and improve outcomes. FMT, while showing promising results in restoring microbial balance and alleviating GVHD, still requires careful monitoring due to potential risks in immunocompromised patients. Despite positive findings, more research is needed to optimize microbiome-based therapies and ensure their safety and efficacy in pediatric leukemia care.}, } @article {pmid40002939, year = {2025}, author = {Vučinić, D and Redžović, A and Hauser, G and Mikolašević, I}, title = {Microbiota and Radiotherapy: Unlocking the Potential for Improved Gastrointestinal Cancer Treatment.}, journal = {Biomedicines}, volume = {13}, number = {2}, pages = {}, pmid = {40002939}, issn = {2227-9059}, abstract = {Radiotherapy (RT) is one of the major cornerstones in managing gastrointestinal (GI) cancers. However, several side effects, such as intestinal inflammation, mucosal injury, and dysbiosis, often compromise this. The gut microbiota increasingly attracts much interest as an essential modulator of RT effects influencing immune responses and tissue repair. Through short-chain fatty acids such as butyrate, representatives of certain bacterial species play a crucial role under normal conditions, keeping the mucosal integrity intact and reducing oxidative stress-mediated damage. Dysbiosis, a state where diminished microbial diversity and increased pathogenic species in the microbiota are seen, amplifies RT-induced toxicity in patients. Clinical investigations highlight that microbiota-targeted interventions, including probiotics, prebiotics, and fecal microbiota transplantation, hold the means to augment RT efficacy and lessen toxicity. Increased microflora diversity and specific microbial profiles have yielded serious patient improvements. Advanced RT methods use stereotactic body radiotherapy combined with microbiota modulation as a promising technique to shield healthy tissue and maximize immune-mediated antitumor effects. Additionally, there is an implication in tumor behavior regulated by the intratumoral microbiota regarding the response to radiotherapy. Notably, the modulation of gut and tumor microbiota provides an avenue to optimize RT benefits in GI cancers, underscoring the importance of personalized therapy.}, } @article {pmid40002835, year = {2025}, author = {Mafe, AN and Büsselberg, D}, title = {Microbiome Integrity Enhances the Efficacy and Safety of Anticancer Drug.}, journal = {Biomedicines}, volume = {13}, number = {2}, pages = {}, pmid = {40002835}, issn = {2227-9059}, support = {NPRP 14S0311-210033//QNRF/ ; }, abstract = {The intricate relationship between anticancer drugs and the gut microbiome influences cancer treatment outcomes. This review paper focuses on the role of microbiome integrity in enhancing the efficacy and safety of anticancer drug therapy, emphasizing the pharmacokinetic interactions between anticancer drugs and the gut microbiota. It explores how disruptions to microbiome composition, or dysbiosis, can alter drug metabolism, immune responses, and treatment side effects. By examining the mechanisms of microbiome disruption caused by anticancer drugs, this paper highlights specific case studies of drugs like cyclophosphamide, 5-fluorouracil, and irinotecan, and their impact on microbial diversity and clinical outcomes. The review also discusses microbiome-targeted strategies, including prebiotics, probiotics, postbiotics, and fecal microbiota transplantation (FMT), as promising interventions to enhance cancer treatment. Furthermore, the potential of microbiome profiling in personalizing therapy and integrating these interventions into clinical practice is explored. Finally, this paper proposes future research directions, including developing novel biomarkers and a deeper comprehension of drug-microbiome interactions, to respond to current gaps in knowledge and improve patient outcomes in cancer care.}, } @article {pmid40002529, year = {2025}, author = {Kalaga, P and Ray, SK}, title = {Mental Health Disorders Due to Gut Microbiome Alteration and NLRP3 Inflammasome Activation After Spinal Cord Injury: Molecular Mechanisms, Promising Treatments, and Aids from Artificial Intelligence.}, journal = {Brain sciences}, volume = {15}, number = {2}, pages = {}, pmid = {40002529}, issn = {2076-3425}, support = {R01 CA091460/CA/NCI NIH HHS/United States ; R01 NS057811/NS/NINDS NIH HHS/United States ; }, abstract = {Aside from its immediate traumatic effects, spinal cord injury (SCI) presents multiple secondary complications that can be harmful to those who have been affected by SCI. Among these secondary effects, gut dysbiosis (GD) and the activation of the NOD (nucleotide-binding oligomerization domain) like receptor-family pyrin-domain-containing three (NLRP3) inflammasome are of special interest for their roles in impacting mental health. Studies have found that the state of the gut microbiome is thrown into disarray after SCI, providing a chance for GD to occur. Metabolites such as short-chain fatty acids (SCFAs) and a variety of neurotransmitters produced by the gut microbiome are hampered by GD. This disrupts healthy cognitive processes and opens the door for SCI patients to be impacted by mental health disorders. Additionally, some studies have found an increased presence and activation of the NLRP3 inflammasome and its respective parts in SCI patients. Preclinical and clinical studies have shown that NLRP3 inflammasome plays a key role in the maturation of pro-inflammatory cytokines that can initiate and eventually aggravate mental health disorders after SCI. In addition to the mechanisms of GD and the NLRP3 inflammasome in intensifying mental health disorders after SCI, this review article further focuses on three promising treatments: fecal microbiome transplants, phytochemicals, and melatonin. Studies have found these treatments to be effective in combating the pathogenic mechanisms of GD and NLRP3 inflammasome, as well as alleviating the symptoms these complications may have on mental health. Another area of focus of this review article is exploring how artificial intelligence (AI) can be used to support treatments. AI models have already been developed to track changes in the gut microbiome, simulate drug-gut interactions, and design novel anti-NLRP3 inflammasome peptides. While these are promising, further research into the applications of AI for the treatment of mental health disorders in SCI is needed.}, } @article {pmid40002492, year = {2025}, author = {Gao, A and Lv, J and Su, Y}, title = {The Inflammatory Mechanism of Parkinson's Disease: Gut Microbiota Metabolites Affect the Development of the Disease Through the Gut-Brain Axis.}, journal = {Brain sciences}, volume = {15}, number = {2}, pages = {}, pmid = {40002492}, issn = {2076-3425}, support = {Grant No. 81601330-YS//National Natural Science Foundation of China/ ; Grant No. 2022CFB178-YS//Natural Science Foundation of Hubei Province/ ; }, abstract = {Parkinson's disease is recognized as the second most prevalent neurodegenerative disorder globally, with its incidence rate projected to increase alongside ongoing population growth. However, the precise etiology of Parkinson's disease remains elusive. This article explores the inflammatory mechanisms linking gut microbiota to Parkinson's disease, emphasizing alterations in gut microbiota and their metabolites that influence the disease's progression through the bidirectional transmission of inflammatory signals along the gut-brain axis. Building on this mechanistic framework, this article further discusses research methodologies and treatment strategies focused on gut microbiota metabolites, including metabolomics detection techniques, animal model investigations, and therapeutic approaches such as dietary interventions, probiotic treatments, and fecal transplantation. Ultimately, this article aims to elucidate the relationship between gut microbiota metabolites and the inflammatory mechanisms underlying Parkinson's disease, thereby paving the way for novel avenues in the research and treatment of this condition.}, } @article {pmid40001573, year = {2025}, author = {Mafe, AN and Büsselberg, D}, title = {Modulation of the Neuro-Cancer Connection by Metabolites of Gut Microbiota.}, journal = {Biomolecules}, volume = {15}, number = {2}, pages = {}, pmid = {40001573}, issn = {2218-273X}, support = {NPRP 14S0311-210033//QNRF/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Animals ; *Brain Neoplasms/metabolism/microbiology ; Dysbiosis/metabolism/microbiology ; Fatty Acids, Volatile/metabolism ; }, abstract = {The gut-brain-cancer axis represents a novel and intricate connection between the gut microbiota, neurobiology, and cancer progression. Recent advances have accentuated the significant role of gut microbiota metabolites in modulating systemic processes that influence both brain health and tumorigenesis. This paper explores the emerging concept of metabolite-mediated modulation within the gut-brain-cancer connection, focusing on key metabolites such as short-chain fatty acids (SCFAs), tryptophan derivatives, secondary bile acids, and lipopolysaccharides (LPS). While the gut microbiota's impact on immune regulation, neuroinflammation, and tumor development is well established, gaps remain in grasping how specific metabolites contribute to neuro-cancer interactions. We discuss novel metabolites with potential implications for neurobiology and cancer, such as indoles and polyamines, which have yet to be extensively studied. Furthermore, we review preclinical and clinical evidence linking gut dysbiosis, altered metabolite profiles, and brain tumors, showcasing limitations and research gaps, particularly in human longitudinal studies. Case studies investigating microbiota-based interventions, including dietary changes, fecal microbiota transplantation, and probiotics, demonstrate promise but also indicate hurdles in translating these findings to clinical cancer therapies. This paper concludes with a call for standardized multi-omics approaches and bi-directional research frameworks integrating microbiome, neuroscience, and oncology to develop personalized therapeutic strategies for neuro-cancer patients.}, } @article {pmid40001396, year = {2025}, author = {Sher, AA and Whitehead-Tillery, CE and Peer, AM and Bell, JA and Vocelle, DB and Dippel, JT and Zhang, L and Mansfield, LS}, title = {Dynamic Spread of Antibiotic Resistance Determinants by Conjugation to a Human-Derived Gut Microbiota in a Transplanted Mouse Model.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {2}, pages = {}, pmid = {40001396}, issn = {2079-6382}, support = {RN031097-DEHN//Albert C. and Lois E. Dehn Chair Endowment/ ; NC1202//United States Department of Agriculture/ ; GS100019//University Distinguished Professor Endowment, Michigan State University/ ; U19AI090872//National Institutes of Health, Enterics Research Investigational Network, Cooperative Research Center/ ; Stipend to Azam A. Sher//College of Veterinary Medicine/ ; }, abstract = {BACKGROUND: Antibiotic-resistant (AR) bacteria pose an increasing threat to public health, but the dynamics of antibiotic resistance gene (ARG) spread in complex microbial communities are poorly understood. Conjugation is a predominant direct cell-to-cell mechanism for the horizontal gene transfer (HGT) of ARGs. We hypothesized that commensal Escherichia coli donor strains would mediate the conjugative transfer of ARGs to phylogenetically distinct bacteria without antibiotic selection pressure in gastrointestinal tracts of mice carrying a human-derived microbiota with undetectable levels of E. coli. Our objective was to identify a mouse model to study the factors regulating AR transfer by conjugation in the gut.

METHODS: Two donor E. coli strains were engineered to carry chromosomally encoded red fluorescent protein, and an ARG- and green fluorescent protein (GFP)-encoding broad host range RP4 conjugative plasmid. Mice were orally gavaged with two donor strains (1) E. coli MG1655 or (2) human-derived mouse-adapted E. coli LM715-1 and their colonization assessed by culture over time. Fluorescence-activated cell sorting (FACS) and 16S rDNA sequencing were performed to trace plasmid spread to the microbiota.

RESULTS: E. coli LM715-1 colonized mice for ten days, while E. coli MG1655 was not recovered after 72 h. Bacterial cells from fecal samples on days 1 and 3 post inoculation were sorted by FACS. Samples from mice given donor E. coli LM715-1 showed an increase in cells expressing green but not red fluorescence compared to pre-inoculation samples. 16S rRNA gene sequencing analysis of FACS GFP positive cells showed that bacterial families Lachnospiraceae, Clostridiaceae, Pseudomonadaceae, Rhodanobacteraceae, Erysipelotrichaceae, Oscillospiraceae, and Butyricicoccaceae were the primary recipients of the RP4 plasmid.

CONCLUSIONS: Results show this ARG-bearing conjugative RP4 plasmid spread to diverse human gut bacterial taxa within a live animal where they persisted. These fluorescent marker strategies and human-derived microbiota transplanted mice provided a tractable model for investigating the dynamic spread of ARGs within gut microbiota and could be applied rigorously to varied microbiotas to understand conditions facilitating their spread.}, } @article {pmid40000989, year = {2025}, author = {Zhao, M and Zhang, Y and Liu, S and Wang, F and Zhang, P}, title = {Eradication of Helicobacter pylori reshapes gut microbiota and facilitates the evolution of antimicrobial resistance through gene transfer and genomic mutations in the gut.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {90}, pmid = {40000989}, issn = {1471-2180}, support = {32201393//National Natural Science Foundation of China/ ; }, mesh = {*Helicobacter pylori/drug effects/genetics ; Humans ; *Gastrointestinal Microbiome/genetics/drug effects ; *Helicobacter Infections/microbiology/drug therapy ; *Gene Transfer, Horizontal ; *Drug Resistance, Bacterial/genetics ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; Feces/microbiology ; Mutation ; Metagenomics ; Female ; Evolution, Molecular ; Male ; Bacteria/genetics/classification/drug effects ; Middle Aged ; Genome, Bacterial ; Adult ; Klebsiella/genetics/drug effects ; }, abstract = {Treating Helicobacter pylori (H. pylori) infection requires large quantities of antibiotics, thus dramatically promoting the enrichment and dissemination of antimicrobial resistance (AMR) in feces. However, the influence of H. pylori eradication on the AMR mobility and the gut microbiota evolution has yet to be thoroughly investigated. Here, a study involving 12 H. pylori-positive participants was conducted, and the pre- and post- eradication fecal samples were sequenced. Metagenomic analysis revealed that the eradication treatment drastically altered the gut microbiome, with the Escherichia and Klebsiella genera emerging as the predominant bacteria. Interestingly, the eradication treatment significantly increased the relative abundance and diversity of resistome and mobilome in gut microbiota. Eradication of H. pylori also enriched AMR genes (ARGs) conferring resistance to antibiotics not administered because of the co-location with other ARGs or mobile genetic elements (MGEs). Additionally, the Escherichia and Klebsiella genera were identified as the primary bacterial hosts of these highly transferable ARGs. Furthermore, the genomic variations associated with ARGs in Escherichia coli (E. coli) caused by the eradication treatment were profiled, including the parC, parE, and gyrA genes. These findings revealed that H. pylori eradication promoted the enrichment of ARGs and MGEs in the Escherichia and Klebsiella genera, and further facilitated bacterial evolution through the horizontal transfer of ARGs and genomic variations.}, } @article {pmid39999537, year = {2025}, author = {Dhanasekaran, D and Venkatesan, M and Sabarathinam, S}, title = {Efficacy of microbiome-targeted interventions in obesity management- A comprehensive systematic review.}, journal = {Diabetes & metabolic syndrome}, volume = {19}, number = {2}, pages = {103208}, doi = {10.1016/j.dsx.2025.103208}, pmid = {39999537}, issn = {1878-0334}, mesh = {Humans ; *Obesity/therapy/microbiology ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; Prebiotics/administration & dosage ; *Fecal Microbiota Transplantation/methods ; *Obesity Management/methods ; Body Composition ; Prognosis ; Synbiotics/administration & dosage ; }, abstract = {BACKGROUND: Obesity is a global health crisis linked to numerous chronic diseases. The gut microbiome plays a crucial role in human metabolism, and emerging evidence suggests that modulating the microbiome may offer novel therapeutic avenues for obesity management.

OBJECTIVE: This systematic review aimed to assess the efficacy and safety of microbiome-targeted interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, in improving body composition, metabolic parameters, and inflammatory markers in overweight and obese adults.

METHODS: A comprehensive search of PubMed, Scopus, and ScienceDirect was conducted to identify relevant studies published between 2005 and 2023. Included studies were assessed for methodological quality and risk of bias using the Cochrane Collaboration tool.

RESULTS: Body composition: Most studies demonstrated significant reductions in body weight, Body mass index, and body fat percentage.

METABOLIC PARAMETERS: Improvements were observed in lipid profiles (reduced cholesterol, triglycerides) and glucose metabolism (improved insulin sensitivity).

INFLAMMATORY MARKERS: Significant reductions were observed in inflammatory markers such as Interleukins (IL-6, IL-8) and C-reactive protein.

MICROBIAL COMPOSITION: Interventions generally led to shifts in microbial composition, with increases in beneficial bacteria such as Bifidobacterium and Lactobacillus.

ADVERSE EVENTS: Adverse events were generally minimal and limited.

CONCLUSION: This review provides strong evidence that microbiome-targeted interventions can effectively improve body composition, metabolic parameters, and inflammatory markers in individuals with obesity. Further research is needed to optimize intervention strategies, identify specific microbial targets, and translate these findings into effective clinical applications.}, } @article {pmid39999013, year = {2025}, author = {Tashkent, Y and Choo, JM and Richard, A and Wang, Z and Calzadilla-Bertot, L and Vasil, E and Miller, S and Taylor, SL and Ivey, KL and Woodman, R and Adler, B and Ayonrinde, OT and Olynyk, JK and Beilin, LJ and Mori, TA and Wigg, AJ and Muller, KR and Adams, LA and Rogers, GB}, title = {Steatotic Liver Disease in Younger Adults is Associated With Altered Gut Microbiology.}, journal = {Liver international : official journal of the International Association for the Study of the Liver}, volume = {45}, number = {3}, pages = {e70032}, pmid = {39999013}, issn = {1478-3231}, support = {//Gastroenterological Society of Australia/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Adult ; Male ; Female ; Cross-Sectional Studies ; *Fatty Liver/microbiology/diagnostic imaging ; Magnetic Resonance Imaging ; Feces/microbiology ; Liver/diagnostic imaging/pathology ; }, abstract = {BACKGROUND AND AIMS: Steatotic liver disease (SLD) is a leading cause of chronic liver disease worldwide. As SLD pathogenesis has been linked to gut microbiome alterations, we aimed to identify SLD-associated gut microbiome features early in SLD development by utilising a highly characterised cohort of community-dwelling younger adults.

METHODS AND RESULTS: At age 27 years, 588 participants of the Raine Study Generation 2 underwent cross-sectional assessment. Hepatic steatosis was quantified using a validated magnetic resonance imaging (MRI) volumetric liver fat fraction (VLFF) equation (HepaFat). Of the 588 participants, 488 (83%) were classified as having 'no SLD' (VLFF ≤ 3.55%), 76 (12.9%) with 'mild-moderate' SLD (VLFF: 3.56%-13.4%) and 24 (4.10%) with 'severe' SLD (VLFF > 13.4%). Stool microbiome profiling identified an association between severe SLD and lower microbiota alpha diversity (observed features [p = 0.015], Pielou evenness [p = 0.001] and Shannon diversity [p = 0.002]) compared to no SLD. Faecal microbiota composition differed significantly between no SLD and both mild-moderate (p = 0.004) and severe SLD groups (p = 0.001). There was no significant difference in microbiota dispersion between SLD groups. Reduced relative abundance of short-chain fatty acid producing bacteria, and higher levels of proinflammatory bacterial taxa, were both significantly associated with severe SLD (q < 0.05).

CONCLUSIONS: SLD in younger adults is associated with reduced intestinal microbial diversity and a pattern of bacterial taxa depletion that is consistent with other chronic inflammatory conditions. Our characterisation of gut microbiome characteristics in early SLD development provides a potential basis for risk identification and reduction.

TRIAL REGISTRATION: The Raine Study is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617001599369).}, } @article {pmid39998920, year = {2025}, author = {Lundgrin, EL and Hatipoglu, B}, title = {Trending Modalities in Type 2 Diabetes Prevention.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {110}, number = {Supplement_2}, pages = {S187-S192}, doi = {10.1210/clinem/dgaf040}, pmid = {39998920}, issn = {1945-7197}, support = {//This work was supported by the Deborah and Ronald Ratner Fund/ ; //Mary B. Lee Chair/ ; }, mesh = {Humans ; *Diabetes Mellitus, Type 2/prevention & control ; *Prediabetic State/therapy ; Gastrointestinal Microbiome ; Hypoglycemic Agents/therapeutic use ; Life Style ; Incretins/therapeutic use ; Fecal Microbiota Transplantation ; Insulin Resistance ; }, abstract = {CONTEXT: Prediabetes now affects a substantial proportion of the population, marking a growing group of individuals at increased risk for the development of type 2 diabetes (T2D). Given the profound effect of T2D on an individual's morbidity and mortality, T2D prevention is of critical importance.

EVIDENCE ACQUISITION: We searched PubMed and Ovid MEDLINE databases for recent systematic reviews, meta-analyses, and original research articles pertaining to prediabetes and the prevention of T2D.

EVIDENCE SYNTHESIS: T2D prevention strategies have focused on intensive lifestyle modification as well as numerous medications that ultimately improve insulin resistance. Recently, a better understanding of the gut microbiome's role in diabetes progression has suggested a possible preventive role for fecal transplant. Finally, multiple incretin pharmaceutical agents have been developed that show promise in the prevention and treatment of T2D.

CONCLUSION: The number of novel ways to prevent T2D is rapidly growing. A thorough understanding of the indications, outcomes, and limitations of these new therapies is critical for all who care for individuals with diabetes.}, } @article {pmid39998294, year = {2025}, author = {Wolfe, TM and Jo, J and Pinkham, NV and Garey, KW and Walk, ST}, title = {The impact of ibezapolstat and other Clostridioides difficile infection-relevant antibiotics on the microbiome of humanized mice.}, journal = {Antimicrobial agents and chemotherapy}, volume = {69}, number = {4}, pages = {e0160424}, pmid = {39998294}, issn = {1098-6596}, support = {R01AI139261//HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; TL1 TR002318/TR/NCATS NIH HHS/United States ; R01 CA215784/CA/NCI NIH HHS/United States ; R01 AI139261/AI/NIAID NIH HHS/United States ; 5TL1TR002318-08//HHS | NIH | National Center for Advancing Translational Sciences (NCATS)/ ; R01CA215784//HHS | NIH | National Cancer Institute (NCI)/ ; //Acurx Pharmaceuticals, Inc/ ; }, mesh = {Animals ; *Anti-Bacterial Agents/pharmacology ; Mice ; *Clostridium Infections/drug therapy/microbiology ; *Gastrointestinal Microbiome/drug effects/genetics ; Vancomycin/pharmacology ; Humans ; *Clostridioides difficile/drug effects/pathogenicity ; RNA, Ribosomal, 16S/genetics ; Metronidazole/pharmacology ; Fecal Microbiota Transplantation ; Fidaxomicin/pharmacology ; Feces/microbiology ; Purine Nucleosides ; }, abstract = {Ibezapolstat (IBZ) is a competitive inhibitor of the bacterial Pol IIIC enzyme in clinical development for the treatment of Clostridioides difficile infection (CDI). Previous studies demonstrated that IBZ carries a favorable microbiome diversity profile compared to vancomycin (VAN). However, head-to-head comparisons with other CDI antibiotics have not been done. The purpose of this study was to compare microbiome changes associated with IBZ to other clinically used CDI antibiotics. Groups of germ-free (GF) mice received a fecal microbiota transplant from one of two healthy human donors and were subsequently exposed to either IBZ, VAN, fidaxomicin (FDX), metronidazole (MET), or no antibiotic (control). 16S rRNA encoding gene sequencing of temporally collected stool samples was used to compare the gut microbiome perturbations between treatment and no-drug control groups. Among the tested antibiotics, the most significant change in microbiome diversity was observed in MET-treated mice. Each antibiotic had a unique effect, but changes in alpha and beta diversities following FDX- and IBZ-treated groups were less pronounced than those observed in VAN- or MET-treated groups. By the end of therapy, both IBZ and FDZ increased the relative abundance of Bacteroidota (phylum), with IBZ additionally increasing the relative abundance of Actinomycetota (phylum). In microbiome-humanized mice, IBZ and FDX had smaller effects on gut microbiome diversity than VAN and MET. Notable differences were observed between the microbiome of IBZ- and FDX-treated groups, which may allow for differentiation of these two antibiotics in future studies.}, } @article {pmid39996827, year = {2025}, author = {Lu, D and Ma, X and Tao, K and Lei, H}, title = {Advancements in the Pathogenesis, Diagnosis, and Therapeutic Implications of Intestinal Bacteria.}, journal = {Current issues in molecular biology}, volume = {47}, number = {2}, pages = {}, pmid = {39996827}, issn = {1467-3045}, support = {2024AFB070//Hubei Natural Science Foundation/ ; 2023XHYN043//Science Foundation of Union Hospital/ ; 82403220//National Natural Science Foundation of China/ ; }, abstract = {Intestinal bacteria form one of the most complex microbial communities in the human body, playing a crucial role in maintaining host health and contributing to the development of various diseases. Here, we provide a comprehensive overview of the composition and function of intestinal bacteria, the factors affecting their homeostasis, and their association and mechanisms with a range of diseases (e.g., inflammatory bowel diseases, colorectal cancer, metabolic diseases). Additionally, their advanced potential in disease diagnosis and treatment is highlighted. Therapies, such as chemotherapy, radiotherapy, and immunotherapy, are significantly impacted by intestinal bacteria, with research indicating that bacteria can enhance chemoimmunotherapy efficiency by affecting T cell recruitment and immune cell infiltration. Fecal microbiota transplantation has emerged as a promising option for treating recurrent Clostridium difficile infections and certain metabolic and neurological disorders. Gut bacteria-related serum metabolites serve as non-invasive indicators for diagnosing CRC, while fecal immunochemical tests offer promising applications in CRC screening. Future research is needed to better understand the causal relationships between intestinal bacteria and diseases, develop more precise diagnostic tools, and evaluate the effectiveness and safety of microbiome-targeted therapies in clinical treatment. This study provides deeper insights into the role of intestinal bacteria in human health and disease, providing a scientific basis for innovative therapeutic strategies that have the potential to transform the landscape of healthcare.}, } @article {pmid39996473, year = {2025}, author = {Wang, X and Hu, M and Wu, W and Lou, X and Gao, R and Ma, T and Dheen, ST and Cheng, J and Xiong, J and Chen, X and Wang, J}, title = {Indole derivatives ameliorated the methamphetamine-induced depression and anxiety via aryl hydrocarbon receptor along "microbiota-brain" axis.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2470386}, pmid = {39996473}, issn = {1949-0984}, mesh = {Animals ; *Receptors, Aryl Hydrocarbon/metabolism/genetics ; *Anxiety/chemically induced/drug therapy/metabolism ; Mice ; *Depression/chemically induced/drug therapy/metabolism/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Methamphetamine/adverse effects ; *Indoles/pharmacology ; Male ; Humans ; Mice, Inbred C57BL ; *Brain/metabolism/drug effects ; Tryptophan/metabolism ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Bacteria/classification/genetics/isolation & purification/metabolism ; }, abstract = {In addition to the high neurotoxicity, depression, and anxiety are the most prominent characteristics of methamphetamine (Meth) withdrawal. Studies to date on the issue of Meth-associated depression and anxiety are focused on the brain, however, whether peripheral homeostasis, especially the "microbiota-gut" axis participates in these adverse outcomes, remains poorly understood. In the current study, with the fecal microbiota transplantation (FMT) assay, the mice received microbiota from Meth withdrawal mice displayed marked depression and anxiety behaviors. The 16S rRNA sequencing results showed that Meth withdrawal contributed to a striking reduction of Akkermansia, Bacteroides, Faecalibaculum, Desulfovibrio, and Anaerostipes, which are known to be associated with tryptophan (TRP) metabolism. Noteworthily, the substantial decreases of the indole derivatives from the TRP metabolic pathway, including IAA, IPA, ILA, IET, IArA, IAld, and TRM were observed in the serum of both Meth abusing humans and mice during Meth withdrawal with the UHPLC-MS/MS analysis. Combining the high and low TRP diet mouse model, the mice with high TRP diet obviously impeded Meth-associated depression and anxiety behaviors, and these results were further strengthened by the evidence that administration of IPA, IAA, and indole dramatically ameliorated the Meth induced aberrant behaviors. Importantly, these protective effects were remarkably counteracted in aryl hydrocarbon receptor knockout (AhR KO) mice, underlining the key roles of microbiota-indoles-AhR signaling in Meth-associated depression and anxiety. Collectively, the important contribution of the present work is that we provide the first evidence that peripheral gut homeostasis disturbance but not limited to the brain, plays a key role in driving the Meth-induced depression and anxiety in the periods of withdrawal, especially the microbiota and the indole metabolic disturbance. Therefore, targeting AhR may provide novel insight into the therapeutic strategies for Meth-associated psychological disorders.}, } @article {pmid39996135, year = {2025}, author = {Sehgal, K and Berry, P and Cho, J and Saffouri, G and Dierkhising, RA and Battaglioli, E and Kashyap, PC and Pardi, D and Khanna, S}, title = {Body mass index changes after fecal microbiota transplantation for recurrent Clostridioides difficile infection.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848251321121}, pmid = {39996135}, issn = {1756-283X}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a successful therapy for Clostridioides difficile infection (CDI). FMT from overweight donors is speculated to influence the recipient's body mass index (BMI) after administration for CDI.

OBJECTIVES: We investigated changes in the recipient's BMI after FMT in relation to the donor's BMI.

DESIGN: We conducted a retrospective cohort study involving patients who underwent FMT for recurrent CDI at Mayo Clinic between 2012 and 2019.

METHODS: We analyzed demographic and donor data for patients undergoing FMT at Mayo Clinic (2012-2019). Recipient BMI (pre- and post-FMT) and donor BMI were extracted from medical records. Mixed-effects linear regression was used to evaluate the impact of donor BMI, donor BMI category, recipient baseline BMI, time before and after FMT, and interactions between these variables on overall BMI change and BMI change per month. Kaplan-Meier curves were used to assess BMI changes (⩾5 units) based on the last recorded post-FMT BMI.

RESULTS: We analyzed data from 401 patients with recorded BMI measurements before and after FMT. The median age of the recipients at the time of FMT was 59.1 years (interquartile range (IQR): 40.5-70.1 years), with 61.6% being female. The median BMI for recipients prior to FMT was 26.7 kg/m² (IQR: 22.7-31.6 kg/m²), while the median BMI of the donors was 24.5 kg/m[2] (IQR: 23.9-27.5 kg/m[2]). Stool from donors with a normal BMI was used for 58.2% of recipients, while 41.8% received stool from pre-obese donors. Donor BMI data were missing for 3.2% of recipients. Donor BMI was not significantly associated with changes in recipient BMI; for each 1-unit increase in donor BMI, a 0.01-unit monthly increase was observed (95% confidence interval: -0.0003, 0.02; p = 0.11). The log-rank test for BMI increases (⩾+5) and decreases (⩽-5) revealed no significant differences among the donor BMI groups (Chi-squared = 4.4, p = 0.1 for increases, Chi-squared = 2, p = 0.4 for decreases).

CONCLUSION: The lack of impact of donor BMI on BMI changes post-FMT suggests that these changes are more dependent on the recipient's metabolic profile. Prospective, controlled trials are required to analyze these results more comprehensively.}, } @article {pmid39996003, year = {2025}, author = {Ren, K and Yong, C and Jin, Y and Rong, S and Xue, K and Cao, B and Wei, H}, title = {Unraveling the microbial mysteries: gut microbiota's role in ulcerative colitis.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1519974}, pmid = {39996003}, issn = {2296-861X}, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon. Recent research has highlighted the significant role of gut microbiota in the pathogenesis and treatment of UC. This review aims to provide a comprehensive overview of the current understanding of the relationship between gut microbiota and UC. We discuss the involvement of gut microbiota in the onset of UC, including the dysbiosis observed in patients and its potential mechanisms. Additionally, the role of extra-intestinal microbiota in UC pathogenesis is explored, which has been less studied but is gaining attention. The influence of gut microbiota on the efficacy of biological immunotherapy for UC is also examined, highlighting how microbial composition can influence treatment outcomes. Furthermore, we review microbiota transplantation, and their potential benefits in UC management. Finally, we consider the combined use of antibiotics and biological agents in UC treatment, discussing their synergistic effects and potential drawbacks. This review underscores the importance of gut microbiota in UC and suggests that targeting microbial communities could offer new avenues for effective treatment.}, } @article {pmid39995913, year = {2025}, author = {Morshedbak, M and Rahimi, K and Tabandeh, MR}, title = {Effect of fecal microbiota transplantation on ulcerative colitis model in rats: The gut-brain axis.}, journal = {Heliyon}, volume = {11}, number = {3}, pages = {e42430}, pmid = {39995913}, issn = {2405-8440}, abstract = {STUDY OBJECTIVES: The impact of fecal microbiota transplantation (FMT) on the TLR4/MYD88/NF-kB signaling pathway in the colon in the ulcerative colitis model, as well as the incidence of anxiety behaviors caused by the colitis model was investigated.

METHODS: Twenthy four ats were induced with ulcerative colitis using a 4 % acetic acid solution administered intrarectally and were subsequently treated with prednisolone and FMT. The study examined several indicators, such as TLR4, MYD88, and NF-κB mRNA expression, along with oxidative stress factors. Additionally, it examined the relationship between anxiety-related behaviors and colitis and assessed the pro-inflammatory cytokines in the hippocampus.

RESULTS: FMT led to lower disease score index and improved colon tissue pathology findings. This was associated with reduced mRNA expression of TLR4, MYD88, and NF-κB, as well as lower levels of TOS, and higher levels of TAC, GSH, and GSSG in colon tissues. FMT was found to reduce anxiety in both the open field and elevated plus maze tests. Additionally, levels of IL-6 and TNF-a were decreased in the hippocampus.

CONCLUSIONS: FMT suppressed acetic acid-induced colitis by inhibiting the TLR4/MYD88/NF-kB signaling pathway. FMT reduced anxiety in open field and plus maze tests, and resulted in decreased levels of IL-6 and TNF-a in the hippocampus.}, } @article {pmid39994836, year = {2025}, author = {Wan, J and Zhou, J and Wang, Z and Liu, D and Zhang, H and Xie, S and Wu, K}, title = {Epidemiology, pathogenesis, diagnosis, and treatment of inflammatory bowel disease: Insights from the past two years.}, journal = {Chinese medical journal}, volume = {138}, number = {7}, pages = {763-776}, pmid = {39994836}, issn = {2542-5641}, mesh = {Humans ; *Inflammatory Bowel Diseases/epidemiology/diagnosis/therapy ; }, abstract = {Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic inflammation of the gastrointestinal tract with unknown etiology. The cause of IBD is widely considered multifactorial, with prevailing hypotheses suggesting that the microbiome and various environmental factors contribute to inappropriate activation of the mucosal immune system in genetically susceptible individuals. Although the incidence of IBD has stabilized in Western countries, it is rapidly increasing in newly industrialized countries, particularly China, making IBD a global disease. Significant changes in multiple biomarkers before IBD diagnosis during the preclinical phase provide opportunities for earlier diagnosis and intervention. Advances in technology have driven the development of telemonitoring tools, such as home-testing kits for fecal calprotectin, serum cytokines, and therapeutic drug concentrations, as well as wearable devices for testing sweat cytokines and heart rate variability. These tools enable real-time disease activity assessment and timely treatment strategy adjustments. A wide range of novel drugs for IBD, including interleukin-23 inhibitors (mirikizumab, risankizumab, and guselkumab) and small-molecule drugs (etrasimod and upadacitinib), have been introduced in the past few years. Despite these advancements, approximately one-third of patients remain primary non-responders to the initial treatment, and half eventually lose response over time. Precision medicine integrating multi-omics data, advanced combination therapy, and complementary approaches, including stem cell transplantation, psychological therapies, neuromodulation, and gut microbiome modulation therapy, may offer solutions to break through the therapeutic ceiling.}, } @article {pmid39994634, year = {2025}, author = {Almheiri, RT and Hajjar, B and Alkhaaldi, SMI and Rabeh, N and Aljoudi, S and Abd-Elrahman, KS and Hamdan, H}, title = {Beyond weight loss: exploring the neurological ramifications of altered gut microbiota post-bariatric surgery.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {223}, pmid = {39994634}, issn = {1479-5876}, mesh = {Humans ; *Bariatric Surgery ; *Gastrointestinal Microbiome ; *Weight Loss ; *Nervous System Diseases/microbiology ; Animals ; }, abstract = {This review discusses findings related to neurological disorders, gut microbiota, and bariatric surgery, focusing on neurotransmitters, neuroendocrine, the pathophysiology of bacteria contributing to disorders, and possible therapeutic interventions. Research on neurotransmitters suggests that their levels are heavily influenced by gut microbiota, which may link them to neurological disorders such as Alzheimer's disease, Parkinson's disease, Multiple sclerosis, Depression, and Autism spectrum disorder. The pathophysiology of bacteria that reach and influence the central nervous system has been documented. Trends in microbiota are often observed in specific neurological disorders, with a prominence of pro-inflammatory bacteria and a reduction in anti-inflammatory types. Furthermore, bariatric surgery has been shown to alter microbiota profiles similar to those observed in neurological disorders. Therapeutic interventions, including fecal microbiota transplants and probiotics, have shown potential to alleviate neurological symptoms. We suggest a framework for future studies that integrates knowledge from diverse research areas, employs rigorous methodologies, and includes long-trial clinical control groups.}, } @article {pmid39991465, year = {2025}, author = {Ahmadi, A and Kouhsari, E and Razavi, S and Mohamadzadeh, N and Besharat, S and Vakili, MA and Amiriani, T}, title = {Comparative analysis of dominant gut microbiota in Inflammatory Bowel Disease patients and healthy individuals: A case-control study.}, journal = {New microbes and new infections}, volume = {64}, number = {}, pages = {101567}, pmid = {39991465}, issn = {2052-2975}, abstract = {BACKGROUND: Chronic inflammation in the gut might be linked to microbiota dysbiosis.

OBJECTIVE: This study aimed to investigate alterations in the gut microbiota composition of adult IBD patients compared to healthy controls.

METHODS: This case-control study investigated the relationship between faecal microbiota composition and IBD in adults. Real-time qPCR analysis using bacterial 16S rRNA gene quantified the abundance of six key bacterial groups (Firmicutes, Lactobacillus spp., Bifidobacterium spp., Fusobacterium spp., Bacteroides fragilis, and Faecalibacterium prausnitzii) in faecal samples from 30 IBD patients (13 Crohn's disease, 17 ulcerative colitis) and 30 healthy controls. A correlation matrix was employed to assess relationships between these bacteria.

RESULTS: Real-time qPCR revealed significant differences (p-value <0.05) in the abundance of several bacterial groups between IBD patients and healthy controls. Firmicutes, Fusobacterium spp., and B. fragilis were significantly more abundant (p-value <0.05) in IBD patients compared to controls. Conversely, Lactobacillus spp. and F. prausnitzii were both significantly less abundant (p-value <0.05) in IBD patients. While some bacterial groups exhibited trends toward higher abundance in either CD or UC patients, these differences were not statistically significant (p-value >0.111). The correlation matrix analysis revealed specific co-occurrence patterns: Bacteroides showed a strong negative correlation with Prevotella, more abundant in healthy controls, suggesting a shift in dominance in IBD patients. Lactobacillus spp. and F. prausnitzii exhibited a positive correlation in healthy individuals, indicating their potential cooperative role in maintaining gut homeostasis.

CONCLUSION: This study identified significant alterations in gut microbiota composition in adult IBD patients compared to healthy controls, with notable differences in the abundance of specific bacterial groups. These findings suggest that gut microbiota dysbiosis may play a critical role in IBD pathogenesis. The identification of specific bacterial imbalances provides a foundation for developing microbiota-based therapies, such as probiotics, prebiotics, and fecal microbiota transplantation, as potential interventions for restoring microbial balance and mitigating disease progression. Further research is needed to translate these insights into targeted therapeutic strategies and to explore their effectiveness in clinical settings.}, } @article {pmid39989875, year = {2025}, author = {Bednárik, DS and Földvári-Nagy, KC and Simon, V and Rancz, A and Gede, N and Veres, DS and Paraskevopoulos, P and Schnabel, T and Erőss, B and Hegyi, P and Lenti, K and Földvári-Nagy, L}, title = {Comparative effectiveness of different therapies for Clostridioides difficile infection in adults: a systematic review and network meta-analysis of randomized controlled trials.}, journal = {The Lancet regional health. Europe}, volume = {49}, number = {}, pages = {101151}, pmid = {39989875}, issn = {2666-7762}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated diarrhea, with substantial morbidity and mortality. CDI is a severe and growing problem with numerous treatment options. We evaluated the effectiveness of all therapies in recurrent and non-recurrent infections and their prevention.

METHODS: This network meta-analysis and systematic review of randomized controlled trials (RCTs) compared all CDI therapies and preventions. We included RCTs published until 19 August 2024 and focused on adult population. We performed a systematic search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials. Inclusion criteria were patients: adults (>16) treated against CDI; study type: randomized controlled trial; outcome: cure rate, recurrence or effectiveness of prevention. Any publication not meeting all criteria was considered to be ineligible and excluded. We applied random-effects meta-analysis using frequentist methods. We reported our main results as odds ratios (as a symmetric effect size measure, OR) with 95% confidence interval (95% CI). We used the Cochrane risk-of-bias tool to assess the risk of bias. Our study protocol was preregistered in PROSPERO (CRD42022371210).

FINDINGS: We assessed 73 RCTs with 28 interventions, involving 27,959 patients (49.2% female) in five networks. Fecal microbiota transplantation (FMT) was the most effective treatment in terms of the cure rate overall (P-score: 0.9952) and in recurrent cases (P-score: 0.9836). In recurrent cases, fidaxomicin (P-score: 0.6734) showed significantly greater effectiveness than vancomycin (P-score: 0.3677) and tolevamer (P-score: 0.0365). For non-recurrent CDI treatments ridinilazole, fidaxomicin, FMT and nitazoxanide were equally effective. Ridinilazole (P-score: 0.7671) and fidaxomicin (P-score: 0.7627) emerged as the most effective in preventing recurrence. Probiotics were not effective in preventing CDI, since network meta-analyses did not show significant differences between probiotics and placebo. In probiotics' subgroups pairwise meta-analyses Lactobacillaceae proved to be significantly more effective in prevention than placebo. Oral and colonoscopic FMT administration methods were equally effective. The study-level aggregated risk of bias of the publications included ranged from low to high. We observed relevant heterogeneity among studies in therapeutic doses, treatment durations, and follow-up times.

INTERPRETATION: The superiority of FMT in the treatment of CDI highlights the potential for increased use of FMT in clinical settings. Further research on optimizing FMT protocols and exploring its long-term safety and efficacy in larger samples is needed. Our findings suggest that the preventive use of probiotics might be questioned.

FUNDING: None.}, } @article {pmid39989768, year = {2025}, author = {Reddi Sree, R and Kalyan, M and Anand, N and Mani, S and Gorantla, VR and Sakharkar, MK and Song, BJ and Chidambaram, SB}, title = {Newer Therapeutic Approaches in Treating Alzheimer's Disease: A Comprehensive Review.}, journal = {ACS omega}, volume = {10}, number = {6}, pages = {5148-5171}, pmid = {39989768}, issn = {2470-1343}, abstract = {Alzheimer's disease (AD) is an aging-related irreversible neurodegenerative disease affecting mostly the elderly population. The main pathological features of AD are the extracellular Aβ plaques generated by APP cleavage through the amyloidogenic pathway, the intracellular neurofibrillary tangles (NFT) resulting from the hyperphosphorylated tau proteins, and cholinergic neurodegeneration. However, the actual causes of AD are unknown, but several studies suggest hereditary mutations in PSEN1 and -2, APOE4, APP, and the TAU genes are the major perpetrators. In order to understand the etiology and pathogenesis of AD, various hypotheses are proposed. These include the following hypotheses: amyloid accumulation, tauopathy, inflammation, oxidative stress, mitochondrial dysfunction, glutamate/excitotoxicity, cholinergic deficiency, and gut dysbiosis. Currently approved therapeutic interventions are donepezil, galantamine, and rivastigmine, which are cholinesterase inhibitors (ChEIs), and memantine, which is an N-methyl-d-aspartate (NMDA) antagonist. These treatment strategies focus on only symptomatic management of AD by attenuating symptoms but not regeneration of neurons or clearance of Aβ plaques and hyperphosphorylated Tau. This review focuses on the pathophysiology, novel therapeutic targets, and disease-altering treatments such as α-secretase modulators, active immunotherapy, passive immunotherapy, natural antioxidant products, nanomaterials, antiamyloid therapy, tau aggregation inhibitors, transplantation of fecal microbiota or stem cells, and microtubule stabilizers that are in clinical trials or still under investigation.}, } @article {pmid39989751, year = {2025}, author = {Arantes, JA and Di Pietro, R and Ratté, M and Arroyo, LG and Leclère, M and Costa, MC}, title = {Changes in bacterial viability after preparation and storage of fecal microbiota transplantation solution using equine feces.}, journal = {PeerJ}, volume = {13}, number = {}, pages = {e18860}, pmid = {39989751}, issn = {2167-8359}, mesh = {Animals ; Horses/microbiology ; *Feces/microbiology ; *Fecal Microbiota Transplantation/methods/veterinary ; *Microbial Viability/drug effects ; Cryoprotective Agents/pharmacology ; Freezing ; Glycerol/pharmacology ; Oxygen ; Cryopreservation ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been used as a treatment option for horses (Equus caballus) with gastrointestinal diseases. Several preparation and conservation protocols to improve bacterial survival have been studied in other species.

METHODS: This study aimed to evaluate the impact of oxygen exposure and different protectant solutions on bacterial viability before and after freezing using horse feces. Fecal samples from 10 healthy horses were aliquoted and diluted in cryoprotectant solutions containing antioxidants (n = 40) or 10% glycerol (n = 40). Half of the aliquots from each dilution condition were prepared inside an anaerobic chamber, while the other half were prepared under ambient air conditions. Each sample was also analyzed fresh and after freezing at -20 °C for 90 days. Bacterial viability was assessed using flow cytometry. A mixed linear model and the Friedman and Wilcoxon tests were used depending on data distribution.

RESULTS: Freeze-thawing decreased bacterial viability by 47% (mean ± SD: 51 ± 27% before, 27 ± 8% after; p < 0.001). Glycerol was superior to the cryoprotectant after freezing (32 ± 8% glycerol, 24 ± 8% cryoprotectant; p < 0.001). Oxygen exposure did not affect viability (p = 0.13). There was no statistical difference between protectant solutions in fresh samples (p = 0.16).

CONCLUSIONS: Fresh FMT solutions may be better for treating horses with dysbiosis, but if freezing cannot be avoided, glycerol should be used to dilute feces.}, } @article {pmid39988618, year = {2025}, author = {Liang, Y and Du, M and Li, X and Gao, J and Li, Q and Li, H and Li, J and Gao, X and Cong, H and Huang, Y and Li, X and Wang, L and Cui, J and Gan, Y and Tu, H}, title = {Upregulation of Lactobacillus spp. in gut microbiota as a novel mechanism for environmental eustress-induced anti-pancreatic cancer effects.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2470372}, pmid = {39988618}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome ; Animals ; Humans ; Mice ; Fecal Microbiota Transplantation ; Killer Cells, Natural/immunology ; *Lactobacillus/genetics/physiology ; *Pancreatic Neoplasms/therapy/microbiology/immunology ; *Carcinoma, Pancreatic Ductal/therapy/microbiology/immunology ; Probiotics/administration & dosage ; Tumor Microenvironment ; Feces/microbiology ; Male ; Up-Regulation ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; Female ; Cell Line, Tumor ; Limosilactobacillus reuteri/physiology ; }, abstract = {Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited effective treatment options. Emerging evidence links enriched environment (EE)-induced eustress to PDAC inhibition. However, the underlying mechanisms remain unclear. In this study, we explored the role of gut microbiota in PDAC-suppressive effects of EE. We demonstrated that depletion of gut microbiota with antibiotics abolished EE-induced tumor suppression, while fecal microbiota transplantation (FMT) from EE mice significantly inhibited tumor growth in both subcutaneous and orthotopic PDAC models housed in standard environment. 16S rRNA sequencing revealed that EE enhanced gut microbiota diversity and selectively enriched probiotic Lactobacillus, particularly L. reuteri. Treatment with L. reuteri significantly suppressed PDAC tumor growth and increased natural killer (NK) cell infiltration into the tumor microenvironment. Depletion of NK cells alleviated the anti-tumor effects of L. reuteri, underscoring the essential role of NK cell-mediated immunity in anti-tumor response. Clinical analysis of PDAC patients showed that higher fecal Lactobacillus abundance correlated with improved progression-free and overall survival, further supporting the therapeutic potential of L. reuteri in PDAC. Overall, this study identifies gut microbiota as a systemic regulator of PDAC under psychological stress. Supplementation of psychobiotic Lactobacillus may offer a novel therapeutic strategy for PDAC.}, } @article {pmid39984137, year = {2025}, author = {Dai, J and Yang, J and Han, S and Li, N and Wang, S and Xia, S and Kim, HH and Jun, Y and Lee, S and Kitagawa, Y and Xie, F and Yang, L and Shen, S and Chen, L and Turner, DP and Hodin, RA and Martyn, JAJ and Mao, J and You, Z}, title = {Deficiency of intestinal alkaline phosphatase affects behavior and microglia activity in mice.}, journal = {Brain, behavior, and immunity}, volume = {126}, number = {}, pages = {297-310}, pmid = {39984137}, issn = {1090-2139}, support = {R61 NS133083/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Microglia/metabolism/physiology ; *Alkaline Phosphatase/metabolism/deficiency/genetics ; Gastrointestinal Microbiome/physiology ; Mice ; Mice, Knockout ; *Behavior, Animal/physiology ; Mice, Inbred C57BL ; Male ; Brain/metabolism ; Fecal Microbiota Transplantation ; Anxiety/metabolism ; Phagocytosis/physiology ; }, abstract = {The gut microbiota plays crucial roles in the development and functions of the central nervous system (CNS) as well as in modulation of neurobehavior in heath and disease. The gut brush border enzyme intestinal alkaline phosphatase (IAP) is an important positive regulator of gut microbial homeostasis. In mice, IAP is encoded by Akp3 gene, which is specifically expressed in the duodenum of the small intestine. IAP deficiency alters gut bacterial composition and gut barrier function. Decreased IAP activity has been observed in aging, gut inflammatory diseases, and metabolic disorders. We hypothesized that this enzyme could also play an important role in modulating neurobehavior. We performed deep sequencing of gut bacterial 16S rRNA and found that IAP deficiency changed gut microbiota composition at various taxonomic levels. Using targeted metabolomic analysis, we also found that IAP deficiency resulted in changes of gut bacteria-derived metabolites in serum and brain metabolism. Neurobehavioral analyses revealed that Akp3[-/-] (IAP knockout) mice had decreased basal nociception thresholds, increased anxiety-like behavior, and reduced locomotor activity. Furthermore, Akp3[-/-] mice had more pronounced brain microglial phagocytic activity, together with an increase in the activated microglia population. Fecal microbiota transplantation from wildtype to Akp3[-/-] mice partially improved neurobehavior and reduced brain microglial phagocytic activity in Akp3[-/-] mice. This study demonstrates that deficiency of the endogenous gut-derived host factor IAP induces behavioral phenotype changes (nociception; motor activity, and anxiety) and affects brain microglia activity. Changes in the gut microbiota induced by knocking down Akp3 contribute to behavioral changes, which is probably mediated by microglia activity modulated by the gut bacteria-derived metabolites.}, } @article {pmid39983749, year = {2025}, author = {Davido, B and Merrick, B and Kuijper, E and Benech, N and Biehl, LM and Corcione, S and , }, title = {How can the gut microbiome be targeted to fight multidrug-resistant organisms?.}, journal = {The Lancet. Microbe}, volume = {6}, number = {8}, pages = {101063}, doi = {10.1016/j.lanmic.2024.101063}, pmid = {39983749}, issn = {2666-5247}, mesh = {*Gastrointestinal Microbiome/drug effects ; Humans ; *Drug Resistance, Multiple, Bacterial ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Phage Therapy ; *Bacterial Infections/microbiology/therapy/prevention & control ; *Bacteria/drug effects ; Vancomycin-Resistant Enterococci ; }, abstract = {The rise of antimicrobial resistance presents a challenge to public health, undermines the efficacy of antibiotics, and compromises the management of infectious diseases. Gut colonisation by multidrug-resistant organisms, such as multidrug-resistant Enterobacterales and vancomycin-resistant enterococci, is associated with increased morbidity and mortality rates, as well as health-care costs. Of late, the role of the gut microbiome in combating colonisation by multidrug-resistant organisms, which could precede invasive infection, has garnered interest. Innovative interventions, including faecal microbiota transplantation, probiotics, phage therapy, and bacterial consortia, represent potential preventive or therapeutic options to counteract colonisation by multidrug-resistant organisms. In this Personal View, we have synthesised the current findings on these interventions and elucidated their potential as solutions to the crisis of antimicrobial resistance.}, } @article {pmid39981255, year = {2025}, author = {Yao, K and Zheng, L and Chen, W and Xie, Y and Liao, C and Zhou, T}, title = {Characteristics, pathogenic and therapeutic role of gut microbiota in immunoglobulin A nephropathy.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1438683}, pmid = {39981255}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Glomerulonephritis, IGA/therapy/microbiology/immunology/etiology ; Animals ; Fecal Microbiota Transplantation ; Immunoglobulin A/immunology ; Immunity, Mucosal ; }, abstract = {Immunoglobulin A nephropathy (IgAN) is the most prevalent glomerulonephritis in the world, and it is one of the leading causes of end-stage kidney disease. It is now believed that the pathogenesis of IgAN is the mesangial deposition of immune complex containing galactose-deficient IgA1, resulting in glomerular injury. Current treatments for IgAN include supportive care and immunosuppressive therapy. A growing number of studies found that the gut microbiota in IgAN was dysregulated. Gut microbiota may be involved in the development and progression of IgAN through three main aspects: destruction of intestinal barrier, changes in metabolites and abnormal mucosal immunity. Interestingly, therapies by modulating the gut microbiota, such as fecal microbiota transplantation, antibiotic treatment, probiotic treatment, Chinese herbal medicine Zhen Wu Tang treatment, gluten-free diet, and hydroxychloroquine treatment, can improve IgAN. In this review, the alteration of gut microbiota in IgAN, potential pathogenic roles of gut microbiota on IgAN and potential approaches to treat IgAN by modulating the gut microbiota are summarized.}, } @article {pmid39979990, year = {2025}, author = {Xie, H and Zhang, H and Zhou, L and Chen, J and Yao, S and He, Q and Li, Z and Zhou, Z}, title = {Fecal microbiota transplantation promotes functional recovery in mice with spinal cord injury by modulating the spinal cord microenvironment.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {210}, pmid = {39979990}, issn = {1479-5876}, support = {202201010803//Science and Technology Project Foundation of Guangzhou City/ ; 2024A03J1068//Science and Technology Project Foundation of Guangzhou City/ ; }, mesh = {Animals ; *Spinal Cord Injuries/therapy/physiopathology/microbiology/pathology ; *Fecal Microbiota Transplantation ; *Recovery of Function ; *Spinal Cord/pathology/physiopathology ; Gastrointestinal Microbiome ; Mice, Inbred C57BL ; Mice ; *Cellular Microenvironment ; Axons/pathology ; Inflammation/pathology ; Neurons/pathology ; RNA, Ribosomal, 16S/genetics ; Nerve Regeneration ; Female ; Disease Models, Animal ; }, abstract = {BACKGROUND: spinal cord injury (SCI) disrupts the gut microbiota, worsening the injury's impact. Fecal microbiota transplantation (FMT) is increasingly recognized as a promising strategy to improve neural function post-SCI, yet its precise mechanisms are still far from clear. The present study aims to elucidate how FMT influences motor function recovery and its underlying mechanisms utilizing a SCI mouse model.

METHODS: Mice with SCI received FMT from healthy donors. We used 16 S rRNA amplicon sequencing to analyze the alterations of gut microbes. Pathological alterations in the spinal cord tissue, including neuronal survival, axonal regeneration, cell proliferation, and neuroinflammation, were assessed among experimental groups. Additionally, RNA sequencing (RNA-seq) was used to explore alterations in relevant signaling pathways.

RESULTS: Significant shifts in gut microbiota composition following SCI were observed through 16 S rRNA analysis. On day 7 post-SCI, the FMT group exhibited a significantly higher diversity of gut microbiota compared to the ABX group, with the composition in the FMT group more closely resembling that of healthy mice. FMT promoted neuronal survival and axonal regeneration, leading to notable improvements in motor function compared to control mice. Immunofluorescence staining showed increased neuronal survival, alleviated extracellular matrix (ECM) deposition, diminished glial scar formation, and reduced inflammation in FMT-treated mice. RNA-seq analysis indicated that FMT induced transcriptomic changes associated with material metabolism, ECM remodeling, and anti-inflammatory responses.

CONCLUSIONS: FMT restored gut microbiota balance in SCI mice, mitigated inflammation, and promoted ECM remodeling, establishing an optimal environment for neural recovery. These findings demonstrated that FMT may represent a valuable approach to enhance functional recovery following SCI.}, } @article {pmid39979777, year = {2025}, author = {Nagy, M and Wychera, C and Schemm, J and Brewster, R and Duncan, CN}, title = {Bacterial and Parasitic Stool Studies Have Limited Utility in Pediatric Hematopoietic Stem Cell Transplant Patients.}, journal = {Pediatric blood & cancer}, volume = {72}, number = {5}, pages = {e31617}, doi = {10.1002/pbc.31617}, pmid = {39979777}, issn = {1545-5017}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Child ; *Feces/parasitology/microbiology/virology ; Male ; Female ; Child, Preschool ; Adolescent ; *Graft vs Host Disease/etiology ; *Diarrhea/microbiology/etiology/parasitology/diagnosis ; Retrospective Studies ; Follow-Up Studies ; Infant ; *Bacteria/isolation & purification ; Parasites/isolation & purification ; Prognosis ; *Bacterial Infections/diagnosis/etiology/microbiology ; }, abstract = {BACKGROUND: Diarrhea is a common complication among pediatric hematopoietic stem cell transplantation (HCT) recipients. Although many of the cases are secondary to graft-versus-host disease (GVHD), stool microbiological studies are often performed to evaluate an underlying infectious etiology. The aim of this study was to assess the frequency and utility of stool studies in children who have undergone HCT.

METHODS: Demographics, clinical characteristics, and stool study results (viral, parasitic, and bacterial) of all patients who underwent HCT at a large, academic, freestanding children's hospital between January 2006 and December 2023 were obtained. Statistical analysis conducted included t tests, chi-square, and linear regression.

RESULTS: Overall, 1381 HCT recipients (9.2 ± 6.6 years) were included. Altogether, 6509 stool studies were obtained among 741 (54%) patients. Salmonella, Shigella, Yersinia, Campylobacter, and Escherichia coli (SSYCE) studies were sent on 363 (26%, 2252 studies) patients with 1 (0.04%) positive result. Clostridium difficile was sent on 706 (51%, 2055 studies) patients, with 156 positive studies (7.6%). Stool ova and parasite testing was sent on 143 (10%, 242 studies) patients, with two positive results (0.8%). Viral studies were sent on 638 (46%, 1960 studies) patients, with 107 positive studies (5.5%).

CONCLUSIONS: While testing for Clostridium difficile and enteric viruses may have value in the work-up of pediatric HCT patients, SSYCE and O&P studies hold little to no value. Clinical practices surrounding routine stool microbiological studies should be reconsidered.}, } @article {pmid39979287, year = {2025}, author = {Tsenkova, M and Brauer, M and Pozdeev, VI and Kasakin, M and Busi, SB and Schmoetten, M and Cheung, D and Meyers, M and Rodriguez, F and Gaigneaux, A and Koncina, E and Gilson, C and Schlicker, L and Herebian, D and Schmitz, M and de Nies, L and Mayatepek, E and Haan, S and de Beaufort, C and Cramer, T and Meiser, J and Linster, CL and Wilmes, P and Letellier, E}, title = {Ketogenic diet suppresses colorectal cancer through the gut microbiome long chain fatty acid stearate.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {1792}, pmid = {39979287}, issn = {2041-1723}, support = {OT2 OD030544/OD/NIH HHS/United States ; U2C DK119886/DK/NIDDK NIH HHS/United States ; }, mesh = {*Diet, Ketogenic ; *Gastrointestinal Microbiome/physiology ; Animals ; *Stearic Acids/metabolism ; *Colorectal Neoplasms/diet therapy/microbiology/pathology/metabolism ; Humans ; Mice ; Male ; Apoptosis ; Female ; Bacteria/metabolism/genetics ; Disease Models, Animal ; Colon/microbiology/pathology ; Cell Line, Tumor ; Fecal Microbiota Transplantation ; }, abstract = {Colorectal cancer (CRC) patients have been shown to possess an altered gut microbiome. Diet is a well-established modulator of the microbiome, and thus, dietary interventions might have a beneficial effect on CRC. An attenuating effect of the ketogenic diet (KD) on CRC cell growth has been previously observed, however the role of the gut microbiome in driving this effect remains unknown. Here, we describe a reduced colonic tumor burden upon KD consumption in a CRC mouse model with a humanized microbiome. Importantly, we demonstrate a causal relationship through microbiome transplantation into germ-free mice, whereby alterations in the gut microbiota were maintained in the absence of continued selective pressure from the KD. Specifically, we identify a shift toward bacterial species that produce stearic acid in ketogenic conditions, whereas consumers were depleted, resulting in elevated levels of free stearate in the gut lumen. This microbial product demonstrates tumor-suppressing properties by inducing apoptosis in cancer cells and decreasing colonic Th17 immune cell populations. Taken together, the beneficial effects of the KD are mediated through alterations in the gut microbiome, including, among others, increased stearic acid production, which in turn significantly reduces intestinal tumor growth.}, } @article {pmid39978693, year = {2025}, author = {Jiang, Y and Shi, L and Qu, Y and Ou, M and Du, Z and Zhou, Z and Zhou, H and Zhu, H}, title = {Multi-omics analysis reveals mechanisms of FMT in Enhancing antidepressant effects of SSRIs.}, journal = {Brain, behavior, and immunity}, volume = {126}, number = {}, pages = {176-188}, doi = {10.1016/j.bbi.2025.02.011}, pmid = {39978693}, issn = {1090-2139}, mesh = {Animals ; Male ; Mice ; Gastrointestinal Microbiome/drug effects/physiology ; Mice, Inbred C57BL ; *Depression/therapy/metabolism/drug therapy ; *Selective Serotonin Reuptake Inhibitors/pharmacology/therapeutic use ; Fluoxetine/pharmacology ; *Fecal Microbiota Transplantation/methods ; Antidepressive Agents/pharmacology ; Disease Models, Animal ; Hippocampus/metabolism ; Multiomics ; }, abstract = {OBJECTIVE: This study explores the behavioral and molecular biological impacts of Fecal Microbiota Transplantation (FMT) on depressive mice unresponsive to treatment with Selective Serotonin Reuptake Inhibitors (SSRIs).

METHODS: Healthy male C57BL/6 mice were used to establish a depression model through chronic restraint stress, treated with fluoxetine, and categorized into Response and Non-response groups. An FMT treatment was added to the Non-response group. Behavioral tests were conducted to assess symptoms of depression. The gut microbiome, plasma metabolites, and hippocampal tissue gene expression and function changes were analyzed using 16S rRNA gene sequencing, LC-MS, and RNA sequencing.

RESULTS: FMT significantly improved the depressive symptoms in SSRIs-resistant mice. There was a partial restoration in the diversity and structure of the gut microbiota in the FMT group. Compared to the Non-response group, significant changes were noted in the metabolomic profiles of the FMT group, identifying various differential metabolites. Functional annotations indicated that these metabolites are involved in multiple metabolic pathways. In the Non-response group, certain gene expression levels were significantly restored. GO and KEGG enrichment analyses revealed that these differential genes mainly involve cytokine activity, receptor signaling regulation, and NOD-like receptor signaling pathways. Joint analysis suggested that FMT may exert its effects through an increase in the abundance of g__Paraprevotella, leading to decreased baicalin content and increased Tal2 expression.

CONCLUSION: FMT has potential in improving depressive symptoms unresponsive to SSRIs treatment. Its mechanism may be related to the modulation of the gut microbiota and its metabolites, subsequently affecting gene expression.}, } @article {pmid39978276, year = {2025}, author = {Luo, X and Cheng, P and Fang, Y and Wang, F and Mao, T and Shan, Y and Lu, Y and Wei, Z}, title = {Yinzhihuang formula modulates the microbe‒gut‒liver axis and bile acid excretion to attenuate cholestatic liver injury.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {139}, number = {}, pages = {156495}, doi = {10.1016/j.phymed.2025.156495}, pmid = {39978276}, issn = {1618-095X}, mesh = {Animals ; *Bile Acids and Salts/metabolism ; *Drugs, Chinese Herbal/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Male ; Mice ; Liver/drug effects/pathology/metabolism ; Mice, Inbred C57BL ; *Cholestasis, Intrahepatic/drug therapy/chemically induced ; Disease Models, Animal ; 1-Naphthylisothiocyanate ; Cholestasis/drug therapy ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Cholestatic liver injury is a hepatobiliary disorder primarily characterized by cholestasis, which significantly contributes to liver damage. The Yinzhihuang (YZH) oral preparation is an effective clinical treatment for cholestatic liver injury; however, the specific mechanism of action has not been clarified.

PURPOSE: This study investigated YZH's pharmacological mechanisms associated with the microbe‒gut‒liver axis in cholestatic mice, offering new perspectives for the treatment of cholestasis.

METHODS: YZH's protective effects were evaluated by evaluating serum liver injury indices and liver staining in an alpha-nephthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis mouse model. Colon hematoxylin‒eosin (H&E) and alcian blue staining and FITC‒dextran leakage assays were performed to assess intestinal barrier integrity. Fluorescence in situ hybridization was employed to analyze bacterial translocation. Additionally, 16S rRNA sequencing, fecal microbiota transplantation, and bile acid metabolomics analysis were conducted to examine the relationships among the microbiome, bile acid metabolism, and YZH formula.

RESULTS: We found that YZH administration alleviated symptoms of ANIT-induced hepatic pathological injury and fibrosis. In addition, YZH reduced the transfer of gut bacteria to liver tissue by maintaining an intact intestinal barrier. Notably, YZH influenced the intestinal microbiota composition, upregulated the abundance of bile acid metabolism-associated probiotic bacteria, including Clostridiales, Lachnospiraceae and Bifidobacterium pseudolongum; and downregulated the abundance of Escherichia-Shigella and Serratia, thereby promoting bile acid excretion.

CONCLUSION: YZH protects against cholestatic liver damage by promoting bile excretion and maintaining intestinal mucosal barrier integrity. Furthermore, YZH alleviates cholestasis in a gut microbiota-dependent manner, and upregulation of probiotics may be crucial for YZH's influence on bile acid metabolism.}, } @article {pmid39975140, year = {2025}, author = {Oppenheimer, M and Tao, J and Moidunny, S and Roy, S}, title = {Anxiety-like behavior during protracted morphine withdrawal is driven by gut microbial dysbiosis and attenuated with probiotic treatment.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.01.29.633224}, pmid = {39975140}, issn = {2692-8205}, abstract = {The development of anxiety during protracted opioid withdrawal heightens the risk of relapse into the cycle of addiction. Understanding the mechanisms driving anxiety during opioid withdrawal could facilitate the development of therapeutics to prevent negative affect and promote continued abstinence. Our lab has previously established the gut microbiome as a driver of various side effects of opioid use, including analgesic tolerance and somatic withdrawal symptoms. We therefore hypothesized that the gut microbiome contributes to the development of anxiety-like behavior during protracted opioid withdrawal. In this study, we first established a mouse model of protracted morphine withdrawal, characterized by anxiety-like behavior and gut microbial dysbiosis. Next, we used fecal microbiota transplantation (FMT) to show that gut dysbiosis alone is sufficient to induce anxiety-like behavior. We further demonstrate that probiotic therapy during morphine withdrawal attenuates the onset of anxiety-like behavior, highlighting its therapeutic potential. Lastly, we examined transcriptional changes in the amygdala of morphine-withdrawn mice treated with probiotics to explore mechanisms by which the gut-brain axis mediates anxiety-like behavior. Our results support the use of probiotics as a promising therapeutic strategy to prevent gut dysbiosis and associated anxiety during opioid withdrawal, with potential implications for improving treatment outcomes in opioid recovery programs.}, } @article {pmid39975029, year = {2025}, author = {Zhang, XS and Wang, Y and Sun, H and Zerbe, C and Falcone, E and Bhattacharya, S and Zhang, M and Gao, Z and Diaz-Rubio, ME and Bharj, D and Patel, D and Pan, S and Ro, G and Grenard, J and Armstrong, A and Yin, YS and Dominguez-Bello, MG and Holland, S and Su, X and Blaser, MJ}, title = {Gut microbiota phospholipids regulate intestinal gene expression and can counteract the effects of antibiotic treatment.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39975029}, issn = {2692-8205}, abstract = {The gut microbiome influences immune and metabolic homeostasis. Our research using non-obese diabetic (NOD) mice revealed that early-life antibiotic exposure remodels the gut microbiome affecting metabolism and accelerating type 1 diabetes (T1D) incidence, with cecal material transplant (CMT) mitigating the damage. Now examining murine intestinal lipidomic profiles, we identified 747 compounds. Comparing the lipidomic profiles of cecal contents of conventional and germ-free mice and their diets, we identified 87 microbially-produced lipids reduced by antibiotic exposure but CMT-restored. Parallel analysis of human fecal lipid profiles after azithromycin-exposure showed significant alterations with substantial overlap with mice. In vitro co-culture with mouse macrophages or small intestinal epithelial cells and human colonic epithelial cells identified phospholipids that repress inflammation through the NFκB pathway. Oral administration of these phospholipids to antibiotic-treated NOD mice reduced expression of ileal genes involved in early stages of T1D pathogenesis. These findings indicate potential therapeutic anti-inflammatory roles of microbially-produced lipids.}, } @article {pmid39974080, year = {2025}, author = {McCann, JR and Yang, C and Bihlmeyer, NA and Tang, R and Truong, T and An, J and Jawahar, J and Ilkayeva, O and Muehlbauer, MJ and Hu, Z and Dressman, HK and Poppe, L and Granek, JA and David, LA and Shi, P and Balikcioglu, PG and Shah, SH and Armstrong, SC and Newgard, CB and Seed, PC and Rawls, JF}, title = {Branched chain amino acid metabolism and microbiome in adolescents with obesity during weight loss therapy.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.02.03.25321363}, pmid = {39974080}, abstract = {BACKGROUND: Obesity and weight loss in adults have been associated with distinct metabolome and gut microbiome features, but the extent to which those associations apply to adolescent stages remain unclear.

METHODS: The Pediatric Obesity Microbiome and Metabolism Study (POMMS) enrolled 220 adolescents aged 10-18 with severe obesity (OB) and 67 healthy weight controls (HWC). Blood, stool, and clinical measures were collected at baseline and after a 6-month obesity intervention for the OB group. Metabolomic profiling in serum using targeted quantitative mass spectrometry and microbiome profiling in stool were performed, and those features were assessed for associations with BMI, insulin resistance, and inflammation. Fecal microbiome transplants were performed on germ-free mice using samples from both groups to assess effects on weight gain and metabolic pathways.

RESULTS: Adolescents with OB exhibited higher serum branched-chain amino acid (BCAA) but lower ketoacid metabolite (BCKA) levels compared with HWC. This pattern was sex- and age-dependent, unlike adults with OB, who show elevated levels of both. Longitudinal analysis identified metabolic and microbial features correlated with changes in health measures during the intervention. The fecal microbiomes of adolescents with OB and HWC had similar diversity but differed in membership and functional potential. FMT from both OB and HWC donors had similar effects on mouse body weight, but specific taxa were linked to weight gain in FMT recipients.

CONCLUSION: Adolescents with OB have unique metabolomic adaptations and microbiome signatures compared to their HWC counterparts and adults with OB.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03139877 (Observational Study) and NCT02959034 (Repository).

FUNDING SOURCES: American Heart Association Grants: 17SFRN33670990, 20PRE35180195National Institute of Diabetes and Digestive and Kidney Diseases Grant: R24-DK110492.}, } @article {pmid39973149, year = {2025}, author = {Zhang, T and Liu, S and Liu, S and Zhao, P and Zhang, C and Wang, X and Meng, Y and Lu, Y}, title = {Oleanolic Acid Alleviates Hyperuricemia via Gut Microbiota Control the Integrity of Gut Barrier and the Expressions of Urate Transporter in Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {10}, pages = {5899-5914}, doi = {10.1021/acs.jafc.4c09270}, pmid = {39973149}, issn = {1520-5118}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Oleanolic Acid/administration & dosage ; *Hyperuricemia/metabolism/drug therapy/microbiology/genetics ; Mice ; Mice, Inbred C57BL ; Male ; Uric Acid/metabolism/blood ; *Organic Anion Transporters/metabolism/genetics ; Humans ; Kidney/metabolism/drug effects ; ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism/genetics ; Intestinal Mucosa/metabolism ; Glucose Transport Proteins, Facilitative/metabolism/genetics ; Fecal Microbiota Transplantation ; Bacteria/classification/genetics/isolation & purification/metabolism ; }, abstract = {Hyperuricemia (HUA) is a globally prevalent metabolic disorder characterized by an imbalance in uric acid (UA) production and excretion. In this study, we found that oleanolic acid (OA), a natural pentacyclic triterpene, effectively reduced HUA and associated kidney injury in C57BL/6J mice. A 12-week OA treatment significantly and dose-dependently reduced UA and creatinine levels in serum and urine while suppressing hepatic xanthine oxidase activity in HUA mice. Mechanistic analysis revealed that OA modulates the expression of urate transporters including ABCG2, GLUT9, and URAT1 in the kidney and small intestine. Furthermore, OA restored gut microbiota imbalances, increased short-chain fatty acid production, and enhanced the expressions of intestinal tight junction proteins in HUA mice, thereby improving gut barrier integrity in HUA mice. Consequently, fecal microbiota transplantation (FMT) was employed to illustrate the major mediating role of gut microbiota in OA's alleviation of HUA in mice. Recipient HUA mice transplanted with feces from OA-treated HUA mice exhibited significantly lower blood and urinary UA levels, reduced kidney inflammation, and improved gut microbiota balance compared to those receiving feces from untreated HUA mice (p < 0.05). Additionally, FMT normalized urate transporter expression and reinforced intestinal tight junctions in recipient mice. These findings underscore that OA mitigates HUA primarily by modulating gut microbiota, regulating urate transporter expression, and reinforcing gut barrier integrity, offering novel insights into its preventive potential for managing HUA and related complications.}, } @article {pmid40741483, year = {2024}, author = {Hunter, C and Dia, K and Boykins, J and Perry, K and Banerjee, N and Cuffee, J and Armstrong, E and Morgan, G and Banerjee, HN and Banerjee, A and Bhattacharya, S}, title = {An investigation for phylogenetic characterization of human pancreatic cancer microbiome by 16S rDNA sequencing and bioinformatics techniques.}, journal = {Journal of solid tumors}, volume = {14}, number = {1}, pages = {1-9}, pmid = {40741483}, issn = {1925-4067}, support = {T34 GM100831/GM/NIGMS NIH HHS/United States ; }, abstract = {Pancreatic cancer is a significant public health concern, with increasing incidence rates and limited treatment options. Recent studies have highlighted the role of the human microbiome, particularly the gut microbiota, in the development and progression of this disease. Microbial dysbiosis, characterized by alterations in the composition and function of the gut microbiota, has been implicated in pancreatic carcinogenesis through mechanisms involving chronic inflammation, immune dysregulation, and metabolic disturbances. Researchers have identified specific microbial signatures associated with pancreatic cancer, offering potential biomarkers for early detection and prognostication. By leveraging advanced sequencing and bioinformatics tools, scientists have delineated differences in the gut microbiota between pancreatic cancer patients and healthy individuals, providing insights into disease pathogenesis and potential diagnostic strategies. Moreover, the microbiome holds promise as a therapeutic target in pancreatic cancer treatment. Interventions aimed at modulating the microbiome, such as probiotics, prebiotics, and fecal microbiota transplantation, have demonstrated potential in enhancing the efficacy of existing cancer therapies, including chemotherapy and immunotherapy. These approaches can influence immune responses, alter tumor microenvironments, and sensitize tumors to treatment, offering new avenues for improving patient outcomes and overcoming therapeutic resistance. Overall, understanding the complex interplay between the microbiome and pancreatic cancer is crucial for advancing our knowledge of disease mechanisms and identifying innovative therapeutic strategies. Here we report phylogenetic analysis of the 16S rDNA microbial sequences of the pancreatic cancer mice microbiome and corresponding age matched healthy mice microbiome. We successfully identified differentially abundant microbiota in pancreatic cancer.}, } @article {pmid40734779, year = {2024}, author = {Lo, K and Kavarian, P and Wang, B and Parsana, R and Durazo-Arvizu, R and Sun, F and Michail, S}, title = {Fecal bile acid profiles before and after fecal microbial transplant in pediatric onset ulcerative colitis.}, journal = {Gut microbes reports}, volume = {1}, number = {1}, pages = {}, pmid = {40734779}, issn = {2993-3935}, support = {R01 HD081197/HD/NICHD NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; }, abstract = {Fecal bile acids (BAs) are key metabolites altered in patients with inflammatory bowel disease (IBD), therefore serving as potential targets of fecal microbial transplant (FMT). To compare changes in fecal BA composition and corresponding microbial transformation pathways in pediatric ulcerative colitis (UC) patients before and after FMT for up to 48 weeks. Fecal BAs, as well as enzymes and bacteria related to BA metabolism were measured in 28 healthy children, and 48 children with mild to moderate UC before and after FMT. Several primary BAs were higher in UC patients at baseline, and subsequently decreased over the 48 weeks following FMT. In particular, the primary BA cholic acid (CA) was higher in UC children at baseline (11.73 pg/mg) compared to healthy controls (8.47 pg/mg), decreased to 10.82 pg/mg at 4 weeks post FMT (p = 0.001) then 10.07 pg/mg at 48 weeks (p = 0.077). Following FMT, the ratio of secondary to primary BAs became more similar to healthy children. The genes coding for bile salt hydrolase, 7α/β-hydroxysteroid dehydrogenase, and bile acid induced operon enzymes were lower in UC patients at baseline, with the majority of them increasing following FMT. Similarly, many of the bacterial genera involved in bile acid metabolism had corresponding increases after FMT.}, } @article {pmid40303777, year = {2023}, author = {De Sabato, L and Ianiro, G and Alborali, GL and Kroneman, A and Grierson, SS and Krumova-Valcheva, GL and Hakze-van der Honing, RW and Johne, R and Kolackova, I and Kozyra, I and Gyurova, E and Pavoni, E and Reisp, K and Sassu, EL and Schilling-Loeffler, K and Smith, RP and Vasickova, P and Żmudzki, J and Rzeżutka, A and Di Bartolo, I}, title = {Molecular Characterization and Phylogenetic Analysis of Hepatitis E Virus (HEV) Strains from Pigs Farmed in Eight European Countries between 2020 and 2022.}, journal = {Transboundary and emerging diseases}, volume = {2023}, number = {}, pages = {2806835}, pmid = {40303777}, issn = {1865-1682}, mesh = {Animals ; *Hepatitis E virus/genetics/isolation & purification/classification ; Swine ; *Hepatitis E/veterinary/virology/epidemiology ; *Swine Diseases/virology/epidemiology ; Phylogeny ; Europe/epidemiology ; Feces/virology ; Genotype ; }, abstract = {In high-income countries, the hepatitis E virus (HEV) is considered an emerging threat causing autochthonous acute hepatitis in humans, with an increased number of reported cases over the last 10 years and related increased burden of chronic hepatitis in immunocompromised and transplant patients. Pigs are the main reservoir of the HEV-3 genotype, which is the most common in Europe, and can be transmitted to humans through the consumption of raw and undercooked pork products. Extensive sequencing revealed the existence of several HEV-3 subtypes in both humans and pigs, confirming a broad heterogeneity of the virus, with some subtypes, such as 3e, 3f, and 3c, which are predominant in Europe. In this study, 291 HEV sequences were obtained from pig feces sampled in more than 74 farms located in Austria, Bulgaria, Czech Republic, Germany, Italy, Poland, the United Kingdom, as well as an unknown number of farms in Netherlands. Of the 99 nonidentical sequences (99/291), 90 were assigned to seven established HEV-3 subtypes: 3a, 3c, 3e, 3f, 3g (here named 3g-like), 3i, and 3l (named 3l-like), already described in Europe, while nine sequences of HEV-3 could not be assigned to any existing subtype (here named 3 [∗]). The 3e subtype was the most common, detected in six out of eight countries, followed by 3f and 3c, which were also present in several countries; 3g-like, 3i, and 3l-like subtypes showed only a limited circulation. The distribution of frequently (3e, 3f, and 3c) and rarely (3g-like, 3i, and 3l-like) detected HEV-3 subtypes in pigs was correlated with their detection rates in human patients in Europe. The results from this study confirm the wide circulation of several HEV-3 strains in European pigs and confirm that sequencing is needed to monitor the different strains and to identify possible zoonotic transmission paths.}, } @article {pmid40503501, year = {2023}, author = {Kim, SY}, title = {[Gut Microbiota and Obesity].}, journal = {The Korean journal of helicobacter and upper gastrointestinal research}, volume = {23}, number = {4}, pages = {240-246}, pmid = {40503501}, issn = {2671-826X}, abstract = {Obesity is a global health concern associated with a wide range of diseases, including diabetes, metabolic syndrome, fatty liver, and cardiovascular conditions. Recent studies highlight the significant role of gut microbiota in obesity. Research indicates notable changes in the composition and diversity of gut microbiota in individuals diagnosed with obesity. The gut microbiota participate in energy metabolism, lipid synthesis, and regulation of inflammation and therefore play a key role in the pathogenesis of obesity. Therapeutic approaches based on the use of probiotics, prebiotics, Akkermansia muciniphila, and fecal microbiota transplantation have shown promise in animal studies as useful strategies against obesity and metabolic syndrome. However, further research is warranted to conclusively establish the specific strains, dosages, and mechanisms underlying the effectiveness of these novel strategies against obesity in humans.}, } @article {pmid39971913, year = {2025}, author = {Cune, D and Pitasi, CL and Rubiola, A and Jamma, T and Simula, L and Boucher, C and Fortun, A and Adoux, L and Letourneur, F and Saintpierre, B and Donnadieu, E and Terris, B and Bossard, P and Chassaing, B and Romagnolo, B}, title = {Inhibition of Atg7 in intestinal epithelial cells drives resistance against Citrobacter rodentium.}, journal = {Cell death & disease}, volume = {16}, number = {1}, pages = {112}, pmid = {39971913}, issn = {2041-4889}, mesh = {Animals ; *Autophagy-Related Protein 7/metabolism/genetics/deficiency ; *Citrobacter rodentium/pathogenicity ; *Enterobacteriaceae Infections/microbiology/immunology/pathology ; Mice ; Gastrointestinal Microbiome ; Autophagy ; *Intestinal Mucosa/microbiology/metabolism/pathology ; *Epithelial Cells/metabolism/microbiology ; Colitis/microbiology/pathology/immunology ; Mice, Inbred C57BL ; T-Lymphocytes, Regulatory/immunology ; }, abstract = {Autophagy, a cytoprotective mechanism in intestinal epithelial cells, plays a crucial role in maintaining intestinal homeostasis. Beyond its cell-autonomous effects, the significance of autophagy in these cells is increasingly acknowledged in the dynamic interplay between the microbiota and the immune response. In the context of colon cancer, intestinal epithelium disruption of autophagy has been identified as a critical factor influencing tumor development. This disruption modulates the composition of the gut microbiota, eliciting an anti-tumoral immune response. Here, we report that Atg7 deficiency in intestinal epithelial cells shapes the intestinal microbiota leading to an associated limitation of colitis induced by Citrobacter rodentium infection. Mice with an inducible, intestinal epithelial-cell-specific deletion of the autophagy gene, Atg7, exhibited enhanced clearance of C. rodentium, mitigated hyperplasia, and reduced pathogen-induced goblet cell loss. This protective effect is linked to a higher proportion of neutrophils and phagocytic cells in the early phase of infection. At later stages, it is associated with the downregulation of pro-inflammatory pathways and an increase in Th17 and Treg responses-immune responses known for their protective roles against C. rodentium infection, modulated by specific gut microbiota. Fecal microbiota transplantation and antibiotic treatment approaches revealed that the Atg7-deficiency-shapped microbiota, especially Gram-positive bacteria, playing a central role in driving resistance to C. rodentium infection. In summary, our findings highlight that inhibiting autophagy in intestinal epithelial cells contributes to maintaining homeostasis and preventing detrimental intestinal inflammation through microbiota-mediated colonization resistance against C. rodentium. This underscores the central role played by autophagy in shaping the microbiota in promoting immune-mediated resistance against enteropathogens.}, } @article {pmid39971742, year = {2025}, author = {Akagbosu, CO and McCauley, KE and Namasivayam, S and Romero-Soto, HN and O'Brien, W and Bacorn, M and Bohrnsen, E and Schwarz, B and Mistry, S and Burns, AS and Perez-Chaparro, PJ and Chen, Q and LaPoint, P and Patel, A and Krausfeldt, LE and Subramanian, P and Sellers, BA and Cheung, F and Apps, R and Douagi, I and Levy, S and Nadler, EP and Hourigan, SK}, title = {Gut microbiome shifts in adolescents after sleeve gastrectomy with increased oral-associated taxa and pro-inflammatory potential.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2467833}, pmid = {39971742}, issn = {1949-0984}, support = {R25 DK096944/DK/NIDDK NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome ; Adolescent ; Humans ; Animals ; Mice ; *Gastrectomy ; Feces/microbiology/chemistry ; Female ; Male ; *Bacteria/classification/isolation & purification/genetics ; Bariatric Surgery ; Metabolome ; Th17 Cells/immunology ; T-Lymphocytes, Regulatory/immunology ; Pediatric Obesity/surgery/microbiology ; Leukocyte L1 Antigen Complex/analysis ; *Mouth/microbiology ; }, abstract = {Bariatric surgery is highly effective in achieving weight loss in children and adolescents with severe obesity, however the underlying mechanisms are incompletely understood, and gut microbiome changes are unknown. Here, we show that adolescents exhibit significant gut microbiome and metabolome shifts several months after laparoscopic vertical sleeve gastrectomy (VSG), with increased alpha diversity and notably with enrichment of oral-associated taxa. To assess causality of the microbiome/metabolome changes in phenotype, pre-VSG and post-VSG stool was transplanted into germ-free mice. Post-VSG stool was not associated with any beneficial outcomes such as adiposity reduction compared pre-VSG stool. However, post-VSG stool exhibited a potentially inflammatory phenotype with increased intestinal Th17 and decreased regulatory T cells. Concomitantly, we found elevated fecal calprotectin and an enrichment of proinflammatory pathways in a subset of adolescents post-VSG. We show that in some adolescents, microbiome changes post-VSG may have inflammatory potential, which may be of importance considering the increased incidence of inflammatory bowel disease post-VSG.}, } @article {pmid39969373, year = {2024}, author = {Li, Q and Obi, E and Marciniak, A and Newman, R and Whittle, I and Kufakwaro, J}, title = {Clinical and economic outcomes associated with fidaxomicin in comparison to vancomycin, metronidazole, and FMT: A systematic literature review.}, journal = {Medicine}, volume = {103}, number = {52}, pages = {e39219}, pmid = {39969373}, issn = {1536-5964}, mesh = {Humans ; *Fidaxomicin/therapeutic use/economics ; *Vancomycin/therapeutic use/economics ; *Metronidazole/therapeutic use/economics ; *Anti-Bacterial Agents/therapeutic use/economics ; *Clostridium Infections/therapy/drug therapy/economics ; *Fecal Microbiota Transplantation/economics/methods ; Cost-Benefit Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND: There are an estimated half a million cases of Clostridioides difficile infection (CDI), in the United States annually. Fidaxomicin, vancomycin, and metronidazole are commonly used for CDI treatment, with fidaxomicin recommended by clinical guidelines as the preferred treatment for initial and recurrent CDI. This systematic literature review aimed to explore clinical and economic outcomes associated with fidaxomicin use with or without comparison to vancomycin, metronidazole, or fecal microbiota transplantation (FMT).

METHODS: The EMBASE, Medline, EconLit, and Evidence Based Medicine Reviews databases were searched from January 1st, 2012 to December 6th, 2022, as fidaxomicin was first approved for adult use in 2011. Identified publications were assessed and extracted by 2 independent reviewers.

RESULTS: Seventy-nine publications were included. Articles reporting at least 50 patients with follow-up ≤90 days were selected to obtain comparable outcome definitions (N = 14). Sustained clinical cure rate at 30- and 60-days follow-up was higher among fidaxomicin-treated patients (70.0-75.1% and 63.2-78.9%; N = 3) than vancomycin (45.1-58.2% and 38.9-50.0%; N = 3). Lower recurrence rates were reported post-fidaxomicin treatment compared to vancomycin, however the ranges overlapped at 30-, 60-, and 90-days follow-up. Limited outcomes for comparators metronidazole and FMT were identified. Healthcare resource use data were limited, with 2 studies reporting direct costs finding that fidaxomicin use-associated savings were driven by reduced hospital admission-related costs. Fidaxomicin was cost-effective in 14 of 21 economic analyses (11 vs vancomycin). Three studies reported vancomycin or FMT as more cost-effective than fidaxomicin. Fidaxomicin was consistently cost-effective or cost-saving among patients receiving concomitant antibiotics, and patients with cancer or renal impairment. Ten publications reported that the higher acquisition cost of fidaxomicin was offset by reduced recurrence and hospital readmission costs.

CONCLUSIONS: Fidaxomicin was clinically effective compared to vancomycin. Fidaxomicin is often reported as cost-effective, consistently within high-risk subpopulations.}, } @article {pmid39968682, year = {2025}, author = {Yu, RL and Weber, HC}, title = {Irritable bowel syndrome, the gut microbiome, and diet.}, journal = {Current opinion in endocrinology, diabetes, and obesity}, volume = {32}, number = {3}, pages = {102-107}, doi = {10.1097/MED.0000000000000905}, pmid = {39968682}, issn = {1752-2978}, mesh = {Humans ; *Irritable Bowel Syndrome/microbiology/therapy/metabolism/diet therapy/physiopathology ; *Gastrointestinal Microbiome/physiology ; *Diet/adverse effects ; Fecal Microbiota Transplantation ; Brain-Gut Axis ; }, abstract = {PURPOSE OF REVIEW: To provide an update of recent studies exploring the role of the gut microbiota and diet in the pathogenesis and treatment of irritable bowel syndrome (IBS).

RECENT FINDINGS: The human gut microbiome has been recognized as an important, active source of signaling molecules that explain in part the disorder of the gut brain interaction (DGBI) in IBS. Subsequent changes in the metabolome such as the production of short-chain fatty acids (SCFA) and serotonin are associated with IBS symptoms. Dietary components are recognized as important triggers of IBS symptoms and a diet low in fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) has been shown effective and safe, even when used long-term. Fecal microbiota transplantation (FMT) in IBS has not shown sustained and effective IBS symptom reduction in controlled clinical trials.

SUMMARY: This update elucidates recent developments in IBS as it relates to clinical trial results targeting dietary and gut microbiota interventions. The gut microbiome is metabolically active and affects the bi-directional signaling of the gut-brain axis.}, } @article {pmid39968343, year = {2025}, author = {Sun, T and Song, B and Li, B}, title = {Gut microbiota and atrial cardiomyopathy.}, journal = {Frontiers in cardiovascular medicine}, volume = {12}, number = {}, pages = {1541278}, pmid = {39968343}, issn = {2297-055X}, abstract = {Atrial cardiomyopathy is a multifaceted heart disease characterized by structural and functional abnormalities of the atria and is closely associated with atrial fibrillation and its complications. Its etiology involves a number of factors, including genetic, infectious, immunologic, and metabolic factors. Recent research has highlighted the critical role of the gut microbiota in the pathogenesis of atrial cardiomyopathy, and this is consistent with the gut-heart axis having major implications for cardiac health. The aim of this work is to bridge the knowledge gap regarding the interactions between the gut microbiota and atrial cardiomyopathy, with a particular focus on elucidating the mechanisms by which gut dysbiosis may induce atrial remodeling and dysfunction. This article provides an overview of the role of the gut microbiota in the pathogenesis of atrial cardiomyopathy, including changes in the composition of the gut microbiota and the effects of its metabolites. We also discuss how diet and exercise affect atrial cardiomyopathy by influencing the gut microbiota, as well as possible future therapeutic approaches targeting the gut-heart axis. A healthy gut microbiota can prevent disease, but ecological dysbiosis can lead to a variety of symptoms, including the induction of heart disease. We focus on the pathophysiological aspects of atrial cardiomyopathy, the impact of gut microbiota dysbiosis on atrial structure and function, and therapeutic strategies exploring modulation of the microbiota for the treatment of atrial cardiomyopathy. Finally, we discuss the role of gut microbiota in the treatment of atrial cardiomyopathy, including fecal microbiota transplantation and oral probiotics or prebiotics. Our study highlights the importance of gut microbiota homeostasis for cardiovascular health and suggests that targeted interventions on the gut microbiota may pave the way for innovative preventive and therapeutic strategies targeting atrial cardiomyopathy.}, } @article {pmid39963784, year = {2025}, author = {Li, J and Jia, J and Teng, Y and Wang, X and Xia, X and Song, S and Zhu, B and Xia, X}, title = {Sea cucumber polysaccharides overcome immunotherapy resistance in tumor-bearing mice via modulation of the gut microbiome.}, journal = {Food & function}, volume = {16}, number = {5}, pages = {2073-2083}, doi = {10.1039/d4fo05449k}, pmid = {39963784}, issn = {2042-650X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Polysaccharides/pharmacology/administration & dosage ; Mice ; *Sea Cucumbers/chemistry ; Immunotherapy ; *Colorectal Neoplasms/drug therapy/immunology/therapy ; Cell Line, Tumor ; Programmed Cell Death 1 Receptor/immunology ; Mice, Inbred BALB C ; Female ; Humans ; CD8-Positive T-Lymphocytes/immunology ; }, abstract = {Cancer immunotherapy has been successful in patients with different types of cancers, but its efficacy in treating certain types of colorectal cancer (CRC) is limited. The aim of this study was to explore whether sea cucumber polysaccharides (SCP) could impact resistance to anti-programmed cell death-1 (anti-PD1) immunotherapy of CRC and the role of microbiota in mediating their effects. Mice inoculated with immunotherapy resistant CT-26 CRC cells were pretreated with SCP, followed by treatment with/without the anti-PD1 antibody. SCP alone exhibited no inhibitory effect on tumor growth, but they drastically enhanced the efficacy of anti-PD1 treatment, which alone showed minimal effect on tumor development. Compared to anti-PD1 only treatment, a combination of SCP and anti-PD1 increased CD8[+] T cells, especially IFN-γ[+] cytotoxic CD8[+] T cells, and decreased regulatory CD4[+] T cells. SCP modulated gut microbiota and increased the relative abundance of bacteria including Bifidobacterium and Faecalibaculum. A fecal microbiota transplantation experiment showed that the sensitizing effect of SCP was at least partly mediated by microbiota. Furthermore, oral supplementation of Bifidobacterium pseudolongum or Faecalibaculum rodentium recapitulated the beneficial effect of SCP in potentiating anti-PD1 efficacy. Altogether, these findings demonstrated that SCP could be potentially developed as a dietary adjuvant to increase the efficacy of immunotherapy in CRC.}, } @article {pmid39963663, year = {2025}, author = {Lin, DJ and Hu, DX and Wu, QT and Huang, LG and Lin, ZH and Xu, JT and He, XX and Wu, L}, title = {Analysis of influencing factors of washed microbiota transplantation in treating patients with metabolic syndrome.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1508381}, pmid = {39963663}, issn = {2296-861X}, abstract = {BACKGROUND AND AIMS: Metabolic Syndrome (MS) is a cluster of metabolic abnormalities closely associated with hypertension, diabetes, hyperlipidemia, obesity, etc. Our previous research indicated that fecal microbiota transplantation (FMT) could improve MS, but the factors influencing the efficacy of washed microbiota transplantation (WMT) in treating MS patients remain unclear. The objective of this study is to analyze the influencing factors of WMT in treating MS patients.

METHODS: The clinical data and influencing factors related to MS patients were collected retrospectively. Not only the changes in body mass index [BMI = weight (kg)/height (m)[2]], blood glucose, blood lipids, and blood pressure were analyzed, but also the influencing factors of WMT in treating MS patients were carried out based on Logistic Regression. The 16S rRNA gene amplicon sequencing was performed on fecal samples before and after WMT treatment.

RESULTS: A total of 210 patients were included, including 68 patients in the WMT group and 142 patients in the drug treatment (DT) group. WMT had a significant improvement and ASCVD downregulation effect on MS patients, and 42.65% of MS patients removed the label of MS after WMT treatment. Independent influencing factors for treating MS patients through WMT include age < 60 years old, high smoking index, infection, single donor selection, single-course WMT treatment, and having hypertension, diabetes, or obesity. WMT treated MS patients by maintaining the balance of gut microbiota.

CONCLUSIONS: WMT has a significant effect in improving MS and downregulating ASCVD risk stratification. The therapeutic effect of WMT on MS patients is closely related to their age, smoking index, infection, chronic disease status, donor type, and WMT courses. Therefore, we can improve the efficacy of WMT by reducing independent influencing factors that affect gut microbiota homeostasis.}, } @article {pmid39962884, year = {2025}, author = {Marasco, G and Cannarile, DC and Cremon, C and Papalia, G and Marangoni, A and Zucchelli, A and Barone, M and Lazzarotto, T and Brigidi, P and Stanghellini, V and Barbara, G}, title = {Fecal microbiota transplantation for Clostridioides difficile infection in a peritoneal dialysis patient: A case report.}, journal = {Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis}, volume = {45}, number = {4}, pages = {247-250}, doi = {10.1177/08968608251316165}, pmid = {39962884}, issn = {1718-4304}, mesh = {Humans ; *Clostridioides difficile/isolation & purification ; *Clostridium Infections/therapy/etiology ; *Fecal Microbiota Transplantation/methods ; *Kidney Failure, Chronic/therapy ; *Peritoneal Dialysis/adverse effects/methods ; }, abstract = {Chronic kidney disease (CKD) may be associated with dysbiosis which may increase the risk of gastrointestinal infections. Patients with kidney failure have a predominance of bacteria responsible for the exacerbation of chronic inflammation through the production of ureases, uricase, and uremic toxins and a reduction of bacteria-producing protective molecules as short-chain fatty acids. Patients with CKD have an increased risk of Clostridioides difficile infection. Currently, besides antibiotic therapy, fecal microbiota transplantation (FMT) is the only effective gut microbiota-targeted therapy for treating this infection. Scant evidence is available on FMT in those receiving peritoneal dialysis (PD). In this case, we report a successful FMT performed by colonoscopy in a patient receiving PD for polycystic kidney disease suffering from recurrent Clostridioides difficile infections. The FMT was repeated to enhance microbiota engraftment. The role of FMT in treating Clostridioides difficile in individuals receiving PD may be an important and promising therapeutic strategy but requires further prospective study.}, } @article {pmid39961405, year = {2025}, author = {Wang, Z and Liu, T and Liu, L and Xie, J and Tang, F and Pi, Y and Zhong, Y and He, Z and Zhang, W and Zheng, C}, title = {Lactobacillus vaginalis alleviates DSS induced colitis by regulating the gut microbiota and increasing the production of 3-indoleacrylic acid.}, journal = {Pharmacological research}, volume = {213}, number = {}, pages = {107663}, doi = {10.1016/j.phrs.2025.107663}, pmid = {39961405}, issn = {1096-1186}, mesh = {Animals ; *Gastrointestinal Microbiome ; Dextran Sulfate ; *Probiotics/therapeutic use/pharmacology ; Mice, Inbred C57BL ; Mice ; *Indoles/metabolism ; *Colon/microbiology/metabolism/pathology/drug effects ; Fecal Microbiota Transplantation ; *Colitis, Ulcerative/chemically induced/microbiology/metabolism/therapy ; Disease Models, Animal ; *Colitis/chemically induced/microbiology ; Lactobacillus ; Feces/microbiology ; Intestinal Mucosa/metabolism/microbiology ; Female ; Male ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory disorder, and its incidence is experiencing an upward trend worldwide. UC can result in gut microbiota dysbiosis, impaired intestinal epithelial barrier, and systemic inflammation, for all of which there is presently no definitive treatment available. Lactobacillus is known to regulate gut microbiota and related metabolites to intervene in the development of UC. The objective of this study was to explore the underlying mechanism through which a novel probiotic, Lactobacillus vaginalis, alleviates DSS-induced colitis. Specifically, L. vaginalis were found to ameliorate the DSS-induced UC phenotype, restore intestinal microbiota balance and intestinal barrier function, and elevate the levels of 3-indoleacrylic acid (IAA) in mouse feces. Furthermore, fecal microbiota transplantation and fecal filtrate transplantation provide additional evidence that L. vaginalis alleviate DSS-induced colitis through metabolic products. Additionally, IAA has been shown to alleviate DSS-induced colitis symptoms, decrease inflammatory responses, and enhance intestinal barrier function. Finally, our findings confirm that L. vaginal and metabolites possess the capability to regulate the immune microenvironment in mice with colitis. And the RNA-seq analysis suggests that L. vaginal may play a pivotal role in alleviating colitis by modulating the PPAR signaling pathway. In conclusion, our findings suggest that oral administration of L. vaginalis alleviates DSS induced colonic inflammation by increasing the levels of IAA. L. vaginalis, as an emerging probiotic, provides a potential therapeutic strategy for clinical UC.}, } @article {pmid39959619, year = {2025}, author = {Hao, J and Xu, H and Chang, B and Ren, J and Wang, H and Ji, L}, title = {Acupuncture mediates the "gut-testis axis" to improve asthenozoospermia.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1514010}, pmid = {39959619}, issn = {1664-2392}, mesh = {Male ; Animals ; *Asthenozoospermia/therapy/microbiology/pathology/metabolism ; *Acupuncture Therapy/methods ; Mice ; *Testis/metabolism/pathology ; *Gastrointestinal Microbiome/physiology ; Sperm Motility ; Spermatozoa ; Fecal Microbiota Transplantation ; Blood-Testis Barrier/metabolism ; }, abstract = {BACKGROUND: Asthenozoospermia is a common cause of male infertility. Studies have shown that sperm quality and motility are affected by the gut-testis axis that can regulate testicular metabolism and function through the gut microbiota and its metabolites. Acupuncture is an important modality of complementary and alternative medicine. It can improve sperm motility, but it remains unclear whether acupuncture can enhance sperm vitality by influencing the gut-testis axis.

METHODS: In this study, sperm quality, testicular pathology, and serum hormone levels were assessed using a cyclophosphamide-induced mouse model. Real-time PCR, a western blot analysis, and immunofluorescence techniques were used to assess the effects of acupuncture on the gut barrier and blood-testis barrier functions. In addition, gut microbiome and metabolomics were used to study the impact of acupuncture on the gut microbiota structure, serum, and testicular metabolites in asthenozoospermic mice. Further validation was obtained by performing a fecal microbiota transplantation (FMT).

RESULTS: Acupuncture improved the sperm quality; ameliorated testicular pathology; increased serum testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels; and repaired gut and blood-testis barrier damage in asthenozoospermic mice. The abundances of Bacteroidota, Firmicutes, Faecalibaculum, and Dubosiella were associated with sperm motility, as shown by a gut microbiome analysis. Serum metabolomics revealed that differentially expressed metabolites (DEMs), such as cytosine and N-oleyl-leucine, were closely related to sperm motility. Testicular metabolomics analysis revealed DEMs, such as 5-fluorouridine and 1-acetylimidazole, were also associated with sperm motility. Furthermore, reproductive function improvements in asthenozoospermic mice through acupuncture were achieved via an FMT.

CONCLUSION: Acupuncture may alleviate asthenozoospermia symptoms by modulating the gut-testis axis and repairing the gut-testis barrier.}, } @article {pmid39958442, year = {2025}, author = {Ozbey, D and Saribas, S and Kocazeybek, B}, title = {Gut microbiota in Crohn's disease pathogenesis.}, journal = {World journal of gastroenterology}, volume = {31}, number = {6}, pages = {101266}, pmid = {39958442}, issn = {2219-2840}, mesh = {Humans ; Colon/microbiology/pathology/immunology ; *Crohn Disease/therapy/microbiology/immunology/pathology ; Dysbiosis/therapy ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/immunology ; Ileum/microbiology/pathology/immunology ; Intestinal Mucosa/microbiology/pathology/immunology ; Treatment Outcome ; }, abstract = {Inflammatory bowel diseases (IBDs) are classified into two distinct types based on the area and severity of inflammation: Crohn's disease (CD) and ulcerative colitis. In CD, gut bacteria can infiltrate mesenteric fat, causing expansion known as creeping fat, which may limit bacterial spread and inflammation but can promote fibrosis. The gut bacteria composition varies depending on whether the colon or ileum is affected. Fecal microbiota transplantation (FMT) transfers feces from a healthy donor to restore gut microbiota balance, often used in IBD patients to reduce inflammation and promote mucosal repair. The use of FMT for CD remains uncertain, with insufficient evidence to fully endorse it as a definitive treatment. While some studies suggest it may improve symptoms, questions about the duration of these improvements and the need for repeated treatments persist. There is a pressing need for methods that provide long-term benefits, as highlighted by Wu et al's research.}, } @article {pmid39957504, year = {2025}, author = {Jiang, X and Zheng, Y and Sun, H and Dang, Y and Yin, M and Xiao, M and Wu, T}, title = {Fecal Microbiota Transplantation Improves Cognitive Function of a Mouse Model of Alzheimer's Disease.}, journal = {CNS neuroscience & therapeutics}, volume = {31}, number = {2}, pages = {e70259}, pmid = {39957504}, issn = {1755-5949}, support = {81971237//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Alzheimer Disease/therapy/psychology/pathology/genetics/complications ; Disease Models, Animal ; Mice ; Gastrointestinal Microbiome/physiology ; Mice, Transgenic ; Male ; Mice, Inbred C57BL ; *Cognition/physiology ; Amyloid beta-Peptides/metabolism ; Hippocampus/metabolism ; Maze Learning/physiology ; Amyloid Precursor Protein Secretases/metabolism ; }, abstract = {BACKGROUND: A growing body of evidence suggests a link between the gut microbiota and Alzheimer's disease (AD), although the underlying mechanisms remain elusive. This study aimed to investigate the impact of fecal microbiota transplantation (FMT) on cognitive function in a mouse model of AD.

METHODS: Four-month-old 5 × FAD (familial Alzheimer's disease) mice underwent antibiotic treatment to deplete their native gut microbiota. Subsequently, they received FMT either weekly or every other day. After 8 weeks, cognitive function and β-amyloid (Aβ) load were assessed through behavioral testing and pathological analysis, respectively. The composition of the gut microbiota was analyzed using 16S rRNA sequencing.

RESULTS: Initial weekly FMT failed to alleviate memory deficits or reduce brain Aβ pathology in 5 × FAD mice. In contrast, FMT administered every other day effectively restored gut dysbiosis in 5 × FAD mice and decreased Aβ pathology and lipopolysaccharide levels in the colon and hippocampus. Mechanistically, FMT reduced the expression of amyloid β precursor protein, β-site APP cleaving enzyme 1, and presenilin-1, potentially by inhibiting the Toll-like receptor 4/inhibitor of kappa B kinase β/nuclear factor kappa-B signaling pathway. However, the cognitive benefits of FMT on 5 × FAD mice diminished over time.

CONCLUSION: These findings demonstrate the dose- and time-dependent efficacy of FMT in mitigating AD-like pathology, underscoring the potential of targeting the gut microbiota for AD treatment.}, } @article {pmid39955611, year = {2025}, author = {Launspach, M and Mindermann, A and Schulz, J and Alasfar, L and Cyrull, S and Zirngibl, F and Oevermann, L and Künkele, A and Deubzer, HE and von Bernuth, H and Pruß, A and Lang, P and Bufler, P and Eggert, A and von Stackelberg, A and Schulte, JH}, title = {High Incidence and Impact of Suspected Exocrine Pancreatic Insufficiency in Patients Post-Hematopoietic Stem Cell Transplantation: A Single-Center Prospective Observational Study.}, journal = {United European gastroenterology journal}, volume = {13}, number = {2}, pages = {257-267}, pmid = {39955611}, issn = {2050-6414}, support = {//Charité - Universitätsmedizin Berlin & the Berlin Institute of Health;/ ; }, mesh = {Humans ; *Exocrine Pancreatic Insufficiency/epidemiology/etiology/diagnosis ; Male ; Female ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Incidence ; Prospective Studies ; Risk Factors ; Child ; Adolescent ; Young Adult ; Pancreatic Elastase/analysis ; Feces/enzymology ; Child, Preschool ; Adult ; Ultrasonography ; }, abstract = {Exocrine pancreatic insufficiency (EPI) is suspected but remains understudied in immunosuppressed conditions such as post-hematopoietic stem cell transplantation (HSCT). This prospective observational study aimed to investigate the incidence, impact, and risk factors of EPI in a cohort of 83 pediatric and young adult patients who underwent allogeneic HSCT at Charité - Universitätsmedizin Berlin between 2020 and 2023. Fecal pancreatic elastase (PE) measurements and transabdominal ultrasound were utilized to evaluate pancreatic function over a one-year period. Secondary analysis explored the association of EPI with clinical complications and included a multivariable regression analysis of potential risk factors. Low PE levels significantly correlated with pathological pancreatic imaging findings, independent of concurrent diarrhea. EPI was suspected in 45% (32/71) of patients (95%CI: [34.1%, 56.6%]), with 29% (13/45) (95%CI: [17.7%, 43.4%]) showing signs of prolonged EPI (pEPI) lasting at least 8 weeks. After excluding cases with confounding factors such as missing enteral nutrition and diarrhea, the cumulative incidence of prolonged EPI was 20% (8/41) (95%CI: 10.2%-34.0%) in the overall cohort. EPI was associated with weight loss, prolonged dependence on parenteral nutrition, and extended hospitalizations. Adenovirus (ADV) infection emerged as a significant risk factor for EPI (hazard ratio 3.22 [95%CI:1.26-8.2], p = 0.014), along with additional factors such as higher BMI pre-HSCT, pre-existing pancreatic damage and early post-HSCT fasting. The persistence of pancreatic atrophy and EPI beyond two years post-HSCT in individual cases suggests a potential for permanent pancreatic damage. This study underscores that EPI is a common complication following HSCT, with ADV infection being an important risk factor. The findings support routine PE measurements and early initiation of pancreatic enzyme replacement therapy (PERT), alongside aggressive treatment of ADV infections. Further research is necessary to evaluate the effects of PERT in this population and to explore the applicability of these findings in other immunosuppressed groups.}, } @article {pmid39947548, year = {2025}, author = {Ma, X and Liu, J and Jiang, L and Gao, Z and Shi, Z and Zhang, N and Wang, Z and Li, S and Zhang, R and Xu, S}, title = {Dynamic changes in the gut microbiota play a critical role in age-associated cognitive dysfunction via SCFAs and LPS synthesis metabolic pathways during brain aging.}, journal = {International journal of biological macromolecules}, volume = {304}, number = {Pt 2}, pages = {140945}, doi = {10.1016/j.ijbiomac.2025.140945}, pmid = {39947548}, issn = {1879-0003}, mesh = {*Gastrointestinal Microbiome ; Animals ; *Cognitive Dysfunction/microbiology/metabolism ; Mice ; *Fatty Acids, Volatile/metabolism/biosynthesis ; Humans ; *Aging/metabolism ; *Lipopolysaccharides/biosynthesis/metabolism ; Male ; *Brain/metabolism ; RNA, Ribosomal, 16S/genetics ; *Metabolic Networks and Pathways ; Aged ; Female ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Gut microbiota plays an essential role in cognitive dysfunction during aging. The aim of this study was to investigate the dynamic alterations in the gut microbiota and screen for key gut bacterial taxa correlated with age-associated cognitive dysfunction during natural aging.

METHODS: 16S rRNA gene sequencing was performed to determine the composition of the gut microbiota in faecal samples from SAMR1 and SAMP8 mice, cognitively normal controls (NC), and patients with amnestic mild cognitive impairment (aMCI). Faecal microbiota transplantation (FMT) and GMrepo database were used to screen key gut microbiota associated with cognitive decline in aging mice and humans.

RESULTS: The composition of the gut microbiota dynamically changed during natural aging in SAMR1 and SAMP8 mice, as well as in healthy subjects of different ages extracted from the GMrepo database. FMT from SAMR1 to SAMP8 mice altered the gut microbiota composition and improved the cognitive impairment in SAMP8 mice. Key gut bacterial taxa, including Lactobacillus, Akkermansia, Clostridium, Oscillospira and Dorea, were screened and validated to correlate with aging-associated cognitive decline. The function of the key gut bacterial taxa predicted by PICRUSt2 indicated that the metabolic pathways related to short-chain fatty acids (SCFAs) and lipopolysaccharide (LPS) synthesis were involved in age-associated cognitive dysfunction during natural aging.

CONCLUSION: These results demonstrate that the composition of the gut microbiota changes dynamically during brain aging, with some key gut bacterial taxa playing critical roles in age-associated cognitive dysfunction through SCFAs and LPS synthesis metabolic pathways.}, } @article {pmid39946793, year = {2025}, author = {Chen, C and Xiao, Q and Wen, Z and Gong, F and Zhan, H and Liu, J and Li, H and Jiao, Y}, title = {Gut microbiome-derived indole-3-carboxaldehyde regulates stress vulnerability in chronic restraint stress by activating aryl hydrocarbon receptors.}, journal = {Pharmacological research}, volume = {213}, number = {}, pages = {107654}, doi = {10.1016/j.phrs.2025.107654}, pmid = {39946793}, issn = {1096-1186}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Receptors, Aryl Hydrocarbon/metabolism ; *Stress, Psychological/metabolism/microbiology ; Male ; Hippocampus/metabolism ; *Indoles/metabolism/pharmacology ; Restraint, Physical ; Rats, Sprague-Dawley ; Fecal Microbiota Transplantation ; Limosilactobacillus reuteri/metabolism ; Rats ; Colon/metabolism/microbiology ; Behavior, Animal/drug effects ; Neurogenesis ; Signal Transduction ; }, abstract = {Chronic stress constitutes a major precipitating factor for Major Depressive Disorder (MDD), and comprehending individual differences in stress responses is crucial for the development of effective intervention strategies for MDD. Recent studies indicate that an individual's vulnerability to chronic stress is closely associated with gut microbiota composition, but the underlying mechanisms remain unclear. This study aims to investigate whether the gut microbiota and its metabolites can serve as gut-brain signaling molecules and explores how the gut microbiota affects stress sensitivity. Here, we showed that gut microbiome-derived indole-3-carboxaldehyde (I3C) can act as a gut-brain signaling molecule that links tryptophan metabolism by gut microbes to stress vulnerability in the host. First, we identified a specific reduction in gut microbiome-derived I3C levels in the hippocampus and colon through untargeted and targeted metabolomic analyses. Then, the study of gut microbiota suggested that the relative abundance of lactobacillus was reduced significantly in stress-susceptible rats, whereas fecal microbiota transplantation regulates stress vulnerability. Furthermore, supplementation with I3C and the representative I3C-producing strain, Lactobacillus reuteri, was shown to alleviate depression-like behaviors induced by chronic stress. Further research confirms that I3C can inhibit neuroinflammation and promote hippocampal neurogenesis through the aryl hydrocarbon receptors (AhR) signal pathway, thereby mitigating the host's susceptibility to stress. In conclusion, our findings elucidate that the gut microbiome-derived-I3C can help buffer the host's stress through the AhR/SOCS2/NF-κB/NLRP3 pathway, providing a gut-brain signaling basis for emotional behavior.}, } @article {pmid39946032, year = {2025}, author = {Karam, F and El Deghel, Y and Iratni, R and Dakroub, AH and Eid, AH}, title = {The Gut Microbiome and Colorectal Cancer: An Integrative Review of the Underlying Mechanisms.}, journal = {Cell biochemistry and biophysics}, volume = {}, number = {}, pages = {}, pmid = {39946032}, issn = {1559-0283}, abstract = {Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. While the incidence and mortality of CRC have decreased overall due to better screening, rates in adults under 50 have risen. CRC can manifest as inherited syndromes (10%), familial clustering (20%), or sporadic forms (70%). The gut microbiota, comprising mainly firmicutes and bacteroidetes, play a key role in CRC development and prevention. Indeed, CRC progression is influenced by the dynamic interaction between the gut microbiota, the intestinal barrier, the immune system, and the production of short-chain fatty acids. Not surprisingly, imbalance in the gut microbiota, termed dysbiosis, has been linked to CRC due to ensuing chronic inflammation, DNA damage, and oxidative stress. This may explain the notion that probiotics and fecal microbiota transplantation offer potential strategies for CRC prevention and treatment by restoring microbial balance and enhancing anti-cancer immune responses. This review appraises the roles of gut microbiota in promoting or preventing CRC. It also discusses the mechanistic interplay between microbiota composition, the intestinal barrier, and the immune system, with the hope of developing potential therapeutic strategies.}, } @article {pmid39945558, year = {2025}, author = {Zhang, L and Liu, ZX and Liu, YH and Chen, Y and Chen, J and Lu, CH}, title = {Auricularia auriculaPolysaccharides Exert Anti-inflammatory Effects in Hepatic Fibrosis by the Gut-Liver Axis and Enhancing SCFA Metabolism.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {8}, pages = {4617-4629}, pmid = {39945558}, issn = {1520-5118}, mesh = {Gastrointestinal Microbiome/drug effects ; Animals ; *Anti-Inflammatory Agents/administration & dosage/chemistry ; *Liver/drug effects/metabolism/immunology ; Male ; Humans ; *Liver Cirrhosis/drug therapy/microbiology/immunology/metabolism/genetics ; *Auricularia/chemistry ; *Fatty Acids, Volatile/metabolism/immunology ; Mice ; *Polysaccharides/administration & dosage ; NF-kappa B/immunology/genetics ; Bacteria/isolation & purification/genetics/classification/metabolism ; Mice, Inbred C57BL ; Toll-Like Receptor 4/immunology/genetics ; }, abstract = {Auricularia auricula, esteemed in Chinese culture for their culinary and medicinal properties, exhibits notable metabolic and immunomodulatory effects. The principal active constituents are indigestible fermentable polysaccharides, which not only exhibit anti-inflammatory activities but also facilitate the proliferation of beneficial gut microbiota. However, the influence of gut-derived components on liver-regulated metabolic products remains insufficiently understood. This item offers insights into the therapeutic potential of wood ear mushrooms for treating hepatic fibrosis and the associated mechanisms. Following 8 weeks of treatment, a substantial reduction in ECM deposition was recorded, linked to modulation of the NLRP3 inflammasome activation. This study aims to reveal the potential microbiome-mediated mechanisms behind its therapeutic effects. Insights from antibiotic combination treatments indicate that the protective effects against ECM deposition rely on the presence of specific gut microbiota. This fecal microbiota intervention enhances key physiological mechanisms, underscoring the contributions of Lactobacillales, Rikenellaceae, and Bacteroidaceae in potentially mitigating fibrosis. Collectively, these findings suggest that interventions utilizing wood ear mushrooms may reduce inflammation and ECM deposition, mediated by the TLR4/NF-κB pathway.}, } @article {pmid39944648, year = {2025}, author = {Lu, J and Jiang, M and Chai, D and Sun, Y and Wu, L}, title = {Integrative analysis of intestinal flora and untargeted metabolomics in attention-deficit/hyperactivity disorder.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1452423}, pmid = {39944648}, issn = {1664-302X}, abstract = {Attention Deficit Hyperactivity Disorder (ADHD) is a clinically common neurodevelopmental disorder of the brain. In addition to genetic factors, an imbalance in gut flora may also play a role in the development of ADHD. Currently, it is critical to investigate the function of gut flora and related metabolites, which may form the fundamental basis of bidirectional cross-linking between the brain and the gut, in addition to focusing on the changed gut flora in ADHD. This study aimed to investigate the possible relationship between changes in gut flora and metabolites and ADHD by analyzing metagenome and untargeted metabolomics of fecal samples from ADHD patients. Specifically, we attempted to identify key metabolites and the metabolic pathways they are involved in, as well as analyze in detail the structure and composition of the gut flora of ADHD patients. In order to further investigate the relationship between gut flora and ADHD symptoms, some behavioral studies were conducted following the transplantation of gut flora from ADHD patients into rats. The results of the metagenome analysis revealed several distinct strains, including Bacteroides cellulosilyticus, which could be important for diagnosing ADHD. Additionally, the ADHD group showed modifications in several metabolic pathways and metabolites, including the nicotinamide and nicotinic acid metabolic pathways and the metabolite nicotinamide in this pathway. The behavioral results demonstrated that rats with ADHD gut flora transplants displayed increased locomotor activity and interest, indicating that the onset of behaviors such as ADHD could be facilitated by the flora associated with ADHD. This research verified the alterations in gut flora and metabolism observed in ADHD patients and provided a list of metabolites and flora that were significantly altered in ADHD. Simultaneously, our findings revealed that modifications to the microbiome could potentially trigger behavioral changes in animals, providing an experimental basis for comprehending the function and influence of gut flora on ADHD. These results might provide new perspectives for the development of novel treatment strategies.}, } @article {pmid39944265, year = {2024}, author = {Ye, ZN and Eslick, GD and Huang, SG and He, XX}, title = {Faecal microbiota transplantation for eradicating Helicobacter pylori infection: clinical practice and theoretical postulation.}, journal = {eGastroenterology}, volume = {2}, number = {4}, pages = {e100099}, pmid = {39944265}, issn = {2976-7296}, abstract = {The sustained increase in antibiotic resistance leads to a declining trend in the eradication rate of Helicobacter pylori (H. pylori) infection with antibiotic-based eradication regimens. Administration of a single probiotic shows limited efficacy in eradicating H. pylori infection. This review indicates that faecal microbiota transplantation (FMT), a novel therapeutic approach, either as a monotherapy or adjunctive therapy, exhibits beneficial effects in terms of the eradication of H. pylori infection and the prevention of adverse events. The role of FMT in H. pylori eradication may be associated directly or indirectly with some therapeutic constituents within the faecal suspension, including bacteria, viruses, antimicrobial peptides and metabolites. In addition, variations in donor selection, faecal suspension preparation and delivery methods are believed to be the main factors determining the effectiveness of FMT for the treatment of H. pylori infection. Future research should refine the operational procedures of FMT to achieve optimal efficacy for H. pylori infection and explore the mechanisms by which FMT acts against H. pylori.}, } @article {pmid39943805, year = {2025}, author = {Ju, H and Zhou, Y and Wei, W and Hu, Y and Fang, H and Chen, Z and Sun, X and Shi, Y and Fang, H}, title = {Ageing-associated gut dysbiosis deteriorates mouse cognition.}, journal = {Acta biochimica et biophysica Sinica}, volume = {57}, number = {8}, pages = {1234-1243}, doi = {10.3724/abbs.2024217}, pmid = {39943805}, issn = {1745-7270}, abstract = {Ageing is an independent factor for cognitive dysfunction. Ageing-associated alterations in the gut microbiota also affect cognition. The present study is designed to investigate changes in the gut microbiota and their participation in ageing-associated cognitive impairment. Both 10-week-old and 18-month-old mice are used. Mouse cognition is examined by novel object recognition and T-maze tests. Mouse feces are collected for sequencing and transplantation. Protein expression in the mouse intestine and hippocampus is studied using immunohistochemistry and immunofluorescence staining. Senescent neurons are induced by hydrogen peroxide in vitro. The cell lysates are used for western blot analysis and adenosine triphosphate (ATP) measurement. Our results show that 18-month-old mice exhibit cognitive dysfunction compared with young mice. In aged mice, transplanting the microbiota of young mice increases the protein presence of synaptophysin in the hippocampus and partially restores cognition. The protein expressions of mucin-2 and E-cadherin in the intestine are reduced in aged mice but are increased by transplantation. Gut microbiota analyses reveal that the reduced abundance of the microbe Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus in aged mice is restored by transplantation. Fecal microbiota transplantation in young mice increases the serum level of acetic acid in aged mice. Hydrogen peroxide stimulation induces senescence and reduces the protein expression levels of synaptophysin and acetyl-coenzyme A synthetase member 2 (ACSS2) in primary neurons. Incubation with acetic acid upregulates the protein expressions of ACSS2 and synaptophysin and further increases ATP production in senescent neurons. In summary, gut microbiota transplantation increases the abundance of Lactobacillales, elevates serum acetic acid level, and improves cognitive function in aged mice. Gut microbiota transplantation has therapeutic importance for ageing-associated cognitive decline.}, } @article {pmid39941980, year = {2025}, author = {Li, J and Jia, J and Teng, Y and Wang, X and Xia, X and Song, S and Zhu, B and Xia, X}, title = {Polysaccharides from Sea Cucumber (Stichopus japonicus) Synergize with Anti-PD1 Immunotherapy to Reduce MC-38 Tumor Burden in Mice Through Shaping the Gut Microbiome.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {3}, pages = {}, pmid = {39941980}, issn = {2304-8158}, support = {Dljswgj202403//Dalian Jinshiwan Laboratory Project/ ; 81972692//National Natural Science of Foundation of China/ ; 2022YFD2100104//National Key Research and Development Program of China/ ; }, abstract = {Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and significantly improved outcomes for patients with certain malignancies. However, immunotherapy with ICIs is only effective in a subset of patients and the gut microbiota have been identified as an important factor associated with response to ICI therapy. Polysaccharides from sea cucumber (Stichopus japonicus) (SCP) have been shown to modulate the gut microbiota and exhibit beneficial health functions, but whether SCP could synergize with anti-PD1 immunotherapy remains unexplored. In this study, mice with ICI-sensitive MC38 tumors were treated with anti-PD1 antibody after supplementation with or without SCP to examine the potential impact of SCP on the efficacy of immunotherapy. SCP strongly amplified the anti-tumor activity of anti-PD1 in MC38 tumor-bearing mice. Flow cytometry and immunohistological staining demonstrated that SCP treatment increased cytotoxic CD8[+] T lymphocytes while decreasing regulatory Foxp3[+] CD4[+] T lymphocytes. Gut microbiota and metabolomic analysis revealed that SCP modulated the microbiota and increased the abundance of certain metabolites such as indole-3-carboxylic acid. Furthermore, fecal microbiota transplantation experiments justified that the synergistic effect of SCP with anti-PD1 was partially mediated through the gut microbiota. Mice receiving microbiota from SCP-treated mice showed a boosted response to anti-PD1, along with enhanced anti-tumor immunity. These findings indicate that SCP could be utilized as a dietary strategy combined with anti-PD1 therapy to achieve improved outcomes in patients.}, } @article {pmid39939643, year = {2025}, author = {Tandoro, Y and Chiu, HF and Tan, CL and Hsieh, MH and Huang, YW and Yu, J and Wang, LS and Chan, CH and Wang, CK}, title = {Black raspberry supplementation on overweight and Helicobacter pylori infected mild dementia patients a pilot study.}, journal = {NPJ science of food}, volume = {9}, number = {1}, pages = {9}, pmid = {39939643}, issn = {2396-8370}, support = {R01 CA148818/CA/NCI NIH HHS/United States ; }, abstract = {Alzheimer's disease (AD) is the most common form of dementia. H. pylori infection and overweight have been implicated in AD via the gut-brain axis (GBA). This study aimed to determine whether supplementation of BRBs has a meaningful effect on H. pylori infection, overweight, and AD development in a clinical trial setting. We conducted a randomized placebo-controlled clinical trial in patients with mild clinical dementia who also had H. pylori infection and were overweight. The study was conducted over 10 weeks, consisting of an 8-week intervention period (25 g powder of black raspberries, BRBs, or placebo twice daily, morning and evening) and a 2-week follow-up. The primary outcomes were changes in Clinical Dementia Rating (CDR), Urea Breath Test (UBT), and Body Mass Index (BMI). Consumption of BRBs improved cognitive functions (p < 0.00001), compared to the placebo group (p > 0.05). Besides, BRBs ingestion decreased H. pylori infection and BMI (p < 0.00001 and p < 0.05 respectively) while the placebo group stayed statistically the same (p = 0.98 and p = 0.25 respectively). BRBs significantly decreased inflammatory markers, improved oxidative index, and adiponectin (p < 0.05) compared to the placebo group, while adenosine monophosphate-activated protein kinase (AMPK) and leptin did not significantly change. BRBs modulated the abundance of several fecal probiotics, particularly, Akkermansia muciniphila. Our results provided that BRBs suppressed H. pylori infection, decreased BMI, and rebalanced the gut microbiome, which could improve cognitive functions in mild dementia patients. Longer and larger randomized clinical trials of BRB interventions targeting H. pylori infection, overweight, or mild dementia are warranted to confirm the results from this pilot trial. Trial Registration: ClinicalTrials.gov identifier: NCT05680532.}, } @article {pmid39938959, year = {2025}, author = {Støy, S and Eriksen, LL and Lauszus, JS and Damsholt, S and Baunwall, SMD and Erikstrup, C and Vilstrup, H and Jepsen, P and Hvas, C and Thomsen, KL}, title = {Cirrhosis and Faecal microbiota Transplantation (ChiFT) protocol: a Danish multicentre, randomised, placebo-controlled trial in patients with decompensated liver cirrhosis.}, journal = {BMJ open}, volume = {15}, number = {2}, pages = {e091078}, pmid = {39938959}, issn = {2044-6055}, mesh = {Female ; Humans ; Male ; Denmark ; Disease Progression ; Double-Blind Method ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; *Liver Cirrhosis/therapy/mortality ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {INTRODUCTION: Liver cirrhosis is a progressive disease with high mortality. Gut microbiota derangement, increased gut permeability, bacterial translocation and chronic inflammation all drive disease progression. This trial aims to investigate whether faecal microbiota transplantation (FMT) may improve the disease course in patients with acute decompensation of liver cirrhosis.

METHODS AND ANALYSIS: In this Danish, multicentre, randomised, double-blinded, placebo-controlled trial, 220 patients with acute decompensation of liver cirrhosis and a Child-Pugh score≤12 will be randomised (1:1) to oral, encapsulated FMT or placebo in addition to standard of care. Before the intervention, the patients will be examined and biological samples obtained, and this is repeated at 1 and 4 weeks and 3, 6 and 12 months after the intervention. The primary outcome is the time from randomisation to new decompensation or death. Secondary endpoints include mortality, number of decompensation events during follow-up and changes in disease severity and liver function.

ETHICS AND DISSEMINATION: The Central Denmark Region Research Ethics Committee approved the trial protocol (no. 1-10-72-302-20). The results will be published in an international peer-reviewed journal, and all patients will receive a summary of the results.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov study identifier NCT04932577.}, } @article {pmid39935515, year = {2024}, author = {Yao, L and Zhou, X and Jiang, X and Chen, H and Li, Y and Xiong, X and Tang, Y and Zhang, H and Qiao, P}, title = {High-fat diet promotes gestational diabetes mellitus through modulating gut microbiota and bile acid metabolism.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1480446}, pmid = {39935515}, issn = {1664-302X}, abstract = {INTRODUCTION: Gestational diabetes mellitus (GDM) is a condition characterized by glucose intolerance during pregnancy, estimated to affect approximately 20% of the whole pregnancies and is increasing in prevalence globally. However, there is still a big gap in knowledge about the association between gut microbiota associated metabolism alterations and GDM development.

METHODS: All the participants accomplished the validated internet-based dietary questionnaire for Chinese and serum, fecal samples were collected. HFD, control diet or colesevelam intervention was fed to GDM mice models or Fxr-/- mice models, with or without antibiotics cocktail treatment. Fecal microbiota transplantation were used for further validation. Gut microbiota and metabolites were detected by metagenomic sequencing and high-performance liquid chromatography-mass spectrometry, respectively. Bile acids of serum, fecal samples from human and mice were analysised. Body weight, average feed intake, blood glucose, insulin levels and oral glucose tolerance test was performed among each groups. Expression levels of Fxr, Shp and Fgf15 mRNA and protein were detected by quantitative reverse transcription polymerase chain reaction and western blot, respectively.

RESULTS: Our data indicated that high fat diet (HFD) was linked with higher prevalence of GDM, and HFD was positively associated with poor prognosis in GDM patients. Moreover, compared with normal diet (ND) group, GDM patients from HFD group performed a loss of gut microbiota diversity and enrichment of Alistipes onderdonkii, Lachnospiraceae bacterium 1_7_58FAA, and Clostridium aspaaragiforme while ruduction of Akkermansiaceae, Paraprevotell xylaniphila, and Prevotella copri. Additionally, HFD aggravated GDM in mice and gut microbiota depletion by antibiotics crippled the effect of excess fat intake. BAs profile altered in HFD GDM patients and mice models. Fecal microbiota transplantation (FMT) further confirmed that gut microbiota contributed to bile acids (BAs) metabolic dysfunction during HFD-associated GDM development. Mechanically, HFD-FMT administration activated Fxr, Shp, and Fgf15 activity, disturbed the glucose metabolism and aggravated insulin resistance but not in HFD-FMT Fxr-/- mice and ND-FMT Fxr-/- mice. Furthermore, colesevelam intervention alleviated HFD-associated GDM development, improved BAs metabolism, suppressed Fxr, Shp, and Fgf15 activity only in WT mice but not in the Fxr-/- HFD + Colesevelam group and Fxr-/- HFD group. HFD induced GDM and contributed to poor prognosis in GDM parturients through inducing gut microbial dysbiosis and metabolic alteration, especially appeared in BAs profile. Moreover, Fxr pathway participated in regulating HFD-associated gut microbiota disordered BAs metabolites and aggravating GDM in mice.

DISCUSSION: Modulating gut microbiota and BAs metabolites could be a potential therapeutic strategy in the prevention and treatment of HFD-associated GDM.}, } @article {pmid39933444, year = {2025}, author = {Rob, M and Yousef, M and Lakshmanan, AP and Mahboob, A and Terranegra, A and Chaari, A}, title = {Microbial signatures and therapeutic strategies in neurodegenerative diseases.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {184}, number = {}, pages = {117905}, doi = {10.1016/j.biopha.2025.117905}, pmid = {39933444}, issn = {1950-6007}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neurodegenerative Diseases/microbiology/therapy/metabolism ; Animals ; Dysbiosis ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Metabolome ; }, abstract = {Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), arise from complex interactions between genetic factors, environmental exposures, and aging. Additionally, gut dysbiosis has been linked to systemic inflammation and neurodegeneration. Advances in microbiome and metabolome profiling techniques have provided deeper insights into how alterations in gut microbiota and dietary patterns affect metabolic pathways and contribute to the progression of NDs. This review explores the profiles of gut microbiome and metabolome derived biomarkers and their roles in NDs. Across phyla, families, and genera, we identified 55 microbial alterations in PD, 24 in AD, 4 in ALS, and 17 in MS. Some notable results include an increase in Akkermansia in PD, AD, and MS and a decrease in short-chain fatty acids (SCFAs) in PD and AD. We examined the effects of probiotics, prebiotics, fecal microbiota transplants (FMT), sleep, exercise, and diet on the microbiota, all of which contributed to delayed onset and alleviation of symptoms. Further, artificial intelligence (AI) and machine learning (ML) algorithms applied to omics data have been crucial in identifying novel therapeutic targets, diagnosing and predicting prognosis, and enabling personalized medicine using microbiota-modulating therapies in NDs patients.}, } @article {pmid39933221, year = {2025}, author = {Cao, Y and Fan, X and Zang, T and Li, Y and Tu, Y and Wei, Y and Bai, J and Liu, Y}, title = {Gut microbiota causes depressive phenotype by modulating glycerophospholipid and sphingolipid metabolism via the gut-brain axis.}, journal = {Psychiatry research}, volume = {346}, number = {}, pages = {116392}, doi = {10.1016/j.psychres.2025.116392}, pmid = {39933221}, issn = {1872-7123}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Sphingolipids/metabolism ; Mice ; *Glycerophospholipids/metabolism ; Female ; *Depression/metabolism/microbiology ; *Brain/metabolism ; Humans ; Pregnancy ; Phenotype ; Fecal Microbiota Transplantation ; Lipid Metabolism ; Disease Models, Animal ; }, abstract = {Emerging evidence suggests that changes in the gut microbiota (GM) are related to prenatal depression onset, but the underlying molecular mechanisms remain obscure. This study was conducted to explore how disordered GM is involved in the onset of prenatal depression through the microbiome-gut-brain (MGB) axis. We transplanted fecal microbiota from women with and without prenatal depression into germ-free mice. Fecal metagenomic sequencing and LC-MS untargeted metabolomics analysis were performed to identify the GM composition, function, and metabolites in mice. Lipid metabolomics analysis was then used to characterize the lipid metabolism of brain tissue in mice. We found that mice transplanted with fecal microbiota from women with prenatal depression exhibited depressive-like behaviors as well as characteristic disorders of the phylum Firmicutes. Weighted Gene Correlation Network Analysis identified three microbial and one metabolic module in the gut, alongside two lipid metabolic modules in the brain, as significantly related to all depressive-like behaviors. These modules were enriched for glycerophospholipid and sphingolipid metabolism. In addition, the GM of mice with depressive-like behaviors were enriched and deficient in relevant functions and enzymes in the glycerophospholipid (mainly phosphatidylethanolamine) and sphingolipid (mainly hexosyl-ceramide) metabolic pathways, respectively. Consistently, glycerophospholipid and sphingolipid metabolites in the brains of depressive-like mice were up- and down-regulated. Increased phosphatidylethanolamine and decreased hexosyl-ceramide were significantly related to differential genera in the gut. Collectively, our findings provide a novel microbial and metabolic framework for understanding the role of the MGB axis in prenatal depression, indicating that the GM may be involved in the onset of depressive phenotypes by modulating central glycerophospholipid and sphingolipid metabolic homeostasis.}, } @article {pmid39932857, year = {2025}, author = {Lopetuso, LR and Deleu, S and Puca, P and Abreu, MT and Armuzzi, A and Barbara, G and Caprioli, F and Chieng, S and Costello, SP and Damiani, A and Danese, S and Del Chierico, F and D'Haens, G and Dotan, I and Facciotti, F and Falony, G and Fantini, MC and Fiorino, G and Gionchetti, P and Godny, L and Hart, A and Kupčinskas, J and Iqbal, T and Laterza, L and Lombardini, L and Maharshak, N and Marasco, G and Masucci, L and Papa, A and Paramsothy, S and Petito, V and Piovani, D and Pugliese, D and Putignani, L and Raes, J and Ribaldone, DG and Sanguinetti, M and Savarino, EV and Sokol, H and Vetrano, S and Ianiro, G and Cammarota, G and Cominelli, F and Pizarro, TT and Tilg, H and Gasbarrini, A and Vermeire, S and Scaldaferri, F}, title = {Guidance for Fecal Microbiota Transplantation Trials in Ulcerative Colitis: The Second ROME Consensus Conference.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izaf013}, pmid = {39932857}, issn = {1536-4844}, support = {//European Crohn's and Colitis Organization/ ; //Crohn's & Colitis Foundation: Clinical Research Investigator Initiated Award (CRIA)/ ; 882725//Senior Research Award (SRA)/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is emerging as a potential treatment modality for individuals living with inflammatory bowel disease (IBD). Despite its promise, the effectiveness of FMT for treating IBD, particularly for ulcerative colitis (UC), still requires thorough clinical investigation. Notwithstanding differences in methodologies, current studies demonstrate its potential for inducing remission in UC patients. Therefore, standardized and robust randomized clinical trials (RCTs) are needed to further support its efficacy for managing UC. The aim of the second Rome Consensus Conference was to address gaps and uncertainties identified in previous research regarding FMT and to offer a robust framework for future studies applied to the treatment of UC.

METHODS: Global experts in the field of clinical IBD, mucosal immunology, and microbiology (N = 48) gathered to address the need for standardized clinical trials in FMT investigation. The group focused on key issues, such as stool donation, donor selection, characterization of fecal biomass, potential administration routes, as well as the process of induction, maintenance, and endpoint readouts.

RESULTS AND CONCLUSIONS: The consensus achieved during this conference established standardization of methods and protocols to enhance the current quality of research, with the aim of eventual implementation of FMT in managing UC and the ultimate goal of improving patient outcomes.}, } @article {pmid39931541, year = {2025}, author = {Dong, S and Du, Y and Wang, H and Yuan, W and Ai, W and Liu, L}, title = {Research progress on the interaction between intestinal flora and microRNA in pelvic inflammatory diseases.}, journal = {Non-coding RNA research}, volume = {11}, number = {}, pages = {303-312}, pmid = {39931541}, issn = {2468-0540}, abstract = {Pelvic inflammatory disease (PID) is a common infectious disease of the female upper reproductive tract, and its pathological basis is immune inflammatory response. The imbalance of gut microflora (GM) may lead to the development of inflammatory process. A large number of studies have shown that fecal microbiota transplantation, probiotics, bacteria, prebiotics, and dietary intervention may play a potential role in remodeling GM and treating diseases. MicroRNAs (miRNAs) are involved in cell development, proliferation, apoptosis and other physiological processes. In addition, they play an important role in the inflammatory process, participating in the regulation of proinflammatory and anti-inflammatory pathways. Differences in miRNA profiles may be PID diagnostic tools and serve as prognostic markers of the disease. The relationship between miRNA and GM has not been fully elucidated. Recent studies have shown the role of miRNA in the regulation and induction of GM dysbiosis. In turn, microbiota can regulate the expression of miRNA and improve the immune status of the body. Therefore, this review aims to describe the interaction between GM and miRNA in PID, and to find potential precise targeted therapy for PID.}, } @article {pmid39931312, year = {2025}, author = {Zhu, L and Yang, X}, title = {Gut Microecological Prescription: A Novel Approach to Regulating Intestinal Micro-Ecological Balance.}, journal = {International journal of general medicine}, volume = {18}, number = {}, pages = {603-626}, pmid = {39931312}, issn = {1178-7074}, abstract = {The intestinal microecology is comprises intestinal microorganisms and other components constituting the entire ecosystem, presenting characteristics of stability and dynamic balance. Current research reveals intestinal microecological imbalances are related to various diseases. However, fundamental research and clinical applications have not been effectively integrated. Considering the importance and complexity of regulating the intestinal microecological balance, this study provides an overview of the high-risk factors affecting intestinal microecology and detection methods. Moreover, it proposes the definition of intestinal microecological imbalance and the definition, formulation, and outcomes of gut microecological prescription to facilitate its application in clinical practice, thus promoting clinical research on intestinal microecology and improving the quality of life of the population.}, } @article {pmid39931240, year = {2025}, author = {Wang, H and Li, S and Zhang, L and Zhang, N}, title = {Corrigendum: The role of fecal microbiota transplantation in type 2 diabetes mellitus treatment.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1555601}, doi = {10.3389/fendo.2025.1555601}, pmid = {39931240}, issn = {1664-2392}, abstract = {[This corrects the article DOI: 10.3389/fendo.2024.1469165.].}, } @article {pmid39931170, year = {2025}, author = {Wang, H and Huang, W and Pan, X and Tian, M and Chen, J and Liu, X and Li, Q and Qi, J and Ye, Y and Gao, L}, title = {Quzhou Aurantii Fructus Flavonoids Ameliorate Inflammatory Responses, Intestinal Barrier Dysfunction in DSS-Induced Colitis by Modulating PI3K/AKT Signaling Pathway and Gut Microbiome.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {1855-1874}, pmid = {39931170}, issn = {1178-7031}, abstract = {PURPOSE: To explore the protective effect and underlying mechanism of Quzhou Aurantii Fructus flavonoids (QAFF) on Ulcerative colitis (UC).

METHODS: The constituents of QAFF were accurately determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The therapeutic impacts of QAFF were assessed in dextran sulfate sodium (DSS)-induced UC mice, focusing on the changes in body weight, disease activity index (DAI), colon length, histological assessment of colonic tissues, levels of pro-inflammatory cytokines, and expression of tight junction proteins. Western blotting confirmed key regulatory proteins within the differential signaling pathways, guided by transcriptome analysis. Additionally, the influence of QAFF on the gut microbiome was explored through 16S ribosomal RNA (rRNA) sequencing. The alterations in endogenous metabolites were detected by untargeted metabolomics, and their potential correlation with intestinal flora was then examined utilizing Spearman correlation analysis. Subsequently, the regulation of gut microbiome by QAFF was validated by fecal microbiota transplantation (FMT).

RESULTS: Eleven flavonoids, including Naringin and hesperidin, were initially identified from QAFF. In vivo experiments demonstrated that QAFF effectively ameliorated colitis symptoms, reduced IL-6, IL-1β, and TNF-α levels, enhanced intestinal barrier integrity, and downregulated PI3K/AKT pathway activation. Furthermore, QAFF elevated the levels of beneficial bacteria like Lachnospiraceae_NK4A136_group and Alloprevotella and concurrently reduced the pathogenic bacteria such as Escherichia-Shigella, [Eubacterium]_siraeum_group, and Parabacteroides. Metabolomics analysis revealed that 34 endogenous metabolites exhibited significant alterations, predominantly associated with Glycerophospholipid metabolism. These metabolites were significantly correlated with those differential bacteria modulated by QAFF. Lastly, the administration of QAFF via FMT ameliorated the colitis symptoms.

CONCLUSION: QAFF could ameliorate inflammatory responses and intestinal barrier dysfunction in DSS-induced UC mice probably by modulating the PI3K/AKT signaling pathway and gut microbiome, offering promising evidence for the therapeutic potential of QAFF in UC treatment.}, } @article {pmid39930537, year = {2025}, author = {Liu, Q and Akhtar, M and Kong, N and Zhang, R and Liang, Y and Gu, Y and Yang, D and Nafady, AA and Shi, D and Ansari, AR and Abdel-Kafy, EM and Naqvi, SU and Liu, H}, title = {Early fecal microbiota transplantation continuously improves chicken growth performance by inhibiting age-related Lactobacillus decline in jejunum.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {49}, pmid = {39930537}, issn = {2049-2618}, support = {2017YFE0113700//National Key Research and Development Program of China/ ; HBZY2023B007//Supporting High Quality Development of Seed Industry Fund Project of Hubei Province/ ; }, mesh = {*Fecal Microbiota Transplantation/veterinary ; *Chickens/growth & development/microbiology ; *Jejunum/microbiology ; *Lactobacillus/physiology ; Age Factors ; Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Body Weight ; Insulin-Like Growth Factor I/genetics/metabolism ; Growth Hormone/genetics/metabolism ; Gene Expression ; Gene Expression Profiling/veterinary ; Male ; Animals ; }, abstract = {BACKGROUND: At an early age, chickens commonly exhibit a rise in the average daily gain, which declines as they age. Further studies indicated that the decrease in chicken growth performance at a later age is closely associated with an age-related decline in Lactobacillus abundance in the small intestines. Whether inhibiting the age-related decline in Lactobacillus in the small intestine by early fecal microbiota transplantation (FMT) could improve chicken growth performance is an interesting question.

RESULTS: 16S rRNA gene sequencing revealed a higher jejunal Lactobacillus abundance in high body weight chickens in both two different chicken breeds (yellow feather chickens, H vs L, 85.96% vs 55.58%; white feather chickens, H vs L, 76.21% vs 31.47%), which is significantly and positively associated with body and breast/leg muscle weights (P < 0.05). Moreover, the jejunal Lactobacillus abundance declined with age (30 days, 74.04%; 60 days, 50.80%; 120 days, 34.03%) and the average daily gain rose in early age and declined in later age (1 to 30 days, 5.78 g; 30 to 60 days, 9.86 g; 60 to 90 days, 7.70 g; 90 to 120 days, 3.20 g), indicating the age-related decline in jejunal Lactobacillus abundance is closely related to chicken growth performance. Transplanting fecal microbiota from healthy donor chickens with better growth performance and higher Lactobacillus abundance to 1-day-old chicks continuously improved chicken growth performance (Con vs FMT; 30 days, 288.45 g vs 314.15 g, P < 0.05; 60 days, 672.77 g vs 758.15 g, P < 0.01; 90 days, 1146.08 g vs 1404.43 g, P < 0.0001) even after stopping fecal microbiota transplantation at 4th week. Four-week FMT significantly inhibited age-related decline in jejunal Lactobacillus abundance (Con vs FMT, 30 days, 65.07% vs 85.68%, P < 0.01; 60 days, 38.87% vs 82.71%, P < 0.0001 and 90 days, 34.23% vs 60.86%, P < 0.01). Moreover, the numbers of goblet and Paneth cells were also found significantly higher in FMT groups at three time points (P < 0.05). Besides, FMT triggered GH/IGF-1 underlying signaling by significantly increasing the expressions of GH, GHR, and IGF-1 in the liver and IGF-1 and IGF-1R in muscles along age (P < 0.05).

CONCLUSION: These findings revealed that age-related decline in jejunal Lactobacillus abundance compromised chicken growth performance, while early fecal microbiota transplantation continuously improved chicken growth performance by inhibiting age-related jejunal Lactobacillus decline, promoting the integrity of jejunal mucosal barrier and up-regulating the expression level of genes related to growth axis. Video Abstract.}, } @article {pmid39929593, year = {2025}, author = {Harigai, W and Mikami, K and Choudhury, ME and Yamauchi, H and Yajima, C and Shimizu, S and Miyaue, N and Nagai, M and Kubo, M and Tanaka, J and Katayama, T}, title = {Effects of fecal microbiota transplantation on behavioral abnormality in attention deficit hyperactivity disorder-like model rats.}, journal = {Journal of pharmacological sciences}, volume = {157}, number = {3}, pages = {189-198}, doi = {10.1016/j.jphs.2025.01.007}, pmid = {39929593}, issn = {1347-8648}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Attention Deficit Disorder with Hyperactivity/therapy/microbiology/psychology ; *Gastrointestinal Microbiome/genetics ; Disease Models, Animal ; Male ; *Behavior, Animal ; Rats, Sprague-Dawley ; Dysbiosis/therapy ; Rats ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity. ADHD symptoms not only impact patients and their families but also impose societal costs. Current treatments for ADHD, including environmental adjustments and medication, are symptomatic and require long-term management. Recently, the link between gut microbiota dysbiosis and various psychiatric and neurological disorders has become evident. The effectiveness of fecal microbiota transplantation (FMT) from healthy individuals in treating autism spectrum disorder, a neurodevelopmental disorder related to ADHD, has been demonstrated. However, despite suggestions of a relationship between ADHD and gut microbiota, few studies have explored the efficacy of FMT for ADHD. In the current study, we used 16S rDNA analysis to show that ADHD-like model rats possess a gut microbiota that is distinct from that of healthy rats, and we demonstrated that FMT from healthy rats improved hyperactivity in ADHD-like model rats. Our findings suggest that differences in gut microbiota underlie ADHD-like behaviors and that FMT may be an effective treatment for ADHD.}, } @article {pmid39926318, year = {2025}, author = {Rågård, N and Baumwall, SMD and Paaske, SE and Hansen, MM and Høyer, KL and Mikkelsen, S and Erikstrup, C and Dahlerup, JF and Hvas, CL}, title = {Validation methods for encapsulated faecal microbiota transplantation: a scoping review.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848251314820}, pmid = {39926318}, issn = {1756-283X}, abstract = {Faecal microbiota transplantation (FMT) is increasingly used for diseases associated with a disrupted intestinal microbiome, mainly Clostridioides difficile infection. Encapsulated FMT is a patient-friendly application method that improves accessibility and convenience. Capsule processing may be standardised, but validation protocols are warranted. This review aimed to describe published validation methods for encapsulated FMT. Original studies reporting using encapsulated faecal formulations were included, regardless of indication. Studies were excluded if they did not address processing and validation or used non-donor-derived content. We conducted a comprehensive scoping review, implementing a systematic search strategy in PubMed, Embase and Web of Science. Processing data and validation methods were registered during full-text analysis and combined to create an overview of approaches for assessing quality in encapsulated FMT processing. The searches identified 324 unique studies, of which 44 were included for data extraction and analysis. We identified eight validation covariables: donor selection, pre-processing, preservation, oxygen-sparing processing, microbial count, viability, engraftment and clinical effect outcomes, from which we constructed a model for quality assessment of encapsulated FMT that exhaustively categorised processing details and validation measures. Our model comprised three domains: (1) Processing (donor selection and processing protocol), (2) Content analysis (microbiota measures and dose measures) and (3) Clinical effect (engraftment and clinical outcomes). No studies presented a reproducible capsule protocol; their validation strategies were sparse and divergent. The validation of FMT capsules is heterogeneous, and processing requires relevant standardisation protocols, mainly focusing on capsule content. Future studies should report validation covariables to enable accurate comparative assessments of clinical effects.}, } @article {pmid39926224, year = {2025}, author = {Paul, JK and Azmal, M and Haque, ASNB and Meem, M and Talukder, OF and Ghosh, A}, title = {Unlocking the secrets of the human gut microbiota: Comprehensive review on its role in different diseases.}, journal = {World journal of gastroenterology}, volume = {31}, number = {5}, pages = {99913}, pmid = {39926224}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/physiology ; *Dysbiosis/microbiology/immunology/therapy ; Probiotics/therapeutic use/administration & dosage ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; Neoplasms/microbiology/immunology ; Autoimmune Diseases/microbiology/immunology ; *Bacteria/pathogenicity/immunology ; Metabolic Diseases/microbiology/immunology ; }, abstract = {The human gut microbiota, a complex and diverse community of microorganisms, plays a crucial role in maintaining overall health by influencing various physiological processes, including digestion, immune function, and disease susceptibility. The balance between beneficial and harmful bacteria is essential for health, with dysbiosis - disruption of this balance - linked to numerous conditions such as metabolic disorders, autoimmune diseases, and cancers. This review highlights key genera such as Enterococcus, Ruminococcus, Bacteroides, Bifidobacterium, Escherichia coli, Akkermansia muciniphila, Firmicutes (including Clostridium and Lactobacillus), and Roseburia due to their well-established roles in immune regulation and metabolic processes, but other bacteria, including Clostridioides difficile, Salmonella, Helicobacter pylori, and Fusobacterium nucleatum, are also implicated in dysbiosis and various diseases. Pathogenic bacteria, including Escherichia coli and Bacteroides fragilis, contribute to inflammation and cancer progression by disrupting immune responses and damaging tissues. The potential for microbiota-based therapies, such as probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, to improve health outcomes is examined. Future research directions in the integration of multi-omics, the impact of diet and lifestyle on microbiota composition, and advancing microbiota engineering techniques are also discussed. Understanding the gut microbiota's role in health and disease is essential for formulating personalized, efficacious treatments and preventive strategies, thereby enhancing health outcomes and progressing microbiome research.}, } @article {pmid39924929, year = {2025}, author = {Zhong, H and Jiang, M and Yuan, K and Sheng, F and Xu, X and Cui, Y and Sun, X and Tan, W}, title = {Alterations in gut microbiota and metabolites contribute to postoperative sleep disturbances.}, journal = {Animal models and experimental medicine}, volume = {8}, number = {6}, pages = {977-989}, pmid = {39924929}, issn = {2576-2095}, support = {82171187//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Male ; *Sleep Wake Disorders/etiology/microbiology/metabolism ; *Postoperative Complications/microbiology/etiology/metabolism ; Tryptophan/metabolism ; Feces/microbiology/chemistry ; Rats, Sprague-Dawley ; Rats ; Fecal Microbiota Transplantation ; Kynurenine/metabolism ; }, abstract = {BACKGROUND: The composition of the intestinal flora and the resulting metabolites affect patients' sleep after surgery.

METHODS: We intended to elucidate the mechanisms by which disordered intestinal flora modulate the pathophysiology of postoperative sleep disturbances in hosts. In this study, we explored the impacts of anesthesia, surgery, and postoperative sleep duration on the fecal microbiota and metabolites of individuals classified postprocedurally as poor sleepers (PS) and good sleepers (GS), as diagnosed by the bispectral index. We also performed fecal microbiota transplantation in pseudo-germ-free (PGF) rats and applied Western blotting, immunohistochemistry, and gut permeability analyses to identify the potential mechanism of its effect.

RESULTS: Research finding shows the PS group had significantly higher postoperative stool levels of the metabolites tryptophan and kynurenine than the GS group. PGF rats that received gut microbiota from PSs exhibited less rapid eye movement (REM) sleep than those that received GS microbiota (GS-PGF: 11.4% ± 1.6%, PS-PGF: 4.8% ± 2.0%, p < 0.001). Measurement of 5-hydroxytryptophan (5-HTP) levels in the stool, serum, and prefrontal cortex (PFC) indicated that altered 5-HTP levels, including reduced levels in the PFC, caused sleep loss in PGF rats transplanted with PS gut flora. Through the brain-gut axis, the inactivity of tryptophan hydroxylase 1 (TPH1) and TPH2 in the colon and PFC, respectively, caused a loss of REM sleep in PGF rats and decreased the 5-HTP level in the PFC.

CONCLUSIONS: These findings indicate that postoperative gut dysbiosis and defective 5-HTP metabolism may cause postoperative sleep disturbances. Clinicians and sleep researchers may gain new insights from this study.}, } @article {pmid39924893, year = {2025}, author = {Chen, Y and Fang, H and Chen, H and Liu, X and Zhao, J and Stanton, C and Ross, RP and Chen, W and Yang, B}, title = {Bifidobacterium inhibits the progression of colorectal tumorigenesis in mice through fatty acid isomerization and gut microbiota modulation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2464945}, pmid = {39924893}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; Mice ; *Colorectal Neoplasms/microbiology/prevention & control/pathology/metabolism ; Humans ; *Bifidobacterium/metabolism/physiology ; Linoleic Acids, Conjugated/metabolism ; Male ; Female ; *Fatty Acids/metabolism/chemistry ; Disease Models, Animal ; *Carcinogenesis ; Butyric Acid/metabolism ; Fecal Microbiota Transplantation ; Probiotics/administration & dosage ; PPAR gamma/metabolism ; Mice, Inbred C57BL ; Bacteria/classification/metabolism/genetics/isolation & purification ; }, abstract = {Colorectal cancer (CRC) represents the third most common cancer worldwide. Consequently, there is an urgent need to identify novel preventive and therapeutic strategies for CRC. This study aimed to screen for beneficial bacteria that have a preventive effect on CRC and to elucidate the potential mechanisms. Initially, we compared gut bacteria and bacterial metabolites of healthy volunteers and CRC patients, which demonstrated that intestinal conjugated linoleic acid (CLA), butyric acid, and Bifidobacterium in CRC patients were significantly lower than those in healthy volunteers, and these indicators were significantly negatively correlated with CRC. Next, spontaneous CRC mouse model were conducted to explore the effect of supplemental CLA-producing Bifidobacterium on CRC. Supplementation of mice with CLA-producing Bifidobacterium breve CCFM683 and B. pseudocatenulatum MY40C significantly prevented CRC. Moreover, molecular approaches demonstrated that CLA and the CLA-producing gene, bbi, were the key metabolites and genes for CCFM683 to prevent CRC. Inhibitor intervention results showed that PPAR-γ was the key receptor for preventing CRC. CCFM683 inhibited the NF-κB signaling pathway, up-regulated MUC2, Claudin-1, and ZO-1, and promoted tumor cell apoptosis via the CLA-PPAR-γ axis. Additionally, fecal microbiota transplantation (FMT) and metagenomic analysis showed that CCFM683 up-regulated Odoribacter splanchnicus through CLA production, which then prevented CRC by producing butyric acid, up-regulating TJ proteins, regulating cytokines, and regulating gut microbiota. These results will contribute to the clinical trials of Bifidobacterium and the theoretical research and development of CRC dietary products.}, } @article {pmid39924042, year = {2025}, author = {Wu, T and Song, F and Huang, J and Cui, S and Wang, L and Yang, Q and Wu, Y and Li, B and Tu, Y and Wan, X and Liu, J}, title = {Gut microbiota: The pivotal conduit in the onset of constipation and its alleviation by tea flower polysaccharides (TFP) in a mouse model.}, journal = {International journal of biological macromolecules}, volume = {304}, number = {Pt 1}, pages = {140808}, doi = {10.1016/j.ijbiomac.2025.140808}, pmid = {39924042}, issn = {1879-0003}, mesh = {Animals ; *Constipation/drug therapy/microbiology/chemically induced ; *Gastrointestinal Microbiome/drug effects ; *Polysaccharides/pharmacology/chemistry/therapeutic use ; Mice ; Disease Models, Animal ; *Flowers/chemistry ; Male ; *Tea/chemistry ; Fecal Microbiota Transplantation ; Gastrointestinal Transit/drug effects ; }, abstract = {Plant-derived bioactive components, such as polysaccharides, provide promising alleviating effects on constipation with minimal side-effects compared to pharmacological interventions. This study aimed to explore the therapeutic potential of tea flower polysaccharides (TFP) on constipation and the involved mechanisms. In a loperamide-induced constipation mouse model, TFP administration significantly increased fecal water content from 54.23-57.30 % to 63.70-79.36 %, enhanced intestinal transit rate from 30.80 % to 38.81 %, and reduced gastrointestinal (GI) transit time from 234.4 min to 186.2 min. TFP restored levels of both excitatory and inhibitory hormones related to GI motility. Transcriptomic analysis of colonic epithelial cells revealed that TFP restored expression of 544 genes involved in various pathways, including the NF-κB and JAK-STAT signaling pathways, which are associated with the improvement of constipation. Gut microbiota analysis demonstrated that TFP mitigated dysbiosis by normalizing the Firmicutes/Bacteroidota ratio, inhibiting pathogenic genera (e.g., Helicobacter), and promoting beneficial genera (e.g., Muribaculaceae, Bacteroides, Parabacteroides). The mediating role of gut microbiota in the onset of constipation and its alleviation was confirmed through fecal microbiota transplantation (FMT). Furthermore, TFP and its combination with anti-constipation drugs alleviated constipation-induced hepatorenal damage. This study highlights TFP's potential in treating constipation and underscores the essential role of gut microbiota in its therapeutic effects.}, } @article {pmid39923429, year = {2025}, author = {Yang, F and Yan, Q and Wang, Y and Li, Q and Wang, J and Zeng, X and Pi, Y and Zhang, M and Wei, L}, title = {AMP1-1 alleviates bone loss in weightless rats by reducing peripheral 5-HT content via the microbiota-gut-bone axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {139}, number = {}, pages = {156447}, doi = {10.1016/j.phymed.2025.156447}, pmid = {39923429}, issn = {1618-095X}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Rats ; Rats, Sprague-Dawley ; *Atractylodes/chemistry ; *Serotonin/metabolism ; Male ; *Polysaccharides/pharmacology ; X-Ray Microtomography ; Fecal Microbiota Transplantation ; Weightlessness/adverse effects ; Bone and Bones/drug effects/metabolism ; Osteogenesis/drug effects ; Bone Density/drug effects ; }, abstract = {BACKGROUND: Weightlessness-induced bone loss (WIBL) refers to the reduction of bone mass and the decline of bone resistance to load in a weightless environment. However, current treatment strategies aimed at increasing bone mass are associated with various limitations and side effects, highlighting the urgent need for safer and more effective therapeutic options to address WIBL.

PURPOSE: We aimed to further explore the potential mechanism of the anti-WIBL effect of Atractylodes macrocephalon polysaccharide1-1(AMP1-1). To find a better way to treat WIBL and provide new insights for the development of therapeutic drugs for this condition.

METHODS: Firstly, the anti-weightlessness bone loss of AMP1-1 was verified by micro-computed tomography (Micro-CT), three-point mechanical bending test and Western Blot (WB). Subsequently, the intestinal barrier was examined using histopathology, immunohistochemistry (IHC), and WB. Finally, validation experiments were performed using fecal microbiota transplantation (FMT). After FMT, 16S rDNA sequencing was used to analyze the gut microbiota composition in the rat feces.

RESULTS: AMP1-1 was able to inhibit WIBL by enhancing bone mass, improving toughness, and increasing osteogenic activity. Meanwhile, AMP1-1 reduced peripheral 5-HT content by restoring enterochromaffin cell function through gut microbiota regulation and tight junction repair. FMT of rat fecal microbiota after gavage of AMP1-1 into tail suspension rats still has the effects of regulating gut microbiota, repairing intestinal barrier and reducing bone loss.

CONCLUSION: Our results demonstrate that AMP1-1 exerts a protective effect against WIBL in rats, potentially by modulating 5-HT content and 5-HT-related metabolism in bone tissue through microbiota-gut-bone axis. This study is the first to elucidate the mechanism of AMP1-1 in mitigating WIBL through the perspective of the microbiota-gut-bone axis. Moreover, this research integrates plant extract research with the issue of bone loss induced by microgravity (aerospace medicine), thereby opening new avenues for natural drug research.}, } @article {pmid39922394, year = {2025}, author = {Xu, W and Liu, A and Gong, Z and Xiao, W}, title = {L-theanine prevents ulcerative colitis by regulating the CD4+ T cell immune response through the gut microbiota and its metabolites.}, journal = {The Journal of nutritional biochemistry}, volume = {139}, number = {}, pages = {109845}, doi = {10.1016/j.jnutbio.2025.109845}, pmid = {39922394}, issn = {1873-4847}, mesh = {Male ; Animals ; Mice ; Mice, Inbred C57BL ; *Threonine/metabolism/pharmacology ; *Colitis, Ulcerative/diet therapy/immunology/metabolism/microbiology ; *Gastrointestinal Microbiome/drug effects ; *CD4-Positive T-Lymphocytes/drug effects/immunology ; Feces/microbiology ; Macrophages/drug effects/immunology ; Antigen Presentation ; }, abstract = {The disturbance of gut microbiota and its metabolites are considered to be the causes of ulcerative colitis (UC), which leads to immune abnormalities. Diet is the most important regulator of gut microbiota; therefore, it has a beneficial impact on UC. A novel food ingredient, l-theanine, alters the gut microbiota, thereby regulating gut immunity. However, whether l-theanine prevents UC by altering the gut microbiota, as well as the underlying mechanisms, remains unknown. Here, l-theanine was used to optimize the gut microbiota and its metabolites. Furthermore, to explore the mechanism by which l-theanine prevents UC, an l-theanine fecal microbiota solution was used to prevent dextran sulfate sodium-induced UC via fecal microbiota transplantation. Improvements in the colonic structure, colon histology scores, immune factors (IL-10), and inflammatory factors (IL-1β) demonstrated the preventive effect of l-theanine on UC. The 16S rDNA and metabolomic results showed that tryptophan-, short chain fatty acid-, and bile acid-related microbiota, such as Muribaculaceae, Lachnospiraceae, Alloprevotella, and Prevotellaceae were the dominant. Flow cytometry results showed that l-theanine decreased helper T (Th)1 and Th17 immune responses, and increased Th2 and T-regulatory immune responses via regulation of antigen-presenting cell responses, such as dendritic cells and macrophages. Therefore, l-theanine regulated the immune response of colon CD4 + T cells to dendritic cell and macrophage antigen presentation via tryptophan-, short chain fatty acid-, and bile acid-related microbiota, thereby preventing dextran sulfate sodium-induced UC.}, } @article {pmid39921898, year = {2025}, author = {Cohen, S and Spencer, EA and Dolinger, MT and Suskind, DL and Mitrova, K and Hradsky, O and Conrad, MA and Kelsen, JR and Uhlig, HH and Tzivinikos, C and Henderson, P and Wlazlo, M and Hackl, L and Shouval, DS and Bramuzzo, M and Urlep, D and Olbjørn, C and D'Arcangelo, G and Pujol-Muncunill, G and Yogev, D and Kang, B and Gasparetto, M and Rungoe, C and Kolho, KL and Hojsak, I and Norsa, L and Rinawi, F and Sansotta, N and Rimon, RM and Granot, M and Scarallo, L and Trindade, E and Rodríguez-Belvís, MV and Turner, D and Yerushalmy-Feler, A}, title = {Upadacitinib for Induction of Remission in Paediatric Crohn's Disease: An International Multicentre Retrospective Study.}, journal = {Alimentary pharmacology & therapeutics}, volume = {61}, number = {8}, pages = {1372-1380}, pmid = {39921898}, issn = {1365-2036}, mesh = {Humans ; Retrospective Studies ; *Crohn Disease/drug therapy ; Male ; Female ; Adolescent ; Remission Induction ; *Heterocyclic Compounds, 3-Ring/therapeutic use/adverse effects ; Treatment Outcome ; Child ; }, abstract = {BACKGROUND: There are scarce data available on upadacitinib in children with Crohn's disease (CD).

AIM: To evaluate the effectiveness and safety of upadacitinib as an induction therapy in paediatric CD.

METHODS: This was a multicentre retrospective study between 2022 and 2024 of children treated with upadacitinib for induction of remission of active CD conducted in 30 centres worldwide affiliated with the IBD Interest and Porto group of the ESPGHAN. We recorded demographic, clinical and laboratory data and adverse events (AEs) at week 8 post-induction. The analysis of the primary outcome was based upon the intention-to-treat (ITT) principle.

RESULTS: We included 100 children (median age 15.8 [interquartile range 14.3-17.2]). All were previously treated with biologic therapies including 89 with ≥ 2 biologics. At the end of the 8-week induction period, we observed clinical response, clinical remission and corticosteroid- and exclusive enteral nutrition-free clinical remission (CFR) in 75%, 56% and 52%, respectively. By the end of induction, 68% had achieved normalisation of C-reactive protein, and 58% had faecal calprotectin (FC) < 150 mcg/g. There was combined CFR and FC remission in 13/31 children with available data at 8 weeks (13% of the ITT population). AEs were recorded in 24 children; the most frequent was acne in 12. Two AEs (severe acne and hypertriglyceridemia) led to discontinuation of therapy.

CONCLUSION: Upadacitinib is an effective induction therapy for refractory paediatric CD. Efficacy should be weighed against the potential risks of AEs.}, } @article {pmid39920804, year = {2025}, author = {Mooyottu, S and Muyyarikkandy, MS and Yousefi, F and Li, G and Sahin, O and Burrough, E and Scaria, J and Sponseller, B and Ramirez, A}, title = {Fecal microbiota transplantation modulates jejunal host-microbiota interface in weanling piglets.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {45}, pmid = {39920804}, issn = {2049-2618}, support = {2022-67015-40720//National Institute of Food and Agriculture/ ; 19-216 IPPA//Iowa Pork Producers Association/ ; }, mesh = {Animals ; Swine ; *Fecal Microbiota Transplantation ; *Jejunum/microbiology ; *Gastrointestinal Microbiome ; Weaning ; Feces/microbiology ; Diarrhea/microbiology/therapy/veterinary ; Bacteria/classification/genetics/isolation & purification ; Swine Diseases/microbiology/therapy ; Enterotoxigenic Escherichia coli ; *Host Microbial Interactions ; }, abstract = {BACKGROUND: Weaning-associated enteric diseases are a major concern in the swine industry. This study investigates the effects of fecal microbiota transplantation (FMT) on the jejunum of weanling piglets, a segment of bowel less studied in terms of microbiomic changes despite its primary involvement in major post-weaning enteric diseases, including postweaning diarrhea (PWD). Thirty-two 3-week-old piglets were divided equally into two groups: Control and FMT. The FMT group received fecal microbiota preparation from 3-month-old healthy pigs on the 1st and 3rd day after weaning. Half of each group was inoculated with an enterotoxigenic E. coli (ETEC) isolate 10 days post-FMT. Piglets were euthanized in the third week (14th and 18th days post-FMT) after weaning to collect intestinal tissues and contents for microbiomic, metabolomic, and transcriptomic analyses.

RESULTS: The jejunal microbiota showed a significant increase in alpha diversity in the third week post-FMT compared with the ileum and colon. FMT significantly enriched the jejunal microbiota composition, while multiple bacterial genera were specifically lacking in control weanling piglets. FMT was strongly associated with the enrichment of the genus Pseudoscardovia of the Bifidobacteriaceae family, which was found lacking in the jejunum of weanling control piglets and inversely associated with the abundance of the genus Bifidobacterium within the same family. Other genera associated with FMT included Solobacterium, Shuttleworthia, and Pseudoraminibacter, whereas bacteria such as Erysipelotrichaceae and Acidaminococcus were identified as most abundant in the control piglets. Metabolomic analysis revealed a significant modulatory effect of FMT on carbohydrate, amino acid, nucleotide, vitamin, and xenobiotic metabolisms, suggesting improved nutrient utilization. Transcriptomic analyses further confirmed the regulatory effects of FMT on gene expression associated with immune, metabolic, barrier, and neuroendocrine functions. Prior FMT treatment in the context of ETEC infection indicated a potential protective role, as evidenced by a significant shift in microbial diversity and metabolomic compositions and decreased diarrhea severity even though no effect on pathogen shedding was evident.

CONCLUSIONS: This study underscores the promise of FMT in enhancing jejunal health. In addition, the results suggest that FMT could be considered a potential strategy to address conditions associated with small intestinal dysbiosis in swine and other monogastric species with similar gut anatomy and physiology, such as humans. Video Abstract.}, } @article {pmid39917846, year = {2025}, author = {Jeong, S and Davis, CK and Chokkalla, AK and Kim, B and Park, S and Vemuganti, R}, title = {Fecal microbiota transplantation fails to impart the benefits of circadian-dependent intermittent fasting following ischemic stroke.}, journal = {Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism}, volume = {45}, number = {4}, pages = {779-789}, pmid = {39917846}, issn = {1559-7016}, support = {R35 NS132184/NS/NINDS NIH HHS/United States ; IK6 BX005690/BX/BLRD VA/United States ; I01 BX006062/BX/BLRD VA/United States ; R01 NS130763/NS/NINDS NIH HHS/United States ; I01 BX005127/BX/BLRD VA/United States ; }, mesh = {*Fasting/physiology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Male ; *Ischemic Stroke/therapy/microbiology ; *Circadian Rhythm/physiology ; Animals ; Humans ; Female ; Intermittent Fasting ; }, abstract = {Intermittent fasting (IF) is known to induce significant ischemic tolerance. Diet is a major proponent of gut microbiota, and gut microbial dysbiosis plays a role in post-stroke brain damage. Hence, we currently evaluated whether IF-mediated ischemic tolerance is mediated by gut microbiota. Additionally, circadian cycle is known to modulate post-ischemic outcomes, and thus we further evaluated if gut microbiota would be influenced by prophylactic IF during the inactive phase (fasting during daytime; IIF) or active phase (fasting during nighttime; AIF). The AIF, but not IIF, cohort showed a significantly decreased fecal Firmicutes/Bacteroidetes ratio compared with the ad libitum (AL) cohort. Moreover, the levels of gut microbiota-derived metabolites butyrate and propionate decreased in AL cohort following focal ischemia, whereas they increased in AIF cohort. However, fecal microbiota transplantation (FMT) from IIF or AIF cohort had no significant effects on post-ischemic motor and cognitive function recovery, anxiety-, and depression-like behaviors compared with FMT from AL cohort. Furthermore, FMT from IIF or AIF cohort did not influence the post-ischemic infarct volume, atrophy volume or white matter damage. Overall, the current findings indicate that the beneficial effects of IF after focal ischemia are not mediated by the gut microbiota.}, } @article {pmid39916498, year = {2025}, author = {Chen, Q and Gao, Y and Li, F and Yuan, L}, title = {The role of gut-islet axis in pancreatic islet function and glucose homeostasis.}, journal = {Diabetes, obesity & metabolism}, volume = {27}, number = {4}, pages = {1676-1692}, pmid = {39916498}, issn = {1463-1326}, support = {82170812//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Homeostasis/physiology ; *Gastrointestinal Microbiome/physiology ; *Islets of Langerhans/metabolism/physiology ; Animals ; *Gastrointestinal Tract/metabolism/microbiology ; *Glucose/metabolism ; Signal Transduction ; }, abstract = {The gastrointestinal tract plays a vital role in the occurrence and treatment of metabolic diseases. Recent studies have convincingly demonstrated a bidirectional axis of communication between the gut and islets, enabling the gut to influence glucose metabolism and energy homeostasis in animals strongly. The 'gut-islet axis' is an essential endocrine signal axis that regulates islet function through the dialogue between intestinal microecology and endocrine metabolism. The discovery of glucagon-like peptide-1 (GLP-1), gastric inhibitory peptide (GIP) and other gut hormones has initially set up a bridge between gut and islet cells. However, the influence of other factors remains largely unknown, such as the homeostasis of the gut microbiota and the integrity of the gut barrier. Although gut microbiota primarily resides and affect intestinal function, they also affect extra-intestinal organs by absorbing and transferring metabolites derived from microorganisms. As a result of this transfer, islets may be continuously exposed to gut-derived metabolites and components. Changes in the composition of gut microbiota can damage the intestinal barrier function to varying degrees, resulting in increased intestinal permeability to bacteria and their derivatives. All these changes contribute to the severe disturbance of critical metabolic pathways in peripheral tissues and organs. In this review, we have outlined the different gut-islet axis signalling mechanisms associated with metabolism and summarized the latest progress in the complex signalling molecules of the gut and gut microbiota. In addition, we will discuss the impact of the gut renin-angiotensin system (RAS) on the various components of the gut-islet axis that regulate energy and glucose homeostasis. This work also indicates that therapeutic approaches aiming to restore gut microbial homeostasis, such as probiotics and faecal microbiota transplantation (FMT), have shown great potential in improving treatment outcomes, enhancing patient prognosis and slowing down disease progression. Future research should further uncover the molecular links between the gut-islet axis and the gut microbiota and explore individualized microbial treatment strategies, which will provide an innovative perspective and approach for the diagnosis and treatment of metabolic diseases.}, } @article {pmid39915986, year = {2025}, author = {Escobar, C and Aldeguer, X and Vivas, D and Manzano Fernández, S and Gonzalez Caballero, E and Garcia Martín, A and Barrios, V and Freixa-Pamias, R}, title = {The gut microbiota and its role in the development of cardiovascular disease.}, journal = {Expert review of cardiovascular therapy}, volume = {23}, number = {1-2}, pages = {23-34}, doi = {10.1080/14779072.2025.2463366}, pmid = {39915986}, issn = {1744-8344}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Cardiovascular Diseases/microbiology/physiopathology/etiology/therapy ; *Dysbiosis/complications/therapy/microbiology/physiopathology ; Probiotics/administration & dosage ; Prebiotics/administration & dosage ; Fecal Microbiota Transplantation/methods ; Animals ; }, abstract = {INTRODUCTION: The pathophysiology of cardiovascular diseases encompasses a complex interplay of genetic and environmental risk factors. Even if traditional risk factors are treated to target, there remains a residual risk.

AREAS COVERED: This manuscript reviews the potential role of gut microbiota in the development of cardiovascular disease, and as potential target. A systematic search was conducted until 30 October 2024 on PubMed (MEDLINE), using the MeSH terms [Gut microbiota] + [Dysbiosis] + [Cardiovascular] + [TMAO] + [bile acids] + [short-chain fatty acids].

EXPERT OPINION: The term dysbiosis implies changes in equilibrium, with modifications in the composition and functionality of microbiota and a series of additional factors: reduced diversity and uniformity of microorganisms; reduced short-chain fatty acid-producing bacteria; increased gut permeability; release of metabolites, such as trimethylamine N-oxide, betaine, phenylalanine, tryptophan-kynurenine, phenylacetylglutamine, and lipopolysaccharides; and reduced secondary bile acid excretion, leading to inflammation, oxidative stress, and endothelial dysfunction and facilitating the onset of pathological conditions, including obesity, hypertension, diabetes, atherosclerosis, and heart failure. Attempts to restore gut microbiota balance through different interventions, mainly changes in diet, have been shown to positively affect individual components and metabolites and reduce the risk of cardiovascular disease. In addition, probiotics and prebiotics are potentially useful. Fecal microbiota transplantation is a promising therapy.}, } @article {pmid39915243, year = {2025}, author = {Zhao, S and Lin, H and Li, W and Xu, X and Wu, Q and Wang, Z and Shi, J and Chen, Y and Ye, L and Xi, L and Chen, L and Yuan, M and Su, J and Gao, A and Jin, J and Ying, X and Wang, X and Ye, Y and Sun, Y and Zhang, Y and Deng, X and Shen, B and Gu, W and Ning, G and Wang, W and Hong, J and Wang, J and Liu, R}, title = {Post sleeve gastrectomy-enriched gut commensal Clostridia promotes secondary bile acid increase and weight loss.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2462261}, pmid = {39915243}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; *Bile Acids and Salts/metabolism ; *Weight Loss ; Humans ; Mice ; *Clostridium/genetics/metabolism/isolation & purification/classification ; *Gastrectomy ; Male ; *Obesity/surgery/microbiology/metabolism ; Receptors, G-Protein-Coupled/metabolism/genetics ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Feces/microbiology ; Female ; Adult ; Bariatric Surgery ; }, abstract = {The gut microbiome is altered after bariatric surgery and is associated with weight loss. However, the commensal bacteria involved and the underlying mechanism remain to be determined. We performed shotgun metagenomic sequencing in obese subjects before and longitudinally after sleeve gastrectomy (SG), and found a significant enrichment in microbial species in Clostridia and bile acid metabolizing genes after SG treatment. Bile acid profiling further revealed decreased primary bile acids (PBAs) and increased conjugated secondary bile acids (C-SBAs) after SG. Specifically, glycodeoxycholic acid (GDCA) and taurodeoxycholic acid (TDCA) were increased at different follow-ups after SG, and were associated with the increased abundance of Clostridia and body weight reduction. Fecal microbiome transplantation with post-SG feces increased SBA levels, and alleviated body weight gain in the recipient mice. Furthermore, both Clostridia-enriched spore-forming bacteria and GDCA supplementation increased the expression of genes responsible for lipolysis and fatty acid oxidation in adipose tissue and reduced adiposity via Takeda G-protein-coupled receptor 5 (TGR5) signaling. Our findings reveal post-SG gut microbiome and C-SBAs as contributory to SG-induced weight loss, in part via TGR5 signaling, and suggest SBA-producing gut microbes as a potential therapeutic target for obesity intervention.}, } @article {pmid39912727, year = {2025}, author = {Ma, X and Li, M and Zhang, Y and Xu, T and Zhou, X and Qian, M and Yang, Z and Han, X}, title = {Akkermansia muciniphila identified as key strain to alleviate gut barrier injury through Wnt signaling pathway.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {39912727}, issn = {2050-084X}, support = {32172765//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Wnt Signaling Pathway ; Mice ; *Gastrointestinal Microbiome ; Swine ; *Fecal Microbiota Transplantation ; Bacteroides fragilis/physiology ; *Intestinal Mucosa/microbiology ; Enterotoxigenic Escherichia coli ; *Akkermansia ; *Escherichia coli Infections/therapy/microbiology ; Disease Models, Animal ; Anti-Bacterial Agents ; Mice, Inbred C57BL ; }, abstract = {As the largest mucosal surface, the gut has built a physical, chemical, microbial, and immune barrier to protect the body against pathogen invasion. The disturbance of gut microbiota aggravates pathogenic bacteria invasion and gut barrier injury. Fecal microbiota transplantation (FMT) is a promising treatment for microbiome-related disorders, where beneficial strain engraftment is a significant factor influencing FMT outcomes. The aim of this research was to explore the effect of FMT on antibiotic-induced microbiome-disordered (AIMD) models infected with enterotoxigenic Escherichia coli (ETEC). We used piglet, mouse, and intestinal organoid models to explore the protective effects and mechanisms of FMT on ETEC infection. The results showed that FMT regulated gut microbiota and enhanced the protection of AIMD piglets against ETEC K88 challenge, as demonstrated by reduced intestinal pathogen colonization and alleviated gut barrier injury. Akkermansia muciniphila (A. muciniphila) and Bacteroides fragilis (B. fragilis) were identified as two strains that may play key roles in FMT. We further investigated the alleviatory effects of these two strains on ETEC infection in the AIMD mice model, which revealed that A. muciniphila and B. fragilis relieved ETEC-induced intestinal inflammation by maintaining the proportion of Treg/Th17 cells and epithelial damage by moderately activating the Wnt/β-catenin signaling pathway, while the effect of A. muciniphila was better than B. fragilis. We, therefore, identified whether A. muciniphila protected against ETEC infection using basal-out and apical-out intestinal organoid models. A. muciniphila did protect the intestinal stem cells and stimulate the proliferation and differentiation of intestinal epithelium, and the protective effects of A. muciniphila were reversed by Wnt inhibitor. FMT alleviated ETEC-induced gut barrier injury and intestinal inflammation in the AIMD model. A. muciniphila was identified as a key strain in FMT to promote the proliferation and differentiation of intestinal stem cells by mediating the Wnt/β-catenin signaling pathway.}, } @article {pmid39911724, year = {2025}, author = {Dutta, SK and Firnberg, E and Verma, S and Phillips, L and Nair, PP}, title = {Detection of Human Y Chromosome and the SRY Gene in Fecal Samples of Female Patients Following Fecal Microbiota Transplantation.}, journal = {Gastro hep advances}, volume = {4}, number = {2}, pages = {100568}, pmid = {39911724}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: We have postulated that fecal microbiota transplantation (FMT) is associated with transfer of microbiota from the donor and engraftment of intestinal epithelial cells in the recipient's colonic mucosa enabling the restoration of a stable microbial environment.

METHODS: We analyzed the presence of human Y chromosome (ChrY) and sex-determining region Y (SRY) gene within total human DNA extracted from fecal samples collected from 30 donors and 22 recurrent Clostridium difficile infection (RCDI) patients before and up to 24 months after FMT. A next-generation sequencing data analysis pipeline was applied to quantify the percentage of reads aligning to human ChrY. SRY gene detection was also performed by quantitative polymerase chain reaction and droplet digital polymerase chain reaction.

RESULTS: A significantly higher percentage of ChrY reads were identified in fecal samples of male donors as compared to female donor (P < .0001). Fecal samples collected from female RCDI patients who received FMT from male donors showed a significantly (P < .05) higher percentage of ChrY reads compared to female samples without male FMT donors. Four female patients with RCDI who received FMT from male donors showed a very large percent ChrY increase post-FMT even several months after FMT. SRY gene signal was detected by droplet digital polymerase chain reaction in 7 of the 11 fecal samples collected from the male donor pool but none from the female pool.

CONCLUSION: These observations clearly demonstrate the presence of ChrY and SRY gene signal in stool samples collected from male patients. The presence of increased ChrY in the stool samples of female RCDI patients after FMT from a male donor suggests possible engraftment of exfoliated intestinal epithelial cells in a subset of these patients.}, } @article {pmid39910418, year = {2025}, author = {Li, L and Mo, Q and Wan, Y and Zhou, Y and Li, W and Li, W}, title = {Antimicrobial peptide AP2 ameliorates Salmonella Typhimurium infection by modulating gut microbiota.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {64}, pmid = {39910418}, issn = {1471-2180}, support = {No. 82003436//Young Scientists Fund of the National Natural Science Foundation of China/ ; No. 2011BAD26B02//the 'twelfth five-year-plan' in National Support Program for Science and Technology for rural development in China/ ; No. 31472128//Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Salmonella typhimurium/drug effects ; Mice ; Cecum/microbiology/pathology ; *Antimicrobial Peptides/pharmacology/administration & dosage ; RNA, Ribosomal, 16S/genetics ; *Salmonella Infections/microbiology/drug therapy ; Feces/microbiology ; Cytokines/blood ; Disease Models, Animal ; *Antimicrobial Cationic Peptides/administration & dosage/pharmacology ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Male ; Bacteria/classification/genetics/drug effects ; *Salmonella Infections, Animal/microbiology/drug therapy ; }, abstract = {BACKGROUND: Endogenous antimicrobial peptides and proteins are essential for shaping and maintaining a healthy gut microbiota, contributing to anti-inflammatory responses and resistance to pathogen colonization. Salmonella enterica subsp. enterica serovar Typhimurium (ST) infection is one of the most frequently reported bacterial diseases worldwide. Manipulation of the gut microbiota through exogenous antimicrobial peptides may protect against ST colonization and improve clinical outcomes.

RESULTS: This study demonstrated that oral administration of the antimicrobial peptide AP2 (2 µg /mouse), an optimized version of native apidaecin IB (AP IB), provided protective effects against ST infection in mice. These effects were evidenced by reduced ST-induced body weight loss and lower levels of serum inflammatory cytokines. A 16 S rRNA-based analysis of the cecal microbiota revealed that AP2 significantly modulated the gut microbiota, increasing the relative abundance of Bifidobacterium while decreasing that of Akkermansia at the genus level. Furthermore, the transplantation of fecal microbiota from AP2-treated donor mice, rather than from Control mice, significantly reduced cecal damage caused by ST and decreased the concentration of ST by one order of magnitude after infection.

CONCLUSIONS: These findings reveal a novel mechanism by which exogenous antimicrobial peptides mitigate Salmonella Typhimurium infection through the modulation of gut microbiota.}, } @article {pmid39909032, year = {2025}, author = {Zhu, X and Hu, M and Huang, X and Li, L and Lin, X and Shao, X and Li, J and Du, X and Zhang, X and Sun, R and Tong, T and Ma, Y and Ning, L and Jiang, Y and Zhang, Y and Shao, Y and Wang, Z and Zhou, Y and Ding, J and Zhao, Y and Xuan, B and Zhang, H and Zhang, Y and Hong, J and Fang, JY and Xiao, X and Shen, B and He, S and Chen, H}, title = {Interplay between gut microbial communities and metabolites modulates pan-cancer immunotherapy responses.}, journal = {Cell metabolism}, volume = {37}, number = {4}, pages = {806-823.e6}, doi = {10.1016/j.cmet.2024.12.013}, pmid = {39909032}, issn = {1932-7420}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Immunotherapy/methods ; *Neoplasms/therapy/metabolism/microbiology/immunology ; Metabolome ; Female ; Male ; Immune Checkpoint Inhibitors/therapeutic use ; Middle Aged ; Aged ; }, abstract = {Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment but remains effective in only a subset of patients. Emerging evidence suggests that the gut microbiome and its metabolites critically influence ICB efficacy. In this study, we performed a multi-omics analysis of fecal microbiomes and metabolomes from 165 patients undergoing anti-programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) therapy, identifying microbial and metabolic entities associated with treatment response. Integration of data from four public metagenomic datasets (n = 568) uncovered cross-cohort microbial and metabolic signatures, validated in an independent cohort (n = 138). An integrated predictive model incorporating these features demonstrated robust performance. Notably, we characterized five response-associated enterotypes, each linked to specific bacterial taxa and metabolites. Among these, the metabolite phenylacetylglutamine (PAGln) was negatively correlated with response and shown to attenuate anti-PD-1 efficacy in vivo. This study sheds light on the interplay among the gut microbiome, the gut metabolome, and immunotherapy response, identifying potential biomarkers to improve treatment outcomes.}, } @article {pmid39908366, year = {2025}, author = {Wu, F and Lin, S and Luo, H and Wang, C and Liu, J and Zhu, X and Pang, Y}, title = {Noncontact microbiota transplantation by core-shell microgel-enabled nonleakage envelopment.}, journal = {Science advances}, volume = {11}, number = {6}, pages = {eadr7373}, pmid = {39908366}, issn = {2375-2548}, mesh = {*Gastrointestinal Microbiome ; *Microgels/chemistry ; Humans ; Animals ; *Fecal Microbiota Transplantation/methods ; Probiotics ; Methacrylates/chemistry ; Hydrogen-Ion Concentration ; }, abstract = {Transplantation of beneficial bacteria to specific microbiota has been widely exploited to treat diseases by reshaping a healthy microbial structure. However, direct exposure of exogenous bacteria in vivo suffers from low bioavailability and infection risk. Here, we describe a noncontact microbiota transplantation system (NMTS) by core-shell microgel-enabled nonleakage envelopment. Bacteria are encapsulated into the core of core-shell microgels via two-step light-initiated emulsion polymerization of gelatin methacrylate. NMTS is versatile for biocontainment of diverse strains, showing near complete encapsulation and negligible influence on bacterial activity. As a proof-of-concept study on probiotic transplantation to the gut microbiota, NMTS demonstrates the shielding effect to protect sealed bacteria from intraluminal insults of low pH and bile acid, the toughness to prevent bacterial leakage during entire gastrointestinal passage and reduce infection risk, and the permeability to release beneficial metabolites and reconstruct a balanced intestinal microbial structure, proposing a contactless fashion for advanced microbiota transplantation.}, } @article {pmid39908176, year = {2025}, author = {}, title = {Correction to: A Randomized Controlled Trial of Efficacy and Safety of Fecal Microbiota Transplant for Preventing Recurrent Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {80}, number = {1}, pages = {242-243}, doi = {10.1093/cid/ciaf032}, pmid = {39908176}, issn = {1537-6591}, } @article {pmid39907559, year = {2025}, author = {Ding, Q and Xue, J and Li, N and Hu, Z and Song, J}, title = {Fecal microbiota transplantation alleviates radiation enteritis by modulating gut microbiota and metabolite profiles.}, journal = {Biomolecules & biomedicine}, volume = {25}, number = {9}, pages = {1992-2003}, doi = {10.17305/bb.2025.11835}, pmid = {39907559}, issn = {2831-090X}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Rats ; *Enteritis/therapy/microbiology/metabolism/etiology/pathology ; Male ; *Metabolome ; Rats, Sprague-Dawley ; Metabolomics ; Feces/microbiology ; *Radiation Injuries/therapy/microbiology/metabolism ; }, abstract = {This study investigates the safety and underlying mechanisms of fecal microbiota transplantation (FMT) in treating radiation enteritis (RE). A rat model of RE was established with six groups: NC, RT, H-FMT, modified FMT (M-FMT), L-FMT, and BTAC. The therapeutic effects of FMT were assessed using the Disease Activity Index (DAI), histological analysis, and biochemical tests, including ink-propelling, xylitol exclusion, and enzyme-linked immunosorbent assay (ELISA). Gut microbiota alterations and fecal metabolism were analyzed via 16S rDNA sequencing and targeted metabolomics. The results demonstrated that FMT, particularly in the M-FMT group, effectively alleviated RE by reducing DAI scores, histological damage, and inflammatory markers while enhancing enzyme activity, superoxide dismutase (SOD) levels, and intestinal absorption. FMT also modulated gut microbiota composition, increasing beneficial species, such as Blautia wexlerae and Romboutsia timonensis while decreasing Enterococcus ratti. Metabolomics analysis revealed that FMT influenced niacin, nicotinamide, and starch metabolism, with notable changes in pantothenic acid and fatty acid levels. Spearman correlation analysis further indicated that these microbial shifts were associated with improved metabolic profiles. Overall, FMT mitigates RE by regulating gut microbiota and metabolites, with pantothenic acid and fatty acids emerging as potential therapeutic targets. Further research is needed to explore the underlying mechanisms in greater detail.}, } @article {pmid39906503, year = {2025}, author = {Song, Q and Zhang, K and Li, S and Weng, S}, title = {Trichosanthes kirilowii Maxim. Polysaccharide attenuates diabetes through the synergistic impact of lipid metabolism and modulating gut microbiota.}, journal = {Current research in food science}, volume = {10}, number = {}, pages = {100977}, pmid = {39906503}, issn = {2665-9271}, abstract = {Polysaccharide, a chain of sugars bound by glycosidic bonds, have a wide range of physiological activities, including hypoglycemic activity. In present study, we established T2DM mice models to explore the effects and mechanism of Trichosanthes kirilowii Maxim polysaccharide (TMSP1) on high-fat diet/streptozotocin (HF-STZ) induced diabetes mice. The results showed that high-fat diet significantly increased the oral glucose tolerance test (OGTT), viscera index, oxidative stress, impaired glucose tolerance, decreased body weight, immune response and short-chain fatty acid (SCFAs) content, and disrupted the balance of intestinal flora structure. However, after 6 weeks of TMSP1 intervention decreased lipid accumulation, ameliorated gut microbiota dysbiosis by increasing SCFAs-producing bacteria and mitigated intestinal inflammation and oxidative stress. Moreover, TMSP1 significantly restored the integrity of the intestinal epithelial barrier and mucus barrier. The results of fecal microbiota transplantation confirmed that TMSP1 exerted hypoglycemic effect through regulating intestinal flora to a certain extent. Collectively, the findings revealed TMSP1 intervention inhibits hyperglycemia by improving gut microbiota disorder, lipid metabolism, and inflammation. Hence, TMSP1 may be an effective measure to ameliorate HF-STZ induced diabetes.}, } @article {pmid39905483, year = {2025}, author = {Lin, Z and Feng, Y and Wang, J and Men, Z and Ma, X}, title = {Microbiota governs host chenodeoxycholic acid glucuronidation to ameliorate bile acid disorder induced diarrhea.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {36}, pmid = {39905483}, issn = {2049-2618}, mesh = {Animals ; *Chenodeoxycholic Acid/metabolism ; *Diarrhea/microbiology/metabolism/etiology ; Mice ; *Gastrointestinal Microbiome/physiology ; *Bile Acids and Salts/metabolism ; Swine ; Limosilactobacillus reuteri/metabolism ; *Glucuronides/metabolism ; Fecal Microbiota Transplantation ; Intestinal Mucosa/metabolism/microbiology ; Sirtuin 1/metabolism ; Colon/microbiology/metabolism ; Disease Models, Animal ; Humans ; }, abstract = {BACKGROUND: Disorder in bile acid (BA) metabolism is known to be an important factor contributing to diarrhea. However, the pathogenesis of BA disorder-induced diarrhea remains unclear.

METHODS: The colonic BA pool and microbiota between health piglets and BA disorder-induced diarrheal piglets were compared. Fecal microbiota transplantation and various cell experiments further indicated that chenodeoxycholic acid (CDCA) metabolic disorder produced CDCA-3β-glucuronide, which is the main cause of BA disorder diarrhea. Non-targeted metabolomics uncovered the inhibition of the BA glucuronidation by Lactobacillus reuteri (L. reuteri) is through deriving indole-3-carbinol (I3C). In vitro, important gene involved in the reduction of BA disorder induced-diarrhea were screened by RNA transcriptomics sequencing, and activation pathway of FXR-SIRT1-LKB1 to alleviate BA disorder diarrhea and P53-mediated apoptosis were proposed in vitro by multifarious siRNA interference, CO-IP, immunofluorescence, and so on, which mechanism was also verified in a variety of mouse models.

RESULTS: Here, we reveal for the first time that core microbiota derived I3C represses gut epithelium glucuronidation, particularly 3β-glucuronic CDCA production, which reaction is mediated by host UDP glucuronosyltransferase family 1 member A4 (UGT1A4) and necessary of BA disorder induced diarrhea. Mechanistically, L. reuteri derived I3C activates aryl hydrocarbon receptor to decrease UGT1A4 transcription and CDCA-3β-glucuronide content, thereby upregulating FXR-SIRT1-LKB1 signal. LKB1 binds with P53 based on protein interaction, ultimately resists to apoptosis and diarrhea. Moreover, I3C assists CDCA to attain the ameliorative effects of FXR activation in BA disorder diarrhea, through reversion of abnormal metabolism pathway, improving the outcomes of CDCA supplement.

CONCLUSION: These findings uncover the crucial interplay between gut epithelial cells and microbes, highlighting UGT1A4-mediated conversion of CDCA-3β-glucuronide as a key target for ameliorating BA disorder-induced diarrhea. Video Abstract.}, } @article {pmid39904968, year = {2025}, author = {Ashiqueali, SA and Hayslip, N and Chaudhari, DS and Schneider, A and Zhu, X and Rubis, B and Seavey, CE and Alam, MT and Hussein, R and Noureddine, SA and Golusinska-Kardach, E and Pazdrowski, P and Yadav, H and Masternak, MM}, title = {Fecal microbiota transplant from long-living Ames dwarf mice alters the microbial composition and biomarkers of liver health in normal mice.}, journal = {GeroScience}, volume = {47}, number = {3}, pages = {4733-4750}, pmid = {39904968}, issn = {2509-2723}, support = {RF1 AG071762/AG/NIA NIH HHS/United States ; W81XWH-18-PRARP AZ180098//U.S. Department of Defense/ ; R56 AG074499/AG/NIA NIH HHS/United States ; R56AG069676/NH/NIH HHS/United States ; HORIZON 2020-MSCA-RISE//HORIZON EUROPE Marie Sklodowska-Curie Actions/ ; U01 AG076928/AG/NIA NIH HHS/United States ; 22A17//Florida Department of Health/ ; R56AG064075/NH/NIH HHS/United States ; R56AG074499/NH/NIH HHS/United States ; R21 AG072379/AG/NIA NIH HHS/United States ; RF1AG071762/NH/NIH HHS/United States ; R56 AG064075/AG/NIA NIH HHS/United States ; R21AG072379/NH/NIH HHS/United States ; R56 AG069676/AG/NIA NIH HHS/United States ; U01AG076928/NH/NIH HHS/United States ; R56AG074499/NH/NIH HHS/United States ; R56AG069676/NH/NIH HHS/United States ; R56AG064075/NH/NIH HHS/United States ; RF1AG071762/NH/NIH HHS/United States ; R21AG072379/NH/NIH HHS/United States ; U01AG076928/NH/NIH HHS/United States ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Mice ; *Gastrointestinal Microbiome/physiology ; *Liver/metabolism ; Biomarkers/metabolism ; Dysbiosis/therapy ; Male ; Transcriptome ; Aging ; }, abstract = {Aging is associated with intestinal dysbiosis, a condition characterized by diminished microbial biodiversity and inflammation. This leads to increased vulnerability to extraintestinal manifestations such as autoimmune, metabolic, and neurodegenerative conditions thereby accelerating mortality. As such, modulation of the gut microbiome is a promising way to extend healthspan. In this study, we explore the effects of fecal microbiota transplant (FMT) from long-living Ames dwarf donors to their normal littermates, and vice versa, on the recipient gut microbiota and liver transcriptome. Importantly, our previous studies highlight differences between the microbiome of Ames dwarf mice relative to their normal siblings, potentially contributing to their extended lifespan and remarkable healthspan. Our findings demonstrate that FMT from Ames dwarf mice to normal mice significantly alters the recipient's gut microbiota, potentially reprogramming bacterial functions related to healthy aging, and changes the liver transcriptome, indicating improved metabolic health. Particularly, the microbiome of Ames dwarf mice, characterized by a higher abundance of beneficial bacterial families such as Peptococcaceae, Oscillospiraceae, and Lachnospiraceae, appears to play a crucial role in modulating these effects. Alongside, our mRNA sequencing and RT-PCR validation reveals that FMT may contribute to the significant downregulation of p21, Elovl3, and Insig2, genes involved with cellular senescence and liver metabolic pathways. Our data suggest a regulatory axis exists between the gut and liver, highlighting the potential of microbiome-targeted therapies in promoting healthy aging. Future research should focus on functional validation of altered microbial communities and explore the underlying biomolecular pathways that confer geroprotection.}, } @article {pmid39904603, year = {2025}, author = {Lou, F and Yan, L and Luo, S and Dong, Y and Xu, J and Kang, N and Wang, H and Liu, Y and Pu, J and Yang, B and Cannon, RD and Xie, P and Ji, P and Jin, X}, title = {Dysbiotic oral microbiota-derived kynurenine, induced by chronic restraint stress, promotes head and neck squamous cell carcinoma by enhancing CD8[+] T cell exhaustion.}, journal = {Gut}, volume = {74}, number = {6}, pages = {935-947}, pmid = {39904603}, issn = {1468-3288}, mesh = {Animals ; Mice ; *CD8-Positive T-Lymphocytes/immunology/metabolism ; *Squamous Cell Carcinoma of Head and Neck/etiology/immunology/microbiology/metabolism ; *Dysbiosis/complications/microbiology/metabolism ; *Kynurenine/metabolism ; *Head and Neck Neoplasms/microbiology/etiology/immunology/metabolism ; Restraint, Physical ; *Stress, Psychological/complications/metabolism/microbiology ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; *Mouth/microbiology ; 4-Nitroquinoline-1-oxide ; Microbiota ; T-Cell Exhaustion ; }, abstract = {BACKGROUND: Chronic restraint stress (CRS) is a tumour-promoting factor. However, the underlying mechanism is unknown.

OBJECTIVE: We aimed to investigate whether CRS promotes head and neck squamous cell carcinoma (HNSCC) by altering the oral microbiota and related metabolites and whether kynurenine (Kyn) promotes HNSCC by modulating CD8[+] T cells.

DESIGN: 4-nitroquinoline-1-oxide (4NQO)-treated mice were exposed to CRS. Germ-free mice treated with 4NQO received oral microbiota transplants from either CRS or control mouse donors. 16S rRNA gene sequencing and liquid chromatography-mass spectrometry were performed on mouse saliva, faecal and plasma samples to investigate alterations in their microbiota and metabolites. The effects of Kyn on HNSCC were studied using the 4NQO-induced HNSCC mouse model.

RESULTS: Mice subjected to CRS demonstrated a higher incidence of HNSCC and oral microbial dysbiosis than CRS-free control mice. Pseudomonas and Veillonella species were enriched while certain oral bacteria, including Corynebacterium and Staphylococcus species, were depleted with CRS exposure. Furthermore, CRS-altered oral microbiota promoted HNSCC formation, caused oral and gut barrier dysfunction, and induced a host metabolome shift with increased plasma Kyn in germ-free mice exposed to 4NQO treatment. Under stress conditions, we also found that Kyn activated aryl hydrocarbon receptor (AhR) nuclear translocation and deubiquitination in tumour-reactive CD8[+] T cells, thereby promoting HNSCC tumourigenesis.

CONCLUSION: CRS-induced oral microbiota dysbiosis plays a protumourigenic role in HNSCC and can influence host metabolism. Mechanistically, under stress conditions, Kyn promotes CD8[+] T cell exhaustion and HNSCC tumourigenesis through stabilising AhR by its deubiquitination.}, } @article {pmid39903739, year = {2025}, author = {Men, J and Li, H and Cui, C and Ma, X and Liu, P and Yu, Z and Gong, X and Yao, Y and Ren, J and Zhao, C and Song, B and Yin, K and Wu, J and Liu, W}, title = {Fecal bacteria transplantation replicates aerobic exercise to reshape the gut microbiota in mice to inhibit high-fat diet-induced atherosclerosis.}, journal = {PloS one}, volume = {20}, number = {2}, pages = {e0314698}, pmid = {39903739}, issn = {1932-6203}, mesh = {Animals ; *Diet, High-Fat/adverse effects ; *Atherosclerosis/therapy/etiology/microbiology/pathology ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Male ; Mice ; *Physical Conditioning, Animal ; Mice, Inbred C57BL ; Disease Models, Animal ; Lipids/blood ; }, abstract = {Aerobic exercise exerts a significant impact on the gut microbiota imbalance and atherosclerosis induced by a high-fat diet. However, whether fecal microbiota transplantation, based on aerobic exercise, can improve atherosclerosis progression remains unexplored. In this study, we utilized male C57 mice to establish models of aerobic exercise and atherosclerosis, followed by fecal microbiota transplantation(Fig 1a). Firstly, we analyzed the body weight, somatotype, adipocyte area, and aortic HE images of the model mice. Our findings revealed that high-fat diet -induced atherosclerosis mice exhibited elevated lipid accumulation, larger adipocyte area, and more severe atherosclerosis progression. Additionally, we assessed plasma lipid levels, inflammatory factors, and gut microbiota composition in each group of mice. high-fat diet -induced atherosclerosis mice displayed dyslipidemia along with inflammatory responses and reduced gut microbiota diversity as well as abundance of beneficial bacteria. Subsequently performing fecal microbiota transplantation demonstrated that high-fat diet -induced atherosclerosis mice experienced weight loss accompanied by reduced lipid accumulation while normalizing their gut microbiota profile; furthermore it significantly improved blood lipids and inflammation markers thereby exhibiting notable anti- atherosclerosis effects. The findings suggest that aerobic exercise can modify gut microbiota composition and improve high-fat diet-induced atherosclerosis(Fig 1b). Moreover, these beneficial effects can be effectively transmitted through fecal microbiota transplantation, offering a promising therapeutic approach for managing atherosclerosis.}, } @article {pmid39902926, year = {2025}, author = {Rahman, R and Fouhse, JM and Ju, T and Fan, Y and Bhardwaj, T and Brook, RK and Nosach, R and Harding, J and Willing, BP}, title = {The impact of wild-boar-derived microbiota transplantation on piglet microbiota, metabolite profile, and gut proinflammatory cytokine production differs from sow-derived microbiota.}, journal = {Applied and environmental microbiology}, volume = {91}, number = {3}, pages = {e0226524}, pmid = {39902926}, issn = {1098-5336}, support = {res0030386//Alberta Livestock and Meat Agency (ALMA)/ ; RGPIN-2019-06336//Canadian Government | Natural Sciences and Engineering Research Council of Canada (NSERC)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Cytokines/metabolism/immunology ; Swine/microbiology ; *Sus scrofa/microbiology ; *Fecal Microbiota Transplantation/veterinary ; *Metabolome ; }, abstract = {Colonization of co-evolved, species-specific microbes in early life plays a crucial role in gastrointestinal development and immune function. This study hypothesized that modern pig production practices have resulted in the loss of co-evolved species and critical symbiotic host-microbe interactions. To test this, we reintroduced microbes from wild boars (WB) into conventional piglets to explore their colonization dynamics and effects on gut microbial communities, metabolite profiles, and immune responses. At postnatal day (PND) 21, 48 piglets were assigned to four treatment groups: (i) WB-derived mixed microbial community (MMC), (ii) sow-derived MMC, (iii) a combination of WB and sow MMC (Mix), or (iv) Control (PBS). Post-transplantation analyses at PND 48 revealed distinct microbial communities in WB-inoculated piglets compared with Controls, with trends toward differentiation from Sow but not Mix groups. WB-derived microbes were more successful in colonizing piglets, particularly in the Mix group, where they competed with Sow-derived microbes. WB group cecal digesta enriched with Lactobacillus helveticus, Lactobacillus mucosae, and Lactobacillus pontis. Cecal metabolite analysis showed that WB piglets were enriched in histamine, acetyl-ornithine, ornithine, citrulline, and other metabolites, with higher histamine levels linked to Lactobacillus abundance. WB piglets exhibited lower cecal IL-1β and IL-6 levels compared with Control and Sow groups, whereas the Mix group showed reduced IFN-γ, IL-2, and IL-6 compared with the Sow group. No differences in weight gain, fecal scores, or plasma cytokines were observed, indicating no adverse effects. These findings support that missing WB microbes effectively colonize domestic piglets and may positively impact metabolite production and immune responses.IMPORTANCEThis study addresses the growing concern over losing co-evolved, species-specific microbes in modern agricultural practices, particularly in pig production. The implementation of strict biosecurity measures and widespread antibiotic use in conventional farming systems may disrupt crucial host-microbe interactions that are essential for gastrointestinal development and immune function. Our research demonstrates that by reintroducing wild boar-derived microbes into domestic piglets, these microbes can successfully colonize the gut, influence microbial community composition, and alter metabolite profiles and immune responses without causing adverse effects. These findings also suggest that these native microbes can fill an intestinal niche, positively impacting immune activation. This research lays the groundwork for future strategies to enhance livestock health and performance by restoring natural microbial populations that produce immune-modulating metabolites.}, } @article {pmid39901991, year = {2025}, author = {Hemachandra, S and Rathnayake, SN and Jayamaha, AA and Francis, BS and Welmillage, D and Kaur, DN and Zaw, HK and Zaw, LT and Chandra, HA and Abeysekera, ME}, title = {Fecal Microbiota Transplantation as an Alternative Method in the Treatment of Obesity.}, journal = {Cureus}, volume = {17}, number = {1}, pages = {e76858}, pmid = {39901991}, issn = {2168-8184}, abstract = {Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach for various health conditions, particularly obesity and metabolic disorders. This review examines the mechanisms underlying FMT, including its role in restoring gut microbiota diversity and enhancing immunomodulatory functions, which are essential for maintaining overall health. Recent studies indicate that FMT can significantly improve body weight and metabolic parameters, suggesting its potential as an alternative or complementary treatment to current obesity therapies. However, the effectiveness of FMT depends on several factors, including the composition of the donor microbiota, recipient characteristics, and concomitant medications or dietary interventions. Despite its great promise, challenges such as standardized protocols, donor screening, and the need for a deeper understanding of gut microbiota dynamics remain key hurdles. Future research should focus on elucidating the specific microbial compositions necessary for optimal therapeutic outcomes and exploring personalized FMT approaches tailored to individual patient profiles. This evolving field presents exciting opportunities for innovative strategies in obesity treatment, warranting further investigation and clinical application.}, } @article {pmid39901521, year = {2025}, author = {Kappel, SS and Sangild, PT and Zachariassen, G and Andersen, JH and Rasmussen, KK and Jeppesen, PB and Aunsholt, L}, title = {Protein and energy digestibility in preterm infants fed fortified human milk.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {80}, number = {5}, pages = {855-860}, pmid = {39901521}, issn = {1536-4801}, support = {//Innovation Fund Denmark (NEOCOL grant 6150-00004B)./ ; }, mesh = {Humans ; *Food, Fortified ; Infant, Newborn ; *Milk, Human ; *Digestion/physiology ; *Infant, Premature/metabolism ; *Dietary Proteins/metabolism ; Female ; Male ; *Energy Intake ; *Colostrum ; Cattle ; *Infant Nutritional Physiological Phenomena ; Animals ; Feces/chemistry ; Gestational Age ; }, abstract = {OBJECTIVES: The objective of the present study is to determine whether the apparent nutrient digestibility differs between very preterm infants fortified with bovine colostrum (BC) compared to those fortified with a conventional fortifier (CF), building on previous findings that BC was associated with looser stools and reduced need for laxatives in very preterm infants (VPI).

METHODS: We conducted a 24-h digestibility balance study in 10 VPIs to assess the retention of protein, energy, and wet-weight following the intake of fortified human milk and collection of faecal excretions. Infants (n = 5) were matched by gestational age and birthweight.

RESULTS: In the 10 infants, the mean gestational age and birthweight were 28 ± 1 weeks and 899 ± 182 g, respectively. Infants fortified with BC had a higher faecal energy loss compared with infants fortified with CF (BC: 178 [range 111-205] vs. CF: 153 [96-235] kJ/kg, p < 0.05). No differences (p > 0.05) were found for wet-weight intake (421 [360-427] vs. 494 [328-500] kJ/kg), relative absorption of protein (60 [33-75] vs. 50 [33-75]%) or absolute protein absorption (249 [159-310) vs. 281 [210-347]).

CONCLUSION: Nutrient absorption was similar between groups although higher energy loss indicates reduced overall digestibility of BC versus CF, however, with a large variation within each group. Studies on more infants are required to confirm these results. A 24-h digestibility balance study can successfully be used to assess nutrient and energy retention in preterm infants.}, } @article {pmid39900090, year = {2025}, author = {Tay, SW and Low, AHL}, title = {Is faecal microbiota transplantation ready for prime time in systemic sclerosis?.}, journal = {The Lancet. Rheumatology}, volume = {7}, number = {5}, pages = {e305-e307}, doi = {10.1016/S2665-9913(24)00376-X}, pmid = {39900090}, issn = {2665-9913}, } @article {pmid39900089, year = {2025}, author = {Fretheim, H and Barua, I and Bakland, G and Dhainaut, A and Halse, AK and Carstens, MN and Didriksen, H and Midtvedt, Ø and Lundin, KEA and Aabakken, L and Sarna, VK and Zaré, HK and Khanna, D and Distler, O and Midtvedt, T and Bækkevold, ES and Olsen, IC and Domanska, D and Pesonen, ME and Molberg, Ø and Hoffmann-Vold, AM}, title = {Faecal microbiota transplantation in patients with systemic sclerosis and lower gastrointestinal tract symptoms in Norway (ReSScue): a phase 2, randomised, double-blind, placebo-controlled trial.}, journal = {The Lancet. Rheumatology}, volume = {7}, number = {5}, pages = {e323-e332}, doi = {10.1016/S2665-9913(24)00334-5}, pmid = {39900089}, issn = {2665-9913}, mesh = {Humans ; Female ; Middle Aged ; Male ; Double-Blind Method ; *Fecal Microbiota Transplantation/methods ; *Scleroderma, Systemic/complications/therapy ; Adult ; Aged ; Norway ; Aged, 80 and over ; Treatment Outcome ; Adolescent ; Young Adult ; *Diarrhea/therapy/etiology ; *Gastrointestinal Diseases/therapy/etiology ; Gastrointestinal Microbiome ; }, abstract = {BACKGROUND: Gastrointestinal tract involvement is highly prevalent in systemic sclerosis, with few treatment options. We assessed the efficacy and safety of faecal microbiota transplantation using standardised anaerobic cultivated human intestinal microbiome (ACHIM) as a novel treatment option for patients with systemic sclerosis and symptomatic lower gastrointestinal tract involvement.

METHODS: In this phase 2, randomised, double-blind, placebo-controlled trial done at four university hospitals in Norway, we enrolled adults aged 18-85 years with systemic sclerosis and moderate-to-severe lower gastrointestinal tract symptoms (bloating or diarrhoea). Participants were randomly assigned 1:1 to intestinal infusions of placebo or ACHIM at weeks 0 and 2, stratified by worst symptom (bloating or diarrhoea). The primary endpoint was change in worst lower gastrointestinal tract symptom (bloating or diarrhoea) from week 0 to week 12, measured using the University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 scoring system in the intention-to-treat population. Safety was assessed at weeks 0, 2, 4, 6, and 12 in all participants who received at least one infusion. A person with lived experience of systemic sclerosis was involved in the study planning and conduct. This trial was registered at ClinicalTrials.gov, NCT04300426.

FINDINGS: Between Sept 24, 2020, and Jan 14, 2022, 67 participants were enrolled and randomly allocated to placebo (n=34) or ACHIM (n=33). Mean age was 58·91 years (SD 11·59). 62 (93%) of 67 participants were women, five (7%) were men, and 50 (75%) were anti-centromere antibody positive. Change in worst lower gastrointestinal tract symptom from week 0 to week 12 did not differ between participants who received ACHIM (-0·13, 95% CI -0·37 to 0·11) and participants who received placebo (-0·33, -0·57 to -0·09; average marginal effect 0·20, 95% CI -0·12 to 0·52; p=0·22). Adverse events, mostly mild and short-lived gastrointestinal tract symptoms, were reported by 16 (48%) of 33 participants in the ACHIM group and 19 (56%) of 34 in the placebo group. During gastroscopy, one participant had a duodenal perforation.

INTERPRETATION: Faecal microbiota transplantation with ACHIM was well tolerated in participants with systemic sclerosis but did not result in an improvement in lower gastrointestinal tract symptoms.

FUNDING: KLINBEFORSK.

TRANSLATION: For the Norwegian translation of the abstract see Supplementary Materials section.}, } @article {pmid39899452, year = {2025}, author = {Chaki, T and Horiguchi, Y and Tachibana, S and Sato, S and Hirahata, T and Nishihara, N and Kii, N and Yoshikawa, Y and Hayamizu, K and Yamakage, M}, title = {Gut Microbiota Influences Developmental Anesthetic Neurotoxicity in Neonatal Rats.}, journal = {Anesthesia and analgesia}, volume = {141}, number = {2}, pages = {422-434}, doi = {10.1213/ANE.0000000000007410}, pmid = {39899452}, issn = {1526-7598}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/physiology ; Animals, Newborn ; *Sevoflurane/toxicity ; Fecal Microbiota Transplantation ; Rats ; *Behavior, Animal/drug effects ; *Neurotoxicity Syndromes/microbiology/psychology/etiology ; *Anesthetics, Inhalation/toxicity ; Female ; Rats, Sprague-Dawley ; Male ; Maze Learning/drug effects ; *Brain/drug effects/growth & development ; }, abstract = {BACKGROUND: Anesthetic exposure during childhood is significantly associated with impairment of neurodevelopmental outcomes; however, the causal relationship and detailed mechanism of developmental anesthetic neurotoxicity remain unclear. Gut microbiota produces various metabolites and influences the brain function and development of the host. This relationship is referred to as the gut-brain axis. Gut microbiota may influence developmental anesthetic neurotoxicity caused by sevoflurane exposure. This study investigated the effect of changes in the composition of gut microbiota after fecal microbiota transplantation on spatial learning disability caused by developmental anesthetic neurotoxicity in neonatal rats.

METHODS: Neonatal rats were allocated into the Control (n = 10) and Sevo (n = 10) groups in Experiment 1 and the Sevo (n = 20) and Sevo+FMT (n = 20) groups in Experiment 2, according to the randomly allocated mothers' group. The rats in Sevo and Sevo+FMT groups were exposed to 2.1% sevoflurane for 2 hours on postnatal days 7 to 13. Neonatal rats in the Sevo+FMT group received fecal microbiota transplantation immediately after sevoflurane exposure on postnatal days 7 to 13. The samples for fecal microbiota transplantation were obtained from nonanesthetized healthy adult rats. Behavioral tests, including Open field, Y-maze, Morris water maze, and reversal Morris water maze tests, were performed to evaluate spatial learning ability on postnatal days 26 to 39.

RESULTS: Experiment 1 revealed that sevoflurane exposure significantly altered the gut microbiota composition. The relative abundance of Roseburia (effect value: 1.01) and Bacteroides genus (effect value: 1.03) increased significantly after sevoflurane exposure, whereas that of Lactobacillus (effect value: -1.20) decreased significantly. Experiment 2 revealed that fecal microbiota transplantation improved latency to target (mean ± SEM; Sevo group: 9.7 ± 8.2 seconds vs, Sevo+FMT group: 2.7 ± 2.4 seconds, d =1.16, 95% confidence interval: -12.7 to -1.3 seconds, P = .019) and target zone crossing times (Sevo group: 2.4 ± 1.6 vs, Sevo+FMT group: 5.4 ± 1.4, d =1.99, 95% confidence interval: 2.0-5.0, P < .001) in the reversal Morris water maze test. Microbiota analysis revealed that the α-diversity of gut microbiota increased after fecal microbiota transplantation. Similarly, the relative abundance of the Firmicutes phylum (effect value: 1.44), Ruminococcus genus (effect value: 1.69), and butyrate-producing bacteria increased after fecal microbiota transplantation. Furthermore, fecal microbiota transplantation increased the fecal concentration of butyrate and induced histone acetylation and the mRNA expression of brain-derived neurotrophic factor in the hippocampus, thereby suppressing neuroinflammation and neuronal apoptosis.

CONCLUSIONS: The alternation of gut microbiota after fecal microbiota transplantation influenced spatial learning ability in neonatal rats with developmental anesthetic neurotoxicity. Modulation of the gut microbiota may be an effective prophylaxis for developmental anesthetic neurotoxicity in children.}, } @article {pmid39897551, year = {2025}, author = {Yu, C and Sun, R and Yang, W and Gu, T and Ying, X and Ye, L and Zheng, Y and Fan, S and Zeng, X and Yao, S}, title = {Exercise ameliorates osteopenia in mice via intestinal microbial-mediated bile acid metabolism pathway.}, journal = {Theranostics}, volume = {15}, number = {5}, pages = {1741-1759}, pmid = {39897551}, issn = {1838-7640}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; *Bile Acids and Salts/metabolism ; *Bone Diseases, Metabolic/therapy/metabolism/microbiology ; *Physical Conditioning, Animal/physiology ; Female ; Fecal Microbiota Transplantation/methods ; Mice, Inbred C57BL ; Osteoporosis ; Ovariectomy ; Metabolomics ; Osteogenesis ; Disease Models, Animal ; RNA, Ribosomal, 16S/genetics ; Metabolome ; }, abstract = {Rationale: Physical exercise is essential for skeletal integrity and bone health. The gut microbiome, as a pivotal modulator of overall physiologic states, is closely associated with skeletal homeostasis and bone metabolism. However, the potential role of intestinal microbiota in the exercise-mediated bone gain remains unclear. Methods: We conducted microbiota depletion and fecal microbiota transplantation (FMT) in ovariectomy (OVX) mice and aged mice to investigate whether the transfer of gut ecological traits could confer the exercise-induced bone protective effects. The study analyzed the gut microbiota and metabolic profiles via 16S rRNA gene sequencing and LC-MS untargeted metabolomics to identify key microbial communities and metabolites responsible for bone protection. Transcriptome sequencing and RNA interference were employed to explore the molecular mechanisms. Results: We found that gut microbiota depletion hindered the osteogenic benefits of exercise, and FMT from exercised osteoporotic mice effectively mitigated osteopenia. Comprehensive profiling of the microbiome and metabolome revealed that the exercise-matched FMT reshaped intestinal microecology and metabolic landscape. Notably, alterations in bile acid metabolism, specifically the enrichment of taurine and ursodeoxycholic acid, mediated the protective effects on bone mass. Mechanistically, FMT from exercised mice activated the apelin signaling pathway and restored the bone-fat balance in recipient MSCs. Conclusion: Our study underscored the important role of the microbiota-metabolic axis in the exercise-mediated bone gain, heralding a potential breakthrough in the treatment of osteoporosis.}, } @article {pmid39897545, year = {2025}, author = {Hou, W and Cao, Y and Wang, J and Yin, F and Wang, J and Guo, N and Wang, Z and Lv, X and Ma, C and Chen, Q and Yang, R and Wei, H and Li, J and Wang, R and Qin, H}, title = {Single-cell nanocapsules of gut microbiota facilitate fecal microbiota transplantation.}, journal = {Theranostics}, volume = {15}, number = {5}, pages = {2069-2084}, pmid = {39897545}, issn = {1838-7640}, mesh = {Animals ; *Nanocapsules/chemistry/administration & dosage ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Mice ; Disease Models, Animal ; Colitis/therapy/microbiology ; Mice, Inbred C57BL ; Humans ; Fibroins/chemistry ; Male ; Phosphatidylcholines/chemistry ; }, abstract = {Rationale: Fecal microbiota transplantation (FMT) is advantageous for treating intractable diseases via the microbiota-gut-organ axis. However, invasive administration of gut microbiota via nasal feeding tubes limits the widespread application of FMT. Here, we attempted to develop a novel strategy to deliver gut microbiota using nanocapsules. Methods: Single-cell nanocapsules were fabricated within 1 h by layer-by-layer assembly of silk fibroin and phosphatidylcholine to generate a protective nanoshell on the cell surface of complicated microbiota. The physical properties of the microbiota nanocapsules were analyzed. The protective effects of nanocapsules on the gastrointestinal tract were analyzed both in vitro and in vivo. The efficacy of FMT assisted by single-cell nanocapsules (NanoFMT) was evaluated using the inflammatory response, gut microbiota balance, and histopathological analysis in animal model. Results: The nanocapsules achieved a good coating ratio for a single type of microbe and complex microbiota, resulting in a remarkable increase in the survival rate of microbes in the gastrointestinal tract. NanoFMT improved the diversity and abundance of the gut microbiota better than common FMT in germ-free mice. Moreover, NanoFMT alleviated intestinal inflammation and positively reversed the microbiota balance in a mouse model of colitis compared with common FMT, assisted by the inherent anti-inflammatory effects of silk fibroin and phosphatidylcholine. Conclusions: Considering its rapid preparation, convenient delivery, and perfect therapeutic effect, we anticipate that NanoFMT may be a promising clinical candidate for next-generation FMT treatment.}, } @article {pmid39896755, year = {2025}, author = {Zhao, B and Zhou, H and Lin, K and Xu, J and Zhou, B and Xie, D and Ma, J and Yang, L and Su, C and Yang, L}, title = {Antimicrobial peptide DP7 alleviates dextran sulfate sodium (DSS)-induced colitis via modifying gut microbiota and regulating intestinal barrier function.}, journal = {MedComm}, volume = {6}, number = {2}, pages = {e70085}, pmid = {39896755}, issn = {2688-2663}, abstract = {Inflammatory bowel diseases (IBDs), such as Crohn's disease (CD) and ulcerative colitis (UC), represent a growing global health concern. Restoring the balance of the gut microbiota, a crucial factor in intestinal health, offers potential for treating IBD. DP7, a novel antimicrobial peptide with potent antibacterial activity, was investigated for its anti-inflammatory effects in a dextran sulfate sodium (DSS)-induced UC mouse model. DP7 significantly ameliorated key disease parameters, including disease activity index, weight loss, and shortened colon length, while preserving colonic epithelial integrity and reducing inflammatory infiltration. Further analysis revealed potential targets of DP7, highlighting the significant role of Muribaculaceae bacteria during inflammatory states. To further explore the role of the gut microbiota in DP7's efficacy, fecal microbiota transplantation (FMT) was performed using feces from DP7-treated mice. FMT successfully ameliorated colitis in recipient mice, providing further evidence for the crucial role of the gut microbiome in IBD treatment and DP7's ability to modulate the gut microbiota for therapeutic benefit. Moreover, our findings suggest that DP7's modulation of the immune system is intricately linked to the complex microbial environment. Our findings demonstrate that DP7 effectively mitigates inflammation, attenuates barrier dysfunction, and shapes the gut microbiota, suggesting its potential as a therapeutic agent for UC.}, } @article {pmid39896483, year = {2025}, author = {Gray, SM and Wood, MC and Mulkeen, SC and Ahmed, S and Thaker, SD and Chen, B and Sander, WR and Bibeva, V and Zhang, X and Yang, J and Herzog, JW and Zhang, S and Dogan, B and Simpson, KW and Balfour Sartor, R and Montrose, DC}, title = {Dietary protein source mediates colitis pathogenesis through bacterial modulation of bile acids.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39896483}, issn = {2692-8205}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P30 DK056350/DK/NIDDK NIH HHS/United States ; T32 DK007737/DK/NIDDK NIH HHS/United States ; }, abstract = {Evidence-based dietary recommendations for individuals with inflammatory bowel diseases (IBD) are limited. Red meat consumption is associated with increased IBD incidence and relapse in patients, suggesting that switching to a plant-based diet may limit gut inflammation. However, the mechanisms underlying the differential effects of these diets remain poorly understood. Feeding diets containing plant- or animal-derived proteins to murine colitis models revealed that mice given a beef protein (BP) diet exhibited the most severe colitis, while mice fed pea protein (PP) developed mild inflammation. The colitis-promoting effects of BP were microbially-mediated as determined by bacterial elimination or depletion and microbiota transplant studies. In the absence of colitis, BP-feeding reduced abundance of Lactobacillus johnsonii and Turicibacter sanguinis and expanded Akkermansia muciniphila, which localized to the mucus in association with decreased mucus thickness and quality. BP-fed mice had elevated primary and conjugated fecal bile acids (BAs), and taurocholic acid administration to PP-fed mice worsened colitis. Dietary psyllium protected against BP-mediated inflammation, restored BA-modulating commensals and normalized BA ratios. Collectively, these data suggest that the protein component of red meat may be responsible, in part, for the colitis-promoting effects of this food source and provide insight into dietary factors that may influence IBD severity.}, } @article {pmid39895632, year = {2025}, author = {Gazzaniga, FS and Kasper, DL}, title = {The gut microbiome and cancer response to immune checkpoint inhibitors.}, journal = {The Journal of clinical investigation}, volume = {135}, number = {3}, pages = {}, pmid = {39895632}, issn = {1558-8238}, mesh = {*Gastrointestinal Microbiome/immunology/drug effects ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Humans ; Animals ; *Neoplasms/immunology/therapy/microbiology/drug therapy/pathology ; Mice ; Fecal Microbiota Transplantation ; }, abstract = {Immune checkpoint inhibitors (ICIs) are widely used for cancer immunotherapy, yet only a fraction of patients respond. Remarkably, gut bacteria impact the efficacy of ICIs in fighting tumors outside of the gut. Certain strains of commensal gut bacteria promote antitumor responses to ICIs in a variety of preclinical mouse tumor models. Patients with cancer who respond to ICIs have a different microbiome compared with that of patients who don't respond. Fecal microbiota transplants (FMTs) from patients into mice phenocopy the patient tumor responses: FMTs from responders promote response to ICIs, whereas FMTs from nonresponders do not promote a response. In patients, FMTs from patients who have had a complete response to ICIs can overcome resistance in patients who progress on treatment. However, the responses to FMTs are variable. Though emerging studies indicate that gut bacteria can promote antitumor immunity in the absence of ICIs, this Review will focus on studies that demonstrate relationships between the gut microbiome and response to ICIs. We will explore studies investigating which bacteria promote response to ICIs in preclinical models, which bacteria are associated with response in patients with cancer receiving ICIs, the mechanisms by which gut bacteria promote antitumor immunity, and how microbiome-based therapies can be translated to the clinic.}, } @article {pmid39895628, year = {2025}, author = {Si, W and Zhao, X and Li, R and Li, Y and Ma, C and Zhao, X and Bugno, J and Qin, Y and Zhang, J and Liu, H and Wang, L}, title = {Lactobacillus rhamnosus GG induces STING-dependent IL-10 in intestinal monocytes and alleviates inflammatory colitis in mice.}, journal = {The Journal of clinical investigation}, volume = {135}, number = {3}, pages = {}, pmid = {39895628}, issn = {1558-8238}, mesh = {Animals ; *Interleukin-10/immunology/genetics ; *Lacticaseibacillus rhamnosus/immunology ; Mice ; *Monocytes/immunology/pathology/metabolism ; *Colitis/immunology/pathology/therapy/genetics/microbiology ; *Membrane Proteins/immunology/genetics/metabolism ; *Probiotics/pharmacology ; Signal Transduction/immunology ; Mice, Inbred C57BL ; Gastrointestinal Microbiome/immunology ; Mice, Knockout ; }, abstract = {Preclinical and clinical observations indicate that the probiotic Lactobacillus rhamnosus GG (LGG) can modulate colonic inflammation. However, the underlying mechanisms have not been explored in depth. Here, we demonstrate that oral administration of live LGG alleviated inflammatory colitis by increasing IL-10 expression in intestinal Ly6C+ monocytes. Mechanistically, LGG induced IL-10 production via the stimulator of IFN genes (STING)/TBK1/NF-κB (RELA) signaling pathway in intestinal Ly6C+ monocytes, enhancing their immune-suppressive function. Elevated IL-10 subsequently activated IL-10 signaling in Ly6C+ monocytes, resulting in an IL-10-based autocrine regulatory loop and inhibition of proinflammatory cytokine production. Furthermore, LGG shifted the gut microbial community and its metabolic functions, leading to intestinal immune responses against colitis. Fecal microbiota transplantation from LGG-colonized mice alleviated immune checkpoint blockade-associated colitis. Our findings highlight the importance of STING signaling in IL-10-dependent antiinflammatory immunity and establish an empirical basis for developing oral administration of live LGG as an efficient and safe therapeutic strategy against inflammatory colitis.}, } @article {pmid39892949, year = {2025}, author = {McGann, C and Phyu, R and Bittinger, K and Mukhopadhyay, S}, title = {Role of the Microbiome in Neonatal Infection: Pathogenesis and Implications for Management.}, journal = {Clinics in perinatology}, volume = {52}, number = {1}, pages = {147-166}, doi = {10.1016/j.clp.2024.10.010}, pmid = {39892949}, issn = {1557-9840}, mesh = {Humans ; Infant, Newborn ; Probiotics/therapeutic use ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; *Neonatal Sepsis/microbiology/therapy ; Anti-Bacterial Agents/therapeutic use ; *Microbiota ; }, abstract = {The human microbiome refers to the collective genome of microorganisms, including bacteria, fungi, and viruses residing on human body surfaces that are in contact with the environment. Together these communities protect against invasive infections. Conversely, when disrupted, the microbiome can be the source of pathogens causing invasive infection. Interventions to manipulate it via probiotics, antibiotics, and fecal transplantation are available. The risk benefit of these interventions remains unclear. In this review, the authors discuss evidence linking the gut microbiome to neonatal sepsis and also discuss the challenges for translating this knowledge into better clinical care.}, } @article {pmid39890521, year = {2024}, author = {Rafie, E and Zugman, M and Pal, SK and Routy, B and Elkrief, A}, title = {What Is the Role of Fecal Microbiota Transplantation in Immunotherapy Trials? Current Perspectives and Future Directions.}, journal = {European urology focus}, volume = {10}, number = {6}, pages = {882-885}, doi = {10.1016/j.euf.2024.12.009}, pmid = {39890521}, issn = {2405-4569}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Immunotherapy/methods ; *Immune Checkpoint Inhibitors/therapeutic use ; Gastrointestinal Microbiome/immunology ; *Urogenital Neoplasms/therapy/immunology ; Forecasting ; }, abstract = {Immune checkpoint inhibitors (ICIs) are rapidly transforming the treatment landscape of genitourinary and other immunogenic malignancies. Despite these advances, biomarkers for the prediction of ICI response remain to be established. The gut microbiome has been identified as a modulator of immune regulation and a potential regulator of response to ICIs. Fecal microbiota transplantation (FMT) has emerged as a potential novel therapeutic tool to enhance ICI response, as demonstrated in several trials, spanning across genitourinary malignancies as well as others. While safety and clinical potential of FMT have been demonstrated, FMT parameters including optimal treatment regimens, bowel preparation protocols, patient selection, and donor-host compatibility need to be defined. Furthermore, targeted interventions including probiotic supplementation represent promising therapeutic avenues meriting further study.}, } @article {pmid39889629, year = {2025}, author = {Zhu, W and Hu, Y and Shi, Y and Bao, H and Cheng, X and Jiang, M and Peng, Z and Song, J and Fang, F and Jian, C and Yuan, W and Chen, J and Shu, X}, title = {Sleep deprivation accelerates Parkinson's disease via modulating gut microbiota associated microglial activation and oxidative stress.}, journal = {Microbiological research}, volume = {293}, number = {}, pages = {128077}, doi = {10.1016/j.micres.2025.128077}, pmid = {39889629}, issn = {1618-0623}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Oxidative Stress ; *Microglia/metabolism ; Mice ; *Parkinson Disease/microbiology/etiology ; *Sleep Deprivation/complications/microbiology ; Disease Models, Animal ; Male ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S/genetics ; Disease Progression ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Bacteria/classification/genetics/isolation & purification ; }, abstract = {The interplay between Parkinson's disease (PD) and sleep disturbances suggests that sleep problems constitute a risk factor for PD progression, but the underlying mechanisms remain unclear. Microglial activation and oxidative stress are considered to play an important role in the pathogenesis of aging and neurodegenerative diseases. We hypothesized that sleep deprivation (SD) could exacerbate PD progression via modulating microglial activation and oxidative stress. To test this hypothesis, we established a PD mouse model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), then subjected the mice to SD. A battery of behavioral tests, including rotarod, pole, adhesive removal, and open field tests, were used to assess motor function. Our study showed that SD exacerbated motor deficits, loss of tyrosine hydroxylase (TH), microglial activation and oxidative stress damage in PD model mice. Fecal microbiota transplantation experiments revealed that SD mediated PD progression, microglial activation and oxidative stress via the gut microbiota. 16S rRNA sequencing analysis indicated that SD increased the abundances of bacteria such as Bacteroidaceae, while decreasing the abundances of bacteria including Lactobacillus. Non-targeted metabolomic analysis of gut microbiota-derived metabolites revealed that SD significantly increased the production of adenosine (ADO), a purine metabolite. Probiotic supplementation reversed the effects of SD on motor deficits, dopaminergic neuron loss, microglial activation and oxidative stress damage in PD mice; it also decreased SD-induced ADO production. Administration of Adenosine A2A receptor (A2AR) inhibitors, Istradefylline (Ist), attenuated the roles of SD and ADO in promoting microglial activation, oxidative stress and PD progression. Taken together, our findings indicate that SD accelerates PD progression via regulating microbiota associated microglial activation and oxidative stress, suggesting that efforts to improve sleep quality can be used to prevent and treat PD.}, } @article {pmid39887665, year = {2025}, author = {Zeng, X and Sun, L and Xie, H and Gong, S and Lu, C and Xu, Z and Guan, H and Han, B and Wang, W and Zhang, Z and Zhou, J and Wang, S and Chen, Y and Xiao, W}, title = {Lactobacillus johnsonii Generates Cyclo(pro-trp) and Promotes Intestinal Ca[2+] Absorption to Alleviate CKD-SHPT.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {16}, pages = {e2414678}, pmid = {39887665}, issn = {2198-3844}, support = {82270585//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Mice ; *Renal Insufficiency, Chronic/metabolism/complications/microbiology ; *Calcium/metabolism ; Gastrointestinal Microbiome/physiology ; *Hyperparathyroidism, Secondary/metabolism/microbiology/etiology ; *Lactobacillus johnsonii/metabolism ; Male ; *Intestinal Absorption/physiology ; Mice, Inbred C57BL ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Humans ; Parathyroid Hormone/metabolism ; }, abstract = {Patients with chronic kidney disease (CKD) are at a high risk of developing secondary hyperparathyroidism (SHPT), which may cause organ dysfunction and increase patient mortality. The main clinical interventions for CKD-SHPT involve calcium supplements to boost absorption, but ineffective for some patients, and the reasons remain unclear. Here, CKD mice are divided into high and low groups based on intact parathyroid hormone (iPTH) levels. The high group exhibits significant changes in gut microbes, including a decrease in Lactobacillus, an increase in parathyroid hyperplasia, and a decrease in intestinal calcium. Fecal microbiota transplantation and L. johnsonii colonization indicate a link between gut microbes and CKD-SHPT. Clinically, higher L. johnsonii levels are correlated with milder hyperparathyroidism CKD-SHPT. The receiver operating characteristic (ROC) curve for L. johnsonii abundance and surgical risk is 0.81, with the calibration curve confirming predictive accuracy, and decision curve analysis revealing good clinical applicability. In vivo and in vitro experiments show that cyclo(pro-trp) enhance calcium inflow and lower iPTH levels in intestinal epithelial cells via a calcium-sensing receptor and transient receptor potential vanilloid 4 pathways. This study identified the crucial role of L. johnsonii in CKD-SHPT, unveiling a new mechanism for calcium imbalance and offering novel strategies for SHPT treatment and drug development.}, } @article {pmid39887373, year = {2025}, author = {Byrd, DA and Damerell, V and Gomez Morales, MF and Hogue, SR and Lin, T and Ose, J and Himbert, C and Ilozumba, MN and Kahlert, C and Shibata, D and Toriola, AT and Li, CI and Figueiredo, J and Stephens, WZ and Warby, CA and Hardikar, S and Siegel, EM and Round, J and Ulrich, CM and Gigic, B}, title = {The gut microbiome is associated with disease-free survival in stage I-III colorectal cancer patients.}, journal = {International journal of cancer}, volume = {157}, number = {1}, pages = {64-73}, pmid = {39887373}, issn = {1097-0215}, support = {01KD2101D//German Federal Ministry of Education and Research/ ; R01 AG083580/AG/NIA NIH HHS/United States ; R01 CA189184/CA/NCI NIH HHS/United States ; //Stiftung LebensBlicke/ ; //ERA-NET on Translational Cancer Research (TRANSCAN)/ ; //Rahel Goitein-Straus-Program/ ; 01KT1503//German Federal Ministry of Education and Research/ ; //Matthias-Lackas Foundations/ ; U01 CA206110/NH/NIH HHS/United States ; //Heidelberger Stiftung Chirurgie, Heidelberg University Hospital/ ; R01 CA189184/NH/NIH HHS/United States ; //Medizinische Fakultät Heidelberg, Universität Heidelberg/ ; U01 CA206110/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Colorectal Neoplasms/microbiology/pathology/mortality ; Female ; Male ; Middle Aged ; Aged ; Feces/microbiology ; Disease-Free Survival ; RNA, Ribosomal, 16S/genetics ; Prospective Studies ; Neoplasm Staging ; Bacteria/genetics/classification/isolation & purification ; }, abstract = {Colorectal cancer (CRC) is the second overall leading cause of cancer death in the United States, with recurrence being a frequent cause of mortality. Approaches to improve disease-free survival (DFS) are urgently needed. The gut microbiome, reflected in fecal samples, is likely mechanistically linked to CRC progression and may serve as a non-invasive biomarker. Accordingly, we leveraged baseline fecal samples from N = 166 stage I-III CRC patients in the ColoCare Study, a prospective cohort of newly diagnosed CRC patients. We sequenced the V3 and V4 regions of the 16S rRNA gene to characterize fecal bacteria. We calculated estimates of alpha diversity, beta diversity, and a priori- and exploratory-selected bacterial presence/absence and relative abundance. Associations of microbial metrics with DFS were estimated using multivariable Cox proportional hazards models. We found that alpha diversity was strongly associated with improved DFS, most strongly among rectal cancer patients (Shannon HRrectum = 0.40 95% CI = 0.19, 0.87; p = .02). Overall microbiome composition differences (beta diversity), as characterized by principal coordinate axes, were statistically significantly associated with DFS. Peptostreptococcus was statistically significantly associated with worse DFS (HR = 1.62, 95% CI = 1.13, 2.31; p = .01 per 1-SD) and Order Clostridiales was associated with improved DFS (HR = 0.62, 95% CI = 0.43-0.88; p = .01 per 1-SD). In exploratory analyses, Coprococcus and Roseburia were strongly associated with improved DFS. Overall, higher bacterial diversity and multiple bacteria were strongly associated with DFS. Metagenomic sequencing to elucidate species, gene, and functional level details among larger, diverse patient populations are critically needed to support the microbiome as a biomarker of CRC outcomes.}, } @article {pmid39887250, year = {2025}, author = {Tang, X and Zeng, T and Deng, W and Zhao, W and Liu, Y and Huang, Q and Deng, Y and Xie, W and Huang, W}, title = {Gut microbe-derived betulinic acid alleviates sepsis-induced acute liver injury by inhibiting macrophage NLRP3 inflammasome in mice.}, journal = {mBio}, volume = {16}, number = {3}, pages = {e0302024}, pmid = {39887250}, issn = {2150-7511}, support = {82302480//MOST | National Natural Science Foundation of China (NSFC)/ ; 2022A1515111071//GDSTC | Natural Science Foundation of Guangdong Province ()/ ; 2022M721503//China Postdoctoral Science Foundation (China Postdoctoral Foundation Project)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/antagonists & inhibitors ; Mice ; *Sepsis/complications ; Betulinic Acid ; *Pentacyclic Triterpenes/metabolism/pharmacology ; *Inflammasomes/metabolism/drug effects ; *Macrophages/drug effects/metabolism/immunology ; Male ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Physical Conditioning, Animal ; Disease Models, Animal ; Liver ; }, abstract = {UNLABELLED: Sepsis-induced acute liver injury (SALI) is a prevalent and life-threatening complication associated with sepsis. The gut microbiota plays a crucial role in the maintenance of health and the development of diseases. The impact of physical exercise on gut microbiota modulation has been well-documented. However, the potential impact of gut microbiome on exercise training-induced protection against SALI remains uncertain. Here, we discovered exercise training ameliorated SALI and systemic inflammation in septic mice. Notably, gut microbiota pre-depletion abolished the protective effects of exercise training in SALI mice. Fecal microbiota transplantation treatment revealed that exercise training-associated gut microbiota contributed to the beneficial effect of exercise training on SALI. Exercise training modulated the metabolism of Ligilactobacillus and enriched betulinic acid (BA) levels in mice. Functionally, BA treatment conferred protection against SALI by inhibiting the hepatic inflammatory response in mice. BA bound and inactivated hnRNPA2B1, thus suppressing NLRP3 inflammasome activation in macrophages. Collectively, this study reveals gut microbiota is involved in the protective effects of exercise training against SALI, and gut microbiota-derived BA inhibits the hepatic inflammatory response via the hnRNPA2B1-NLRP3 axis, providing a potential therapeutic strategy for SALI.

IMPORTANCE: Sepsis is characterized by a dysregulated immune response to an infection that leads to multiple organ dysfunction. The occurrence of acute liver injury is frequently observed during the initial stage of sepsis and is directly linked to mortality in the intensive care unit. The preventive effect of physical exercise on SALI is well recognized, yet the underlying mechanism remains poorly elucidated. Exercise training alters the gut microbiome in mice, increasing the abundance of Ligilactobacillus and promoting the generation of BA. Additionally, BA supplementation can suppress the NLRP3 inflammasome activation in macrophages by directly binding to hnRNPA2B1, thereby mitigating SALI. These results highlight the beneficial role of gut microbiota-derived BA in inhibiting the hepatic inflammatory response, which represents a crucial stride toward implementing microbiome-based therapeutic strategies for the clinical management of sepsis.}, } @article {pmid39885417, year = {2025}, author = {Abdel-Raoof Fouda, M and Abdel-Wahhab, M and Abdelkader, AE and Ibrahim, ME and Elsheikh, TA and Aldeweik, HM and Elfeky, N}, title = {Effect of gut microbiota changes on cytokines IL-10 and IL-17 levels in liver transplantation patients.}, journal = {BMC infectious diseases}, volume = {25}, number = {1}, pages = {140}, pmid = {39885417}, issn = {1471-2334}, mesh = {Humans ; *Liver Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Male ; *Interleukin-17/blood ; Female ; Middle Aged ; *Interleukin-10/blood ; Adult ; Feces/microbiology ; Bacteria/classification/isolation & purification/genetics ; Aged ; Dysbiosis ; }, abstract = {BACKGROUND: Liver transplantation (LT) is a critical intervention for individuals with end-stage liver disease; yet, post-transplant problems, especially infections, graft rejection, and chronic liver disease, are often linked to systemic inflammation. Cytokines, small signaling molecules, significantly influence immune responses during and post-liver transplantation. Nonetheless, the intricate relationships among cytokines, immune responses, and the gut microbiota, especially gut dysbiosis, are still inadequately comprehended. Thus, this study aims to identify the gut microbiota (GM) and determine their relationship to cytokines (IL-17 and IL-10) in LT patients, due to their importance in enhancing the recovery rate.

RESULT: The research included 31 liver transplant (LT) patients from the Gastroenterology Surgical Center at Mansoura University, resulting in the collection of 174 stool and blood samples from all participants. Fourteen bacterial species have been identified in samples collected at three intervals: one week before, one week post, and two weeks post LT. A change in gut microbiota composition was noted, characterized by a rise in potentially pathogenic bacteria such as Enterococci and Enterobacteriaceae (including Escherichia coli and Klebsiella) and a reduction in beneficial bacteria such as Bacteroidetes and Firmicutes. The examination of patient demographic and clinical data revealed no significant correlations between sex, age, or diagnostic categories and gut microbiota composition. The findings of the Multivariate Analysis of Variance (MANOVA) indicated a substantial effect of gut microbiota composition on cytokine levels (IL-10 and IL-17), with all tests producing p-values of 0.001. The assessment of cytokine levels indicated fluctuating variations at several time points following surgery. IL-10 levels in the GM groups exhibited a statistically significant elevation during the second week post-surgery (p = 0.036), suggesting a potential recovery-related anti-inflammatory response. In contrast, IL-17 levels rose in the NI group over time, indicating a transition to a pro-inflammatory condition.

CONCLUSION: This study emphasizes the pivotal role of the gut microbiota in regulating immune responses following transplantation.}, } @article {pmid39881980, year = {2024}, author = {Renk, H and Schoppmeier, U and Müller, J and Kuger, V and Neunhoeffer, F and Gille, C and Peter, S}, title = {Oxygenation and intestinal perfusion and its association with perturbations of the early life gut microbiota composition of children with congenital heart disease.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1468842}, pmid = {39881980}, issn = {1664-302X}, abstract = {BACKGROUND: Early life gut microbiota is known to shape the immune system and has a crucial role in immune homeostasis. Only little is known about composition and dynamics of the intestinal microbiota in infants with congenital heart disease (CHD) and potential influencing factors.

METHODS: We evaluated the intestinal microbial composition of neonates with CHD (n = 13) compared to healthy controls (HC, n = 30). Fecal samples were analyzed by shotgun metagenomics. Different approaches of statistical modeling were applied to assess the impact of influencing factors on variation in species composition. Unsupervised hierarchical clustering of the microbial composition of neonates with CHD was used to detect associations of distinct clusters with intestinal tissue oxygenation and perfusion parameters, obtained by the "oxygen to see" (O2C) method.

RESULTS: Overall, neonates with CHD showed an intestinal core microbiota dominated by the genera Enterococcus (27%) and Staphylococcus (20%). Furthermore, a lower abundance of the genera Bacteroides (8% vs. 14%), Parabacteroides (1% vs. 3%), Bifidobacterium (4% vs. 12%), and Escherichia (8% vs. 23%) was observed in CHD compared to HCs. CHD patients that were born by vaginal delivery showed a lower fraction of the genera Bacteroides (15% vs. 21%) and Bifidobacterium (7% vs. 22%) compared to HCs and in those born by cesarean section, these genera were not found at all. In infants with CHD, we found a significant impact of oxygen saturation (SpO2) on relative abundances of the intestinal core microbiota by multivariate analysis of variance (F[8,2] = 24.9, p = 0.04). Statistical modeling suggested a large proportional shift from a microbiota dominated by the genus Streptococcus (50%) in conditions with low SpO2 towards the genus Enterococcus (61%) in conditions with high SpO2. We identified three distinct compositional microbial clusters, corresponding neonates differed significantly in intestinal blood flow and global gut perfusion.

CONCLUSION: Early life differences in gut microbiota of CHD neonates versus HCs are possibly linked to oxygen levels. Delivery method may affect microbiota stability. However, further studies are needed to assess the effect of potential interventions including probiotics or fecal transplants on early life microbiota perturbations in neonates with CHD.}, } @article {pmid39880356, year = {2025}, author = {Wang, S and Yan, K and Dong, Y and Chen, Y and Song, J and Chen, Y and Liu, X and Qi, R and Zhou, X and Zhong, J and Li, J}, title = {The influence of microplastics on hypertension-associated cardiovascular injury via the modulation of gut microbiota.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {368}, number = {}, pages = {125760}, doi = {10.1016/j.envpol.2025.125760}, pmid = {39880356}, issn = {1873-6424}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Microplastics/toxicity ; *Hypertension ; Mice ; Male ; Blood Pressure/drug effects ; Humans ; Feces/chemistry ; }, abstract = {Microplastics (MPs) have been found to interfere with the gut microbiota and compromise the integrity of the gut barrier. Excessive exposure to MPs markedly elevates the risk of cardiovascular disease, yet their influence on hypertension remains elusive, calling for investigation into their potential impacts on blood pressure (BP) regulation. In the present study, an increase in the concentration of MPs was observed in the fecal samples of individuals suffering from hypertension, as compared to the controls. Oral administration of MPs led to obvious increases in systolic, diastolic and mean BP levels in mice. MPs were associated with promoting myocardial hypertrophy, fibrosis, and cardiac remodeling through alterations in gut microbial composition, such as Prevotella and Coprobacillus, or fecal metabolites Betaine and Glycyrrhetinic acid. The hypertensive damage mediated by MPs was significantly mitigated by the high-fiber diet or antibiotics that targeted the gut microbiota. Notablely, fecal microbiota transplantation from mice treated with MPs led to an increase in systolic BP levels and the development of cardiac dysfunction. Our findings offer valuable insights into the complex interplay between MPs and the gut microbiome in the context of hypertension, and suggest potential strategies for reducing the vascular and cardiac injury caused by MPs.}, } @article {pmid39879970, year = {2025}, author = {Stallmach, A}, title = {[The gastrointestinal microbiome - vision and mission].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {150}, number = {4}, pages = {157-162}, doi = {10.1055/a-2303-3368}, pmid = {39879970}, issn = {1439-4413}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Germany ; Dysbiosis/therapy/microbiology ; }, abstract = {The gastrointestinal microbiome influences physiological functions and is altered in a variety of diseases. The causality of "dysbiosis" in the pathogenesis is not always proven; association studies are often involved. Patients with IBD, bacteria, fungi, bacteriophages, and archaea show disease-typical patterns associated with metabolome disturbances. Fecal microbiome transfer (FMT) for treating various diseases is the subject of numerous clinical studies. Currently, recurrent Clostridioides difficile infection (rCDI) is the only confirmed indication recommended in medical guidelines. In Germany, the FMT is subject to the Medicines Act and may only be carried out as part of individual healing attempts or clinical studies. For patient safety, repeated donor screening, ideally with the construction of a chair bench, is necessary. This significantly limits the nationwide availability of the FMT in Germany. Microbiota-based therapeutics prepared from the stool of tested donors have recently been approved by the US Food and Drug Administration (FDA) for the prevention of rCDI. More microbiome-based medicines can be expected in the future.}, } @article {pmid39879969, year = {2025}, author = {Weirauch, T and Vehreschild, MJGT}, title = {[Nosocomial gastrointestinal infections and Clostridioides difficile].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {150}, number = {4}, pages = {149-156}, doi = {10.1055/a-2303-3321}, pmid = {39879969}, issn = {1439-4413}, mesh = {Humans ; *Cross Infection/epidemiology/therapy/diagnosis/drug therapy ; *Clostridium Infections/epidemiology/therapy/diagnosis/drug therapy ; *Clostridioides difficile ; Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; Diarrhea/epidemiology/microbiology ; Vancomycin/therapeutic use ; Gastrointestinal Microbiome ; Germany/epidemiology ; }, abstract = {German surveillance data from 2022 reported a prevalence of nosocomial infections among hospitalized patients of 5,2%. Clostridioides-difficile-infections (CDI) are the most frequent cause of nosocomial diarrhea. They are usually caused by antibiotic exposure and the subsequent changes in the gut microbiota. Clinical manifestation ranges from asymptomatic colonization over moderate diarrhea to severe pseudomembranous colitis. According to the current German Gastrointestinal Infection Guidelines, fidaxomicin is the preferred treatment option for CDI, especially in patients at high risk of recurrence or those already suffering from recurrence. Vancomycin can also be used as an alternative for initial CDI treatment. Fecal microbiota transplantation is considered a treatment approach for patients with multiple recurrences.}, } @article {pmid39879083, year = {2025}, author = {Carroll, A and Bell, MJ and Bleach, ECL and Turner, D and Williams, LK}, title = {Impact of dairy calf management practices on the intestinal tract microbiome pre-weaning.}, journal = {Journal of medical microbiology}, volume = {74}, number = {1}, pages = {}, doi = {10.1099/jmm.0.001957}, pmid = {39879083}, issn = {1473-5644}, mesh = {Animals ; Cattle/microbiology/growth & development ; *Gastrointestinal Microbiome ; Weaning ; *Animal Husbandry/methods ; *Dairying/methods ; }, abstract = {Introduction. Microbiota in the gastrointestinal tract (GIT) consisting of the rumen and hindgut (the small intestine, cecum and colon) in dairy calves play a vital role in their growth and development. This review discusses the development of dairy calf intestinal microbiomes with an emphasis on the impact that husbandry and rearing management have on microbiome development, health and growth of pre-weaned dairy calves.Discussion. The diversity and composition of the microbes that colonize the lower GIT (small and large intestine) can have a significant impact on the growth and development of the calf, through influence on nutrient metabolism, immune modulation, resistance or susceptibility to infection, production outputs and behaviour modification in adult life. The colonization of the calf intestinal microbiome dynamically changes from birth, increasing microbial richness and diversity until weaning, where further dynamic and drastic microbiome change occurs. In dairy calves, neonatal microbiome development prior to weaning is influenced by direct and indirect factors, some of which could be considered stressors, such as maternal interaction, environment, diet, husbandry and weaning practices. The specific impact of these can dictate intestinal microbial colonization, with potential lifelong consequences.Conclusion. Evidence suggests the potential detrimental effect that sudden changes and stress may have on calf health and growth due to management and husbandry practices, and the importance of establishing a stable yet diverse intestinal microbiome population at an early age is essential for calf success. The possibility of improving the health of calves through intestinal microbiome modulation and using alternative strategies including probiotic use, faecal microbiota transplantation and novel approaches of microbiome tracking should be considered to support animal health and sustainability of dairy production systems.}, } @article {pmid39878866, year = {2025}, author = {Zheng, Y and Yu, Y and Chen, M and Zhang, H and Wang, W and Fan, X and Sun, L and Tang, L and Ta, D}, title = {Abdominal LIPUS Stimulation Prevents Cognitive Decline in Hind Limb Unloaded Mice by Regulating Gut Microbiota.}, journal = {Molecular neurobiology}, volume = {62}, number = {6}, pages = {7313-7329}, pmid = {39878866}, issn = {1559-1182}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Cognitive Dysfunction/prevention & control/microbiology ; Male ; Mice ; Mice, Inbred C57BL ; *Ultrasonic Waves ; *Hindlimb Suspension ; Fecal Microbiota Transplantation ; *Abdomen ; }, abstract = {Weightlessness usually causes disruption of the gut microbiota and impairs cognitive function. There is a close connection between gut microbiota and neurological diseases. Low-intensity pulsed ultrasound (LIPUS) has a beneficial effect on reducing intestinal inflammation. So we wondered if abdominal LIPUS stimulation can have a positive impact on weightlessness induced cognitive decline by reducing intestinal dysfunction. The findings revealed that the hind limb unloaded mice exhibited evident disruption in intestinal structure and gut microbial homeostasis, along with impairment in their learning and memory capabilities. However, 4-week abdominal LIPUS treatment improved intestinal function in hind limb unloaded mice, characterized by upregulation of tight junction proteins ZO-1 and Occludin expression in the colon, increased diversity and abundance of intestinal microbiota, decreased serum lipopolysaccharide (LPS), and increased short chain fatty acids in colon contents. The hind limb unloaded mice treated with LIPUS exhibited heightened activity levels, improved exploratory tendencies, and significantly enhanced learning and memory faculties, and elevated expression of neuroadaptation-related proteins such as PSD95, GAP43, P-CREB, BDNF, and its receptor TRKB in the hippocampus. Furthermore, the hind limb unloaded mice receiving fecal transplants from the mice whose abdomens were irradiated with LIPUS displayed enhanced cognitive abilities and improved intestinal structure, akin to the outcomes observed in hind limb unloaded mice who received LIPUS abdominal treatment directly. The above results indicate that LIPUS enhances intestinal structure and microbiota, which helps alleviate cognitive impairment caused by weightlessness. LIPUS could be a potential strategy to simultaneously improve gut dysfunction and cognitive decline in astronauts or bedridden patients.}, } @article {pmid39875017, year = {2025}, author = {Qin, L and Fan, B and Zhou, Y and Zheng, J and Diao, R and Wang, F and Liu, J}, title = {Targeted gut microbiome therapy: Applications and prospects of probiotics, fecal microbiota transplantation and natural products in the management of type 2 diabetes.}, journal = {Pharmacological research}, volume = {213}, number = {}, pages = {107625}, doi = {10.1016/j.phrs.2025.107625}, pmid = {39875017}, issn = {1096-1186}, mesh = {Humans ; *Diabetes Mellitus, Type 2/therapy/microbiology ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; *Probiotics/therapeutic use ; Animals ; *Biological Products/therapeutic use ; }, abstract = {Type 2 diabetes mellitus (T2DM) is considered as one of the most pressing public health challenges worldwide. Studies have shown significant differences in the gut microbiota between healthy individuals and T2DM patients, suggesting that gut microorganisms may play a key role in the onset and progression of T2DM. This review systematically summarizes the relationship between gut microbiota and T2DM, and explores the mechanisms through which gut microorganisms may alleviate T2DM. Additionally, it evaluates the potential of probiotics, fecal microbiota transplantation (FMT)/virome transplantation (FVT), and natural products in modulating gut microbiota to treat T2DM. Although existing studies have suggested that these interventions may delay or even halt the progression of T2DM, most research remained limited to animal models and observational clinical studies, with a lack of high-quality clinical data. This has led to an imbalance between theoretical research and clinical application. Although some studies have explored the regulatory role of the gut virome on the gut microbiota, research in this area remains in its early stages. Based on these current studies, future research should be focused on large-scale, long-term clinical studies and further investigation on the potential role of the gut virome in T2DM. In conclusion, this review aims to summarize the current evidence and explore the applications of gut microbiota in T2DM treatment, as well as providing recommendations for further investigation in this field.}, } @article {pmid39874238, year = {2025}, author = {Scher, JU and Nayak, R and Clemente, JC}, title = {Microbiome research in autoimmune and immune-mediated inflammatory diseases: lessons, advances and unmet needs.}, journal = {Annals of the rheumatic diseases}, volume = {84}, number = {1}, pages = {9-13}, pmid = {39874238}, issn = {1468-2060}, support = {R01 AR074500/AR/NIAMS NIH HHS/United States ; T32 AR069515/AR/NIAMS NIH HHS/United States ; UC2 AR081034/AR/NIAMS NIH HHS/United States ; }, mesh = {Humans ; *Autoimmune Diseases/microbiology/immunology/therapy ; *Gastrointestinal Microbiome/immunology ; Dysbiosis/immunology/microbiology ; Fecal Microbiota Transplantation ; Arthritis, Rheumatoid/microbiology/immunology ; Lupus Erythematosus, Systemic/microbiology/immunology ; *Microbiota/immunology ; Inflammation/microbiology/immunology ; *Immune System Diseases/microbiology/immunology ; }, abstract = {The increasing prevalence of autoimmune and immune-mediated diseases (AIMDs) underscores the need to understand environmental factors that contribute to their pathogenesis, with the microbiome emerging as a key player. Despite significant advancements in understanding how the microbiome influences physiological and inflammatory responses, translating these findings into clinical practice remains challenging. This viewpoint reviews the progress and obstacles in microbiome research related to AIMDs, examining molecular techniques that enhance our understanding of microbial contributions to disease. We discuss significant discoveries linking specific taxa and metabolites to diseases such as rheumatoid arthritis, systemic lupus erythematosus and spondyloarthritis, highlighting the role of gut dysbiosis and host-microbiome interactions. Furthermore, we explore the potential of microbiome-based therapeutics, including faecal microbiota transplantation and pharmacomicrobiomics, while addressing the challenges of identifying robust microbial targets. We advocate for integrative, transdisease studies and emphasise the need for diverse cohort research to generalise findings across populations. Understanding the microbiome's role in AIMDs will pave the way for personalised medicine and innovative therapeutic strategies.}, } @article {pmid39873952, year = {2025}, author = {Pezeshki, B and Abdulabbas, HT and Alturki, AD and Mansouri, P and Zarenezhad, E and Nasiri-Ghiri, M and Ghasemian, A}, title = {Synergistic Interactions Between Probiotics and Anticancer Drugs: Mechanisms, Benefits, and Challenges.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {39873952}, issn = {1867-1314}, abstract = {Research into the role of probiotics-often referred to as "living supplements"-in cancer therapy is still in its early stages, and uncertainties regarding their effectiveness remain. Relevantly, chemopreventive and therapeutic effects of probiotics have been determined. There is also substantial evidence supporting their potential in cancer treatment such as immunotherapy. Probiotics employ various mechanisms to inhibit cancer initiation and progression. These include colonizing and protecting the gastrointestinal tract (GIT), producing metabolites, inducing apoptosis and autophagy, exerting anti-inflammatory properties, preventing metastasis, enhancing the effectiveness of immune checkpoint inhibitors (ICIs), promoting cancer-specific T cell infiltration, arresting the cell cycle, and exhibiting direct or indirect synergistic effects with anticancer drugs. Additionally, probiotics have been shown to activate tumor suppressor genes and inhibit pro-inflammatory transcription factors. They also increase reactive oxygen species production within cancer cells. Synergistic interactions between probiotics and various anticancer drugs, such as cisplatin, cyclophosphamide, 5-fluorouracil, trastuzumab, nivolumab, ipilimumab, apatinib, gemcitabine, tamoxifen, sorafenib, celecoxib and irinotecan have been observed. The combination of probiotics with anticancer drugs holds promise in overcoming drug resistance, reducing recurrence, minimizing side effects, and lowering treatment costs. In addition, fecal microbiota transplantation (FMT) and prebiotics supplementation has increased cytotoxic T cells within tumors. However, probiotics may leave some adverse effects such as risk of infection and gastrointestinal effects, antagonistic effects with drugs, and different responses among patients. These findings highlight insights for considering specific strains and engineered probiotic applications, preferred doses and timing of treatment, and personalized therapies to enhance the efficacy of cancer therapy. Accordingly, targeted interventions and guidelines establishment needs extensive randomized controlled trials as probiotic-based cancer therapy has not been approved by Food and Drug Administration (FDA).}, } @article {pmid39873191, year = {2025}, author = {An, L and Li, S and Chang, Z and Lei, M and He, Z and Xu, P and Zhang, S and Jiang, Z and Iqbal, MS and Sun, X and Liu, H and Duan, X and Wu, W}, title = {Gut microbiota modulation via fecal microbiota transplantation mitigates hyperoxaluria and calcium oxalate crystal depositions induced by high oxalate diet.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2457490}, pmid = {39873191}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Hyperoxaluria/therapy/metabolism/microbiology ; *Fecal Microbiota Transplantation ; *Calcium Oxalate/metabolism/chemistry ; Rats ; *Oxalates/metabolism ; Male ; Rats, Sprague-Dawley ; Disease Models, Animal ; Diet/adverse effects ; Bacteria/classification/genetics/isolation & purification/metabolism ; Kidney/pathology/metabolism ; }, abstract = {Hyperoxaluria, including primary and secondary hyperoxaluria, is a disorder characterized by increased urinary oxalate excretion and could lead to recurrent calcium oxalate kidney stones, nephrocalcinosis and eventually end stage renal disease. For secondary hyperoxaluria, high dietary oxalate (HDOx) or its precursors intake is a key reason. Recently, accumulated studies highlight the important role of gut microbiota in the regulation of oxalate homeostasis. However, the underlying mechanisms involving gut microbiota and metabolite disruptions in secondary hyperoxaluria remain poorly understood. Here, we investigated the therapeutic efficacy of fecal microbiota transplantation (FMT) sourced from healthy rats fed with standard pellet diet against urinary oxalate excretion, renal damage and calcium oxalate (CaOx) crystal depositions via using hyperoxaluria rat models. We observed dose-dependent increases in urinary oxalate excretion and CaOx crystal depositions due to hyperoxaluria, accompanied by significant reductions in gut microbiota diversity characterized by shifts in Ruminococcaceae_UCG-014 and Parasutterella composition. Metabolomic analysis validated these findings, revealing substantial decreases in key metabolites associated with these microbial groups. Transplanting microbes from healthy rats effectively reduced HDOx-induced urinary oxalate excretion and CaOx crystal depositions meanwhile restoring Ruminococcaceae_UCG-014 and Parasutterella populations and their associated metabolites. Furthermore, FMT treatment could significantly decrease the urinary oxalate excretion and CaOx crystal depositions in rat kidneys via, at least in part, upregulating the expressions of intestinal barrier proteins and oxalate transporters in the intestine. In conclusion, our study emphasizes the effectiveness of FMT in countering HDOx-induced hyperoxaluria by restoring gut microbiota and related metabolites. These findings provide insights on the complex connection between secondary hyperoxaluria caused by high dietary oxalate and disruptions in gut microbiota, offering promising avenues for targeted therapeutic strategies.}, } @article {pmid39870907, year = {2025}, author = {Misselwitz, B and Haller, D}, title = {[The intestinal microbiota in inflammatory bowel diseases].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {66}, number = {2}, pages = {146-155}, pmid = {39870907}, issn = {2731-7099}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Inflammatory Bowel Diseases/microbiology/therapy ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Dysbiosis/therapy ; }, abstract = {BACKGROUND: The intestinal microbiota comprises all living microorganisms in the gastrointestinal tract and is crucial for its function. Clinical observations and laboratory findings confirm a central role of the microbiota in chronic inflammatory bowel diseases (IBD). However, many mechanistic details remain unclear.

OBJECTIVES: Changes in the microbiota and the causal relationship with the pathogenesis of IBD are described and current and future diagnostic and therapeutic options are discussed.

MATERIALS AND METHODS: Narrative review.

RESULTS: The intestinal microbiota is altered in composition, diversity, and function in IBD patients, but specific (universal) IBD-defining bacteria have not been identified. The healthy microbiota has numerous anti-inflammatory functions such as the production of short-chain fatty acids or competition with pathogens. In contrast, the IBD microbiota promotes inflammation through the destruction of the intestinal barrier and direct interaction with the immune system. The balance between pro- and anti-inflammatory effects of the microbiota appears to be crucial for the development of intestinal inflammation. Microbiota-based IBD diagnostics show promise but are not yet ready for clinical use. Probiotics and fecal microbiota transplantation have clinical effects, especially in ulcerative colitis, but the potential of microbiota-based therapies is far from being fully realized.

CONCLUSION: IBD dysbiosis remains undefined so far. It is unclear how the many parallel pro- and anti-inflammatory mechanisms contribute to IBD pathogenesis. An inadequate mechanistic understanding hinders the development of microbiota-based diagnostics and therapies.}, } @article {pmid39870349, year = {2025}, author = {Vázquez-Cuesta, S and Olmedo, M and Kestler, M and Álvarez-Uría, A and De la Villa, S and Alcalá, L and Marín, M and Rodríguez-Fernández, S and Sánchez-Martínez, C and Muñoz, P and Bouza, E and Reigadas, E}, title = {Prospective analysis of biomarkers associated with successful faecal microbiota transplantation in recurrent Clostridioides difficile infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {31}, number = {7}, pages = {1187-1195}, doi = {10.1016/j.cmi.2025.01.026}, pmid = {39870349}, issn = {1469-0691}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Clostridium Infections/therapy/microbiology ; Prospective Studies ; Male ; Female ; Biomarkers/analysis ; Middle Aged ; Aged ; *Leukocyte L1 Antigen Complex/analysis ; Feces/microbiology ; Recurrence ; Clostridioides difficile ; Gastrointestinal Microbiome ; Adult ; Treatment Outcome ; RNA, Ribosomal, 16S/genetics ; Aged, 80 and over ; }, abstract = {OBJECTIVES: Faecal microbiota transplantation (FMT) is an established treatment for recurrent Clostridioides difficile infection (CDI). This study aimed to identify calprotectin and microbiome characteristics as potential biomarkers of FMT success.

METHODS: We conducted a prospective study of patients who underwent oral FMT (single dose of 4-5 capsules) for recurrent CDI (January 2018 to December 2022). Samples were collected at three time points: at CDI diagnosis, within 24 hours before FMT administration, and 30 days post-FMT. Calprotectin levels were assessed and the V4 region of the 16S rRNA gene was sequenced to analyse the microbiota composition. Sequencing data analysis and statistical analysis were performed using MOTHUR and R.

RESULTS: Ninety-seven patients underwent FMT (totalling 105 procedures). A total of 221 samples were processed, including 21 donor samples, 24 capsule contents, and 176 patient faecal samples (39 at diagnosis, 63 pre-FMT, and 74 post-FMT). FMT achieved an overall success rate of 85.1% (86/101 cases). The abundance of Bacteroides, Ruminococcus, Megamonas, and certain Prevotella operational taxonomic units was significantly higher in capsules associated with 100% success compared with less effective capsules. FMT engraftment was observed in 95% of patients with favourable outcomes versus 62% of those with recurrences (p 0.006). Additionally, a negative correlation was found between calprotectin levels and specific microbial genera, suggesting an association with successful outcomes.

DISCUSSION: This study highlights differences in the evolution of faecal microbiota, bacterial engraftment, and inflammation markers (e.g. calprotectin) between patients with varying FMT outcomes. Potential biomarkers for successful FMT were identified, providing valuable insights for optimizing FMT strategies.}, } @article {pmid39870263, year = {2025}, author = {Ren, P and Liu, M and Wei, B and Tang, Q and Wang, Y and Xue, C}, title = {Fucoidan exerts antitumor effects by regulating gut microbiota and tryptophan metabolism.}, journal = {International journal of biological macromolecules}, volume = {300}, number = {}, pages = {140334}, doi = {10.1016/j.ijbiomac.2025.140334}, pmid = {39870263}, issn = {1879-0003}, mesh = {*Tryptophan/metabolism ; *Polysaccharides/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Animals ; Mice ; *Antineoplastic Agents/pharmacology ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; Kynurenine/blood ; }, abstract = {Fucoidan, a water-soluble polysaccharide derived from marine organisms, has garnered significant attention for its ability to regulate gut microbiota and its anti-tumor properties. However, the existence of a correlation between the anti-tumor effect of fucoidan and its regulation of the gut microbiota remains unknown. In pursuit of this objective, we culled the gut microbiota of mice with broad-spectrum antibiotics to generate pseudo-sterile tumor-bearing mice. Subsequently, fecal microbial transplants were introduced into the pseudo-sterile tumor-bearing mice. The antitumor effects of fucoidan were found to be dependent on the gut microbiota. Fucoidan promoted the proliferation of Akkermansia, Bifidobacterium and Lactobacillus, which have immunomodulatory effects. Furthermore, through regulation of gut microbiota, fucoidan influenced the metabolic process of tryptophan and facilitated its conversion to indole-3-acetic acid. In addition, fucoidan decreased the kynurenine/tryptophan ratio in serum, increased the proportion of CD8+ T cells, and suppressed the expression level of IDO1 in tumor tissues. Our results confirm that fucoidan enhances anti-tumor immune responses and subsequently exhibits anti-tumor effects by modulating the gut microbiota. Our research contributes to the comprehension of the mechanism of anti-tumor effects of fucoidan and facilitates the development of fucoidan as a dietary supplement for cancer patients.}, } @article {pmid39869016, year = {2025}, author = {Martin Fuentes, A}, title = {The role of the microbiome in skin cancer development and treatment.}, journal = {Current opinion in oncology}, volume = {37}, number = {2}, pages = {121-125}, doi = {10.1097/CCO.0000000000001120}, pmid = {39869016}, issn = {1531-703X}, mesh = {Humans ; *Skin Neoplasms/microbiology/immunology/therapy ; *Microbiota/immunology ; Probiotics/therapeutic use ; *Melanoma/microbiology/immunology/therapy ; Immune Checkpoint Inhibitors/therapeutic use ; Prebiotics ; *Gastrointestinal Microbiome/immunology ; Fecal Microbiota Transplantation ; Animals ; Immunotherapy/methods ; }, abstract = {PURPOSE OF REVIEW: Recent research underscores the significant influence of the skin and gut microbiota on melanoma and nonmelanoma skin cancer (NMSC) development and treatment outcomes. This review aims to synthesize current findings on how microbiota modulates immune responses, particularly enhancing the efficacy of immunotherapies such as immune checkpoint inhibitors (ICIs).

RECENT FINDINGS: The microbiota's impact on skin cancer is multifaceted, involving immune modulation, inflammation, and metabolic interactions. Beneficial strains like Bifidobacterium and Lactobacillus have shown potential in supporting anti-PD-1 and anti-CTLA-4 therapies by promoting T-cell activation and immune surveillance. Evidence from preclinical and clinical studies, including fecal microbiota transplantation (FMT), highlights improved response rates in patients with microbiota-rich profiles. Notably, certain bacterial metabolites, such as inosine, contribute to enhanced antitumor activity by stimulating IFN-γ in CD8 + T cells.

SUMMARY: Understanding the interplay between microbiota and skin cancer treatment opens promising avenues for adjunctive therapies. Probiotic and prebiotic interventions, FMT, and microbiota modulation are emerging as complementary strategies to improve immunotherapy outcomes and address treatment resistance in melanoma and NMSC.}, } @article {pmid39868555, year = {2025}, author = {Chatterjee, J and Qi, X and Mu, R and Li, X and Eligator, T and Ouyang, M and Bozeman, SL and Rodgers, R and Aggarwal, S and Campbell, DE and Schriefer, LA and Baldridge, MT and Gutmann, DH}, title = {Intestinal Bacteroides drives glioma progression by regulating CD8+ T cell tumor infiltration.}, journal = {Neuro-oncology}, volume = {27}, number = {6}, pages = {1579-1593}, pmid = {39868555}, issn = {1523-5866}, support = {R35NS097211/NH/NIH HHS/United States ; //Vision Restoration Initiative/ ; //Schnuck Markets/ ; }, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome/immunology ; *CD8-Positive T-Lymphocytes/immunology/pathology ; Disease Progression ; *Bacteroides/immunology ; *Lymphocytes, Tumor-Infiltrating/immunology/pathology ; Mice, Inbred C57BL ; Disease Models, Animal ; *Optic Nerve Glioma/pathology/immunology/microbiology ; Neurofibromatosis 1/pathology ; *Glioma/pathology/immunology/microbiology ; *Brain Neoplasms/pathology ; }, abstract = {BACKGROUND: The intestinal microbiota regulates normal brain physiology and the pathogenesis of several neurological disorders. While prior studies suggested that this operates through immune cells, the underlying mechanisms remain unclear. Leveraging 2 well-characterized murine models of low-grade glioma occurring in the setting of the neurofibromatosis type 1 (NF1) cancer predisposition syndrome, we sought to determine the impact of the gut microbiome on optic glioma progression.

METHODS: Neurofibromatosis type 1 (Nf1)-mutant mice genetically engineered to develop optic pathway gliomas (Nf1OPG mice) by 3 months of age were reared under germ-free (GF) conditions, treated with specific cocktails of antibiotics, or given fecal matter transplants (FMTs). Intestinal microbial species were identified by 16S genotyping. Neutralizing transforming growth factor-beta (TGFβ) antibodies were delivered systemically, while in vitro experiments used isolated murine microglia and T cells. Single-cell RNA sequencing analysis was performed using established methods.

RESULTS: Nf1 OPG mice raised in a GF environment or postnatally treated with vancomycin did not harbor optic gliomas or exhibit OPG-induced retinal nerve fiber layer thinning, which was reversed following conventionally raised mouse FMT or colonization with Bacteroides species. Moreover, this intestinal microbiota-regulated gliomagenesis was mediated by circulating TGFβ, such that systemic TGFβ neutralization reduced Nf1-OPG growth. TGFβ was shown to act on tumor-associated monocytes to induce Ccl3 expression and recruit CD8+ T cells necessary for glioma growth.

CONCLUSIONS: Taken together, these findings establish, for the first time, a mechanistic relationship between Bacteroides in the intestinal microbiome and NF1-LGG pathobiology, suggesting both future predictive risk assessment strategies and therapeutic opportunities.}, } @article {pmid39868290, year = {2025}, author = {Weagley, JS and Cárdenas, LAC and Romani, A and Sullender, ME and Aggarwal, S and Makimaa, H and Hogarty, MP and Rodgers, R and Kennedy, EA and Foster, L and Schriefer, LA and Baldridge, MT}, title = {Dynamics of Bacterial and Viral Transmission in Experimental Microbiota Transplantation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39868290}, issn = {2692-8205}, support = {F31 AI167499/AI/NIAID NIH HHS/United States ; R01 AI139314/AI/NIAID NIH HHS/United States ; U01 AT012998/AT/NCCIH NIH HHS/United States ; R01 AI173360/AI/NIAID NIH HHS/United States ; R25 GM103757/GM/NIGMS NIH HHS/United States ; T32 AI007172/AI/NIAID NIH HHS/United States ; }, abstract = {Mouse models are vital tools for discerning the relative contributions of host and microbial genetics to disease, often requiring the transplantation of microbiota between different mouse strains. Transfer methods include antibiotic treatment of recipients and colonization using either co-housing with donors or the transplantation of fecal or cecal donor material. However, the efficiency and dynamics of these methods in reconstituting recipients with donor microbes is not well understood. We thus directly compared co-housing, fecal transplantation, and cecal transplantation methods. Donor mice from Taconic Biosciences, possessing distinct microbial communities, served as the microbial source for recipient mice from Jackson Laboratories, which were treated with antibiotics to disrupt their native microbiota. We monitored bacterial and viral populations longitudinally over the course of antibiotics treatment and reconstitution using 16S rRNA gene sequencing, quantitative PCR, and shotgun sequencing of viral-like particles. As expected, antibiotic treatment rapidly depleted microbial biomass and diversity, with slow and incomplete natural recovery of the microbiota in non-transplanted control mice. While all transfer methods reconstituted recipient mice with donor microbiota, co-housing achieved this more rapidly for both bacterial and viral communities. This study provides valuable insights into microbial transfer methods, enhancing reproducibility and informing best practices for microbiota transplantation in mouse models.}, } @article {pmid39864578, year = {2025}, author = {Attiq, A}, title = {Early-life antibiotic exposures: Paving the pathway for dysbiosis-induced disorders.}, journal = {European journal of pharmacology}, volume = {991}, number = {}, pages = {177298}, doi = {10.1016/j.ejphar.2025.177298}, pmid = {39864578}, issn = {1879-0712}, mesh = {Humans ; *Dysbiosis/chemically induced/microbiology ; *Anti-Bacterial Agents/adverse effects ; *Gastrointestinal Microbiome/drug effects ; Animals ; Probiotics ; }, abstract = {Microbiota encompasses a diverse array of microorganisms inhabiting specific ecological niches. Gut microbiota significantly influences physiological processes, including gastrointestinal motor function, neuroendocrine signalling, and immune regulation. They play a crucial role in modulating the central nervous system and bolstering body defence mechanisms by influencing the proliferation and differentiation of innate and adaptive immune cells. Given the potential consequences of antibiotic therapy on gut microbiota equilibrium, there is a need for prudent antibiotic use to mitigate associated risks. Observational studies have linked increased antibiotic usage to various pathogenic conditions, including obesity, inflammatory bowel disease, anxiety-like effects, asthma, and pulmonary carcinogenesis. Addressing dysbiosis incidence requires proactive measures, including prophylactic use of β-lactamase drugs (SYN-004, SYN-006, and SYN-007), hydrolysing the β-lactam in the proximal GIT for maintaining intestinal flora homeostasis. Prebiotic and probiotic supplementations are crucial in restoring intestinal flora equilibrium by competing with pathogenic bacteria for nutritional resources and adhesion sites, reducing luminal pH, neutralising toxins, and producing antimicrobial agents. Faecal microbiota transplantation (FMT) shows promise in restoring gut microbiota composition. Rational antibiotic use is essential to preserve microflora and improve patient compliance with antibiotic regimens by mitigating associated side effects. Given the significant implications on gut microbiota composition, concerted intervention strategies must be pursued to rectify and reverse the occurrence of antibiotic-induced dysbiosis. Here, antibiotics-induced microbiota dysbiosis mechanisms and their systemic implications are reviewed. Moreover, proposed interventions to mitigate the impact on gut microflora are also discussed herein.}, } @article {pmid39863610, year = {2025}, author = {Reddi, S and Senyshyn, L and Ebadi, M and Podlesny, D and Minot, SS and Gooley, T and Kabage, AJ and Hill, GR and Lee, SJ and Khoruts, A and Rashidi, A}, title = {Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {1034}, pmid = {39863610}, issn = {2041-1723}, support = {P30 CA015704/CA/NCI NIH HHS/United States ; ACT9016-24//Leukemia and Lymphoma Society (Leukemia & Lymphoma Society)/ ; }, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Acute Disease ; Double-Blind Method ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; *Gastrointestinal Microbiome ; *Graft vs Host Disease/prevention & control/microbiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Tissue Donors ; Transplantation, Homologous/adverse effects ; Treatment Outcome ; }, abstract = {Gut microbiota disruptions after allogeneic hematopoietic cell transplantation (alloHCT) are associated with increased risk of acute graft-versus-host disease (aGVHD). We designed a randomized, double-blind placebo-controlled trial to test whether healthy-donor fecal microbiota transplantation (FMT) early after alloHCT reduces the incidence of severe aGVHD. Here, we report the results from the single-arm run-in phase which identified the best of 3 stool donors for the randomized phase. The primary and key secondary endpoints were microbiota engraftment and severe aGVHD, respectively. Three cohorts of patients (20 total) received FMT, each from a different donor. FMT was safe and effective in restoring microbiota diversity and commensal species. Microbiota engraftment, determined from shotgun sequencing data, correlated with larger microbiota compositional shifts toward donor and better clinical outcomes. Donor 3 yielded a median engraftment rate of 66%, higher than donors 1 (P = 0.02) and 2 (P = 0.03) in multivariable analysis. Three patients developed severe aGVHD; all 3 had received FMT from donor 1. Donor 3 was selected as the sole donor for the randomized phase. Our findings suggest a clinically relevant donor effect and demonstrate feasibility of evidence-based donor selection. FMT is a holistic microbiota restoration approach that can be performed as a precision therapeutic. ClinicalTrials.gov identifier NCT06026371.}, } @article {pmid39863438, year = {2025}, author = {Jin, J and Cai, X and Rao, P and Xu, J and Li, J}, title = {Microbiota and immune dynamics in rheumatoid arthritis: Mechanisms and therapeutic potential.}, journal = {Best practice & research. Clinical rheumatology}, volume = {39}, number = {1}, pages = {102035}, doi = {10.1016/j.berh.2025.102035}, pmid = {39863438}, issn = {1532-1770}, mesh = {Humans ; *Arthritis, Rheumatoid/immunology/microbiology/therapy ; *Dysbiosis/immunology/therapy ; *Gastrointestinal Microbiome/immunology ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Rheumatoid arthritis (RA) is a complex autoimmune disease with growing evidence implicating the microbiota as a critical contributor to its pathogenesis. This review explores the multifaceted roles of microbial dysbiosis in RA, emphasizing its impact on immune cell modulation, autoantibody production, gut barrier integrity, and joint inflammation. Animal models reveal how genetic predisposition and environmental factors interact with specific microbial taxa to influence disease susceptibility. Dysbiosis-driven metabolic disruptions, including alterations in short-chain fatty acids and bile acids, further exacerbate immune dysregulation and systemic inflammation. Emerging therapeutic strategies-probiotics, microbial metabolites, fecal microbiota transplantation, and antibiotics-offer innovative avenues for restoring microbial balance and mitigating disease progression. By integrating microbiota-targeted approaches with existing treatments, this review highlights the potential to revolutionize RA management through precision medicine and underscores the need for further research to harness the microbiota's therapeutic potential.}, } @article {pmid39863236, year = {2025}, author = {Qin, N and Liu, H and Wang, X and Liu, Y and Chang, H and Xia, X}, title = {Sargassum fusiforme polysaccharides protect mice against Citrobacter rodentium infection via intestinal microbiota-driven microRNA-92a-3p-induced Muc2 production.}, journal = {International journal of biological macromolecules}, volume = {300}, number = {}, pages = {140271}, doi = {10.1016/j.ijbiomac.2025.140271}, pmid = {39863236}, issn = {1879-0003}, mesh = {Animals ; *MicroRNAs/genetics/metabolism ; *Mucin-2/metabolism/genetics/biosynthesis ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Sargassum/chemistry ; *Polysaccharides/pharmacology/chemistry ; *Citrobacter rodentium/drug effects ; *Enterobacteriaceae Infections/microbiology/prevention & control/drug therapy/genetics ; Intestinal Mucosa/drug effects/microbiology/metabolism ; Male ; Signal Transduction/drug effects ; Dysbiosis ; Mice, Inbred C57BL ; Edible Seaweeds ; Receptor, Notch1 ; }, abstract = {Sargassum fusiforme, widely consumed in Asian countries, has been proven to have various biological activities. However, the impacts and mechanisms of Sargassum fusiforme polysaccharides (SFPs) on intestinal bacterial infection are not yet fully understood. Our findings indicate that SFPs pretreatment ameliorates intestinal inflammation by reducing C. rodentium colonization, increasing colon length and levels of IL-10 and IL-22, decreasing IL-1β, IL-6, TNF-α, and IL-17 levels, inhibiting colonic crypt elongation and hyperplasia, and enhancing the intestinal mucosal barrier. The protective effects against intestinal bacterial infection are linked to enhanced clearance of C. rodentium and improvements in the intestinal mucosal barrier and C. rodentium-induced intestinal microbiota dysbiosis. Fecal microbiota transplantation experiments were conducted to evaluate the functional impact of microbiota induced by SFPs. The results suggest that intestinal microbiota modified by SFPs effectively countered C. rodentium infection. In addition, our study identified that miRNA-92a-3p is partially complementary to the 3'-UTR of the Notch1 gene, thereby repressing the Notch1-Hes1 signaling pathway and enhancing Muc2 secretion. Taken together, these findings reveal that SFPs protect mice from C. rodentium infection by activating the miR-92a-3p/Notch1-Hes1 regulatory axis driven by the intestinal microbiota, which stimulates Muc2 production to maintain intestinal barrier homeostasis.}, } @article {pmid39862968, year = {2025}, author = {Huang, P and Di, L and Cui, S and Wang, X and Cao, T and Jiang, S and Huang, L}, title = {Postoperative delirium after cardiac surgery associated with perioperative gut microbiota dysbiosis: Evidence from human and antibiotic-treated mouse model.}, journal = {Anaesthesia, critical care & pain medicine}, volume = {44}, number = {2}, pages = {101484}, doi = {10.1016/j.accpm.2025.101484}, pmid = {39862968}, issn = {2352-5568}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Dysbiosis/microbiology/complications ; Animals ; Humans ; Male ; Mice ; Aged ; Female ; *Anti-Bacterial Agents/therapeutic use ; Middle Aged ; Case-Control Studies ; *Delirium/etiology/microbiology ; *Postoperative Complications/microbiology/etiology ; *Cardiac Surgical Procedures/adverse effects ; Fatty Acids, Volatile/metabolism/analysis ; Fecal Microbiota Transplantation ; Feces/microbiology/chemistry ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Research links gut microbiota to postoperative delirium (POD) through the gut-brain axis. However, changes in gut microbiota and fecal short-chain fatty acids (SCFAs) in POD patients during the perioperative period and their association with POD are unclear.

METHODS: We conducted a nested case-control study among patients undergoing off-pump coronary artery bypass grafting, focusing on POD as the main outcome. POD patients were matched 1:1 with non-POD patients based on sociodemographic characteristics, health, and diet. Fecal samples were collected pre- and post-surgery to assess gut microbiota and SCFAs changes. Postoperative fecal samples were transplanted into antibiotic-treated mice to evaluate delirium-like behavior and neuroinflammation.

RESULTS: Out of 120 patients, 60 were matched. Before surgery, gut microbiota in both groups was similar. After surgery, POD patients had lower alpha diversity and distinct microbiota compared to non-POD patients. LEfSe analysis showed POD was linked to increased opportunistic pathogens (Enterococcus) and decreased SCFAs producers (Bacteroides, Ruminococcus, etc.). SCFAs were significantly reduced in POD patients and negatively correlated with delirium severity and plasma inflammation. Mice receiving fecal transplants from POD patients exhibited delirium-like behavior and neuroinflammation.

CONCLUSIONS: Postoperative delirium is associated with gut microbiota dysbiosis, marked by an increase in opportunistic pathogens and a decrease in SCFA-producing genera.

REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300070477.}, } @article {pmid39862808, year = {2025}, author = {Xiao, Y and He, X and Zhang, H and Wu, X and Ai, R and Xu, J and Wen, Q and Zhang, F and Cui, B}, title = {Washed microbiota transplantation effectively improves nutritional status in gastrointestinal disease-related malnourished children.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {132}, number = {}, pages = {112679}, doi = {10.1016/j.nut.2024.112679}, pmid = {39862808}, issn = {1873-1244}, mesh = {Humans ; Male ; Female ; *Nutritional Status ; Prospective Studies ; Child, Preschool ; *Gastrointestinal Diseases/complications/therapy/microbiology ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/methods/adverse effects ; Infant ; Treatment Outcome ; Child ; *Child Nutrition Disorders/therapy/etiology ; *Malnutrition/therapy/etiology ; Dysbiosis/therapy ; }, abstract = {BACKGROUND AND AIM: Gut microbiota dysbiosis plays a critical role in malnutrition caused by food intolerance and intestinal inflammation in children, which needs to be addressed. We assessed the efficacy and safety of washed microbiota transplantation (WMT) for gastrointestinal disease-related malnourished children.

METHODS: This was a prospective observational study involving gastrointestinal disease-related malnourished pediatric patients who underwent WMT. The primary outcome was the clinical response rate at 3 mo post-WMT. Clinical response was defined as an improvement in the children's nutritional status of one level or more. The secondary outcomes were changes in gastrointestinal symptoms, laboratory nutritional indicators, and adverse events during the WMT procedure.

RESULTS: 29 patients undergoing 74 WMTs were included for analysis. In total, 48.3% (14/29) of patients achieved clinical response post-WMT. Gastrointestinal symptoms, including diarrhea, mucous stool, abdominal pain, abdominal distention, and hematochezia, were significantly relieved post-WMT (all P < 0.05). Serum albumin and prealbumin levels were increased significantly post-WMT (P = 0.028 and 0.028, respectively). Eight self-limiting and transient adverse events, including diarrhea, abdominal pain, and abdominal distension, occurred after WMT.

CONCLUSION: This study indicated that WMT might be effective and safe for improving nutritional status and gastrointestinal symptoms in gastrointestinal disease-related malnourished children at 3-mo follow-up. WMT was expected to be a new therapeutic option for these patients.}, } @article {pmid39861773, year = {2025}, author = {Ortiz-Islas, E and Montes, P and Rodríguez-Pérez, CE and Ruiz-Sánchez, E and Sánchez-Barbosa, T and Pichardo-Rojas, D and Zavala-Tecuapetla, C and Carvajal-Aguilera, K and Campos-Peña, V}, title = {Evolution of Alzheimer's Disease Therapeutics: From Conventional Drugs to Medicinal Plants, Immunotherapy, Microbiotherapy and Nanotherapy.}, journal = {Pharmaceutics}, volume = {17}, number = {1}, pages = {}, pmid = {39861773}, issn = {1999-4923}, support = {CF-2023-G-971 and CBF-2023-2024-1982//Ciencia de Frontera/ ; }, abstract = {Alzheimer's disease (AD) represents an escalating global health crisis, constituting the leading cause of dementia among the elderly and profoundly impairing their quality of life. Current FDA-approved drugs, such as rivastigmine, donepezil, galantamine, and memantine, offer only modest symptomatic relief and are frequently associated with significant adverse effects. Faced with this challenge and in line with advances in the understanding of the pathophysiology of this neurodegenerative condition, various innovative therapeutic strategies have been explored. Here, we review novel approaches inspired by advanced knowledge of the underlying pathophysiological mechanisms of the disease. Among the therapeutic alternatives, immunotherapy stands out, employing monoclonal antibodies to specifically target and eliminate toxic proteins implicated in AD. Additionally, the use of medicinal plants is examined, as their synergistic effects among components may confer neuroprotective properties. The modulation of the gut microbiota is also addressed as a peripheral strategy that could influence neuroinflammatory and degenerative processes in the brain. Furthermore, the therapeutic potential of emerging approaches, such as the use of microRNAs to regulate key cellular processes and nanotherapy, which enables precise drug delivery to the central nervous system, is analyzed. Despite promising advances in these strategies, the incidence of Alzheimer's disease continues to rise. Therefore, it is proposed that achieving effective treatment in the future may require the integration of combined approaches, maximizing the synergistic effects of different therapeutic interventions.}, } @article {pmid39859091, year = {2025}, author = {Almonajjed, MB and Wardeh, M and Atlagh, A and Ismaiel, A and Popa, SL and Rusu, F and Dumitrascu, DL}, title = {Impact of Microbiota on Irritable Bowel Syndrome Pathogenesis and Management: A Narrative Review.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {1}, pages = {}, pmid = {39859091}, issn = {1648-9144}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/microbiology/physiopathology/etiology ; *Gastrointestinal Microbiome/physiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation/methods ; Quality of Life/psychology ; Dysbiosis/complications ; }, abstract = {Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder, affecting 3-5% of the global population and significantly impacting patients' quality of life and healthcare resources. Alongside physical symptoms such as abdominal pain and altered bowel habits, many individuals experience psychological comorbidities, including anxiety and depression. Recent research has highlighted the critical role of the gut microbiota in IBS, with dysbiosis, characterized by an imbalance in microbial diversity, frequently observed in patients. The gut-brain axis, a bidirectional communication network between the gut and central nervous system, plays a central role in the development of IBS symptoms. Although interventions such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) have demonstrated potential in modulating the gut microbiota and alleviating symptoms, their efficacy remains an area of ongoing investigation. This review examines the interactions between the gut microbiota, immune system, and brain, emphasizing the need for personalized therapeutic strategies. Future research should aim to identify reliable microbiota-based biomarkers for IBS and refine microbiome-targeted therapies to enhance patient outcomes.}, } @article {pmid39858858, year = {2025}, author = {Onisiforou, A and Charalambous, EG and Zanos, P}, title = {Shattering the Amyloid Illusion: The Microbial Enigma of Alzheimer's Disease Pathogenesis-From Gut Microbiota and Viruses to Brain Biofilms.}, journal = {Microorganisms}, volume = {13}, number = {1}, pages = {}, pmid = {39858858}, issn = {2076-2607}, support = {#101031962//European Commission Marie Skłodowska-Curie fellowship/ ; EXCELLENCE/0421/0543//Research & Innovation Foundation of Cyprus - Excellence Hubs 2021/ ; NA//IDSA Foundation/ ; }, abstract = {For decades, Alzheimer's Disease (AD) research has focused on the amyloid cascade hypothesis, which identifies amyloid-beta (Aβ) as the primary driver of the disease. However, the consistent failure of Aβ-targeted therapies to demonstrate efficacy, coupled with significant safety concerns, underscores the need to rethink our approach to AD treatment. Emerging evidence points to microbial infections as environmental factors in AD pathoetiology. Although a definitive causal link remains unestablished, the collective evidence is compelling. This review explores unconventional perspectives and emerging paradigms regarding microbial involvement in AD pathogenesis, emphasizing the gut-brain axis, brain biofilms, the oral microbiome, and viral infections. Transgenic mouse models show that gut microbiota dysregulation precedes brain Aβ accumulation, emphasizing gut-brain signaling pathways. Viral infections like Herpes Simplex Virus Type 1 (HSV-1) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may lead to AD by modulating host processes like the immune system. Aβ peptide's antimicrobial function as a response to microbial infection might inadvertently promote AD. We discuss potential microbiome-based therapies as promising strategies for managing and potentially preventing AD progression. Fecal microbiota transplantation (FMT) restores gut microbial balance, reduces Aβ accumulation, and improves cognition in preclinical models. Probiotics and prebiotics reduce neuroinflammation and Aβ plaques, while antiviral therapies targeting HSV-1 and vaccines like the shingles vaccine show potential to mitigate AD pathology. Developing effective treatments requires standardized methods to identify and measure microbial infections in AD patients, enabling personalized therapies that address individual microbial contributions to AD pathogenesis. Further research is needed to clarify the interactions between microbes and Aβ, explore bacterial and viral interplay, and understand their broader effects on host processes to translate these insights into clinical interventions.}, } @article {pmid39858421, year = {2024}, author = {Gabrielli, M and Zileri Dal Verme, L and Zocco, MA and Nista, EC and Ojetti, V and Gasbarrini, A}, title = {The Role of the Gastrointestinal Microbiota in Parkinson's Disease.}, journal = {Biomolecules}, volume = {15}, number = {1}, pages = {}, pmid = {39858421}, issn = {2218-273X}, mesh = {*Parkinson Disease/microbiology/therapy ; Humans ; *Gastrointestinal Microbiome/drug effects ; *Dysbiosis/microbiology/complications ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Helicobacter Infections/microbiology/complications ; Helicobacter pylori/pathogenicity ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {BACKGROUND/OBJECTIVES: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons leading to debilitating motor and non-motor symptoms. Beyond its well-known neurological features, emerging evidence underscores the pivotal role of the gut-brain axis and gastrointestinal microbiota in PD pathogenesis. Dysbiosis has been strongly linked to PD and is associated with increased intestinal permeability, chronic inflammation, and the production of neurotoxic metabolites that may exacerbate neuronal damage.

METHODS: This review delves into the complex interplay between PD and dysbiosis, shedding light on two peculiar subsets of dysbiosis, Helicobacter pylori infection and small-intestinal bacterial overgrowth. These conditions may not only contribute to PD progression but also influence therapeutic responses such as L-dopa efficacy.

CONCLUSIONS: The potential to modulate gut microbiota through probiotics, prebiotics, and synbiotics; fecal microbiota transplantation; and antibiotics represents a promising frontier for innovative PD treatments. Despite this potential, the current evidence is limited by small sample sizes and methodological variability across studies. Rigorous, large-scale, randomized placebo-controlled trials with standardized treatments in terms of composition, dosage, and duration are urgently needed to validate these findings and pave the way for microbiota-based therapeutic strategies in PD management.}, } @article {pmid39858303, year = {2024}, author = {Morado, F and Nanda, N}, title = {A Review of Therapies for Clostridioides difficile Infection.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, pmid = {39858303}, issn = {2079-6382}, abstract = {Clostridioides difficile is an urgent public health threat that affects approximately half a million patients annually in the United States. Despite concerted efforts aimed at the prevention of Clostridioides difficile infection (CDI), it remains a leading cause of healthcare-associated infections. CDI is associated with significant clinical, social, and economic burdens. Therefore, it is imperative to provide optimal and timely therapy for CDI. We conducted a systematic literature review and offer treatment recommendations based on available evidence for the treatment and prevention of CDI.}, } @article {pmid39857680, year = {2025}, author = {Radoš, L and Golčić, M and Mikolašević, I}, title = {The Relationship Between the Modulation of Intestinal Microbiota and the Response to Immunotherapy in Patients with Cancer.}, journal = {Biomedicines}, volume = {13}, number = {1}, pages = {}, pmid = {39857680}, issn = {2227-9059}, abstract = {The intestinal microbiota is an important part of the human body, and its composition can affect the effectiveness of immunotherapy. In the last few years, the modulation of intestinal microbiota in order to improve the effectiveness of immunotherapy has become a current topic in the scientific community, but there is a lack of research in this area. In this review, the goal was to analyze the current relevant literature related to the modulation of intestinal microbiota and the effectiveness of immunotherapy in the treatment of cancer. The effects of antibiotics, probiotics, diet, and fecal microbial transplantation were analyzed separately. It was concluded that the use of antibiotics, especially broad-spectrum types or larger quantities, causes dysbiosis of the intestinal microbiota, which can reduce the effectiveness of immunotherapy. While dysbiosis could be repaired by probiotics and thus improve the effectiveness of immunotherapy, the use of commercial probiotics without evidence of intestinal dysbiosis has not yet been sufficiently tested to confirm its safety for cancer for immunotherapy-treated cancer patients. A diet consisting of sufficient amounts of fiber, as well as a diet with higher salt content positively correlates with the success of immunotherapy. Fecal transplantation is a safe and realistic adjuvant option for the treatment of cancer patients with immunotherapy, but more clinical trials are necessary. Modulating the microbiota composition indeed changes the effectiveness of immunotherapy, but in the future, more human studies should be organized to precisely determine the types and procedures of microbiota modulation.}, } @article {pmid39857657, year = {2024}, author = {Li, W and Gao, W and Yan, S and Yang, L and Zhu, Q and Chu, H}, title = {Gut Microbiota as Emerging Players in the Development of Alcohol-Related Liver Disease.}, journal = {Biomedicines}, volume = {13}, number = {1}, pages = {}, pmid = {39857657}, issn = {2227-9059}, support = {National Nature Science Foundation of China (No.81974078, No.81570530, and No.81370550)//Ling Yang/ ; National Key R&D Program of China (No.2022YFA1305600)//Huikuan Chu/ ; Ministry of Science and Technology of China (No.2023YFC2413804)//Ling Yang/ ; Natural Science Foundation of Hubei Province (No.2019ACA1333)//Ling Yang/ ; }, abstract = {The global incidence and mortality rates of alcohol-related liver disease are on the rise, reflecting a growing health concern worldwide. Alcohol-related liver disease develops due to a complex interplay of multiple reasons, including oxidative stress generated during the metabolism of ethanol, immune response activated by immunogenic substances, and subsequent inflammatory processes. Recent research highlights the gut microbiota's significant role in the progression of alcohol-related liver disease. In patients with alcohol-related liver disease, the relative abundance of pathogenic bacteria, including Enterococcus faecalis, increases and is positively correlated with the level of severity exhibited by alcohol-related liver disease. Supplement probiotics like Lactobacillus, as well as Bifidobacterium, have been found to alleviate alcohol-related liver disease. The gut microbiota is speculated to trigger specific signaling pathways, influence metabolite profiles, and modulate immune responses in the gut and liver. This research aimed to investigate the role of gut microorganisms in the onset and advancement of alcohol-related liver disease, as well as to uncover the underlying mechanisms by which the gut microbiota may contribute to its development. This review outlines current treatments for reversing gut dysbiosis, including probiotics, fecal microbiota transplantation, and targeted phage therapy. Particularly, targeted therapy will be a vital aspect of future alcohol-related liver disease treatment. It is to be hoped that this article will prove beneficial for the treatment of alcohol-related liver disease.}, } @article {pmid39855927, year = {2025}, author = {Wang, X and Zhao, D and Bi, D and Li, L and Tian, H and Yin, F and Zuo, T and Ianiro, G and Li, N and Chen, Q and Qin, H}, title = {Fecal microbiota transplantation: transitioning from chaos and controversial realm to scientific precision era.}, journal = {Science bulletin}, volume = {70}, number = {6}, pages = {970-985}, doi = {10.1016/j.scib.2025.01.029}, pmid = {39855927}, issn = {2095-9281}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; Precision Medicine ; }, abstract = {With the popularization of modern lifestyles, the spectrum of intestinal diseases has become increasingly diverse, presenting significant challenges in its management. Traditional pharmaceutical interventions have struggled to keep pace with these changes, leaving many patients refractory to conventional pharmaceutical treatments. Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach for enterogenic diseases. Still, controversies persist regarding its active constituents, mechanism of action, scheme of treatment evaluation, indications, and contraindications. In this review, we investigated the efficacy of FMT in addressing gastrointestinal and extraintestinal conditions, drawing from follow-up data on over 8000 patients. We systematically addressed the controversies surrounding FMT's clinical application. We delved into key issues such as its technical nature, evaluation methods, microbial restoration mechanisms, and impact on the host-microbiota interactions. Additionally, we explored the potential colonization patterns of FMT-engrafted new microbiota throughout the entire intestine and elucidated the specific pathways through which the new microbiota modulates host immunity, metabolism, and genome.}, } @article {pmid39855612, year = {2025}, author = {Sutanto, H and Elisa, E and Rachma, B and Fetarayani, D}, title = {Gut Microbiome Modulation in Allergy Treatment: The Role of Fecal Microbiota Transplantation.}, journal = {The American journal of medicine}, volume = {138}, number = {5}, pages = {769-777.e3}, doi = {10.1016/j.amjmed.2025.01.005}, pmid = {39855612}, issn = {1555-7162}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/immunology ; *Hypersensitivity/therapy/microbiology/immunology ; Dysbiosis/therapy/immunology ; }, abstract = {The prevalence of allergic diseases has been rising, paralleling lifestyle changes and environmental exposures that have altered human microbiome composition. This review article examines the intricate relationship between the gut microbiome and allergic diseases, emphasizing the potential of fecal microbiota transplantation as a promising novel treatment approach. It explains how reduced microbial exposure in modern societies contributes to immune dysregulation and the increasing incidence of allergies. The discussion also addresses immune homeostasis and its modulation by the gut microbiome, highlighting the shift from eubiosis to dysbiosis in allergic conditions. Furthermore, this article reviews existing studies and emerging research on the role of fecal microbiota transplantation in restoring microbial balance, providing insights into its mechanisms, efficacy, and safety.}, } @article {pmid39854760, year = {2025}, author = {Chen, S and Zhang, D and Li, D and Zeng, F and Chen, C and Bai, F}, title = {Microbiome characterization of patients with Crohn disease and the use of fecal microbiota transplantation: A review.}, journal = {Medicine}, volume = {104}, number = {4}, pages = {e41262}, pmid = {39854760}, issn = {1536-5964}, support = {2021818//Hainan Province Clinical Medical Center/ ; YSPTZX202313//The specific research fund of The Innovation Platform for Academicians of Hainan Province/ ; 22A200078//Hainan Provincial Health Industry Research Project/ ; Qhyb2022-133//Hainan Provincial Postgraduate Innovation Research Project/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Crohn Disease/therapy/microbiology ; *Gastrointestinal Microbiome ; }, abstract = {Inflammatory bowel disease is a chronic inflammatory condition predominantly affecting the intestines, encompassing both ulcerative colitis and Crohn disease (CD). As one of the most common gastrointestinal disorders, CD's pathogenesis is closely linked with the intestinal microbiota. Recently, fecal microbiota transplantation (FMT) has gained attention as a potential treatment for CD, with the effective reestablishment of intestinal microecology considered a crucial mechanism of FMT therapy. This article synthesizes the findings of population-based cohort studies to enhance our understanding of gut microbial characteristics in patients with CD. It delves into the roles of "beneficial" and "pathogenic" bacteria in CD's development. This article systematically reviews and compares data on clinical response rates, remission rates, adverse events, and shifts in bacterial microbiota. Among these studies, gut microbiome analysis was conducted in only 7, and a single study examined the metabolome. Overall, FMT has demonstrated a partial restoration of typical CD-associated microbiological alterations, leading to increased α-diversity in responders and a moderate shift in patient microbiota toward the donor profile. Several factors, including donor selection, delivery route, microbial state (fresh or frozen), and recipient condition, are identified as pivotal in influencing FMT's effectiveness. Future prospective clinical studies with larger patient cohorts and improved methodologies are imperative. In addition, standardization of FMT procedures, coupled with advanced genomic techniques such as macroproteomics and culture genomics, is necessary. These advancements will further clarify the bacterial microbiota alterations that significantly contribute to FMT's therapeutic effects in CD treatment, as well as elucidate the underlying mechanisms of action.}, } @article {pmid39854205, year = {2025}, author = {Yang, CJ and Peng, YS and Sung, PC and Hsieh, SY}, title = {Protocol for oral fecal gavage to reshape the gut microbiota in mice.}, journal = {STAR protocols}, volume = {6}, number = {1}, pages = {103585}, pmid = {39854205}, issn = {2666-1667}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; *Fecal Microbiota Transplantation/methods ; *Feces/microbiology ; Administration, Oral ; Mice, Inbred C57BL ; }, abstract = {Fecal microbiota transplantation (FMT) is clinically applied, while oral FMT (oral fecal gavage [OFG]) is preferred for experimental mice. Here, we present a protocol for OFG in antibiotic-pretreated mice, demonstrating the progressive, time-dependent evolution of the gut microbiota in the recipients. We describe steps for fecal sample collection and preparation procedures, oral gavage, and monitoring gut microbiota changes. This protocol serves as a general guide for reshaping the gut microbiota in recipient mice for various experimental applications. For complete details on the use and execution of this protocol, please refer to Yang et al.[1].}, } @article {pmid39854158, year = {2025}, author = {Lau, RI and Su, Q and Ng, SC}, title = {Long COVID and gut microbiome: insights into pathogenesis and therapeutics.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2457495}, pmid = {39854158}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *COVID-19/complications/microbiology/therapy ; Fecal Microbiota Transplantation ; *Dysbiosis/therapy/microbiology ; Probiotics/therapeutic use ; SARS-CoV-2/physiology ; Post-Acute COVID-19 Syndrome ; Prebiotics/administration & dosage ; }, abstract = {Post-acute coronavirus disease 2019 syndrome (PACS), following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19), is typically characterized by long-term debilitating symptoms affecting multiple organs and systems. Unfortunately, there is currently a lack of effective treatment strategies. Altered gut microbiome has been proposed as one of the plausible mechanisms involved in the pathogenesis of PACS; extensive studies have emerged to bridge the gap between the persistent symptoms and the dysbiosis of gut microbiome. Recent clinical trials have indicated that gut microbiome modulation using probiotics, prebiotics, and fecal microbiota transplantation (FMT) led to improvements in multiple symptoms related to PACS, including fatigue, memory loss, difficulty in concentration, gastrointestinal upset, and disturbances in sleep and mood. In this review, we highlight the latest evidence on the key microbial alterations observed in PACS, as well as the use of microbiome-based therapeutics in managing PACS symptoms. These novel findings altogether shed light on the treatment of PACS and other chronic conditions.}, } @article {pmid39851261, year = {2025}, author = {Zhao, X and Qiu, Y and Liang, L and Fu, X}, title = {Interkingdom signaling between gastrointestinal hormones and the gut microbiome.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2456592}, pmid = {39851261}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; Animals ; *Gastrointestinal Hormones/metabolism ; Dysbiosis/microbiology/metabolism ; Bacteria/metabolism/classification/genetics ; Fecal Microbiota Transplantation ; Signal Transduction ; Inflammatory Bowel Diseases/microbiology/metabolism/therapy ; Gastrointestinal Tract/microbiology/metabolism ; }, abstract = {The interplay between the gut microbiota and gastrointestinal hormones plays a pivotal role in the health of the host and the development of diseases. As a vital component of the intestinal microecosystem, the gut microbiota influences the synthesis and release of many gastrointestinal hormones through mechanisms such as modulating the intestinal environment, producing metabolites, impacting mucosal barriers, generating immune and inflammatory responses, and releasing neurotransmitters. Conversely, gastrointestinal hormones exert feedback regulation on the gut microbiota by modulating the intestinal environment, nutrient absorption and utilization, and the bacterial biological behavior and composition. The distributions of the gut microbiota and gastrointestinal hormones are anatomically intertwined, and close interactions between the gut microbiota and gastrointestinal hormones are crucial for maintaining gastrointestinal homeostasis. Interventions leveraging the interplay between the gut microbiota and gastrointestinal hormones have been employed in the clinical management of metabolic diseases and inflammatory bowel diseases, such as bariatric surgery and fecal microbiota transplantation, offering promising targets for the treatment of dysbiosis-related diseases.}, } @article {pmid39851236, year = {2025}, author = {Golob, JL and Hou, G and Swanson, BJ and Berinstein, JA and Bishu, S and Grasberger, H and Zataari, ME and Lee, A and Kao, JY and Kamada, N and Bishu, S}, title = {Inflammation-Induced Th17 Cells Synergize with the Inflammation-Trained Microbiota to Mediate Host Resiliency Against Intestinal Injury.}, journal = {Inflammatory bowel diseases}, volume = {31}, number = {4}, pages = {1082-1094}, doi = {10.1093/ibd/izae293}, pmid = {39851236}, issn = {1536-4844}, support = {R01 DK134486/DK/NIDDK NIH HHS/United States ; K08DK123403//the NIDDK/ ; }, mesh = {Animals ; *Th17 Cells/immunology ; Mice ; Mice, Inbred C57BL ; Citrobacter rodentium ; *Colitis/immunology/chemically induced/microbiology/pathology ; *Inflammation/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Dextran Sulfate/toxicity ; *Intestinal Mucosa/immunology/pathology/microbiology ; Disease Models, Animal ; Mice, Knockout ; Fecal Microbiota Transplantation ; *Enterobacteriaceae Infections/immunology ; *Dysbiosis/immunology/microbiology ; }, abstract = {BACKGROUND AND AIMS: Inflammation can generate pathogenic Th17 cells and cause an inflammatory dysbiosis. In the context of inflammatory bowel disease (IBD), these inflammatory Th17 cells and dysbiotic microbiota may perpetuate injury to intestinal epithelial cells. However, many models of IBD like T-cell transfer colitis and IL-10-/- mice rely on the absence of regulatory pathways, so it is difficult to tell if inflammation can also induce protective Th17 cells.

METHODS: We subjected C57BL6, RAG1-/-, or JH-/- mice to systemic or gastrointestinal (GI) Citrobacter rodentium (Cr). Mice were then subjected to 2.5% dextran sodium sulfate (DSS) to cause epithelial injury. Fecal microbiota transfer was performed by bedding transfer and co-housing. Flow cytometry, qPCR, and histology were used to assess mucosal and systemic immune responses, cytokines, and tissue inflammation. 16s sequencing was used to assess gut bacterial taxonomy.

RESULTS: Transient inflammation with GI but not systemic Cr was protective against subsequent intestinal injury. This was replicated with sequential DSS collectively indicating that transient inflammation provides tissue-specific protection. Inflammatory Th17 cells that have a tissue-resident memory (TRM) signature expanded in the intestine. Experiments with reconstituted RAG1-/-, JH-/- mice, and cell trafficking inhibitors showed that inflammation-induced Th17 cells were required for protection. Fecal microbiota transfer showed that the inflammation-trained microbiota was necessary for protection, likely by maintaining protective Th17 cells in situ.

CONCLUSION: Inflammation can generate protective Th17 cells that synergize with the inflammation-trained microbiota to provide host resiliency against subsequent injury, indicating that inflammation-induced Th17 TRM T cells are heterogenous and contain protective subsets.}, } @article {pmid39850178, year = {2024}, author = {Gandhi, DN and Pande, DN and Harikrishna, A and Advilkar, A and Basavan, I and Ansari, R}, title = {Beyond the Brain: Attention Deficit/Hyperactivity Disorder and the Gut-Brain Axis.}, journal = {Cureus}, volume = {16}, number = {12}, pages = {e76291}, pmid = {39850178}, issn = {2168-8184}, abstract = {Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental condition, predominantly affecting children, characterized by inattention, hyperactivity, and impulsivity. A growing body of evidence has highlighted the potential influence of the gut microbiota on the onset and presentation of ADHD symptoms. The gut microbiota, a diverse microbial ecosystem residing within the gastrointestinal tract, exerts multiple effects on systemic physiology, including immune modulation, metabolic regulation, and neuronal signalling. The bidirectional gut-brain axis serves as a conduit for communication between gut microbes and the central nervous system, implicating its disruption in neurodevelopmental disorders such as ADHD. This comprehensive literature review aims to shed light on how alterations in the gut microbiota influence the development and manifestation of ADHD symptoms. Examining potential mechanisms involving gut microbial metabolites and their impact on neurotransmitter modulation, neuro-endocrine signalling and neuroinflammation, we dissect the intricate interplay shaping ADHD pathology. Insights into these complex interactions hold promise for personalized therapeutic interventions aimed at modulating the gut microbiota to ameliorate ADHD symptoms. Discussions encompass dietary interventions, faecal microbiota-targeted therapies, and emerging probiotic approaches, underscoring their potential as adjunctive or alternative strategies in managing ADHD. Further research elucidating the precise mechanisms driving these interactions may pave the way for targeted and personalized interventions for individuals grappling with ADHD.}, } @article {pmid39848238, year = {2025}, author = {Szajewska, H}, title = {An Overview of Early-Life Gut Microbiota Modulation Strategies.}, journal = {Annals of nutrition & metabolism}, volume = {81}, number = {Suppl 1}, pages = {28-33}, doi = {10.1159/000541492}, pmid = {39848238}, issn = {1421-9697}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Breast Feeding ; Probiotics/therapeutic use/administration & dosage ; Milk, Human ; Infant, Newborn ; Infant ; Female ; Fecal Microbiota Transplantation ; Dysbiosis ; Infant Formula ; Dietary Supplements ; Infant, Premature ; Pregnancy ; Gastrointestinal Diseases/microbiology/prevention & control ; }, abstract = {BACKGROUND: The gut microbiota, or microbiome, is essential for human health. Early-life factors such as delivery mode, diet, and antibiotic use shape its composition, impacting both short- and long-term health outcomes. Dysbiosis, or alterations in the gut microbiota, is linked to conditions such as allergies, asthma, obesity, diabetes, inflammatory bowel disease, and necrotizing enterocolitis in preterm infants.

SUMMARY: This article reviews current strategies to influence the early-life gut microbiome and their potential health impacts. It also briefly summarizes guidelines on using biotics for gastrointestinal and allergic diseases in children. Key strategies include vaginal or fecal microbiota transplantation for cesarean-born infants, breastfeeding, and biotic-supplemented formulas. While vaginal microbial transfer and maternal fecal microbiota transplantation show short-term benefits, further research is needed to determine long-term safety and efficacy. Breast milk, rich in human milk oligosaccharides, promotes a healthy microbiota and offers protection against infections. Biotic-supplemented formulas can improve the gut microbiota in formula-fed infants and show clinical effects, though each biotic must be evaluated separately. Probiotics given as dietary supplements outside of infant formulas show promise for treating gastrointestinal disorders but require further investigation.}, } @article {pmid39845805, year = {2024}, author = {Shen, Y and Gao, Y and Yang, G and Zhao, Z and Zhao, Y and Gao, L and Li, S}, title = {Anti-colorectal cancer effect of total minor ginsenosides produced by lactobacilli transformation of major ginsenosides by inducing apoptosis and regulating gut microbiota.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1496346}, pmid = {39845805}, issn = {1663-9812}, abstract = {OBJECTIVE: Minor ginsenosides have demonstrated promising anticancer effects in previous reports. Total minor ginsenosides (TMG) were obtained through the fermentation of major ginsenosides with Lactiplantibacillus plantarum, and potential anticancer effects of TMGs on the mouse colon cancer cell line CT26.WT, in vitro and in vivo, were investigated.

MATERIALS AND METHODS: We employed the Cell Counting Kit-8 (CCK-8), TdT-mediated dUTP nick end labeling (TUNEL), and Western blot analysis in vitro to explore the anti-proliferative and pro-apoptotic functions of TMG in CT26.WT cells. In vivo, a xenograft model was established by subcutaneously injecting mice with CT26.WT cells and administering a dose of 100 mg/kg/day TMG to the tumor-bearing mice. The level of apoptosis and expression of various proteins in the tumor tissues were detected by immunohistochemistry and Western blot. High-throughput 16S rRNA sequencing was used to determine the alterations in the gut microbiota.

RESULTS: In vitro studies demonstrated that TMG significantly inhibited proliferation and promoted apoptosis in CT26.WT cells. Interestingly, TMG induced apoptosis in CT26.WT cells by affecting the Bax/Bcl-2/caspase-3 pathway. Furthermore, the result of the transplanted tumor model indicated that TMG substantially enhanced the activities of Bax and caspase-3, reduced the activity of Bcl-2, and suppressed the expression of Raf/MEK/ERK protein levels. Fecal analysis revealed that TMG reconstructed the gut microbiota in colorectal cancer-affected mice by augmenting the abundance of the advantageous bacterium Lactobacillus and decreasing the abundance of the harmful bacterium Proteus.

CONCLUSION: TMG can exhibit potent anti-colorectal cancer effects through diverse apoptotic mechanisms, with their mode of action closely related to the regulation of gut microbiota.}, } @article {pmid39845049, year = {2024}, author = {Wu, R and Mai, Z and Song, X and Zhao, W}, title = {Hotspots and research trends of gut microbiome in polycystic ovary syndrome: a bibliometric analysis (2012-2023).}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1524521}, pmid = {39845049}, issn = {1664-302X}, abstract = {INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common gynecological condition affecting individuals of reproductive age and is linked to the gut microbiome. This study aimed to identify the hotspots and research trends within the domain of the gut microbiome in PCOS through bibliometric analysis.

METHODS: Utilizing bibliometric techniques, we examined the literature on the gut microbiome in PCOS from the Web of Science Core Collection spanning the period from 2012 to 2023. Analytical tools such as CiteSpace, VOSviewer, and Bibliometric R packages were employed to evaluate various metrics, including countries/regions, institutions, authors, co-cited authors, authors' H-index, journals, co-references, and keywords.

RESULTS: A total of 191 publications were identified in the field of gut microbiome in PCOS, with an increase in annual publications from 2018 to 2023. People's Republic of China was the most productive country, followed by the United States of America (USA), India. Shanghai Jiao Tong University, Fudan University, and Beijing University of Chinese Medicine were the top three most publications institutions. Thackray VG was identified as the most prolific author, holding the highest H-index, while Liu R received the highest total number of citations. The journal "Frontiers in Endocrinology" published the most articles in this domain. The most frequently co-cited reference was authored by Qi XY. The analysis of keyword burst detection identified "bile acids" (2021-2023) as the leading frontier keyword. Additionally, "gut dysbiosis," "phenotypes," "adolescents," "metabolomics," "metabolites," "fecal microbiota transplantation," and "IL-22" have emerged as the primary keywords reflecting recent research trends.

CONCLUSION: This bibliometric analysis explores how the gut microbiome influences endocrine and metabolic disorders related to PCOS, emphasizing its role in the development of PCOS and treatments targeting the gut microbiome. The findings serve as a valuable resource for researchers, enabling them to identify critical hotspots and emerging areas of investigation in this field.}, } @article {pmid39844078, year = {2025}, author = {Fan, X and Li, J and Gao, Y and Li, L and Zhang, H and Bi, Z}, title = {The mechanism of enterogenous toxin methylmalonic acid aggravating calcium-phosphorus metabolic disorder in uremic rats by regulating the Wnt/β-catenin pathway.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {31}, number = {1}, pages = {19}, pmid = {39844078}, issn = {1528-3658}, mesh = {Animals ; *Uremia/metabolism/etiology/pathology ; Rats ; *Wnt Signaling Pathway/drug effects ; *Calcium/metabolism ; *Phosphorus/metabolism ; Male ; *Methylmalonic Acid/toxicity/metabolism ; Disease Models, Animal ; Podocytes/metabolism/drug effects ; Gastrointestinal Microbiome ; Apoptosis/drug effects ; Rats, Sprague-Dawley ; beta Catenin/metabolism ; }, abstract = {BACKGROUND: Uremia (UR) is caused by increased UR-related toxins in the bloodstream. We explored the mechanism of enterogenous toxin methylmalonic acid (MMA) in calcium-phosphorus metabolic disorder in UR rats via the Wnt/β-catenin pathway.

METHODS: The UR rat model was established by 5/6 nephrectomy. The fecal bacteria of UR rats were transplanted into Sham rats. Sham rats were injected with exogenous MMA or Salinomycin (SAL). Pathological changes in renal/colon tissues were analyzed. MMA concentration, levels of renal function indicators, serum inflammatory factors, Ca[2+]/P[3+], and parathyroid hormone, intestinal flora structure, fecal metabolic profile, intestinal permeability, and glomerular filtration rate (GFR) were assessed. Additionally, rat glomerular podocytes were cultured, with cell viability and apoptosis measured.

RESULTS: Intestinal flora richness and diversity in UR rats were decreased, along with unbalanced flora structure. Among the screened 133 secondary differential metabolites, the MMA concentration rose, showing the most significant difference. UR rat fecal transplantation caused elevated MMA concentration in the serum and renal tissues of Sham rats. The intestinal flora metabolite MMA or exogenous MMA promoted intestinal barrier impairment, increased intestinal permeability, induced glomerular podocyte loss, and reduced GFR, causing calcium-phosphorus metabolic disorder. The intestinal flora metabolite MMA or exogenous MMA induced inflammatory responses and facilitated glomerular podocyte apoptosis by activating the Wnt/β-catenin pathway, which could be counteracted by repressing the Wnt/β-catenin pathway.

CONCLUSIONS: Enterogenous toxin MMA impelled intestinal barrier impairment in UR rats, enhanced intestinal permeability, and activated the Wnt/β-catenin pathway to induce glomerular podocyte loss and reduce GFR, thus aggravating calcium-phosphorus metabolic disorder.}, } @article {pmid39843757, year = {2025}, author = {Pitashny, M and Kesten, I and Shlon, D and Hur, DB and Bar-Yoseph, H}, title = {The Future of Microbiome Therapeutics.}, journal = {Drugs}, volume = {85}, number = {2}, pages = {117-125}, pmid = {39843757}, issn = {1179-1950}, mesh = {Humans ; *Microbiota/drug effects ; Fecal Microbiota Transplantation/methods ; Phage Therapy/methods ; Probiotics/therapeutic use ; *Gastrointestinal Microbiome ; Synthetic Biology/methods ; Animals ; }, abstract = {The human microbiome exerts profound influence over various biological processes within the body. Unlike many host determinants, it represents a readily accessible target for manipulation to promote health benefits. However, existing commercial microbiome-directed products often exhibit low efficacy. Advancements in technology are paving the way for the development of novel microbiome therapeutics, across a wide range of indications. In this narrative review, we provide an overview of state-of-the-art technologies in late-stage development, examining their advantages and limitations. By covering a spectrum, from fecal-derived products to live biotherapeutics, phage therapy, and synthetic biology, we illuminate the path toward the future of microbiome therapeutics.}, } @article {pmid39840995, year = {2025}, author = {Hua, D and Yang, Q and Li, X and Zhou, X and Kang, Y and Zhao, Y and Wu, D and Zhang, Z and Li, B and Wang, X and Qi, X and Chen, Z and Cui, G and Hong, W}, title = {The combination of Clostridium butyricum and Akkermansia muciniphila mitigates DSS-induced colitis and attenuates colitis-associated tumorigenesis by modulating gut microbiota and reducing CD8[+] T cells in mice.}, journal = {mSystems}, volume = {10}, number = {2}, pages = {e0156724}, pmid = {39840995}, issn = {2379-5077}, support = {32160015,32170134,32460046//MOST | National Natural Science Foundation of China (NSFC)/ ; (2022)101//Excellent Young Talents Plan of Guizhou Medical University/ ; (2022-08)//Innovation and Entrepreneurship project for overseas talents in Guizhou/ ; (QJJ [2022] 019)//Guizhou Provincical Key Laboratory of Pathogen Biology/ ; (D20009)//111 Program/ ; ([2020]4101)//International sciencesn and technology cooperation base of Guizhou/ ; (GCC[2022] 036-1)//Guizhou province high-level innovation talent team and talent baseproject/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Clostridium butyricum ; Mice ; *Probiotics/pharmacology/administration & dosage ; *Colitis/chemically induced/microbiology/therapy/complications ; *CD8-Positive T-Lymphocytes/immunology ; Dextran Sulfate/toxicity ; Mice, Inbred C57BL ; Colorectal Neoplasms ; Disease Models, Animal ; Carcinogenesis/drug effects ; Male ; Akkermansia ; }, abstract = {UNLABELLED: The gut microbiota is closely associated with inflammatory bowel disease (IBD) and colorectal cancer (CRC). Probiotics such as Clostridium butyricum (CB) or Akkermansia muciniphila (AKK) have the potential to treat inflammatory bowel disease (IBD) or colorectal cancer (CRC). However, research on the combined therapeutic effects and immunomodulatory mechanisms of CB and AKK in treating IBD or CRC has never been studied. This study evaluates the potential of co-administration of CB and AKK in treating DSS/AOM-induced IBD and colitis-associated CRC. Our results indicate that compared to mono-administration, the co-administration of CB and AKK not only significantly alleviates symptoms such as weight loss, colon shortening, and increased Disease Activity Index in IBD mice but also regulates the gut microbiota composition and effectively suppresses colonic inflammatory responses. In the colitis-associated CRC mice model, a combination of CB and AKK significantly alleviates weight loss and markedly reduces inflammatory infiltration of macrophages and cytotoxic T lymphocytes (CTLs) in the colon, thereby regulating anti-tumor immunity and inhibiting the occurrence of inflammation-induced CRC. In addition, we found that the combined probiotic therapy of CB and AKK can enhance the sensitivity of colitis-associated CRC mice to the immune checkpoint inhibitor anti-mouse PD-L1 (aPD-L1), significantly improving the anti-tumor efficacy of immunotherapy and the survival rate of colitis-associated CRC mice. Furthermore, fecal microbiota transplantation therapy showed that transplanting feces from CRC mice treated with the co-administration of CB and AKK into other CRC mice alleviated the tumor loads in the colon and significantly extended their survival rate. Our study suggests that the combined use of two probiotics, CB and AKK, can not only alleviate chronic intestinal inflammation but also inhibit the progression to CRC. This may be a natural and relatively safe method to support the gut microbiota and enhance the host's immunity against cancer.

IMPORTANCE: Our study suggests that the combined administration of CB and AKK probiotics, as opposed to a single probiotic strain, holds considerable promise in preventing the advancement of IBD to CRC. This synergistic effect is attributed to the ability of this probiotic combination to more effectively modulate the gut microbiota, curb inflammatory reactions, bolster the efficacy of immunotherapeutic approaches, and optimize treatment results via fecal microbiota transplantation.}, } @article {pmid39840614, year = {2025}, author = {Liu, W and Wang, J and Yang, H and Li, C and Lan, W and Chen, T and Tang, Y}, title = {The Metabolite Indole-3-Acetic Acid of Bacteroides Ovatus Improves Atherosclerosis by Restoring the Polarisation Balance of M1/M2 Macrophages and Inhibiting Inflammation.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {11}, pages = {e2413010}, pmid = {39840614}, issn = {2198-3844}, support = {82360105//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 20232ACB206001//Natural Science Foundation of Jiangxi Province/ ; 20223BBG71010//Key Research and Development Program of Jiangxi Province/ ; 2024SSY07061//Jiangxi Province Key Laboratory of bioengineering drugs/ ; }, mesh = {*Atherosclerosis/metabolism/microbiology ; Humans ; *Indoleacetic Acids/metabolism/pharmacology ; *Macrophages/metabolism/drug effects ; *Gastrointestinal Microbiome/physiology/drug effects ; *Bacteroides/metabolism ; *Inflammation/metabolism ; Male ; Animals ; Female ; Mice ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Middle Aged ; }, abstract = {Emerging research has highlighted the significant role of the gut microbiota in atherosclerosis (AS), with microbiota-targeted interventions offering promising therapeutic potential. A central component of this process is gut-derived metabolites, which play a crucial role in mediating the distal functioning of the microbiota. In this study, a comprehensive microbiome-metabolite analysis using fecal and serum samples from patients with atherosclerotic cardiovascular disease and volunteers with risk factors for coronary heart disease and culture histology is performed, and identified the core strain Bacteroides ovatus (B. ovatus). Fecal microbiota transplantation experiments further demonstrated that the gut microbiota significantly influences AS progression, with B. ovatus alone exerting effects comparable to volunteer feces from volunteers. Notably, B. ovatus alleviated AS primarily by restoring the intestinal barrier and enhancing bile acid metabolism, particularly through the production of indole-3-acetic acid (IAA), a tryptophan-derived metabolite. IAA inhibited the TLR4/MyD88/NF-κB pathway in M1 macrophages, promoted M2 macrophage polarisation, and restored the M1/M2 polarisation balance, ultimately reducing aortic inflammation. These findings clarify the mechanistic interplay between the gut microbiota and AS, providing the first evidence that B. ovatus, a second-generation probiotic, can improve bile acid metabolism and reduce inflammation, offering a theoretical foundation for future AS therapeutic applications involving this strain.}, } @article {pmid39840031, year = {2024}, author = {Lim, MY and Hong, S and Nam, YD}, title = {Understanding the role of the gut microbiome in solid tumor responses to immune checkpoint inhibitors for personalized therapeutic strategies: a review.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1512683}, pmid = {39840031}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/drug effects ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Neoplasms/immunology/therapy/drug therapy/microbiology ; Precision Medicine/methods ; Immunotherapy/methods ; Animals ; Fecal Microbiota Transplantation ; Treatment Outcome ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Immunotherapy, especially immune checkpoint inhibitor (ICI) therapy, has yielded remarkable outcomes for some patients with solid cancers, but others do not respond to these treatments. Recent research has identified the gut microbiota as a key modulator of immune responses, suggesting that its composition is closely linked to responses to ICI therapy in cancer treatment. As a result, the gut microbiome is gaining attention as a potential biomarker for predicting individual responses to ICI therapy and as a target for enhancing treatment efficacy. In this review, we discuss key findings from human observational studies assessing the effect of antibiotic use prior to ICI therapy on outcomes and identifying specific gut bacteria associated with favorable and unfavorable responses. Moreover, we review studies investigating the possibility of patient outcome prediction using machine learning models based on gut microbiome data before starting ICI therapy and clinical trials exploring whether gut microbiota modulation, for example via fecal microbiota transplantation or live biotherapeutic products, can improve results of ICI therapy in patients with cancer. We also briefly discuss the mechanisms through which the gut microbial-derived products influence immunotherapy effectiveness. Further research is necessary to fully understand the complex interactions between the host, gut microbiota, and immunotherapy and to develop personalized strategies that optimize responses to ICI therapy.}, } @article {pmid39839105, year = {2024}, author = {Correa Lopes, B and Turck, J and Tolbert, MK and Giaretta, PR and Suchodolski, JS and Pilla, R}, title = {Prolonged storage reduces viability of Peptacetobacter (Clostridium) hiranonis and core intestinal bacteria in fecal microbiota transplantation preparations for dogs.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1502452}, pmid = {39839105}, issn = {1664-302X}, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) has been described useful as an adjunct treatment for chronic enteropathy in dogs. Different protocols can be used to prepare and store FMT preparations, however, the effect of these methods on microbial viability is unknown. We aimed (1) to assess the viability of several core intestinal bacterial species by qPCR and (2) to assess Peptacetobacter (Clostridium) hiranonis viability through culture to further characterize bacterial viability in different protocols for FMT preparations.

METHODS: Bacterial abundances were assessed in feces from six healthy dogs by qPCR after propidium monoazide (PMA-qPCR) treatment for selective quantitation of viable bacteria. Conservation methods tested included lyophilization (stored at 4°C and at -20°C) and freezing with glycerol-saline solution (12.5%) and without any cryoprotectant (stored at -20°C). Additionally, the abundance of P. hiranonis was quantified using bacterial culture.

RESULTS: Using PMA-qPCR, the viability of Faecalibacterium, Escherichia coli, Streptococcus, Blautia, Fusobacterium, and P. hiranonis was reduced in lyophilized fecal samples kept at 4°C and -20°C up to 6 months (p < 0.05). In frozen feces without cryoprotectant, only Streptococcus and E. coli were not significantly reduced for up to 3 months (p > 0.05). Lastly, no differences were observed in the viability of those species in glycerol-preserved samples up to 6 months (p > 0.05). When using culture to evaluate the viability of P. hiranonis, we observed that P. hiranonis abundance was lower in lyophilized samples kept at 4°C than -20°C; and P. hiranonis abundance was higher in glycerol-preserved samples for up to 6 months than in samples preserved without glycerol for up to 3 months. Moreover, the highest abundance of P. hiranonis was observed in glycerol-preserved feces. After 3 months, P. hiranonis was undetectable by culture in 83% (5/6) of the frozen samples without glycerol.

DISCUSSION: While the lyophilization procedure initially reduced P. hiranonis abundance, P. hiranonis viability was stable thereafter for up to 6 months at -20°C. The higher bacterial viability detected in fecal samples preserved with glycerol confirms the use of this cryoprotectant as a reliable method to keep bacteria alive in the presence of fecal matrix for FMT purposes.}, } @article {pmid39838262, year = {2025}, author = {Ye, J and Shi, R and Wu, X and Fan, H and Zhao, Y and Hu, X and Wang, L and Bo, X and Li, D and Ge, Y and Wang, D and Xia, B and Zhao, Z and Xiao, C and Zhao, B and Wang, Y and Liu, X}, title = {Stevioside mitigates metabolic dysregulation in offspring induced by maternal high-fat diet: the role of gut microbiota-driven thermogenesis.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2452241}, doi = {10.1080/19490976.2025.2452241}, pmid = {39838262}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Female ; Diet, High-Fat/adverse effects ; Mice ; Pregnancy ; *Thermogenesis/drug effects ; *Diterpenes, Kaurane/pharmacology/administration & dosage ; *Glucosides/administration & dosage/pharmacology ; Mice, Inbred C57BL ; Male ; Lipid Metabolism/drug effects ; Obesity ; Lactobacillus/drug effects ; *Prenatal Exposure Delayed Effects ; Dietary Supplements ; }, abstract = {Maternal obesity poses a significant threat to the metabolic profiles of offspring. Microorganisms acquired from the mother early in life critically affect the host's metabolic functions. Natural non-nutritive sweeteners, particularly stevioside (STV), play a crucial role in reducing obesity and affecting gut microbiota composition. Based on this, we hypothesized that maternal STV supplementation could improve the health of mothers and offspring by altering their gut microbiota. Our study found that maternal STV supplementation reduced obesity during pregnancy, decreased abnormal lipid accumulation in offspring mice caused by maternal obesity, and modified the gut microbiota of both dams and offspring, notably increasing the abundance of Lactobacillus apodemi (L. apodemi). Co-housing and fecal microbiota transplant experiments confirmed that gut microbiota mediated the effects of STV on metabolic disorders. Furthermore, treatment with L. apodemi alone replicated the beneficial effects of STV, which were associated with increased thermogenesis. In summary, maternal STV supplementation could alleviate lipid metabolic disorders in offspring by enhancing L. apodemi levels and promoting thermogenic activity, potentially involving changes in bile acid metabolism pathways.}, } @article {pmid39837364, year = {2025}, author = {Liu, H and Yang, S and Zhang, Q and Wang, S and Zhang, B and Xu, Y and Fu, X and Zhou, S and Zhang, P and Wang, H and Di, L and Xu, X and Xu, X and Liu, C and Yang, C and Wang, Y and Jiang, R}, title = {S-ketamine alleviates morphine-induced hyperalgesia via decreasing the gut Enterobacteriaceae levels: Comparison with R-ketamine.}, journal = {Neuroscience}, volume = {568}, number = {}, pages = {240-252}, doi = {10.1016/j.neuroscience.2025.01.022}, pmid = {39837364}, issn = {1873-7544}, mesh = {Animals ; *Morphine/toxicity ; *Ketamine/pharmacology/chemistry ; *Hyperalgesia/chemically induced/drug therapy/microbiology ; *Gastrointestinal Microbiome/drug effects ; Male ; Fecal Microbiota Transplantation ; *Enterobacteriaceae/drug effects ; Analgesics, Opioid ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; *Analgesics/pharmacology ; }, abstract = {BACKGROUND: Opioid-induced hyperalgesia (OIH) is a serious complication during the pain treatment. Ketamine has been commonly reported to treat OIH, but the mechanisms remain unclear. Gut microbiota is recently recognized as one of the important mechanisms underlying the occurrence and treatment of OIH. However, whether ketamine enantiomers could alleviate OIH through gut microbiota that still needs to be clarified.

METHODS: The OIH model was established by morphine injection for 3 consecutive days, followed by hierarchical clustering analysis of behavioral results into susceptible or resilient group. Broad-spectrum antibiotic cocktail (ABx) was used to eradicated the gut microbiota of mice. Subsequently, fecal microbiota transplantation (FMT) was performed. S- or R-ketamine was administered as pretreatment 30 min before morphine injection. Fecal samples were collected for 16S rRNA gene sequencing after completion of all behavioral tests.

RESULTS: Approximately 60% of the mice developed OIH after morphine exposure with abnormal locomotion and anxiety-like behaviors. Pseudo germ-free mice treated with ABx did not develop hyperalgesia, whereas pseudo germ-free mice that received fecal microbiota transplantation from OIH mice developed hyperalgesia. Interestingly, S-ketamine but not R-ketamine rescued mice from OIH. The principal co-ordinates analysis (PCoA) suggested that the distribution of gut microbiota differed among the groups. Importantly, levels of Enterobacteriaceae were increased in OIH susceptible group, while decreased after S-ketamine treatment.

CONCLUSION: S-ketamine but not R-ketamine was able to alleviate morphine-induced OIH, and this mechanism is probably related to decreasing the levels of gut Enterobacteriaceae.}, } @article {pmid39836853, year = {2024}, author = {Aristizábal, AM and Montaña, LP and Gutiérrez, J and Medina, D and Franco, AA and Manzi, E and Zapata, ÁD and Mosquera, W}, title = {Intra-mesenteric steroids for steroid-refractory graft-versus-host disease in pediatric patients: A safe option.}, journal = {Biomedica : revista del Instituto Nacional de Salud}, volume = {44}, number = {Sp. 2}, pages = {63-71}, pmid = {39836853}, issn = {2590-7379}, mesh = {Humans ; *Graft vs Host Disease/drug therapy/etiology/mortality ; Child ; Male ; Female ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Child, Preschool ; Adolescent ; *Methylprednisolone/administration & dosage/therapeutic use ; Retrospective Studies ; Drug Resistance ; Infant ; }, abstract = {INTRODUCTION: Graft-versus-host disease is a serious complication after hematopoietic stem cell transplantation and is a major cause of death post-transplantation. Approximately 50% of acute graft-versus-host disease patients do not respond to systemic steroids and their prognosis is poor regardless of the treatment. This study describes our experience with pediatric patients diagnosed with steroid-refractory graft-versus-host disease who received intra-mesenteric steroid treatment.

OBJECTIVE: To determine the outcomes of intra-mesenteric steroid use in the management of pediatric patients diagnosed with refractory graft-versus-host disease.

MATERIALS AND METHODS: The study included patients under 18 years old with allogeneic hematopoietic stem cell transplantation who underwent intra-mesenteric steroid injection for resistant gastrointestinal graft-versus-host disease between January, 2016, and December, 2021. Methylprednisolone was administered via intra-arterial injection through the celiac trunk and the superior and inferior mesenteric arteries.

RESULTS: We collected data on 21 patients: nine (90%) responded with a subjective decrease in fecal output and a reduction in bilirubin and transaminases. Seven patients required a second intra-mesenteric injection and presented a complete response in 85% of the cases. Only one patient experienced local complications after the procedure. Twelve patients (57%) died with one death due to acute graft-versus-host disease.

CONCLUSION: Reports in the adult population have shown an approximately 50% response rate with few complications, making it a second-line management standard. As far as we know, this is the largest pediatric cohort reported in Latin America. Our findings suggest that intra-mesenteric steroid administration for managing hepatic and gastrointestinal graftversus-host disease may be considered an early adjuvant treatment in patients with steroidrefractory graft-versus-host disease.}, } @article {pmid39836604, year = {2025}, author = {Wu, X and Wei, J and Ran, W and Liu, D and Yi, Y and Gong, M and Liu, X and Gong, Q and Li, H and Gao, J}, title = {The Gut Microbiota-Xanthurenic Acid-Aromatic Hydrocarbon Receptor Axis Mediates the Anticolitic Effects of Trilobatin.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {10}, pages = {e2412234}, pmid = {39836604}, issn = {2198-3844}, support = {GCC[2023]042//Guizhou Province/ ; HZ(2024)302//Science and technology project of Zunyi/ ; ZYSE-2022-02//Zunyi Medical University/ ; [2021]1350-037//Talent project of Guizhou platform/ ; 2022(2022JH2/101300058)//Liaoning Province/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Receptors, Aryl Hydrocarbon/metabolism ; Mice ; *Xanthurenates/metabolism ; *Colitis, Ulcerative/drug therapy/metabolism/microbiology ; Disease Models, Animal ; Male ; Mice, Inbred C57BL ; Dextran Sulfate ; }, abstract = {Current treatments for ulcerative colitis (UC) remain limited, highlighting the need for novel therapeutic strategies. Trilobatin (TLB), a naturally derived food additive, exhibits potential anti-inflammatory properties. In this study, a dextran sulfate sodium (DSS)-induced animal model is used to investigate the effects of TLB on UC. It is found TLB significantly alleviates DSS-induced UC in mice, as evidenced by a reduction in the disease activity index, an increase in colon length, improvement in histopathological lesions. Furthermore, TLB treatment results in a decrease in proinflammatory cytokines and an increase in anti-inflammatory cytokines. TLB mitigates UC by modulating the intestinal microbiota, particularly Akkermansia, which enhances tryptophan metabolism and upregulates the production of xanthurenic acid (XANA). To confirm the role of TLB-induced microbiota changes, experiments are performed with pseudogerm-free mice and fecal transplantation. It is also identified XANA as a key metabolite that mediates TLB's protective effects. Both TLB and XANA markedly activate the aromatic hydrocarbon receptor (AhR). Administration of an AhR antagonist abrogates their protective effects, thereby confirming the involvement of AhR in the underlying mechanism. In conclusion, the study reveals a novel mechanism through which TLB alleviates UC by correcting microbiota imbalances, regulating tryptophan metabolism, enhancing XANA production, and activating AhR.}, } @article {pmid39834471, year = {2024}, author = {Song, Y and Liu, S and Zhang, L and Zhao, W and Qin, Y and Liu, M}, title = {The effect of gut microbiome-targeted therapies in nonalcoholic fatty liver disease: a systematic review and network meta-analysis.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1470185}, pmid = {39834471}, issn = {2296-861X}, abstract = {BACKGROUND: The incidence of NAFLD is increasing. Preclinical evidences indicate that modulation of the gut microbiome could be a promising target in nonalcoholic fatty liver disease.

METHOD: A systematic review and network meta-analysis was conducted to compare the effect of probiotics, synbiotics, prebiotics, fecal microbiota transplant, and antibiotics on the liver-enzyme, metabolic effects and liver-specific in patients with NAFLD. The randomized controlled trails (RCTs), limited to English language were searched from database such as Pubmed, Embase, Web of science and Cochrane Library from inception to November 2024. Review Manager 5.3 was used to to draw a Cochrane bias risk. Inconsistency test and publication-bias were assessed by Stata 14.0. Random effect model was used to assemble direct and indirect evidences. The effects of the intervention were presented as mean differences with 95% confidence interval.

RESULTS: A total of 1921 patients from 37 RCTs were eventually included in our study. 23 RCTs evaluated probiotics, 10 RCTs evaluated synbiotics, 4 RCTs evaluated prebiotics, 3 RCTs evaluated FMT and one RCT evaluated antibiotics. Probiotics and synbiotics were associated with a significantly reduction in alanine aminotransferase [ALT, (MD: -5.09; 95%CI: -9.79, -0.39), (MD: -7.38, 95CI%: -11.94, -2.82)] and liver stiffness measurement by elastograph [LSM, (MD: -0.37;95%CI: -0.49, -0.25), (MD: -1.00;95%CI: -1.59, -0.41)]. In addition to, synbiotics was superior to probiotics in reducing LSM. Synbiotics was associated with a significant reduction of Controlled Attenuation Parameter [CAP, (MD: -39.34; 95%CI: -74.73, -3.95)]. Both probiotics and synbiotics were associated with a significant reduction of aspartate transaminase [AST, (MD: -7.81; 95%CI: -15.49, -0.12), (MD: -13.32; 95%CI: -23, -3.64)]. Probiotics and Allogenic FMT was associated with a significant reduction of Homeostatic Model Assessment for Insulin Resistance [HOMA-IR, (MD: -0.7, 95%CI: -1.26, -0.15), (MD: -1.8, 95%CI: -3.53, - 0.07)]. Probiotics was associated with a significant reduction of body mass index [BMI, MD: -1.84, 95%CI: -3.35, -0.33].

CONCLUSION: The supplement of synbiotics and probiotics maybe a promising way to improve liver-enzyme, LSM, and steatosis in patients with NAFLD. More randomized controlled trials are needed to determine the efficacy of FMT and antibiotics on NAFLD. And the incidence of adverse events of MTTs should be further explored.

https://www.crd.york.ac.uk/prospero/, CRD42023450093.}, } @article {pmid39829898, year = {2025}, author = {Ni, M and Fan, Y and Liu, Y and Li, Y and Qiao, W and Davey, LE and Zhang, XS and Ksiezarek, M and Mead, EA and Tourancheau, A and Jiang, W and Blaser, MJ and Valdivia, RH and Fang, G}, title = {Epigenetic phase variation in the gut microbiome enhances bacterial adaptation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39829898}, issn = {2692-8205}, support = {R35 GM139655/GM/NIGMS NIH HHS/United States ; }, abstract = {The human gut microbiome within the gastrointestinal tract continuously adapts to variations in diet, medications, and host physiology. A strategy for bacterial genetic adaptation is epigenetic phase variation (ePV) mediated by bacterial DNA methylation, which can regulate gene expression, enhance clonal heterogeneity, and enable a single bacterial strain to exhibit variable phenotypic states. Genome-wide and site-specific ePVs have been characterized in human pathogens' antigenic variation and virulence factor production. However, the role of ePV in facilitating adaptation within the human microbiome remains poorly understood. Here, we comprehensively cataloged genome-wide and site-specific ePV in human infant and adult gut microbiomes. First, using long-read metagenomic sequencing, we detected genome-wide ePV mediated by complex structural variations of DNA methyltransferases, highlighting those associated with antibiotics or fecal microbiota transplantation. Second, we analyzed a collection of public short-read metagenomic sequencing datasets, uncovering a great prevalence of genome-wide ePV in the human gut microbiome. Third, we quantitatively detected site-specific ePVs using single-molecule methylation analysis to identify dynamic variation associated with antibiotic treatment or probiotic engraftment. Finally, we performed an in-depth assessment of an Akkermansia muciniphila isolate from an infant, highlighting that ePVs can regulate gene expression and enhance the bacterial adaptive capacity by employing a bet-hedging strategy to increase tolerance to differing antibiotics. Our findings indicate that epigenetic modifications are a common strategy used by gut bacteria to adapt to the fluctuating environment.}, } @article {pmid39829204, year = {2025}, author = {Liu, C and Wong, PY and Barua, N and Li, B and Wong, HY and Zhang, N and Chow, SKH and Wong, SH and Yu, J and Ip, M and Cheung, WH and Duque, G and Brochhausen, C and Sung, JJY and Wong, RMY}, title = {From Clinical to Benchside: Lacticaseibacillus and Faecalibacterium Are Positively Associated With Muscle Health and Alleviate Age-Related Muscle Disorder.}, journal = {Aging cell}, volume = {24}, number = {5}, pages = {e14485}, pmid = {39829204}, issn = {1474-9726}, support = {C4032-21GF//Collaborative Research Fund, HKSAR Research Grants Council/ ; 14116223//General Research Fund, HKSAR Research Grants Council/ ; }, mesh = {Humans ; Animals ; Mice ; *Sarcopenia/microbiology/therapy ; *Gastrointestinal Microbiome ; Male ; Aged ; Female ; Fecal Microbiota Transplantation ; Probiotics ; Aging ; Lacticaseibacillus ; }, abstract = {Sarcopenia is an age-related muscle disorder that increases risks of adverse clinical outcomes, but its treatments are still limited. Gut microbiota is potentially associated with sarcopenia, and its role is still unclear. To investigate the role of gut microbiota in sarcopenia, we first compared gut microbiota and metabolites composition in old participants with or without sarcopenia. Fecal microbiota transplantation (FMT) from human donors to antibiotic-treated recipient mice was then performed. Specific probiotics and their mechanisms to treat aged mice were identified. Old people with sarcopenia had different microbial composition and metabolites, including Paraprevotella, Lachnospira, short-chain fatty acids, and purine. After FMT, mice receiving microbes from people with sarcopenia displayed lower muscle mass and strength compared with those receiving microbes from non-sarcopenic donors. Lacticaseibacillus rhamnosus (LR) and Faecalibacterium prausnitzii (FP) were positively related to muscle health of old people, and enhanced muscle mass and function of aged mice. Transcriptomics showed that genes related to tricarboxylic acid cycle (TCA) were enriched after treatments. Metabolic analysis showed increased substrates of TCA cycle in both LR and FP supernatants. Muscle mitochondria density, ATP content, NAD[+]/NADH, mitochondrial dynamics and biogenesis proteins, as well as colon tight junction proteins of aged mice were improved by both probiotics. LR and the combination of two probiotics also benefit intestinal immune health by reducing CD8[+] IFNγ[+] T cells. Gut microbiota dysbiosis is a pathogenesis of sarcopenia, and muscle-related probiotics could alleviate age-related muscle disorders mainly through mitochondria improvement. Further clinical translation is warranted.}, } @article {pmid39827989, year = {2025}, author = {Cheng, CK and Ye, L and Wang, Y and Wang, YL and Xia, Y and Wong, SH and Chen, S and Huang, Y}, title = {Exercised gut microbiota improves vascular and metabolic abnormalities in sedentary diabetic mice through gut‒vascular connection.}, journal = {Journal of sport and health science}, volume = {14}, number = {}, pages = {101026}, pmid = {39827989}, issn = {2213-2961}, abstract = {BACKGROUND: Exercise elicits cardiometabolic benefits, reducing the risks of cardiovascular diseases and type 2 diabetes. This study aimed to investigate the vascular and metabolic effects of gut microbiota from exercise-trained donors on sedentary mice with type 2 diabetes and the potential mechanism.

METHODS: Leptin receptor-deficient diabetic (db/db) and nondiabetic (db/m[+]) mice underwent running treadmill exercise for 8 weeks, during which fecal microbiota transplantation (FMT) was parallelly performed from exercise-trained to sedentary diabetic (db/db) mice. Endothelial function, glucose homeostasis, physical performance, and vascular signaling of recipient mice were assessed. Vascular and intestinal stresses, including inflammation, oxidative stress, and endoplasmic reticulum (ER) stress, were investigated. RNA sequencing analysis on mouse aortic and intestinal tissues was performed. Gut microbiota profiles of recipient mice were evaluated by metagenomic sequencing.

RESULTS: Chronic exercise improved vascular and metabolic abnormalities in donor mice. Likewise, FMT from exercised donors retarded body weight gain and slightly improved grip strength and rotarod performance in recipient mice. Exercise-associated FMT enhanced endothelial function in different arteries, suppressed vascular and intestinal stresses, and improved glucose homeostasis in recipient mice, with noted microRNA-181b upregulation in aortas and intestines. Altered gut microbiota profiles and gut-derived factors (e.g., short-chain fatty acids and glucagon-like peptide-1) as well as improved intestinal integrity shall contribute to the cardiometabolic benefits, implying a gut‒vascular connection.

CONCLUSION: This proof-of-concept study indicates that exercised microbiota confers cardiometabolic benefits on sedentary db/db mice, extending the beneficial mechanism of exercise through gut‒vascular communication. The findings open up new therapeutic opportunities for cardiometabolic diseases and shed light on the development of exercise mimetics by targeting the gut microbiota.}, } @article {pmid39827465, year = {2025}, author = {Zhang, Y and Hao, R and Chen, J and Huang, K and Li, S and Cao, H and Guan, X}, title = {Gut-Derived Ursodeoxycholic Acid from Saponins of Quinoa Regulated Colitis via Inhibiting the TLR4/NF-κB Pathway.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {4}, pages = {2415-2429}, doi = {10.1021/acs.jafc.4c09151}, pmid = {39827465}, issn = {1520-5118}, mesh = {*Toll-Like Receptor 4/genetics/metabolism ; Animals ; Gastrointestinal Microbiome/drug effects ; *NF-kappa B/genetics/metabolism ; Humans ; Mice ; *Saponins/administration & dosage/metabolism/chemistry ; *Chenopodium quinoa/chemistry/metabolism ; *Ursodeoxycholic Acid/administration & dosage/metabolism ; *Colitis/drug therapy/genetics/microbiology/metabolism ; Mice, Inbred C57BL ; Male ; Signal Transduction/drug effects ; Caco-2 Cells ; Bacteria/isolation & purification/classification/genetics/metabolism ; *Plant Extracts/administration & dosage ; }, abstract = {Alteration of the gut microbiota and its metabolites plays a key role in the development of inflammatory bowel disease (IBD). Here, we investigated the mechanism of saponins, a byproduct from quinoa (SQ) processing, in regulating IBD. SQ ameliorated gut microbiota dysbiosis revealed by 16S rRNA sequencing and improved colonic antioxidant activities and barrier integrity in dextran sulfate sodium (DSS)-treated mice. Broad-spectrum antibiotics further proved that the gut-protective effects of SQ were mediated by gut microbiota. Next, fecal microbiota transplantation (FMT) of SQ-induced gut microbiota/metabolites to inoculate DSS-treated mice alleviated colitis significantly. Untargeted metabolomics and lipidomics revealed that ursodeoxycholic acid (UDCA) was enriched as a microbial metabolite after SQ supplementation. UDCA was then found to attenuate DSS-induced colitis in vivo by targeting the TLR4/NF-κB pathway, which was also verified in a Caco-2 cell model treated with a TLR4 agonist/antagonist. Overall, our findings established that gut microbiota-UDCA-TLR4/NF-κB signaling plays a key role in mediating the protective effects of SQ.}, } @article {pmid39826789, year = {2025}, author = {Du, X and Liu, L and Yang, L and Zhang, Y and Dong, K and Li, Y and Chen, Y and Yang, Q and Zhu, X and Li, Q}, title = {Cumulative experience meets modern science: Remarkable effects of TongXieYaoFang formula on facilitating intestinal mucosal healing and secretory function.}, journal = {Journal of ethnopharmacology}, volume = {341}, number = {}, pages = {119370}, doi = {10.1016/j.jep.2025.119370}, pmid = {39826789}, issn = {1872-7573}, mesh = {Animals ; *Intestinal Mucosa/drug effects/pathology/metabolism ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Dextran Sulfate ; Mice ; Mice, Inbred C57BL ; *Wound Healing/drug effects ; Male ; Disease Models, Animal ; *Colitis, Ulcerative/drug therapy/chemically induced/pathology ; *Colitis/drug therapy/chemically induced/pathology ; Colon/drug effects/pathology ; }, abstract = {TongXieYaoFang (TXYF), a classical formula used in Traditional Chinese Medicine, is renowned for its efficacy in treating chronic abdominal pain and diarrhoea. Modern research suggests that fundamental relief from these symptoms depends on complete intestinal mucosal healing, which normalises gut secretory functions. Consensus between traditional and modern medical theories indicates that TXYF is particularly suitable for treating the remission phase of ulcerative colitis (UC). Unfortunately, its potential in the remission phase has not received sufficient attention, and its use has been largely limited to a supportive role during the acute phase.

AIM OF THE STUDY: This study aimed to elucidate the efficacy of TXYF in promoting intestinal mucosal healing and enhancing gut secretory function during the non-acute damage phase, as well as to identify the underlying mechanisms contributing to its effects.

METHODS: A mouse model of dextran sulphate sodium salt (DSS)-induced colitis was optimised to specifically evaluate the effects of TXYF on mucosal healing during the repair phase. The effects of TXYF on murine colon function were assessed by measuring faecal pellet count and water content, and further evaluated through immunohistochemical analyses. The underlying mechanisms of action of TXYF were elucidated using mouse intestinal organoid cultures, intestinal stem cell (ISCs) transplantation, immunofluorescence, and western blotting. Active components of TXYF were identified via LC-MS/MS analysis and integrated with network pharmacology for bioinformatics assessment.

RESULTS: TXYF significantly promoted mucosal healing, as reflected by reduced disease activity scores, increased colon length, enhanced epithelial proliferation, and decreased histological damage. Furthermore, TXYF enhanced the recovery of critical intestinal functions, including barrier integrity, absorption, secretion, and motility. Notably, the improvement in the secretory function was particularly pronounced. Mechanistically, these therapeutic effects were mediated by the upregulation of the Atonal homolog 1/SAM pointed domain containing ETS transcription factor/Mucin 2 pathway, which facilitates the differentiation and maturation of ISCs into goblet cells, thereby contributing to both mucosal repair and enhanced secretory function.

CONCLUSIONS: Our study demonstrated that TXYF significantly promotes intestinal mucosal healing and enhances secretory function. These findings offer a solid basis for exploring the potential applications of TXYF in UC management during the remission phase.}, } @article {pmid39826698, year = {2025}, author = {Song, Y and Cui, Y and Zhong, Y and Wang, Y and Zheng, X}, title = {Fecal microbiota transplantation combined with inulin promotes the development and function of early immune organs in chicks.}, journal = {Journal of biotechnology}, volume = {399}, number = {}, pages = {81-90}, doi = {10.1016/j.jbiotec.2025.01.012}, pmid = {39826698}, issn = {1873-4863}, mesh = {Animals ; *Inulin/pharmacology ; *Chickens/immunology/growth & development ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; }, abstract = {Modern management of chicks hinders the vertical transmission of intestinal microbiota, which is closely related to immunity. Inulin is a substrate that can be utilized by the microbiota. This study aimed to determine whether fecal microbiota transplantation (FMT) combined with inulin played a "1 + 1 > 2" role in enhancing the development and function of immune organs. Chicks were treated with 1 % inulin and/or fecal microbiota suspension on days 1-6. The growth performance, immune organ development, and immune indicators were evaluated on days 7, 14, and 21. Results showed that the combination of FMT and inulin significantly increased the immune organ index on day 7 and promoted the morphological structure and the expression of proliferating cell nuclear antigen (PCNA) in immune organs on days 7, 14, and 21. Each treatment increased the gene expression of interferon-gamma (IFN-γ), interleukin-4 (IL-4), interleukin-2 (IL-2), B cell-activating factor receptor (BAFFR), B cell linker (BLNK), C-X-C Motif Chemokine Ligand 12 (CXCL12), C-X-C Motif Chemokine Receptor 4 (CXCR4), and Biotin (Bu-1) to varying degrees. FMT combined with inulin significantly increased the expression of IgA-positive cells on days 7 and 14. In conclusion, the synergistic effect of FMT and inulin had beneficial impacts on the development and function of immune organs.}, } @article {pmid39826450, year = {2025}, author = {Zhu, Z and Zuo, S and Zhu, Z and Wang, C and Du, Y and Chen, F}, title = {THSWD upregulates the LTF/AMPK/mTOR/Becn1 axis and promotes lysosomal autophagy in hepatocellular carcinoma cells by regulating gut flora and metabolic reprogramming.}, journal = {International immunopharmacology}, volume = {148}, number = {}, pages = {114091}, doi = {10.1016/j.intimp.2025.114091}, pmid = {39826450}, issn = {1878-1705}, mesh = {*Carcinoma, Hepatocellular/drug therapy/pathology/metabolism ; *Liver Neoplasms/drug therapy/pathology/metabolism ; Animals ; *Gastrointestinal Microbiome/drug effects ; Humans ; TOR Serine-Threonine Kinases/metabolism ; Autophagy/drug effects ; AMP-Activated Protein Kinases/metabolism ; Mice ; Beclin-1/metabolism ; Lysosomes/metabolism/drug effects ; Signal Transduction/drug effects ; Cell Line, Tumor ; Male ; Up-Regulation ; Apoptosis/drug effects ; Metabolic Reprogramming ; }, abstract = {THSWD has the effect of reducing inflammation, improving microcirculation, and regulating immune status in patients with hepatocellular carcinoma. Regardless of its clear therapeutic effect, the underlying mechanism of action against hepatocellular carcinoma is not clear. To identify critical gut microbiota and its associated metabolites related to THSWD inhibition against hepatocellular carcinoma progression, we assessed the microbe-dependent anti-hepatocellular carcinoma effects of THSWD through 16 s rRNA gene sequencing, fecal microbial transplantation and antibiotic treatment. Metabolic analyses, transcriptomic analyses, and molecular experiments were performed to explore how THSWD modulates the gut microbiota against hepatocellular carcinoma progression. As confirmed by in vivo and in vitro assays, THSWD reduced tumour growth rate and promoted apoptosis in hepatocellular carcinoma cells in hepatocellular carcinoma model mice, and liver and kidney indexes were detected and confirmed the safety of THSWD. Transcriptomic analysis revealed that the targets of THSWD were significantly enriched in multiple lysosomal autophagy signalling pathways, suggesting that lysosomal autophagy is probably associated with THSWD's therapeutic effect. Based on the integrated data analysis, THSWD delays hepatocellular carcinoma progression by increasing the intestinal microbiota Duncaniella and augmenting the metabolite glabrol, and the joint analysis of metabolic and genomic data suggests that this metabolite is associated with lysosomal autophagy, and cellular experiments confirmed that the The differential metabolite glabrol induces apoptosis in hepatocellular carcinoma cells by triggering the lysosomal autophagy-mediated apoptosis signalling pathway. Supplementation with glabrol metabolites up regulates the LTF/AMPK/mTOR/Beclin1 axis and promotes hepatocellular carcinoma cells with lysosomal autophagy and induced apoptosis in hepatocellular carcinoma cells.}, } @article {pmid39826104, year = {2025}, author = {Lin, A and Jiang, A and Huang, L and Li, Y and Zhang, C and Zhu, L and Mou, W and Liu, Z and Zhang, J and Cheng, Q and Wei, T and Luo, P}, title = {From chaos to order: optimizing fecal microbiota transplantation for enhanced immune checkpoint inhibitors efficacy.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2452277}, doi = {10.1080/19490976.2025.2452277}, pmid = {39826104}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Immune Checkpoint Inhibitors/therapeutic use ; *Gastrointestinal Microbiome ; *Neoplasms/therapy/immunology/microbiology ; Animals ; Tumor Microenvironment ; Immunotherapy/methods ; Treatment Outcome ; }, abstract = {The integration of fecal microbiota transplantation (FMT) with immune checkpoint inhibitors (ICIs) presents a promising approach for enhancing cancer treatment efficacy and overcoming therapeutic resistance. This review critically examines the controversial effects of FMT on ICIs outcomes and elucidates the underlying mechanisms. We investigate how FMT modulates gut microbiota composition, microbial metabolite profiles, and the tumor microenvironment, thereby influencing ICIs effectiveness. Key factors influencing FMT efficacy, including donor selection criteria, recipient characteristics, and administration protocols, are comprehensively discussed. The review delineates strategies for optimizing FMT formulations and systematically monitoring post-transplant microbiome dynamics. Through a comprehensive synthesis of evidence from clinical trials and preclinical studies, we elucidate the potential benefits and challenges of combining FMT with ICIs across diverse cancer types. While some studies report improved outcomes, others indicate no benefit or potential adverse effects, emphasizing the complexity of host-microbiome interactions in cancer immunotherapy. We outline critical research directions, encompassing the need for large-scale, multi-center randomized controlled trials, in-depth microbial ecology studies, and the integration of multi-omics approaches with artificial intelligence. Regulatory and ethical challenges are critically addressed, underscoring the imperative for standardized protocols and rigorous long-term safety assessments. This comprehensive review seeks to guide future research endeavors and clinical applications of FMT-ICIs combination therapy, with the potential to improve cancer patient outcomes while ensuring both safety and efficacy. As this rapidly evolving field advances, maintaining a judicious balance between openness to innovation and cautious scrutiny is crucial for realizing the full potential of microbiome modulation in cancer immunotherapy.}, } @article {pmid39825784, year = {2025}, author = {Zhang, R and Sun, X and Lu, H and Zhang, X and Zhang, M and Ji, X and Yu, X and Tang, C and Wu, Z and Mao, Y and Zhu, J and Ji, M and Yang, Z}, title = {Akkermansia muciniphila Mediated the Preventive Effect of Disulfiram on Acute Liver Injury via PI3K/Akt Pathway.}, journal = {Microbial biotechnology}, volume = {18}, number = {1}, pages = {e70083}, pmid = {39825784}, issn = {1751-7915}, support = {2024YQFH05//"YiQi''funding project/ ; }, mesh = {Gastrointestinal Microbiome/drug effects ; Animals ; *Proto-Oncogene Proteins c-akt/metabolism ; *Phosphatidylinositol 3-Kinases/metabolism ; *Chemical and Drug Induced Liver Injury/prevention & control ; *Disulfiram/pharmacology/therapeutic use ; Signal Transduction/drug effects ; Male ; Mice ; RNA, Ribosomal, 16S/genetics ; Akkermansia ; Acetaminophen/adverse effects ; Fecal Microbiota Transplantation ; Hepatocytes/drug effects ; Apoptosis/drug effects ; Disease Models, Animal ; }, abstract = {Acetaminophen induced acute liver injury (ALI) has a high incidence and is a serious medical problem, but there is a lack of effective treatment. The enterohepatic axis is one of the targets of recent attention due to its important role in liver diseases. Disulfiram (DSF) is a multitarget drug that has been proven to play a role in a variety of liver diseases and can affect intestinal flora, but whether it can alleviate ALI is not clear. We utilised bacterial 16S rRNA gene profiling, antimicrobial treatments, and faecal microbiota transplantation tests to explore whether DSF therapy for ALI is dependent on gut microbiota. Our findings indicate that DSF primarily restores intestinal microbiome balance by modulating the abundance of Akkermansia muciniphila (A. muciniphila), leading to significant alleviation of ALI symptoms in a gut microbiota dependent manner. We also found that A. muciniphila can promote the activation of PI3K/Akt pathway, correct the Bcl-2/Bax ratio, and further inhibit hepatocyte apoptosis. In conclusion, DSF ameliorates ALI by modulating the intestinal microbiome and activating the PI3K/AKT pathway through A. muciniphila.}, } @article {pmid39824679, year = {2024}, author = {Elyas, S and Barata, P and Vaishampayan, U}, title = {Clinical Applications of Microbiome in Renal Cell Carcinoma.}, journal = {European urology focus}, volume = {10}, number = {6}, pages = {898-901}, doi = {10.1016/j.euf.2024.12.006}, pmid = {39824679}, issn = {2405-4569}, mesh = {Humans ; *Carcinoma, Renal Cell/therapy/microbiology ; *Kidney Neoplasms/therapy/microbiology ; *Gastrointestinal Microbiome/drug effects ; Probiotics/therapeutic use ; Immune Checkpoint Inhibitors/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics ; }, abstract = {Advancements in microbiome research reveal its impact on cancer treatment outcomes, particularly in renal cell carcinoma (RCC). While immune checkpoint inhibitors (ICIs) have improved survival in metastatic RCC, composition of the gut microbiome has the potential to influence their efficacy. Antibiotic-induced microbiome disruptions correlate with diminished outcomes, while strains such as Akkermansia muciniphila, Clostridium butyricum, and others enhance immune responses and progression-free survival. Some prebiotics such as inulin gel can alter the gut flora to overcome the resistant strains occurring in response to immune therapy. This mini-review explores microbiome-targeted interventions, such as pre/probiotics and fecal microbiota transplantation, for overcoming ICI resistance. Although promising, prospective randomized trials are needed to standardize clinical applications and optimize microbiome-targeted treatments. The standard use of gut-modulating therapy cannot be recommended at present outside of clinical trials. A double-blind placebo-controlled randomized trial of ICI ± gut modulating therapy is being planned in frontline therapy of advanced RCC (BIOFRONT trial by the Southwest Oncology Group).}, } @article {pmid39821840, year = {2025}, author = {Vinterberg, JE and Oddsdottir, J and Nye, M and Pinton, P}, title = {Management of Recurrent Clostridioides difficile Infection (rCDI): A Systematic Literature Review to Assess the Feasibility of Indirect Treatment Comparison (ITC).}, journal = {Infectious diseases and therapy}, volume = {14}, number = {2}, pages = {327-355}, pmid = {39821840}, issn = {2193-8229}, abstract = {Recurrent Clostridioides difficile infection (rCDI) is a major cause of increased morbidity, mortality, and healthcare costs. Fecal-microbiota-based therapies are recommended for rCDI on completion of standard-of-care (SoC) antibiotics to prevent further recurrence: these therapies include conventional fecal-microbiota transplantation and the US Food and Drug Administration-approved therapies REBYOTA® (RBL) and VOWST Oral Spores™ (VOS). As an alternative to microbiota-based therapies, bezlotoxumab, a monoclonal antibody, is used as adjuvant to SoC antibiotics to prevent rCDI. There are no head-to-head clinical trials comparing different microbiota-based therapies or bezlotoxumab for rCDI. To address this gap, we conducted a systematic literature review to identify clinical trials on rCDI treatments and assess the feasibility of using them to conduct an indirect treatment comparison (ITC). The feasibility analysis determined that trial heterogeneity, particularly relating to inclusion criteria, may significantly compromise ITC and prevent cross-trial comparisons. Our analysis underlines the need to adopt standardized protocols to ensure comparability across trials.}, } @article {pmid39821715, year = {2025}, author = {Berry, P and Khanna, S}, title = {The evolving landscape of live biotherapeutics in the treatment of Clostridioides difficile infection.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {44}, number = {2}, pages = {129-141}, pmid = {39821715}, issn = {0975-0711}, mesh = {Humans ; *Clostridium Infections/therapy/epidemiology/microbiology ; *Fecal Microbiota Transplantation/methods ; *Biological Therapy/methods ; *Clostridioides difficile ; Anti-Bacterial Agents/therapeutic use ; Gastrointestinal Microbiome ; Recurrence ; Treatment Outcome ; }, abstract = {Clostridioides difficile (C. difficile) infection (CDI) is common after antibiotic exposure and presents significant morbidity, mortality and healthcare costs worldwide. The rising incidence of recurrent CDI, driven by hypervirulent strains, widespread antibiotic use and increased community transmission, has led to an urgent need for novel therapeutic strategies. Conventional antibiotic treatments, although effective, face limitations due to rising antibiotic resistance and high recurrence rates, which can reach up to 60% after multiple infections. This has prompted exploration of alternative therapies such as fecal microbiota-based therapies, including fecal microbiota transplantation (FMT) and live biotherapeutics (LBPs), which demonstrate superior efficacy in preventing recurrence. They are aimed at restoring the gut microbiota. Fecal microbiota, live-jslm and fecal microbiota spores, live-brpk have been approved by the U.S. Food and Drug Administration in individuals aged 18 years or older for recurrent CDI after standard antimicrobial treatment. They have demonstrated high efficacy and a favorable safety profile in clinical trials. Another LBP under study includes VE-303, which is not derived from human donor stool. This review provides a comprehensive overview of the current therapeutic landscape for CDI, including its epidemiology, pathophysiology, risk factors, diagnostic modalities and treatment strategies. The review delves into the emerging role of live biotherapeutics, with a particular focus on fecal microbiota-based therapies. We explore their development, mechanisms of action, clinical applications and potential to revolutionize CDI management.}, } @article {pmid39821305, year = {2025}, author = {Shi, L and Duan, Y and Fang, N and Zhang, N and Yan, S and Wang, K and Hou, T and Wang, Z and Jiang, X and Gao, Q and Zhang, S and Li, Y and Zhang, Y and Gong, Y}, title = {Lactobacillus gasseri prevents ibrutinib-associated atrial fibrillation through butyrate.}, journal = {Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology}, volume = {27}, number = {2}, pages = {}, pmid = {39821305}, issn = {1532-2092}, support = {HMUMIF-22001//HMU Marshal Initiative Funding/ ; No. 81974024, No. 82200413, and No. 82300430//National Natural Science Foundation of China/ ; HYD2020J00001//First Affiliated Hospital of Harbin Medical University/ ; HMUMIF-22001//Heilongjiang Province 'Jiebang guashuai' Science and Technology Research/ ; //Excellent Young Medical Talents Training Fund/ ; }, mesh = {Animals ; Adenine/analogs & derivatives ; *Atrial Fibrillation/prevention & control/chemically induced/microbiology/physiopathology/metabolism ; *Gastrointestinal Microbiome/drug effects ; Piperidines ; Disease Models, Animal ; Male ; *Butyrates/pharmacology/metabolism ; *Lactobacillus gasseri/growth & development/metabolism ; Dysbiosis ; Fecal Microbiota Transplantation ; *Pyrazoles ; *Pyrimidines ; Rats, Sprague-Dawley ; Rats ; *Protein Kinase Inhibitors ; Reactive Oxygen Species/metabolism ; Heart Rate/drug effects ; Heart Atria/physiopathology/drug effects/metabolism ; }, abstract = {BACKGROUND: Ibrutinib, a widely used anti-cancer drug, is known to significantly increase the susceptibility to atrial fibrillation (AF). While it is recognized that drugs can reshape the gut microbiota, influencing both therapeutic effectiveness and adverse events, the role of gut microbiota in ibrutinib-induced AF remains largely unexplored.

METHOD: Utilizing 16S rRNA gene sequencing, faecal microbiota transplantation, metabonomics, electrophysiological examination, and molecular biology methodologies, we sought to validate the hypothesis that gut microbiota dysbiosis promotes ibrutinib-associated AF and to elucidate the underlying mechanisms.

RESULT: We found that ibrutinib administration pre-disposes rats to AF. Interestingly, ibrutinib-associated microbial transplantation conferred increased susceptibility to AF in rats. Notably, ibrutinib induced a significantly decrease in the abundance of Lactobacillus gasseri (L. gasseri), and oral supplementation of L. gasseri or its metabolite, butyrate (BA), effectively prevented rats from ibrutinib-induced AF. Mechanistically, BA inhibits the generation of reactive oxygen species, thereby ameliorating atrial structural remodelling. Furthermore, we demonstrated that ibrutinib inhibited the growth of L. gasseri by disrupting the intestinal barrier integrity.

CONCLUSION: Collectively, our findings provide compelling experimental evidence supporting the potential efficacy of targeting gut microbes in preventing ibrutinib-associated AF, opening new avenues for therapeutic interventions.}, } @article {pmid39816955, year = {2025}, author = {Wang, Q and Ji, J and Xiao, S and Wang, J and Yan, X and Fang, L}, title = {Explore Alteration of Lung and Gut Microbiota in a Murine Model of OVA-Induced Asthma Treated by CpG Oligodeoxynucleotides.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {445-461}, pmid = {39816955}, issn = {1178-7031}, abstract = {AIM: We sought to investigate the impact of CpG oligodeoxynucleotides (CpG-ODN) administration on the lung and gut microbiota in asthmatic mice, specifically focusing on changes in composition, diversity, and abundance, and to elucidate the microbial mechanisms underlying the therapeutic effects of CpG-ODN and identify potential beneficial bacteria indicative of its efficacy.

METHODS: HE staining were used to analyze inflammation in lung, colon and small intestine tissues. High-throughput sequencing technology targeting 16S rRNA was employed to analyze the composition, diversity, and correlation of microbiome in the lung, colon and small intestine of control, model and CpG-ODN administration groups.

RESULTS: (1) Histopathologically, both lung and intestinal tissue in asthmatic mice exhibited significant structural damage and inflammatory response, whereas the structure of both lung and intestinal tissue approached normal levels, accompanied by a notable improvement in the inflammatory response after CpG-ODN treatment. (2) In the specific microbiota composition analysis, bacterial dysbiosis observed in the asthmatic mice, accompanied by enrichment of Proteobacteria found to cause lung and intestinal epithelial damage and inflammatory reaction. After CpG-ODN administration, bacterial dysbiosis was improved, and a notable enrichment of beneficial bacteria, indicating a novel microecology. Meanwhile Oscillospira and Clostridium were identified as two biomarkers of the CpG-ODN treatment. (3) Heatmap analysis revealed significant correlations among lung, small intestine, and colon microbiota.

CONCLUSION: CpG-ODN treatment can ameliorate OVA-induced asthma in mice. One side, preserving the structural integrity of the lung and intestine, s