@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.},
}

Humans
*Gastrointestinal Microbiome/immunology
*Enteritis/immunology/metabolism/microbiology/therapy
Animals
Immunomodulation
Bile Acids and Salts/metabolism
Fatty Acids, Volatile/metabolism
Probiotics

@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.},
}

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

@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.},
}

Humans
*Carcinoma, Hepatocellular/therapy/microbiology/immunology/metabolism
*Liver Neoplasms/therapy/microbiology/immunology/metabolism
*Bacteria/metabolism
Tumor Microenvironment/immunology
Animals

@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.},
}

Humans
*Gastrointestinal Microbiome/genetics
*Epigenome/genetics
*Psychophysiologic Disorders/genetics/microbiology
Animals
*Epigenesis, Genetic

@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.},
}

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

@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.},
}

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

@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.},
}

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

@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.},
}

*Gastrointestinal Microbiome/drug effects
Humans
Animals
Probiotics
*Bacteria/drug effects/metabolism/classification/genetics
Fecal Microbiota Transplantation
Pharmaceutical Preparations/metabolism
Prebiotics
Biotransformation

@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.},
}

*Fecal Microbiota Transplantation/veterinary
Animals
*Intestinal Diseases/therapy/veterinary
*Gastrointestinal Microbiome
Chronic Disease

@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.},
}

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

@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.},
}

*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

@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.},
}

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

@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.},
}

Humans
*Breast Neoplasms/therapy/microbiology/diagnosis
*Gastrointestinal Microbiome/physiology
Female
*Biomarkers, Tumor
Dysbiosis/microbiology
Probiotics/therapeutic use
Fecal Microbiota Transplantation

@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.},
}

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

@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.},
}

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

@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.},
}

Humans
Retrospective Studies
*Pelvic Floor/surgery
*Fascia/transplantation
*Rectal Prolapse/surgery
Female
Treatment Outcome
Male
Laparoscopy
Middle Aged
Aged
Adult
Quality of Life

@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.},
}

Humans
*Constipation/therapy
Chronic Disease
Fecal Microbiota Transplantation

@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.},
}

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

@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.},
}

*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

@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.},
}

*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

@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.},
}

Humans
*Dermatitis, Atopic/therapy/microbiology/immunology
*Gastrointestinal Microbiome/immunology
*Skin/microbiology/immunology
*Dysbiosis/immunology/therapy
Probiotics/therapeutic use
Animals
Fecal Microbiota Transplantation

@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.},
}

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

@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.},
}

Humans
*Fecal Microbiota Transplantation/methods
Female
Adult
*Gastrointestinal Microbiome
*Multiple Sclerosis/therapy/microbiology
Treatment Outcome
Capsules
Dysbiosis/therapy

@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.},
}

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

@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.},
}

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

@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.},
}

Humans
*Diabetes Mellitus, Type 2/microbiology/metabolism/therapy
*Gastrointestinal Microbiome
Probiotics/therapeutic use
Dysbiosis/microbiology
Animals
Fecal Microbiota Transplantation
Prebiotics

@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.},
}

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

@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.},
}

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

@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.},
}