@article {pmid41503571,
year = {2026},
author = {Bajaj, JS and Fagan, A and Sterling, RK and Sikaroodi, M and Gallagher, ML and Lee, H and Matherly, SC and Bartels, A and Mousel, T and Davis, BC and Puri, P and Fuchs, M and Thacker, LR and McGinley, JP and Khoruts, A and Gillevet, PM},
title = {The multi-omic basis for hepatic encephalopathy recurrence: Analysis of the THEMATIC trial.},
journal = {JHEP reports : innovation in hepatology},
volume = {8},
number = {1},
pages = {101634},
doi = {10.1016/j.jhepr.2025.101634},
pmid = {41503571},
issn = {2589-5559},
abstract = {BACKGROUND & AIMS: The THEMATIC trial demonstrated that fecal microbiota transplantation (FMT) reduces recurrence of hepatic encephalopathy (HE) in patients already receiving lactulose and rifaximin. The aim of this analysis was to identify multi-omic predictors of HE recurrence among THEMATIC trial participants.

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

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

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

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

TRIAL REGISTRATION: www.clinicaltrials.gov: NCT03796598.},
}

@article {pmid41503356,
year = {2025},
author = {Alobaidi, S},
title = {The gut-kidney axis in chronic kidney disease: mechanisms, microbial metabolites, and microbiome-targeted therapeutics.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1675458},
doi = {10.3389/fmed.2025.1675458},
pmid = {41503356},
issn = {2296-858X},
abstract = {Chronic kidney disease (CKD) remains a major global health issue, affecting millions and presenting persistent diagnostic and therapeutic challenges. Conventional biomarkers such as serum creatinine and estimated glomerular filtration rate have well-recognized limitations, underscoring the need for novel diagnostic tools and interventions. Emerging evidence highlights the gut-kidney axis as a central contributor to CKD pathogenesis, shaped by microbial dysbiosis and altered metabolite production. Harmful metabolites such as indoxyl sulfate, p-cresyl sulfate, and trimethylamine-N-oxide promote inflammation, endothelial dysfunction, and fibrosis, while loss of protective short-chain fatty acids impairs barrier integrity and immune regulation. This review integrates mechanistic, translational, clinical, and therapeutic perspectives, offering a comprehensive and distinctive synthesis of current knowledge. We emphasize both harmful and protective microbial metabolites, incorporate the often-overlooked oral-gut-kidney axis, and highlight advances in multi-omics and computational approaches for biomarker discovery. Microbiome-targeted interventions-including dietary strategies, prebiotics, probiotics, synbiotics, oral adsorbents, and fecal microbiota transplantation-are critically evaluated with respect to efficacy, safety, and translational readiness. By bridging basic science, clinical evidence, and therapeutic implications, this review provides a forward-looking framework for integrating microbiome insights into CKD diagnosis and management. Our synthesis complements existing literature while highlighting unmet needs, thereby informing future research priorities and guiding the development of clinically relevant microbiome-based strategies.},
}

@article {pmid41502951,
year = {2025},
author = {Oliveira, RA and McSpadden, E and Pandey, B and Lee, K and Yousef, M and Chen, RY and Triebold, C and Haro, F and Aksianiuk, V and Patel, R and Shriram, K and Ramanujam, R and Kuehn, S and Raman, AS},
title = {Statistical design of a synthetic microbiome that suppresses diverse gut pathogens.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.02.28.582635},
pmid = {41502951},
issn = {2692-8205},
abstract = {Engineering functional microbiomes is challenging due to complex interactions between bacteria and their environments [1-6] . Using a set of 848 gut commensal strains and clearance of multi-drug resistant Klebsiella pneumoniae (Kp -MH258) as a target function, we engineered a functional 15-member synthetic microbiome-SynCom15-through a statistical approach agnostic to strain phenotype, mechanism of action, bacterial interactions, or composition of natural microbiomes. Our approach involved designing, building, and testing 96 metagenomically diverse consortia, learning a generative model using community strain presence/absence as input, and distilling model constraints through statistical inference. SynCom15 cleared Kp -MH258 across in vitro , ex vivo , and in vivo environments, matching the efficacy of a fecal microbiome transplant in a clinically relevant murine model of infection. The mechanism of suppression by SynCom15 was related to fatty acid production coupled with environmental acidification. SynCom15 also suppressed other pathogens- Clostridioides difficile , Escherichia coli , and other K. pneumoniae strains-but through different mechanisms. Sensitivity analysis revealed models trained on strain presence/absence captured the statistical structure of pathogen suppression, illustrating that community representation was key to our approach succeeding. Our framework, 'Constraint Distillation', could be a general and efficient strategy for building emergent complex systems, offering a path towards synthetic ecology more broadly.},
}

@article {pmid41500422,
year = {2026},
author = {Jin, J and Li, F and Hu, Y and Zhang, Z and Zhang, R and Xing, F},
title = {Gut microbiota dysbiosis transmits deoxynivalenol toxicity and triggers liver inflammation.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2026.01.011},
pmid = {41500422},
issn = {2090-1224},
abstract = {INTRODUCTION: Deoxynivalenol (DON), a mycotoxin produced by Fusarium species, is known to compromise gut barrier integrity and induce systemic inflammation.

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

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

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

CONCLUSION: These findings underscore that dysbiosis, especially involving specific bacterial genera, can independently trigger liver inflammation, highlighting a microbiota-mediated pathogenic mechanism in mycotoxin toxicity.},
}

@article {pmid41498910,
year = {2026},
author = {Li, Y and Shen, X and Wang, D and Sun, K},
title = {The gut microbiome in colorectal cancer: mechanisms of carcinogenesis and emerging microbiota-targeted therapies.},
journal = {Discover oncology},
volume = {},
number = {},
pages = {},
doi = {10.1007/s12672-025-04367-1},
pmid = {41498910},
issn = {2730-6011},
}

@article {pmid41497693,
year = {2025},
author = {Rusman, RD and Akil, F and Parewangi, ML and Daud, NA and Bachtiar, R and Kusuma, SH and Rifai, A},
title = {Gut microbiota and metabolic-associated steatosis liver disease: Unveiling mechanisms and opportunities for therapeutic intervention.},
journal = {World journal of experimental medicine},
volume = {15},
number = {4},
pages = {107316},
pmid = {41497693},
issn = {2220-315X},
abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a leading cause of chronic liver disease, closely linked with metabolic syndrome. Recent evidence spotlights the gut-liver axis as a major player in MASLD pathogenesis. Dysbiosis of gut microbiota alters the intestinal barrier and enhances endotoxemia, hepatic inflammation, insulin resistance and fibrosis. Microbial metabolites including short-chain fatty acids, bile acids and ethanol impact host metabolism and immunity, and their dysregulation contributes to disease progression. This review summarises the mechanistic associations between dysbiosis and MASLD involving altered microbial composition, leaky gut, toll-like receptor signalling and immune dysregulation. It also reviews microbially targeted therapeutic strategies, such as probiotics, prebiotics, synbiotics, faecal microbiota transplantation, diet changes, and postbiotic metabolites. Although these interventions may have clinical potential, the heterogeneity of outcomes highlights the interindividual nature of the microbiome and warrant personalized interventions. Developments in multi-omics and precision medicine provide possibilities to discover microbial biomarkers and customize therapeutic approach. Resolving methodological heterogeneity and providing a clear definition of MASLD-related dysbiosis are key for translating microbiome science into the clinic. In conclusion, modulation of gut microbiota is an emerging strategy for the adjunctive treatment of MASLD alongside lifestyle and pharmacologic therapies.},
}

@article {pmid41496455,
year = {2026},
author = {Ramesh, A and Subbarayan, R and Shrestha, R and Adtani, PN},
title = {Exploring Fecal Microbiota Transplantation: Potential Benefits, Associated Risks, and Challenges in Cancer Treatment.},
journal = {Cancer reports (Hoboken, N.J.)},
volume = {9},
number = {1},
pages = {e70455},
doi = {10.1002/cnr2.70455},
pmid = {41496455},
issn = {2573-8348},
mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Neoplasms/therapy/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Tumor Microenvironment/immunology ; Immunotherapy/methods ; Animals ; Risk Assessment ; },
abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has emerged as a groundbreaking strategy for modulating the gut microbiome and improving cancer treatment outcomes. This review synthesizes the current evidence on the role of FMT in oncology, focusing on its potential to enhance the efficacy of immunotherapy, restore microbiome homeostasis, and mitigate cancer-associated complications.

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

CONCLUSION: While FMT holds transformative potential in cancer care, its integration into oncological practice requires robust clinical validation, long-term safety assessments, and interdisciplinary collaboration to harness its full therapeutic potential.},
}

Humans
*Fecal Microbiota Transplantation/methods/adverse effects
*Neoplasms/therapy/immunology/microbiology
*Gastrointestinal Microbiome/immunology
Tumor Microenvironment/immunology
Immunotherapy/methods
Animals
Risk Assessment

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

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

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

CONCLUSION: FMT effectively improves hepatic inflammation and steatosis in MASLD, with age modulating ALT response. Lack of BMI improvement suggests localized liver effects rather than systemic metabolic impact, supporting FMT as a targeted adjunctive therapy.},
}

Humans
*Fecal Microbiota Transplantation/methods
Alanine Transaminase/blood
Aspartate Aminotransferases/blood
Randomized Controlled Trials as Topic
Body Mass Index
Treatment Outcome
*Fatty Liver/therapy
Gastrointestinal Microbiome
*Non-alcoholic Fatty Liver Disease/therapy
Male
Middle Aged
Liver/pathology

@article {pmid41494302,
year = {2025},
author = {Yi, J and Tang, Y and Chen, Y and Chen, L and Geng, D and Liu, L and Yu, J and Zou, L and Zeng, J and Lan, M and Gao, W and Gao, M},
title = {Kudzu root-derived carbon dots modulate gut microbiota and metabolites for pan-organ targeted macrophage polarization in synergistic diabetes therapy.},
journal = {Biomaterials},
volume = {329},
number = {},
pages = {123967},
doi = {10.1016/j.biomaterials.2025.123967},
pmid = {41494302},
issn = {1878-5905},
abstract = {Type 2 diabetes is a systemic disorder characterized by metabolic dysfunction and chronic inflammation, yet strategies that address both aspects remain limited. Here, we present kudzu root-derived carbon dots (KRCDs) as a natural nanomaterial that reprograms the gut microbiota-metabolite-immune axis to restore systemic homeostasis. KRCDs exhibit nanoscale crystallinity, abundant O/N functional groups, and strong antioxidant activity. In high-fat diet/streptozotocin-induced diabetic mice, KRCDs significantly lowered fasting glucose, improved glucose tolerance and insulin sensitivity, corrected lipid profiles, and reduced hepatic steatosis without detectable toxicity. Multi-omics analyses revealed increased microbial diversity, enrichment of beneficial genera such as Anaerostipes, and remodeling of fecal metabolites with a marked rise in indole-3-carboxaldehyde (I3A). This metabolite correlated with enhanced M2-like macrophage polarization across adipose tissue, intestine, kidney, liver, and pancreas, as confirmed by flow cytometry and immunofluorescence. Fecal microbiota transplantation from KRCDs-treated donors reproduced both the metabolic improvements and the organ-wide M2 polarization, confirming a microbiota-dependent mechanism. By establishing a gut microbiota-metabolite-macrophage polarization pathway, KRCDs act as safe, plant-based nanoplatforms that simultaneously correct metabolic and immune imbalance, offering a promising strategy for multi-target intervention in diabetes.},
}

@article {pmid41494100,
year = {2026},
author = {Wang, D and Dai, S and Li, D and Du, P and Zhao, Y and Chen, Y and Ye, Y and Zhou, M and Ren, W and Liu, X and Zhao, B},
title = {Bovine Milk-Derived Extracellular Vesicles Attenuate Liver Injury by Modulating the Gut-Liver Axis via Faecalibaculum-Mediated SCFA Production.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c12208},
pmid = {41494100},
issn = {1520-5118},
abstract = {Chronic liver injury represents a core pathological substrate in a spectrum of hepatic disorders, wherein gut-liver axis homeostasis critically drives progression. Although bovine milk extracellular vesicles (mEVs) positively regulate intestinal homeostasis, the mechanisms underlying their gut microbiota-linked hepatoprotection remain unclear. Herein, we demonstrated that mEVs (0.6 mg/kg/d) effectively alleviated carbon tetrachloride (CCl4, 1 mg/kg)-induced liver injury, as evidenced by reduced hepatic inflammation and fibrosis. Concurrently, mEVs also markedly attenuated colonic barrier disruption and inflammation concomitant with liver injury. Gut microbiota analysis revealed that mEVs notably enriched the relative abundances of Faecalibaculum and Lactobacillus, which correlated positively with mEV-enhanced colonic short-chain fatty acid (SCFA)/free fatty acid receptor (FFAR) signaling. Furthermore, a causal link between the mEV-reshaped gut microbiota and the resulting hepatoprotection was further established via fecal microbiota transplantation (FMT). In summary, these findings revealed that mEVs attenuated liver injury in a gut microbiota-dependent manner, offering valuable insights into microbiota-targeted and mEV-based therapeutic strategies for hepatic disorders.},
}

@article {pmid41493848,
year = {2026},
author = {Kawaguchi, Y and Terui, K and Fumita, T and Shibata, R and Yoshizawa, H and Ogasawara, S and Kondo, T and Ozawa, Y and Inaba, Y and Hishiki, T},
title = {Cholestasis-reducing effects of bezafibrate on survivors of biliary atresia with native livers: A prospective phase II trial.},
journal = {Hepatology communications},
volume = {10},
number = {1},
pages = {},
pmid = {41493848},
issn = {2471-254X},
mesh = {Humans ; Male ; Female ; *Bezafibrate/therapeutic use/administration & dosage ; *Biliary Atresia/complications/surgery ; *Cholestasis/drug therapy/etiology ; Prospective Studies ; Adult ; *Hypolipidemic Agents/therapeutic use/administration & dosage ; Young Adult ; Adolescent ; Alkaline Phosphatase/blood ; Liver ; Treatment Outcome ; Survivors ; gamma-Glutamyltransferase/blood ; },
abstract = {BACKGROUND: Long-term survivors of biliary atresia (BA) require liver transplantation owing to cholestasis-associated complications. Bezafibrate (BZF), an antihyperlipidemic agent, can improve cholestasis-induced liver damage. Herein, we evaluated the cholestasis-reducing effect of BZF on survivors of BA with native livers, a condition that has not been previously assessed in any study.

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

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

CONCLUSIONS: BZF decreased cholestasis markers in survivors of BA with native livers, indicating its potential as an alternative to delayed liver transplantation for this population.},
}

Humans
Male
Female
*Bezafibrate/therapeutic use/administration & dosage
*Biliary Atresia/complications/surgery
*Cholestasis/drug therapy/etiology
Prospective Studies
Adult
*Hypolipidemic Agents/therapeutic use/administration & dosage
Young Adult
Adolescent
Alkaline Phosphatase/blood
Liver
Treatment Outcome
Survivors
gamma-Glutamyltransferase/blood

@article {pmid41492974,
year = {2026},
author = {Qiu, Y and Lyu, X and Zhang, D and Xu, H and He, X and Chen, J and Liu, H and Liu, Y and Xie, L},
title = {Gut Microbiota in Pulmonary Arterial Hypertension: Murine Models and Human Microbial Signatures, Pathogenic Mechanisms, and Emerging Therapeutic Avenues.},
journal = {Comprehensive Physiology},
volume = {16},
number = {1},
pages = {e70094},
doi = {10.1002/cph4.70094},
pmid = {41492974},
issn = {2040-4603},
support = {U21A20333//National Natural Science Foundation of China/ ; 2023YFC2705701//National Key Research and Development Program of China/ ; XZ202501ZY0116//Science and Technology Projects of Xizang Autonomous Region/ ; XZ202401ZY0013//Science and Technology Projects of Xizang Autonomous Region/ ; 2023NSFSC0530//Sichuan Province Science and Technology Support Program/ ; },
mesh = {Humans ; Animals ; *Gastrointestinal Microbiome/physiology ; *Pulmonary Arterial Hypertension/microbiology/therapy/metabolism ; Mice ; Disease Models, Animal ; Fecal Microbiota Transplantation ; },
abstract = {Pulmonary arterial hypertension (PAH) is a chronic, severe cardiopulmonary disease characterized by the progressive increase in pulmonary vascular resistance (PVR) because of the proliferation and fibrosis of the pulmonary arterioles. Although the disease originates in the pulmonary vasculature, it ultimately leads to right heart failure and death. PAH is associated with high mortality rates and poor prognosis, with no therapies currently available to reverse pulmonary vascular remodeling, imposing substantial socioeconomic burdens. Growing interest in the gut-lung axis has highlighted the role of gut microbiota and their metabolites in the occurrence and development of PAH. Evidence showed that gut dysbiosis and metabolite imbalances, involving reduced short-chain fatty acids (SCFAs), increased trimethylamine-N-oxide (TMAO), and dysregulated tryptophan metabolism, contributed to pulmonary vascular remodeling. This review systematically compares gut microbiota and metabolites across PAH murine models (including chronic hypoxia, SU5416/hypoxia [SuHx], monocrotaline [MCT], and non-classical models) and patients (adults and children). The analysis aims to identify disease-specific microbial and metabolic signatures. It is also discussed how the microbiota and their metabolites may influence inflammation around the pulmonary vasculature. Furthermore, the potential of probiotic therapy, fecal microbiota transplantation (FMT), and mesenchymal stem cells (MSCs) therapies as novel treatment strategies for PAH is discussed.},
}

Humans
Animals
*Gastrointestinal Microbiome/physiology
*Pulmonary Arterial Hypertension/microbiology/therapy/metabolism
Mice
Disease Models, Animal
Fecal Microbiota Transplantation

@article {pmid41492376,
year = {2026},
author = {Huang, L and Zheng, Y and Liu, Q and Feng, Y and Ma, Z and Zhao, X and Wei, X and Yu, X and Lv, X and Lv, J and Li, L and Liu, H and Ze, X and Zhang, M},
title = {Milk fat globule membrane ameliorates depressive-like behaviors in chronic unpredictable mild stress rats by modulating the microbiota-gut-brain axis.},
journal = {Bioscience of microbiota, food and health},
volume = {45},
number = {1},
pages = {66-78},
pmid = {41492376},
issn = {2186-6953},
abstract = {Depression is one of the common psychiatric disorders, and it has been reported that the imbalance in the microbiota-gut-brain (MGB) axis contributes to the pathogenesis of depression. Milk fat globule membrane (MFGM) can impact the gut-brain axis by regulating the intestinal flora and metabolite production. The aim of this study was to investigate whether MFGM could ameliorate depressive-like behaviors induced by chronic unpredictable mild stress (CUMS) and further elucidate the potential mechanism through a fecal microbiota transplantation (FMT) experiment. Male Sprague-Dawley rats were provided with an MFGM diet for 5 weeks after the induction with CUMS. Depressive-like behaviors were assessed, and the levels of neurotransmitters, neuroendocrine hormones, microbiota, short-chain fatty acids (SCFAs), and tight junction proteins, including occludin and zonula occludens-1 (ZO-1), were measured. It was revealed that MFGM could alleviate the depressive-like behaviors in CUMS rats. MFGM up-regulated the expression of occludin and ZO-1 and ameliorated intestine pathological changes in CUMS rats. Moreover, MFGM increased the levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine and decreased the levels of neuroendocrine hormones in CUMS rats. Furthermore, it was confirmed that the concentrations of SCFAs, DA, 5-HT, and tight junction proteins significantly increased in the recipient rats that were inoculated with the fecal microbiota from the rats after MFGM treatment. These findings demonstrated that MFGM could alleviate depressive-like behaviors in CUMS rats and was possibly associated with modulation of the gut microbiota and up-regulation of SCFAs and monoamine neurotransmitters.},
}

@article {pmid41484843,
year = {2026},
author = {Sadeghi, R and Abdol Homayuni, MR and Fateh, A and Ebrahimzadeh, N and Riazi-Esfahani, H and Yazdani Moghadam, M and Nikfar, R and Pakzamir, P and Siadat, SD},
title = {The gut-eye axis: microbiota and their role in diabetic retinopathy: a systematic review and meta-analysis.},
journal = {BMC ophthalmology},
volume = {26},
number = {1},
pages = {7},
pmid = {41484843},
issn = {1471-2415},
abstract = {PURPOSE: To systematically evaluate the relationship between gut microbiota dysbiosis and diabetic retinopathy (DR), exploring microbial diversity, composition, metabolic function, and causal associations via the gut–eye axis.

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

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

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

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12886-025-04599-3.},
}

@article {pmid41491927,
year = {2026},
author = {Yao, T and Xiong, Y and Hu, Q and Chen, Y and Li, D and Yan, J and Yang, J and Wang, Y and Cao, H and Zhang, F and Zhuang, R and Sun, J},
title = {Maternal gestational diabetes mellitus leads to adverse growth patterns and disease risk in offspring in vivo: evidence from cross-generational effects on gut microbiota.},
journal = {BMC microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12866-025-04591-3},
pmid = {41491927},
issn = {1471-2180},
support = {2023YFF1104301//National Key R&D Program of China/ ; BK20241756//Basic Research Program of Jiangsu/ ; HB2023063//Medical Key Discipline Program of Wuxi Health Commission/ ; KX-25-A14; KX-25-C108//The Soft Science Project of Wuxi Science and Technology Association/ ; },
}

@article {pmid41490838,
year = {2026},
author = {Gao, W and Yan, S and Zhang, L and Chen, L and Che, J and Huang, W and Chen, Y and Liu, A and Zhu, Y and Yang, Y and Peng, Z and Tan, C and Schnabl, B and Hou, X and Yang, L and Chu, H},
title = {Escherichia coli expressing the kpsM gene exacerbates drug-induced liver injury through up-regulating α1,2-fucosyltransferase and disturbing the host taurine metabolism-from animal models and clinical studies.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2025.12.012},
pmid = {41490838},
issn = {2090-1224},
abstract = {BACKGROUND AND AIMS: Drug-induced liver injury (DILI) is a leading cause of acute liver failure. Patients with DILI have disorders of the gut microbiota, yet little is known about the influence of gut microbes on this disease. Herein, we investigated the alterations of gut microbiota in DILI patients, and elucidated the mechanism by which Escherichia coli expressing kpsM gene (kpsM[+]E. coli) exacerbates DILI, in order to provide targets for intervention of related signaling pathways to improve DILI.

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

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

CONCLUSIONS: The kpsM[+] E. coli was associated with the severity of DILI in human. This strain can exacerbate DILI in mice through up-regulating intestinal Fut2 expression and disrupting taurine metabolism.},
}

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

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

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

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

CONCLUSION: Taken together, our study demonstrates that PCP alleviates DSS-induced colitis symptoms and restores intestinal barrier by gut microbiota-BA metabolism-FXR axis.},
}

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

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

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

CONCLUSION: EcN ameliorates obesity and insulin resistance by modulating the gut-adipose axis via RNF150/ELAVL1 in macrophages, suggesting novel therapeutic targets for metabolic disorders.},
}

@article {pmid41490238,
year = {2025},
author = {Ni, S and Chen, K and Wang, H and Chen, S and Qiu, Y and Wang, T and Mo, F and Wang, S and Li, B and Bai, Y and Zhao, J and Zhai, X and Li, Z},
title = {A new paradigm of bidirectional regulation of the gut-spinal cord axis.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-01016},
pmid = {41490238},
issn = {1673-5374},
abstract = {The bidirectional interactions of spinal cord injury, multiple sclerosis, and amyotrophic lateral sclerosis with the gut operate through a distinct gut-spinal cord axis, rather than being fully explained by the conventional gut-brain axis. The spinal cord, with its unique anatomical and physiological features, serves as a central hub of communication. The gut and spinal cord communicate through various pathways, including the immune system and the autonomic and enteric nervous systems. This review summarizes existing clinical and basic research on the relationship between gut homeostasis and spinal cord diseases. First, we present findings from epidemiological studies showing that patients with spinal cord disorders often exhibit altered gut function, which may be influenced by antibiotic exposure and environmental factors. Second, we review the key physiological and anatomical structures of the gut-spinal cord axis, including the intestinal barrier, gut microbiota, and enteric nervous system, all of which are involved in maintaining gut health, as well as sensory neurons, motor neurons, and interneurons in spinal nerve regulation. Third, we describe the roles of the three axes (microbial, immune, and neural) in bidirectional regulation and their pathological mechanisms. Moreover, vicious cycles involving these axes can exacerbate spinal cord disorders. Fourth, we outline potential biomarkers in the gut-spinal cord axis, such as uridine, hypoxanthine, and 5-methoxytryptophan. Fifth, we propose several treatment strategies with potential clinical applications, including fecal microbiota transplantation and the use of probiotics and prebiotics. Finally, this review emphasizes the gut-spinal cord axis as a promising therapeutic target, highlighting the need for multi-omics integration, longitudinal cohort studies, and individualized interventions to resolve existing debates. Overall, the recognition of the gut-spinal cord axis provides a conceptual shift that extends beyond the gut-brain framework.},
}

@article {pmid41488894,
year = {2025},
author = {Lin, B and Zhu, Z and Yang, X and Li, Z and Zhou, H and Luo, M and Guan, J and Zou, Y and Chen, H and Zhuang, Z and Meng, S and Li, W and Yang, Q and Dai, D},
title = {Protocol for the efficacy and safety of fecal microbiota transplantation in children with autism spectrum disorder: a prospective single-center, single-arm interventional study.},
journal = {Frontiers in pediatrics},
volume = {13},
number = {},
pages = {1660773},
pmid = {41488894},
issn = {2296-2360},
abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition affecting 0.7% of children globally, with 90% experiencing comorbid gastrointestinal (GI) symptoms. Fecal microbiota transplantation (FMT) may modulate ASD symptoms via the microbiota-gut-brain axis (MGBA).

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

ETHICS AND DISSEMINATION: Ethical approval obtained from Shenzhen Children's Hospital Ethics Committee. Results will be disseminated via peer-reviewed publications and conference presentations.Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=229136, identifier ChiCTR2400083998. Registered on 2024-05-08. Registered title: "Efficacy and safety of fecal microbiota transplantation in treatment of autism spectrum disorder: a prospective single-center intervention study".},
}

@article {pmid41488304,
year = {2025},
author = {Duan, Y and Li, X and Chai, Y and Chen, H and Hou, H},
title = {Adlercreutzia-modulated polyunsaturated fatty acid metabolism underlies nicotine's anti-obesity effects.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1682370},
pmid = {41488304},
issn = {1664-302X},
abstract = {BACKGROUND: The regulatory effects of nicotine on energy balance through central and peripheral mechanisms have been reported. However, its impact on obesity and gut microbiota at safe doses remains unclear.

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

CONCLUSION: Collectively, our study elucidates the critical involvement of gut microbiota in nicotine-induced obesity amelioration, uncovers a novel Adlercreutzia-PUFA metabolic axis mediating nicotine's anti-obesity effects, and highlight Adlercreutzia potentiation as a promising microbiota-directed invention strategy for obesity and metabolic syndrome.},
}

@article {pmid41488302,
year = {2025},
author = {Liu, S},
title = {Mechanisms of gut microbiota in host fat deposition: metabolites, signaling pathways, and translational applications.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1675155},
pmid = {41488302},
issn = {1664-302X},
abstract = {Obesity and metabolic diseases are global health challenges, with gut microbiota playing a critical role in host fat deposition through symbiotic interactions. In recent years, the gut microbiota, as an important factor regulating fat deposition, has received widespread attention. Numerous studies have confirmed that gut microbes influence host fat accumulation by regulating energy metabolism, inflammatory response, and gut barrier function. In this review, we summarized the key roles of gut microbial metabolites, including short-chain fatty acids (SCFAs), bile acids, tryptophan metabolites, lipopolysaccharides (LPS), branched-chain amino acids (BCAAs), and trimethylamine N-oxide (TMAO) in host epigenetic regulation and lipid metabolism, and explored their regulatory mechanisms through mediated signaling pathways, including Wnt/β-catenin signaling pathway, transforming growth factor beta/SMAD3 pathway (TGF-β/SMAD3), peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). In terms of translational applications, we described the research progress and application potentials of intervention strategies, such as probiotics, prebiotics, synbiotics, postbiotics, and fecal transplantation in obesity control and animal production. Finally, we proposed the current bottlenecks and translational challenges in obesity control by precision nutrition and microecological intervention, and look forward to future directions. This review provides a theoretical basis for the in-depth understanding of the interactions between gut microbiota and host metabolism, and serves as a reference for the prevention and control of metabolic diseases by developing nutritional intervention strategies for animals.},
}

@article {pmid41487047,
year = {2026},
author = {Xie, W and Wang, X and Liu, Y and Cai, L and Song, B and Zhang, S and Shao, Y and Wang, W and Xue, X and Li, J and Cui, W and Jiang, Y and Wang, X and Tang, L},
title = {Gut Microbiota-Derived Ursodeoxycholic Acid Mediates the Resistance to Colonic Inflammation in Pigs.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c08687},
pmid = {41487047},
issn = {1520-5118},
abstract = {Microbes in the gut are crucial for host health, yet their role in disease resistance remains unclear. Using fecal microbiota transplantation from disease-resistant Min pigs to Duroc × Landrace × Yorkshire (DLY) pigs, combined with 16S rRNA sequencing and metabolomics, we investigated this relationship. The transferred microbiota alleviated lipopolysaccharide-induced intestinal inflammation and barrier damage in the DLY piglets. Key bacterial genera and bile acid metabolites have been identified, with in vitro evidence showing that the gut microbiome can convert bile acids to secondary forms, primarily ursodeoxycholic acid (UDCA). Subsequent mechanistic validation in a mouse model demonstrated that UDCA acts via the gut-liver axis on the farnesoid X receptor, inhibiting PI3K/AKT/NF-κB pathways and reducing inflammatory responses, thereby preserving tissue structure in the liver and colon. These findings establish a causal link between gut microbiota and disease resistance, indicating that targeting microbial bile acid metabolism may restore intestinal and hepatic health.},
}

@article {pmid41486395,
year = {2026},
author = {Hajjar, R and Mars, RAT and Kashyap, PC},
title = {Harnessing the microbiome for cancer therapy.},
journal = {Nature reviews. Microbiology},
volume = {},
number = {},
pages = {},
pmid = {41486395},
issn = {1740-1534},
abstract = {The microbiome is increasingly recognized as a key player in cancer pathogenesis and treatment response, acting through both local and systemic mechanisms. Microbial communities and their metabolites can directly influence drug metabolism, shape the immune landscape, and alter transcriptional and epigenetic programmes in the gut, systemically and in the tumour microenvironment. Emerging data support the potential of microbiome-targeted interventions (such as faecal microbiota transplantation, diet, prebiotics and probiotics) as adjuncts to conventional cancer therapies, with the goal of enhancing efficacy and reducing toxicity. This Review highlights the promise of the microbiome as a prognostic and predictive biomarker, a modifiable factor in cancer care and prevention, and a therapeutic target. We also discuss major knowledge gaps, limitations in current study designs, and the need for mechanism-guided, personalized strategies to advance clinical translation.},
}

@article {pmid40662627,
year = {2026},
author = {Schmidt, AC and Seyferth, A and Hughes, M and Hughes, WB},
title = {Diverting Ostomy Practices in Burn Surgeons Treating Full-Thickness Perianal Injuries.},
journal = {Journal of burn care & research : official publication of the American Burn Association},
volume = {47},
number = {1},
pages = {231-235},
doi = {10.1093/jbcr/iraf141},
pmid = {40662627},
issn = {1559-0488},
mesh = {Humans ; *Burns/surgery ; *Anal Canal/injuries/surgery ; *Ostomy/methods ; Skin Transplantation ; Wound Healing ; Male ; *Practice Patterns, Physicians'/statistics & numerical data ; Surveys and Questionnaires ; Female ; },
abstract = {Burns to the perianal region pose specific challenges in management due to the complex structure of the surrounding tissue, bacterial contamination, and repetitive stress. Fecal diversion via diverting ostomy may be elected in these injuries because of its potential to enhance wound healing and skin graft adherence; however, its use introduces alternative risks such as prolonged ileus, fistula, leakage, and failure of reversal. This study aimed to determine the perspectives of burn surgeons regarding the use of diverting ostomy for perianal burn injuries. We conducted a survey of 12 physicians who are burn center directors in the Northeast Region of the American Burn Association regarding their practices for patients with full-thickness perianal burn injuries requiring a skin graft. Response rate was 11/12 (92%). Six individuals (54.5%) reported "Never (0%)" to performing a diverting ostomy in this context; the remaining 5 individuals responded "Rarely (<10%)." Reasons stated for performing a diverting ostomy in the "Rarely" group included cases where the patient suffered an intra-anal or anorectal injury. These results were summarized with a relevant review of the literature and experience in our clinical practice. Our findings indicate that diverting ostomy is a relatively uncommon practice for burn surgeons treating full-thickness buttocks injuries. With appropriate wound care and critical care management, good outcomes can be obtained without the need for diverting ostomy. Non-surgical alternatives to fecal diversion are commonly used by burn specialists and should be considered in perianal burn injuries.},
}

Humans
*Burns/surgery
*Anal Canal/injuries/surgery
*Ostomy/methods
Skin Transplantation
Wound Healing
Male
*Practice Patterns, Physicians'/statistics & numerical data
Surveys and Questionnaires
Female

@article {pmid41486262,
year = {2026},
author = {Wu, J and Xiu, M and Wang, X and Zhang, P and Qin, Y and Li, J and Jiang, X and Duan, Y and Liu, Y and He, J},
title = {Dunhuang Gancao Fuling Xingren decoction and its components alleviate CPT-11 induced intestinal mucositis by regulating gut microbiota related innate immunity and inflammatory response in Drosophila and mice.},
journal = {Chinese medicine},
volume = {21},
number = {1},
pages = {4},
pmid = {41486262},
issn = {1749-8546},
support = {DHYX24-15//Foundation from Key Laboratory of Dunhuang Medicine/ ; 2024-QN-35//Lanzhou Youth Science and Technology Talent Innovation Project/ ; 25JRRA1177//Natural Science Foundation of Gansu Province/ ; 25JRRA303//Gansu Natural Science Foundation/ ; },
abstract = {BACKGROUND: Dunhuang Gancao Fuling Xingren decoction (GFXD) is a traditional formulation derived from the Dunhuang Ancient Medical Prescriptions, has been historically utilized for its immunomodulatory and anti-inflammatory properties. However, the protective effect against irinotecan (CPT-11)-induced intestinal mucositis (CIM) remains poorly elucidated.

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

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

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

CONCLUSIONS: GFXD alleviates CPT-11-induced intestinal mucositis by modulating gut microbiota composition, suppressing JAK-STAT and Toll-Imd pathways. Thus, this study demonstrates GFXD and its bioactive constituents as novel therapeutic agents to mitigate CIM.},
}

@article {pmid41485840,
year = {2026},
author = {Jurgiel, J and Gromowski, T and Król, J and Bomba-Opoń, D and Kościółek, T and Wielgoś, M},
title = {The impact of maternal microbial transfer on the infant gut microbiome after cesarean delivery: a systematic review.},
journal = {American journal of obstetrics and gynecology},
volume = {233},
number = {6S},
pages = {S541.e1-S541.e16},
doi = {10.1016/j.ajog.2025.09.001},
pmid = {41485840},
issn = {1097-6868},
mesh = {Humans ; *Gastrointestinal Microbiome ; *Cesarean Section ; Female ; Infant, Newborn ; Pregnancy ; *Fecal Microbiota Transplantation ; Vagina/microbiology ; Bacteroides ; Lactobacillus ; Bifidobacterium ; },
abstract = {OBJECTIVE: To systematically review the results of maternal microbial transfer in shaping microbial diversity, improving neonatal development, and evaluating the microbial transfer procedure's adverse events.

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

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

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

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

CONCLUSION: The efficacy of maternal microbial transfer in restoring neonatal microbiota and promoting health outcomes remains uncertain, with neonatal outcomes addressed in only 3 of the included studies-one on allergy and one on neurodevelopment. However, while no serious adverse effects have been consistently reported, data on safety remain limited.},
}

Humans
*Gastrointestinal Microbiome
*Cesarean Section
Female
Infant, Newborn
Pregnancy
*Fecal Microbiota Transplantation
Vagina/microbiology
Bacteroides
Lactobacillus
Bifidobacterium

@article {pmid41485542,
year = {2026},
author = {Allani, M and Nath, G and Juyal, G and Chandra Joshi, M and Tiwari, V},
title = {Fecal Microbiota Transplantation Attenuates Neuropathic Pain in Rats via Gut Microbiota-Mediated Immunomodulation of Ion Channels and Nociceptors.},
journal = {Microbial pathogenesis},
volume = {},
number = {},
pages = {108275},
doi = {10.1016/j.micpath.2026.108275},
pmid = {41485542},
issn = {1096-1208},
abstract = {INTRODUCTION: Neuropathic pain, resulting from somatosensory nervous system damage, presents significant treatment challenges due to limited effectiveness and adverse side effects of current therapies. Emerging evidence highlights the gut microbiome's potential role in pain regulation, yet the specific microbial species and mechanisms underlying chronic neuropathic pain remain largely unexplored.

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

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

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

CONCLUSION: Our findings demonstrate that the composition of gut bacteria influences pain-like behaviors through nerve injury-induced microbial dysbiosis, operating in a bidirectional manner. Additionally, the study suggests that a cocktail of Bifidobacterium animalis, Corynebacterium urealyticum, and Desulfovibrio piger could serve as a promising alternative for managing neuropathic pain.},
}

@article {pmid41485442,
year = {2025},
author = {Ma, C and Liu, Y and Zeng, T and Li, X and Tan, X and Ma, X and Lu, X and Wang, Y and Wu, X},
title = {Zexie-Baizhu herb pair attenuates MASH via the gut-liver Axis by suppressing NLRP3 Inflammasome activation and M1-macrophage polarization.},
journal = {Bioorganic chemistry},
volume = {169},
number = {},
pages = {109451},
doi = {10.1016/j.bioorg.2025.109451},
pmid = {41485442},
issn = {1090-2120},
abstract = {Metabolic dysfunction-associated steatohepatitis (MASH), a severe form of MASLD lacking effective treatments, may be therapeutically targeted by the Traditional Chinese Medicine herb pair Zexie-Baizhu (ZB), known for its lipid-modulating and anti-inflammatory properties. This study investigated ZB's effects and mechanisms in diet-induced MASH mouse models. We began by identifying potential active ingredients in ZB using UPLC-MS/MS. When administered preventively over an 8-week period, ZB significantly improved serum lipids, reduced hepatic inflammation, and alleviated liver lipid accumulation. Mechanistic studies revealed that ZB restores beneficial gut microbiota, enhances intestinal barrier integrity, modulate the hepatic bile acid receptor FXR signaling pathway to regulate bile acid metabolism, and crucially suppresses NLRP3 inflammasome activation and M1 macrophage polarization. Fecal microbiota transplantation confirmed the role of gut microbiota modulation. Collectively, these results demonstrate that ZB alleviates MASH progression primarily via the gut-liver axis by inhibiting NLRP3 inflammasome and M1 macrophage polarization, highlighting this axis as a promising therapeutic target.},
}

@article {pmid41485293,
year = {2025},
author = {Meng, Y and Hou, Y and Zhang, R and Guo, Z and Zhang, Z and Li, J and Yan, Y and Chang, Y and Li, D and Chang, L and Li, M and Gao, H},
title = {Jinlida ameliorates diabetic kidney disease via gut microbiota-dependent production of pyridoxamine targeting renal AGEs/RAGE and TGF-β pathways.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {150},
number = {},
pages = {157744},
doi = {10.1016/j.phymed.2025.157744},
pmid = {41485293},
issn = {1618-095X},
abstract = {BACKGROUND: Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage renal disease (ESRD), necessitating novel therapies beyond conventional approaches. Emerging evidence indicates that gut microbiota dysbiosis promotes DKD progression through metabolite-mediated renal injury. Jinlida (JLD) is a clinically validated traditional Chinese medicine with antidiabetic activity, but its microbiota-mediated renoprotective mechanism remains unclear.

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

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

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

CONCLUSION: JLD remodels the gut microbiota and enhances its de novo vitamin B6 biosynthetic capacity, leading to accumulation of PM. Gut-derived PM enters the circulation and functions as an effector molecule targeting the kidney; through PM's direct carbonyl-trapping activity it scavenges AGEs and suppresses the AGEs-RAGE axis as well as downstream inflammatory and profibrotic signaling, thereby exerting renoprotective effects. This study reveals PM as a microbially derived metabolite with therapeutic potential in DKD and offers a new metabolism-directed strategy for DKD treatment.},
}

@article {pmid41484558,
year = {2025},
author = {Zhang, B and Zheng, T and He, Z and Su, S and Yuan, S and Chen, D and Li, H and Guan, W and Zhang, S},
title = {Maternal purified fiber supplementation-enriched Akkermansia muciniphila regulates lactation and offspring growth via the gut-mammary axis.},
journal = {Science China. Life sciences},
volume = {},
number = {},
pages = {},
pmid = {41484558},
issn = {1869-1889},
abstract = {Maternal fiber intake alters the maternal gut microbiota and metabolites, which benefits offspring health through unclear mechanisms. Using a sow model, the study showed that supplementing with purified fiber (cellulose:guar gum=3:1) increased weaning weight and resistance to LPS-induced intestinal injury. Milk analysis revealed higher levels of immunoglobulins and milk fat. Fecal microbiota transplantation (FMT) from fiber-fed sows to mice replicated these benefits, increasing milk fat, immunoglobulins, and pup growth. Akkermansia muciniphila (AKK) abundance was positively associated with milk quality in both models. Supplementing with AKK mimicked the effects of fiber, boosting milk fat and immunoglobulins. In in vitro experiments with HC11 mammary epithelial cells showed that AKK metabolites enhanced milk fat synthesis and immunoglobulin transporter expression. Metabolite analysis indicated that AKK influences mammary gland function by increasing acetate and propionate levels, with acetate promoting milk fat synthesis via GPR43 and propionate regulating immunoglobulin transport through GPR41. Therefore, maternal fiber intake promotes intestinal AKK abundance, increases short-chain fatty acids (SCFAs) production, and influences lactation via GPR41/43 signaling.},
}

@article {pmid41483616,
year = {2026},
author = {Zhong, Y and Liu, J and Huang, J and Yu, J and Liu, Y and Zhuo, W and Xu, Y and Zhang, Y and Zhou, Z and Chen, L and Xiao, Q and Liu, D},
title = {Astragaloside IV alleviates ulcerative colitis via gut microbiota - butyrate metabolism axis to reshape Th17/Treg balance.},
journal = {International immunopharmacology},
volume = {171},
number = {},
pages = {116135},
doi = {10.1016/j.intimp.2025.116135},
pmid = {41483616},
issn = {1878-1705},
abstract = {Gut microbiota dysbiosis and Th17/Treg cell imbalance play critical roles in the pathogenesis of ulcerative colitis (UC). Astragaloside IV (AS-IV) exhibits extensive anti-inflammatory and immunomodulatory activities; however, the crosstalk between gut microbiota and Th17/Treg cells modulated by AS-IV remains unreported. Here, chronic colitis was induced in mice by free access to 2.5 % dextran sulfate sodium (DSS) solution over three 7-day cycles, with concurrent AS-IV administration. AS-IV effectively alleviated DSS-induced chronic colitis in mice, as evidenced by increased body weight and colon length, decreased disease activity index (DAI), colon weight, colon weight/colon length, and colon weight index, and enhanced the gene and protein expression of tight junction molecules Claudin-1, Occludin, ZO-1. Notably, AS-IV not only effectively regulated the differentiation balance of Th17/Treg cells, but also significantly improved the composition of gut microbiota and butyric acid metabolism in chronic colitis mice. Intriguingly, Th17/Treg cells and butyric acid were significantly correlated with α/β diversity, as well as the genera Enterorhabdus, Mucispirillum, and Helicobacter. However, AS-IV lost its therapeutic efficacy against colitis and its regulatory effects on Th17/Treg cell balance and butyric acid metabolism following gut microbiota depletion. Critically, FMT from AS-IV-treated mice restored the protective effects against colitis and the regulation of Th17/Treg cell balance and butyric acid metabolism. Collectively, AS-IV inhibits chronic colitis by regulating gut microbiota composition, butyric acid metabolism, and Th17/Treg cell differentiation balance, whose protective effects are dependent on the regulatory mechanism of Th17/Treg cell differentiation balance mediated by gut microbiota-derived butyrate metabolism.},
}

@article {pmid41483363,
year = {2026},
author = {Yang, J and Yan, H and Liu, J and Shen, X and Liu, H and Kang, X and Yang, X and Che, Y and Wang, X and Guo, L and Zhang, F and Fan, W},
title = {Lactobacillus Acidophilus Protects against alcohol-associated Liver Disease in Mice Via Gut Microbiota Modulation and Alleviation of Inflammation and Oxidative Stress.},
journal = {Probiotics and antimicrobial proteins},
volume = {},
number = {},
pages = {},
pmid = {41483363},
issn = {1867-1314},
support = {202203021211239//Shanxi Provincial Natural Fund Project/ ; 202303021211126//Shanxi Provincial Natural Fund Project/ ; BYJL045//Shanxi Province Higher Education "Billion Project" Science and Technology Guidance Project/ ; },
abstract = {Alcohol-associated liver disease (ALD) is a severe liver disease caused by excessive alcohol consumption. ALD remains a clinical challenge with limited therapeutic options. Following 5-day pretreatment with Lactobacillus acidophilus (Lac), mice were administered ethanol by gavage to induce ALD. Tissues were collected and analyzed for serum markers, hepatic pathology/inflammation/oxidative stress, ileal morphology/tight junctions, and cecal microbiota via 16 S rRNA gene sequencing. The fecal microbiota transplantation (FMT) experiment was performed, and tissues were then collected and analyzed as above. Moreover, the anti-inflammatory and antioxidant properties of Lac-derived particulate matter (pLac) were evaluated on RAW264.7 macrophages in vitro. Lac administration improved gut microbiota composition, enhanced intestinal barrier integrity and reduced lipopolysaccharide (LPS) translocation to the liver, thereby inhibiting the toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB) pro-inflammatory pathway and activating the adenosine monophosphate activated protein kinase (AMPK)- peroxisome proliferator activated receptor α (PPARα) signaling axis. This led to significant attenuation of hepatic inflammation, oxidative stress and steatosis. The FMT experiments further validated that Lac-mediated protection is dependent on gut microbiota modulation. In vitro studies revealed that pLac exhibit direct anti-inflammatory and antioxidant properties. These findings elucidate the mechanistic basis for Lac in alleviating acute ALD, positioning it as a promising treatment or dietary intervention to enhance clinical management.},
}

@article {pmid41483189,
year = {2026},
author = {Rathee, S and Sen, D and Jain, A and Jain, SK},
title = {Advances in understanding, diagnosing, and treating hepatic encephalopathy: from epidemiology to emerging therapies.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {41483189},
issn = {1432-1912},
abstract = {This comprehensive review explores the multifaceted landscape of hepatic encephalopathy (HE), encompassing its epidemiology, pathophysiology, classification, and evolving therapeutic approaches. Delving into the prevalence and incidence of HE, it is found that the burden of this condition is on individuals and healthcare systems. The intricate mechanisms underlying HE, including abnormalities in synapse transmission, the ammonia hypothesis, the false neurotransmitter theory, the GABAergic theory, and the benzodiazepine theory, are scrutinized, providing a nuanced understanding of the disorder. The review examines altered gene expression, hyponatremia, neurosteroids, oxidative stress, electrolyte imbalance, and manganese accumulation as contributing factors to HE. Classifying HE and identifying precipitating risk factors form crucial aspects of the discussion, shedding light on the most widely used diagnostic tools. Conventional approaches for HE management are discussed, focusing on reducing elevated ammonia formation, improving ammonia-detoxifying liver capacity, and inhibiting false neurotransmitters. Antibiotics, metabolic ammonia scavengers, albumin, probiotics, dietary management, zinc, and secondary prophylaxis are analyzed as current therapeutic targets. Furthermore, the review examines emerging therapies at various stages, including clinical and pre-clinical development, such as glycerol/sodium phenylbutyrate, ornithine phenylacetate, fecal microbiota transplantation, engineered bacteria, liposome-supported peritoneal dialysis, GABAA receptor modulating steroid antagonists (GAMSA), activated carbon microspheres, and glutamine synthetase replacement. This review consolidates knowledge on HE, providing a comprehensive resource for clinicians, researchers, and healthcare professionals involved in managing this complex disorder. The synthesis of epidemiological data, pathophysiological insights, and therapeutic advancements offers a holistic view of HE, paving the way for improved diagnosis and targeted interventions.},
}

@article {pmid41482667,
year = {2026},
author = {Chen, Y and Du, H and Zhou, W and Qin, M and Li, M and Jin, Y and Xu, Y and Ma, C and Xia, J and Mo, Y and Chen, N and Huang, H and Li, H and Xie, Z and Wang, P and Hong, Y},
title = {Tamoxifen induced hepatotoxicity via gut microbiota-mediated hyodeoxycholic acid depletion and Farnesoid X receptor signaling disruption.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2610077},
doi = {10.1080/19490976.2025.2610077},
pmid = {41482667},
issn = {1949-0984},
mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; *Tamoxifen/adverse effects/toxicity ; Mice ; *Chemical and Drug Induced Liver Injury/metabolism/microbiology ; Dysbiosis/microbiology/chemically induced ; Signal Transduction/drug effects ; Mice, Inbred C57BL ; Liver/metabolism/drug effects ; Bile Acids and Salts/metabolism ; Humans ; Fecal Microbiota Transplantation ; Male ; Feces/chemistry ; Bacteria/classification/genetics/isolation & purification/metabolism ; },
abstract = {Tamoxifen (TAM) is a widely used estrogen receptor modulator for breast cancer treatment. However, TAM exhibits significant hepatotoxicity in the clinic, affecting nearly 50% of patients and thereby limiting its clinical utility. The specific mechanisms underlying TAM-induced liver injury remain poorly understood. In this study, we elucidated the mechanistic role of the gut microbiota in the hepatotoxicity associated with TAM. TAM administration induced substantial liver injury and gut microbiota dysbiosis in mice, characterized by an increased abundance of Escherichia and a reduction in Lachnospiraceae NK4A136 group. These microbial shifts resulted in decreased levels of total fecal bile acids (BA), particularly hyodeoxycholic acid (HDCA), which was inversely correlated with TAM-induced liver injury. Additionally, TAM disrupted BA homeostasis by enhancing intestinal Farnesoid X receptor (FXR) activity and concurrently stimulating hepatic BA synthesis through an alternative nonintestinal FXR mechanism. Notably, gut microbiota depletion reversed these effects, demonstrating the critical role of the microbiota in modulating the gut‒liver FXR axis in TAM-induced liver injury. Fecal microbiota transplantation (FMT) further confirmed that TAM directly stimulated hepatic BA synthesis through a microbiota-dependent mechanism. The disruption of the gut‒liver BA‒FXR axis impaired enterohepatic BA circulation, contributing to the liver toxicity associated with TAM administration. Importantly, HDCA supplementation restored the gut‒liver BA‒FXR axis and alleviated TAM-induced liver injury. These findings highlight the intricate relationship between TAM, gut microbiota, and BA metabolism, suggesting that targeting the gut-liver FXR axis with HDCA may serve as a promising therapeutic strategy for alleviating TAM-associated liver injury.},
}

*Gastrointestinal Microbiome/drug effects
Animals
*Receptors, Cytoplasmic and Nuclear/metabolism/genetics
*Tamoxifen/adverse effects/toxicity
Mice
*Chemical and Drug Induced Liver Injury/metabolism/microbiology
Dysbiosis/microbiology/chemically induced
Signal Transduction/drug effects
Mice, Inbred C57BL
Liver/metabolism/drug effects
Bile Acids and Salts/metabolism
Humans
Fecal Microbiota Transplantation
Male
Feces/chemistry
Bacteria/classification/genetics/isolation & purification/metabolism

@article {pmid41482085,
year = {2025},
author = {Yang, B and Xia, Q and Ji, X and Su, K and Yu, T and Xiao, Z and Shi, C and Luo, Z and Wang, X and Xu, W and Gao, Y and Hua, H and Shan, J},
title = {Ganjie Decoction protects against respiratory syncytial virus infection by activating PI3K/AKT-apoptosis axis and regulating gut microbiota metabolism.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {121142},
doi = {10.1016/j.jep.2025.121142},
pmid = {41482085},
issn = {1872-7573},
abstract = {Ganjie Decoction (GJD), a traditional Chinese medicine (TCM) formula commonly used for respiratory diseases, has shown therapeutic potential against RSV pneumonia. However, its pharmacological mechanisms against respiratory syncytial virus (RSV) pneumonia are not fully understood.

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

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

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

CONCLUSIONS: These findings suggest that GJD alleviates RSV pneumonia through a synergistic mechanism that modulates the PI3K/AKT-apoptosis pathway, restores gut microbial balance, and normalizes metabolic disturbances. This study systematically elucidates the mechanistic basis underlying the therapeutic effects of GJD against RSV pneumonia.},
}

@article {pmid41481427,
year = {2026},
author = {Wang, J and Zi, F and Liu, W and Liu, C and Zhang, Z and Kong, L and Xu, X and Wei, J and Chen, T and Li, J},
title = {Clostridium butyricum alleviates multiple myeloma by remodeling the bone marrow microenvironment and inhibiting PI3K/AKT pathway through the gut‒bone axis.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2609455},
doi = {10.1080/19490976.2025.2609455},
pmid = {41481427},
issn = {1949-0984},
mesh = {*Clostridium butyricum/physiology/metabolism ; Animals ; *Multiple Myeloma/microbiology/therapy/metabolism/pathology ; Humans ; *Gastrointestinal Microbiome/physiology ; Mice ; Phosphatidylinositol 3-Kinases/metabolism/genetics ; *Proto-Oncogene Proteins c-akt/metabolism/genetics ; Butyrates/metabolism ; Fecal Microbiota Transplantation ; Male ; *Bone Marrow/metabolism/pathology ; Signal Transduction ; Tumor Microenvironment ; Dysbiosis/microbiology ; Female ; Th17 Cells/immunology ; },
abstract = {Emerging evidence reveals a strong connection between the gut microbiota and cancer. However, the exact role of gut microbiota dysbiosis in multiple myeloma (MM) is poorly understood, and the therapeutic potential of microbiota-targeted interventions represents a promising strategy that demands urgent mechanistic and translational investigation. First, we conducted a comprehensive microbiome-metabolite analysis between MM patients and healthy individuals. The result revealed a marked compositional difference characterized by reduced abundances of butyrate-producing bacteria and diminished butyrate levels in the MM cohort. Subsequent fecal microbiota transplantation demonstrated that the gut microbiota critically modulates MM progression, with healthy donor-derived microbiota reducing the tumor burden and concomitantly elevating serum butyrate. Furthermore, through function-based culturomics screening, Clostridium butyricum (C. butyricum) was identified as a key butyrate-producing specialist. C. butyricum or its metabolite butyrate significantly reduced the systemic tumor burden in 5TGM1 mice. Notably, C. butyricum and butyrate alleviated bone marrow inflammation and osteolytic lesions by suppressing Th17 cells and IL-17 levels in the bone marrow. Moreover, cellular assays and transcriptome sequencing further revealed that butyrate could induce MM cells' apoptosis via HDAC inhibition-mediated upregulation of PPARγ, leading to sequential suppression of the PI3K/AKT pathway and antiapoptotic BCL-2 expression. This apoptotic signaling cascade was reversed by PPARγ antagonism. The direct antitumor effect was further confirmed in M-NSG mice. Our research systematically verifies the specific role of the gut microbiota in MM and provides the first evidence of the immune and molecular mechanisms by which C. butyricum alleviates MM progression, offering preclinical support for probiotic-based therapies against MM.},
}

*Clostridium butyricum/physiology/metabolism
Animals
*Multiple Myeloma/microbiology/therapy/metabolism/pathology
Humans
*Gastrointestinal Microbiome/physiology
Mice
Phosphatidylinositol 3-Kinases/metabolism/genetics
*Proto-Oncogene Proteins c-akt/metabolism/genetics
Butyrates/metabolism
Fecal Microbiota Transplantation
Male
*Bone Marrow/metabolism/pathology
Signal Transduction
Tumor Microenvironment
Dysbiosis/microbiology
Female
Th17 Cells/immunology

@article {pmid41480316,
year = {2025},
author = {Majeed, AA and Butt, AS},
title = {Gut microbiota: An overlooked target in dyslipidemia management.},
journal = {World journal of gastroenterology},
volume = {31},
number = {48},
pages = {113178},
pmid = {41480316},
issn = {2219-2840},
mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/physiology/immunology ; *Dyslipidemias/therapy/microbiology/metabolism ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; Lipid Metabolism ; Cardiovascular Diseases/prevention & control ; Bile Acids and Salts/metabolism ; Circadian Rhythm ; },
abstract = {With the global rise in sedentary lifestyles, obesity, and unhealthy dietary patterns, dyslipidemia has emerged as a leading modifiable risk factor for atherosclerotic cardiovascular disease. Beyond host genetics and diet, the gut microbiota has gained recognition as a critical regulator of lipid homeostasis through mechanisms involving bile acid metabolism, short-chain fatty acid signaling, and microbial modulation of inflammation. Lv et al provide a comprehensive synthesis of the diet microbe-lipid axis and therapeutic strategies, including probiotics, prebiotics, and fecal microbiota transplantation. In this correspondence, we expand on their framework by highlighting underexplored yet clinically relevant dimensions, including circadian rhythm alignment, pharmacotherapy microbe crosstalk, population-specific microbial signatures, and functional microbial phenotyping. Addressing these overlooked aspects could accelerate the translation of microbiome science into precision dyslipidemia management, with the potential to improve cardiovascular outcomes worldwide.},
}

Humans
*Gastrointestinal Microbiome/drug effects/physiology/immunology
*Dyslipidemias/therapy/microbiology/metabolism
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Prebiotics/administration & dosage
Lipid Metabolism
Cardiovascular Diseases/prevention & control
Bile Acids and Salts/metabolism
Circadian Rhythm

@article {pmid41480095,
year = {2025},
author = {Wang, B and Ma, D and Li, N and Luo, T},
title = {The application of fecal microbiota transplantation in Parkinson's disease.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1713899},
pmid = {41480095},
issn = {1663-4365},
abstract = {BACKGROUND: Parkinson's disease (PD) is a multisystem neurodegenerative disorder characterized by the aggregation of α-synuclein (α-syn) in dopaminergic neurons of the substantia nigra. The pathogenesis of PD remains incompletely understood, and disease-modifying therapies are lacking. Emerging evidence suggests that gut microbiota and their metabolites influence both intestinal and central nervous system (CNS) functions via the microbiota-gut-brain axis (MGBA). Recent studies have identified dysbiosis in the gut microbiota of PD patients, which may contribute to disease progression through two primary mechanisms: First, increased intestinal permeability, allowing pro-inflammatory factors and microbial metabolites to affect the enteric nervous system (ENS) and subsequently spread to the CNS via the vagal neurons; Secondly, disruption of the Blood-Brain barrier (BBB), leading to neuroinflammation and aberrant α-syn aggregation, ultimately resulting in dopaminergic neuron degeneration. These findings underscore the critical role of the MGBA in PD pathogenesis, which makes gut microbiota modulation a promising therapeutic target.

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

CONCLUSION: FMT has demonstrated efficacy in ameliorating PD symptoms via the MGBA. However, further preclinical and clinical studies are needed to fully elucidate its mechanisms and optimize therapeutic protocols. Targeting the gut microbiota may offer novel biomarkers and intervention strategies for PD.},
}

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

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

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

CONCLUSION: These findings demonstrate that C. myrrha extract effectively mitigates Eimeria-induced intestinal damage, inflammation, and immune dysregulation, highlighting its potential as a natural, plant-based intervention for managing pigeon coccidiosis.},
}

Animals
*Eimeria/drug effects/immunology
*Coccidiosis/veterinary/immunology/parasitology/drug therapy
*Commiphora/chemistry
*Plant Extracts/pharmacology
*Columbidae/parasitology/immunology
Cytokines/metabolism
*Bird Diseases/parasitology/immunology/prevention & control/drug therapy
*Inflammation
*Resins, Plant/pharmacology

@article {pmid41479812,
year = {2025},
author = {Song, YJ and Yang, B and Feng, QS and Ma, FF and Xing, B and Bin, XL and Ha, XQ},
title = {Gut microbiota-derived trimethylamine N-oxide exacerbates diabetic nephropathy by promoting renal fibrosis.},
journal = {World journal of nephrology},
volume = {14},
number = {4},
pages = {112066},
pmid = {41479812},
issn = {2220-6124},
abstract = {BACKGROUND: Background diabetic nephropathy (DN), a major complication of diabetes, is linked to gut microbiota dysbiosis. Elevated trimethylamine N-oxide (TMAO), a microbiota-derived metabolite, plays a central role in inducing renal injury during DN pathogenesis.

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

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

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

CONCLUSION: DN is associated with gut microbiota alterations that potentiate TMAO generation, contributing to renal injury and fibrotic progression. While TMAO's role in fibrosis warrants further validation, these findings implicate the gut-kidney axis in DN pathogenesis.},
}

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

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

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

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

CLINICAL TRIAL REGISTRATION: chictr.org, identifier ChiCTR2100041976.},
}

Humans
*Hematopoietic Stem Cell Transplantation/adverse effects
Middle Aged
Male
Adult
Female
*Carbapenems/pharmacology
Prospective Studies
Anti-Bacterial Agents/pharmacology/therapeutic use
Transplant Recipients
beta-Lactamases/genetics
*Carbapenem-Resistant Enterobacteriaceae/isolation & purification
Aged
Bacterial Proteins/genetics
Feces/microbiology
Young Adult
Mass Screening/methods

@article {pmid41479037,
year = {2026},
author = {El-Daly, SM and Fayed, B and Talaat, RM and Gouhar, SA and Fahmy, CA and El-Jawad, AMA and Hamdy, NM and Abd Elmageed, ZY},
title = {The Intricate Interplay of Noncoding RNAs and the Gut Microbiome in Gastrointestinal and Endocrine-Related Cancers.},
journal = {Sub-cellular biochemistry},
volume = {114},
number = {},
pages = {61-121},
pmid = {41479037},
issn = {0306-0225},
mesh = {Humans ; *Gastrointestinal Microbiome ; *Gastrointestinal Neoplasms/microbiology/genetics/pathology/metabolism ; *RNA, Untranslated/genetics/metabolism ; *Endocrine Gland Neoplasms/microbiology/genetics/metabolism/pathology ; Dysbiosis/microbiology/genetics ; Animals ; },
abstract = {The human gut microbiome and noncoding RNAs (ncRNAs) represent interconnected regulatory networks that profoundly influence cancer development, particularly in gastrointestinal and endocrine-related malignancies. This chapter delineates the intricate interplay of microbiome-ncRNA crosstalk in the context of gastrointestinal and endocrine-related cancers.The chapter begins with a comprehensive overview of the taxonomic and functional landscape of the healthy adult gut microbiome. The gut microbiome, comprising trillions of microorganisms, plays a crucial role in endocrine regulation through hormone metabolism, synthesis of bioactive compounds, and modulation of immune responses, thereby establishing a critical crosstalk with the host endocrine system. Dysbiosis, or microbial imbalance, has been linked to endocrine dysfunction and the pathogenesis of various diseases, including gastrointestinal and endocrine-related cancers.We then elucidate the classifications of noncoding RNAs and their function as key molecular regulators in cellular communication, gene expression, and disease progression. NcRNAs contribute significantly to the development and progression of endocrine-related malignancies. The intricate crosstalk between the gut microbiome and host ncRNAs demonstrates how gut dysbiosis can disrupt host ncRNA expression patterns, thereby affecting oncogenic pathways, immune surveillance, and metabolic reprogramming linked to tumor initiation, progression, and metastasis. Conversely, host-derived ncRNAs, secreted into the gut lumen, can directly shape microbial gene expression. In this section, we explore how dysregulation of this axis contributes to carcinogenesis through the promotion of chronic inflammation, epithelial barrier dysfunction, and oncogenic signaling. Therapeutic strategies targeting this interplay, including probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, are introduced in the context of restoring microbial balance.This comprehensive chapter provides crucial insights into the molecular mechanisms governing microbiome-ncRNA interactions and their implications for cancer biology, offering new perspectives for therapeutic interventions in gastrointestinal and endocrine-related malignancies.},
}

Humans
*Gastrointestinal Microbiome
*Gastrointestinal Neoplasms/microbiology/genetics/pathology/metabolism
*RNA, Untranslated/genetics/metabolism
*Endocrine Gland Neoplasms/microbiology/genetics/metabolism/pathology
Dysbiosis/microbiology/genetics
Animals

@article {pmid41478424,
year = {2025},
author = {Zhang, Y and Chen, L and Jin, J and Xin, Y and Wang, J and Zhang, A},
title = {Therapeutic application of fecal microbiota transplantation for neurological diseases: Exploring novel mechanisms and perspectives.},
journal = {Experimental neurology},
volume = {},
number = {},
pages = {115631},
doi = {10.1016/j.expneurol.2025.115631},
pmid = {41478424},
issn = {1090-2430},
abstract = {Recently, fecal microbiota transplantation (FMT) has garnered widespread attention as an emerging therapeutic approach in the field of neurological disorders. In this study, we review the research progress of FMT in treating neurological disorders. First, the development, safety, and efficacy of FMT are introduced. Subsequently, the application and potential mechanisms of FMT in neurodegenerative diseases (such as Parkinson's disease and Alzheimer's disease), neurodevelopmental disorders (such as autism spectrum disorder and attention deficit hyperactivity disorder), and other neurological conditions are elaborated in detail. Particularly, we explore the pivotal role of the microbiota-gut-brain axis in FMT for treating neurological disorders, as well as how FMT influences neurological function by regulating the gut microbiota and its metabolites, immune system and inflammatory responses, and neurotransmitters. However, FMT also faces numerous challenges in the treatment of neurological disorders, such as ethical issues, safety concerns, and standardization problems. Therefore, this review also prospects the future development directions of FMT in the treatment of neurological diseases, including personalized therapy and combination therapies. FMT may be a feasible and promising option for treating various neurological disorders, but a comprehensive understanding of its working principles and continuous improvement of its application in clinical practice are still ongoing.},
}

@article {pmid41478268,
year = {2025},
author = {Chen, J and Xu, J and Xu, J and Xu, F and Gong, F and Xiao, P and Ma, H and Zhang, Q and Feng, J and Min, Y},
title = {Gut microbiota-derived propionic acid mitigates age-related albumen quality deterioration by modulating magnum functions.},
journal = {Poultry science},
volume = {105},
number = {3},
pages = {106357},
doi = {10.1016/j.psj.2025.106357},
pmid = {41478268},
issn = {1525-3171},
abstract = {The declined albumen quality during the late laying phase is associated with age-related magnum dysfunction, in which to the roles of gut microbiota is unclear. This study aimed to elucidate the relationship between gut microbiota and magnum function, and its impact on albumen quality. Hy-Line Brown layers at peak (30 wk) and late (70 wk) laying phases were compared to assess age-related changes in albumen quality, magnum function, and gut microbiota. Fecal microbiota transplantation (FMT) from peak- to late-phase hens was conducted to assess functional effects. Microbiome and metabolome analyses were then integrated to identify key bacterial taxa and metabolites. The role of the leading candidate metabolite was further validated through dietary supplementation. Results showed that late-phase hens exhibited significant reductions in albumen height, magnum mucosal fold height, and tubular gland diameter (P < 0.05), alongside gut microbial dysbiosis. FMT from peak-phase donors effectively reversed age-related declines in magnum histomorphology and albumen height in late-phase hens. It also up-regulated the expression of barrier function genes (Claudin-1, ZO-2, MUC2, AGR2) and magnum secretory markers (OVOA), while down-regulating pro-inflammatory cytokines (IL-4, IFN-γ) (P < 0.05). Microbial analysis identified Anaerotruncus as the only genus consistently enriched following FMT and positively correlated with improved albumen height and magnum morphology. Metabolomic analysis revealed that propionic acid was the top metabolite associated with Anaerotruncus abundance. Crucially, dietary supplementation with sodium propionate recapitulated the key benefits of FMT. In summary, our findings revealed a gut microbiota-oviduct axis through which microbiota from peak-laying hens ameliorate age-related magnum decline and improve albumen quality in aging hens.},
}

@article {pmid41477763,
year = {2025},
author = {He, Z and Zhang, Y and Feng, C and Xie, T and Zhu, K and Yuan, W and Liu, Y and Xie, P and Zhang, N and Zhao, C and Bian, W and Hu, X and Fu, Y},
title = {Gut microbiota induces mammary gland sIgA production to alleviate S. aureus mastitis.},
journal = {Cell reports},
volume = {45},
number = {1},
pages = {116782},
doi = {10.1016/j.celrep.2025.116782},
pmid = {41477763},
issn = {2211-1247},
abstract = {Mastitis threatens dairy cow health and public safety. While gut dysbiosis increases mastitis susceptibility, the mechanism is unclear. We hypothesized that gut dysbiosis exacerbates Staphylococcus aureus (S. aureus)-induced mastitis by reducing milk secretory immunoglobulin A (sIgA). In mice, vancomycin-induced gut dysbiosis reduced sIgA and IgA[+] B cells in milk, gut, and Peyer's patches, impairing the blood-milk barrier and worsening mastitis, effects reversed by fecal microbiota transplantation. Dysbiosis specifically reduced intestinal M. intestinale abundance and GABA levels. Supplementing with M. intestinale or GABA restored sIgA, increased IgA[+] B cells, and alleviated mastitis. We identified an NADP-specific glutamate dehydrogenase (GDH) in M. intestinale; a GDH-expressing E. coli-produced glutamate, elevating gut GABA, enhancing sIgA, and mitigating mastitis. Mechanistically, GABA activated the mTOR pathway to drive macrophage M2 polarization and B cell differentiation. Thus, M. intestinale-derived GABA boosts sIgA to protect against mastitis, offering novel prevention strategies.},
}

@article {pmid41476963,
year = {2025},
author = {Ma, S and Zheng, L and Zhuang, X and Wang, M and Zou, Y},
title = {Pathogenic mechanisms and therapeutic potential of the microbiome in premature ovarian insufficiency.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1734367},
pmid = {41476963},
issn = {1664-3224},
mesh = {Humans ; *Primary Ovarian Insufficiency/therapy/microbiology/metabolism/etiology ; Female ; Animals ; *Microbiota ; Ovary/metabolism/microbiology ; Probiotics/therapeutic use ; },
abstract = {The postponement of childbearing age has become a global issue. Factors such as increased work pressures on women and environmental changes have led to a rising incidence and younger onset of premature ovarian insufficiency (POI). POI not only impacts patients' reproductive function but also heightens the risk of depression, anxiety, cognitive decline, premature mortality, osteoporosis, and cardiovascular disease. Exploring effective prevention and treatment strategies for POI can slow ovarian ageing and safeguard female reproductive health. Microbiome research confirms that most human tissues and organs form dynamic, interactive systems with symbiotic microbes that play a crucial role in female reproductive function. Previous studies on the microbiome and female reproductive health have rarely focused on POI. The proposed 'Microbiota-Ovary Axis' aims to establish an integrated regulatory framework. This theoretical model systematically elucidates how microbial signals influence ovarian function through four core pathways: the hypothalamic-pituitary-ovarian (HPO) axis, metabolism and endocrine regulation, immunoregulation, and oxidative stress. Evaluating the efficacy of dietary modifications, probiotics, and microbiota transplantation in animal models and preliminary clinical studies will establish a robust theoretical foundation for developing microbiota-targeted innovative diagnostic and therapeutic strategies for POI, thereby enhancing reproductive health throughout the female lifespan.},
}

Humans
*Primary Ovarian Insufficiency/therapy/microbiology/metabolism/etiology
Female
Animals
*Microbiota
Ovary/metabolism/microbiology
Probiotics/therapeutic use

@article {pmid41476793,
year = {2025},
author = {Jin, S and Cheng, X and Han, F and Li, Q and Shang, J and Xie, G and Qin, M},
title = {Total alkaloids of Corydalis saxicola Bunting ameliorate ulcerative colitis through regulation of metabolite networks and gut microbiota.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1721116},
pmid = {41476793},
issn = {1663-9812},
abstract = {BACKGROUND: Yanhuanglian (YHL), derived from the dried herb of Corydalis saxicola Bunting, can inhibit diarrhea and alleviate bleeding in traditional Chinese medicine. YHL is used to treat dysentery and hematochezia, which are recognized as ulcerative colitis (UC) in traditional Chinese medicine. However, the effectiveness and mechanisms of YHL treating UC remain largely unknown. This study aimed to reveal anti-colitis effect and mechanisms of YHL's total alkaloids (YTA) against UC.

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

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

CONCLUSION: YTA exhibited potential anti-colitis activity by modulating metabolomic profiles and the gut microbiota, suggesting its potential as a complementary and alternative therapy in phytomedicine.},
}

@article {pmid41476057,
year = {2025},
author = {Wu, Y and Wong, O and Chen, S and Wang, Y and Lu, W and Cheung, CP and Ching, JYL and Cheong, PK and Chan, S and Leung, P and Chan, FKL and Su, Q and Ng, SC},
title = {Distinct diet-microbiome associations in autism spectrum disorder.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-025-67711-7},
pmid = {41476057},
issn = {2041-1723},
abstract = {Autism spectrum disorder (ASD) is linked to both altered gut microbiota and unhealthy diets; however, the mechanistic connections remain elusive. In this study, we conducted a systematic analysis of fecal microbiome metagenomic data, paired with granular dietary assessments and phenotypic profiles, across a cohort of 818 children (462 with ASD, 356 without ASD; mean age = 8.4 years; 27.3% female). By integrating dietary indices, nutrient intake, and food additive exposures, we uncovered ASD-specific linkages to the microbiome. Poor dietary quality correlated with aggregated core autistic symptoms, gastrointestinal complications, and atypical eating behaviors. Notably, children with ASD exhibited a more pronounced diet-microbiome interaction network compared to neurotypical peers, suggesting heightened microbial sensitivity to nutritional inputs. Furthermore, synthetic emulsifiers-specifically polysorbate-80 and carrageenan-were associated with disrupted microbial connectivity in ASD, a phenomenon attenuated in neurotypical children. Our findings elucidate the mechanistic links between dietary factors-particularly synthetic food additives-and microbiome dysregulation in ASD, urging a re-evaluation of dietary guidelines for ASD populations and laying the groundwork for personalized nutritional strategies.},
}

@article {pmid41475762,
year = {2026},
author = {Wu, X and Wei, J and Deng, R and Wang, J and Wu, B and Yan, T and Jia, Y},
title = {The Akkermansia muciniphila-tryptophan metabolism-aromatic hydrocarbon receptor axis mediates the protective effect of Schisandra chinensis pectin polysaccharide against colitis.},
journal = {Carbohydrate polymers},
volume = {375},
number = {},
pages = {124808},
doi = {10.1016/j.carbpol.2025.124808},
pmid = {41475762},
issn = {1879-1344},
mesh = {Animals ; *Tryptophan/metabolism ; *Schisandra/chemistry ; *Receptors, Aryl Hydrocarbon/metabolism ; Mice ; *Pectins/pharmacology/chemistry/therapeutic use ; Gastrointestinal Microbiome/drug effects ; *Colitis, Ulcerative/drug therapy/chemically induced/metabolism ; Mice, Inbred C57BL ; Male ; Dextran Sulfate/toxicity ; Akkermansia/drug effects/metabolism ; *Colitis/drug therapy/chemically induced/metabolism ; *Polysaccharides/pharmacology/chemistry ; Fecal Microbiota Transplantation ; Protective Agents/pharmacology ; },
abstract = {Current therapies for ulcerative colitis (UC) remain inadequate, necessitating novel treatment strategies. This study isolated SCPII-1, a homogeneous pectin polysaccharide (Mw: 278.153 kDa, DM: 57.21 %) from Schisandra chinensis, primarily composed of →4)-α-D-GalpA-(1 → units. In dextran sulfate sodium (DSS)-induced colitis mice, SCPII-1 alleviated symptoms, repaired mucosal ultrastructure (microvilli, mitochondria), and enhanced barrier integrity. Mechanistically, SCPII-1 ameliorated gut dysbiosis in UC mice, notably through the selective enrichment of the beneficial bacterium Akkermansia muciniphila (AKK). Interestingly, SCPII-1 not only promoted the proliferation of AKK but also modulated its tryptophan metabolism, particularly enhancing the production of the tryptophan-derived metabolite indole-3-ethanol (I3E). The beneficial role of SCPII-1-induced microbiota in UC was validated using pseudo-germ-free mice and fecal microbiota transplantation experiments. Moreover, I3E was identified as a key microbiota-derived active metabolite regulated by SCPII-1, and exogenous supplementation of I3E further confirmed its therapeutic efficacy in UC. Importantly, I3E activated the aryl hydrocarbon receptor (AhR), upregulated IL-22 expression, and promoted mucosal repair and immune homeostasis, thereby confirming the protective role of the SCPII-1-AKK-tryptophan metabolism axis in colitis. These findings highlight SCPII-1 as a promising prebiotic agent for UC treatment by modulating AKK-dependent tryptophan metabolism and activating the AhR/IL-22 signaling pathway, offering a novel microbiota-based therapeutic strategy.},
}

Animals
*Tryptophan/metabolism
*Schisandra/chemistry
*Receptors, Aryl Hydrocarbon/metabolism
Mice
*Pectins/pharmacology/chemistry/therapeutic use
Gastrointestinal Microbiome/drug effects
*Colitis, Ulcerative/drug therapy/chemically induced/metabolism
Mice, Inbred C57BL
Male
Dextran Sulfate/toxicity
Akkermansia/drug effects/metabolism
*Colitis/drug therapy/chemically induced/metabolism
*Polysaccharides/pharmacology/chemistry
Fecal Microbiota Transplantation
Protective Agents/pharmacology

@article {pmid41475736,
year = {2026},
author = {Wu, J and Xu, Q and Yang, Y and Yang, Z and Li, Z and Chen, L and Song, Y and Che, H and Wang, G and Lv, Q and Han, J},
title = {A novel fructan from Atractylodes macrocephala ameliorates ulcerative colitis through gut microbiota-mediated PI3K/Akt signaling.},
journal = {Carbohydrate polymers},
volume = {375},
number = {},
pages = {124764},
doi = {10.1016/j.carbpol.2025.124764},
pmid = {41475736},
issn = {1879-1344},
mesh = {Animals ; *Atractylodes/chemistry ; *Colitis, Ulcerative/drug therapy/chemically induced/metabolism/pathology/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Proto-Oncogene Proteins c-akt/metabolism ; *Phosphatidylinositol 3-Kinases/metabolism ; Mice ; Signal Transduction/drug effects ; *Fructans/pharmacology/chemistry/isolation & purification/therapeutic use ; Male ; Mice, Inbred C57BL ; Dextran Sulfate ; Disease Models, Animal ; Fecal Microbiota Transplantation ; },
abstract = {Polysaccharides from edible and medicinal plants are promising natural agents for intestinal health. In this study, a homogeneous polysaccharide (AMP) was isolated from Atractylodes macrocephala Koidz. Structural characterization revealed that AMP (Mw = 3.56 kDa) primarily consisted of fructose (92.4 %) and glucose (7.6 %), with β-D-fructofuranose and α-d-glucopyranose residues linked through →1)-β-D-Fruf-(2→, →1,6)-β-D-Fruf-(2→, and α-D-Glcp-(1 → glycosidic bonds. In vivo studies confirmed the efficacy of AMP against ulcerative colitis (UC) in a DSS-induced mouse model, as evidenced by a significant improvement in disease symptoms, including increased body weight, longer colon length, and elevated goblet cell counts, coupled with a reduction in the disease activity index and histological damage. Mechanistically, AMP attenuated inflammation by restoring intestinal barrier integrity and regulating the gut microbiota to maintain its homeostasis. These regulatory effects were further validated through fecal microbiota transplantation (FMT) and antibiotic intervention (Abx). Olink proteomics and western blotting demonstrated that the ameliorative effect of AMP on UC, mediated via the PI3K/Akt pathway, was entirely dependent on the homeostasis of the gut microbiota. Collectively, these findings position AMP as a promising functional food ingredient or natural therapeutic for UC, providing a scientific basis for the high-value exploitation of A. macrocephala.},
}

Animals
*Atractylodes/chemistry
*Colitis, Ulcerative/drug therapy/chemically induced/metabolism/pathology/microbiology
*Gastrointestinal Microbiome/drug effects
*Proto-Oncogene Proteins c-akt/metabolism
*Phosphatidylinositol 3-Kinases/metabolism
Mice
Signal Transduction/drug effects
*Fructans/pharmacology/chemistry/isolation & purification/therapeutic use
Male
Mice, Inbred C57BL
Dextran Sulfate
Disease Models, Animal
Fecal Microbiota Transplantation

@article {pmid41475679,
year = {2025},
author = {Morel, C and Li, R and Luces, CF and Brougham, MFH and Pascual-Gazquez, JF and Iniesta, RR and Torquati, L},
title = {Interventions targeting the gut microbiome to improve cancer treatment outcomes and their gastrointestinal side effects: a systematic review and meta-analysis.},
journal = {The Journal of nutrition},
volume = {},
number = {},
pages = {101300},
doi = {10.1016/j.tjnut.2025.101300},
pmid = {41475679},
issn = {1541-6100},
abstract = {BACKGROUND: Improvements in cancer treatment are essential to reduce premature mortality. Emerging evidence highlights the role of the gut microbiome (GM) in influencing treatment responses and modulating gastrointestinal adverse events (GIAEs). Because cancer therapy disrupts GM composition, restoring gut health may help mitigate side effects and support gut-associated immunity.

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

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

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

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

PROSPERO REGISTRATION: Registration number: CRD42023443332 LINK TO PROTOCOL: Https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023443332.},
}

@article {pmid41475542,
year = {2025},
author = {Nayak, A and Bera, S and Purohit, S and Jain, CK},
title = {Gut Microbiota Mediated Neuroinflammation in Psychiatric Disorders: Current Perspectives and Challenges.},
journal = {Behavioural brain research},
volume = {},
number = {},
pages = {116019},
doi = {10.1016/j.bbr.2025.116019},
pmid = {41475542},
issn = {1872-7549},
abstract = {Psychiatric disorders remain a major global health concern, with complex diagnostic criteria and a lack of clear biological markers that continue to challenge therapeutic strategies. Current treatment methods, such as psychotherapy, brain stimulation therapy, and pharmacological interventions, often come with their own set of side effects, thus warranting the need to explore alternative approaches. Emerging research highlights the gut brain axis (GBA) and gut microbiota (GM) as key modulators of brain health and disease. Dysbiosis, a disruption in gut microbial composition, can influence blood brain barrier (BBB) integrity, immune signaling, and microbial metabolite production, collectively modulating neuroimmune homeostasis and contributing to the onset of neuroinflammation. While growing preclinical and clinical evidence links altered GM to depression, anxiety, schizophrenia, bipolar disorder (BD), and autism spectrum disorder (ASD), causal relationships remain incompletely defined. This review examines the established and emerging mechanisms connecting the GM to neuroinflammation underlying psychiatric disorders and evaluates current microbiome targeted interventions, such as diet based strategies, probiotics, next generation probiotics (NGPs), and fecal microbiota transplantation (FMT). We also discuss speculative microbiome engineering approaches and highlight translational limitations that must be addressed before clinical implementation. A holistic approach integrating these strategies with conventional psychiatric treatments could facilitate more effective and personalized interventions.},
}

@article {pmid41475279,
year = {2025},
author = {Singh, G and Ansari, S and Yadav, S and Aran, KR},
title = {Gut microbiota's role in NAFLD- and HBV/HCV-related hepatocellular carcinoma: Mechanisms and therapeutic implications.},
journal = {Microbial pathogenesis},
volume = {211},
number = {},
pages = {108273},
doi = {10.1016/j.micpath.2025.108273},
pmid = {41475279},
issn = {1096-1208},
abstract = {Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality globally and has been closely linked to chronic liver conditions, such as viral hepatitis and non-alcoholic fatty liver disease. Recent research has demonstrated that the gut microbiota significantly impacts the gut-liver axis, a crucial aspect of the pathophysiology of HCC. This review emphasizes the mechanisms by which gut dysbiosis contributes to liver inflammation, fibrosis, and tumor formation. In NAFLD-related HCC, modification in the microbiota composition facilitates intestinal barrier dysfunction, endotoxemia, and metabolic disturbances. In HCC associated with HBV/HCV, the microbiome modulates immune surveillance and viral persistence. Shared pathogenic pathways, such as LPS-TLR4 signaling, bile acid dysregulation, and immunosuppressive microenvironments, highlight the role of microbial imbalance across varied etiologies. We also discuss how antibiotics, diet, probiotics, and postbiotics influence gut-liver homeostasis, as well as their therapeutic potential in primary and secondary prevention and treatment of HCC. Short-chain fatty acids and valeric acid are examples of postbiotics with anti-inflammatory and pro-apoptotic anti-IBD effects, while fecal microbiota transplantation and dietary modulation have shown potential in improving outcomes. The review also identifies significant research gaps, particularly in establishing causality, understanding intrahepatic metastasis, and investigating the roles of the fungal and viral microbiome (mycobiome and virome). Finally, the incorporation of microbiome-based interventions into clinical practice could represent an effective future strategy for risk stratification, prevention, and adjuvant therapy of HCC. Future studies focusing on longitudinal analysis, mechanistic validation, and multi-kingdom profiling are essential for translating microbiome research into effective clinical applications.},
}

@article {pmid41474687,
year = {2025},
author = {Abulaiti, A and Yu, H and Ma, J and Wuji, A and Chi, H},
title = {Advancement on the Association between Gut Microbiota and Autism Spectrum Disorder in Children.},
journal = {Annals of nutrition & metabolism},
volume = {},
number = {},
pages = {1-24},
doi = {10.1159/000549716},
pmid = {41474687},
issn = {1421-9697},
abstract = {Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by deficits in social interaction, communication, and the presence of restricted, repetitive behaviors. The rising global prevalence of ASD suggests a multifactorial etiology involving genetic, environmental, and neurodevelopmental factors. This review explores the establishment of the early-life microbiome, highlighting rapid microbial colonization from maternal and environmental sources. Emerging evidence indicates that delivery mode and infant feeding practices may influence ASD susceptibility. Although the concept of a sterile intrauterine environment remains debated, its investigation is valuable. The bidirectional "microbiota-gut-brain axis" has emerged as a critical pathway linking gut microbiota and brain function, offering potential therapeutic targets for ASD. Dietary patterns in children with ASD are often characterized by selectivity and restriction, which may disrupt gut microbiota composition and exacerbate gastrointestinal symptoms, thereby increasing ASD risk. Nutritional interventions and early behavioral therapies are thus essential. The gluten-free, casein-free (GFCF) diet remains controversial, with inconsistent evidence regarding its efficacy. Probiotic supplementation shows strain-specific effects, necessitating rigorous evaluation before clinical application. Given the heterogeneity of ASD, pharmacological treatments have shown limited universal efficacy. This review provides a comprehensive analysis of the interplay between diet, gastrointestinal symptoms, and ASD, evaluates the gut-brain axis as a mechanistic framework, and assesses the therapeutic potential of microbial interventions, including probiotics, prebiotics, and fecal microbiota transplantation (FMT). While promising findings have emerged, further well-designed clinical studies are needed to elucidate the complex etiology of ASD and validate therapeutic strategies.},
}

@article {pmid41473261,
year = {2025},
author = {Zhou, Y and Yang, L and Nan, Y and , },
title = {Expert Consensus on Clinical Applications of Fecal Microbiota Transplantation for Chronic Liver Disease (2025 edition).},
journal = {Journal of clinical and translational hepatology},
volume = {13},
number = {12},
pages = {1107-1116},
pmid = {41473261},
issn = {2310-8819},
abstract = {The gut microbiota is crucial in maintaining host health and liver function. Fecal microbiota transplantation (FMT) has shown promising potential in treating chronic liver diseases. To help clinicians quickly master and standardize the clinical application of FMT for chronic liver disease, the Liver Related Digestive Diseases Group of the Chinese Society of Hepatology of the Chinese Medical Association has developed the "Expert Consensus on the Clinical Application of FMT for Chronic Liver Disease." This consensus addresses the key aspects of FMT, including the indications, contraindications, efficacy, safety, donor selection, transplantation routes, precautions, and the prevention and management of adverse reactions for chronic liver conditions, such as chronic hepatitis, cirrhosis, and liver cancer, thereby offering reference and guidance to clinicians implementing FMT in the treatment of chronic liver disease.},
}

@article {pmid41473248,
year = {2025},
author = {Zhang, Y and Cao, J and Wang, Y and Fan, X and Deng, R and Mi, J},
title = {Effects of fecal microbiota transplantation on glycemic and lipid profiles in overweight or obese patients with metabolic disorders: a systematic review and meta-analysis.},
journal = {Frontiers in endocrinology},
volume = {16},
number = {},
pages = {1737543},
pmid = {41473248},
issn = {1664-2392},
mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Obesity/therapy/blood/complications ; *Metabolic Diseases/therapy/blood ; *Overweight/therapy/blood ; *Lipids/blood ; *Blood Glucose/metabolism ; Gastrointestinal Microbiome ; Randomized Controlled Trials as Topic ; Lipid Metabolism ; },
abstract = {UNLABELLED: Obesity and its associated metabolic disorders (such as type 2 diabetes, metabolic syndrome, and NAFLD/MASLD) represent a global health challenge. Fecal microbiota transplantation (FMT), as a therapy regulating the gut microbiome, has demonstrated inconsistent clinical efficacy. This systematic review aims to evaluate the impact of FMT on key indicators of glucose and lipid metabolism in overweight/obese adults with metabolic diseases. We systematically searched PubMed, Embase, Cochrane, and Web of Science databases up to September 28, 2025, to identify randomized controlled trials evaluating FMT for obesity and metabolic disorders. Data were pooled using a random-effects model, with primary outcomes being changes in BMI, HOMA-IR, and HbA1c relative to baseline. A total of 11 RCTs (320 participants) were included. The primary analysis showed that FMT intervention demonstrated a trend toward improvement in the primary outcome measures, BMI (MD: -0.65, p = 0.070) and HOMA-IR (MD: -0.64, p = 0.062), but these trends did not reach statistical significance. There was no significant effect on HbA1c (MD: 0.06, p = 0.742). However, this negative conclusion based on the conventional assumption (Corr = 0.5) exhibited high instability: sensitivity analysis revealed that FMT's improvement effects on BMI became statistically significant (p = 0.010) when the correlation coefficient (Corr) used to estimate the standard deviation of change was adjusted to 0.75. Furthermore, meta-regression analysis revealed that treatment regimen, follow-up duration, and patient baseline characteristics were significantly associated with HbA1c efficacy. Based on the current "low" certainty evidence, the overall improvement of metabolic parameters in overweight or obese patients with metabolic diseases following FMT did not reach statistical significance in the primary analysis. However, the robustness of this negative finding is limited, exhibiting high sensitivity to statistical hypotheses and likely being significantly confounded by methodological factors (e.g., administration protocols) and donor variability. Consequently, the true efficacy of FMT for treating systemic metabolic disorders remains uncertain. Future trials should shift toward precision medicine, prioritizing the standardization of donor selection and optimization of administration protocols.

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251172011, identifier CRD420251172011.},
}

Humans
*Fecal Microbiota Transplantation/methods
*Obesity/therapy/blood/complications
*Metabolic Diseases/therapy/blood
*Overweight/therapy/blood
*Lipids/blood
*Blood Glucose/metabolism
Gastrointestinal Microbiome
Randomized Controlled Trials as Topic
Lipid Metabolism

@article {pmid41472848,
year = {2025},
author = {Tang, B and Cao, Y and Li, J and Gao, N and Gao, P and Chen, X and Ming, Z and Li, Z and Hou, W},
title = {Whole microbiota transplantation restores gut homeostasis throughout the gastrointestinal tract.},
journal = {iMeta},
volume = {4},
number = {6},
pages = {e70091},
pmid = {41472848},
issn = {2770-596X},
abstract = {This study introduces whole microbiota transplantation (WMT), a synergistic therapeutic approach that concurrently transplants small intestinal and fecal microbiota. In germ-free mice, WMT outperforms conventional fecal microbiota transplantation (FMT) in restoring gut microbiota diversity and abundance. Moreover, in a chemotherapy-induced intestinal mucositis model, WMT alleviates intestinal inflammation and reverses microbiota dysbiosis. Encapsulation in layer-by-layer self-assembled nanocapsules further boosts microbial survival and colonization, amplifying WMT's anti-inflammatory effects and microbiota restoration in a mouse model of pan-intestinal infection. Overall, WMT represents a precise strategy for reshaping microbial homeostasis across the entire gastrointestinal tract, with therapeutic promise for inflammatory bowel diseases and small-intestinal disorders.},
}

@article {pmid41472816,
year = {2025},
author = {Lan, T and Hou, Q and Zhao, H and Luan, Y and Shi, Y and Hu, S and Wang, N and Yan, S and Gong, X and Song, Y},
title = {Gut microbiota dysbiosis impairs TGF-β/Smad4 signaling to drive postoperative metastasis in colorectal cancer.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1654227},
pmid = {41472816},
issn = {1664-302X},
abstract = {BACKGROUND: After surgical intervention, metastasis remains the primary contributor of mortality rates in colorectal cancer (CRC). While compelling evidence implicates gut microbiota dysbiosis as a key driver of CRC progression, its role in postoperative metastasis remains unclear.

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

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

CONCLUSION: Gut microbiota dysbiosis and SCFA depletion exert profound regulatory effects on postoperative CRC metastasis, potentially by promoting EMT through mechanisms involving the TGF-β/Smad4 signaling axis. Thus, targeting gut microbiota may offer promising therapeutic strategies to mitigate CRC metastasis.},
}

@article {pmid41472805,
year = {2025},
author = {Tian, Z and Li, C},
title = {The role of gut microbiota in the onset and development of sepsis and its therapeutic potential: mechanisms and research progress.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1718549},
pmid = {41472805},
issn = {1664-302X},
abstract = {Sepsis is a life-threatening disease triggered by infection-induced immune dysregulation, characterized by multi-organ dysfunction, and is one of the leading causes of death among critically ill patients worldwide. Recent studies have shown that gut microbiota (GM) imbalance plays a crucial role in the progression of sepsis. This review identifies the core mechanisms of GM imbalance: it disrupts the integrity of the intestinal mucosal barrier, induces bacterial and endotoxin translocation, activates systemic inflammatory responses, and forms a vicious cycle of "gut-organ" cross-damage, becoming a key driver of sepsis-associated multi-organ dysfunction. Existing research has confirmed that microbiota modulation strategies, such as probiotic supplementation and fecal microbiota transplantation (FMT), have potential therapeutic value. However, due to issues like strain specificity, lack of standardized protocols, and insufficient clinical evidence, the clinical translation of these strategies still faces significant barriers. Therefore, future research should focus on the identification of sepsis-specific GM core functional biomarkers, the development of personalized combined regulatory strategies, and the advancement of targeted delivery technologies. Multi-center large-scale clinical trials are needed to validate their efficacy and safety, providing innovative solutions for precision treatment of sepsis.},
}

@article {pmid41472740,
year = {2025},
author = {Chen, Q and Zhong, M and Lin, Y},
title = {Exploring gut microbiota and spinal cord injury: pathogenesis, treatment strategies and prospects.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1693883},
pmid = {41472740},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome ; *Spinal Cord Injuries/therapy/microbiology/etiology ; Animals ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; },
abstract = {Spinal cord injury (SCI) is a disabling central nerve system (CNS) injury, often caused by factors such as traffic accidents, falls from heights, violent trauma, and sports injuries, commonly resulting in permanent loss of motor and sensory function below the level of injury. Increasing evidence suggests that gut microbiota influences the occurrence and development of CNS diseases through the brain-gut axis. Recent studies indicate that patients with SCI frequently exhibit gut microbiota dysbiosis. Changes in gut microbiota can lead to gut barrier disruption, triggering neurogenic inflammatory responses, thereby hindering recovery after SCI, while reshaping gut microbiota may benefit the recovery of intestinal function and neurofunction after SCI. In this review, we summarize emerging literature on the role of microbiota after SCI. We elucidate the intrinsic connection between gut microbiota and SCI, explore the role of gut microbiota in the pathogenesis of SCI, and investigate potential intervention strategies targeting gut microbiota, including probiotic therapy, fecal microbiota transplantation (FMT), and regulation of metabolites, aiming to provide theoretical basis and translational prospects for developing innovative microecological targeted therapeutic approaches.},
}

Humans
*Gastrointestinal Microbiome
*Spinal Cord Injuries/therapy/microbiology/etiology
Animals
Dysbiosis/therapy
Fecal Microbiota Transplantation
Probiotics/therapeutic use

@article {pmid41472066,
year = {2025},
author = {Vestad, B and Hanzely, P and Karaliūtė, I and Ramberg, O and Skiecevičienė, J and Lukoševičius, R and Bjørnholt, JV and Holm, K and Kupčinskas, J and Rasmussen, H and Hov, JR and Melum, E},
title = {Modulation of Dextran Sodium Sulfate-Induced Colitis in Germ-Free Mice by Enterococcus faecalis Monocolonization.},
journal = {Microorganisms},
volume = {13},
number = {12},
pages = {},
pmid = {41472066},
issn = {2076-2607},
support = {LT08-2-LMT-K-01-060//EEA Grants 2014-2021/ ; 802544/ERC_/European Research Council/International ; },
abstract = {Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis (UC), are characterized by chronic gastrointestinal inflammation and involve complex interactions of genetic, environmental, and immune factors. Enterococcus faecalis, a gut commensal bacterium, has been implicated in IBD pathogenesis. This study investigated the effects of monocolonization with a UC-derived E. faecalis strain on acute dextran sulfate sodium (DSS)-induced colitis in germ-free (GF) mice, focusing on epithelial injury, inflammatory markers, hematologic indices, and bacterial translocation. In DSS-treated mice, monocolonization was associated with modest and mixed effects, including a higher colitis-related disease activity score, reduced anemia, increased fecal albumin and a trend towards reduced fecal calprotectin. Despite translocation of E. faecalis to mesenteric lymph nodes, no systemic dissemination was observed. Histological analysis revealed broadly similar inflammatory patterns between DSS-treated groups, with slightly more epithelial injury observed in colonized mice. These findings suggest that E. faecalis may influence discrete aspects of DSS injury in a strain-dependent and context-specific manner, rather than broadly altering overall disease severity. This study highlights the utility of GF models for examining strain-specific host-microbe interactions and underscores that individual bacterial isolates may exert heterogeneous and selective effects on acute colitis. Further research is needed to elucidate these complex mechanisms.},
}

@article {pmid41471996,
year = {2025},
author = {Zhang, X and Mao, G and Pei, Z and Sun, Y and Cen, J and Zhang, S and Li, S and Meng, W and Xiao, K and Xu, Q and Sun, M},
title = {Microbial Ecology of Sulfur Mustard Toxicity: From Dysbiosis to Restoration.},
journal = {Microorganisms},
volume = {13},
number = {12},
pages = {},
pmid = {41471996},
issn = {2076-2607},
support = {82103885//National Natural Science Foundation of China/ ; 82273672//National Natural Science Foundation of China/ ; 20ZR1470300//Natural Science Foundation of Shanghai Municipality/ ; 21ZR1477700//Natural Science Foundation of Shanghai Municipality/ ; GWV-10.2-YQ48//Shanghai Municipal Health Commission-Outstanding Youth Foundation of Public Health/ ; },
abstract = {Sulfur mustard (SM) causes multi-organ toxicity, yet its impact on intestinal tissue and the associated gut microbiota remains poorly characterized. This study demonstrates that in a mouse model of SM exposure, gut microbial ecological collapse occurs, characterized by depletion of protective taxa (Bifidobacteriales, Gordonibacter, and Lachnospiraceae UCG010) while promoting a 302-fold expansion of inflammation-associated Escherichia/Shigella. Mendelian randomization analysis established causal relationships between these SM-perturbed taxa and human inflammatory bowel disease. Fecal microbiota transplantation effectively restored microbial diversity (Simpson index: 0.85 to 0.95), suppressed Escherichia/Shigella by 97.4%, and ameliorated intestinal pathology. Longitudinal tracking revealed persistent vulnerability of Bifidobacteriales compared to other depleted taxa. Our findings establish the gut microbiota as a key mediator in SM intestinal toxicity and provide new insights for microbiota-targeted interventions against chemical injuries.},
}

@article {pmid41471872,
year = {2025},
author = {Yang, B and Zhong, S and Wang, J and Yu, W},
title = {Dietary Modulation of the Gut Microbiota in Dogs and Cats and Its Role in Disease Management.},
journal = {Microorganisms},
volume = {13},
number = {12},
pages = {},
pmid = {41471872},
issn = {2076-2607},
support = {No. 20242BAB20315//Natural Science Foundation for Youth of Jiangxi Province/ ; GJJ2200410//The Science and Technology Program of Jiangxi Provincial Department of Education/ ; },
abstract = {Food has a massive influence on the gut microbiota and is one of the most useful therapeutic levers in disease. Recent developments have highlighted how macronutrient balance, food format, and functional ingredients can regulate microbial diversity, metabolism, and host physiology in companion animals such as dogs and cats. This narrative review condenses evidence on the bidirectional gut microbiota-diet connection and on nutritional therapy for gastrointestinal, metabolic, renal, hepatic, and immune-mediated disorders. Protein-based diets including high or hydrolyzed protein, omega-3 acids, fermentative fiber, and probiotics can positively affect microbial composition, stimulate short-chain fatty acid synthesis, and enhance intestinal barrier functions. Conversely, excess fats or refined carbohydrates may cause dysbiosis, inflammation, and metabolic imbalances. Numerous studies have shown that therapeutic nutrition-e.g., low-protein renoprotective, hepatoprotective antioxidants, and allergen-elimination diets-holds enormous potential for treatment. In addition, fecal microbiota transplantation (FMT) can be used as an additive therapy for resistant gastrointestinal illnesses. Despite these developments, constraints remain in terms of standardization, study duration, and species-specific data, especially for cats. This review underscores dietary modification as a clinically actionable tool for microbiota-targeted therapy and calls for integrative, multi-omics research to translate microbiome modulation into precision nutrition for companion animals.},
}

@article {pmid41471163,
year = {2025},
author = {Ziaka, M},
title = {Targeting Gut-Lung Crosstalk in Acute Respiratory Distress Syndrome: Exploring the Therapeutic Potential of Fecal Microbiota Transplantation.},
journal = {Pathogens (Basel, Switzerland)},
volume = {14},
number = {12},
pages = {},
doi = {10.3390/pathogens14121206},
pmid = {41471163},
issn = {2076-0817},
mesh = {*Respiratory Distress Syndrome/therapy/microbiology ; Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Lung/microbiology/immunology ; Animals ; *Gastrointestinal Tract/microbiology ; },
abstract = {The gastrointestinal (GI) tract contributes significantly to the pathogenesis of acute respiratory distress syndrome (ARDS) by influencing systemic inflammation and sepsis, which are key factors in the development of multiple organ dysfunction syndrome (MODS), while the significant impact of gut microbiota in critically ill patients, including those with sepsis and ARDS, further underscores its importance. The intestinal microbiota is vital to immune system function, responsible for triggering around 80% of immune responses. Therefore, it may be hypothesized that modifying fecal microbiota, such as through fecal microbiota transplantation (FMT), could serve as a valuable therapeutic approach for managing inflammatory diseases like lung injury (LI)/ARDS. Indeed, emerging experimental research suggests that FMT may have beneficial effects in ARDS models by improving inflammation, oxidative stress, LI, and oxygenation. However, well-designed randomized clinical trials in patients with ARDS are still lacking. Our study seeks to examine how therapeutic interventions such as FMT might benefit LI/ARDS patients by exploring the interactions between the gut and lungs in this context.},
}

*Respiratory Distress Syndrome/therapy/microbiology
Humans
*Fecal Microbiota Transplantation/methods
*Gastrointestinal Microbiome
*Lung/microbiology/immunology
Animals
*Gastrointestinal Tract/microbiology

@article {pmid41470815,
year = {2025},
author = {Wei, X and Lang, F and Liu, H and Wang, S and Wang, T},
title = {Soluble Dietary Fiber from Highland Barley Bran Reduces Hepatic Lipid Accumulation in Mice via Gut Microbiota Modulation.},
journal = {Nutrients},
volume = {17},
number = {24},
pages = {},
doi = {10.3390/nu17243870},
pmid = {41470815},
issn = {2072-6643},
support = {2024-ZJ-963//Qinghai Provincial Natural Science Youth Foundation Project/ ; },
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Dietary Fiber/pharmacology ; *Hordeum/chemistry ; *Liver/metabolism/drug effects ; Diet, High-Fat/adverse effects ; Mice ; *Lipid Metabolism/drug effects ; Male ; Mice, Inbred C57BL ; Fatty Acids, Volatile/metabolism ; Obesity/prevention & control/etiology/metabolism ; Lipidomics ; },
abstract = {BACKGROUND: Obesity has emerged as a significant public health challenge largely attributed to excessive dietary fat consumption. A growing body of evidence indicates that soluble dietary fiber (SDF) can prevent high-fat-diet (HFD)-induced obesity by modulating the gut microbiota. Our previous studies have shown that SDF derived from highland barley bran exhibits favorable lipid-lowering activity in vitro, but its lipid-lowering effect in vivo remains to be elucidated.

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

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

CONCLUSIONS: The increase in SCFAs activated the hepatic AMP-activated protein kinase α (AMPK) signaling pathway, thereby ameliorating HFD-induced disturbances in lipid metabolism, reducing hepatic lipid accumulation, and lowering serum lipid concentrations.},
}

Animals
*Gastrointestinal Microbiome/drug effects
*Dietary Fiber/pharmacology
*Hordeum/chemistry
*Liver/metabolism/drug effects
Diet, High-Fat/adverse effects
Mice
*Lipid Metabolism/drug effects
Male
Mice, Inbred C57BL
Fatty Acids, Volatile/metabolism
Obesity/prevention & control/etiology/metabolism
Lipidomics

@article {pmid41469665,
year = {2025},
author = {Zheng, SH and Li, KZ and Feng, G and Wang, YT and Wang, JN and Li, SQ and Sun, YD},
title = {Gut microbiota reshaping the pancreatic cancer immune microenvironment: new avenues for immunotherapy.},
journal = {Molecular cancer},
volume = {24},
number = {1},
pages = {313},
pmid = {41469665},
issn = {1476-4598},
mesh = {Humans ; *Tumor Microenvironment/immunology ; *Gastrointestinal Microbiome/immunology ; *Pancreatic Neoplasms/therapy/immunology/etiology/pathology/microbiology/metabolism ; *Immunotherapy/methods ; Animals ; Fecal Microbiota Transplantation ; },
abstract = {Pancreatic cancer remains one of the deadliest malignancies, primarily due to its highly immunosuppressive tumor microenvironment (TME) and poor response to conventional therapies. Increasing evidence highlights the gut microbiota as a pivotal regulator of antitumor immunity, modulating T cell activation, macrophage polarization, and dendritic cell function. Microbial communities and their metabolites can either inhibit or enhance immune surveillance, thereby influencing the efficacy of immunotherapies such as immune checkpoint inhibitors (ICIs) and CAR-T cell therapy. Approaches including dietary modulation, probiotics, fecal microbiota transplantation (FMT), and microbial metabolite supplementation show promise in restoring immune homeostasis and improving treatment outcomes. Additionally, gut microbiome profiling has emerged as a potential source of biomarkers for predicting therapeutic response and immune-related adverse events. This review summarizes current insights into microbiota-immune interactions in pancreatic cancer, emphasizes microbiome-targeted therapeutic strategies, and explores future opportunities for precision immunotherapy guided by microbial modulation.},
}

Humans
*Tumor Microenvironment/immunology
*Gastrointestinal Microbiome/immunology
*Pancreatic Neoplasms/therapy/immunology/etiology/pathology/microbiology/metabolism
*Immunotherapy/methods
Animals
Fecal Microbiota Transplantation

@article {pmid41469027,
year = {2025},
author = {Bu, T and Zhao, X and Kong, X and Huang, Z and Zhu, H and Sun, P and Yang, K and Chen, S and Cai, M},
title = {The Mechanism of Dendrobium officinale Polysaccharides in Alleviating Osteoporosis via Regulation of Wnt/β-Catenin Signaling Pathways and Modulation of Gut Microbiota.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c10301},
pmid = {41469027},
issn = {1520-5118},
abstract = {Osteoporosis (OP) poses a significant global health burden, with emerging therapies targeting the gut microbiota (GM). This study investigated the effects of Dendrobium officinale polysaccharides (DOP), characterized as an acetylated glucomannan with a linear β-(1 → 4)-mannose backbone, on ovariectomy (OVX)-induced OP through the gut-bone axis. DOP administration significantly attenuated bone loss in OVX mice by modulating bone turnover and inflammation markers, activating Wnt/β-catenin signaling, and preserving intestinal barrier function. Furthermore, DOP dose-dependently reshaped the GM composition, increasing the Firmicutes/Bacteroidetes ratio, especially enriching short chain fatty acids (SCFA)-producing genera Allobaculum and Clostridia_UCG-014, which consequently restored butyric and isovaleric acid levels. Crucially, fecal microbiota transplantation from DOP-treated donors reproduced the osteoprotective phenotype in recipient mice, establishing a causal role for DOP-modulated GM. These findings demonstrate that DOP alleviates OP via GM-driven SCFA production, barrier integrity, anti-inflammation, and Wnt/β-catenin signaling activation, underscoring its prebiotic potential for OP management.},
}

@article {pmid41467904,
year = {2026},
author = {Maruyama, D and Tian, X and Doan, TNM and Liao, WI and Chaki, T and Taenaka, H and Maishan, M and Matthay, MA and Prakash, A},
title = {Gut microbiome-derived propionate reprograms alveolar macrophages metabolically and regulates lung injury responses in mice.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2606486},
doi = {10.1080/19490976.2025.2606486},
pmid = {41467904},
issn = {1949-0984},
mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Macrophages, Alveolar/metabolism/immunology ; Mice ; *Lung Injury/microbiology/metabolism/immunology ; Dietary Fiber/metabolism/administration & dosage ; Fatty Acids, Volatile/metabolism ; *Propionates/metabolism ; Mice, Inbred C57BL ; Male ; Bacteria/metabolism/classification/genetics/isolation & purification ; Lung/metabolism/immunology ; },
abstract = {Responses to lung injury can vary between individuals with the diet and gut microbiome representing two underappreciated sources for this variability. The gut microbiome can influence lung injury outcomes through the gut‒lung axis, but exactly how diet and its effects on the microbiota are involved remains unclear. We hypothesized that dietary fiber interventions would favor the presence of short-chain fatty acid (SCFA)-producing fermentative bacteria presence in the gut microbiome, thereby influencing the resting lung immunometabolic tone as well as influencing downstream responses to lung injury and infection. To test this hypothesis, we fed mice fiber-rich (FR) and fiber-free (FF) diets, and observed changes in the steady-state transcriptional programming of alveolar macrophages (AM). Next, we examined the effects of the FR and FF diets on murine responses to sterile and infectious lung injury in vivo while simultaneously profiling the gut microbiota and SCFA levels transmitted along the gut‒lung axis. Finally, we validated our in vivo observations with mechanistic studies of the metabolic, signaling, and chromatin-modifying effects of specific SCFAs on lung AM ex vivo and in vitro. Overall, our fiber-rich diet reprogrammed AMs and attenuated lung inflammation after sterile injury while exacerbating lung infection. This effect of FR diets could be transferred to germ-free (GF) mice by fecal microbiome transplantation (FMT) and depended on the ability of the microbiota to produce propionate. Mechanistically, SCFAs altered the metabolic programming of AMs and lung tissue ex vivo without a clear role for free fatty acid receptors (FFAR) or chromatin remodeling. These findings demonstrate that the gut‒lung axis can regulate resting lung metabolic tone through dietary fiber intake and the enrichment of SCFA-producing gut bacteria, as well as influence sterile and non-sterile lung injury responses. These results provide evidence to support the development of therapeutic dietary interventions to preserve or enhance specific aspects of host pulmonary immunity.},
}

Animals
*Gastrointestinal Microbiome/physiology
*Macrophages, Alveolar/metabolism/immunology
Mice
*Lung Injury/microbiology/metabolism/immunology
Dietary Fiber/metabolism/administration & dosage
Fatty Acids, Volatile/metabolism
*Propionates/metabolism
Mice, Inbred C57BL
Male
Bacteria/metabolism/classification/genetics/isolation & purification
Lung/metabolism/immunology

@article {pmid41466538,
year = {2025},
author = {Zheng, B and Liu, L and Li, J and Chen, Y and Xie, J and Zhao, X and Feng, J and Zhou, Q and Hu, X and Yu, Q},
title = {Bound Polyphenols in Rice Bran Insoluble Dietary Fiber Ameliorate Intestinal Barrier Damage via Butyrate-Mediated Regulation of Apoptosis-Autophagy Signaling.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c12877},
pmid = {41466538},
issn = {1520-5118},
abstract = {Bound polyphenols (BPs) are critical to the anti-obesity effects of dietary fiber. However, their role in dietary-fiber-mediated intestinal barrier protection remains unclear. In this study, we demonstrated that rice bran insoluble dietary fiber (RIDF) alleviated intestinal barrier damage in high-fat-diet (high-fat diet)-fed mice, and this beneficial effect was dependent on BPs, as it was attenuated in mice treated with polyphenol-removed dietary fiber (RIDF_DF). Furthermore, fecal supernatant transplantation from RIDF-treated (not RIDF_DF-treated) mice alleviated obesity and reshaped the gut microbiota in recipient mice. Additionally, the fecal supernatant enhanced the intestinal barrier function and augmented the synthesis of short-chain fatty acids. Notably, butyrate administration upregulated intestinal tight junction proteins in Caco-2 cells and HFD-fed mice and increased Oscillospira abundance. Mechanistically, butyrate inhibited apoptosis and promoted autophagy, accompanied by alterations in the AMPK-Akt signaling pathway. These results indicate that BPs contribute to the ameliorative effect of RIDF on intestinal damage.},
}

@article {pmid41466423,
year = {2025},
author = {Chen, L and Tang, C and Hu, D and Yu, S and Liao, P},
title = {Brevilin a reverses colitis of inflammatory bowel disease via modulation of TNF-α signaling and microbiome dysregulation.},
journal = {Gut pathogens},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13099-025-00792-3},
pmid = {41466423},
issn = {1757-4749},
support = {2024000003-09//Middle-aged Backbone Talents in the Province/ ; },
abstract = {BACKGROUND: Brevilin A (Br) has shown potential in modulating inflammatory bowel disease (IBD). Our study aims to explore its mechanism of anti-inflammatory action.

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

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

CONCLUSION: Br's ability to regulate gut microbiota and metabolites, improve gut barrier function, and eliminate inflammation by inhibiting TNF-α highlights its potential as a novel therapeutic medicine for IBD. Future research should focus on further exploring its mechanisms and clinical applications.},
}

@article {pmid41466331,
year = {2025},
author = {Li, J and Zhang, X and Zhao, X and Gong, G and Li, J and Dalai, B and Mo, Z and Xu, X and Jia, X and Li, Y and Lai, J and Wang, P and Sun, L and Liu, Y and Luo, X},
title = {Characterising gut microbiome dysbiosis in diarrhoea calves from multiple farms in Inner Mongolia using 16S and metagenomics.},
journal = {Microbiome},
volume = {13},
number = {1},
pages = {259},
pmid = {41466331},
issn = {2049-2618},
support = {2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2021GG0171//Key Technology Project of Inner Mongolia Science and Technology Department/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2020ZD0006//Inner Mongolia Autonomous Region Major Science and Technology Special Project/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; 2022LJRC0009//Science and Technology Leading Talent Team in Inner Mongolia Autonomous Region/ ; },
mesh = {Animals ; Cattle ; *Gastrointestinal Microbiome/genetics ; *Diarrhea/microbiology/veterinary/epidemiology ; RNA, Ribosomal, 16S/genetics ; *Metagenomics/methods ; China/epidemiology ; *Dysbiosis/microbiology/veterinary ; *Cattle Diseases/microbiology/epidemiology ; Feces/microbiology ; Escherichia coli/genetics/isolation & purification/pathogenicity ; *Bacteria/classification/genetics/isolation & purification ; Farms ; },
abstract = {BACKGROUND: The pathogenesis of neonatal calf diarrhoea (NCD), a critical disease that contributes to neonatal mortality in calves, remains nebulous.

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

CONCLUSIONS: The findings of this study revealed significant gut microbial dysbiosis in calves with severe diarrhoea, through which two putative NCD-associated pathogens were identified: E. coli (bin.216) and S. ruminantium (bin.338). Marked enrichment of Bacteroides spp. and Methanobrevibacter_A sp. 900313645 was observed in healthy cohorts, suggesting their potential protective roles. Therapeutic strategies employing phage-mediated pathogen targeting combined with probiotic transplantation have demonstrated dual benefits, potentially reducing antimicrobial dependency and preserving microbial homeostasis through ecological network reconstruction. Video Abstract.},
}

Animals
Cattle
*Gastrointestinal Microbiome/genetics
*Diarrhea/microbiology/veterinary/epidemiology
RNA, Ribosomal, 16S/genetics
*Metagenomics/methods
China/epidemiology
*Dysbiosis/microbiology/veterinary
*Cattle Diseases/microbiology/epidemiology
Feces/microbiology
Escherichia coli/genetics/isolation & purification/pathogenicity
*Bacteria/classification/genetics/isolation & purification
Farms

@article {pmid41466105,
year = {2025},
author = {Zhang, H and Shen, C and Lei, W and Wang, J and Liu, J and Qiu, Z},
title = {Pilot Clinical Trial of Fecal Microbiota Transplantation for Constipation in Parkinson's Disease.},
journal = {Journal of microbiology and biotechnology},
volume = {35},
number = {},
pages = {e2509029},
doi = {10.4014/jmb.2509.09029},
pmid = {41466105},
issn = {1738-8872},
mesh = {Humans ; *Constipation/therapy/etiology/microbiology ; *Fecal Microbiota Transplantation/methods ; *Parkinson Disease/complications/therapy/microbiology ; Aged ; Pilot Projects ; Middle Aged ; Male ; Gastrointestinal Microbiome ; Female ; Prospective Studies ; Feces/microbiology ; Treatment Outcome ; Dysbiosis/therapy ; Bacteria/classification/genetics/isolation & purification ; },
abstract = {The purpose of this study was to evaluate the safety and efficacy of fecal microbiota transplantation in patients with constipation due to parkinson's disease. Gut dysbiosis has long been associated with parkinson's and recent studies have shown that FMT can restore the normal flora of the gut. Therefore, this clinical trial aimed to test the therapeutic efficacy of FMT in 5 patients aged 55 to 71 diagnosed with PD who presented with constipation. The study was conducted as an open label, prospective trial and consisted of FMT performed every 3 days via nasojejunal tube placement followed by 8 weeks of patient follow-up to evaluate response to drug therapy and to assess neurological function using UPDRS-III OFF scores, and improvement in constipation assessed with Wexner scores. Samples taken before and after FMT were collected for shotgun metagenomic sequencing to analyze the composition of the microbial communities present in patients. Untargeted non-targeted metabolomic studies were performed to investigate the impact of FMT on metabolome changes due to FMT. The results indicate an improvement in constipation and neurological functioning following FMT, and significant alteration of the gut microbiota. Significant increases in Bifidobacteria bifidus, Alistipes shahi, Anaerotruncus coli, and uncharacterized Flavonifractor were found post-treatment compared to the baseline. Many of the other strains present prior to treatment, including Acinetobacter sp. and Proteobacteria sp., had significantly decreased after the FMT. The metabolomic studies found shifts in metabolic pathways involved with unsaturated fatty acid synthesis and amino acid metabolism due to FMT. FMT may be an effective treatment option for constipation and neurological symptoms associated with PD.},
}

Humans
*Constipation/therapy/etiology/microbiology
*Fecal Microbiota Transplantation/methods
*Parkinson Disease/complications/therapy/microbiology
Aged
Pilot Projects
Middle Aged
Male
Gastrointestinal Microbiome
Female
Prospective Studies
Feces/microbiology
Treatment Outcome
Dysbiosis/therapy
Bacteria/classification/genetics/isolation & purification

@article {pmid41465322,
year = {2025},
author = {Rzeczycki, P and Pęciak, O and Plust, M and Droździk, M},
title = {Gut Microbiota in the Regulation of Intestinal Drug Transporters: Molecular Mechanisms and Pharmacokinetic Implications.},
journal = {International journal of molecular sciences},
volume = {26},
number = {24},
pages = {},
doi = {10.3390/ijms262411897},
pmid = {41465322},
issn = {1422-0067},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; *Intestinal Mucosa/metabolism ; Multidrug Resistance-Associated Protein 2 ; *Membrane Transport Proteins/metabolism ; },
abstract = {Gut microbiota, through both its species composition and its metabolites, impacts expression and activity of intestinal drug transporters. This phenomenon directly affects absorption process of orally administered drugs and contributes to the observed inter-individual variability in pharmacotherapeutic responses. This review summarizes mechanistic evidence from in vitro and animal studies and integrates clinical observations in which alterations in gut microbiota are associated with changes in oral drug exposure, consistent with potential regulation of key intestinal drug transporters-such as P-glycoprotein (P-gp, ABCB1), Breast Cancer Resistance Protein (BCRP, ABCG2), MRP2/3 proteins (ABCC2/3), and selected Organic Anion-Transporting Polypeptides (OATPs, e.g., SLCO1A2, SLCO2B1)-by major bacterial metabolites including short-chain fatty acids (SCFAs), secondary bile acids, and tryptophan-derived indoles. The molecular mechanisms involved include activation of nuclear and membrane receptors (PXR, FXR, AhR, TGR5), modulation of transcriptional and stress-response pathways (Nrf2, AP-1) with simultaneous suppression of pro-inflammatory pathways (NF-κB), and post-translational modifications (e.g., direct inhibition of P-gp ATPase activity by Eggerthella lenta metabolites). The review also highlights the pharmacokinetic implications of, e.g., tacrolimus, digoxin, and metformin. In conclusion, the significance of "drug-transporter-microbiome" interactions for personalized medicine is discussed. Potential therapeutic interventions are also covered (diet, pre-/probiotics, fecal microbiota transplantation, modulation of PXR/FXR/AhR pathways). Considering the microbiota as a "second genome" enables more accurate prediction of drug exposure, reduction in toxicity, and optimization of dosing for orally administered preparations.},
}

Humans
*Gastrointestinal Microbiome/physiology
Animals
*Intestinal Mucosa/metabolism
Multidrug Resistance-Associated Protein 2
*Membrane Transport Proteins/metabolism

@article {pmid41464856,
year = {2025},
author = {Sylwestrzak, T and Ciosek, M and Pastuszak, K and Jastrzębski, T},
title = {Fecal Short-Chain Fatty Acids in Colorectal Cancer Patients Versus Healthy Controls: A Systematic Review and Meta-Analysis.},
journal = {Journal of clinical medicine},
volume = {14},
number = {24},
pages = {},
doi = {10.3390/jcm14248949},
pmid = {41464856},
issn = {2077-0383},
abstract = {Background: Short-chain fatty acids (SCFAs), the main microbial fermentation products in the colon, have immunometabolic and anti-neoplastic properties. Alterations in fecal SCFA profiles have been proposed as potential non-invasive biomarkers for colorectal cancer (CRC), but previous findings remain inconsistent. This systematic review and meta-analysis aimed to determine whether fecal acetate, propionate, and butyrate concentrations differ between patients with CRC and healthy individuals. Methods: A comprehensive search of PubMed, Web of Science and Cochrane Library was conducted on 18 September 2025. Eligible studies were observational, included adults with histologically confirmed CRC and healthy controls, and reported fecal concentrations of at least one SCFA quantified using validated analytical methods. Two independent reviewers performed study screening, data extraction, and risk-of-bias assessment. Random-effects models were applied to calculate pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: Thirteen studies met inclusion criteria for qualitative synthesis, and four (141 CRC cases, 98 controls) were eligible for meta-analysis. Compared with healthy controls, patients with CRC had significantly lower fecal acetate (pooled SMD -0.37; 95% CI -0.63 to -0.10; p = 0.006; I[2] = 0%) and butyrate (pooled SMD -0.59; 95% CI -1.10 to -0.07; p = 0.026; I[2] = 64.4%), whereas propionate did not differ significantly (pooled SMD -0.02; 95% CI -0.85 to 0.82; p = 0.971; I[2] = 89%). Conclusions: CRC is associated with reduced fecal butyrate and, to a lesser extent, acetate, suggesting impaired microbial fermentation. Propionate shows no consistent difference. SCFA profiling currently lacks sufficient standardization and validation for clinical application. Future harmonized, longitudinal studies integrating diet, microbiome, and metabolomic data are warranted to confirm SCFAs as reproducible biomarkers of CRC.},
}

@article {pmid41464526,
year = {2025},
author = {Ichim, C and Boicean, A and Todor, SB and Boeras, I and Anderco, P and Birlutiu, V},
title = {Dynamics of Fecal microRNAs Following Fecal Microbiota Transplantation in Alcohol-Related Cirrhosis.},
journal = {Journal of clinical medicine},
volume = {14},
number = {24},
pages = {},
doi = {10.3390/jcm14248623},
pmid = {41464526},
issn = {2077-0383},
abstract = {Background: Micro-RNAs (miRNAs) are emerging as pivotal regulators of pathophysiological processes, reflecting systemic responses to stress, inflammation and metabolic imbalance. Their role in advanced liver disease and in modulating responses to therapeutic interventions, such as fecal microbiota transfer (FMT), remains insufficiently characterized. Methods: We conducted a prospective study including six male patients with toxic ethanolic liver cirrhosis undergoing FMT and six healthy controls. Stool and blood samples were collected pre- and post-FMT. Fecal micro-RNA expression (miR-21, miR-122, miR-125, miR-146 and miR-155) was quantified using RT-qPCR and normalized to miR-26c. Associations with noninvasive fibrosis markers (FIB-4, APRI, elastography, CAP) and biological parameters were analyzed through multivariable regression and Pearson correlation, with internal validation by bootstrapping. Results: One week after fecal microbiota transfer, miR-21 and miR-146 exhibited significant expression changes, while miR-122, miR-125, and miR-155 showed non-significant trends toward increased expression. Post-FMT increases in miR-21, miR-122, miR-146 and miR-155 were consistently associated with reductions in hepatic fibrosis markers (FIB-4, APRI and liver stiffness), whereas no significant associations were observed with CAP. Conclusions: Fecal micro-RNAs reflect interconnected molecular networks that capture systemic adaptations to FMT. Despite a limited cohort, these findings highlight their potential as integrative biomarkers and as therapeutic targets in advanced liver disease. Larger-scale studies are warranted to validate clinical utility.},
}

@article {pmid41463403,
year = {2025},
author = {Sun, X and Li, P and Chen, B and Chen, C and Zhao, J and Sun, S},
title = {Fucoidan Therapy for Extraintestinal Diseases: Targeting the Microbiota-Gut-Organ Axes.},
journal = {Biomolecules},
volume = {15},
number = {12},
pages = {},
doi = {10.3390/biom15121750},
pmid = {41463403},
issn = {2218-273X},
support = {82374218//National Natural Science Foundation of the People's Republic of China/ ; 82405310//National Natural Science Foundation of the People's Republic of China/ ; 2023DYPLHGG-09//The First Batch of Joint Research Projects of the China Association of Traditional Chinese Medicine/ ; MS2021002//Jiangsu Province Traditional Chinese Medicine Science and Technology Development Project/ ; 1020241792//Natural Science Foundation of the Jiangsu Higher Education Institutions of China/ ; },
mesh = {*Polysaccharides/therapeutic use/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Humans ; Animals ; Prebiotics ; Obesity/drug therapy/microbiology ; },
abstract = {The microbiota-gut-organ axis is widely recognized as a pivotal mediator of systemic health, primarily through gut-derived immune, metabolic, and inflammatory signaling. Fucoidans, a class of fucose-containing sulfated polysaccharides predominantly composed of L-fucose and exclusively found in brown seaweeds, have been demonstrated to modulate gut microbiota composition and function, resulting in the enrichment of beneficial bacteria and the suppression of harmful species. They enhance the production of beneficial metabolites, such as short-chain fatty acids and specific bile acids, while suppressing harmful metabolites, including lipopolysaccharide, thereby ameliorating organ damage via key mechanisms such as the mitigation of oxidative stress and inhibition of inflammatory responses. Furthermore, fucoidan supplementation was found to restore intestinal barrier integrity. Using disease models including Parkinson's disease, alcoholic liver disease, diabetic kidney disease, and obesity, the mechanisms through which fucoidans ameliorate extraintestinal diseases via the microbiota-gut-organ axis were elucidated. Microbiota-dependent mechanisms have been confirmed via experimental approaches such as fecal microbiota transplantation and specific bacterial strain supplementation. Fucoidans represent promising prebiotic agents for the restoration of microbial ecology and the treatment of extraintestinal diseases, highlighting the need for further clinical investigation.},
}

*Polysaccharides/therapeutic use/pharmacology
*Gastrointestinal Microbiome/drug effects
Humans
Animals
Prebiotics
Obesity/drug therapy/microbiology

@article {pmid41462485,
year = {2025},
author = {Wang, D and Chen, Y and Yang, J and Zhang, Y and Deng, X and Liu, Y and Chen, Y and Yang, X and Wang, X and Liang, C and Xie, Q and Hao, Y and Yuan, H},
title = {Modulation of gut microbiota in Graves' orbitopathy: Prevotella dominance and atorvastatin's impact.},
journal = {Microbiome},
volume = {13},
number = {1},
pages = {258},
pmid = {41462485},
issn = {2049-2618},
support = {82270865//National Natural Science Foundation of China under Grant/ ; 231111313200//Henan Provincial Key Research and Development Projects/ ; SBGJ202301001//Henan Provincial Medical Science and Technology Research Program-the Provincial and Ministerial Major Projects/ ; },
mesh = {*Gastrointestinal Microbiome/drug effects ; *Atorvastatin/pharmacology/therapeutic use/administration & dosage ; Humans ; Animals ; Mice ; Male ; Female ; Feces/microbiology ; Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S/genetics ; *Prevotella/drug effects/isolation & purification/genetics ; Middle Aged ; *Graves Ophthalmopathy/microbiology/drug therapy ; Adult ; Glucocorticoids/therapeutic use/administration & dosage ; Anti-Bacterial Agents/pharmacology ; },
abstract = {BACKGROUND: The gut microbiota in patients with Graves' orbitopathy (GO) may influence the disease's progression, but its specific role and function in the progression of GO treatment are not well understood.

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

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

CONCLUSIONS: Gut microbiota imbalance, particularly involving Prevotella, contributes to GO's development and progression. Atorvastatin may slow GO progression by correcting dysregulated gut microbiota, especially reducing Prevotella. Video Abstract.},
}

*Gastrointestinal Microbiome/drug effects
*Atorvastatin/pharmacology/therapeutic use/administration & dosage
Humans
Animals
Mice
Male
Female
Feces/microbiology
Fecal Microbiota Transplantation
RNA, Ribosomal, 16S/genetics
*Prevotella/drug effects/isolation & purification/genetics
Middle Aged
*Graves Ophthalmopathy/microbiology/drug therapy
Adult
Glucocorticoids/therapeutic use/administration & dosage
Anti-Bacterial Agents/pharmacology

@article {pmid41461744,
year = {2025},
author = {Cho, H and Nam, H and Kim, HE and Kim, JE and Park, JI and Park, J and Kim, YC and Lee, JP and Kim, DK and Joo, KW and Kim, YS and Kim, BS and Park, S and Lee, H},
title = {Gut microbiome and metabolite signatures for predicting acute kidney transplant rejection: a prospective study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {44709},
pmid = {41461744},
issn = {2045-2322},
support = {2021R1I1A1A01060190//National Research Foundation grants funded by the Korean government/ ; 2018R1A3B1052328//National Research Foundation grants funded by the Korean government/ ; 2022R1A2C2011190//by National Research Foundation grants funded by the Korean government/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome ; *Kidney Transplantation/adverse effects ; Female ; Male ; Prospective Studies ; Middle Aged ; *Graft Rejection/metabolism/microbiology/diagnosis/etiology ; Adult ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Metabolomics/methods ; Dysbiosis/microbiology ; *Metabolome ; },
abstract = {Acute rejection (AR) remains a significant challenge in kidney transplantation (KT) despite advances in immunosuppressive treatment. Recognizing the critical influence of the gut microbiome on modulating host immunity, we investigated the association between gut dysbiosis and AR in KT recipients. A total of 97 patients with KT were prospectively enrolled from two centers, and their samples were collected at multiple time points, such as pre-transplant (n = 97), three months (n = 66), and twelve months (n = 37) post-transplant. Microbial profiling was performed using 16S rRNA sequencing and fecal metabolomics was done via nuclear magnetic resonance spectroscopy. Thirty-three patients developed AR after KT, exhibiting reduced bacterial richness and diversity compared with KT recipients without AR. In addition, these patients had increased Escherichia-Shigella and decreased Phascolarctobacterium abundance. Pathway analysis identified 47 enriched pathways in AR patients, notably those involved in lipopolysaccharide biosynthesis and short-chain fatty acid metabolism. Consistent results were obtained from stool metabolomics, showing reduced propionate and lactate concentrations compared with patients without AR. Finally, combining pre-KT bacterial and fecal metabolite features with clinical parameters significantly improved AR prediction accuracy. Our results suggest that integrating clinical, microbial, and metabolomic data may provide a more holistic patient care regimen across both pre- and post-transplant phases.},
}

Humans
*Gastrointestinal Microbiome
*Kidney Transplantation/adverse effects
Female
Male
Prospective Studies
Middle Aged
*Graft Rejection/metabolism/microbiology/diagnosis/etiology
Adult
Feces/microbiology
RNA, Ribosomal, 16S/genetics
Metabolomics/methods
Dysbiosis/microbiology
*Metabolome

@article {pmid41461285,
year = {2025},
author = {Bharathi, S and Soundara Rajan, YAPA and Prakash, S and Immanuel, G and Ramasubburayan, R},
title = {Pathobionts in the microbiome: Drivers of disease and targets for treatment.},
journal = {Microbial pathogenesis},
volume = {211},
number = {},
pages = {108268},
doi = {10.1016/j.micpath.2025.108268},
pmid = {41461285},
issn = {1096-1208},
abstract = {Pathobionts are commensal inhabitants of the human microbiome that can transition to a pathogenic state under specific genetic or environmental conditions. They have recently gained attention for their impact on various clinical conditions. This review discusses the key factors behind pathobiont emergence, including microbial dysbiosis, antibiotic use, dietary influences, immune dysfunction and host genetics. It provides a comprehensive overview of pathobionts associated with the gut, oral cavity, and vaginal microbiomes highlighting their roles in disease pathogenesis. A significant focus is also placed on the involvement of pathobiont in immune-related disorders. Furthermore, current and advanced therapeutic strategies aimed at mitigating the effects of pathobionts, such as faecal microbiota transplantation, phage therapy, probiotics and prebiotics, along with their advantages and limitations, were highlighted. Thus, the integrated perspective combining microbial ecology, host immunity, and therapeutic strategies outlines the need for targeted, microbiome-based interventions to address the complex behaviour of pathobionts.},
}

@article {pmid41460363,
year = {2025},
author = {Wang, C and Li, H and Wang, T and Li, X and Liu, J and Deng, A and Jiao, X},
title = {The gut-eye axis in blinding eye diseases: microbiota-driven immune dysregulation and immunomodulatory therapies.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {57},
pmid = {41460363},
issn = {1573-2630},
support = {2024BSQD05//the Doctoral Startup Fund of the Affiliated Hospital of Shandong Second Medical University/ ; ZR2025QC815//the Shandong Provincial Natural Science Foundation/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome/physiology/immunology ; Animals ; Probiotics/therapeutic use ; Dysbiosis ; *Immunomodulation ; *Eye Diseases/therapy/microbiology/immunology ; },
abstract = {PURPOSE: To synthesize recent (2020-2025) advances on how gut, oral, and ocular-surface microbiota contribute to major blinding eye diseases, dry eye disease (DED), non-infectious uveitis, glaucoma, optic neuropathy, age-related macular degeneration (AMD), and diabetic retinopathy (DR), and to evaluate the therapeutic potential of microbiome-based interventions.

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

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

CONCLUSIONS: Microbial dysbiosis acts as a common driver of immune-metabolic dysfunction in blinding eye diseases. Microbiome-targeted strategies show promising efficacy in experimental systems, but large, longitudinal human trials are needed for clinical translation.},
}

Humans
*Gastrointestinal Microbiome/physiology/immunology
Animals
Probiotics/therapeutic use
Dysbiosis
*Immunomodulation
*Eye Diseases/therapy/microbiology/immunology

@article {pmid41459531,
year = {2025},
author = {Nikolaidis, CG and Gyriki, D and Stavropoulou, E and Karlafti, E and Didangelos, T and Tsigalou, C and Thanopoulou, A},
title = {Targeting the TLR4 axis with microbiota-oriented interventions and innovations in diabetes therapy: a narrative review.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1701504},
pmid = {41459531},
issn = {1664-3224},
mesh = {Humans ; *Toll-Like Receptor 4/metabolism/immunology ; *Gastrointestinal Microbiome/immunology/drug effects ; Fecal Microbiota Transplantation ; *Diabetes Mellitus, Type 2/therapy/immunology/microbiology/metabolism ; Animals ; Signal Transduction ; NF-kappa B/metabolism ; *Diabetes Mellitus, Type 1/therapy/immunology/microbiology/metabolism ; Insulin Resistance ; },
abstract = {The gut microbiota-Toll-like receptor 4(TLR4)-nuclear factor kappa B(NF-κB) signaling is a key controller of low-grade chronic inflammation and insulin resistance in type 1 (T1DM) and type 2 diabetes mellitus (T2DM). While TLR4-mediated inflammation contributes to both T1DM and T2DM, the bulk of microbiota-targeted interventions have been studied in T2DM. The focus of the current review is on T2DM, with relevant parallels in T1DM noted where appropriate. Modulation of this pathway by dietary natural bioactive molecules, fecal microbiota transplantation (FMT), and technological innovations hold therapeutic promise for the reconstitution of metabolic and immune homeostasis. Agents like celastrol, berberine, paeoniflorin, and licorice extract exhibit anti-inflammatory and antidiabetic effects by TLR4/Myeloid differentiation primary response 88(MyD88)/NF-κB signaling inhibition. FMT enhanced β-cell function and insulin sensitivity with evidence of immune-metabolic modulation. New technologies, like ingestible biosensors and gut-on-chip platforms, allow real-time monitoring and precision modulating of the microbiota. Gastric bypass-induced microbial remodeling is linked to long-term glycemic benefit. Pharmacological, surgical, and technological manipulation of gut microbiota-immune interactions is a potential complementary strategy to diabetes. The future encompasses personalized microbiota-matching, controlled FMT regimens, and incorporation of digital therapeutics into microbiome-based precision medicine.},
}

Humans
*Toll-Like Receptor 4/metabolism/immunology
*Gastrointestinal Microbiome/immunology/drug effects
Fecal Microbiota Transplantation
*Diabetes Mellitus, Type 2/therapy/immunology/microbiology/metabolism
Animals
Signal Transduction
NF-kappa B/metabolism
*Diabetes Mellitus, Type 1/therapy/immunology/microbiology/metabolism
Insulin Resistance

@article {pmid41415394,
year = {2025},
author = {Barcena-Varela, M and Shang, J and Mogno, I and Lozano, A and Liebling, I and Mead, KR and Li, Z and Grinspan, LT and Lindblad, KE and Ruiz de Galarreta, M and Donne, R and Gnjatic, S and Merad, M and Jun, T and Ang, C and Marron, TU and Faith, J and Lujambio, A},
title = {Bacteroidetes promote hepatocellular carcinoma progression and resistance to immunotherapy.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41415394},
issn = {2692-8205},
support = {S10 OD026880/OD/NIH HHS/United States ; S10 OD030463/OD/NIH HHS/United States ; T32 AI078892/AI/NIAID NIH HHS/United States ; P30 CA196521/CA/NCI NIH HHS/United States ; T32 CA078207/CA/NCI NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; R01 DK124133/DK/NIDDK NIH HHS/United States ; R37 CA230636/CA/NCI NIH HHS/United States ; UL1 TR004419/TR/NCATS NIH HHS/United States ; },
abstract = {BACKGROUND AND AIMS: Growing evidence highlight the critical role of the gut microbiome in tumorigenesis and response to immunotherapies. However, the impact of gut microbes on hepatocellular carcinoma (HCC) progression and response to immune-checkpoint blockade (ICB) remains unclear due to the lack of combined preclinical and clinical studies.

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

CONCLUSIONS: This study identified Bacteroidetes enrichment as a potential biomarker of ICB resistance in HCC and, by using immunogenic mouse models, established that Bacteroidetes abundance influences tumor development.},
}

@article {pmid41459433,
year = {2025},
author = {Bhojiya, AA and Saurabh, A and Jain, D},
title = {Editorial: Microbial therapeutics: harnessing the human microbiome for disease treatment and prevention.},
journal = {Frontiers in medical technology},
volume = {7},
number = {},
pages = {1751147},
doi = {10.3389/fmedt.2025.1751147},
pmid = {41459433},
issn = {2673-3129},
}

@article {pmid41459234,
year = {2025},
author = {Xu, X and Zhang, Y and Zu, Y and Xu, Y and Liao, T and Li, X and Yan, J},
title = {The role of gut microbiota imbalance in preeclampsia pathogenesis: insights into FMO3-mediated inflammatory mechanisms.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1682007},
pmid = {41459234},
issn = {1664-302X},
abstract = {BACKGROUND: Preeclampsia (PE) is a severe pregnancy complication linked to systemic inflammation and metabolic dysregulation. Emerging evidence suggests gut microbiota imbalance may contribute to PE pathogenesis, but the underlying mechanisms remain unclear. This study investigated whether gut dysbiosis triggers PE through flavin-containing monooxygenase 3 (FMO3)-mediated inflammatory pathways.

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

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

CONCLUSION: A disruption of gut microbiota could result in PE through the FMO3-driven inflammatory response, and targeting FMO3 may prove valuable in treating PE.},
}

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

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

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

CONCLUSION: Gut dysbiosis contributes to the development of AR by disrupting immune-metabolic pathways along the gut-lung axis. Microbiota-targeted interventions hold promise for both the prevention and management of AR, especially in pediatric populations. To achieve long-term impact, public health strategies that combine dietary modifications with measures to reduce air pollution are urgently needed.},
}

@article {pmid41458114,
year = {2025},
author = {Pan, D and Li, J and Chen, S and Gu, S and Jiang, M and Xu, Q},
title = {Microbiota-gut-brain axis pathogenesis and targeted therapeutics in sleep disorders.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1721606},
pmid = {41458114},
issn = {1664-2295},
abstract = {Sleep constitutes an essential physiological process that is vital for maintaining physical and mental wellbeing. However, the science of sleep focusing on basic questions such as "how" we sleep and "why" we sleep is still not clear. Over the past decade, substantial progress has also been made in elucidating the interactions between sleep and other biological processes, providing insights into the basic questions of sleep. Among these, emerging evidence highlights the microbiota-gut-brain axis (MGBA) as a pivotal bidirectional network that connects gut microorganisms with the central nervous system to regulate sleep architecture and homeostasis. This interaction is inherently bidirectional: sleep deprivation alters gut motility, mucosal integrity, and microbial composition, while microbial metabolites in turn influence neurotransmission (γ-aminobutyric acid, serotonin), immune-endocrine balance, and inflammatory signaling. In this article, we will review recent studies about MGBA-targeted therapeutic strategies for sleep disorders, such as probiotics, prebiotics, and fecal microbiota transplantation, which aim to restore microbial homeostasis and improve sleep quality. Furthermore, we discuss emerging interventions that modulate microbial metabolites and neuroimmune-endocrine signaling, as well as innovative pharmacological approaches targeting MGBA dysfunction. Collectively, we hope this review will contribute to a deeper understanding of MGBA-mediated mechanisms in sleep disorders promises to inform novel preventive and therapeutic strategies, ultimately improving clinical outcomes and quality of life for affected individuals.},
}

@article {pmid41455148,
year = {2025},
author = {Uoti, A and Neulasalmi, O and Hiippala, K and Oksanen, T and Arkkila, P and Puustinen, L and Satokari, R and Sjöstedt, N},
title = {Characterization of fecal deglucuronidation activity in healthy subjects and in patients treated with fecal microbiota transplantation.},
journal = {Drug metabolism and disposition: the biological fate of chemicals},
volume = {53},
number = {12},
pages = {100205},
doi = {10.1016/j.dmd.2025.100205},
pmid = {41455148},
issn = {1521-009X},
abstract = {Gut bacterial β-glucuronidase (GUS) enzymes contribute to the intestinal toxicity and/or enterohepatic recycling of glucuronidated compounds by cleaving glucuronide conjugates excreted into the intestinal lumen. The activities and substrate specificities of several GUS isoforms have been recently described. However, the extent of intraindividual and interindividual variability in gut microbial deglucuronidation activity has remained poorly characterized. In this study, we used pan-GUS reporter substrates as well as drug and steroid glucuronides to study the deglucuronidation activities of fecal lysates produced from individual fecal samples from healthy donors (n = 12), and sequential samples collected from fecal microbiota transplantation (FMT) donors (n = 3) and patients with recurrent Clostridioides difficile infection who underwent FMT (n = 7). To determine relationships between fecal deglucuronidation activity and gut microbiota composition, we used 16S rRNA gene sequencing to characterize the healthy donors' fecal microbiotas. Although we observed considerable interindividual variability specifically in the processing of steroid glucuronides, intraindividual variability in the fecal deglucuronidation activity of FMT donors was relatively modest. We observed the female sex and Alistipes, Faecalibacterium, and Gemmiger taxa to be associated with higher deglucuronidation activity, whereas the abundance of Roseburia correlated negatively with deglucuronidation activity. In addition, the baseline deglucuronidation activity of patients with recurrent C. difficile infection was low but increased by FMT treatment. The results of this study further highlight deglucuronidation as a function of a healthy gut microbiota. Moreover, these results improve our understanding of deglucuronidation activity as a source of individual variability in the pharmacokinetics and pharmacodynamics of glucuronidated drugs that undergo enterohepatic recycling. SIGNIFICANCE STATEMENT: Gut microbial deglucuronidation rates of specific compounds may vary considerably between individuals. Deglucuronidation activity is relatively stable within healthy individuals for ≥1 year, but fecal microbiota transplantation can significantly alter the deglucuronidation activity of an individual.},
}

@article {pmid41454672,
year = {2026},
author = {Aldriwesh, MG and Alotibi, RS and Alqurainy, N and Alrabiah, S and Arafah, AM and Alghoribi, MF and Ajina, R},
title = {The role of gut microbiome in aging-associated diseases: where do we stand now and how technology will transform the future.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2607076},
doi = {10.1080/19490976.2025.2607076},
pmid = {41454672},
issn = {1949-0984},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Aging ; *Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Animals ; Precision Medicine ; },
abstract = {The gut microbiome has emerged as a critical regulator of human aging and healthspan, with age-related dysbiosis increasingly implicated in a broad spectrum of aging-associated diseases. This review synthesizes evidence linking gut microbial alterations to infectious diseases, antimicrobial resistance, autoimmune, neurodegenerative, psychiatric, cancer, metabolic, kidney, cardiovascular, bone, and muscular diseases, highlighting shared mechanisms such as chronic inflammation, immune dysregulation, and metabolite imbalance. We further explore how enabling technologies, including functional multi-omics, synthetic biology, artificial intelligence-driven analytics, biobanking, and autologous fecal microbiota transplantation, are revolutionizing microbiome research and the design of interventions. Ethical considerations surrounding microbiome-based therapies are also addressed. To translate these scientific insights into clinical innovations, we formulate the PRIME framework: a five-phase roadmap encompassing Profiling, Reviewing, Identifying, Mapping, and Evaluating microbiome-based interventions. By integrating microbiome science, aging biology, and emerging technologies, this review provides a comprehensive blueprint for advancing precision medicine and promoting healthy aging. Furthermore, it emphasizes the importance of building future-ready capabilities to navigate the evolving landscape of age-related diseases and microbiome-driven therapeutic innovations.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Aging
*Dysbiosis/microbiology
Fecal Microbiota Transplantation
Animals
Precision Medicine

@article {pmid41453546,
year = {2025},
author = {Huang, S and Huang, F and Yang, L and Li, J and Qin, B and Zhou, R and Zhou, D and Tang, Y},
title = {Shentao Ruangan Formula Ameliorates Cholestatic Liver Disease via Gut Microbiota Remodeling: Deciphering the "Gan Bing Zhi Pi" Mechanism of Traditional Chinese Medicine Through the Gut-Liver Axis.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {121069},
doi = {10.1016/j.jep.2025.121069},
pmid = {41453546},
issn = {1872-7573},
abstract = {The Shentao Ruangan (STR) formula, developed under Traditional Chinese Medicine (TCM)'s "Gan Bing Zhi Pi" (treating liver via spleen) theory, shows promise in cholestatic liver disease (CLD). TCM's "Pi Xu" (spleen deficiency) in CLD links to gut microbiota dysregulation, but STR's mechanisms remain unclear.

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

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

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

CONCLUSION: STR ameliorates CLD via a microbiota-dependent "Gan Bing Zhi Pi" mechanism. By reshaping the gut microbiota, it coordinates bile acid excretion, repairs intestinal barrier, and suppresses LPS-driven hepatic inflammation to regulate the gut-liver axis. This bridges TCM theory with modern microbiology, validating the therapeutic potential of STR for CLD.},
}

@article {pmid41452713,
year = {2025},
author = {Gong, X and Wang, S and Xia, Q},
title = {The Emerging Triad in Cancer and Aging: Cellular Senescence, Microbiome, and Tumor Microenvironment.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2025.1495},
pmid = {41452713},
issn = {2152-5250},
abstract = {Aging is accompanied by a marked increase in cancer incidence and mortality, yet most studies still consider cellular senescence, the tumor microenvironment, and the microbiome as largely separate axes. Here, we propose an integrative triad framework in aging-related cancers in which cellular senescence, tumor microenvironment (conceptualized here as part of a broader tumor microecology), and the microbiome dynamically interact to shape tumor initiation, evolution, and treatment response. We summarize how senescent cells, via context-dependent senescence-associated secretory phenotypes (SASPs), remodel stromal, immune, and metabolic niches in aging hosts and how gut and intratumoral microbiota both induce and are reshaped by senescence. Focusing on colorectal cancer (CRC), hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC), together with pan-cancer transcriptomic and microbiome analyses. We highlight disease and subtype-specific patterns in which senescence signatures, immune contexture, and microbial features co-stratify prognosis and therapeutic outcomes, and integrate pan-cancer transcriptomic and microbiome analyses to illustrate shared and divergent triad configurations across tumor types. Finally, we discuss the therapeutic implications of this triad, including timing-dependent use of senolytics and senomorphics, diet and microbiome-targeted interventions, fecal microbiota transplantation (FMT), and the ecological risks of antibiotics, particularly in multimorbid older patients. We argue that triad-informed biomarkers and trial designs integrating senescence, microenvironment, and microbiome readouts will be important for mechanism-based, age-adapted cancer prevention and therapy in older adults, especially those with CRC, HCC, and PDAC.},
}

@article {pmid41452451,
year = {2025},
author = {Zhang, X and Li, C and Feng, X and Yuan, X},
title = {The interplay of microbiome, molecular mechanisms, and fertility -an integrated review.},
journal = {Folia microbiologica},
volume = {},
number = {},
pages = {},
pmid = {41452451},
issn = {1874-9356},
support = {LBH-Z21218//Postdoctoral funding of Heilongjiang Province/ ; },
abstract = {The human microbiome, particularly the gut and reproductive tract microbiota, plays a critical role in regulating fertility through complex molecular and immunological mechanisms. This review synthesizes emerging evidence on the bidirectional communication along the gut-reproductive axis, emphasizing how microbial-derived metabolites, such as short-chain fatty acids (butyrate), bile acids, and indoles, modulate systemic inflammation, immune tolerance, hormone metabolism, and energy homeostasis. Dysbiosis, or microbial imbalance, is strongly associated with a range of reproductive pathologies, including polycystic ovary syndrome, endometriosis, premature ovarian insufficiency, impaired spermatogenesis, and recurrent implantation failure. Furthermore, site-specific microbiomes, such as Lactobacillus-dominated vaginal and uterine communities, are vital for successful implantation and pregnancy maintenance. External factors including diet, environmental toxins, and antibiotic use can disrupt these microbial ecosystems, whereas interventions like probiotics like Lactobacillus and Clostridium butyricum, prebiotics, postbiotics, and fecal microbiota transplantation offer promising avenues for restoring microbial and reproductive health. However, translational challenges remain, including methodological heterogeneity in microbiome research and the need to establish causal mechanisms beyond correlation. Future efforts should prioritize multi-omics integration, randomized controlled trials, and personalized microbiome-based diagnostics and therapeutics to effectively address infertility.},
}

@article {pmid41451964,
year = {2025},
author = {Felippe, MFP and Fink, IA and Motta, LCN and de Macêdo Neto, MP and Lopes, JV and Petry, ACG and Sorato, GB and Gonçalves, DP and Maia, GG and Koehler, LB},
title = {Drug Development.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 5},
number = {},
pages = {e107684},
doi = {10.1002/alz70859_107684},
pmid = {41451964},
issn = {1552-5279},
mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Alzheimer Disease/therapy ; *Drug Development ; Gastrointestinal Microbiome ; *Cognitive Dysfunction/therapy ; Clostridium Infections/therapy ; },
abstract = {BACKGROUND: The gut-brain axis plays a crucial role in neurodegenerative diseases, such as Alzheimer's disease (AD). Fecal microbiota transplantation (FMT) has emerged as a potential therapy for AD by restoring microbial balance and reducing neuroinflammation. However, clinical evidence remains limited. This study reviews its potential effects on cognition in AD and other cognitive disorders.

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

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

CONCLUSION: Preliminary evidence suggests FMT may have cognitive benefits in AD patients and recurrent CDI. However, the limited number of studies and the presence of CDI as a common comorbidity highlight the need for larger, controlled trials to better define its role in AD management.},
}

Humans
*Fecal Microbiota Transplantation/methods
*Alzheimer Disease/therapy
*Drug Development
Gastrointestinal Microbiome
*Cognitive Dysfunction/therapy
Clostridium Infections/therapy

@article {pmid41450949,
year = {2025},
author = {Perzon, O and Ilan, Y},
title = {Understanding gut microbial diversity using systems based on the Constrained-Disorder Principle provides a novel approach to targeting gut microbiome therapies.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1713775},
pmid = {41450949},
issn = {1664-302X},
abstract = {BACKGROUND/AIMS: The diverse composition of the gut microbiome is vital for human health, influencing digestion, immune regulation, and disease resistance. While higher diversity is generally associated with resilience, reduced and excessive diversity can lead to health issues.

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

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

CONCLUSION: This platform can pave the way for adaptive, individualized disease prevention and treatment strategies, bridging the gap between microbial ecology and precision medicine. It provides a powerful tool for harnessing the therapeutic potential of gut microbial diversity to enhance human health.},
}

@article {pmid41448004,
year = {2025},
author = {Gao, J and Li, L and Zhang, S and Zhao, H and Feng, B and Liu, C and Wang, X and Li, S and Li, Y and Zhao, D},
title = {Taurodeoxycholic acid alleviates intestinal inflammation by modulating gut microbiota and TGR5-NF-kappaB axis in DSS-induced colitis.},
journal = {International immunopharmacology},
volume = {170},
number = {},
pages = {116056},
doi = {10.1016/j.intimp.2025.116056},
pmid = {41448004},
issn = {1878-1705},
abstract = {Taurodeoxycholic acid (TDCA), a metabolite of cholesterol, has been shown to be able to regulate various inflammatory responses and improve intestinal inflammation. However, its potential to alleviate colitis through modulating the gut microbiota-bile acid axis remains unclear. Mice were simultaneously administered dextran sulfate sodium (DSS) and TDCA via drinking water to estimate the effect of TDCA on colitis. TDCA-treated mice showed markedly relieved DSS-induced colitis. 16S rDNA sequencing revealed TDCA selectively remodeled the gut microbiota, notably decreasing the abundances of Desulfovibrionaceae_unclassified, Escherichia-Shigella and increasing Akkermansia. Furthermore, the reshaping of the microbial community was functionally characterized by a marked alteration in the gut bile acid profile, specifically a significant increase in secondary bile acids. Fecal microbiota transplantation (FMT) confirmed the protective role of the TDCA-shaped microbiota, which also transferred the reduction of Desulfovibrionaceae_unclassified and the characteristic bile acid profile to recipient mice. Similarly, transplanting feces after TDCA intervention into recipient mice still increased secondary bile acid levels in the gut to a certain extent. Spearman's correlation analysis further solidified the negative correlation between Desulfovibrionaceae_unclassified and secondary bile acids. Mechanistically, the altered bile acid profiles restored the activation of the bile acid receptor TGR5, but not FXR, thereby inhibiting the NF-κB signaling pathway. The essential role of TGR5 was substantiated as its inhibitor, SBI-115, largely abolished the protective effects of TDCA. In conclusion, our findings demonstrate that TDCA alleviates colitis by orchestrating a microbiota-bile acid-TGR5 signaling cascade, positioning it as a promising therapeutic candidate for inflammatory bowel disease.},
}

@article {pmid41447836,
year = {2025},
author = {Qiao, Z and Tong, H and Wang, Z and Liu, J and Chen, X and Song, Z and Wang, Y},
title = {Dehydrodiisoeugenol attenuates ulcerative colitis via regulating Anaerostipes caccae-mediated uric acid metabolism.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {150},
number = {},
pages = {157721},
doi = {10.1016/j.phymed.2025.157721},
pmid = {41447836},
issn = {1618-095X},
abstract = {BACKGROUND: The gut microbiota plays a crucial role in the pathogenesis of ulcerative colitis (UC). Dehydrodiisoeugenol (DEH) is a major benzofuran-type neolignane isolated from Myristica fragrans Houtt., a plant whose fruit has been incorporated into traditional Chinese medicine (TCM) formulations for clinical treatment of gastrointestinal disorders. However, the pharmacological mechanisms underlying the anti-colitic efficacy of DEH remain to be elucidated.

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

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

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

CONCLUSION: Our study highlights that the A. caccae-mediated maintenance of UA metabolic homeostasis restrains UC pathogenesis, a process that is the core mechanism through which DEH exerts its anti-colitic efficacy.},
}

@article {pmid41445729,
year = {2025},
author = {Yu, S and Zhang, M and Dou, Z and Tian, B and Lu, J},
title = {Gut microbiota metabolites in the immunoregulation of enteritis: research progress.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1706472},
pmid = {41445729},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Enteritis/immunology/metabolism/microbiology/therapy ; Animals ; Immunomodulation ; Bile Acids and Salts/metabolism ; Fatty Acids, Volatile/metabolism ; Probiotics ; },
abstract = {The interaction between gut microbiota metabolites and the host immune system plays a crucial role in maintaining intestinal homeostasis and in the development of inflammatory bowel disease and other enteric conditions. This article presents a systematic review of the sources and functions of short-chain fatty acids, tryptophan metabolites, bile acids, and other microbial metabolites, focusing on how these metabolites regulate the function of immune cells, such as T cells, B cells, neutrophils, macrophages, and dendritic cells, as well as key inflammatory signaling pathways, including the NF-κB, NLRP3 inflammasome, and JAK-STAT pathways, thereby influencing intestinal barrier integrity. Also explored are potential therapeutic strategies based on microbial metabolites, including the application status and prospects of probiotic and prebiotic interventions, the direct administration of metabolites, and fecal microbiota transplantation. Although current research faces challenges such as unclear mechanisms, significant differences among individuals, and barriers to clinical translation, the development of multiomics technologies and precision medicine holds promise for providing more effective and personalized treatment strategies targeting gut microbiota metabolites for patients with enteritis.},
}

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

@article {pmid41445292,
year = {2025},
author = {Govindarajan, M and Aware, C and Ivanich, K and Pathak, I and Zhu, Y and Balchandani, P and Davis, D and Ericsson, A and Ma, L and Lin, AL},
title = {Basic Science and Pathogenesis.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 1},
number = {},
pages = {e105884},
doi = {10.1002/alz70855_105884},
pmid = {41445292},
issn = {1552-5279},
mesh = {Animals ; Mice ; *Alzheimer Disease/microbiology ; *Nitric Oxide Synthase Type II/genetics ; Humans ; *Gastrointestinal Microbiome ; Disease Models, Animal ; *Cognitive Dysfunction/microbiology ; Mice, Knockout ; *Dysbiosis ; Male ; Aged ; Fecal Microbiota Transplantation ; Female ; Cerebrovascular Circulation ; Mice, Transgenic ; Middle Aged ; Aged, 80 and over ; },
abstract = {BACKGROUND: Inducible Nitric Oxide Synthase (iNOS) is implicated in exacerbating Alzheimer's Disease (AD) mechanisms. The relationship between imbalanced gut microbiota composition (dysbiosis) and AD pathology is well characterized. Many gut bacteria, including E. Coli induce iNOS production, potentially contributing to AD development. To investigate the antagonistic role of iNOS, we created a novel iNOS knockout (iNOS-KO) mouse model using the 3xTg-AD mouse model background and performed fecal microbiome transplantation (FMT) to iNOS-KO/3xTg-AD mice from mild cognitive impairment (MCI) patients and age-matched healthy controls (HC). We aim to determine, whether iNOS-KO can protect cerebral blood flow (CBF), an early marker of AD progression, despite dysbiosis induced by FMT from MCI donors.

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

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

CONCLUSION: We observe that MCI patients had higher gut dysbiosis than HC. However, despite increased dysbiosis, iNOS-KO may preserve CBF and mitigate AD-like symptoms, highlighting its potential neuroprotective role in the 3xTg-AD model. Future studies should investigate the impact of iNOS-KO on mitigating AD pathology, such as amyloid-β and tau accumulation, or preserving cognitive functions. Our preliminary data shows that iNOS could be a potential target to ameliorate AD risk.},
}

Animals
Mice
*Alzheimer Disease/microbiology
*Nitric Oxide Synthase Type II/genetics
Humans
*Gastrointestinal Microbiome
Disease Models, Animal
*Cognitive Dysfunction/microbiology
Mice, Knockout
*Dysbiosis
Male
Aged
Fecal Microbiota Transplantation
Female
Cerebrovascular Circulation
Mice, Transgenic
Middle Aged
Aged, 80 and over

@article {pmid41444705,
year = {2025},
author = {Oladele, P and Dong, W and Richert, BT and Johnson, TA},
title = {Route of fecal microbiota transplantation delivery determined the dynamics and predictability of donor microbe colonization.},
journal = {Animal microbiome},
volume = {7},
number = {1},
pages = {130},
pmid = {41444705},
issn = {2524-4671},
support = {ICASASHTWG0000000082//Foundation for Food and Agriculture Research,United States/ ; },
abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) and the colonization of delivered donor microbes has been reported to improve the negative effects (decrease in body weight, diarrhea, and gut barrier disruption) associated with weaning in pigs. However, delivery of FMT in pigs is still invasive and predicting the colonization or rejection of donor microbes remains challenging. Therefore, this study developed a non-invasive in-feed delivery of FMT and evaluated the effect of FMT mode of delivery on growth performance, gut physiology, microbiota dynamics, and predictability of colonization or rejection of donor microbes in recipient pigs. Forty weaned piglets (10 per group) were administered FMT through one of three routes; oral, rectal, or amended in-feed. The control group was orally administered sterile saline to simulate handling stress.

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

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

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42523-025-00495-9.},
}

@article {pmid41443865,
year = {2025},
author = {Takeda, T and Hojo, M and Asaoka, D and Nagahara, A},
title = {Targeting Gut Microbiota in the Management of Functional Constipation: A Narrative Review.},
journal = {Internal medicine (Tokyo, Japan)},
volume = {},
number = {},
pages = {},
doi = {10.2169/internalmedicine.6457-25},
pmid = {41443865},
issn = {1349-7235},
abstract = {Functional constipation (FC) is a prevalent gastrointestinal disorder that negatively affects the quality of life. Recent studies have suggested that the gut microbiota plays a key role in the pathophysiology of FC, with dysbiosis, reduced diversity, and altered production of short-chain fatty acids that influence intestinal motility. Probiotics have shown potential for improving bowel movements and related symptoms in adults with FC. However, clinical outcomes vary depending on strain, dosage, and study design. Fecal microbiota transplantation has also emerged as a promising treatment, demonstrating improved stool frequency and colonic transit in selected patients. This narrative review summarizes the current understanding of the relationship between gut microbiota and FC and highlights the therapeutic potential of probiotics and fecal microbiota transplantation. Further research is warranted to clarify the underlying mechanisms and optimize microbiota-targeted interventions for effective management of FC.},
}