@article {pmid41136355,
year = {2025},
author = {Chen, D and Yang, X and Jiao, D and Chen, X and Xiao, W and Zheng, J and Li, YX and Bao, C and Li, Y and Xu, B and Yuan, M},
title = {Electroacupuncture ameliorates Autism Spectrum Disorder via modulating the gut-brain axis depending on the integrity of vagus nerve.},
journal = {Translational psychiatry},
volume = {15},
number = {1},
pages = {428},
pmid = {41136355},
issn = {2158-3188},
mesh = {Animals ; *Autism Spectrum Disorder/therapy/chemically induced ; *Electroacupuncture ; *Gastrointestinal Microbiome/physiology ; Mice ; *Vagus Nerve/physiopathology ; Disease Models, Animal ; Male ; Microglia/metabolism ; Female ; *Brain-Gut Axis/physiology ; Behavior, Animal/physiology ; Mice, Inbred C57BL ; Brain ; Fecal Microbiota Transplantation ; },
abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by behavioral and neurological abnormalities. Numerous pieces of evidence indicate a strong association between ASD and neuroinflammation mediated by gut microbiota and microglial activation. Previous studies have shown that the therapeutic effects of an acupuncture protocol targeting the bacteria-gut-brain axis in a well-established ASD mouse model induced by prenatal exposure to valproic acid (VPA). We demonstrated that electroacupuncture significantly alleviates behavioral symptoms in VPA model. However, the precise mechanisms remain insufficiently elucidated. In this study, we confirmed that electroacupuncture markedly improved behavioral symptoms in ASD mice. We conducted gut microbiota transplantation from electroacupuncture-treated mice to untreated ASD mice, improving behavioral outcomes in untreated ASD mice. Conversely, by transplanting gut microbiota from ASD mice into electroacupuncture-treated mice, we successfully mitigated the beneficial behavioral effects of acupuncture. We analyzed inflammatory markers in the microglial activation from cerebral cortex and hippocampus tissues, revealing that acupuncture exerts robust anti-neuroinflammatory effects in ASD mice. To further validate the mechanism, we performed vagotomy in ASD mice, which abolished the therapeutic benefits of acupuncture. Our findings establish that the behavioral improvements observed in ASD mice are intricately linked to the diversity and abundance of gut microbiota. Furthermore, regulatory effects of electroacupuncture on ASD behaviors are mediated via bacteria-gut-brain axis, dependent on intact vagus nerve signaling. This study provides compelling evidence for the potential of acupuncture to modulate central neuroinflammation through vagus nerve-mediated gut microbiota regulation, offering novel avenue into its therapeutic application for neurodevelopmental disorders such as ASD.},
}

Animals
*Autism Spectrum Disorder/therapy/chemically induced
*Electroacupuncture
*Gastrointestinal Microbiome/physiology
Mice
*Vagus Nerve/physiopathology
Disease Models, Animal
Male
Microglia/metabolism
Female
*Brain-Gut Axis/physiology
Behavior, Animal/physiology
Mice, Inbred C57BL
Brain
Fecal Microbiota Transplantation

@article {pmid41133518,
year = {2025},
author = {Abdullah, IA and Khan, S and Hassan, FE},
title = {Gut-Brain Axis and Perioperative Gut Microbiome in Postoperative Cognitive Dysfunction: Implications for Neurosurgical Patients.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {13},
number = {4},
pages = {},
doi = {10.3390/medsci13040236},
pmid = {41133518},
issn = {2076-3271},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Postoperative Cognitive Complications/microbiology/etiology/prevention & control ; *Brain ; *Neurosurgical Procedures/adverse effects ; Dysbiosis ; Animals ; Probiotics/therapeutic use ; },
abstract = {Background: Postoperative cognitive dysfunction (POCD) is a common postoperative condition after neurosurgery, and in patients of advancing age, with far-reaching implications for recovery and quality of life. Current evidence points to the gut-brain axis as the main mechanism for the regulation of perioperative neuroinflammation and cognition. Objective: The aim of this review is to consolidate the existing evidence for perioperative gut microbiome dysbiosis in POCD, specifically in neurosurgical patients. Methods: A review of preclinical and clinical evidence on the gut microbiome, surgical stress, and cognitive recovery was conducted. Both mechanistic and therapeutic evidence were examined. Results: Surgery and anesthesia enhance gut microbial diversity, intestinal permeability, and systemic inflammation, thereby compromising neuroplasticity and the integrity of blood-brain barriers. Preclinical models show that interventions to reestablish microbial homeostasis with probiotics, prebiotics, or fecal microbiota transplantation decrease postoperative cognition. Clinical studies offer evidence supporting the associations between decreased short-chain fatty acid-producing bacteria and POCD risk. Randomized controlled trials have demonstrated that perioperative probiotics lower the incidence and markers of POCD. Multi-omic approaches to integrating microbiome, metabolome, and neuroimaging signatures are being engineered to discern recovery phenotypes prior to surgery. Conclusions: Perioperative gut microbiota are a modifiable target for the optimization of cognitive recovery from neurosurgery. The inclusion of microbiome treatments and diagnostics into standard surgical care pathways is one potential pathway to POCD minimization, but large randomized trials will be necessary to establish this.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Postoperative Cognitive Complications/microbiology/etiology/prevention & control
*Brain
*Neurosurgical Procedures/adverse effects
Dysbiosis
Animals
Probiotics/therapeutic use

@article {pmid41133095,
year = {2025},
author = {Cui, X and Yuan, Q and Long, J and Zhou, J},
title = {Recent advances in gut microbiota-mediated regulation of fat deposition and metabolic disorders.},
journal = {Microbiome research reports},
volume = {4},
number = {3},
pages = {31},
pmid = {41133095},
issn = {2771-5965},
abstract = {The gut microbiota critically regulates lipid metabolism through microbial metabolites and host signaling pathways. Short-chain fatty acids (SCFAs), derived from dietary fiber fermentation, suppress hepatic lipogenesis via inhibition of SREBP-1c and enhance mitochondrial β-oxidation through GPR41/43 activation. Microbial enzymes convert primary bile acids into secondary bile acids, which activate FXR to inhibit lipogenesis and TGR5 to promote adipose thermogenesis. Lipopolysaccharide (LPS) from dysbiotic microbiota triggers TLR4-NF-κB signaling, exacerbating insulin resistance and adipose inflammation. Branched-chain amino acids (BCAAs), metabolized by gut microbes, drive adipogenesis via mTORC1-PPARγ signaling, with elevated circulating BCAAs linked to obesity. In livestock, microbiota modulation optimizes fat deposition: probiotics in pigs enhance intramuscular fat via Lactobacillus-enriched communities, while dietary succinate or coated sodium propionate reduces abdominal fat in broilers by reshaping cecal microbiota. Fecal microbiota transplantation confirms microbial causality in transferring fat phenotypes. Dysbiosis-associated mechanisms are conserved across species, where SCFAs and bile acids ameliorate metabolic inflammation, whereas LPS and BCAA imbalances worsen lipid dysregulation. Metabolic disorders, including obesity, type 2 diabetes (T2D), and non-alcoholic fatty liver disease (NAFLD), are tightly linked to gut microbiota perturbations. Dysbiosis drives LPS translocation and barrier impairment. These changes, along with altered metabolites, promote inflammation and fat deposition. Future strategies should integrate multi-omics and precision engineering of microbial consortia to advance therapies for both livestock and human metabolic health.},
}

@article {pmid41133047,
year = {2025},
author = {Al-Juhani, A and Desoky, MS and Almuhaimid, AA and Zaheer, M and Alhaqbani, HF and Abalkhail, EA and Alanazi, SA and Alzahrani, RS and Alrefaai, M and Desoky, R},
title = {Efficacy of Gut Microbiome-Targeted Therapies in Modulating Systemic Inflammation and Low-Grade Chronic Inflammatory States in Adults With Metabolic Disorders: A Systematic Review.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e92881},
pmid = {41133047},
issn = {2168-8184},
abstract = {Gut microbiome-targeted therapies have shown promise in promoting the outcomes of metabolic inflammation-related disease management. This review aims to assess the effectiveness of microbiome-targeted interventions and pinpoint the most promising therapies for clinical implementation. Following the PRISMA 2020 standards, we searched four main databases: PubMed, EMBASE, Scopus, and the Cochrane Library. We integrated medical subject headings (MeSH) and free-text keywords search pertinent to gut microbiome-targeted interventions, along with related outcomes such as inflammation and insulin resistance. English studies were conducted on primary adults with a metabolic disease diagnosis or deemed a high risk, and were mandated to report at least one outcome pertinent to metabolic health or systemic inflammation. To assess the risk bias, data were extracted, and the Cochrane Risk of Bias (RoB) 2.0 tool was employed. Fifteen studies fulfilled the inclusion criteria. A narrative synthesis was conducted. We found that probiotics significantly enhanced insulin resistance (HOMA-IR), reduced circulating endotoxin levels, decreased visceral fat, BMI, and fat mass, and increased beneficial taxa with obesity-associated bacteria reduction. However, inconsistent outcomes were shown for lipid parameters. Prebiotic therapies showed significant decreases in fasting glucose in overweight people, and insulin levels and HOMA-IR in patients with metabolic syndrome, enhanced anti-inflammatory effects (31% C-reactive protein (CRP) reduction, decreased interleukin (IL)-6, tumor necrosis factor-alpha (TNF)-α, and lipopolysaccharide (LPS) levels), and promoted butyrate-producing bacteria. Synbiotic interventions showed complementary benefits for glucose metabolism and body composition. Fecal microbiota transplantation (FMT) studies indicated improved insulin sensitivity and donor microbiota engraftment in responders. Fiber-rich diet trials markedly improved HbA1c levels in diabetic and prediabetic individuals. In conclusion, prebiotics demonstrated the most consistent metabolic and anti-inflammatory benefits across multiple parameters. Probiotics showed targeted effects on insulin resistance and body composition but inconsistent lipid outcomes. FMT and synbiotics require further investigation to establish clinical efficacy. This evidence supports prebiotics as a priority intervention for metabolic disease management through microbiome modulation.},
}

@article {pmid41132656,
year = {2025},
author = {Hu, Y and Yang, Y and Li, Y and Zhang, Q and Zhang, W and Jia, J and Han, Z and Wang, J},
title = {Th17/Treg imbalance in inflammatory bowel disease: immunological mechanisms and microbiota-driven regulation.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1651063},
pmid = {41132656},
issn = {1664-3224},
mesh = {Humans ; *Th17 Cells/immunology/metabolism ; *T-Lymphocytes, Regulatory/immunology/metabolism ; *Gastrointestinal Microbiome/immunology ; *Inflammatory Bowel Diseases/immunology/microbiology/therapy/metabolism ; Animals ; Dysbiosis/immunology ; Cytokines/metabolism ; },
abstract = {Inflammatory bowel disease (IBD) is a group of conditions characterized by chronic and recurrent intestinal inflammation, primarily including Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis of IBD is closely linked to abnormal immune responses, particularly T-cell mediated immune reactions. Th17 cells promote persistent intestinal inflammation by secreting pro-inflammatory cytokines such as IL-17, while regulatory T (Treg) cells help maintain immune homeostasis by secreting anti-inflammatory cytokines like IL-10 and TGF-β. In patients with IBD, Th17 cell function is enhanced, whereas Treg cell function is impaired or their numbers are reduced, leading to an imbalance in the immune system and exacerbating intestinal inflammation. The gut microbiota plays a crucial role in the immune regulation of IBD. Dysbiosis can lead to excessive activation of Th17 cells and suppression of Treg cell function, further aggravating clinical symptoms. Studies have shown that restoring gut microbiota balance through probiotics, antibiotics, dietary interventions, or fecal microbiota transplantation can not only improve immune responses but also restore the balance between Th17 and Treg cells, which has a positive impact on IBD treatment. This review summarizes how gut microbiota modulates the Th17/Treg cell balance to influence IBD immune responses and explores therapeutic strategies targeting Th17/Treg balance, including cytokine antagonists and immunosuppressive agents, which provide new directions and approaches for clinical IBD treatment.},
}

Humans
*Th17 Cells/immunology/metabolism
*T-Lymphocytes, Regulatory/immunology/metabolism
*Gastrointestinal Microbiome/immunology
*Inflammatory Bowel Diseases/immunology/microbiology/therapy/metabolism
Animals
Dysbiosis/immunology
Cytokines/metabolism

@article {pmid41132492,
year = {2025},
author = {Zhang, L and Xu, T and Chen, W and Chai, Y and Wu, Y and Du, X},
title = {The potential of the microbiome as a target for prevention and treatment of carbapenem-resistant Enterobacteriaceae infections.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1674534},
pmid = {41132492},
issn = {2235-2988},
mesh = {Humans ; *Carbapenem-Resistant Enterobacteriaceae/drug effects/physiology ; *Enterobacteriaceae Infections/prevention & control/microbiology/therapy ; *Gastrointestinal Microbiome/drug effects ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use/administration & dosage ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Animals ; Dysbiosis ; Carbapenems/pharmacology ; Fatty Acids, Volatile ; },
abstract = {Carbapenem-resistant Enterobacteriaceae (CRE) present an escalating threat to global health due to their high transmissibility, limited treatment options, and high mortality rates. The gastrointestinal tract serves as both a major reservoir and a transmission hub for CRE, especially under conditions of antibiotic-induced dysbiosis. This review highlights the growing interest in the gut microbiome as a potential target for preventing and managing CRE infections. Building upon the understanding of CRE pathogenesis, we examine how commensal microbiota contribute to colonization resistance through mechanisms such as nutrient competition, spatial niche exclusion, immune modulation, and the production of antimicrobial metabolites. We further discuss microbiome-based therapeutic strategies, including probiotic administration, fecal microbiota transplantation (FMT), and supplementation with short-chain fatty acids (SCFAs), that have shown encouraging results in reducing intestinal CRE colonization. In addition, we explore emerging microbiome engineering approaches, particularly CRISPR-Cas9-mediated systems, which enable the selective elimination of resistant strains while maintaining microbial homeostasis. Current microbiome-based approaches have shown promise in the treatment and prevention of CRE infections, but further research is still needed to clarify their mechanisms, evaluate long-term safety, and determine their effectiveness in different clinical settings. With continued studies and thoughtful integration into existing infection control and antibiotic stewardship practices, these strategies may gradually contribute to a more practical and sustainable way to manage CRE.},
}

Humans
*Carbapenem-Resistant Enterobacteriaceae/drug effects/physiology
*Enterobacteriaceae Infections/prevention & control/microbiology/therapy
*Gastrointestinal Microbiome/drug effects
Fecal Microbiota Transplantation
Probiotics/therapeutic use/administration & dosage
Anti-Bacterial Agents/pharmacology/therapeutic use
Animals
Dysbiosis
Carbapenems/pharmacology
Fatty Acids, Volatile

@article {pmid41131460,
year = {2025},
author = {Li, G and Hou, Y and Zhang, L and Chen, L and Yang, Y and Yu, D},
title = {Gut microbiota and metabolomic profiles of tacrolimus-induced DILI in renal transplant recipients: a population-based case control study.},
journal = {BMC microbiology},
volume = {25},
number = {1},
pages = {684},
pmid = {41131460},
issn = {1471-2180},
support = {2025ZNSFSC0718//Sichuan Science and Technology Support Program/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Kidney Transplantation/adverse effects ; Male ; Female ; Middle Aged ; *Tacrolimus/adverse effects ; Case-Control Studies ; Adult ; *Immunosuppressive Agents/adverse effects ; *Bacteria/classification/genetics/metabolism/isolation & purification ; Transplant Recipients ; *Chemical and Drug Induced Liver Injury/microbiology/metabolism/etiology ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Metabolomics ; *Metabolome ; Aged ; },
abstract = {BACKGROUND: In clinical practice, cases of drug-induced liver injury (DILI) often occur in renal transplant recipients treated with tacrolimus (Tac) as an immunosuppressive therapy. Numerous studies have confirmed the close relationship between gut microbiota (GM) and DILI. However, systematic studies on the GM and metabolomic characteristics of Tac-associated DILI are lacking, and the role of GM and its metabolites in DILI remains incompletely understood.

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

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

CONCLUSIONS: In renal transplant recipients, distinct GM and enteric metabolic profiles differentiate patients with DILI from those with stable liver function. Key microbial taxa-including Oscillibacter, Bacteroides, Ruminococcus gnavus group, and Lachnospiraceae NK4A136 group-potentially contribute to DILI pathogenesis through modulation of bile acid metabolism and inflammatory signaling pathways.},
}

Humans
*Gastrointestinal Microbiome/drug effects
*Kidney Transplantation/adverse effects
Male
Female
Middle Aged
*Tacrolimus/adverse effects
Case-Control Studies
Adult
*Immunosuppressive Agents/adverse effects
*Bacteria/classification/genetics/metabolism/isolation & purification
Transplant Recipients
*Chemical and Drug Induced Liver Injury/microbiology/metabolism/etiology
Feces/microbiology
RNA, Ribosomal, 16S/genetics
Metabolomics
*Metabolome
Aged

@article {pmid41130540,
year = {2025},
author = {Li, J and Yue, Y and Pan, J and Liang, F},
title = {Research progress on gut microbiota in colorectal cancer immunotherapy.},
journal = {Biochimica et biophysica acta. Reviews on cancer},
volume = {1880},
number = {6},
pages = {189476},
doi = {10.1016/j.bbcan.2025.189476},
pmid = {41130540},
issn = {1879-2561},
abstract = {Immune checkpoint inhibitors (ICIs) have demonstrated significant clinical benefits in treating various malignancies. However, their therapeutic efficacy exhibits considerable interindividual variability in patients with colorectal cancer (CRC). In recent years, growing attention has been focused on the regulatory role of the gut microbiota and its metabolic microenvironment in modulating ICIs responses. This article systematically reviews key advances in understanding how the gut microbiota and its metabolites influence ICIs efficacy. For example: Specific bacterial species (e.g., Lactobacillus paracasei and Fusobacterium nucleatum) may regulate ICIs efficacy by modulating antigen presentation or the tumor immune microenvironment. Microbial metabolites, such as short-chain fatty acids (SCFAs), can enhance immune function and thereby improve ICIs outcomes. Potential microbiome-targeted interventions-including probiotic/prebiotic combinations, optimized antibiotic administration timing, refined fecal microbiota transplantation (FMT) protocols, and engineered synthetic biology-based bacterial therapies-are also discussed. By synthesizing current evidence, this review provides a theoretical foundation for developing novel personalized immunotherapy strategies for CRC, with a focus on microbiome modulation to optimize ICIs treatment efficacy.},
}

@article {pmid41130528,
year = {2025},
author = {Wang, J and Luo, Y and Wang, S and Zhou, Y and Gan, G and Xie, J and Cheng, ASK},
title = {Gut microbiota and late-life depression: from mechanistic insights to clinical rehabilitation.},
journal = {Life sciences},
volume = {},
number = {},
pages = {124041},
doi = {10.1016/j.lfs.2025.124041},
pmid = {41130528},
issn = {1879-0631},
abstract = {Emerging evidence identifies the gut microbiota as a promising therapeutic target for late-life depression, yet its mechanisms and clinical applications remain insufficiently defined in aging populations. This review synthesizes findings from animal studies and clinical trials to examine how the gut microbiota contributes to late-life depression and to evaluate potential intervention. We first outline the association between microbial ecosystem alterations and mental health, emphasizing their relevance for late-life depression. Mechanistic pathways are then discussed in sequence: disruption of intestinal microbial networks that impair barrier integrity, dysregulation of microbial metabolites that disturb gut-brain communication, and maladaptive immune activation and signal transduction at the host-microbe interface. Building on these insights, we assess the therapeutic approaches, including dietary interventions, probiotics, prebiotics, postbiotics, and fecal microbiota transplantation. Recovery outcomes are also summarized, covering microbial composition, metabolite changes, neurological biomarkers and neuroimaging findings. Finally, we address major translational challenges, including individual variability, dynamic monitoring, technological limitations, and safety concerns. We highlight the methodological gaps that limit current research and propose future directions to advance mechanistic understanding and clinical translation. By integrating ecological balance with personalized strategies, gut microbiota-based interventions hold potential to improve prevention and treatment of late-life depression.},
}

@article {pmid41129310,
year = {2025},
author = {Mao, ZH and Liu, Y and Pan, S and Zhang, Q and Qiao, Y and Zhang, X and Li, D and Chen, J and Liu, D and Feng, Q and Liu, Z},
title = {The Gut-Kidney Dialogue: Unraveling the Microbial Symphony in Renal Fibrosis.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {20},
pages = {e71179},
doi = {10.1096/fj.202502675R},
pmid = {41129310},
issn = {1530-6860},
support = {U21A20348//National Natural Science Foundation of China (NSFC)/ ; 82200796//National Natural Science Young Scientists Foundation of China/ ; LHGJ20230165//Medical Science and Technology Research Project of Henan Province/ ; LHGJ20240215//Medical Science and Technology Research Project of Henan Province/ ; 252300421112//Natural Science Foundation of Henan Province/ ; YQRC2024011//Young and Middle-aged Innovation Talents of Health Science and Technology Project in Henan Province/ ; 242102310009//Key R&D and Promotion Special Projects of Henan Province/ ; 242102310098//Key R&D and Promotion Special Projects of Henan Province/ ; //Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University/ ; },
mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; Animals ; Fibrosis/microbiology ; *Renal Insufficiency, Chronic/microbiology/pathology ; *Kidney/pathology/microbiology ; *Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Mice ; Probiotics/therapeutic use ; },
abstract = {Renal fibrosis is a maladaptive pathological endpoint common to the diverse etiologies of chronic kidney disease (CKD), resulting in irreversible nephron loss and functional decline. Emerging evidence has highlighted the potential role of the gut microbiota in renal fibrosis through bidirectional interactions between the gut and kidney. In animal models, broad-spectrum antibiotic regimens have been confirmed to attenuate renal fibrosis, whereas fecal microbiota transplantation from fibrotic donors transmits renal disease in recipient germ-free mice, providing rudimentary evidence of microbial causality. Human-based studies have demonstrated that, in patients with CKD exhibiting progressive fibrosis, there are modifications in the composition of the gut microbiota, including decreased microbial variety and shifts in the distribution of specific bacterial groups. Furthermore, metabolomic profiling revealed that the severity of fibrosis was independently predicted by increased levels of circulating trimethylamine N-oxide and indoxyl sulfate. Preliminary clinical studies exploring the therapeutic potential of regulating the gut microbiota have demonstrated promising results. Interventions, such as high-purity probiotic formulations, result in improved renal function and decreased levels of fibrotic markers. These findings suggest a potential correlation between gut microbiota dysbiosis and renal fibrosis. However, further research is necessary to determine the causal correlations, elucidate the underlying mechanisms, and identify specific microbial species and metabolites related to the regulation of renal fibrosis. This review provides a systematic summary of the current understanding of the important connection between gut microbiota dysbiosis and renal fibrosis. Understanding the influence of gut microbiota on renal fibrosis may open new avenues for the development of innovative therapeutic strategies to prevent or manage renal fibrosis and its associated complications.},
}

*Gastrointestinal Microbiome/physiology
Humans
Animals
Fibrosis/microbiology
*Renal Insufficiency, Chronic/microbiology/pathology
*Kidney/pathology/microbiology
*Dysbiosis/microbiology
Fecal Microbiota Transplantation
Mice
Probiotics/therapeutic use

@article {pmid41128412,
year = {2025},
author = {Peng, L and Song, H and Shi, H and Wu, L and Ma, Y and Fan, X and Wu, M and Duan, L and Li, Z and Yuan, H},
title = {Oral Multi-Enzymatic Manganese-Carbon Dots Alleviate Sepsis-Associated Lung Injury via the Gut-Lung Axis.},
journal = {ACS nano},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsnano.5c10625},
pmid = {41128412},
issn = {1936-086X},
abstract = {Sepsis-induced pulmonary injury represents a life-threatening global health challenge due to poorly defined pathological mechanisms. The gut-lung axis has been proven to be widely involved in sepsis-induced lung injury, yet effective interventions targeting gut microbiota homeostasis remain unknown. Single-cell sequencing revealed increased alveolar apoptosis and impaired macrophage efferocytosis during sepsis pathogenesis. Thus, we designed oral manganese-doped carbon dots (Mn-CDs) to alleviate septic lung injury by remodeling gut microbiota homeostasis and targeting the gut-lung axis. Biochemical characterization demonstrated Mn-CDs possess multienzyme mimetic activities (SOD-, CAT-, POD-, GPx-like) and potent ROS scavenging capacity. In murine sepsis models, Mn-CDs significantly improved systemic indices and were associated with macrophage anti-inflammatory states with enhanced efferocytosis, as evidenced by transcriptomic profiling. Integrated metagenomic/metabolomic analyses identified Mn-CDs-mediated enrichment of g_Clostridium and g_Bacteroides, concomitant with elevated indole-3-propionic acid (IPA) production. Subsequent in vitro studies demonstrate that IPA likely binds primarily to the aryl hydrocarbon receptor (AHR), promoting both efferocytosis and anti-inflammatory polarization in macrophages, thereby mitigating septic lung injury. Notably, the fecal microbiota transplantation (FMT) from Mn-CDs-treated mice not only alleviated systemic symptoms but also effectively promoted efferocytic polarization of pulmonary macrophages in septic mice. Depletion of the gut microbiota resulted in a significant loss of the protective efficacy of Mn-CDs in a murine model of septic lung injury. Collectively, the gut-lung axis mediated by microbiota-derived IPA and macrophage efferocytosis contributes to the remediation of septic lung injury, highlighting the potential of Mn-CDs in microbiome-directed critical care.},
}

@article {pmid41126840,
year = {2025},
author = {Liu, T and Li, Y and Xiong, X and Lai, X and Xu, X},
title = {The Microbiota-gut-brain axis in vascular cognitive impairment: unraveling the mysterious link and therapeutic prospects.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1648800},
pmid = {41126840},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome ; *Brain/metabolism ; *Cognitive Dysfunction/microbiology/therapy/etiology ; *Brain-Gut Axis ; *Dementia, Vascular/microbiology/therapy/etiology ; Medicine, Chinese Traditional ; Animals ; },
abstract = {BACKGROUND: Vascular cognitive impairment (VCI) exhibits particularly high prevalence in East Asian populations. However, its pathogenesis remains elusive due to its multifactorial and complex nature. Emerging evidence highlights the microbiota-gut-brain axis as a novel and promising paradigm for elucidating VCI mechanisms and developing therapeutic interventions. This systematic review aims to synthesize recent advances in this field, offering critical perspectives to guide future research on VCI through the lens of gut-brain interactions. Notably, given Traditional Chinese Medicine's (TCM) holistic and multi-target therapeutic advantages, we incorporate TCM studies to complement conventional approaches.

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

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

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

https://www.crd.york.ac.uk/prospero, identifier CRD42024560293.},
}

Humans
*Gastrointestinal Microbiome
*Brain/metabolism
*Cognitive Dysfunction/microbiology/therapy/etiology
*Brain-Gut Axis
*Dementia, Vascular/microbiology/therapy/etiology
Medicine, Chinese Traditional
Animals

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

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

CONCLUSION: These findings underscore the importance of encapsulation and donor microbiota modulation in FMT and provide valuable strategies for improving transplantation precision and outcomes.},
}

Animals
*Fecal Microbiota Transplantation/methods
*Probiotics/administration & dosage/pharmacology
Mice
*Gastrointestinal Microbiome
Feces/microbiology
Germ-Free Life
Bacteria/classification/genetics/isolation & purification
Pediococcus pentosaceus/physiology
Male
Mice, Inbred C57BL

@article {pmid41125958,
year = {2025},
author = {Fan, Y and Ni, M and Aggarwala, V and Mead, EA and Ksiezarek, M and Cao, L and Kamm, MA and Borody, TJ and Paramsothy, S and Kaakoush, NO and Grinspan, A and Faith, JJ and Fang, G},
title = {Long-read metagenomics for strain tracking after faecal microbiota transplant.},
journal = {Nature microbiology},
volume = {},
number = {},
pages = {},
pmid = {41125958},
issn = {2058-5276},
support = {R35 GM139655/GM/NIGMS NIH HHS/United States ; },
abstract = {Accurate tracking of bacterial strains that stably engraft in faecal microbiota transplant (FMT) recipients is critical for understanding the determinants of strain engraftment, evaluating correlations with clinical outcomes and guiding the development of therapeutic consortia. While short-read sequencing has advanced FMT research, it faces challenges in strain-level de novo metagenomic assembly. Here we describe LongTrack, a method that uses long-read metagenomic assemblies for FMT strain tracking. LongTrack shows higher precision and specificity than short-read approaches, especially when multiple strains co-exist in the same sample. We uncovered 648 engrafted strains across six FMT cases involving patients with recurrent Clostridioides difficile infection and inflammatory bowel disease. Furthermore, long reads enabled assessment of the genomic and epigenomic stability of engrafted strains at the 5-year follow-up timepoint, revealing structural variations that may be associated with strain adaptation in a new host environment. Our findings support the use of long-read metagenomics to track microbial strains and their adaptations.},
}

@article {pmid41123871,
year = {2025},
author = {Krawczyk, A and Kasperski, T and Gosiewski, T and Nikiforuk, A and Potasiewicz, A and Arent, Z and Salamon, D},
title = {Effects of fecal microbiota transplantation on the abundance and diversity of selected fungal and archaeal species in the gut microbiota in the rat model of schizophrenia.},
journal = {Pharmacological reports : PR},
volume = {},
number = {},
pages = {},
pmid = {41123871},
issn = {2299-5684},
abstract = {BACKGROUND: The gut microbiome has been increasingly recognized for its potential role in schizophrenia through gut-brain interactions involving immune, neural, and metabolic pathways. This pilot study evaluated the impact of fecal microbiota transplantation (FMT) on the abundance and variability of selected fungal and archaeal species in the gut microbiota in the rat model of schizophrenia.

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

CONCLUSIONS: Overall, the results suggest that FMT has limited impact on gut fungal populations, possibly due to the developmental stage of microbiome maturation or procedural interventions. The absence of archaea underscores the complexity of the microbiome's role in neurodevelopmental disorders, highlighting the necessity for continued research into microbial influences on schizophrenia pathophysiology.},
}

@article {pmid41123835,
year = {2025},
author = {Saha, J and Goswami, R},
title = {Modulation of Innate Immunity by Short-Chain Fatty Acids in Probiotic and Fecal Microbiota Transplantation Therapies for the Treatment of Colon Disorders.},
journal = {Probiotics and antimicrobial proteins},
volume = {},
number = {},
pages = {},
pmid = {41123835},
issn = {1867-1314},
abstract = {Short-chain fatty acids (SCFAs) are produced by microbes in the gut from macronutrient fermentation. As the key bacterial metabolites, three SCFAs-acetate, propionate, and butyrate-are abundant in the gut and are presently linked to a number of homeostatic and pathophysiologic immune regulatory processes. The significance of these metabolites in the control of numerous immunological processes is currently being closely examined especially in gut immunity in gut-liver and gut-brain axes. Besides affecting cell metabolism and functions that confer immunity to the host, interestingly, SCFAs are currently in the spotlight for their role in innate immune cell maturation and differentiation having potential translational benefits. Dysbiosis in the gut leading to alterations of gut microbe population affects wide array of physiologic functions including both local and systemic immune regulation. Affecting millions worldwide, inflammatory bowel disease (IBD) and colorectal cancer (CRC) are the major gut diseases where the etiology can be partially attributed to gut dysbiosis and short-chain fatty acid alterations. We closely monitored the impact of intervention strategies of IBD and CRC by alteration of gut microbiota through probiotic administration and fecal microbiota transplantation on innate immunity. Although ongoing studies underscore the implications of these strategies in combatting gut inflammation but the importance of SCFA metabolism on innate immunity needs to be addressed. With the current narrative, we aim to connect the dots and find any missing links, between how probiotic administration and fecal microbiota transplantation as therapies impact gut inflammation via innate immune cell regulation through SCFAs as gut microbial metabolites.},
}

@article {pmid41123566,
year = {2025},
author = {Omar, TM and Al-Hussainy, AF and Jyothi, SR and Priyadarshini Nayak, P and Bethanney Janney, J and Singh, G and Polatova, D and Sameer, HN and Salih, RM and Adil, M and Salajegheh, P},
title = {Invisible influencers: the tumor microbiome's impact on immunotherapy in colorectal cancer (CRC).},
journal = {Expert review of anticancer therapy},
volume = {},
number = {},
pages = {},
doi = {10.1080/14737140.2025.2579656},
pmid = {41123566},
issn = {1744-8328},
abstract = {INTRODUCTION: The tumor microbiome, a diverse microbial community within the tumor microenvironment (TME), significantly influences cancer progression and immunotherapy outcomes in colorectal cancer (CRC). Understanding its role in modulating immune responses and therapeutic resistance is critical for advancing precision oncology.

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

EXPERT OPINION: The tumor microbiome shapes CRC immunotherapy efficacy by modulating immune evasion and TME dynamics. Targeted interventions like FMT and probiotics show promise in enhancing ICI responses, but challenges include microbial variability, safety concerns, and ethical considerations. Future research should prioritize personalized microbiome profiling and standardized protocols to optimize therapeutic outcomes and overcome resistance in CRC.},
}

@article {pmid41123497,
year = {2025},
author = {Mali, J and Salusjärvi, J and Leppäniemi, A and Mentula, P and Sallinen, V},
title = {Comparison of classification systems for acute diverticulitis and updating of Helsinki staging.},
journal = {The journal of trauma and acute care surgery},
volume = {},
number = {},
pages = {},
doi = {10.1097/TA.0000000000004795},
pmid = {41123497},
issn = {2163-0763},
abstract = {BACKGROUND: Helsinki classification for acute colonic diverticulitis, based on radiological and clinical parameters, stratifies patients according to their prognosis and recommended treatment into five stages. This study aims to update Helsinki classification to improve it in patients with abscesses and peritonitis and validate the classification by comparing it with other classifications of diverticulitis.

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

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

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

LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.},
}

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

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

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

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

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42025638185.},
}

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

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

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

TRIAL REGISTRATION NUMBER: jRCTs031240344.},
}

Humans
*Fecal Microbiota Transplantation/methods
*Parkinson Disease/therapy/microbiology
Double-Blind Method
*Anti-Bacterial Agents/therapeutic use
Randomized Controlled Trials as Topic
*Gastrointestinal Microbiome
Treatment Outcome
Male
Middle Aged
Female

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

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

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

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

CONCLUSION: KF1 protects against ALI by modulating the gut microbiota and associated metabolites, thereby promoting a more favorable state and inhibiting pro-inflammatory pathways.},
}

@article {pmid41118252,
year = {2025},
author = {Qi, X and Li, Y and Zhu, Y and Shen, R and Xie, Z},
title = {Rebuilding the gut ecosystem: Emerging strategies targeting the microbiota in antibiotic-associated diarrhea.},
journal = {Acta microbiologica et immunologica Hungarica},
volume = {},
number = {},
pages = {},
doi = {10.1556/030.2025.02690},
pmid = {41118252},
issn = {1588-2640},
abstract = {Antibiotic-associated diarrhea (AAD) is a prevalent iatrogenic complication of antibiotic therapy, primarily triggered by dysbiosis and loss of intestinal homeostasis. The traditional interventions, such as empirical probiotic use, have shown a modest and a heterogeneous efficacy. This review integrates the current mechanistic understanding of AAD through the lens of the microbiota-mucosal-immune axis and provides a comprehensive overview of emerging therapeutic strategies. By integrating evidence from metagenomics, metabolomics, and immunology, we highlight next-generation approaches, including rationally engineered probiotics, standardized fecal microbiota transplantation (FMT), and synthetic-biology-derived interventions. Recent progress in multi-omics technologies and machine learning has enabled patient-stratified modulation of the gut microbiota, moving beyond empirical supplementation toward precision ecological reprogramming. These advanced therapies demonstrate superior outcomes in restoring microbial diversity, strengthening epithelial barrier function, and re-establishing immunological homeostasis. Ultimately, the management of AAD requires a systems-biology strategy that leverages real-time microbiome analytics for targeted, accurate, and sustainable restoration of gut health.},
}

@article {pmid41115965,
year = {2025},
author = {Göttert, S and Thiele Orberg, E and Fan, K and Heinrich, P and Matthe, DM and Khalid, O and Klostermeier, L and Suriano, C and Strieder, N and Gebhard, C and Vonbrunn, E and Mamilos, A and Hirsch, D and Meedt, E and Kleigrewe, K and Hiergeist, A and Schwarz, A and Gläsner, J and Ghimire, S and Joachim, L and Voll, F and Neuhaus, K and Janssen, KP and Perl, M and Pielmeier, F and Ruland, J and Kreutz, M and Weber, D and Schmidl, C and Köhler, N and Tschurtschenthaler, M and Hoffmann, P and Edinger, M and Wolff, D and Bassermann, F and Rehli, M and Haller, D and Evert, M and Hildner, K and Büttner-Herold, M and Herr, W and Gessner, A and Heidegger, S and Holler, E and Poeck, H},
title = {The microbial metabolite desaminotyrosine protects against graft-versus-host disease via mTORC1 and STING-dependent intestinal regeneration.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {9282},
pmid = {41115965},
issn = {2041-1723},
support = {324392634//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; },
mesh = {Animals ; *Graft vs Host Disease/prevention & control ; *Mechanistic Target of Rapamycin Complex 1/metabolism ; *Gastrointestinal Microbiome/drug effects ; Mice ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; *Intestines/physiology/drug effects ; *Membrane Proteins/metabolism/genetics ; *Regeneration/drug effects ; Mice, Inbred C57BL ; *Tyrosine/analogs & derivatives/pharmacology/metabolism ; Male ; Female ; Fecal Microbiota Transplantation ; Transplantation, Homologous ; },
abstract = {Changes in the intestinal microbiome and microbiota-derived metabolites predict clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, we report that desaminotyrosine (DAT), a product of bacterial flavonoid metabolism, correlates with improved overall survival and reduced relapse rates in patients receiving allo-HSCT. In preclinical mouse models, treatment with synthetic DAT prevents graft-versus-host disease by protecting the intestinal barrier and promoting intestinal regeneration and contributes to graft-vs.-leukemia responses. DAT´s beneficial effects on intestinal regeneration remain effective despite broad-spectrum antibiotics-induced dysbiosis, also when administered by fecal microbiota transfer with flavonoid-degrading F. plautii. Mechanistically, DAT promotes mTORC1-dependent activation and proliferation of intestinal stem cells, with concomitant engagement of the innate immune receptor STING required to mitigate metabolic stress and maintain an undifferentiated stem cell state independently of type-I interferon responses. Additionally, DAT can skew T cells towards an effector phenotype to modulate graft-versus-leukemia responses. Our data uncover DAT's dual, tissue- and immune-modulating properties and underscore its potential in precision microbiome-based therapies to improve tissue regeneration and minimize immune-mediated side effects.},
}

Animals
*Graft vs Host Disease/prevention & control
*Mechanistic Target of Rapamycin Complex 1/metabolism
*Gastrointestinal Microbiome/drug effects
Mice
Hematopoietic Stem Cell Transplantation/adverse effects
Humans
*Intestines/physiology/drug effects
*Membrane Proteins/metabolism/genetics
*Regeneration/drug effects
Mice, Inbred C57BL
*Tyrosine/analogs & derivatives/pharmacology/metabolism
Male
Female
Fecal Microbiota Transplantation
Transplantation, Homologous

@article {pmid41115539,
year = {2025},
author = {Meng, M and Zhao, L and Liu, W and Yi, G and Song, Y and Gan, Z and Tan, X and Dou, H and Liu, Y and Zhang, Y},
title = {Effect of polysaccharides from Aconitum pendulum Bush on rheumatoid arthritis.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {148405},
doi = {10.1016/j.ijbiomac.2025.148405},
pmid = {41115539},
issn = {1879-0003},
abstract = {The Tibetan people of China have used the roots of Aconitum pendulum Bush as a folk remedy for rheumatoid arthritis (RA). In this study, we investigated the effects of A. pendulum polysaccharides (APPs) on RA. Chemical analysis revealed that APPs were mostly composed of galacturonic acid, glucose, and glucuronic acid. Structural characterization showed that it is an α-glucan with (1 → 4) and (1 → 3,6) glycosidic linkages. Furthermore, we examined the therapeutic potential of APPs (100 and 400 mg/kg) in a rat model of bovine collagen-induced arthritis (CIA). Results indicated that APP administration markedly reduced the critical characteristics of CIA, including foot swelling, thymic and splenic indices, and serum concentrations of pro-inflammatory cytokines. Histopathological analysis further validated that APPs mitigated vascular opacities and synovial inflammation in the ankle joints. Moreover, initial analysis of fecal samples revealed changes in the abundance of specific intestinal microbial taxa after APP treatment. These findings collectively establish an experimental basis for the potential of APPs as adjunctive therapeutic agents for RA. However, additional research, encompassing fecal microbiota transplantation and studies in germ-free models, is essential to clarify the potential causal relationship between the observed alterations in gut microbiota and the anti-arthritic effects of APPs.},
}

@article {pmid41114583,
year = {2025},
author = {Xia, Y and Yang, J and Lu, S and Cheng, W and Ren, M and Liu, Z and Yang, L and Shen, Q and Liang, Y and Huang, H and Chen, M and Zhou, X and Yu, M and Ji, F and Xu, C},
title = {Microbial changes resulting from VSG attenuate MASLD by modulating bile acid metabolism and the intestinal FXR-FGF19 axis.},
journal = {mSystems},
volume = {},
number = {},
pages = {e0063425},
doi = {10.1128/msystems.00634-25},
pmid = {41114583},
issn = {2379-5077},
abstract = {UNLABELLED: Vertical sleeve gastrectomy (VSG) is a highly effective intervention for metabolic dysfunction-associated steatotic liver disease (MASLD) and is associated with significant alterations in the gut microbiota. However, the precise mechanisms underlying its metabolic benefits remain poorly understood. In this study, we revealed that VSG mitigates MASLD by reshaping gut microbiota-mediated bile acid metabolism. Through integrated 16S rRNA sequencing, targeted metabolomics, and functional validation experiments, we demonstrated that VSG markedly enhances bile salt hydrolase (BSH) activity within the gut microbiota, resulting in elevated levels of unconjugated bile acids. These unconjugated bile acids serve as potent agonists for the intestinal farnesoid X receptor (FXR), thereby activating the intestinal FXR-fibroblast growth factor 19 signaling pathway. This activation leads to significant improvements in metabolic health, including enhanced glucose regulation and attenuated hepatic lipid accumulation. Fecal microbiota transplantation (FMT) from VSG-treated rats replicated these metabolic improvements, whereas antibiotic treatment abolished these beneficial effects, highlighting the indispensable role of the gut microbiota in mediating the anti-MASLD effects of VSG. Importantly, inhibition of intestinal FXR signaling negated the metabolic benefits of FMT, further emphasizing the critical role of the gut microbiota-BSH-FXR axis. Our findings reveal a novel mechanism by which VSG alleviates MASLD through gut microbiota-dependent activation of intestinal FXR, offering new perspectives for microbiome-targeted therapeutic strategies in MASLD.

IMPORTANCE: Fecal transplantation from bariatric surgery patients and mice to germ-free mice has shown that the gut microbiota may contribute to metabolic benefits after bariatric surgery. However, the mechanisms by which the gut microbiota contributes to metabolic benefits after bariatric surgery require further investigation. To address this gap, we investigated the effects of the vertical sleeve gastrectomy (VSG) gut microbiota on metabolic dysfunction-associated steatotic liver disease (MASLD) in vivo and elucidated its underlying mechanisms. Our study demonstrated that VSG significantly improved the gut microbiota, especially by increasing bile salt hydrolase (BSH) activity, in MASLD rats. Increased BSH activity significantly increased the proportion of FXR-agonistic bile acids and further activated the intestinal FXR-FGF19 axis, thereby improving MASLD. These findings explored the key roles and mechanisms of the gut microbiota in the metabolic benefits of VSG, offering new microbiome-based treatment strategies.},
}

@article {pmid41114530,
year = {2025},
author = {Xiao, Y and Zhang, X and Shao, B and Wu, Z and Li, X and Yi, D and Li, T and Yang, T and Zhu, J and Huang, T and Deng, Y and Qiu, T and Yang, G and Sun, X and Wang, N},
title = {Hydroxytyrosol Improves Metabolic Dysfunction-Associated Fatty Liver Disease Dependent on the Modulation of Gut Microbiota.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c07003},
pmid = {41114530},
issn = {1520-5118},
abstract = {The global threat of metabolic dysfunction-associated fatty liver disease (MAFLD) is significant, but effective measures are still lacking. To explore the potential impact of hydroxytyrosol (HT), a plant polyphenol, in the metabolic outcomes of MAFLD and the mediating role of the gut microbiota, we performed an 8-week randomized placebo-controlled clinical trial in MAFLD patients and collected fecal bacteria for metagenomics analysis and targeted metabolomics. In this population-based trial, we have revealed that HT mitigates liver injury and steatosis in patients with MAFLD, as well as systemic glucolipid metabolism disorder. Through analysis of the differences in bacterial taxon and functional profiles, as well as correlation analysis between species and metabolic indicators, it was found that Fusicatenibacter saccharivorans (F. saccharivorans), the microbial species with the greatest difference after HT intervention, was also the most significantly correlated with metabolic parameters of MAFLD and showed a significant positive correlation with the content of fecal butanoic acid. Butanoic acid was further associated with MAFLD-related metabolic indexes. To confirm the potential causal relationship between alterations in gut microbiota induced by HT intervention and improved MAFLD metabolic phenotypes, fecal microbiota transplantation (FMT) was conducted using a model of pseudogerm-free mice. We have further demonstrated that the fecal microbiota from donors of MAFLD patients receiving HT supplementation can ameliorate liver and systemic phenotypes in western-diet-induced MAFLD mice, interpreting the robust action of gut microbiota remodeled by HT in improving MAFLD. Consequently, HT supplementation may represent a tactic for improving MAFLD by modulating the composition and functionality of the gut microbiota.},
}

@article {pmid41114029,
year = {2025},
author = {Li, X and Liu, Q and Wang, Y and Zhang, H and Wu, Z and Fan, R and Ma, Y and Gong, W and Li, X},
title = {Two modified colonoscopically guided fecal microbiota transplantation catheter placement methods: a retrospective study (with video).},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1641325},
pmid = {41114029},
issn = {2296-858X},
abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) transfers fecal microbiota from a healthy person into a patient for the treatment of various diseases. This study introduces two modified colonoscopically guided fecal microbiota transplantation catheter placement methods and evaluates their effectiveness and safety in clinical use.

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

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

CONCLUSION: Both modified colonoscopically guided fecal microbiota transplantation catheter placement methods demonstrated safety and effectiveness in securing the FMT catheter, meeting the needs of patients requiring multiple FMT treatments over a short period. However, further validation through large-scale randomized controlled trials is needed.},
}

@article {pmid41113141,
year = {2025},
author = {Waseem, MH and Abideen, ZU and Shoaib, A and Rehman, N and Osama, M and Sajid, B and Ahmad, R and Fahim, Z and Ansari, MW and Aimen, S and Cheema, AH and Thada, PK},
title = {Fecal Microbiota Transplantation for Treatment of Parkinson's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.},
journal = {Journal of central nervous system disease},
volume = {17},
number = {},
pages = {11795735251388781},
pmid = {41113141},
issn = {1179-5735},
abstract = {BACKGROUND: Emerging evidence has indicated gut dysbiosis as a potential modifiable contributor to the pathogenesis of Parkinson's disease (PD). Fecal microbiota transplantation (FMT), a microbiome-centric model aimed at modulating the intestinal microbial taxa, represents a novel therapeutic approach. However, its safety and efficacy profile in improving PD symptoms remains inadequately researched.

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

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

CONCLUSION: FMT shows no evidence of superiority compared to placebo. Variations in the findings of existing studies suggest that donor fecal composition, host-microbiota interactions, and methodological heterogeneity may determine outcomes. Further RCTs employing tailored microbiota and standardized endpoint metrics are required to establish a correlation between FMT and PD.},
}

@article {pmid41112298,
year = {2025},
author = {Ma, T and Zhang, T and Peng, C and Liu, K and Xiong, Y and Chen, K and Peng, N and Wei, Z and Kuang, J and Ou, L},
title = {Immune cells: the key mediator between the gut microbiota and osteoporosis.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1680021},
pmid = {41112298},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Osteoporosis/immunology/microbiology/metabolism/therapy/etiology ; Animals ; Bone and Bones/immunology/metabolism ; Probiotics ; },
abstract = {As the body's largest immunological interface, the intestine harbors a complex ecosystem of gut microbiota (GM) that orchestrates mucosal immune maturation while sustaining local immunological equilibrium. Emerging evidence reveals the gut's influence on skeletal homeostasis via neuro-immune-endocrine pathways-termed the gut-bone axis-though its mechanistic intricacies remain incompletely defined. Since the concept of osteoimmunology was proposed in 2000 by Arron & Choi, immune-skeletal interactions have garnered significant research traction. Immune cells primarily contribute to the maintenance of bone homeostasis through the release of pro- and anti-inflammatory factors. Consequently, the immune system represents a crucial intermediary in understanding the relationship between GM and metabolic bone diseases. This review synthesizes the interrelationships among gut microbiota, immune cells, and osteoporosis, and elucidates how GM modulate bone metabolism in osteoporosis through this critical intermediary. Furthermore, building upon the microbiome-immune-bone axis, we highlight several emerging microbiota-targeted interventions-such as probiotics, prebiotics, dietary modifications, fecal microbiota transplantation, and engineered microbes-and evaluate their clinical translational potential, with the aim of advancing diagnostic and therapeutic strategies for metabolic bone disorders.},
}

Humans
*Gastrointestinal Microbiome/immunology
*Osteoporosis/immunology/microbiology/metabolism/therapy/etiology
Animals
Bone and Bones/immunology/metabolism
Probiotics

@article {pmid41112050,
year = {2025},
author = {Wang, W and Bu, N and Cao, H and Chen, N and Chen, W and Cheng, L and Cui, B and Dai, L and Gao, H and Guo, M and He, X and Hu, J and Jiang, C and Jiang, X and Li, J and Li, P and Li, W and Liao, W and Liu, H and Liu, J and Liu, L and Liu, S and Liu, X and Lv, M and Ma, Y and Man, C and Pi, Z and Ren, Q and Sang, L and Sun, Z and Suo, H and Tan, Y and Tao, W and Wang, G and Wang, J and Wang, L and Wang, X and Wang, X and Wang, Y and Wu, K and Wu, R and Wu, Z and Xiao, X and Xiang, B and Yang, S and Yi, H and Yu, H and Yu, J and Zeng, Y and Zhai, H and Zhai, Q and Zhang, C and Zhang, G and Zhang, J and Zhang, W and Zhao, F and Zhao, L and Zhou, H and Zhu, L and Lan, C and Zhang, H and Zhu, S and Zhang, F},
title = {Shaping the future of probiotics, live biotherapeutic products, and fecal microbiota transplantation: 30 scientific recommendations from the CHINAGUT Conference.},
journal = {iMeta},
volume = {4},
number = {5},
pages = {e70083},
pmid = {41112050},
issn = {2770-596X},
abstract = {The 2025 CHINAGUT Conference has assembled a panel of 63 experts (30 scientists, 26 physicians, and 7 corporate R&D personnel) collaborated in three groups to present 30 scientific recommendations to advance probiotics, live biotherapeutic products, and fecal microbiota transplantation, addressing key issues on standardization, translation, supervision, regulation, and regulatory harmonization. These interdisciplinary guidelines aim to synthesize cutting-edge knowledge and practical needs to transform microbiota-based treatments from applications into precision-driven medical solutions, and serve as reference by scientific researchers, medical educators, pharmaceutical enterprises, clinicians, food and drug administrations, policymakers, and patients.},
}

@article {pmid41112042,
year = {2025},
author = {Lin, A and Xiong, M and Jiang, A and Huang, L and Wong, HZH and Feng, S and Zhang, C and Li, Y and Chen, L and Chi, H and Zhang, P and Ye, B and Zhang, H and Zhang, N and Zhu, L and Mou, W and Shen, J and Li, K and Xu, W and Ying, H and Zhang, C and Zeng, D and Xie, J and Deng, X and Wang, Q and Xu, J and Shi, W and Qi, C and Qu, C and Huang, X and Hajdu, A and Li, C and Peng, C and Cao, X and Pei, G and Zhang, L and Huo, Y and Xu, J and Glaviano, A and Szöllősi, AG and Bian, S and Li, Z and Tang, H and Tang, B and Liu, Z and Zhang, J and Miao, K and Cheng, Q and Wei, T and Yuan, S and Luo, P},
title = {The microbiome in cancer.},
journal = {iMeta},
volume = {4},
number = {5},
pages = {e70070},
pmid = {41112042},
issn = {2770-596X},
abstract = {The human microbiome is now recognized as a central regulator of cancer biology, intricately shaping tumor development, immune dynamics, and therapeutic response. This comprehensive review delineates the multifaceted roles of bacteria, viruses, and fungi in modulating the tumor microenvironment and systemic immunity across diverse cancer types. We synthesize current evidence on how microbial dysbiosis promotes carcinogenesis via chronic inflammation, metabolic reprogramming, genotoxic stress, immune evasion, and epigenetic remodeling. This review emphasizes organ-specific microbiome signatures and highlights their potential as non-invasive biomarkers for early detection, treatment stratification, and prognosis. Furthermore, we explore the impact of intratumoral microbiota on cancer therapies, uncovering how microbial metabolites and host-microbe interactions shape therapeutic efficacy and resistance. Finally, advances in microbiome-targeted strategies, such as probiotics, fecal microbiota transplantation, and engineered microbes offer new avenues for adjunctive cancer therapy. This review provides a roadmap for future investigation and underscores the transformative promise of microbiome modulation in cancer prevention and treatment.},
}

@article {pmid41111893,
year = {2025},
author = {Fu, Z and Yu, T and Meng, C and Zhang, G and Huang, S and Li, Y and Fu, L and Deng, Z},
title = {Tortoise Oligopeptides Augment Cyclophosphamide's Antitumor Activity Through Dual Modulation of Therapeutic Efficacy and Hematologic Toxicity.},
journal = {Food science & nutrition},
volume = {13},
number = {10},
pages = {e71078},
pmid = {41111893},
issn = {2048-7177},
abstract = {Cyclophosphamide (CTX) is a widely used chemotherapeutic agent, but its efficacy is often limited by leukopenia, a common adverse effect for which effective preventive strategies are currently lacking. In this study, oligopeptides were prepared from a blend of three edible tortoise species (Cuora trifasciata, Mauremys mutica, and Chinemys reevesii) and evaluated for their potential to alleviate CTX-induced leukopenia. The resulting Tortoise Oligopeptides (TOPs) were characterized primarily as small molecules with molecular weights under 5 kDa and peptide lengths between 4 and 15 amino acids, rich in glycine, glutamic acid, and proline. In a mouse model, TOPs administration significantly ameliorated CTX-induced leukopenia in a dose-dependent manner, attenuated pathological damage in the spleen and femur, and correlated with elevated serum levels of IL-4, IL-1β, TNF-α, and IFN-γ. In CTX-treated tumor-bearing mice, TOPs not only reduced leukopenia but also enhanced the antitumor efficacy of CTX. Correlation analyses linked leukocyte recovery to increased relative abundance of gut microbiota genera such as Colidextribacter, Tyzzerella, Prevotellaceae_UCG_001, and Rikenella. KEGG pathway analysis and fecal microbiota transplantation (FMT) experiments indicated that TOPs alleviate CTX-induced granulocytopenia partly through modulation of the gut microbiota. Additionally, LC-MS/MS sequencing combined with bioinformatic prediction and molecular docking identified several peptides-including PAIPAPPVGPGPK, FSFPTLPF, and PGLPFHP-with high binding affinity to key tumor targets (BCL-2, MDM2, EGFR), suggesting intrinsic antitumor properties. These findings indicate that TOPs may serve as a specialized medical food to mitigate CTX-induced leukopenia through multimodal mechanisms involving immunonutrition, gut microbiota regulation, and direct antitumor peptide effects.},
}

@article {pmid41111149,
year = {2025},
author = {Cai, K and Chen, Z and Wu, J and Wang, Q and Zhou, X and Pan, B and Xie, Z and Li, P and Chen, F and Chen, H and Liao, Q},
title = {Qing-Kai-Ling oral liquid alleviates non-alcoholic fatty liver disease via remodeling gut microbiota and activating AMPK/ACC1 axis.},
journal = {Chinese medicine},
volume = {20},
number = {1},
pages = {177},
pmid = {41111149},
issn = {1749-8546},
support = {2023B03J1382//Guangzhou Science and Technology Program/ ; 2022ZD004//Nansha Science and Technology Program/ ; 2024A1515011747//Guangdong Basic and Applied Basic Research Foundation/ ; },
abstract = {BACKGROUND: Qing-Kai-Ling (QKL) oral liquid, evolving from a classical Chinese formula known as An-Gong-Niu-Huang pills, has demonstrated hepatoprotective, lung-protective, and gut microbiota-modulating properties. However, its efficacy in preventing high fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and its relationship with gut microbiota and hepatic inflammation remain unclear.

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

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

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

CONCLUSION: These findings established QKL as a microbiota-modulating therapeutic agent for NAFLD through SCFA-AMPK/ACC1 axis activation, providing a foundation for developing QKL-based treatments.},
}

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

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

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

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

IMPACT AND IMPLICATIONS: The majority of patients with hepatocellular carcinoma (HCC) are diagnosed losing the chance of surgical resection. Transarterial chemoembolization (TACE) is widely used for treating unresectable HCC; however, its long-term outcome is significantly limited by its main complication, i.e., liver injury (LI). In addition to traditional cognition of the direct liver damage of the ischemic necrosis or regional chemotherapy induced by TACE, the deeper mechanisms underlying TACE-induced LI (TACE-LI) remain largely unclear. Gut microbiota can modulate various liver diseases but its exact role in TACE-LI has not been reported. We found that TACE could disturb the gut microbiota. This disturbance was characterized by reduced levels of Limosilactobacillus reuteri (L. reuteri) and its metabolite indole-3-lactic acid (ILA), which were correlated with aggravated TACE-LI and poor overall survival in HCC. Administration of L. reuteri or ILA significantly improved TACE-LI by inhibiting the inflammation of macrophages. Our study is the first report highlighting gut microbiota disturbances as an important cause of TACE-LI; administration of L. reuteri or ILA represents a viable and secure strategy for preventing TACE-LI, thereby reducing the adverse effects of TACE and yielding better prognoses in patients with HCC.},
}

@article {pmid41110352,
year = {2025},
author = {Yuan, Y and Hu, J and Lu, X and Han, H and Wang, M and Zhang, W and Jiao, Y and Li, Y and Lin, Z and Liang, C and Yu, Y and Xie, C and Li, J and Mao, T},
title = {Oral rhein attenuate nonalcoholic steatohepatitis in mice through the modulation of gut microbiota and Th17 cell differentiation.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {148},
number = {},
pages = {157409},
doi = {10.1016/j.phymed.2025.157409},
pmid = {41110352},
issn = {1618-095X},
abstract = {BACKGROUND: Non-alcoholic steatohepatitis (NASH) is an important clinical issue and a challenge in the field of global public health. However, there are very few clinically approved drugs that can effectively treat NASH. Rhein is a natural organic compound with anti-inflammatory and antioxidant properties, but the specific role and mechanism on NASH remain unexplored.

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

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

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

CONCLUSIONS: Collectively, our results suggested that orally administrated rhein reduced hepatic lipid deposition through the modulation of dysregulated gut microbiota and bile acids metabolism, thus regulating Th17/Treg immune balance. This study uncovers a novel mechanistic axis in NASH pathogenesis and providing new research directions for microbiota-targeted clinical strategies.},
}

@article {pmid41109696,
year = {2025},
author = {Bunchorntavakul, C and Reddy, KR},
title = {Current Status and Future Directions in the Pharmacologic Management of Cirrhosis.},
journal = {Clinics in liver disease},
volume = {29},
number = {4},
pages = {657-672},
doi = {10.1016/j.cld.2025.06.003},
pmid = {41109696},
issn = {1557-8224},
mesh = {Humans ; *Liver Cirrhosis/drug therapy/complications ; Adrenergic beta-Antagonists/therapeutic use ; Angiotensin Receptor Antagonists/therapeutic use ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Anticoagulants/therapeutic use ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Fecal Microbiota Transplantation ; Albumins/therapeutic use ; Rifaximin ; },
abstract = {In recent years, the necessity for pharmacologic treatments to mitigate the risk of hepatic decompensation has been highlighted, with non-selective beta-blockers identified as the most effective option. However, a significant therapeutic gap persists, and additional or alternative treatments have been proposed, including statins, rifaximin, albumin, anticoagulants, angiotensin receptor blockers, granulocyte-colony stimulating factor, and fecal microbial transplant. According to the data from limited clinical trials, these pharmacotherapies offer promising possibilities; nonetheless, additional investigations, particularly randomized controlled trials, are required, in some instances, prior to their incorporation into routine clinical practice.},
}

Humans
*Liver Cirrhosis/drug therapy/complications
Adrenergic beta-Antagonists/therapeutic use
Angiotensin Receptor Antagonists/therapeutic use
Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
Anticoagulants/therapeutic use
Granulocyte Colony-Stimulating Factor/therapeutic use
Fecal Microbiota Transplantation
Albumins/therapeutic use
Rifaximin

@article {pmid41109693,
year = {2025},
author = {Wagh, RS and Shasthry, SM and Sarin, SK},
title = {New Approaches to Alcohol-Associated Hepatitis.},
journal = {Clinics in liver disease},
volume = {29},
number = {4},
pages = {595-626},
doi = {10.1016/j.cld.2025.06.012},
pmid = {41109693},
issn = {1557-8224},
mesh = {Humans ; *Hepatitis, Alcoholic/therapy ; Liver Transplantation ; Fecal Microbiota Transplantation ; Plasma Exchange ; Granulocyte Colony-Stimulating Factor/therapeutic use ; },
abstract = {Severe alcohol-associated hepatitis (SAH) remains a difficult-to-treat severe liver ailment with limited therapeutic options and high mortality. The article reviews new data to help identify the steroid non-responders at the baseline to reduce the risk of infections and increased mortality. New information on the use of growth factors, such as granulocyte-colony stimulating factor, plasma exchange, and fecal microbiota transplantation, has been provided to choose as a monotherapy or with steroids for SAH. Early selection for liver transplantation after careful ethical considerations and risks of recidivism post-transplant can help improve survival upto 70% to 80%.},
}

Humans
*Hepatitis, Alcoholic/therapy
Liver Transplantation
Fecal Microbiota Transplantation
Plasma Exchange
Granulocyte Colony-Stimulating Factor/therapeutic use

@article {pmid41109415,
year = {2025},
author = {Alasbly, G and Alotaishan, S and Algindan, Y and Khattab, R},
title = {Risk Factors for Nosocomial Clostridioides Difficile Infection-Induced Diarrhea in Patients Receiving Enteral Feeding: A Scoping Review.},
journal = {The Journal of hospital infection},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jhin.2025.10.005},
pmid = {41109415},
issn = {1532-2939},
abstract = {BACKGROUND: Nosocomial Clostridioides difficile infection (CDI)-induced diarrhea is a major healthcare-associated infection, particularly in critically ill patients. Antibiotic use and disruptions in gut microbiota are known risk factors, and the role of enteral feeding (EF) requires further exploration.

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

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

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

CONCLUSION: EF may contribute to CDI risk through its impact on gut microbiota and related factors. While certain EF strategies show potential benefits, further research is needed to determine their role in CDI prevention and to develop evidence-based nutritional guidelines for at-risk patients.},
}

@article {pmid41108334,
year = {2025},
author = {Chang, A and Oh, J and Shin, A and Oser, M and Manitius, N and Ghaffari, A and Limketkai, BN},
title = {Similar Symptoms, Distinct Syndromes: Multi-modal Approach to the Patient with an IBD-IBS Overlap.},
journal = {Digestive diseases and sciences},
volume = {},
number = {},
pages = {},
pmid = {41108334},
issn = {1573-2568},
abstract = {Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are distinct gastrointestinal conditions, but they frequently share overlapping clinical symptoms such as abdominal pain, bloating, and altered bowel habits. IBD is defined by the presence of chronic immune-mediated inflammation, and IBS is characterized by gastrointestinal symptoms in the absence of endoscopic and histologic inflammation. When patients with IBD continue to experience IBS-like symptoms despite remission of inflammation, this phenomenon is commonly referred to as IBD-IBS overlap. These patients pose diagnostic and therapeutic challenges, as symptom persistence may reflect lingering immune activation, disrupted barrier function, visceral hypersensitivity, gut-brain axis dysfunction, or microbiome alterations. This review synthesizes emerging evidence on the shared mechanisms underlying IBD and IBS and outlines a multimodal treatment approach that includes pharmacologic management, dietary interventions, mind-body therapies, and microbiome-directed strategies such as probiotics and fecal microbiota transplantation.},
}

@article {pmid41107170,
year = {2025},
author = {Taylor, NA and Sivam, S and van Dorst, J and Coffey, MJ and Visser, S and Haber, P and Volovets, A and Ooi, CY},
title = {Stool and symptom testing in ColoREctal Evaluation for Neoplasia in Cystic Fibrosis (SCREEN-CF).},
journal = {Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jcf.2025.09.008},
pmid = {41107170},
issn = {1873-5010},
abstract = {BACKGROUND: People with cystic fibrosis (pwCF) have increased colorectal cancer (CRC) risk. Colonoscopy is recommended, yet CF comorbidities increase complexity and risk.

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

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

CONCLUSION: CRC screening in pwCF is critical given the high prevalence of neoplasia. Alternative non-invasive screening may support risk stratification among individuals with comorbidities, or reluctance, though performance could be influenced by CFTR modulator therapy.},
}

@article {pmid41106539,
year = {2025},
author = {Wang, R and Tang, D and Wu, L and Ou, L and Ding, L and Jiang, J and Wu, Y},
title = {Bielong Ruangan decoction inhibits tumor growth and improves immune response in a hepatocellular carcinoma mouse model through gut microbiota.},
journal = {The international journal of biochemistry & cell biology},
volume = {},
number = {},
pages = {106873},
doi = {10.1016/j.biocel.2025.106873},
pmid = {41106539},
issn = {1878-5875},
abstract = {Hepatocellular carcinoma (HCC) is a leading cause of cancer fatality worldwide. It is closely linked to the gut-liver axis, which plays a crucial role in nutrient metabolism, immune responses, and the biotransformation of bacterial metabolites. Traditional Chinese Medicine (TCM), as an adjuvant treatment, is important in the treatment course of HCC. This study aimed to explore the effects of Bielong Ruangan decoction (BLRG) on HCC. It is a traditional Chinese medicine formula used for liver fibrosis and cancer. The study focuses on its impact on gut microbiota and associated mechanisms. An orthotopic liver transplantation model was established in mice in the presence or absence of BLRG treatment, and the therapeutic effects of BLRG were evaluated. BLRG significantly inhibited tumor growth in an orthotopic liver transplantation mouse model, by reducing tumor size, liver weight, volume, Ki-67, and serum AFP levels. It also enhanced intestinal barrier functions by lowering serum LPS levels, increasing intestinal mucus thickness, and boosting ZO-1 and occludin mRNA levels. Moreover, BLRG modulated immune responses, decreasing inflammatory cytokines (IL-10 and IL-1β) while increasing anti-tumor cytokines (IFN-α, IFN-γ, and IL-2). A notable shift in gut microbiota composition was observed, accompanied by a decrease in Mucispirillum_sp. and Helicobacter_typhlonius post-treatment. Serum metabolomic profiling confirmed these findings and revealed a positive correlation between Mucispirillum and triglycerides (TG). Fecal Microbiota Transplantation (FMT) experiments further highlighted the gut microbiota's role in mediating BLRG's anti-tumor effects, demonstrating decreased tumor metrics and improved serum AFP levels, intestinal permeability, and immune responses in recipient mice. These results underscore BLRG's potential as an adjunctive therapeutic agent in liver cancer, demonstrating its ability to modulate tumor growth, gut microbiota, and immune responses, thereby potentially reshaping the HCC therapeutic landscape.},
}

@article {pmid41106199,
year = {2025},
author = {Yu, Z and Wu, J and Han, J and Wang, L and Lu, R and Chen, J and Wang, K and Shi, Z},
title = {Triclosan induced obesity via gut microbiota dysbiosis and butyrate reduction.},
journal = {Ecotoxicology and environmental safety},
volume = {305},
number = {},
pages = {119227},
doi = {10.1016/j.ecoenv.2025.119227},
pmid = {41106199},
issn = {1090-2414},
abstract = {Triclosan (TCS) can influence energy metabolism and is a potential obesogen. However, its underlying mechanisms remain largely unknown. This study investigated how low-dose TCS exposure (0.5 mg/kg/day) disrupts energy metabolism in Sprague-Dawley rats. TCS increased body weight, visceral fat, liver lipid accumulation, and serum triglyceride levels. It also promoted hyperphagia by altering hypothalamic appetite regulation, activating orexigenic neuropeptide Y neurons and suppressing anorexigenic pro-opiomelanocortin neurons. Furthermore, TCS may reduce brown adipose tissue thermogenesis, as indicated by decreased mitochondrial uncoupling protein 1 and tyrosine hydroxylase. These metabolic effects were blocked by subdiaphragmatic vagotomy, confirming gut-brain neural circuit involvement. Mechanistically, TCS reduced gut microbial diversity and butyrate levels. Crucially, both fecal microbiota transplantation from control rats and butyrate supplementation reversed TCS-induced metabolic dysregulation. These findings reveal that TCS-induced gut dysbiosis and butyrate reduction as key drivers of metabolic disturbances and offer insights into the role of environmental chemicals in obesity and potential therapeutic strategies targeting the gut microbiota and butyrate.},
}

@article {pmid41105383,
year = {2025},
author = {Carlsen, A and Steinsbø, Ø and Kvaløy, JT and Aabakken, L and Bolstad, N and Warren, DJ and Karlsen, L and Lundin, KEA and Omdal, R and Grimstad, T},
title = {Optimizing serum adalimumab levels in maintenance therapy via proactive therapeutic drug monitoring improves markers of disease activity in Crohn's disease.},
journal = {Scandinavian journal of gastroenterology},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/00365521.2025.2573725},
pmid = {41105383},
issn = {1502-7708},
abstract = {OBJECTS: The benefit of a proactive therapeutic drug monitoring (TDM) strategy in patients with inflammatory bowel disease receiving biological therapy remains disputed. We aimed to evaluate whether optimizing serum adalimumab levels (s-ADL), guided by proactive TDM, is associated with improved markers of disease activity in patients with Crohn's disease.

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

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

CONCLUSION: Proactive TDM-guided optimization of s-ADL levels in Crohn's disease patients on adalimumab maintenance therapy was associated with the modest but significant improvements in markers of disease activity over one year of follow-up.},
}

@article {pmid41104042,
year = {2025},
author = {Yassin, LK and Skrabulyte-Barbulescu, J and Alshamsi, SH and Saeed, S and Alkuwaiti, SH and Almazrouei, S and Alnuaimi, A and BaniYas, S and Aldhaheri, D and Alderei, M and Shehab, S and Hamad, MIK},
title = {The microbiota-gut-brain axis in mental and neurodegenerative disorders: opportunities for prevention and intervention.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1667448},
pmid = {41104042},
issn = {1663-4365},
abstract = {The microbiota-gut-brain axis (MGBA) is increasingly recognized as a critical regulator of brain health, influencing both neurodevelopment and age-related neurological decline. Disruptions in this axis, driven by gut dysbiosis, have been implicated in the pathogenesis of a wide range of neurodegenerative and neuropsychiatric disorders. This review synthesizes current evidence linking microbiota alterations to Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and stroke-including post-stroke cognitive impairment (PSCI), as well as major depressive disorder (MDD), bipolar disorder (BD), anxiety disorders, post-traumatic stress disorder (PTSD), and chronic fatigue syndrome (CFS). Common findings include reduced microbial diversity, depletion of short-chain fatty acid (SCFA)-producing genera, and enrichment of pro-inflammatory taxa. These changes contribute to neuroinflammation, blood-brain barrier (BBB) dysfunction, microglial activation, and neurotransmitter imbalances. The review further explores the neurotoxic effects of external factors such as radiation and xenobiotics on the MGBA. Despite disorder-specific variations, shared microbial and immunological mechanisms emerge across the spectrum of conditions. Importantly, we present current and emerging strategies aimed at restoring gut-brain communication, including dietary interventions such as fiber-rich and Mediterranean diets, SCFA supplementation, probiotics, and fecal microbiota transplantation (FMT). These approaches show promise in alleviating cognitive and emotional symptoms, modulating immune responses, and potentially slowing disease progression. By integrating mechanistic insights with therapeutic perspectives, this review underscores the gut microbiota as a modifiable factor in neuropsychiatric and neurodegenerative disease. Targeting the MGBA offers a novel, translational approach to intervention that may ultimately contribute to healthier brain aging and improved outcomes across the lifespan.},
}

@article {pmid41103946,
year = {2025},
author = {Zhou, L and Li, B and Ren, J and Wang, S and Wang, J},
title = {Microbiome-mediated regulation of chemoradiotherapy response.},
journal = {Frontiers in oncology},
volume = {15},
number = {},
pages = {1659467},
pmid = {41103946},
issn = {2234-943X},
abstract = {The gut microbiota critically influences patient responses to chemoradiotherapy through bidirectional interactions with host physiology, modulating both therapeutic efficacy and toxicity. Radiotherapy and chemotherapy disrupt microbial homeostasis, exacerbating intestinal damage, systemic inflammation, and immune dysfunction, while specific commensals and metabolites enhance treatment response via metabolic reprogramming, DNA repair regulation, and immune activation. Key mechanisms include microbiota-mediated TLR/NF-κB signaling, SCFA-dependent epigenetic modifications, and microbial enhancement of immune checkpoint inhibitors. Clinical interventions such as probiotics, fecal microbiota transplantation, and targeted antibiotics demonstrate potential to mitigate toxicity and overcome resistance. This review summarizes emerging evidence on how microbial dysbiosis induced by radiotherapy and chemotherapy exacerbates intestinal damage, systemic inflammation, and immune dysfunction, while specific commensals and metabolites enhance chemoradiotherapy response via metabolic reprogramming, DNA repair modulation, and immune activation. These findings underscore the gut microbiota as a critical determinant of chemoradiotherapy precision, offering actionable targets for microbiome-guided therapeutic optimization.},
}

@article {pmid41102296,
year = {2025},
author = {Udomkarnjananun, S and Chuaypen, N and Metta, K and Dissayabutra, T and Sodsai, P and Kittiskulnam, P and Tangkijvanich, P},
title = {Dietary composition modulate gut microbiota and related biomarkers in patients with chronic kidney disease.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {36274},
pmid = {41102296},
issn = {2045-2322},
support = {PMU-B, grant number B36G660010//the NSRF via the Program Management Unit for Human Resources & Institutional Development, Research and Innovation (PMU-B, grant number B36G660010)/ ; },
mesh = {Humans ; *Renal Insufficiency, Chronic/microbiology/blood ; *Gastrointestinal Microbiome ; Male ; Female ; *Biomarkers/blood ; Middle Aged ; Methylamines/blood ; Cross-Sectional Studies ; Aged ; Cytokines/blood ; Feces/microbiology ; *Diet ; Dietary Fiber ; Adult ; RNA, Ribosomal, 16S/genetics ; },
abstract = {Emerging evidence indicates gut microbiota is essential to chronic kidney disease (CKD) progression. This study investigated the association between gut microbiota profiles, plasma trimethylamine-N-oxide (TMAO), and circulating inflammatory markers in CKD patients according to dietary patterns, particularly low-protein, high-fiber (LP-HF) versus high-protein, low-fiber (HP-LF) diet. In this cross-sectional study, patients with non-dialysis CKD and healthy subjects were enrolled. Dietary patterns among participants were assessed using three-day diet records with detailed nutrient analysis. The 16 S ribosomal RNA sequencing was conducted to examine fecal gut microbiota composition. Plasma samples were analyzed for TMAO concentration and cytokine levels. A total of 135 CKD patients were recruited. A distinct shift in gut microbiota composition in CKD patients was observed compared to 19 healthy controls, particularly a significant reduction of short-chain fatty acid (SCFA)-producing bacteria. TMAO and several cytokine levels were significantly elevated in CKD patients compared to healthy subjects. Within CKD, patients with LP-HF diet displayed a greater abundance of SCFA-producing bacteria, such as the Lachnospiraceae NK4A136 group and Eubacterium ruminantium group, than those with the HP-LF diet. The HP-LF subgroup showed enriched proteolytic bacterial genera such as Klebsiella. The HP-LF subgroup also exhibited significantly higher plasma levels of TMAO, interleukin (IL)-18, and monocyte chemoattractant protein-1 (MCP-1). CKD patients displayed marked alterations in gut bacterial composition compared to healthy controls. Our results also highlighted the potential advantages of adopting a high fiber-rich and low-protein diet intake in reducing gut dysbiosis in CKD patients.},
}

Humans
*Renal Insufficiency, Chronic/microbiology/blood
*Gastrointestinal Microbiome
Male
Female
*Biomarkers/blood
Middle Aged
Methylamines/blood
Cross-Sectional Studies
Aged
Cytokines/blood
Feces/microbiology
*Diet
Dietary Fiber
Adult
RNA, Ribosomal, 16S/genetics

@article {pmid41101217,
year = {2025},
author = {Liu, XL and Wu, SY and Zou, ZP and Xian, X and Wang, J and Min, L and Zhou, Y and Houf, K and Yu, Z},
title = {Characterization and intestinal pathogenicity of Proteus mirabilis isolated from broiler carcasses and processing environments.},
journal = {International journal of food microbiology},
volume = {445},
number = {},
pages = {111487},
doi = {10.1016/j.ijfoodmicro.2025.111487},
pmid = {41101217},
issn = {1879-3460},
abstract = {Proteus mirabilis, a well-known urinary tract pathogen, is increasingly recognized as a food safety concern due to its frequent detection in meat products, particularly poultry. Sporadic reports indicate gastrointestinal symptoms linked to P. mirabilis, but the relationship between its genome, antibiotic resistance, and variable pathogenicity remains unclear. In this study, 142 P. mirabilis isolates were collected from broiler carcasses and processing environments in wet markets and industrial facilities to assess contamination levels. Thirty-six representative isolates were characterized for genomic heterogeneity, antibiotic resistance, and virulence gene profiles using whole-genome sequencing and phenotypic susceptibility testing. Selected strains were further assessed for intestinal pathogenicity in a murine model. Broiler carcasses from wet markets had significantly higher contamination rates (80.77 %, 21/26) than industrial sources (41.67 %, 5/12), with all wet market samples (13/13) testing positive. Overall, 94.4 % of isolates were multidrug-resistant, with carcass isolates showing higher resistance than environmental isolates. Animal experiments demonstrated variable pathogenicity, including intestinal injury, villus disruption, epithelial shedding, goblet cell loss, inflammatory cytokine elevation, and gut dysbiosis. Dysbiosis induced by certain strains (e.g., R638) was linked to intestinal injury, as confirmed by fecal microbiota transplantation. These findings highlight P. mirabilis as a highly heterogeneous foodborne pathogen, emphasizing the need for targeted hygiene practices, particularly in wet market processing environments.},
}

@article {pmid41100443,
year = {2025},
author = {Shi, F and Zou, D and Zhang, L and Guo, N and Yu, J and Degen, AA and Tang, X and Ren, S and Ru, Y and Zheng, S and Zhang, Y and Wang, D},
title = {Increased urea nitrogen salvaging by a remodeled gut microbiota helps nonhibernating pikas maintain protein homeostasis during winter.},
journal = {PLoS biology},
volume = {23},
number = {10},
pages = {e3003436},
doi = {10.1371/journal.pbio.3003436},
pmid = {41100443},
issn = {1545-7885},
mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; *Nitrogen/metabolism ; *Urea/metabolism ; Seasons ; *Lagomorpha/metabolism/microbiology/physiology ; Homeostasis ; *Proteostasis/physiology ; Feces/microbiology ; Diet, Protein-Restricted ; Male ; Liver/metabolism ; Herbivory ; Fecal Microbiota Transplantation ; },
abstract = {Nitrogen balance is a major challenge for herbivores when consuming a low-nitrogen diet. Gut microbiota-mediated urea nitrogen recycling facilitates protein homeostasis during times of nitrogen deficiency, yet its relevance to wild nonhibernating small mammals remains unclear. Here, through a combination of isotope tracing, metagenomics, targeted short-chain fatty acid analysis, and fecal microbiota transplantation, we investigated the effects of protein restriction in winter on urea nitrogen recycling in plateau pikas (Ochotona curzoniae) of the Qinghai-Tibetan Plateau. Hepatic urea-cycle metabolism was downregulated during winter protein restriction, accompanied by increases in beneficial bacteria with ureolytic capacity (such as the genus Alistipes), gut urease activity, and urea transporters, and acetate production, with a consequent increase in nitrogen reincorporation into the pika's protein pool. Critically, supplementing a low-protein diet with yak fecal microbiota enhanced the ureolytic capacity by increasing Alistipes abundance, revealing a critical mechanism whereby interspecies horizontal microbial transfer between sympatric species enhances host protein homeostasis. Our results reveal a functional role for the gut microbiota in urea nitrogen recycling to maintain protein balance in winter-active herbivorous small mammals and contribute to our understanding of species coexistence and mammalian adaptation to high-altitude environments. Our findings establish that microbiota-driven urea nitrogen recycling is a key adaptive strategy for protein homeostasis in winter-active herbivores. This work provides new insights into the mechanisms of mammalian adaptation to high-altitude environments and the dynamics of interspecies coexistence.},
}

*Gastrointestinal Microbiome/physiology
Animals
*Nitrogen/metabolism
*Urea/metabolism
Seasons
*Lagomorpha/metabolism/microbiology/physiology
Homeostasis
*Proteostasis/physiology
Feces/microbiology
Diet, Protein-Restricted
Male
Liver/metabolism
Herbivory
Fecal Microbiota Transplantation

@article {pmid41098769,
year = {2025},
author = {Li, Y and Xin, Y and Zong, W and Li, X},
title = {The role of oral microbiota in digestive system diseases: current advances and perspectives.},
journal = {Journal of oral microbiology},
volume = {17},
number = {1},
pages = {2566403},
pmid = {41098769},
issn = {2000-2297},
abstract = {The oral microbiota is intimately linked to human health and various disease states. With the advent of the Human Microbiome Project, our comprehension of the oral microbiota has substantially improved. This microbial community is not only associated with a range of oral diseases, such as dental caries and periodontal diseases, but also with numerous digestive disorders, as demonstrated by recent clinical studies. Specific bacteria residing in the oral cavity, such as Porphyromonas gingivalis, Fusobacterium species and Streptococcus species, have been shown to translocate to the gastrointestinal tract, thereby establishing a potential connection between the oral and gut microbiota. The transfer and ectopic colonization of oral microbiota within the gastrointestinal tract may contribute to both the onset and exacerbation of gastrointestinal diseases. Following the principles of dysregulation characteristics, mechanism research and innovative treatment, this paper systematically reviews the association between the oral microbiota and various digestive system diseases. This paper explores how specific oral microbiota drive digestive system diseases mechanisms and evaluates treatments including probiotics, prebiotics, fecal microbiota transplantation, and targeted antimicrobial therapies. By clarifying the oral-gut microbiota-disease link, it highlights oral microbiota monitoring as a promising tool for early detection, diagnosis, and therapy.},
}

@article {pmid41097970,
year = {2025},
author = {Ma, Y and Huang, J and Zhuo, Q and Shen, S and Zhang, B and Wang, H and Zhang, J and Wang, O},
title = {[Impact of high-fat diet on intestinal fat absorption and fatty acid metabolism in rats transplanted with gut microbiota from hypertriglyceridemic individuals].},
journal = {Wei sheng yan jiu = Journal of hygiene research},
volume = {54},
number = {5},
pages = {757-762},
doi = {10.19813/j.cnki.weishengyanjiu.2025.05.008},
pmid = {41097970},
issn = {1000-8020},
mesh = {Animals ; Male ; *Diet, High-Fat/adverse effects ; Rats ; *Gastrointestinal Microbiome/physiology ; Rats, Sprague-Dawley ; *Fatty Acids/metabolism ; *Fecal Microbiota Transplantation ; *Intestinal Absorption ; *Hypertriglyceridemia/metabolism/microbiology ; Fatty Acids, Volatile/metabolism ; Humans ; Feces/microbiology ; Lipid Metabolism ; },
abstract = {OBJECTIVE: To investigate the effects of fecal microbiota transplantation on fat absorption rate, fatty acid metabolic flux, and short-chain fatty acid production in germ-free Sprague-Dawley(SD) rats.

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

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

CONCLUSION: In contrast to the positive regulation of lipid metabolism in rats by colonization with non-high-TG microbiota, colonization with high-TG microbiota disrupts lipid metabolism balance, inhibits the excretion of saturated fatty acids and oleic acid, reduces butyrate production, increases fat absorption rate, elevates the risk of obesity, and may synergize with a high-fat diet to exacerbate intestinal lipid metabolism disorders.},
}

Animals
Male
*Diet, High-Fat/adverse effects
Rats
*Gastrointestinal Microbiome/physiology
Rats, Sprague-Dawley
*Fatty Acids/metabolism
*Fecal Microbiota Transplantation
*Intestinal Absorption
*Hypertriglyceridemia/metabolism/microbiology
Fatty Acids, Volatile/metabolism
Humans
Feces/microbiology
Lipid Metabolism

@article {pmid41097199,
year = {2025},
author = {Dey, P},
title = {All That Glitters Ain't Gold: The Myths and Scientific Realities About the Gut Microbiota.},
journal = {Nutrients},
volume = {17},
number = {19},
pages = {},
doi = {10.3390/nu17193121},
pmid = {41097199},
issn = {2072-6643},
mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; Dysbiosis/microbiology ; Probiotics ; Diet ; Fecal Microbiota Transplantation ; },
abstract = {Gut microbial modulation through diet is central to human health and disease. Despite tremendous effort in understanding the impact of nutrients and drugs on the gut microbiota, and attempts to develop dietary strategies that facilitate gut-beneficial effects, several erroneous gut microbiota-associated concepts remain prevalent in popular belief. This article discusses widespread misconceptions about the gut microbiota, contrasting them with contemporary scientific facts. In this article, ten prevalent myths, including the obsolete 10:1 bacteria-to-human-cell ratio, the reductive categorization of microbes as 'good' or 'bad', and the discredited universal biomarker status of the Firmicutes/Bacteroidetes ratio in relation to metabolic diseases, have been debunked. Essential facts highlighting the context-dependency of the microbiome, considerable inter-individual heterogeneity, and dynamic reactivity to dietary changes are discussed. This questions the assumptions that increased diversity always signifies health, that probiotics are intrinsically safe, that fecal microbiota transplantation is a universal remedy, or that leaky gut syndrome constitutes a clearly defined diagnosis. It is highlighted that eubiosis and dysbiosis do not possess uniform criteria, and microbiome-drug interactions are extremely individualized. The gut microbiota operates as a dynamic, adaptive ecosystem, necessitating sophisticated, evidence-based methodologies for study and therapeutic application, transcending simplistic misconceptions in favor of tailored insights and therapies.},
}

*Gastrointestinal Microbiome/physiology
Humans
Dysbiosis/microbiology
Probiotics
Diet
Fecal Microbiota Transplantation

@article {pmid41096928,
year = {2025},
author = {Yang, B and Wu, J and Hou, X and Bai, T and Liu, S},
title = {Memory in Misfire: The Gut Microbiome-Trained Immunity Circuit in Inflammatory Bowel Diseases.},
journal = {International journal of molecular sciences},
volume = {26},
number = {19},
pages = {},
doi = {10.3390/ijms26199663},
pmid = {41096928},
issn = {1422-0067},
support = {2022YFC2504005//National Key Research and Development Program of China/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Inflammatory Bowel Diseases/immunology/microbiology/therapy ; Animals ; *Immunologic Memory ; Immunity, Innate ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Trained Immunity ; },
abstract = {Inflammatory bowel disease (IBD) demonstrates chronic relapsing inflammation extending beyond adaptive immunity dysfunction. "Trained immunity"-the reprogramming of innate immune memory in myeloid cells and hematopoietic progenitors-maintains intestinal inflammation; however, the mechanism by which gut microbiome orchestration determines protective versus pathological outcomes remains unclear. Microbial metabolites demonstrate context-dependent dual effects along the gut-bone marrow axis. Short-chain fatty acids typically induce tolerogenic immune memory, whereas metabolites like succinate and polyamines exhibit dual roles: promoting inflammation in certain contexts while enhancing barrier integrity in others, influenced by cell-specific receptors and microenvironmental factors. Interventions include precision probiotics and postbiotics delivering specific metabolites, fecal microbiota transplantation addressing dysbiotic trained immunity, targeted metabolite supplementation, and pharmacologic reprogramming of pathological myeloid training states. Patient stratification based on microbiome composition and host genetics enhances therapeutic precision. Future research requires integration of non-coding RNAs regulating trained immunity, microbiome-immune-neuronal axis interactions, and host genetic variants modulating microbiome-immunity crosstalk. Priorities include developing companion diagnostics, establishing regulatory frameworks for microbiome therapeutics, and defining mechanistic switches for personalized interventions.},
}

Humans
*Gastrointestinal Microbiome/immunology
*Inflammatory Bowel Diseases/immunology/microbiology/therapy
Animals
*Immunologic Memory
Immunity, Innate
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Trained Immunity

@article {pmid41095952,
year = {2025},
author = {Soares Ferreira Júnior, A and Rodrigues da Silva, BF and Luiz da Silva, J and Trovão da Silva, M and Feliciano, JVP and Colturato, I and Barros, GMN and Scheinberg, P and Chao, NJA and de Oliveira, GLV},
title = {Unraveling the Intestinal Microbiota Conundrum in Allogeneic Hematopoietic Stem Cell Transplantation: Fingerprints, Clinical Implications and Future Directions.},
journal = {Journal of clinical medicine},
volume = {14},
number = {19},
pages = {},
doi = {10.3390/jcm14196874},
pmid = {41095952},
issn = {2077-0383},
support = {#2022/12989-6//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; #2023/08142-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; #313190/2021-6//National Council for Scientific and Technological Development/ ; Finance Code 001//Coordenação de Aperfeicoamento de Pessoal de Nível Superior/ ; },
abstract = {Intestinal dysbiosis represents a critical determinant of clinical outcomes in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Distinct microbiota patterns represent potential prognostic biomarkers and therapeutic targets. However, the exponential growth in microbiota research and analytical complexity has created significant interpretive challenges for clinicians. This review provides a synthesis of current literature examining microbiota fingerprints and their clinical implications. We analyzed key studies evaluating the clinical implications of intestinal microbiota fingerprints in allo-HSCT. Additionally, we examined current therapeutic strategies for microbiota modulation and approaches for translating research findings into clinical practice. We identified three major microbiota fingerprints: (1) decreased intestinal microbiota diversity, (2) reduced abundance of short-chain fatty acid-producing bacteria, and (3) Enterococcus domination. These fingerprints are associated with critical clinical outcomes including overall survival, Graft-versus-host disease, transplant-related mortality, and infection-related complications. While fecal microbiota transplantation and dietary interventions appear promising, current studies suffer from limited sample sizes and lack standardized protocols. Despite significant advances in microbiota research, biological, methodological, and logistical challenges continue to hinder its clinical translation. Understanding microbiota fingerprints represents a promising avenue for improving allo-HSCT outcomes. However, successful clinical implementation requires standardized methodologies, mechanistic studies, and multi-center collaborations to translate research into actionable clinical tools.},
}

@article {pmid41094491,
year = {2025},
author = {Wang, Z and Zhou, L and Zheng, Y and Zhong, X and Huang, R and Sun, W and Wang, S and Li, W},
title = {Nuclear receptor Nr1d1 links sleep deprivation to intestinal homeostasis via microbiota-derived taurine.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {1106},
pmid = {41094491},
issn = {1479-5876},
support = {2023YFC2705400//National Key R&D Rrogram of China/ ; 2021B1515420004//Guangdong Basic and Applied Basic Research Foundation/ ; 2025A03J4164//Huadu District Basic and Applied Basic Research Joint Funding Project/ ; GKLBCN-202501-01//Open Project Program of Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Guilin Medical University/ ; 202201020363//Science and Technology Projects in Guangzhou/ ; 2020A1515011031//Natural Science Foundation of Guangdong Province/ ; },
mesh = {Animals ; *Sleep Deprivation/microbiology/metabolism ; *Homeostasis/drug effects ; *Gastrointestinal Microbiome/drug effects ; *Taurine/metabolism/pharmacology ; *Nuclear Receptor Subfamily 1, Group D, Member 1/metabolism ; Male ; Mice, Inbred C57BL ; Intestinal Mucosa/pathology/metabolism ; *Intestines/microbiology/pathology ; Mice ; Fecal Microbiota Transplantation ; Colon/pathology ; },
abstract = {BACKGROUND: Sleep deficiency significantly compromises human health, with the gut being particularly susceptible. However, the molecular mechanisms by which gut microbiota mediate sleep deprivation-induced intestinal dysfunction remain largely undefined. In this study, we employed a chronic sleep deprivation (CSD) mouse model to investigate the impact of sleep loss on intestinal integrity and microbial composition.

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

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

CONCLUSION: Together, these findings reveal a gut microbiota-taurine-Nr1d1 axis underlying sleep deprivation-induced intestinal barrier dysfunction, and suggest that therapeutic modulation of taurine levels or circadian pathways may offer novel strategies to prevent or treat sleep-related gastrointestinal disorders.},
}

Animals
*Sleep Deprivation/microbiology/metabolism
*Homeostasis/drug effects
*Gastrointestinal Microbiome/drug effects
*Taurine/metabolism/pharmacology
*Nuclear Receptor Subfamily 1, Group D, Member 1/metabolism
Male
Mice, Inbred C57BL
Intestinal Mucosa/pathology/metabolism
*Intestines/microbiology/pathology
Mice
Fecal Microbiota Transplantation
Colon/pathology

@article {pmid41090775,
year = {2025},
author = {Baek, JS and Ma, X and Park, HS and Lee, DY and Kim, DH},
title = {Bifidobacterium longum P77 and Lactiplantibacillus plantarum P72 and Their Mix-Live or Heat-Treated-Mitigate Sleeplessness and Depression in Mice: Involvement of Serotonergic and GABAergic Systems.},
journal = {Cells},
volume = {14},
number = {19},
pages = {},
doi = {10.3390/cells14191547},
pmid = {41090775},
issn = {2073-4409},
support = {RS-2024-00486802//the Commercialization Promotion Agency for R&D Outcomes (COMPA) grant/ ; 2017R1A5A2014768//National Research Foundation of Korea/ ; },
mesh = {Animals ; *Depression/therapy ; Mice ; *Serotonin/metabolism ; Humans ; Male ; *Bifidobacterium longum/physiology ; Probiotics/pharmacology ; Anxiety ; Hot Temperature ; gamma-Aminobutyric Acid/metabolism ; Mice, Inbred C57BL ; Stress, Psychological ; },
abstract = {Sleeplessness (insomnia) is a significant symptom associated with stress-induced depression/anxiety. In the present study, we selected Bifidobacterium longum P77, which increased serotonin production in corticosterone-stimulated SH-SY5Y cells, from the fecal bacteria collection of healthy volunteers and examined the effects of B. longum on depression, anxiety, and sleeplessness induced by immobilization stress or by transplantation of cultured fecal microbiota (cFM) from patients with depression. Orally administered B. longum P77 decreased depression/anxiety- and sleeplessness-like behaviors in immobilization stress-exposed mice. B. longum P77 reduced immobilization stress-induced corticosterone, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 expression and the cell population of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)[+] in the prefrontal cortex, while the expression levels of immobilization stress-suppressed IL-10, γ-aminobutyric acid (GABA), its receptor GABAARα1, serotonin, and its receptor 5-HT1AR increased. B. longum P77 also alleviated immobilization stress-induced colitis: it decreased TNF-α and IL-6 expression and increased IL-10 expression in the colon. Furthermore, B. longum P77, Lactiplantibacillus plantarum P72, and their combination decreased cFM- or immobilization stress-induced depression-, anxiety-, and sleeplessness-like behaviors. They also decreased cFM-induced, corticosterone, TNF-α, and IL-6 expression levels in the prefrontal cortex and colon, while increasing cFM- or immobilization stress-suppressed GABA, GABAARα1, serotonin, and 5-HT1AR expression levels in the prefrontal cortex. In particular, the combination of B. longum P77 and L. plantarum P72 (P7277) additively or synergistically alleviated depression-, anxiety-, and sleeplessness-like behaviors, along with their associated biomarkers. Heat-killed P7277 also alleviated immobilization stress-induced depression/anxiety- and sleeplessness-like symptoms. These results imply that L. plantarum P72 and/or B. longum P77 can mitigate depression/anxiety and sleeplessness by upregulating GABAergic and serotonergic systems, along with the suppression of NF-κB activation.},
}

Animals
*Depression/therapy
Mice
*Serotonin/metabolism
Humans
Male
*Bifidobacterium longum/physiology
Probiotics/pharmacology
Anxiety
Hot Temperature
gamma-Aminobutyric Acid/metabolism
Mice, Inbred C57BL
Stress, Psychological

@article {pmid41090697,
year = {2025},
author = {Moore, JE and Millar, BC},
title = {Improving health literacy and patient-directed knowledge of fecal microbiota transplantation (FMT) through analysis of readability: a cross sectional infodemiology study.},
journal = {Expert opinion on biological therapy},
volume = {},
number = {},
pages = {},
doi = {10.1080/14712598.2025.2576509},
pmid = {41090697},
issn = {1744-7682},
abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is increasingly used in geriatric medicine, including intestinal decolonization of antimicrobial-resistant bacterial pathogens and the treatment of inflammatory bowel disease, graft versus host disease and autism spectrum disorders. The aim of this study was to examine readability of patient-facing FMT information.

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

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

CONCLUSION: Readability of FMT information for patients is poor, not reaching readability reference standards. Authors of FMT information should consider using readability calculators when preparing FMT information, so that the final material is within recommended readability reference parameters, to support the health literacy and treatment adherence of readers.},
}

@article {pmid41089557,
year = {2025},
author = {Chen, N and Zhang, M and Shi, B and Luo, X and Huang, R and Luo, Z and He, J and Xue, S and Li, N and Ling, Z and Guo, H and Xu, R and Liu, Y},
title = {Tirzepatide, a dual GLP-1 and GIP receptor agonist, promotes bone loss in obese mice via gut microbial-related metabolites.},
journal = {Journal of orthopaedic translation},
volume = {55},
number = {},
pages = {280-292},
pmid = {41089557},
issn = {2214-031X},
abstract = {BACKGROUND: As a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist, Tirzepatide (TZP) is a recently approved medication for treating type 2 diabetes mellitus (T2DM) and obesity; however, the effect of TZP in bone remodeling remains unclear.

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

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

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

This study indicates that TZP has a negative impact on bone mass, suggesting that clinical attention should be paid to the risk of further decline in bone mass after Tirzepatide treatment, and it is necessary to follow up on their bone metabolism. Additionally, the gut microbiota plays an important role in bone metabolism regulation, and supplementing with certain probiotics may have a preventive effect on bone mass reduction associated with TZP treatment. Our research provides a reference for the prevention and treatment of drug-related osteoporosis in patients with T2DM in the future.},
}

@article {pmid41089551,
year = {2025},
author = {Hearn, J and Malik, G and Stukalin, I and Panaccione, R and Ingram, RJM and Ma, C},
title = {Refractory Immune Checkpoint Inhibitor Colitis Treated With Biologics, Janus Kinase Inhibition, Plasma Exchange, and Fecal Microbiota Transplantation.},
journal = {ACG case reports journal},
volume = {12},
number = {10},
pages = {e01847},
pmid = {41089551},
issn = {2326-3253},
abstract = {Enterocolitis is a common immune-related adverse event associated with cancer immunotherapy. Current guidelines inform first-line pharmacologic management of immune checkpoint inhibitor-related enterocolitis; however, treatment in refractory cases is uncertain. We present a case of a 45-year-old woman with refractory immune checkpoint inhibitor-related enterocolitis requiring treatment with a combination of janus kinase inhibition, therapeutic plasma exchange, and fecal microbiota transplantation after failure of several lines of therapy. This is the first report of the combination of upadacitinib, plasma exchange, and fecal microbiota transplant for refractory enterocolitis.},
}

@article {pmid41089403,
year = {2025},
author = {Wang, J and Zhang, X and Cui, C and Li, M and Xie, Z and Yang, L and Ding, D and Li, X and Zhao, M},
title = {Gut Microbiota and Metabolite Changes Induced by Tacrolimus: Implications for Skin Transplant Immunology in Mice.},
journal = {Journal of inflammation research},
volume = {18},
number = {},
pages = {14059-14073},
pmid = {41089403},
issn = {1178-7031},
abstract = {BACKGROUND: Tacrolimus is the most widely used immunosuppressive therapy in solid organ transplantation. However, whether it can inhibit transplant graft rejection by altering the composition and metabolism of gut microbiota remains unclear.

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

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

CONCLUSION: Overall, our data may provide a basis for establishing gut microbiota-based therapies for allograft rejection.},
}

@article {pmid41088420,
year = {2025},
author = {Zhu, JH and Wu, LP and Deng, L and Zang, SG and Li, XB and Chen, X and Yu, JX},
title = {Gut microbiota and metabolism in systemic lupus erythematosus: from dysbiosis to targeted interventions.},
journal = {European journal of medical research},
volume = {30},
number = {1},
pages = {971},
pmid = {41088420},
issn = {2047-783X},
support = {No.YK2023130//The Medical Research Project of Yancheng Health Commission/ ; No.2024LZ006//The Special Scientific Research Fund for Clinical Medicine of Nantong University/ ; 2024LZ008//The Special Scientific Research Fund for Clinical Medicine of Nantong University/ ; No.YCBE202475//The Special Fund Project of Yancheng Science and Technology Bureau/ ; },
mesh = {Humans ; *Lupus Erythematosus, Systemic/metabolism/microbiology/therapy ; *Gastrointestinal Microbiome ; *Dysbiosis/therapy/metabolism/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; },
abstract = {Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multiorgan involvement, with pathogenesis closely linked to that of gut dysbiosis and metabolic disturbances. Studies indicate that SLE patients exhibit significantly reduced gut microbial diversity, increased abundance of pathogenic bacteria, and decreased beneficial bacteria. Dysbiosis exacerbates disease progression by disrupting the intestinal barrier, triggering autoimmune responses, and promoting proinflammatory cytokine release. Metabolomic analyses further reveal that SLE is associated with dysregulated amino acid metabolism, reduced short-chain fatty acids, and disrupted lipid homeostasis, which correlate with disease activity, renal injury, and increased atherosclerosis risk. Emerging microbiota-targeted interventions, such as fecal microbiota transplantation (FMT), probiotics/prebiotics, phage therapy, and dietary modifications, demonstrate promising therapeutic potential by restoring microbial balance, enhancing immune regulation, and improving metabolic homeostasis. This review systematically summarizes the alterations in gut microbiota and metabolism in SLE, their critical roles in disease progression, diagnosis, and pathogenesis, and explores the clinical value of microbial-targeted strategies in improving SLE outcomes.},
}

Humans
*Lupus Erythematosus, Systemic/metabolism/microbiology/therapy
*Gastrointestinal Microbiome
*Dysbiosis/therapy/metabolism/microbiology
Probiotics/therapeutic use
Fecal Microbiota Transplantation

@article {pmid41087864,
year = {2025},
author = {Chen, H and Wang, Z and Su, W and Li, S and Ye, Q and Zhang, G and Zhou, X},
title = {Helicobacter pylori infection impairs glucose homeostasis through gut microbiota dysbiosis.},
journal = {BMC microbiology},
volume = {25},
number = {1},
pages = {663},
pmid = {41087864},
issn = {1471-2180},
support = {82100594//National Natural Science Foundation of China,China/ ; },
abstract = {BACKGROUND: Epidemiological data show that Helicobacter pylori (H. pylori) infection is not only the most important risk factor for gastric cancer, but is also associated with poor glycemic control in patients with diabetes. However, the direct causal and functional relationship between H. pylori infection and dysglycemia is unclear.

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

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

CONCLUSION: Our studies offer evidence that H. pylori infection significantly contributes to the progression of glucose impairment and insulin resistance. Therefore, incorporating H. pylori status into preventive strategies for diabetes should be taken into account. (Chinese Clinical Trial Registry Center, ChiCTR2200063489, Registered 08 September 2022, https://www.chictr.org.cn/showproj.html?proj=178102).},
}

@article {pmid41087029,
year = {2025},
author = {Tu, D and Lu, C and Guo, J and Chen, Q and Li, X and Wang, Y and Cheng, L and Jiang, H and Jian, J and Ge, Y and Hou, Z and Feng, X and Feng, Y and Zhou, J and Lei, Y and Diao, H and Ran, L and Zhou, Y and Xu, Z and Zhou, J and Tang, B and Yang, S},
title = {Gut microbiota-mediated berberine metabolism ameliorates cholestatic liver disease by suppressing 5-HT production.},
journal = {Clinical and molecular hepatology},
volume = {},
number = {},
pages = {},
doi = {10.3350/cmh.2025.0577},
pmid = {41087029},
issn = {2287-285X},
abstract = {BACKGROUND/AIMS: Cholestatic liver disease (CLD) is a pathological condition characterized by impaired bile formation, secretion, and excretion. However, the key pathophysiological mechanisms of CLD remain elusive, and therapeutic efficacy is unsatisfactory.

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

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

CONCLUSIONS: BBR is transformed by gut microbiota to ameliorate CLD via inhibiting 5-HT, suggesting potential novel strategies for further clinical use.},
}

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

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

KEY MESSAGES: This review provides a symptom‑oriented framework linking specific clinical manifestations of chemotherapy‑related gastrointestinal toxicity with underlying microbial alterations. It further integrates emerging evidence across nutritional, microbial, and herbal approaches, emphasizing shared therapeutic pathways and highlighting prospects for personalized microbiota‑based strategies to improve treatment tolerance and patient outcomes.},
}

@article {pmid41085348,
year = {2025},
author = {Zhang, S and Wu, Z and Zhang, S and Ru, Y and Wang, Q and Tong, H and Qin, Q and Yan, Q and Li, Z and Wu, G},
title = {The intricate microbial-gut-brain axis in Alzheimer's disease: a review of microbiota-targeted strategies.},
journal = {Food & function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5fo03139g},
pmid = {41085348},
issn = {2042-650X},
abstract = {The microbiome-gut-brain axis (MGBA) has emerged as a potential focus for the enhancement of cognitive abilities and the improvement of Alzheimer's disease (AD). Probiotics and prebiotics can improve the imbalance of gut microbiota to alleviate AD symptoms. Current research on probiotics/prebiotics and brain function mainly focuses on metabolic pathways such as those involving microbial metabolites like lipopolysaccharides and short-chain fatty acids, as well as immune pathways that regulate inflammation in the gut and brain. However, the roles played by endocrine and neural pathways remain less explored and warrant further attention. This review explores the intricate mechanisms of gut-brain communication within the MGBA, and especially systematically elaborates on the specific mechanisms of the endocrine pathway (impact of gut-derived and exogenous hormones on brain function) and the neural pathway (regulation of brain function by the sympathetic and parasympathetic systems). It also emphasizes the specific changes in gut microbiota noted in individuals with AD. Additionally, it examines the beneficial effects of probiotics, prebiotics, synbiotics, and postbiotics for cognitive function, reviewing their advancements in preclinical research, clinical trials, and commercial applications. Furthermore, this review delves into novel gut microbiota-related strategies to promote brain health, including antibiotics, certain gut-targeted inhibitors or agonists, fecal microbiota transplantation, whole microbiome transplantation, viral microbiota transplantation, genetically engineered bacteria, and bacteriophage-based in situ intestinal microbiome engineering. Ultimately, this review aims to advance the therapeutic application of gut microbiota-targeted strategies in AD.},
}

@article {pmid41081988,
year = {2025},
author = {Bhat, A and Mansoor, A and Fatima, M and Kumar, A and Mari, T and Ali, A and Bakht, K and Dad, A and Zahra, R and Makhija, V and Southwick, FS},
title = {Safety and efficacy of fecal microbiota transplantation versus antibiotics for treating clostridioides difficile infection: systematic review and meta-analysis.},
journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology},
volume = {},
number = {},
pages = {},
pmid = {41081988},
issn = {1435-4373},
abstract = {BACKGROUND: Recurrent Clostridioides difficile infection (CDI) is a persistent clinical challenge due to the high rate of relapse following treatment with standard antibiotics. Fecal microbiota transplantation (FMT) has emerged as a promising alternative, with comparable results. Aiming to restore intestinal microbial balance and reduce recurrence. Comparative evidence on the efficacy and safety of FMT versus antibiotics remains variable across studies, warranting a comprehensive synthesis to guide clinical decision-making.

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

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

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

CONCLUSION: FMT is more effective than standard antibiotic therapy for achieving resolution and reducing recurrence in patients with recurrent CDI.},
}

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

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

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

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

CONCLUSIONS: In our study, FMT was found to be an effective and safe treatment of recurrent CDI. Use of metronidazole was identified as a risk factor for a suboptimal response to FMT in the studied cohort.},
}

@article {pmid41080577,
year = {2025},
author = {Wang, Z and Yu, J and Liu, Y and Gong, J and Hu, Z and Liu, Z},
title = {Role of the microbiota-gut-lung axis in the pathogenesis of pulmonary disease in children and novel therapeutic strategies.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1636876},
pmid = {41080577},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; Child ; *Lung/immunology/microbiology/metabolism ; *Lung Diseases/therapy/microbiology/immunology/etiology/metabolism ; Dysbiosis ; Animals ; Fatty Acids, Volatile/metabolism ; },
abstract = {Emerging evidence highlights the microbiota-gut-lung axis (MGLA) as a pivotal regulator of pediatric respiratory health, yet mechanistic insights are lacking and therapeutic applications remain unclear. This review synthesizes cutting-edge findings to delineate how gut microbiota-derived metabolites, particularly short-chain fatty acids (SCFAs), orchestrate pulmonary immunity and disease pathogenesis in children. Leveraging multi-omics integration (metagenomics, metabolomics, transcriptomics), emerging studies have uncovered novel microbe-host interactions driving immune dysregulation in asthma, pneumonia, and cystic fibrosis. A comprehensive map of gut-lung crosstalk has been established across these conditions. Current studies suggest that early-life gut dysbiosis, shaped by delivery mode, antibiotics, and diet, disrupts SCFA-mediated immune homeostasis, amplifying T-helper 2 cell inflammation and impairing alveolar macrophage function. Crucially, we identified disease-specific microbial signatures (e.g., depletion of Lachnospira and Faecalibacterium in asthma) and demonstrated that fecal microbiota transplantation and probiotic interventions restore microbial balance, attenuating airway inflammation in preclinical models. This work pioneers the translation of MGLA insights into precision medicine strategies, highlighting dietary modulation and microbial therapeutics as viable alternatives to conventional treatments. By bridging microbial ecology and immune dynamics, our findings provide actionable biomarkers for early diagnosis and personalized interventions, addressing critical gaps in pediatric respiratory disease management. The integration of multi-omics frameworks not only advances mechanistic understanding but also positions the MGLA as a transformative target in reducing global childhood morbidity. Future research must prioritize longitudinal studies and clinical trials to validate these innovations, ultimately redefining therapeutic paradigms for GLA-driven pathologies.},
}

Humans
*Gastrointestinal Microbiome/immunology
Child
*Lung/immunology/microbiology/metabolism
*Lung Diseases/therapy/microbiology/immunology/etiology/metabolism
Dysbiosis
Animals
Fatty Acids, Volatile/metabolism

@article {pmid41080562,
year = {2025},
author = {Zhu, Z and Cheng, Y and Liu, X and Xu, X and Ding, W and Ling, Z and Liu, J and Cai, G},
title = {The microbiota-gut-brain axis in depression: unraveling the relationships and therapeutic opportunities.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1644160},
pmid = {41080562},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Depression/therapy/microbiology/metabolism/etiology ; *Brain/metabolism ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; *Brain-Gut Axis ; },
abstract = {Depression, a highly prevalent and relapsing mental disorder, exacts profound personal and socioeconomic tolls globally, warranting urgent scientific and clinical attention. Emerging evidence from both preclinical models and human clinical investigations has established the microbiota-gut-brain axis (MGBA) as a critical determinant in depression pathogenesis. This intricate bidirectional network integrates gut microbiota with central nervous system function, influencing mental health through mechanisms previously underrecognized. This review systematically synthesizes gut microbiota alterations associated with depression and their impacts on neuroendocrine, neuroimmune, and metabolic pathways. Advanced therapeutic strategies targeting the MGBA are discussed, including probiotics, fecal microbiota transplantation, and artificial intelligence-enabled microbiome interventions for depression management. While challenges in standardization, mechanistic understanding, efficacy and safety remain, MGBA-centered approaches offer a promising shift toward microbiota-based diagnostics and personalized treatments for depression.},
}

Humans
*Gastrointestinal Microbiome/immunology
*Depression/therapy/microbiology/metabolism/etiology
*Brain/metabolism
Animals
Fecal Microbiota Transplantation
Probiotics/therapeutic use
*Brain-Gut Axis

@article {pmid41080326,
year = {2025},
author = {Qureshi, U and Bajwa, A and Aslam, Z and Aggrey, A and Nawaz, UH and Ul Ain, Q},
title = {Gut Microbiota Modulation in Type 2 Diabetes and Cardiometabolic Risk: A Systematic Review.},
journal = {Cureus},
volume = {17},
number = {9},
pages = {e92020},
pmid = {41080326},
issn = {2168-8184},
abstract = {Cardiometabolic complications related to type 2 diabetes mellitus (T2DM) are often due to changes in the gut microbiota. The review analyzed studies looking at the effects of probiotics, prebiotics, high-fiber diets, and fecal microbiota transplantation (FMT) on glucose levels and heart and metabolic health in individuals either having T2DM or being at risk. The review followed the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. The literature was searched using text terms and controlled vocabulary, employing Boolean operators "AND," "OR," and various combinations across PubMed, Embase, and the Cochrane Library. Open-access, full-text English papers from 2005 to 2025, including those authored by people, were searched. The quality was assessed using the Risk of Bias 2.0 (RoB 2.0) tool, and the evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Fifteen randomized controlled trials (RCTs) were analyzed for methodological quality, with three categorized as having a high risk of bias (RoB). The GRADE tool categorized two high RoB RCTs as "low quality." However, two RCTs had low RoB and were classified as "high quality." Ten RCTs had uncertain RoB, lowering the evidence by one point to "moderate quality." A comprehensive review of RCTs was conducted to assess outcomes related to glycemic parameters (e.g., glycated hemoglobin (HbA1c), fasting glucose), lipid profiles, inflammatory markers, anthropometric measures, and gut microbiota composition. Interventions included probiotic and prebiotic supplementation, high-fiber or Mediterranean-style diets, and FMT. Probiotic yogurt containing Lactobacillus acidophilus and Bifidobacterium lactis significantly improved lipid profiles by reducing low-density lipoprotein cholesterol (LDL-C) and total cholesterol. High-fiber diets consistently lowered fasting blood glucose, HbA1c, triglycerides, and LDL-C while elevating high-density lipoprotein cholesterol (HDL-C) and beneficial short-chain fatty acid (SCFA)-producing bacteria. Anti-inflammatory effects were observed across interventions, notably with probiotics and polyphenol-rich Mediterranean diets, which reduced tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and other inflammatory cytokines. The Green-Mediterranean diet significantly improved weight, insulin resistance, and Framingham risk scores. Novel mechanisms involving SCFAs and bile acid metabolism were also identified as key modulators of host metabolic response. Microbiota-based interventions offer promising avenues for glycemic control and cardiometabolic risk reduction in patients with T2DM.},
}

@article {pmid41080149,
year = {2025},
author = {Xu, H and Li, S and Liu, S and Zuo, YG},
title = {A Conceptual Review of Gut, Skin, and Oral Microbiota in Autoimmune Bullous Diseases: From Dysbiosis to Therapeutic Potential.},
journal = {Journal of inflammation research},
volume = {18},
number = {},
pages = {13925-13943},
pmid = {41080149},
issn = {1178-7031},
abstract = {Autoimmune bullous diseases (AIBDs), including pemphigus and bullous pemphigoid, are chronic inflammatory skin disorders characterized by dysregulated immune responses mediated by autoantibodies that target adhesion molecules in the skin and mucous membranes. Emerging evidence highlights the pivotal role of host microbiota dysbiosis in AIBDs pathogenesis, offering novel insights into disease mechanisms and therapeutic strategies. This review systematically synthesizes the current findings on gut, skin, and oral microbiota alterations in AIBDs, emphasizing their contributions via the gut-skin axis, microbial metabolites, and pathogen-host interactions. Key innovations include uncovering how specific pathogenic and commensal microbiota influence disease progression through intriguing skin inflammation and direct barrier impairment. Notably, while some microbiota changes overlap with other dermatoses, AIBDs exhibit distinct microbial signatures associated with their unique autoimmune mechanisms targeting adhesion molecules. Furthermore, we explore microbiota-targeted therapies, such as antibiotics, probiotics, and fecal microbiota transplantation, and demonstrate their potential to restore microbial homeostasis and improve clinical outcomes. By integrating multi-omics evidence and clinical data, this review bridges mechanistic insights with translational applications, proposing microbiota modulation as a promising adjunctive therapy for AIBDs. Our analysis identifies critical research gaps, including the need for longitudinal studies and personalized microbial interventions, positioning this review at the forefront of microbiome-inflammation-autoimmunity research.},
}

@article {pmid41078532,
year = {2025},
author = {Taha, H and Issa, A and Muhanna, Z and Al-Shehab, M and Wadi, T and Awamleh, S and Ateiwi, YA and Abusido, M and Berggren, V},
title = {Microbiota-based interventions for autism spectrum disorder: a systematic review of efficacy and clinical potential.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1648118},
pmid = {41078532},
issn = {1664-302X},
abstract = {PURPOSE: Autism spectrum disorder (ASD) is increasingly linked to gut microbiota imbalances, influencing both behavioral and gastrointestinal (GI) symptoms. This systematic review assesses the efficacy of microbiota-based interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), in improving ASD-related symptoms, aiming to provide insights into their therapeutic potential and inform future clinical applications.

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

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

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

https://www.crd.york.ac.uk/PROSPERO/view/CRD42024615043, identifier CRD42024615043.},
}

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

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

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

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

CONCLUSION: FMT significantly enhances the efficacy of 5FU in reducing pancreatic tumor growth through gut microbiota modulation.},
}

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

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

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

CONCLUSIONS: These findings provide novel insights into microbiota-targeted therapeutic strategies for kidney IRI and highlight propionic acid as a potential therapeutic agent.},
}

Animals
*Fecal Microbiota Transplantation/methods
Rats, Sprague-Dawley
*Reperfusion Injury/therapy/prevention & control
*Propionates/metabolism/pharmacology
*Receptors, G-Protein-Coupled/metabolism/genetics
Gastrointestinal Microbiome/drug effects
Rats
Disease Models, Animal
Kidney/pathology
Male
Guinea Pigs
*Acute Kidney Injury/therapy/prevention & control
Apoptosis/drug effects
Up-Regulation
Signal Transduction

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

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

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

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

https://www.crd.york.ac.uk/prospero/, identifier CRD42024606415.},
}

Humans
*Parkinson Disease/therapy/microbiology
*Gastrointestinal Microbiome/drug effects
Randomized Controlled Trials as Topic
Fecal Microbiota Transplantation
Probiotics/therapeutic use
Treatment Outcome
Anti-Bacterial Agents/therapeutic use
Synbiotics/administration & dosage

@article {pmid41078065,
year = {2025},
author = {Doukas, PG and Doukas, SG and Broder, A},
title = {Effectiveness and Safety of Fecal Microbiota Transplantation for Ulcerative Colitis Treatment: A Systematic Review and Meta-Analysis.},
journal = {Digestive diseases (Basel, Switzerland)},
volume = {},
number = {},
pages = {1-22},
doi = {10.1159/000548568},
pmid = {41078065},
issn = {1421-9875},
abstract = {Despite advances in pharmaceuticals, managing ulcerative colitis (UC) remains challenging. Interest in fecal microbiota transplantation (FMT) for UC is growing, but varying formulations and endpoints in trials complicate safety and efficacy assessment. This systematic review and meta-analysis offer a validated, up-to-date overview of FMT's efficacy and safety in UC. We searched four electronic databases and analyzed only randomized clinical trials (RCT) that investigated the clinical and endoscopic efficacy of FMT in UC, regardless of administration route or dose. Clinical and endoscopic remission was assessed by comparing the odds ratio (OR) and 95% confidence interval (CI). The initial search yielded 6737 studies with 15 meeting inclusion criteria after duplicate removal and screening. The meta-analysis showed clinical remission in 62% receiving FMT vs. 50.5% in controls (OR 2.65; [1.76; 4.00]). The endoscopic response was 42% in the FMT group vs. 22% in controls (OR 2.00; [1.09; 3.68]). Heterogeneity was assessed as low (by I2 index and τ2). Our data show that FMT significantly improves clinical and endoscopic remission rates, offering a promising non-pharmacological option for UC patients unresponsive to conventional treatments. Further prospective studies are needed to optimize the formulation and dosing while also addressing the safety profile of FMT in UC.},
}

@article {pmid41077748,
year = {2025},
author = {Lee, HK and Shin, CM and Chang, YH and Jo, H and Choi, J and Choi, Y and Jun, YK and Yoon, H and Park, YS and Kim, N and Lee, DH},
title = {Predictors of Treatment Response to Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Pilot Study.},
journal = {Journal of neurogastroenterology and motility},
volume = {31},
number = {4},
pages = {462-476},
doi = {10.5056/jnm24183},
pmid = {41077748},
issn = {2093-0879},
abstract = {BACKGROUND/AIMS: We aim to investigate the effectiveness, safety, and predictors of treatment response to fecal microbiota transplantation (FMT) in Korean irritable bowel syndrome (IBS) patients.

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

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

CONCLUSIONS: FMT appears to be a potentially effective treatment for moderate to severe IBS, with significant symptom relief and gut microbiota changes. Lower baseline abundances of Roseburia and Subdoligranulum and greater shifts of gut microbiome profile toward donor microbiota after FMT may predict favorable FMT response. Long-term follow-up is on the way to assessing the durability of these effects.},
}

@article {pmid41077742,
year = {2025},
author = {Gweon, TG},
title = {Is Fecal Microbiota Transplantation Applicable for the Treatment of Irritable Bowel Syndrome? Time for Precision Medicine.},
journal = {Journal of neurogastroenterology and motility},
volume = {31},
number = {4},
pages = {403-404},
doi = {10.5056/jnm25146},
pmid = {41077742},
issn = {2093-0879},
}

@article {pmid41077430,
year = {2025},
author = {Polster, SP},
title = {The Role of the Microbiome and the Neurovascular Unit.},
journal = {The Surgical clinics of North America},
volume = {105},
number = {5},
pages = {857-869},
doi = {10.1016/j.suc.2025.06.008},
pmid = {41077430},
issn = {1558-3171},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Blood-Brain Barrier ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; },
abstract = {The gut-brain axis plays a crucial role in neurovascular diseases, linking gut microbiota to blood-brain barrier integrity, neuroinflammation, and disease progression. Conditions such as cerebral cavernous malformations, traumatic brain injury, radiation-induced damage, and stroke exhibit microbiome-driven modulation that may be relevant to explain disease variance. Microbial metabolites have been shown to influence endothelial function and secondary brain injury mechanisms. Emerging interventions of dietary modifications, probiotics, fecal microbiota transplantation, and metabolite-based therapies show promise in mitigating neurovascular damage. Future research should focus on microbiome-targeted treatments, biomarker discovery, and personalized strategies to optimize neurovascular health through gut microbiome modulation.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Blood-Brain Barrier
Probiotics/therapeutic use
Fecal Microbiota Transplantation

@article {pmid41076929,
year = {2025},
author = {Shi, W and Xi, M and Zhang, K and Yang, J and Cheng, X and Zang, H and Fan, W},
title = {Gut microbiota as a central mediator in hydrogen gas-induced alleviation of colitis via TLR4/NF-κB and Nrf2 pathway regulation.},
journal = {International immunopharmacology},
volume = {167},
number = {},
pages = {115671},
doi = {10.1016/j.intimp.2025.115671},
pmid = {41076929},
issn = {1878-1705},
abstract = {Inflammatory bowel disease (IBD) is a chronic and relapsing autoimmune disorder of the gastrointestinal tract with incompletely elucidated pathogenesis and limited therapeutic options. Although hydrogen gas (H2) has demonstrated therapeutic efficacy in various diseases including IBD, its mechanisms of action, particularly its interaction with the gut microbiota, remain poorly characterized. This study reveals that H2 inhalation effectively reversed dextran sulfate sodium (DSS)-induced dysbiosis by suppressing the expansion of potential pathogenic bacteria (e.g., Enterobacteriaceae and Escherichia-Shigella) and promoting potential beneficial microbes (e.g., Bacteroides and Lactobacillaceae), thereby restoring microbial homeostasis. Furthermore, H2 inhalation enhanced goblet cell density and mucus production, upregulated tight junction proteins (ZO-1 and occludin), and repaired intestinal barrier integrity. It also rebalanced the Treg/Th17 cell ratio, correcting immune dysregulation. At the molecular level, H2 inhalation suppressed the TLR4/NF-κB signaling pathway and activated the Keap1/Nrf2 antioxidant axis, leading to reduced production of pro-inflammatory cytokines and oxidative stress markers, alongside elevated antioxidant enzymes, collectively ameliorating colonic injury. In brief, the ameliorative effects of H2 are likely mediated through remodeling of the gut microbiota, restoration of the epithelial barrier, suppression of inflammatory signaling, and activation of antioxidant pathways. These findings were further validated by fecal microbiota transplantation (FMT) experiments. Collectively, this study links the therapeutic effects of H2 to structural and functional reprogramming of the gut microbiome, indicating that microbial ecological restoration is a central mechanism through which H2 alleviates colitis, thereby providing a mechanistic foundation for the therapeutic application of H2 inhalation in IBD.},
}

@article {pmid41076730,
year = {2025},
author = {Hull, MA and Sun, H},
title = {Omega-3 polyunsaturated fatty acids and gut microbiota.},
journal = {Current opinion in clinical nutrition and metabolic care},
volume = {},
number = {},
pages = {},
pmid = {41076730},
issn = {1473-6519},
abstract = {PURPOSE OF REVIEW: Oral intake of n (omega)-3 polyunsaturated fatty acids (PUFAs) is associated with changes to gut microbiota. We review recent findings from 2024 onwards, which build the scientific case that changes to bacterial abundance, and their metabolites, contribute to the health benefits associated with n-3 PUFAs.

RECENT FINDINGS: There are now multiple studies in rodent disease models that demonstrate that n-3 PUFAs do not significantly alter bacterial diversity but, instead, alter abundance of several species that are implicated in short-chain fatty acid synthesis, in a model-specific manner. Limited intervention studies in humans, backed by larger observational studies, concur with the preclinical findings. Importantly, faecal transplantation experiments have confirmed that n-3 PUFA-induced changes to gut microbiota are causally related to reversal of the disease phenotype in two rodent models. In-vitro colonic models are now being used to understand the mechanism(s) underlying n-3 PUFA-induced changes to the gut microbiota and metabolome.

SUMMARY: Despite emerging proof that the gut microbiota contributes to n-3 PUFA activity in animal models, human data are sparse. It remains unclear how n-3 PUFAs affect changes to the gut microbiota or whether n-3 PUFA metabolism by gut microbes contributes to the host metabolome.},
}

@article {pmid41075966,
year = {2025},
author = {Wang, T and Huang, X and Lu, L and Luo, X and Wang, Y and Ma, Y and Tong, X and Zou, H and Gu, J and Liu, X and Bian, J and Liu, Z and Yuan, Y},
title = {The dysbiosis of gut microbiota attributes to the impairment of blood-brain barrier in rats triggered by cadmium.},
journal = {Toxicology},
volume = {},
number = {},
pages = {154303},
doi = {10.1016/j.tox.2025.154303},
pmid = {41075966},
issn = {1879-3185},
abstract = {Cadmium (Cd) is a non-biodegradable heavy metal with a long biological half-life that is detrimental to human health. As Cd can increase blood-brain barrier (BBB) permeability and disturb the gut microbiota, the relationship between the BBB and gut microbiota disturbance induced by Cd consumption remains unclear. This study aims to identify whether Cd-induced gut microbiota dysbiosis is associated with rat BBB injury and investigate the possible mechanism. Here, we conducted analyses of variations in the composition of the gut microbiota and its metabolites, as well as BBB permeability and the results of the Morris water maze test, in rats treated with Cd by gavage. Fecal microbiota transplantation was performed to verify the role of the microbiota in altering BBB permeability induced by Cd. The results showed that Cd disturbed the gut microbiota, decreasing the levels of short-chain fatty acids (SCFAs). Furthermore, Cd-induced BBB permeability was substantiated by FITC-dextran leakage, ultrastructural observations, and diminished Claudin-5, Occludin, and ZO-1 protein expression, all of which were mitigated by FMT. In vitro, sodium butyrate (SOB) alleviated Cd-induced oxidative stress and increased the expression levels of GPX4 and FTH. Taken together, these findings suggest that Cd disrupts the microbiota and SCFAs components in rats, thereby contributing to BBB damage. SOB prevents Cd-induced BBB damage by suppressing ferroptosis in microvascular endothelial cells. This exhaustive study considerably enhances our comprehension of the health hazards posed by Cd to the central nervous system via the gut-brain axis.},
}

@article {pmid41075893,
year = {2025},
author = {Huang, J and Yu, L and Zhang, C and Fang, Y and Zhou, X and Wang, R and Xing, L and Wang, L and Yu, N and Peng, D and Chen, W and Zhang, Y and Wang, Y},
title = {Water-soluble Poria cocos polysaccharide improves alcoholic liver disease via modulation of gut microbiota-mediated intestinal bile acids-farnesoid X receptor.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {148202},
doi = {10.1016/j.ijbiomac.2025.148202},
pmid = {41075893},
issn = {1879-0003},
abstract = {Alcoholic liver disease (ALD) is characterized by gut microbiota dysbiosis. This study aimed to elucidate the mechanism by which water-soluble Poria cocos polysaccharide (PCP) ameliorates ALD through modulation of the gut microbiota. PCP administration alleviated hepatic injury, reduced lipid accumulation, and attenuated inflammation in ALD mice. It also enhanced intestinal barrier integrity, as indicated by upregulation of tight junction proteins (ZO-1, Occludin, Claudin-1) and reduced lipopolysaccharide (LPS) levels. Additionally, PCP treatment remodeled the gut microbiota profile, characterized by a marked enrichment of Parabacteroides distasonis, which is associated with bile acid metabolism. Targeted metabolomics revealed PCP increased intestinal chenodeoxycholic acid (CDCA) and cholic acid (CA) levels, activating the intestinal farnesoid X receptor/fibroblast growth factor 15 (FXR/FGF15) axis while suppressing hepatic Cholesterol 7α-hydroxylase (CYP7A1), ultimately reducing systemic bile acids. Fecal microbiota transplantation confirmed gut microbiota-mediated protection, while intestinal FXR inhibition with glycine-β-muricholic acid (Gly-β-MCA) abolished PCP's therapeutic effects. These findings reveal that PCP ameliorates ALD by regulating the gut microbiota-bile acid-FXR axis, PCP as a promising natural therapeutic for ALD.},
}

@article {pmid41075520,
year = {2025},
author = {Gong, S and Xu, Y and Zhao, R and Yu, J and Bao, L and Zhang, Y and Li, F and Jiao, L and Kou, J},
title = {Xinqingning tablet attenuates ischemic stroke complicated by gut dysbiosis through regulating the miR-126-driven gut-brain axis.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {148},
number = {},
pages = {157356},
doi = {10.1016/j.phymed.2025.157356},
pmid = {41075520},
issn = {1618-095X},
abstract = {BACKGROUND: Ischemic stroke (IS), the predominant clinical stroke subtype, is increasingly linked to dysregulation of the gut-brain axis (GBA)-a bidirectional neuroendocrine-immune interface connecting intestinal homeostasis with cerebrovascular pathophysiology. Xinqingning Tablet (XQNT) demonstrates neuroprotective potential in IS complicated by gut dysbiosis (GD), yet its mechanisms of GBA modulation remain unclear.

METHODS: A dual-hit IS-GD mouse model was established via fecal slurry transplantation and permanent middle cerebral artery occlusion (pMCAO) surgery. Gut function was evaluated by constipation indices and histopathological changes, while the neuroprotective efficacy of XQNT (0.36, 0.48, and 0.61 g kg⁻¹) was assessed via TTC staining, neurological deficit scores, cerebral water content, and Evans blue (EB) extravasation assays. Additionally, Western blot was employed to quantify blood-brain barrier (BBB) and inflammation-associated proteins. microRNA sequencing was used to screen the differentially expressed miRNAs. miR-126 expression levels were measured by RT-qPCR, while concentrations of LPS, IL-6 and IL-10 were determined by ELISA. Finally, mechanistic validation employed intravenous miR-126 agonism/antagonism coupled with phenotypic rescue experiments.

RESULTS: XQNT conferred robust survival benefits, while concurrently ameliorating intestinal dysfunction and neurovascular injury. Mechanistically, XQNT elevated miR-126 expression, suppressing NF-κB-driven neuroinflammation. Additionally, miR-126 agonism phenocopied XQNT efficacy, whereas miR-126 inhibition abrogated therapeutic benefits.

CONCLUSIONS: This study provides early evidence that XQNT functions as a dual-target GBA modulator that alleviates IS with GD via regulation of the miR-126/NF-κB axis. By simultaneously promoting barrier restoration and inflammatory resolution, XQNT offers a promising therapeutic approach that links regulation of the gastrointestinal system with cerebrovascular protection.},
}

@article {pmid41074196,
year = {2025},
author = {Liu, Y and Dong, B and Yang, YL and Zhang, YQ and Zhang, Y and Pan, D and Du, EZ and Zhu, SJ and Wang, B and Huang, YW},
title = {Intestinal microbiota dynamics in piglets: the interplay with swine enteric coronavirus infections and implications for disease control.},
journal = {Animal microbiome},
volume = {7},
number = {1},
pages = {107},
pmid = {41074196},
issn = {2524-4671},
support = {32302873//National Natural Science Foundation of China/ ; U22A20521//National Natural Science Foundation of China/ ; },
abstract = {Infections of swine enteric coronavirus (SECoV), including porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV), cause severe diarrhea in piglets and result in substantial losses to the pig industry. The intestinal microbiota plays a crucial role in SECoV disease progression and outcomes, yet current research largely focuses on specific age groups or intestinal segments. This review provides a comprehensive analysis of the dynamic microbiota changes in piglets after SECoV infections across different ages and intestinal regions. It discusses differential microbiota analyses, functional changes, metabolic products, alongside their effects on immune responses. Additionally, we explore fecal bacterial transplantation as a potential intervention and highlight the role of the microbiota in either promoting or inhibiting SECoV infections. The development of advanced research tools, including culturomics, sequencing technologies, and multi-omics approaches, is pivotal in understanding the intricate relationship between the porcine intestinal microbiota and SECoV infections, offering potential strategies for preventing and controlling SECoV-related diseases.},
}

@article {pmid41072839,
year = {2025},
author = {Yu, G and Xie, W and Xiang, J and Ke, Y and Wang, Z and Tu, F and Wu, W and Hong, H and Lin, X},
title = {Gut microbiota remodelling alleviates elderly sepsis by microbiota-derived acetic acid via FFAR2/NLRP3 pathway.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {178229},
doi = {10.1016/j.ejphar.2025.178229},
pmid = {41072839},
issn = {1879-0712},
abstract = {BACKGROUND: Elderly patients with sepsis have higher morbidity, mortality, and susceptibility than adults. Young-donor faecal microbiota transplantation (FMT) can remodel and improve intestinal dysbiosis to alleviate age-related diseases via microbiota-derived acetic acid and may be a treatment option for elderly sepsis. This study aimed to elucidate the influence of remodelling of the elderly gut microbiota on sepsis via acetic acid and explore the underlying mechanism. We analyzed the gut microbiota and plasma acetic acid in elderly patients with sepsis, performed young-donor FMT, and acetic acid supplementation in a caecum ligation and puncture-induced aged septic model mice, and assessed the effects of acetic acid on the septic myocardium by examining NLRP3 inflammasome in FFAR2 knockdown mice.

RESULTS: Elderly sepsis had higher mortality, reduced gut microbiota diversity, increased Escherichia-Shigella abundance, and reduced plasma acetic acid levels. Young-donor FMT improved the gut microbiota, increased the abundance of the probiotic genus Akkermansia and faecal acetic acid levels in the gut, and improved colon barrier function and outcomes. Intestinal acetic acid intervention improved age-related intestinal dysbiosis, organ dysfunction, and adverse effects in aged septic mice. These beneficial effects on the myocardium were mediated by activation of the FFAR2/NLRP3 axis, as evidenced by the finding that FFAR2 knockdown abrogated the amelioration of acetic acid. The elderly gut microbiota is fragile, which is related to the severity and poor prognosis of elderly sepsis.

CONCLUSION: Gut microbiota remodelling improves elderly sepsis via acetic acid, which can inhibit inflammatory reactions to alleviate myocardial damage by FFAR2/NLRP3 inflammasome inactivation.},
}

@article {pmid41072600,
year = {2025},
author = {Wang, Y and Wang, X and Gan, B and Jia, T and Xu, T and Xu, H},
title = {The "Butterfly Effect" of Heart Failure: Induced by the Combination of Polylactic Acid Nanoplastics and Copper from the Perspective of Gut Microbiome.},
journal = {Chemico-biological interactions},
volume = {},
number = {},
pages = {111769},
doi = {10.1016/j.cbi.2025.111769},
pmid = {41072600},
issn = {1872-7786},
abstract = {Plastic and heavy metal pollution have received extensive attention, but there is relatively little research on the damage to the gut-heart axis induced by the co-exposure to plastics and heavy metals. This study investigated the impact of the co-exposure of Polylactic acid nanoplastics (PLA-NPs) and copper (Cu) on heart failure (HF) in mice and explored the role of the gut microbiota in mediating this adverse outcome. Male C57BL/6J mice were divided into four groups: the Control group, the PLA-NPs group, the Cu group, and the Co-exposure group (PLA-NPs+Cu group). A 28-day exposure experiment was conducted. The research results indicate that, compared with the Single-exposure groups (PLA-NPs and Cu groups), the mice of Co-exposure group exhibited more severe toxic effects, including more pronounced myocardial hypertrophy and more severe myocardial fibrosis. These damages might be caused by increasing the heart's sensitivity to ferroptosis. Additionally, the co-exposure caused significant damage to the gut barrier and remarkable dysbiosis in the gut microbiota, such as a reduction in the abundances of beneficial bacteria like Lactobacillus. The fecal Microbiota Transplantation experiment confirmed that the alterations in gut microbiota play a pivotal role in the synergistic toxicity induced by PLA-NPs and Cu. This study for the first time reveals the mechanism of the combined effect of PLA-NPs and Cu on cardiac damage and emphasizes the crucial role of gut microbiota in this process.},
}

@article {pmid41071393,
year = {2025},
author = {Wasim, R},
title = {The gut immune axis in ulcerative colitis: insights from microbiome research.},
journal = {Molecular biology reports},
volume = {52},
number = {1},
pages = {1006},
pmid = {41071393},
issn = {1573-4978},
mesh = {Humans ; *Colitis, Ulcerative/microbiology/immunology/therapy ; *Gastrointestinal Microbiome/immunology ; Fecal Microbiota Transplantation/methods ; Dysbiosis/microbiology/immunology ; Probiotics/therapeutic use ; Intestinal Mucosa/immunology/microbiology ; Prebiotics ; Animals ; },
abstract = {Ulcerative colitis (UC) is a chronic, recurrent inflammatory bowel disease (IBD) marked by inflammation of the colonic mucosa. While its precise aetiology remains unclear, emerging evidence underscores the pivotal role of gut microbiota in UC pathogenesis. In healthy individuals, the gut microbiota contributes to immune modulation, nutrient absorption, and maintenance of intestinal barrier integrity. In contrast, individuals with UC exhibit gut dysbiosis-characterized by a reduction in beneficial bacteria such as Faecalibacterium prausnitzii and Bifidobacterium, and an increase in potentially pathogenic microbes like Escherichia coli. This microbial imbalance disrupts mucosal homeostasis, promotes persistent inflammation, and impairs epithelial healing. Contributing factors include genetic predisposition, antibiotic exposure, diet, and environmental influences. Novel microbiota-targeted interventions-such as probiotics, prebiotics, dietary modifications, and faecal microbiota transplantation (FMT)-are being actively explored, with promising preliminary outcomes in symptom relief and microbiome restoration. However, challenges persist in defining a "healthy" microbiome and standardizing therapeutic protocols. This study highlights the potential of microbiome modulation as a transformative approach in UC management and calls for further research into host-microbe interactions to advance precision-based, microbiota-oriented therapies.},
}

Humans
*Colitis, Ulcerative/microbiology/immunology/therapy
*Gastrointestinal Microbiome/immunology
Fecal Microbiota Transplantation/methods
Dysbiosis/microbiology/immunology
Probiotics/therapeutic use
Intestinal Mucosa/immunology/microbiology
Prebiotics
Animals

@article {pmid41067318,
year = {2025},
author = {Zhao, H and Li, Y and Liu, N and Chen, P and Yu, X and Li, G and Deng, B and Li, D and Yang, F and Wang, G},
title = {Ganoderma lucidum polysaccharides alleviate non-alcoholic fatty liver disease by modulating gut microbiota against TLR4/NF-κB/MAPK pathway and activating AMPK pathway.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {120723},
doi = {10.1016/j.jep.2025.120723},
pmid = {41067318},
issn = {1872-7573},
abstract = {Ganoderma lucidum (Leyss. ex Fr.) Karst has been a revered traditional Chinese medicinal herb, widely used in folk medicine to treat various metabolic diseases due to its remarkable bioactivities. Among its active components, G. lucidum polysaccharides are particularly recognized as one of the main contributors to its therapeutic effects. However, the therapeutic efficacy of G. lucidum polysaccharides against non-alcoholic fatty liver disease (NAFLD) and its underlying mechanisms remain to be elucidated.

AIMS OF THE STUDY: This study aimed to assess the therapeutic efficacy of a novel polysaccharide (EPGLa) derived from G. lucidum in the treatment of NAFLD and to elucidate its underlying mechanisms.

MATERIALS AND METHODS: The chemical characterization of the isolated and purified EPGLa was conducted using monosaccharide composition analysis, Fourier-transform infrared (FT-IR) spectroscopy, molecular weight determination, methylation analysis, and 1D/2D nuclear magnetic resonance (NMR) spectroscopy. Following the establishment of a NAFLD mouse model, the therapeutic effect of EPGLa on NAFLD was assessed, and its underlying mechanism was clarified.

RESULTS: The backbone of EPGLa consists of the following glycosidic linkages: →6)-β-D-Glcp-(1→, →3)-β-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, →3,6)-β-D-Manp-(1→, →2)-α-D-Manp-(1→, and →4)-β-D-Galp-(1→. Its branches are composed of β-D-Glcp-(1→, β-D-Glcp-(1→3)-β-D-Glcp-(1→, and α-L-Fucp-(1→. In vivo results demonstrated that EPGLa effectively alleviated NAFLD by promoting the growth of beneficial gut bacteria to repair the intestinal barrier against Lipopolysaccharides (LPS)/toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB)/mitogen-activated protein kinase (MAPK) pathways, and simultaneously enhancing short-chain fatty acid (SCFA) production to activate the AMP-activated protein kinase (AMPK) pathway. To further validate these findings, we employed fecal microbiota transplantation (FMT), which confirmed the role of EPGLa in modulating gut microbiota against NAFLD.

CONCLUSION: Our study provides compelling evidence that EPGLa holds promise as a potential therapeutic agent for the intervention of NAFLD, and our findings also offer novel insights into the therapeutic targets of other bioactive polysaccharides.},
}

@article {pmid41067200,
year = {2025},
author = {Ding, L and Li, Q and Qi, K and Chen, Y and Hu, N and Hu, S and Fang, T and Guan, S and Wang, J and Qiu, J and Deng, X and Xu, L},
title = {Phloretin alleviates Salmonella pullorum infection by modulating gut microbiota-derived 3-phenylpropionic acid and AhR/IL-22/STAT-3 axis.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {148},
number = {},
pages = {157350},
doi = {10.1016/j.phymed.2025.157350},
pmid = {41067200},
issn = {1618-095X},
abstract = {BACKGROUND: Salmonella pullorum (S. pullorum) is an enteric pathogen that impairs growth performance, leading to substantial economic losses. Evidence demonstrates that the natural flavonoid phloretin can modulate gut microbiota functionality, and which underpins its therapeutic efficacy in ameliorating gastrointestinal disorders. However, the protective effects of phloretin against S. pullorum infections and underlying mechanisms remain unelucidated.

PURPOSE: This study aimed to elucidate the protective effects and mechanisms of phloretin in improving defense against S. pullorum infection by modulating gut microbiota in chicks.

METHODS: H&E staining, RT-qPCR and ELISA assays were used to assess the protective potentials of phloretin in S. pullorum-infected chicks. Then, 16S rRNA gene sequencing and untargeted metabolomics were employed to identify key microbiota and metabolites regulating the intestinal microenvironment. Moreover, fecal microbiota transplantation (FMT) and dietary metabolite supplementation were conducted to reshape the gut microbiota, elucidate the interaction between the microbiota and S. pullorum infection.

RESULTS: Phloretin treatment alleviated intestinal injury and enhanced growth performance in S. pullorum-infected chicks via improved intestinal barrier integrity, suppression of inflammatory responses, and restructuring of gut microbial composition. Additionally, these beneficial effects were also observed following FMT from phloretin-treated donors. Subsequent microbial and untargeted metabolomic analysis revealed that phloretin significantly enriched abundance of the functional bacterium Faecalibacterium, and the microbiota-derived phenylalanine metabolites 3-phenylpropionic acid (3-PPA). Importantly, 3-PPA supplementation attenuates S. pullorum-induced intestinal barrier damage and inflammation in chicks through modulation of the AhR/IL-22/STAT-3 signalling axis.

CONCLUSION: These findings provide new insights into the therapeutic potentials of phloretin for S. pullorum-infected chicks.},
}

@article {pmid41066868,
year = {2025},
author = {Zeng, Z and Li, H and Yang, W and Li, L and Ni, P and Chen, Q and Zhou, W and Peng, J and Huang, L},
title = {Probiotic VSL#3 alleviates intrahepatic cholestasis of pregnancy by upregulating farnesoid X receptor-fibroblast growth factor 15 through regulation of the gut microbiota.},
journal = {Journal of reproductive immunology},
volume = {172},
number = {},
pages = {104653},
doi = {10.1016/j.jri.2025.104653},
pmid = {41066868},
issn = {1872-7603},
abstract = {Intrahepatic cholestasis of pregnancy (ICP) poses significant risks to both maternal and fetal health, and treatment options remain limited. This study investigated the efficacy and underlying mechanisms of VSL#3 in alleviating ICP. Clinical fecal and blood samples were collected from 26 patients with ICP and 21 healthy pregnant women. The gut microbiota composition was analyzed using 16S rRNA sequencing. To further explore causality, we established a fecal microbiota transplantation-ICP mouse model using fecal samples from ICP patients, as well as an estrogen-induced ICP mouse model. Compared with healthy pregnant women, ICP patients exhibited a distinct gut microbiota profile, characterized by an increased abundance of Bacteroides and Alistipes. Serum FGF19 levels were significantly lower in ICP patients, showing a negative correlation with liver function markers, such as serum total bile acid (TBA), and a positive correlation with beneficial genera including Bifidobacterium, Ruminococcus, Blautia, Dorea, Eubacterium (hallii group) and Ruminococcus (torques group). VSL#3 treatment in mice alleviated ICP manifestations by improving liver histopathology, reducing TBA and alanine aminotransferase levels, increasing FGF15 concentrations, and enhancing fetal outcomes. These beneficial effects were abolished by co-administration of the FXR antagonist Z-guggulsterone, confirming the role of FXR signaling. In conclusion, VSL#3 alleviated ICP by modulating the gut microbiota to activate the FXR-FGF15 axis, thereby reducing bile acid synthesis and improving maternal and fetal outcomes.},
}

@article {pmid41065216,
year = {2025},
author = {Heer, P and Fernandez Elviro, C and Koutsokera, A and Mornand, A and Rochat, I and Regamey, N and Blanchon, S},
title = {Identification of early changes in multiple biomarkers following CFTR modulator initiation in patients with cystic fibrosis.},
journal = {Therapeutic advances in respiratory disease},
volume = {19},
number = {},
pages = {17534666251376211},
doi = {10.1177/17534666251376211},
pmid = {41065216},
issn = {1753-4666},
mesh = {Humans ; *Cystic Fibrosis/drug therapy/physiopathology/diagnosis/genetics/metabolism ; *Cystic Fibrosis Transmembrane Conductance Regulator/genetics/metabolism/drug effects ; Male ; Female ; *Aminophenols/therapeutic use/adverse effects ; *Benzodioxoles/therapeutic use/adverse effects ; *Quinolones/therapeutic use/adverse effects ; Prospective Studies ; Child ; Biomarkers/metabolism/blood ; Adolescent ; Treatment Outcome ; *Aminopyridines/therapeutic use ; Time Factors ; *Indoles/therapeutic use/adverse effects ; *Chloride Channel Agonists/therapeutic use/adverse effects ; Drug Combinations ; Young Adult ; *Pyrazoles/therapeutic use ; Sweat/chemistry ; Adult ; Pyrrolidines/therapeutic use ; },
abstract = {BACKGROUND: There are currently no early parameters that allow prediction of long-term responses to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator treatment on an individual level.

OBJECTIVES: To identify early parameters measured within 7 to 14 days after initiation of treatment with a CFTR modulator to assess CFTR modulator efficacy.

STUDY DESIGN: Prospective observational study of patients diagnosed with CF who begin elexacaftor/tezacaftor/ivacaftor (ETI) therapy at 3 CF clinics in Switzerland (Geneva, Lausanne, Lucerne).

METHODS: Standardized measurements were taken within 2 months prior to and 7 to 14 days after starting CFTR modulator treatment.

RESULTS: ETI treatment was started on 47 patients [median age: 12 years] of whom 12 (26%) were switching from lumacaftor/ivacaftor (n = 8) or tezacaftor/ivacaftor (n = 4) to ETI. A significant early treatment effect was observed for BMI z-score (p < 0.001) and inflammatory parameters (white blood cells (p = 0.006), neutrophils (p = 0.006), immunoglobulin G (p = 0.012), and fecal calprotectin (p = 0.002)). In CFTR functional assays, sweat chloride concentration and nasal potential difference testing [Δlow-chloride+isoproterenol, Sermet score, and Wilschanski index] improved significantly (all p < 0.001). Improvement was also observed in lung function (FVC, FEV1, MMEF25-75, LCI2.5%) (all p < 0.001). No changes were found for blood pressure, SpO2, respiratory rate, erythrocyte sedimentation rate, C-reactive protein, and fecal elastase.

CONCLUSION: This study identified clinical, biologic, and functional parameters showing treatment effect early after initiation of CFTR modulator therapy. These parameters may serve as potential predictors of long-term responses to CFTR modulator treatment.},
}

Humans
*Cystic Fibrosis/drug therapy/physiopathology/diagnosis/genetics/metabolism
*Cystic Fibrosis Transmembrane Conductance Regulator/genetics/metabolism/drug effects
Male
Female
*Aminophenols/therapeutic use/adverse effects
*Benzodioxoles/therapeutic use/adverse effects
*Quinolones/therapeutic use/adverse effects
Prospective Studies
Child
Biomarkers/metabolism/blood
Adolescent
Treatment Outcome
*Aminopyridines/therapeutic use
Time Factors
*Indoles/therapeutic use/adverse effects
*Chloride Channel Agonists/therapeutic use/adverse effects
Drug Combinations
Young Adult
*Pyrazoles/therapeutic use
Sweat/chemistry
Adult
Pyrrolidines/therapeutic use

@article {pmid41064515,
year = {2025},
author = {Aumpan, N and Chonprasertsuk, S and Pornthisarn, B and Siramolpiwat, S and Bhanthumkomol, P and Issariyakulkarn, N and Gamnarai, P and Bongkotvirawan, P and Wongcha-Um, A and Mahachai, V and Vilaichone, RK},
title = {Efficacy of encapsulated fecal microbiota transplantation and FMT via rectal enema for irritable bowel syndrome: a double-blind, randomized, placebo-controlled trial (CAP-ENEMA FMT Trial).},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1648944},
pmid = {41064515},
issn = {2296-858X},
abstract = {INTRODUCTION: Irritable bowel syndrome (IBS) is a functional bowel disorder. Gut dysbiosis involves in pathogenesis of IBS. Limited studies compared efficacy of fecal microbiota transplantation (FMT) via different routes of administration. This study aimed to compare efficacy of encapsulated FMT, FMT via rectal enema, and placebo in IBS patients.

METHODS: In this double-blind, randomized, placebo-controlled study, we enrolled patients aged 18-70 years with IBS defined by Rome IV criteria at Thammasat university, Thailand. Patients were randomized into three groups: (1) encapsulated FMT (six capsules twice daily for two consecutive days, total 50 g of stool), (2) FMT via rectal enema (50 g of stool in 200 mL of isotonic saline), or (3) placebo. Primary endpoint was clinical response defined by ≥50-point decrease in IBS-symptom severity score (IBS-SSS) at 4 weeks. Secondary outcomes were quality of life and changes of fecal microbiota composition after treatment. The study was registered with ClinicalTrials.gov, number NCT06201182.

RESULTS: From August 20, 2020, to February 15, 2024, 45 patients were randomized to receive encapsulated FMT (n = 15), FMT via rectal enema (n = 15), or placebo (n = 15). There was no difference in patient characteristics and baseline IBS-SSS between groups. Encapsulated FMT provided significantly improved IBS-SSS (166.7 ± 73.7 vs. 269.3 ± 69.5, p = 0.001), clinical response (86.7 vs. 26.7%, p = 0.001), and quality of life (31.7 ± 4.8 vs. 25.1 ± 5.2, p < 0.001) at 4 weeks compared with placebo. FMT via rectal enema demonstrated better IBS-SSS (168.7 ± 101.9 vs. 269.3 ± 69.5, p = 0.004), clinical response (73.3 vs. 26.7%, p = 0.011), and quality of life (30.2 ± 5.0 vs. 21.0 ± 7.4, p < 0.001) than placebo. Clinical response and quality of life between encapsulated FMT and FMT via rectal enema were not different. No serious adverse event was observed. Minor adverse events such as bloating and diarrhea were not different between all groups.

CONCLUSIONS: Higher clinical response and quality of life were demonstrated in both FMT groups than placebo. Either encapsulated FMT or FMT via rectal enema was safe and could provide favorable outcomes for IBS patients.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT06201182, Identifier: NCT06201182.},
}

@article {pmid41063317,
year = {2025},
author = {Gong, K and Zhang, S and Pan, Y and Cai, Q and Wu, M and Yin, X and Ma, J and Ji, H and Wang, Z and Wu, W and Zheng, H},
title = {Alternate day fasting alleviates neuroinflammation in diabetic mice by regulating δ-valerobetaine-carnitine-microglia axis via enrichment of Akkermansia muciniphila.},
journal = {Microbiome},
volume = {13},
number = {1},
pages = {202},
pmid = {41063317},
issn = {2049-2618},
support = {22074106//National Natural Science Foundation of China/ ; LY23H090008//Zhejiang Provincial Natural Science Foundation of China/ ; },
mesh = {Animals ; Mice ; *Carnitine/metabolism ; Gastrointestinal Microbiome/physiology ; *Fasting ; *Microglia/metabolism ; Akkermansia ; *Neuroinflammatory Diseases/metabolism ; *Diabetes Mellitus, Type 1/microbiology/metabolism ; *Verrucomicrobia ; Mice, Inbred C57BL ; *Diabetes Mellitus, Experimental/microbiology ; Male ; *Betaine/metabolism/analogs & derivatives ; Fecal Microbiota Transplantation ; },
abstract = {BACKGROUND: Alternate day fasting (ADF) as a healthy dietary pattern has been reported to improve brain functions and behaviors, but the effect of ADF on diabetes-related brain disorders and the potential mechanisms remain unclear. In this study, we investigated the impact of ADF on neuroinflammation and exploratory behavior in type 1 diabetic (T1D) mice and explored the specific molecular mechanisms from the perspective of the gut microbiota and host metabolism.

RESULTS: ADF can effectively relieve neuroinflammation and exploratory behavioral disorders in T1D mice. According to fecal microbiota transplant and bacterial supplementation, we demonstrated that ADF-driven enrichment of Akkermansia muciniphila (AKK) was necessary for boosting exploratory behavior in T1D mice. The gut microbiota-derived metabolite δ-valerobetaine (VB) reduced hepatic carnitine synthesis by inhibiting BBOX, and caused exploratory behavioral disorders in mice. In vitro and in vivo studies revealed that AKK bacteria had the ability to consume VB, and thereby increased systemic carnitine level. In addition, carnitine was found to deplete lipid droplet accumulation in microglia by enhancing fatty acid oxidation and lipolysis, reduce neuroinflammation and neuron injury, and then increase exploratory behavior in T1D mice.

CONCLUSIONS: Our study sheds light on the gut-liver-brain metabolic axis mechanism on the protective role of ADF in T1D-associated neuroinflammation and exploratory behavioral disorders and AKK bacteria exert as a key mediator. Video Abstract.},
}

Animals
Mice
*Carnitine/metabolism
Gastrointestinal Microbiome/physiology
*Fasting
*Microglia/metabolism
Akkermansia
*Neuroinflammatory Diseases/metabolism
*Diabetes Mellitus, Type 1/microbiology/metabolism
*Verrucomicrobia
Mice, Inbred C57BL
*Diabetes Mellitus, Experimental/microbiology
Male
*Betaine/metabolism/analogs & derivatives
Fecal Microbiota Transplantation

@article {pmid41061446,
year = {2025},
author = {Zhang, J and Lv, Y and Yang, S and Li, H and Luo, Y and Tang, X and Xu, J and Liu, X},
title = {Deciphering the regulatory role of selenium on cadmium bioavailability and toxicity: From the perspective of gut microbiota.},
journal = {Ecotoxicology and environmental safety},
volume = {305},
number = {},
pages = {119193},
doi = {10.1016/j.ecoenv.2025.119193},
pmid = {41061446},
issn = {1090-2414},
abstract = {Residents in areas naturally rich in cadmium (Cd) and selenium (Se) frequently exhibit exceptional longevity, raising intriguing questions about the interplay between the two elements. However, whether co-exposure affects the bioavailability of Cd remains unclear. Meanwhile, it is necessary to unclose the antagonistic mechanisms between Se and Cd. Here, a mouse bioassay was conducted to assess the impact of Se addition at low (0.1 mg/kg), medium (0.5 mg/kg) and high (2 mg/kg) doses, and duration (10 and 30 d) on Cd bioavailability of rice and Cd-induced hepatic toxicity. Results showed that Se cannot reduce Cd bioavailability. Medium Se addition for a duration of 10 days (MSe10) exhibited the highest efficacy in attenuating hepatic inflammation, as evidenced by augmented antioxidant enzyme activity, alleviated pathological damage, and increased levels of anti-inflammatory metabolites within the liver. The benefit was associated with its restoration of the gut microbiota and changes in key metabolic pathways. Notably, MSe10 increased the abundance of Faecalibaculum and Dubosiella, and enhanced the levels of secondary bile acids. Neither 0.1 mg/kg, 2 mg/kg nor long time addition of Se was beneficial for liver recovery. The hepatic lesions were fecal microbiota-dependent, as supported by fecal microbiota transplantation. Microbiota from MSe10 were capable to ameliorate hepatic inflammation, strengthen the intestinal barrier, and inhibit lipopolysaccharides (LPS) accumulation in blood. Additionally, the study provided insights into Se as an intervention for Cd toxicity, highlighting the appropriate dosage and its potential to reduce health risks.},
}

@article {pmid41061376,
year = {2025},
author = {Wekking, D and Ende, TVD and Bijlsma, MF and Vidal-Itriago, A and Nieuwdorp, M and van Laarhoven, HWM},
title = {Fecal microbiota transplantation to enhance cancer treatment outcomes across different cancer types: A systematic literature review.},
journal = {Cancer treatment reviews},
volume = {140},
number = {},
pages = {103025},
doi = {10.1016/j.ctrv.2025.103025},
pmid = {41061376},
issn = {1532-1967},
abstract = {BACKGROUND: The gut microbiome is increasingly recognized as a critical modulator of cancer therapy response. This systematic review evaluates Fecal Microbiota Transplantation (FMT)'s impact on cancer treatment outcomes and treatment-related toxicity and explores its mode of action.

METHODS: A systematic search was conducted for prospective or retrospective clinical studies published until May 2025 that investigated FMT in cancer patients undergoing immunotherapy, chemotherapy, radiotherapy, targeted therapy, or a combination regimen.

RESULTS: 45 studies were included. No large-scale RCTs with published efficacy data were available, and most findings were derived from studies that lacked statistical power to assess efficacy. The majority of the articles demonstrated the safety and feasibility of FMT. Most toxicities reported were grade 1 or 2. Mechanistically, donor FMT restores gut microbiota diversity and reprograms the gut ecosystem, with increases in tumor-infiltrating lymphocytes and lower levels of regulatory T cells being observed. Furthermore, studies reported clinical improvement and endoscopic and/or histologic remission of treatment-induced colitis following FMT, alongside decreased colonic CD8+ T cell infiltration.

CONCLUSION: Donor FMT appears to be a safe and feasible adjunctive strategy during both first and later-line therapy and has potential for managing treatment-related colitis; however, its efficacy and its role in preventing immune-related adverse events remain to be elucidated in RCTs, as well as its application for graft-versus-host disease. The variability in clinical outcomes and context-dependent microbiota-host interactions that result in inconsistent findings underscores the complexity of FMT as a therapeutic modality. Furthermore, subclassifying recipient cancer patients could (based on gut microbiome ecosystem features) enhance biomarker identification for treatment responses.},
}

@article {pmid41059058,
year = {2025},
author = {Wang, Y and Bai, Z and Liu, Y and Wang, Y and Xu, J and Lai, Z},
title = {Influence of the gut microbiota on the pharmacokinetics of tacrolimus in liver transplant recipients: insights from microbiome analysis.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1616985},
pmid = {41059058},
issn = {1664-302X},
abstract = {INTRODUCTION: Tacrolimus is crucial for immunosuppression after liver transplantation, but its pharmacokinetics vary markedly among individuals. Emerging evidence suggests that the gut microbiota may influence its metabolism, although the underlying mechanisms remain unclear.

METHODS: This study analyzed the fecal microbiota from 38 postliver transplant patients and 31 healthy controls via 16S rDNA amplicon and shotgun metagenomic sequencing. Patients were stratified into three groups on the basis of oral tacrolimus dosage and blood concentration: LDLBC (low dose, low blood concentration), LDHBC (low dose, high blood concentration), and SDLBC (standard dose, low blood concentration).

RESULTS: Posttransplant patients presented significantly reduced gut microbial diversity. Specific bacterial taxa, including Enterococcus raffinosus, Intestinibacter bartlettii, and Bacteroides fragilis, were enriched in patients with lower tacrolimus blood concentrations. In contrast, Phascolarctobacterium faecium and Streptococcus salivarius were associated with increased drug levels. Functional analysis revealed differences between patient subgroups in ATP-binding cassette (ABC) transporters and drug efflux pumps, suggesting a potential microbial influence on tacrolimus absorption and metabolism. Additionally, antibiotic resistance genes were more abundant in patients with lower tacrolimus blood concentrations, particularly in the Escherichia coli-enriched groups.

DISCUSSION: These findings underscore the influence of the gut microbiota on tacrolimus pharmacokinetics and support the potential of microbial composition as a biomarker for optimizing immunosuppressive therapy.},
}

@article {pmid41057955,
year = {2025},
author = {Chen, W and Liu, C and Li, X and Yang, X and Liu, Y and Qin, M and Jiang, W and Wang, Y and Sun, H and Li, G and Wen, B and He, S},
title = {5,7-dimethoxyflavone inhibits hepatocellular carcinoma progression via increasing intestinal Akkermansia muciniphila and hepatic CD8[+] T cell infiltration.},
journal = {Chinese medicine},
volume = {20},
number = {1},
pages = {170},
pmid = {41057955},
issn = {1749-8546},
support = {82405072//National Natural Science Foundation of China/ ; 82304927//National Natural Science Foundation of China/ ; 82274286//National Natural Science Foundation of China/ ; 2023A1515110041//Joint Funds of Basic and Applied Basic Research Fund of Guangdong/ ; 2023M741596//China Postdoctoral Science Foundation/ ; },
abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) mainly develops in cases of fibrosis and cirrhosis and is accompanied by intestinal flora disorder. HCC also affects CD8[+] T cell immune function. 5,7-Dimethoxyflavone (DMF), an active flavonoid with anti-tumor effect, is found in Kaempferia parviflora. However, whether DMF can treat HCC remains unclear. This study aims to investigate the effect of DMF on HCC and to explore its possible mechanism, focusing on the gut microbiota regulation and the effect of CD8[+] T cells in a murine model.

METHODS: The HCC mouse model was induced with diethylnitrosamine/carbon tetrachloride and orally administered DMF. DMF effects on HCC progression were assessed using hematoxylin and eosin staining, immunohistochemistry, and serum biochemical marker levels. The causal relationship between gut microbes and HCC was explored using 16S rRNA genome-derived taxonomic profiling, microbial transplantation, fecal high-throughput targeted metabolomics, and untargeted serum metabolomic analyses. Transcriptome analysis, molecular docking, quantitative real-time polymerase chain reaction, and Western blot were applied to study the genes targeted by DMF. CD8[+] T cell infiltration and tumor-killing factors were studied using flow cytometry and immunofluorescence staining.

RESULTS: DMF reduced the number of tumors, the largest tumor size, and the liver-to-body ratio while also improving liver function. An antibiotic cocktail lowered the anti-tumor effect of DMF, indicating that DMF inhibition of HCC is partially dependent on the gut microbiota. DMF considerably upregulates Akkermansia muciniphila during chemical hepatocarcinogenesis in mice. DMF-upregulated A. muciniphila leading to intestinal barrier repair, which inhibited HCC progression by enhancing antioxidant capacity through glutathione regulation and 11,12-DIHETrE down-regulation. An untargeted serum metabolomic analysis showed that there existed additional mechanisms underlying DMF anti-tumor effect following its absorption into the bloodstream. DMF enhances the infiltration effect of CD8[+] T cells and upregulates interferon-gamma expression in HCC tissue. Overall, 822 genes, including chemokine (C-C motif) ligand 2 (CCL2), were significantly downregulated by DMF treatment in HCC cells. Notably, DMF binds strongly with nuclear factor kappa-B (NF-κB) and inhibits NF-κB p65 phosphorylation, sequentially suppressing the expression of downstream protein CCL2, which mediate the crosstalk between tumor cells and CD8[+] T cells.

CONCLUSION: DMF improves A. muciniphila-mediated intestinal barrier repair and inhibits the NF-κB/CCL2 pathway in HCC cells, enhancing the immunity of CD8[+] T cells in the liver. Hence, it may serve as a potential candidate for HCC treatment.},
}

@article {pmid41055380,
year = {2025},
author = {Du, J-Y and Zhang, Z-J and Tan, L and Yang, J-Y and Yang, R-N and Chen, Y-L and Tan, G-F and Li, J and Li, W-J and Yang, L and Cai, J and Shen, D-L and Zhu, H-R and Fan, Z-X and Yuan, M-L and Zhang, W},
title = {Gut microbiota dysbiosis and metabolic perturbations of bile/glyceric acids in major depressive disorder with IBS comorbidity.},
journal = {mBio},
volume = {},
number = {},
pages = {e0244725},
doi = {10.1128/mbio.02447-25},
pmid = {41055380},
issn = {2150-7511},
abstract = {Major depressive disorder (MDD) and irritable bowel syndrome (IBS) exhibit high comorbidity, yet their shared pathophysiology remains unclear. Previous studies have primarily focused on the psychological health in the IBS population, without considering psychiatric diagnoses or stratifying different psychological states, potentially leading to biased findings. This study employed multi-omics approaches to characterize gut microbiota and serum metabolites in 120 MDD patients (47 with IBS and 73 without IBS) and 70 healthy controls (HCs). MDD with IBS patients showed significantly higher depression (Hamilton depression scale [HAMD-17]) and anxiety (Hamilton anxiety scale [HAMA-14]) scores than MDD-only patients (P < 0.05). Metagenomic sequencing of fecal samples revealed increased alpha diversity (Chao1/Shannon indices) and Firmicutes dominance in both MDD groups vs HC, while Actinobacteria enrichment specifically marked MDD with IBS. Functionally, MDD with IBS uniquely activated D-amino acid/glycerolipid metabolism pathways (Kyoto Encyclopedia of Genes and Genomes). Serum metabolomics identified comorbid-specific perturbations: downregulation of bile acids (CDCA, GCDCA, GCDCA-3S) and upregulation of glyceric acid/glutaconic acid. Our study also found that Eggerthella lenta and Clostridium scindens are differentially abundant bacteria that are involved in bile acid metabolism, and that microbial genes (e.g., K03738) are associated with glyceric acid production. These findings implicate gut microbiota-driven bile acid/glyceric acid dysregulation in MDD with IBS comorbidity, supporting the gut-brain axis as a therapeutic target for probiotics or microbiota transplantation.IMPORTANCEMajor depressive disorder (MDD) exhibits a high comorbidity rate with irritable bowel syndrome (IBS). Our study, conducted on 120 MDD patients (47 of whom were comorbid with IBS) and a control group of 70 individuals, revealed that MDD-IBS comorbid patients demonstrated significantly higher depression/anxiety scores. Multi-omics analysis indicated substantial alterations in the gut microbiota (e.g., Firmicutes, Actinobacteria) and serum metabolites (e.g., bile acids, glyceric acid) among MDD-IBS patients, which were associated with specific metabolic pathways. Therefore, the new aspect of this study was the inclusion of patients with MDD but without IBS symptoms, which provided a deeper understanding of the intestinal microbiota dysregulation associated with comorbid IBS and MDD. These findings suggest that there may be involvement of the gut-brain axis, providing new research directions for potential therapeutic targets.CLINICAL TRIALSThis study is registered with the Chinese Clinial Trial Registry as ChiCTR2100041598.},
}

@article {pmid41052982,
year = {2025},
author = {Cao, Y and Fan, X and Zang, T and Qiu, T and Fang, Q and Bai, J and Liu, Y},
title = {Prenatal depression-associated gut microbiota induces depressive-like behaviors and hippocampal neuroinflammation in germ-free mice.},
journal = {Translational psychiatry},
volume = {15},
number = {1},
pages = {383},
pmid = {41052982},
issn = {2158-3188},
support = {2023AFB710//Natural Science Foundation of Hebei Province (Hebei Provincial Natural Science Foundation)/ ; },
mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Female ; *Hippocampus/metabolism/pathology/immunology ; Mice ; Pregnancy ; Fecal Microbiota Transplantation ; *Depression/microbiology/metabolism ; *Dysbiosis/microbiology/complications ; Humans ; Lipopolysaccharides/blood ; Germ-Free Life ; *Neuroinflammatory Diseases/metabolism/microbiology ; Microglia ; *Pregnancy Complications/microbiology ; Disease Models, Animal ; Behavior, Animal ; Interleukin-6/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; },
abstract = {Numerous studies have described the role of the microbiome-gut-brain axis in depression. However, the molecular mechanisms underlying the involvement of gut microbiota in the development of prenatal depression are limited. In this study, fecal microbiota from women with prenatal depression was transplanted into germ-free mice to investigate the potential causal relationships between the gut microbiota and depressive phenotypes. Shotgun metagenomic sequencing and untargeted metabolomics approaches were used to investigate the characteristics of gut microbiota and microbial metabolites. The levels of neuroinflammation in the brain were detected using immunofluorescence and real-time quantitative PCR. We found significant changes in gut microbiota composition and metabolites in mice with fecal microbiota transplantation (FMT) from women with prenatal depression, including decreased Ligilactobacillus, increased Akkermansia, and abnormal glycerophospholipid metabolism. Besides, significant increase in plasma lipopolysaccharide (LPS) levels and significant proliferation of microglia in the hippocampus were observed in mice receiving FMT from women with prenatal depression, accompanied by a significant increase in the expression of nuclear factor-κB (NF-κB) p65, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA. The gut microbiota and its metabolites were strongly associated with depressive-like behaviors, plasma LPS and neuroinflammation. Our study collectively demonstrates that dysbiosis of the gut microbiota may play a causal relationship in the development of prenatal depression. This process potentially involves the activation of neuroinflammation through the LPS-NF-κB signaling pathway.},
}

Animals
*Gastrointestinal Microbiome/physiology
Female
*Hippocampus/metabolism/pathology/immunology
Mice
Pregnancy
Fecal Microbiota Transplantation
*Depression/microbiology/metabolism
*Dysbiosis/microbiology/complications
Humans
Lipopolysaccharides/blood
Germ-Free Life
*Neuroinflammatory Diseases/metabolism/microbiology
Microglia
*Pregnancy Complications/microbiology
Disease Models, Animal
Behavior, Animal
Interleukin-6/metabolism
Tumor Necrosis Factor-alpha/metabolism

@article {pmid41052746,
year = {2025},
author = {Chen, Y and Yu, L and Zhang, L and Liu, C and You, Y and Guo, H and Li, Z and Yin, X and Hong, T and Ding, L and Fang, Q},
title = {Gut microbiota dysbiosis exacerbates post-stroke depression via microglial NLRP3 inflammasome activation.},
journal = {Experimental neurology},
volume = {},
number = {},
pages = {115488},
doi = {10.1016/j.expneurol.2025.115488},
pmid = {41052746},
issn = {1090-2430},
abstract = {BACKGROUND: Post-stroke depression (PSD) is a neuropsychiatric complication prevalent among stroke survivors. Emerging evidence suggests that dysregulation of the microbiota-gut-brain axis is implicated in the pathogenesis of PSD. However, the exact mechanism is not clear and further research is necessary.

METHODS: Initially, Sprague-Dawley (SD) rats were randomly allocated into three experimental groups: Sham, Middle Cerebral Artery Occlusion (MCAO), and PSD. Behavioral tests were conducted to evaluate depressive-like behavior. Fecal samples from all groups underwent 16S rRNA sequencing for comprehensive gut microbiota analysis. Colonic tissues were collected from rats and subjected to immunohistochemical analysis for quantification of tight junction proteins (ZO-1, Occludin, and Claudin). Peripheral blood plasma was obtained for the determination of IL-1β, IL-6, TNF-α, and IL-18 levels using enzyme-linked immunosorbent assay (ELISA). Lastly, hippocampus tissues were harvested for molecular characterization of Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation and inflammatory cytokines expression through tripartite methodology: Reverse Transcription quantitative PCR (RT-qPCR), Western blot, and immunofluorescence. Concurrently, hippocampal concentrations of 5-HT, BDNF, and PSD-95 were also measured by ELISA. Subsequently, Fecal Microbiota Transplantation (FMT) was performed by administering fecal suspensions from PSD and Sham donor rats to healthy SD recipients via oral gavage. Then, use the above methods to test the same indicator.

RESULT: Comparative analyses showed that microbial species richness and diversity indices were significantly reduced in PSD model rats, along with a compositional imbalance of the gut microbiota. Concurrently, reduced expression of the colonic tight junction proteins ZO-1, Occludin, and Claudin was observed, accompanied by elevated levels of peripheral inflammatory cytokines. In PSD rats, NLRP3 inflammasome activation was detected in the ischemic hippocampus, along with increased expression of the inflammatory cytokines IL-18 and IL-1β, and decreased levels of 5-HT, BDNF, and PSD-95. Subsequently, using FMT technology, PSD rat feces were innovatively prepared into a fecal suspension and administered to healthy SD rats. Analysis revealed that FMT-PSD rats exhibited a disrupted gut microbiota structure, impaired colonic barrier integrity, activation of the hippocampal NLRP3 inflammasome, elevated inflammatory cytokine levels, and reduced neurotransmitter expression.

CONCLUSION: In summary, these data demonstrate that dysbiosis of the intestinal microbiota compromises gut barrier integrity and elicits systemic inflammation, which may subsequently activate the NLRP3 inflammasome in hippocampal microglia. This activation promotes the release of pro-inflammatory cytokines IL-18 and IL-1β, and coincides with dysregulation of emotion-related neurotransmitters, collectively contributing to the pathogenesis of PSD.},
}