@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.},
}

@article {pmid41440851,
year = {2025},
author = {Tao, Y and Zhang, N and Wang, Z and Pan, Y and Zhong, S and Liu, H},
title = {SGLT2 Inhibitors Confer Cardiovascular Protection via the Gut-Kidney-Heart Axis: Mechanisms and Translational Perspectives.},
journal = {Journal of cardiovascular development and disease},
volume = {12},
number = {12},
pages = {},
doi = {10.3390/jcdd12120471},
pmid = {41440851},
issn = {2308-3425},
abstract = {Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated significant cardiovascular and renal benefits beyond glycemic control, yet their integrated mechanisms remain incompletely understood. Emerging evidence highlights the gut-kidney-heart axis as a pivotal pathological network, wherein gut dysbiosis, toxic metabolite accumulation, intestinal barrier disruption, and systemic inflammation synergistically drive cardiorenal injury. This review systematically elucidates how SGLT2i modulate this axis through multi-level interventions: reshaping gut microbiota composition, enriching short-chain fatty acid-producing bacteria, suppressing trimethylamine and other toxin-generating microbes, restoring tight junction integrity, and regulating bile acid metabolism. These upstream effects reduce systemic inflammatory and metabolic stress, interrupt kidney-derived toxin amplification, and mitigate myocardial remodeling. Unlike previous reviews focusing on single-organ pathways, this work integrates microecological regulation, metabolite reprogramming, and cross-organ protection into a unified "three-axis convergence to the heart" framework. We also highlight potential species-specific microbiota regulatory profiles among different SGLT2i and propose future directions, including fecal microbiota transplantation and microbiota-targeted co-therapies, to clarify causal relationships and optimize therapeutic strategies. By positioning the gut as a modifiable upstream driver, this framework provides novel mechanistic insight and translational potential for expanding SGLT2i applications in metabolic cardiovascular disease, including in non-diabetic populations.},
}

@article {pmid41440729,
year = {2025},
author = {Hirji, I and John, D and Jith, J and Khoshnaw, H and Ganeshananthan, M},
title = {Challenges and Strategies in Managing Recurrent Clostridioides difficile Infection in Older Adults.},
journal = {Geriatrics (Basel, Switzerland)},
volume = {10},
number = {6},
pages = {},
doi = {10.3390/geriatrics10060158},
pmid = {41440729},
issn = {2308-3417},
abstract = {BACKGROUND: Clostridioides difficile infections (CDIs) are caused by a Gram-positive, spore-forming bacillus and are defined by more than three episodes of watery diarrhoea per day. CDI is a major cause of morbidity and mortality in older adults, particularly over 65 years. Recurrent CDI leads to higher mortality and prolonged, debilitating illness.

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

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

CONCLUSIONS: Recurrent CDI in elderly patients reflects a complex interplay between infection control and managing comorbidities. New guidelines suggest that FMTs can significantly reduce morbidity and mortality. These cases emphasise the need for individualised, multidisciplinary care, adherence to guidelines, and further research to improve safe, effective CDI management in older adults.},
}

@article {pmid41440201,
year = {2025},
author = {Ye, G and Zhang, H and Feng, Q and Xiao, J and Wang, J and Liu, J},
title = {Important Role of Bacterial Metabolites in Development and Adjuvant Therapy for Hepatocellular Carcinoma.},
journal = {Current oncology (Toronto, Ont.)},
volume = {32},
number = {12},
pages = {},
doi = {10.3390/curroncol32120673},
pmid = {41440201},
issn = {1718-7729},
support = {2021ZQNZD009//Major Scientiffc Research Program for Young and Middle-aged Health Professionals of Fujian Province, China/ ; 2023Y9416//Fujian Science and Technology Innovation Joint Fund Project/ ; },
mesh = {Humans ; *Carcinoma, Hepatocellular/therapy/microbiology/immunology/metabolism ; *Liver Neoplasms/therapy/microbiology/immunology/metabolism ; *Bacteria/metabolism ; Tumor Microenvironment/immunology ; Animals ; },
abstract = {Bacterial metabolites play a dual role in hepatocellular carcinoma (HCC), exhibiting both tumor-promoting and tumor-suppressing activities dictated by their structural diversity. This review synthesizes recent advances in understanding how key microbial metabolites-such as bile acids, short-chain fatty acids, and polyamines-remodel the tumor immune microenvironment through mechanisms including immunometabolic reprogramming, epigenetic modification, and regulation of signaling pathways (e.g., FXR, TLR, and mTOR). We highlight their roles in modulating the function of T cells, NK cells, and tumor-associated macrophages and discuss emerging strategies that target these metabolites-including probiotic interventions, fecal microbiota transplantation, and metabolite-based adjuvants-to enhance immunotherapy efficacy and overcome resistance. By integrating mechanistic insight into translational potential, this work outlines a metabolite-immunometabolism-hepatocarcinogenesis framework and proposes novel combinatorial approaches for HCC treatment.},
}

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

@article {pmid41439979,
year = {2025},
author = {Mostafavi Abdolmaleky, H and Pirani, A and Pettinato, G},
title = {Psychosomatic Disorders, Epigenome, and Gut Microbiota.},
journal = {Cells},
volume = {14},
number = {24},
pages = {},
doi = {10.3390/cells14241959},
pmid = {41439979},
issn = {2073-4409},
mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Epigenome/genetics ; *Psychophysiologic Disorders/genetics/microbiology ; Animals ; *Epigenesis, Genetic ; },
abstract = {Psychosomatic disorders are conditions in which physical (somatic) symptoms are triggered or aggravated by psychological distress. These disorders result from complex interactions among the endocrine, central nervous, and immune systems. Emerging evidence indicates that gut microbiota (GM) dysbiosis, epigenetic alterations, and immune system dysregulation play pivotal roles in the pathogenesis of psychosomatic disorders and may serve as potential biomarkers for disease states and therapeutic outcomes. This review first outlines how epigenetic dysregulation contributes to psychosomatic disorders through altered expression of genes such as GRM2, TRPA1, SLC6A4, NR3C1, leptin, BDNF, NAT15, HDAC4, PRKCA, RTN1, PRKG1, and HDAC7. We then examine current evidence linking psychosomatic disorders with changes in GM composition and GM-derived epigenetic metabolites, which influence immune function and neurobiological pathways. The core focus of this review is on therapeutic interventions-including probiotics, prebiotics, postbiotics, fecal microbiota transplantation, and targeted dietary approaches-that modulate the gut-brain axis through epigenetic mechanisms for the management of psychosomatic disorders. Finally, we highlight the current challenges and future directions in elucidating the interplay between epigenetics, the GM, and psychosomatic disease mechanisms. In this context, human iPSC-derived multicellular organoids may serve as powerful platforms to unravel mechanistic pathways underlying inter-organ interactions.},
}

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

@article {pmid41439929,
year = {2025},
author = {Geladari, EV and Kalergi, AC and Evangelopoulos, AA and Sevastianos, VA},
title = {Sepsis and the Liver.},
journal = {Diseases (Basel, Switzerland)},
volume = {13},
number = {12},
pages = {},
doi = {10.3390/diseases13120388},
pmid = {41439929},
issn = {2079-9721},
abstract = {BACKGROUND/OBJECTIVES: Sepsis-associated liver injury (SALI) is a critical and often early complication of sepsis, defined by distinct hyper-inflammatory and immunosuppressive phases that shape patient phenotypes.

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

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

CONCLUSION: Future research should focus on developing representative models, validating biomarkers, and conducting clinical trials to enable personalized therapies that modulate inflammation, restore metabolism, and repair the gut-liver axis, with the goal of improving outcomes in SALI.},
}

@article {pmid41439481,
year = {2026},
author = {Zou, Y and Li, N and Li, X and Kuang, M and Xu, X and Guan, L and Li, X and Zheng, P and Li, L and Wan, J and Lu, N and Liu, J and He, C and Zhu, Y},
title = {Gut microbiota dysbiosis exacerbates acute pancreatitis via Escherichia coli-driven neutrophil heterogeneity and NETosis.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2606480},
doi = {10.1080/19490976.2025.2606480},
pmid = {41439481},
issn = {1949-0984},
mesh = {Animals ; *Dysbiosis/microbiology/immunology/complications ; *Gastrointestinal Microbiome ; Mice ; Humans ; *Neutrophils/immunology ; *Extracellular Traps/immunology/metabolism ; *Escherichia coli/physiology ; *Pancreatitis/microbiology/immunology/pathology ; Male ; Mice, Inbred C57BL ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; Specific Pathogen-Free Organisms ; },
abstract = {Gut microbiota dysbiosis contributes to acute pancreatitis (AP) severity, but the specific microbes and mechanisms remain unclear. In this study, we employed both germ-free (GF) and specific-pathogen-free (SPF) murine models of AP to investigate the role of the intestinal microbiota. Our findings demonstrate that GF mice exhibited markedly attenuated pancreatic injury, inflammatory cell infiltration, and neutrophil extracellular traps (NETs) formation. Through fecal microbiota transplantation (FMT) from AP patients, differential antibiotic modulation, and single-bacterial colonization experiments, we identified Gram-negative bacteria, particularly Escherichia coli (E. coli), as critical microbial drivers of disease exacerbation. Single-cell RNA sequencing revealed that microbiota dysbiosis profoundly reprogrammed both local pancreatic and systemic immune landscapes. Specifically, dysbiosis promoted emergency granulopoiesis in the bone marrow, enhanced neutrophil mobilization and activation, and facilitated the expansion of pro-inflammatory neutrophil subpopulations (Neutrophils_2 and Neutrophils_3). These subsets exhibited upregulated signaling through NETosis-associated pathways, including TLR, NF-κB, and IL-17 axes. Conversely, in GF conditions, we observed a predominance of an anti-inflammatory neutrophil subset (Neutrophils_4), characterized by the expression of tissue repair-associated genes such as Reg1 and Reg2. Shotgun metagenomic profiling of fecal samples from patients with AP revealed an enrichment of E. coli during the acute phase, positively correlating with circulating cell-free DNA, a marker of NETosis. Together, these insights suggest that gut microbiota dysbiosis, notably increased E. coli abundance, may aggravate AP by reshaping immunity and promoting aberrant NETs formation, supporting microbiota or NETs targeted therapies.},
}

Animals
*Dysbiosis/microbiology/immunology/complications
*Gastrointestinal Microbiome
Mice
Humans
*Neutrophils/immunology
*Extracellular Traps/immunology/metabolism
*Escherichia coli/physiology
*Pancreatitis/microbiology/immunology/pathology
Male
Mice, Inbred C57BL
Disease Models, Animal
Fecal Microbiota Transplantation
Female
Specific Pathogen-Free Organisms

@article {pmid41439235,
year = {2026},
author = {Zou, B and Huo, Q and Zhou, X and Lv, Y and Li, G and Fu, G and Shen, H and Shu, S},
title = {Characteristics and longitudinal stability of Gut Microbiota in healthy individuals across different age groups.},
journal = {Current research in microbial sciences},
volume = {10},
number = {},
pages = {100512},
pmid = {41439235},
issn = {2666-5174},
abstract = {Fecal microbiota transplantation (FMT) efficacy relies on donor microbiome composition and temporal stability, yet the influence of donor age remains inadequately investigated. This longitudinal analysis addressed this gap by examining 81 healthy individuals (3-30 years), stratified into four age groups, who provided monthly fecal samples over 12 months (n = 972 samples). Gut microbiota composition (16S rDNA sequencing) and temporal stability were assessed using Bray-Curtis dissimilarity, intraclass correlation coefficient (ICC), and genus-level co-occurrence network analysis. Results demonstrated a strong age-dependency in microbiota stability. The teenage cohort (13-17 years) exhibited the highest stability, characterized by minimal fluctuations in α- and β-diversity and significantly stronger network centrality. Furthermore, specific genera, notably Faecalibacterium and Bifidobacterium, displayed exceptionally high ICC values (>0.90), identifying them as core taxa associated with temporal consistency. These findings underscore the critical role of donor age in microbial stability and highlight teenagers as possessing optimal microbiota characteristics for FMT. They strongly support the development of an ICC-based screening framework to enhance donor selection protocols.},
}

@article {pmid41439197,
year = {2025},
author = {Liang, J and Qiu, Y and Fu, T and Li, J and Yang, J and Tong, Y},
title = {The Gut-Kidney Axis in Uric Acid Nephropathy: Microbiota, Metabolic Crosstalk, and Translational Prospects.},
journal = {Journal of multidisciplinary healthcare},
volume = {18},
number = {},
pages = {8111-8132},
pmid = {41439197},
issn = {1178-2390},
abstract = {Uric acid nephropathy (UAN) represents a critical and multifactorial renal disorder closely linked to hyperuricemia, inflammation, and gut microbiota dysregulation. Recent advances have revealed the pivotal role of the gut-kidney axis in modulating urate metabolism, immune activation, and oxidative stress. This review synthesizes emerging preclinical and clinical evidence to construct an integrative framework for understanding UAN, highlighting both crystal-dependent and crystal-independent mechanisms that drive tubular injury and fibrosis. Accumulating data underscore the reciprocal crosstalk between renal dysfunction and gut dysbiosis, mediated by microbial metabolites such as short-chain fatty acids (SCFAs), indoxyl sulfate, and p-cresol sulfate. We further evaluate therapeutic interventions targeting the gut-kidney axis-including probiotics, synbiotics, postbiotics, fecal microbiota transplantation (FMT), and engineered microbial therapies-which have shown promise in restoring microbial balance and improving urate handling. By integrating multi-omics profiling with systems biology, this review proposes a precision-medicine roadmap that leverages microbiome signatures and metabolic phenotyping for risk stratification and personalized intervention. Moreover, we emphasize the need for supportive regulatory frameworks and interdisciplinary collaboration to enable the clinical translation of microbiota-based strategies. Collectively, this work provides a strengthened conceptual foundation for microbiome-informed prevention and treatment of uric acid-related kidney disease.},
}

@article {pmid41438742,
year = {2025},
author = {Chen, PJ and Devkota, S and Shiao, S and Hendifar, A and Yang, JD},
title = {Gut microbiome, a novel precision medicine biomarker for hepatocellular carcinoma.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1568962},
pmid = {41438742},
issn = {1664-3224},
mesh = {Humans ; *Carcinoma, Hepatocellular/therapy/immunology/microbiology/metabolism ; *Liver Neoplasms/therapy/immunology/microbiology/metabolism ; *Gastrointestinal Microbiome/immunology ; Precision Medicine/methods ; Biomarkers, Tumor ; Animals ; Immune Checkpoint Inhibitors/therapeutic use ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Immunotherapy/methods ; },
abstract = {Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors (ICIs) have transformed systemic therapy, durable responses are achieved in only a subset of patients, highlighting the need for reliable predictive biomarkers. The gut-liver axis, a bidirectional network linking intestinal microbiota, microbial metabolites, and hepatic immune pathways, has emerged as a key regulator of liver immunity and tumor progression. Growing evidence indicates that the gut microbiome modulates ICI efficacy by shaping immune activation, cytokine signaling, and drug metabolism. This review summarizes current insights into how gut microbial composition and metabolites influence immunotherapy outcomes in HCC and discusses microbiome-targeted strategies, including fecal microbiota transplantation (FMT), prebiotics, probiotics, and dietary interventions. Further research and clinical validation are needed before these insights can be effectively integrated into HCC management.},
}

Humans
*Carcinoma, Hepatocellular/therapy/immunology/microbiology/metabolism
*Liver Neoplasms/therapy/immunology/microbiology/metabolism
*Gastrointestinal Microbiome/immunology
Precision Medicine/methods
Biomarkers, Tumor
Animals
Immune Checkpoint Inhibitors/therapeutic use
Probiotics/therapeutic use
Fecal Microbiota Transplantation
Immunotherapy/methods

@article {pmid41438381,
year = {2025},
author = {Chen, X and Zhang, Y and Zhang, G and Wang, D and Dou, L and Wang, Y and Huang, Z and Liu, X},
title = {Spatial microbiome-metabolic crosstalk drives CD8[+] T-cell exhaustion through the butyrate-HDAC axis in colorectal cancer.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1704491},
pmid = {41438381},
issn = {1664-302X},
abstract = {BACKGROUND: The spatial organization of intratumoral microbiota and its metabolic impact on immunotherapy response in colorectal cancer (CRC) is unclear, limiting targeted interventions.

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

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

CONCLUSION: Our study unveils a spatially defined, microbiome-driven metabolic niche that epigenetically programs CD8[+] T-cell exhaustion via the butyrate-HDAC axis, revealing a targetable mechanism to overcome immunotherapy resistance in CRC.},
}

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

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

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

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

CLINICAL TRIAL NUMBER: NCT03056612.

IMPACT AND IMPLICATIONS: The human gut virome is a poorly investigated part of the human gut microbiome, especially in the context of decompensated cirrhosis and acute-on-chronic liver failure. This study identified two phage groups (Lactococcus A phages and Enterococcus B phages) with particular prognostic value. In the future, virome analysis of fecal samples could be useful for patient stratification in clinical practice.},
}

@article {pmid41437855,
year = {2025},
author = {Aware, C and Govindarajan, M and Ivanich, K and Ericsson, A and Gu, Z and Cui, J and Zuckerman, A and Ma, L and Lin, AL},
title = {Basic Science and Pathogenesis.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 1},
number = {},
pages = {e106078},
doi = {10.1002/alz70855_106078},
pmid = {41437855},
issn = {1552-5279},
mesh = {Animals ; Mice ; Male ; Female ; Humans ; Aged ; *Alzheimer Disease/pathology/metabolism ; Mice, Transgenic ; Middle Aged ; Fecal Microbiota Transplantation ; *Dysbiosis ; Aged, 80 and over ; *Brain/metabolism/pathology ; Disease Models, Animal ; Gastrointestinal Microbiome ; *Stroke/complications ; },
abstract = {BACKGROUND: Stroke increases the risk of Alzheimer's disease (AD), but underlying mechanisms remain unclear. This study investigates whether gut dysbiosis (imbalance in gut microbes) from acute ischemic stroke worsens AD pathology. Using fecal microbiota transplantation (FMT) from stroke patients into 3xTg-AD mice, we examine its impact on neuroinflammation and AD markers (Total Tau, GFAP, and IBA1). By integrating immunohistochemistry (IHC) and single-cell spatial transcriptomics, we assess dysbiosis-driven changes in neuroinflammation, AD pathology, cell typing, and targeted gene expression in the brain to elucidate the gut-brain axis and explore therapeutic strategies.

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

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

CONCLUSION: Stroke donor FMT-induced gut dysbiosis exacerbates AD pathology, emphasizing the critical role of the gut-brain axis in linking stroke and AD. Targeting gut dysbiosis may offer a novel therapeutic strategy for stroke-related AD progression.},
}

Animals
Mice
Male
Female
Humans
Aged
*Alzheimer Disease/pathology/metabolism
Mice, Transgenic
Middle Aged
Fecal Microbiota Transplantation
*Dysbiosis
Aged, 80 and over
*Brain/metabolism/pathology
Disease Models, Animal
Gastrointestinal Microbiome
*Stroke/complications

@article {pmid41437305,
year = {2025},
author = {Gong, Z and Zou, J and Fang, Y and Li, J and Luo, Y and Xue, Q and Yu, B and Hua, B and Liu, Z},
title = {The role of gut microbiota in neuropathic pain: insights into immune mechanisms.},
journal = {The journal of headache and pain},
volume = {},
number = {},
pages = {},
doi = {10.1186/s10194-025-02260-4},
pmid = {41437305},
issn = {1129-2377},
abstract = {Neuropathic pain (NP), characterized by its complex pathophysiological mechanisms, has long posed a formidable therapeutic challenge. The burden of NP is further exacerbated by the increasing prevalence of chronic diseases. Emerging evidence highlights the pivotal role of gut microbiota in modulating immune responses, offering novel insights into NP pathogenesis. This review explores recent advancements in understanding how gut microbiota-derived metabolites - including short-chain fatty acids (SCFAs), bile acids, and tryptophan derivatives - regulate immune processes that influence neuroinflammation and nociceptive signaling. We focus on key immune mediators, including macrophages, microglia, T cells, and astrocytes, elucidating their involvement in microbiota-driven immune regulation via pathways such as TLR4/NF-κB signaling, histone deacetylase (HDAC) inhibition, and aryl hydrocarbon receptor (AhR) activation. Additionally, we examine emerging evidence of sex-specific immune mechanisms in NP. Despite promising preclinical findings on microbiota-targeted therapies, such as probiotics and fecal microbiota transplantation, translational challenges, such as microbiota heterogeneity and sex-specific responses, necessitate further investigation. This review aims to bridge microbiology, neuroimmunology, and pain research, offering a multidimensional perspective and actionable insights for the future management of NP.},
}

@article {pmid41436018,
year = {2025},
author = {Yue, CB and Luan, WW and Qiu, D and Ding, X and Gu, HW and Liu, PM and Hashimoto, K and Yang, JJ and Wang, XM},
title = {A vagus-dependent gut microbiota-metabolite axis drives chronic inflammatory pain and working-memory deficits in mice.},
journal = {Brain research bulletin},
volume = {},
number = {},
pages = {111702},
doi = {10.1016/j.brainresbull.2025.111702},
pmid = {41436018},
issn = {1873-2747},
abstract = {Chronic inflammatory pain (CIP) has been increasingly linked to gut microbiota (GM)-brain interactions, yet whether these effects rely on vagal signaling remains unclear. Here, we investigated whether GM from CIP mice is sufficient to transfer pain-like behaviors to healthy recipients and whether this process depends on the vagus nerve. Fecal microbiota transplantation (FMT) from mice treated with complete Freund's adjuvant induced mechanical and thermal hypersensitivity and impaired working memory in recipients, accompanied by hippocampal neuroinflammation and GM dysbiosis. Subdiaphragmatic vagotomy (SDV) performed prior to FMT attenuated these behavioral and neuroinflammatory alterations and partially normalized microbial community structure. Plasma metabolomics further showed that SDV restored phosphatidylcholines while reducing pro-inflammatory lipid classes, with several metabolites and bacterial taxa correlating significantly with pain sensitivity and hippocampal cytokine levels. Collectively, these findings demonstrate that a vagus-dependent GM-metabolite-brain axis contributes to CIP-like behaviors and neuroinflammation. Targeting vagal pathways and GM-regulated lipid metabolism may offer therapeutic strategies and pharmacodynamic biomarkers for inflammatory pain.},
}

@article {pmid41431379,
year = {2026},
author = {Al-Btoosh, S and Donnelly, RF and Kelly, SA},
title = {Microbes and medicines: interrelationships between pharmaceuticals and the gut microbiome.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2604867},
doi = {10.1080/19490976.2025.2604867},
pmid = {41431379},
issn = {1949-0984},
mesh = {*Gastrointestinal Microbiome/drug effects ; Humans ; Animals ; Probiotics ; *Bacteria/drug effects/metabolism/classification/genetics ; Fecal Microbiota Transplantation ; Pharmaceutical Preparations/metabolism ; Prebiotics ; Biotransformation ; },
abstract = {The human gut microbiome plays a critical role in modulating pharmacological and toxicological responses to medications. With a gene pool vastly exceeding that of the human host, the gut microbiome acts as a metabolically active organ capable of transforming, inactivating, or accumulating drugs. This review explores the bidirectional interplay between prescription medicines and the gut microbiome, encompassing three key mechanisms: direct biotransformation by microbial enzymes, indirect modulation of host metabolism and signaling pathways, and drug bioaccumulation within microbial cells. Particular attention is given to six major drug classes: immunotherapeutics, chemotherapeutics, antidepressants, statins, hypoglycemics, and antihypertensives. The ways in which individual microbial profiles can influence therapeutic outcomes are also reviewed. We examined how common non-antibiotic pharmaceuticals can significantly alter microbial diversity and promote antimicrobial resistance. Strategies to enhance drug efficacy through microbiome modulation, including probiotics, prebiotics, and fecal microbiota transplantation (FMT), are critically assessed. Experimental models ranging from in vitro batch and chemostat systems to animal and clinical studies are compared in terms of their utility for studying drug‒microbiome interactions. Finally, emerging evidence suggesting the gut microbiota composition may serve as a predictive biomarker for personalized medicine and therapeutic success is highlighted. Understanding and harnessing the complex interrelationships between medicines and microorganisms could offer novel avenues to optimize treatment outcomes and mitigate adverse drug effects.},
}

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

@article {pmid41430282,
year = {2025},
author = {He, Y and Zhang, Y and Zhao, L and Zhou, Z and Su, N and Zhang, C and Wang, K and Jin, L and Yang, B and Hu, X and Fu, Y},
title = {Vagus nerve stimulation alleviates S. aureus-induced mastitis by regulating gut microbiota S24-7-PPARγ and NF-ΚB/NLRP3 signaling in mice.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-025-03654-6},
pmid = {41430282},
issn = {1742-2094},
support = {212558JC010286222//Jilin Province Department of Science and Technology/ ; 32422086//the National Natural Science Foundation of China/ ; 32301247//the National Natural Science Foundation of China/ ; },
abstract = {Gut microbiota dysbiosis has been implicated in the pathogenesis of mastitis. While the vagus nerve exerts well-documented anti-inflammatory effects and modulates gut microbiota, its potential influence on mastitis progression via gut microbiota modulation remains unclear. To investigate this, we employed vagus nerve stimulation (VNS) in Staphylococcus aureus (S. aureus)-induced mastitis in mice. We demonstrate that VNS significantly attenuated mammary gland inflammation and restored epithelial barrier integrity following S. aureus challenge. Crucially, antibiotic depletion of the gut microbiota abrogated the protective effects of VNS, and fecal microbiota transplantation (FMT) from VNS-treated mice conferred protection against mastitis, establishing a causal role for the gut microbiota in mediating the VNS effect. Specifically, VNS markedly increased the abundance of Muribaculaceae. in the gut. Replenishment with S24-7, a representative strain of this genus, alleviated S. aureus-induced mammary gland inflammation in mice. Transcriptomic analysis revealed that S24-7 exerted its effects by activating peroxisome proliferator-activated receptor gamma (PPARγ), which subsequently suppressed the NF-κB/NLRP3 signaling pathway. Overall, our findings suggest that targeting the vagus nerve - mediated Muribaculaceae/PPARγ axis may represent a promising strategy for mastitis treatment.},
}

@article {pmid41429881,
year = {2025},
author = {Hanzely, P and Holm, K and Bjørnholt, JV and Melum, E and Hov, JR and Rasmussen, H},
title = {Efficacy of oral and rectal administration of human faecal microbiota transplant (FMT) in human microbiota-associated mouse models.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-32072-0},
pmid = {41429881},
issn = {2045-2322},
support = {802544/ERC_/European Research Council/International ; },
abstract = {The gut microbiome has gained significant interest due to its association with immune dysregulation, allergies, autoimmune conditions, metabolic disorders, and inflammation-associated malignancies. Understanding underlying mechanisms requires appropriate in vivo models, such as human microbiota-associated mouse models to study the microbiota-host interactions. This study compared the efficacy of oral and rectal administration of human faecal microbiota transplant (FMT) from a single donor in C57BL/6J germ-free mice as these methods are often used interchangeably. Using 16S rRNA sequencing, we quantified colonisation efficacy in luminal and tissue samples from orally- (n = 6) and rectally- (n = 6) colonised mice. We detected 84 genera in the FMT sample, 17 of which were not transferred at all, while additional 7 genera were found exclusively in rectally-colonised mice. A significantly higher proportion of amplicon sequence variants (ASVs) (33% vs. 26%; P < 0.05) and genera (32% vs. 25%; P < 0.05) were absent in orally- compared to rectally-colonised group. Some taxa showed different relative abundances in human vs. mouse samples (e.g. Alistipes and Bacteroides relatively more abundant in mice while Faecalibacterium considerably decreased). Beta diversity analysis revealed greater similarity between FMT and tissue samples irrespective of the administration route, with distinct separation of the tissue and luminal samples. Overall, rectal administration yielded more overlapping genera and ASVs with FMT, highlighting that it could have advantages compared with oral administration for microbiota establishment studies.},
}

@article {pmid41429215,
year = {2025},
author = {Korenblik, V and Schilder, NKM and de Lange, IGS and Daams, JG and Bockting, CLH and Brul, S and Nieuwdorp, M and Lok, A and Korosi, A},
title = {From gut to glee: Is butyrate a promising antidepressant? A systematic review and mechanistic insights.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106237},
doi = {10.1016/j.bbi.2025.106237},
pmid = {41429215},
issn = {1090-2139},
abstract = {INTRODUCTION: Despite available therapies for depression, many patients do not achieve adequate improvement, illustrating the need for innovative treatment strategies. Nutritional psychiatry is an emerging area, with increasing evidence that microbially derived butyrate contributes to the beneficial effects of dietary, pre-, pro- and synbiotics interventions - raising the exciting possibility that direct butyrate administration might alleviate depressive symptoms. The main objective was to systematically review the effects of butyrate on depressive symptoms in humans and depressive-like behavior in animals (PROSPERO; CRD42023g0739).

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

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

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

ABBREVIATIONS: BDNF, Brain-derived neurotrophic factor; CRS, Chronic restraint stress; CSD, Chronic social defeat; CUMS, Chronic unpredictable mild stress; DASS, Depression, anxiety, Stress Scales; EPM, Elevated plus maze; FMT, Fecal microbiota transplant; FST, Forces swim test; HDAC, Histone deacetylase; HFD, High-fat diet; HPA, Hypothalamic-pituitary-adrenal; ICTRP International Clinical Trials Registry Platform; IL, Interleukin; LDB, Light-dark box; LEIDS-R Leiden Index of Depression Severity-Revised; LPS, Lipopolysaccharide; MD, Maternal deprivation; MDD, Major depressive disorder; MGBA, Microbiota-gut-brain axis; NORT, Novel object recognition test; OFT, Open field test; PFC, Prefrontal cortex; PRISMA Preferred reporting items for systematic reviews and meta-analyses; SCFA, Short-chain fatty acid; SPT, Sucrose preference test; SYRCLE, Systematic Review Centre for Laboratory Animal Experimentation; TCA, Tricarboxylic acid; TNF, Tumor necrosis factor; TST, Tail suspension test; ZO-1, Zonulin-1.},
}

@article {pmid41425939,
year = {2025},
author = {Chen, J and Sun, K and Zhang, X and Chen, X and Chu, Y and Geng, L and Bian, Z and Su, Y and Cong, X and Wang, G},
title = {Psoriasis and gut microbes: research advances from mechanism to therapy.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1711288},
pmid = {41425939},
issn = {1664-302X},
abstract = {BACKGROUND: Psoriasis is a chronic, immune-mediated, relapsing inflammatory skin condition, with its pathogenesis remaining incompletely understood and clinical eradication presenting significant challenges. Recent studies have highlighted the role of gut microbiota in psoriasis pathogenesis, emerging as a focal point of research.

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

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

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

CONCLUSION: Dysbiosis of the gut microbiota is a key factor in the pathogenesis of psoriasis. The regulatory mechanisms of the gut-skin axis offer new insights into the multisystemic associations of psoriasis. Gut microbiota-based therapeutic strategies hold promise as important adjuncts to conventional treatments, laying the foundation for developing novel targeted therapies. This approach carries significant clinical implications for improving the prognosis of psoriasis patients.},
}

@article {pmid41425837,
year = {2025},
author = {Oladele, P and Johnson, TA},
title = {Trehalose and maltodextrin preserve microbial community structure in freeze-dried fecal samples for fecal microbiota transplantation.},
journal = {ISME communications},
volume = {5},
number = {1},
pages = {ycaf204},
pmid = {41425837},
issn = {2730-6151},
abstract = {Fecal microbiota transplantation (FMT) is a promising approach for restoring gut microbial balance in both humans and animals. However, the logistical limitations of transplanting fresh fecal samples have increased interest in freeze-dried (lyophilized) fecal material as a transplant inoculum. While lyophilization facilitates storage, it can compromise bacterial viability, which is essential for FMT effectiveness. Lyoprotectants are often used to protect bacterial cultures during freeze-drying, but their effect on complex microbial communities remains unclear, as they may preferentially preserve some taxa over others. This study investigated the impact of four lyoprotectants-mannitol, maltodextrin, trehalose, and a maltodextrin-trehalose mixture-on bacterial viability and community structure in pig fecal samples post-lyophilization. Propidium monoazide (PMA) treatment combined with 16S rRNA sequencing (PMAseq) was used to differentiate viable from non-viable bacteria. In the total community (without PMA), microbial profiles appeared similar across treatment groups. However, when focusing on the viable community (PMA-treated), lyoprotectant choice significantly influenced the post-lyophilization community composition. Gram-negative bacterial viability was especially sensitive to lyophilization. Trehalose and maltodextrin preserved bacterial viability and community structure more effectively than mannitol. Mannitol-treated samples had reduced viable bacterial cells and altered community composition, while trehalose and maltodextrin better maintained diversity and structure of the viable (PMA-treated) communities. Taken together, lyoprotectants have differential effects on microbial composition during lyophilization. Among those tested, trehalose and maltodextrin best preserved both viability and community structure, making them promising candidates for FMT applications. Future research should explore optimizing lyoprotectant formulations to enhance microbiome stability and functional outcomes.},
}

@article {pmid41424968,
year = {2025},
author = {Shayya, M and Wehbi, Z and Matar, M and Elzein, M and Safieddine, Z and El Khoury, K and Ibrahim, JN and Hassan, HF and Jamal, O and Chatila, R and Kobeissy, PH},
title = {Awareness and perception of fecal microbiota transplantation in Lebanon: a cross-sectional survey among the general population, healthcare workers, physicians, and patients.},
journal = {Therapeutic advances in gastroenterology},
volume = {18},
number = {},
pages = {17562848251399034},
pmid = {41424968},
issn = {1756-283X},
abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection (CDI) and shows promise for other dysbiosis-related conditions such as inflammatory bowel disease (IBD). Awareness and acceptance remain underexplored in the Middle East, where cultural and social factors may influence adoption.

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

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

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

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

CONCLUSION: FMT awareness in Lebanon remains limited, particularly among patients and the public. Although perceptions are generally positive, misconceptions, stigma, and unrealistic expectations persist. These findings stem from a nonprobability sample that overrepresents younger, female, and highly educated participants and is not nationally representative. Targeted education, stronger physician-patient communication, and culturally sensitive approaches are needed to promote FMT acceptance and integration into practice.},
}

@article {pmid41424618,
year = {2025},
author = {Pandey, SN and Goyal, K and Rana, M and Menon, SV and Ray, S and Ali, H and Kumbhar, PS and Disouza, J and Singh, SK and Gupta, G and Wong, LS and Kumarasamy, V and Subramaniyan, V},
title = {Microbiome-derived bile acids as endogenous regenerative mediators in liver repair.},
journal = {Regenerative therapy},
volume = {30},
number = {},
pages = {681-690},
pmid = {41424618},
issn = {2352-3204},
abstract = {The liver's extraordinary capacity for self-repair is often compromised by chronic injury, fibrosis, or extensive resection, creating an urgent need for innovative regenerative therapies to restore liver function. Emerging evidence suggests that microbiome-derived bile acid metabolites are potent endogenous mediators of hepatic regeneration. Beyond their canonical role in lipid emulsification, these chemically diverse molecules engage nuclear and membrane receptors, most notably the farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5), to stimulate hepatocyte proliferation, modulate inflammatory responses, and reactivate quiescent progenitor cells. In this review, we integrate mechanistic insights from partial hepatectomy, germ-free, and antibiotic-treated animal models with early clinical observations to illuminate how primary and secondary bile acids orchestrate cell cycle progression, cytokine balance, and extracellular matrix remodeling. We then examined the therapeutic landscape, from synthetic FXR/TGR5 agonists to live-biotherapeutic approaches, genetically modified probiotic strains, and fecal microbiota transplantation. We highlight the preliminary indicators of efficacy and challenges in manufacturing consistency, safety profiling, and regulatory classification. We address the interindividual variability in microbiome composition, potential biomarkers such as serum FGF19, imaging-based measures of functional liver mass, and considerations for optimal trial design. This is the first comprehensive review to frame microbiome-driven bile acids as direct modulators of liver regeneration and chart a coherent translational development pathway. By integrating stem cell biology, hepatology, microbiology, and bioengineering perspectives, we demonstrate the underexplored therapeutic potential of these approaches to transform the future of hepatic repair.},
}

@article {pmid41424605,
year = {2025},
author = {Kay, E and Kazi, M and Burton, J and Parvathy, SN},
title = {Therapeutic properties of plant-derived prebiotics in melanoma.},
journal = {Exploration of targeted anti-tumor therapy},
volume = {6},
number = {},
pages = {1002354},
pmid = {41424605},
issn = {2692-3114},
abstract = {Immune checkpoint inhibitor (ICI) therapy has revolutionized metastatic melanoma treatment, yet only a subset of patients respond effectively, and the treatment can induce a variety of immune-related adverse events (irAEs), including colitis. The gut microbiome plays a critical role in determining patient responses to immunotherapy, prompting exploration of gut-modifying strategies such as prebiotics, probiotics, and fecal microbiota transplantation (FMT) to overcome both primary and acquired resistance and improve treatment outcomes. Prebiotics, defined as dietary substrates that selectively support the growth and/or activity of beneficial gut microorganisms, represent a feasible and safe strategy for microbiome reshaping. Plant-derived prebiotics like castalagin, inulin, fructooligosaccharides, galactooligosaccharides, mushroom extract, kale extract, and konjac glucomannan offer unique advantages over synthetic or animal-derived alternatives due to their natural fiber content alongside their ability to enhance gut microbial diversity. Prebiotics are known to achieve health benefits by selectively stimulating beneficial gut bacteria, producing short-chain fatty acids (SCFAs) that modulate the host immune system, suppressing pathogenic microbes, enhancing mucin production, and modulating systemic and gut-associated immune responses. SCFAs generated through prebiotic fermentation influence host innate and adaptive immunity and regulate metabolic activity via inhibition of histone deacetylases (HDACs), influencing mTOR/MAPK signaling and cytokine production. They also act as ligands for G-protein-coupled receptors (GPCRs), altering intracellular calcium and cAMP to modulate immune cell gene expression. However, the specific mechanisms by which individual prebiotics interact with host genetics, beneficial gut bacteria, and their metabolites are not very well understood. This is crucial to optimize their therapeutic potential in cancer immunotherapy. This review synthesizes current evidence on plant-derived prebiotics, highlighting the impact of beneficial gut bacteria and their metabolites. Given their established safety for human consumption, prebiotics represent a promising, low-risk option to improve gut microbiome composition and potentially enhance immunotherapy and clinical outcomes in cancer.},
}

@article {pmid41424069,
year = {2025},
author = {Prokopidis, K},
title = {Probiotics, prebiotics, and synbiotics to counteract sarcopenia: Where are we now and what challenges need to be faced?.},
journal = {The Proceedings of the Nutrition Society},
volume = {},
number = {},
pages = {1-17},
doi = {10.1017/S0029665125102036},
pmid = {41424069},
issn = {1475-2719},
abstract = {Sarcopenia, the age-related decline in muscle mass and strength, is a contributor to frailty and reduced quality of life. Emerging evidence suggests an emerging role of the gut microbiome in modulating skeletal muscle through microbial species and metabolites, such as short-chain fatty acids (SCFAs), potentially influencing glucose profile, inflammation, nutrient absorption, and protein metabolism. This review considers the potential of probiotics, prebiotics, and synbiotics as interventions to mitigate sarcopenia based on animal and human studies, while providing a critique of present barriers that need to be addressed. Preclinical models, including germ-free mice and faecal microbiota transplantation, demonstrate that gut microbiota from healthy or young donors may enhance overall muscle health via reductions in inflammatory and muscle atrophy markers. Limited human studies show that probiotics such as Lactobacillus and Bifidobacterium could improve branched chain amino acid (BCAA) bioavailability and potentially sarcopenia indices, although findings have been inconsistent. Particularly, challenges including inconsistent microbial assessments, lack of dietary control, and interindividual variability due to diet, age, genetics, comorbidities, and medications may hinder progress in this field. Delivery methods (e.g., capsules, fermented foods, or fortified products) could further complicate efficacy through probiotic stability and dietary restrictions in older adults. Standardized protocols (e.g., Strengthening The Organization and Reporting of Microbiome Studies (STORMS) checklist), and multi-omics approaches may be critical to address these limitations and identify microbial signatures linked to sarcopenia outcomes. While preclinical evidence highlights mechanistic pathways pertinent to amino acid metabolism, translating findings to humans requires rigorous experimental trials.},
}

@article {pmid41421285,
year = {2025},
author = {Sun, C and Tian, Y and Zheng, Y and Yang, K and Liu, S and Zhao, D and Li, L and Yin, X and Li, H and Duan, J and Mu, H and Liu, Q and Luo, J},
title = {KuiAnNingFang alleviates ulcerative colitis by modulating gut microbiota and NF-κB/NLRP3 pathway.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {150},
number = {},
pages = {157677},
doi = {10.1016/j.phymed.2025.157677},
pmid = {41421285},
issn = {1618-095X},
abstract = {BACKGROUND: Ulcerative colitis (UC), a major form of inflammatory bowel disease, is a chronic and relapsing inflammatory condition of the colonic mucosa. Despite the efficacy of the Traditional Chinese Medicine formula KuiAnNingFang (KANF) in alleviating UC, its therapeutic mechanisms remain incompletely understood.

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

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

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

CONCLUSION: KANF can significantly ameliorate symptoms in both clinical UC patients and DSS-induced colitis mice. KANF exerts its multi-target anti-colitic effects through regulation of the gut microbiota and subsequent suppression of the NF-κB/NLRP3 signaling cascade.},
}

@article {pmid41419954,
year = {2025},
author = {Huang, SJ and Ye, HL and Xu, S and Liu, T and Zhang, WC and Wang, YL and Duan, SZ},
title = {T cell KAT6A deficiency relieves inflammatory bowel disease in mice.},
journal = {Cell & bioscience},
volume = {15},
number = {1},
pages = {167},
pmid = {41419954},
issn = {2045-3701},
support = {82330015//the National Natural Science Foundation of China/ ; 81991503//the National Natural Science Foundation of China/ ; 2023YFA1801100//the National Key Research and Development Program of China/ ; 2023YFA1801104//the National Key Research and Development Program of China/ ; 2024R01003//Zhejiang Provincial Leading Innovation and Entrepreneurship/ ; },
abstract = {The incidence of inflammatory bowel disease (IBD) has been increasing, and while the interaction between T cells and intestinal microorganisms is crucial in its pathogenesis, the related epigenetic mechanisms remain unclear. This study found that the expression of lysine acetyltransferase 6A (KAT6A) was increased in T cells of patients with acute colitis. Knocking out KAT6A in CD4[+] T cells alleviated dextran sulfate sodium (DSS)-induced colitis in mice, as manifested in body weight, disease activity index, colon length, inflammation, and the expression of proinflammatory factors. Mechanistically, KAT6A deficiency upregulated the senescence of CD4[+] T cells and affected the expression of related genes. Moreover, the regulation of colitis by CD4[+] T cell KAT6A was dependent on the gut microbiota. Antibiotic treatment could reverse the protective effect in T cell KAT6A knockout (TK6AKO) mice, and fecal transplantation experiments confirmed that it was related to the change of the microbiota. 16S rRNA sequencing showed that the composition of the gut microbiota was changed, and specific bacteria such as Akkermansia muciniphila were enriched in TK6AKO mice. This study reveals that KAT6A affects colitis through the interaction between regulating T cell senescence and the gut microbiota, providing a new strategy for treatment.},
}

@article {pmid41417461,
year = {2025},
author = {Drew, G and Kraft, CS and Mehta, N},
title = {Fecal Microbiota Therapy: Clinical Laboratory Testing and Metabolomic Approaches for Donor Screening, Product Assessment, and Patient Monitoring.},
journal = {Clinical chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1093/clinchem/hvaf156},
pmid = {41417461},
issn = {1530-8561},
abstract = {BACKGROUND: The safety and efficacy of fecal microbiota transplantation for prevention of recurrent Clostridioides difficile infection relies on complex interactions between the donor and recipient microbiome.

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

SUMMARY: In this review, we discuss the nascent field of metagenomic and metabolic donor and recipient characteristics that may affect efficacy of FMT and future directions for this field to allow for more precise and personalized therapies.},
}

@article {pmid41416604,
year = {2025},
author = {Rychlik, A},
title = {Fecal microbiome transplantation in the treatment of chronic enteropathies.},
journal = {Polish journal of veterinary sciences},
volume = {28},
number = {4},
pages = {691-700},
doi = {10.24425/pjvs.2025.157285},
pmid = {41416604},
issn = {2300-2557},
mesh = {*Fecal Microbiota Transplantation/veterinary ; Animals ; *Intestinal Diseases/therapy/veterinary ; *Gastrointestinal Microbiome ; Chronic Disease ; },
abstract = {The intestinal microbiome is essential for the proper functioning of the immune system and the course of metabolic processes in the living organism. Intestinal bacteria produce a variety of metabolites that affect the health of many organs, especially the intestines. Disturbances in the composition of the intestinal microflora are referred to as dysbiosis. Dysbiosis occurring in chronic enteropathies may exacerbate intestinal inflammation. Therefore, effective methods of treating enteropathy are still being sought, which involve restoring the proper composition of the intestinal microbiome. In recent years, many scientific centers have drawn attention to the possibility of treating enteropathy by transplanting intestinal contents from a healthy donor. This review presents the advantages and disadvantages of this therapeutic method, described in the latest available literature and the newest guidelines regarding the donor and transplant administration methods.},
}

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

@article {pmid41416026,
year = {2025},
author = {Wan, L and Park, A and Lio, P},
title = {Fecal Microbiota Transplantation as a Potential Treatment for Pediatric Atopic Dermatitis.},
journal = {The Journal of clinical and aesthetic dermatology},
volume = {18},
number = {10},
pages = {16},
pmid = {41416026},
issn = {1941-2789},
}

@article {pmid41415268,
year = {2025},
author = {Wei, YF and Wang, YS and Song, JY and Wang, H and He, XX and Zhong, HJ},
title = {Restoration of peripheral ILC3s by washed microbiota transplantation improves lipid profiles in hyperlipidemia patients.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1688070},
pmid = {41415268},
issn = {1664-3224},
mesh = {Humans ; *Hyperlipidemias/therapy/immunology/blood/metabolism ; Animals ; Mice ; Male ; Gastrointestinal Microbiome/immunology ; Female ; Middle Aged ; *Lymphocytes/immunology/metabolism ; *Fecal Microbiota Transplantation/methods ; Immunity, Innate ; *Lipid Metabolism ; *Lipids/blood ; Interleukin-22 ; Interleukins/blood ; Adult ; Liver/metabolism/immunology ; Disease Models, Animal ; Mice, Inbred C57BL ; Prospective Studies ; },
abstract = {BACKGROUND: The contribution of circulating group 3 innate lymphoid cells (ILC3s) to lipid dysregulation has remained poorly defined, and the mechanisms through which washed microbiota transplantation (WMT) improves lipid metabolism require further clarification.

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

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

CONCLUSION: Hyperlipidemia is associated with depletion of circulating ILC3s and reduced IL-22. Restoration of ILC3 subsets and enhancement of integrin α4-dependent hepatic homing are achieved after WMT, accompanying improvements in lipid metabolism.},
}

Humans
*Hyperlipidemias/therapy/immunology/blood/metabolism
Animals
Mice
Male
Gastrointestinal Microbiome/immunology
Female
Middle Aged
*Lymphocytes/immunology/metabolism
*Fecal Microbiota Transplantation/methods
Immunity, Innate
*Lipid Metabolism
*Lipids/blood
Interleukin-22
Interleukins/blood
Adult
Liver/metabolism/immunology
Disease Models, Animal
Mice, Inbred C57BL
Prospective Studies

@article {pmid41413564,
year = {2025},
author = {Han, M and Xie, B and Yu, Y and Xu, D and Shi, Y and Xu, M and Wu, Y and Zhang, Y and Wen, X and Wang, X and Zhen, Z and Zhang, X and Sun, X and Yuan, Y and Shang, Y and Yuan, S and Hashimoto, K and Zhang, J},
title = {Intestinal γδ T17-IL-17A signaling disrupts hippocampal mitophagy in stress-induced depression and is restored by arketamine.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-025-03656-4},
pmid = {41413564},
issn = {1742-2094},
support = {82402568//National Natural Science Foundation of China/ ; 82302471//National Natural Science Foundation of China/ ; 82272231//National Natural Science Foundation of China/ ; 82472223//National Natural Science Foundation of China/ ; 2021YFC2500800//National Key Research and Development program from Ministry of Science and Technology of the People's Republic of China/ ; 2024ZD0529004//Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; },
abstract = {Chronic stress precipitates depression, yet how gut-immune-brain interactions translate stress into mood pathology remains unclear. We tested the hypothesis that stress-primed small intestinal γδ T cells drive hippocampal mitochondrial dysfunction and depression-like behavior via interleukin-17A (IL-1A). In mice exposed to chronic restraint stress (CRS), we combined behavioral assays (open-field, sucrose-preference, tail-suspension, forced-swim), 16S rRNA profiling, fecal microbiota transplantation, Kaede photoconversion, conditional CD8α deletion in γδ T cells, hippocampal IL-17A overexpression, rapamycin treatment, and administration of the antidepressant arketamine. CRS increased gut and brain permeability, induced gut-microbiota dysbiosis, and promoted migration of small intestinal CD8α[+] γδ T17 cells to the meninges and brain; γδ T cells were the predominant IL-17A source in the brain. Kaede tracing confirmed an intestinal origin, and CRS-associated microbiota alone transferred γδ T cell trafficking and depression-like behavior to recipients. In the hippocampus, CRS elevated IL-17A and impaired PINK1/Parkin-mediated mitophagy (decreased PINK1, Parkin, Beclin-1, and LC3B-II/I; increased p62), reduced ATP, and produced mitochondrial and synaptic ultrastructural deficits. IL-17A overexpression further worsened mitophagy and behavior, whereas rapamycin restored both. Conditional deletion of CD8α in γδ T cells reduced brain γδ T17 infiltration, lowered hippocampal IL-17A, rescued mitophagy and synapses, and improved behavior. Arketamine normalized dysbiosis and barrier markers, curtailed γδ T cell trafficking, decreased hippocampal IL-17A, restored mitophagy, and alleviated depression-like behavior in both sexes. These findings delineate a stress-responsive microbiota-γδ T cell-IL-17A pathway that compromises hippocampal mitophagy and identify arketamine as a candidate modulator of this axis, nominating mitophagy and γδ T cell trafficking as translational targets.},
}

@article {pmid41373016,
year = {2025},
author = {Qian, J and Tao, Q and Shen, Y and Wang, L and Wang, M and Wang, N and Liang, Q and Lu, J and Huang, Y and Liao, W and Chen, R and Ge, R and Yuan, Z and Li, Y and Shen, H and Gao, Q and Yan, F},
title = {Periodontitis salivary microbiota exacerbates colitis by CXCL3 derived from gut microbiota-induced macrophages.},
journal = {Microbiome},
volume = {13},
number = {1},
pages = {255},
pmid = {41373016},
issn = {2049-2618},
support = {No. 0224C030//High-Level Hospital Construction Project of Nanjing Stomatological Hospital/ ; No. 82270979, 81970939//The National Natural Science Foundation of China/ ; JSDW202246//Jiangsu Provincial Medical Key Discipline (Laboratory) Cultivation Unit/ ; No. 2019060009//Nanjing Clinical Research Center for Oral Diseases/ ; },
mesh = {*Gastrointestinal Microbiome ; *Periodontitis/complications/microbiology ; *Saliva/microbiology ; *Colitis/microbiology/therapy ; Probiotics/therapeutic use ; Case-Control Studies ; Humans ; Male ; Animals ; Mice ; Mice, Inbred C57BL ; RAW 264.7 Cells ; Lacticaseibacillus rhamnosus ; Fecal Microbiota Transplantation ; },
abstract = {BACKGROUND: Increasing research has focused on the role of the oral-gut axis in the development of colitis. Saliva contains a large number of oral bacteria that influence gut microbiota and colitis, but the underlying mechanisms remain unclear. In this study, we investigated the role and mechanisms of gut microbiota in salivary microbiota-affected colitis.

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

CONCLUSIONS: Gut microbiota was a key factor in PSM-exacerbated colitis, which was by activating macrophage to secrete CXCL3. Our study provides new insights into the role of gut microbiota with macrophages and chemokines in colitis, and the mechanism of oral disease affecting the distal organs systemically.},
}

*Gastrointestinal Microbiome
*Periodontitis/complications/microbiology
*Saliva/microbiology
*Colitis/microbiology/therapy
Probiotics/therapeutic use
Case-Control Studies
Humans
Male
Animals
Mice
Mice, Inbred C57BL
RAW 264.7 Cells
Lacticaseibacillus rhamnosus
Fecal Microbiota Transplantation

@article {pmid41315900,
year = {2025},
author = {Ardis, CK and Bui, TPN and Nieuwdorp, M},
title = {Gut microbiota in cancer cachexia: a new frontier for research and therapy.},
journal = {Genes & nutrition},
volume = {20},
number = {1},
pages = {28},
pmid = {41315900},
issn = {1555-8932},
support = {09150182010020//European Union's Horizon Training Mobility Actions- Consortium Grant agreement MiCCrobioTAckle/ ; 09150182010020//NWO VICI grant 2020/ ; 101141346//ERC Advanced grant/ ; },
abstract = {Cancer cachexia is a multifactorial syndrome characterized by systemic inflammation, progressive weight loss, muscle wasting, and metabolic alterations, which negatively affect quality of life, treatment response, and survival in cancer patients. Despite its prevalence and impact, effective treatments remain limited, in part due to the complex and poorly understood pathophysiology of the syndrome. Recent studies have revealed that gut microbiota alterations may contribute to the development and progression of cachexia through mechanisms involving immune activation, impaired gut barrier function, and disrupted metabolic signaling. This review explores the interplay between the altered gut microbiome and cancer cachexia, focusing on microbial metabolites such as short-chain fatty acids, gut barrier dysfunction and the impact of cancer therapies on microbial homeostasis. We evaluate emerging microbiota-targeted strategies, including traditional and next-generation probiotics and fecal microbiota transplantation, as novel therapeutic avenues. A deeper understanding of host–microbiome interactions may lead to the development of more effective, personalized interventions to improve cancer cachexia patient care.},
}

@article {pmid41409175,
year = {2025},
author = {Ng, DZW and Low, A and Khairul Sani, KRB and Liu, L and Zhang, Z and Koh, XQ and Zhu, M and Mitra, K and Muthiah, M and Dan, YY and Lee, JWJ and Chan, ECY},
title = {Dysbiosis-Driven Reprogramming of Secondary Bile Acid Metabolism in Metabolic Dysfunction-Associated Steatotic Liver Disease: Insights from an Ex Vivo Human Fecal Microbiota Model.},
journal = {ACS pharmacology & translational science},
volume = {8},
number = {12},
pages = {4335-4344},
pmid = {41409175},
issn = {2575-9108},
abstract = {Gut microbial dysbiosis-induced perturbations in bile acid (BA) metabolism are implicated in metabolic dysfunction-associated steatotic liver disease (MASLD), yet evidence remains largely associative. Using an optimized ex vivo fecal microbiota model, we modeled the metabolism kinetics of conjugated- and primary-BA between MASLD and healthy donors. Enzymes for known BA metabolic reactions were inferred using functional metagenomics. MASLD cultures exhibited impaired deconjugation capacity but preserved downstream primary-BA clearance and demonstrated a substrate-independent shift that favored oxidative metabolism over 7α-dehydroxylation. This was marked by increased formation clearance of 7-keto-deoxycholic acid (175%) and 3-oxo-cholic acid (51.7%) from cholic acid (CA) and 7-keto-lithocholic acid (77.9%) from chenodeoxycholic acid (CDCA). C7-oxidized BA constituted the major proportion of total BA clearance (CA = 56.0%, CDCA = 72.3%) in MASLD cultures. Enrichment of C3- and C7-hydroxysteroid dehydrogenases in MASLD compared to control corroborated the differential secondary BA profiles. Together, microbes catalyzing C7-oxidation warrants further investigation as potential pharmacological targets of MASLD.},
}

@article {pmid41408061,
year = {2025},
author = {Wang, Z and Cui, Y and Li, D and Yan, L and Zhu, S and Ma, X and Lu, Z and Li, C and Feng, J and Yuan, W and He, X},
title = {Alternate-day fasting ameliorates α-synuclein pathology and suppresses inflammation via the gut-brain axis in an MPTP-induced subacute mouse model of Parkinson's disease.},
journal = {NPJ biofilms and microbiomes},
volume = {11},
number = {1},
pages = {228},
pmid = {41408061},
issn = {2055-5008},
support = {2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 2022020802-JH2/1015//Basic Research Program of Liaoning Province/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 345 Talent Project//Shengjing Hospital/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; 82271275//National Natural Science Foundation of china/ ; },
mesh = {Animals ; Mice ; *Fasting ; *alpha-Synuclein/metabolism/genetics ; *Gastrointestinal Microbiome ; Disease Models, Animal ; *Parkinson Disease/pathology/metabolism/therapy ; *Brain/metabolism/pathology ; *Inflammation ; Male ; Fecal Microbiota Transplantation ; *Brain-Gut Axis ; Mice, Inbred C57BL ; Dopaminergic Neurons/metabolism ; },
abstract = {Dietary restrictions like alternate-day fasting (ADF) can counteract several age-related disorders, but its role in Parkinson's disease (PD) is still controversial. Recent findings highlight the imbalances in the gut-brain axis in PD, herein, we aim to study whether ADF can confer protection in PD mice through the gut-brain axis. Firstly, we assessed the neuroprotective effect of ADF in a time-dependent manner and found that 16 -week ADF could confer the optimal neuroprotection by preserving dopaminergic neurons and reducing the level of α‑synuclein (α‑syn) in the substantia nigra (SN), and it could decrease inflammatory cytokine levels in both the brain and the gut. Furthermore, ADF reshaped gut microbial composition and altered metabolites associated with PD. Relative abundances of several intestinal flora, including Alistipes, Helicobacter and Lactobacillus, were identified as potential mediators. In addition, we conducted fecal microbiota transplantation (FMT) to further investigate the role of the gut-brain axis in the neuroprotective effects of ADF. Notably, we found that FMT from ADF mice conferred equal protection to ADF in ameliorating the pathology and inflammation in both the brain and the gut. Collectively, our findings suggest that the microbiota-gut-brain axis is crucial to the neuroprotective effect of ADF in PD.},
}

Animals
Mice
*Fasting
*alpha-Synuclein/metabolism/genetics
*Gastrointestinal Microbiome
Disease Models, Animal
*Parkinson Disease/pathology/metabolism/therapy
*Brain/metabolism/pathology
*Inflammation
Male
Fecal Microbiota Transplantation
*Brain-Gut Axis
Mice, Inbred C57BL
Dopaminergic Neurons/metabolism

@article {pmid41408007,
year = {2025},
author = {Abrishami, M and Sabouri, M and Joneidi, F and Haghshenas, Z and Khalili-Tanha, G and Nazari, E},
title = {The role of gut microbiota in breast cancer: biomarker identification and therapeutic applications.},
journal = {Antonie van Leeuwenhoek},
volume = {119},
number = {1},
pages = {14},
pmid = {41408007},
issn = {1572-9699},
support = {1403-1121//Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran/ ; },
mesh = {Humans ; *Breast Neoplasms/therapy/microbiology/diagnosis ; *Gastrointestinal Microbiome/physiology ; Female ; *Biomarkers, Tumor ; Dysbiosis/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; },
abstract = {Recent studies have established the gut microbiome as a crucial player in breast cancer diagnosis, progression, and treatment. Distinct microbial patterns have shown promise as non-invasive diagnostic and prognostic biomarkers, supporting patient stratification and risk assessment based on microbiota composition. The gut microbiome also modulates estrogen metabolism, influencing the risk of hormone receptor-positive breast cancer, while dysbiosis can promote chronic inflammation and tumor expansion. Moreover, accumulating evidence demonstrates that gut bacteria can alter responses to chemotherapy and immunotherapy, suggesting that microbiota modulation may enhance treatment efficacy. With the advent of omics technologies and machine learning, intricate host-microbe interactions are being decoded, revealing new molecular targets and therapeutic opportunities. Importantly, early clinical and interventional studies using probiotics, prebiotics, and fecal microbiota transplantation (FMT) are being explored to restore microbial balance, mitigate therapy-related side effects, and improve antitumor immunity in breast cancer patients. Together, these advances underscore the translational potential of microbiome research, paving the way for microbiota-guided diagnostic, prognostic, and therapeutic strategies in personalized breast cancer management.},
}

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

@article {pmid41406837,
year = {2025},
author = {Wu, C and Hu, S and Li, D and Jiang, X and Bi, G and Wang, P and OuYang, H and Fang, J and Yang, X and Bi, H},
title = {Gut microbiota affects the role of mPXR agonist PCN in alleviating sepsis-induced liver injury by regulating YAP activation.},
journal = {International immunopharmacology},
volume = {169},
number = {},
pages = {116013},
doi = {10.1016/j.intimp.2025.116013},
pmid = {41406837},
issn = {1878-1705},
abstract = {BACKGROUND: Sepsis severity is primarily driven by exaggerated inflammatory responses that contribute to hepatic injury. The pregnane X receptor (PXR), a nuclear receptor that regulates xenobiotic and endobiotic metabolism, plays a crucial protective role against sepsis-induced liver injury and modulates hepatic regeneration. Concurrently, the gut microbiota contributes to sepsis pathogenesis via intestinal signaling and the gut-liver axis. This study aimed to evaluate how the gut microbiota mediates the protective effects exerted by the mouse PXR (mPXR) agonist pregnenolone-16α‑carbonitrile (PCN) against sepsis-induced liver injury and to elucidate the underlying mechanisms.

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

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

CONCLUSIONS: In summary, this study demonstrated that the gut microbiota mediated the protective effects of PCN against sepsis-induced liver injury by activating the YAP pathway. These findings provide novel insights into the role of gut microbiota in PXR-mediated protection during sepsis.},
}

@article {pmid41405935,
year = {2025},
author = {D'Amico, F and Nardone, OM and Bruno, A and Allocca, M and Zilli, A and Furfaro, F and Parigi, TL and Solitano, V and Ungaro, F and Faggiani, I and La Mantia, A and Calabrese, G and Fiorino, G and Jairath, V and Peyrin-Biroulet, L and Massimino, L and Castiglione, F and Danese, S},
title = {Bowel Urgency Improvement Correlates With Clinical, Biochemical, and Intestinal Ultrasound Improvements in Inflammatory Bowel Disease: A Cross Sectional Multicenter Study.},
journal = {United European gastroenterology journal},
volume = {},
number = {},
pages = {},
doi = {10.1002/ueg2.70129},
pmid = {41405935},
issn = {2050-6414},
abstract = {BACKGROUND: Bowel urgency (BU) is reported by over 80% of patients with ulcerative colitis (UC) and 60% of those with Crohn's disease (CD). However, the impact of advanced therapies on BU has not been consistently evaluated.

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

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

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

CONCLUSION: BU improved in approximately half of IBD patients following induction with advanced therapies. Its improvement correlated with clinical, biochemical, and ultrasound remission, supporting the incorporation of BU assessment into routine clinical monitoring.},
}

@article {pmid41403899,
year = {2025},
author = {Shi, W and Wu, L and Qin, Q and Li, Y and Chen, W},
title = {Research progress on the role of microbiome-immune-neurotransmitter network in post-stroke sleep disorders.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1694709},
pmid = {41403899},
issn = {1663-4365},
abstract = {Post-stroke sleep disorders, as a significant complication affecting patient rehabilitation, are closely associated with dysregulation of the microbiome-immune-neurotransmitter network. Following stroke, activation of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system triggers intestinal barrier disruption (reduced tight junction proteins and intestinal permeability) along with microbial imbalance (decreased Bifidobacterium and increased Enterobacteriaceae). Reduced short-chain fatty acids and lipopolysaccharide (LPS) translocation exacerbate systemic inflammatory responses and neurotransmitter imbalances (inhibited serotonin synthesis and excitotoxic glutamate production). These changes further disrupt circadian regulation by the hypothalamic suprachiasmatic nucleus, leading to reduced REM sleep and disrupted slow-wave sleep architecture. Future research should prioritize interventional strategies targeting the gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation, integrated with multi-omics technologies and neural circuit modulation approaches, to elucidate the spatiotemporal dynamics of the microbiome-immune-neurotransmitter network and provide a theoretical basis for clinical translation. Restoring brain-gut axis homeostasis is expected to improve post-stroke sleep disorders and neurological functional outcomes in patients.},
}

@article {pmid41403286,
year = {2025},
author = {Yoshinami, Y and Yamaguchi, S and Shoji, H and Okita, N and Takamaru, H and Hirose, T and Hirano, H and Takashima, A and Imazeki, H and Yamamoto, S and Koyama, S and Ishikawa, D and Terauchi, J and Tanaka, K and Ogawa, K and Watanabe, H and Kato, K},
title = {Feasibility of antibiotic-assisted fecal microbiota transplantation with immunotherapy for esophageal and gastric cancer.},
journal = {Future oncology (London, England)},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/14796694.2025.2599371},
pmid = {41403286},
issn = {1744-8301},
abstract = {AIMS: Immune checkpoint inhibitors (ICIs) have improved outcomes in several malignancies, but survival remains poor for patients with unresectable advanced or recurrent esophageal or gastric cancer. Recent evidence suggests that modulation of the intestinal microbiota may influence the therapeutic response to ICIs. This study aims to evaluate the safety and preliminary efficacy of fecal microbiota transplantation following antibiotic pretreatment (A-FMT) in patients scheduled to receive ICI-containing regimens.

METHODS: This phase I - II, single-institution clinical trial enrolls patients with unresectable advanced or recurrent esophageal or gastric cancer. Participants receive a 1-week course of oral antibiotics (amoxicillin, fosfomycin, and metronidazole) prior to transplantation. A single dose of donor-derived intestinal microbiota solution is administered via colonoscopy, followed by initiation of ICI-based therapy on the next day. The primary endpoint is the incidence of dose-limiting toxicity. Secondary endpoints include response rate, disease control rate, progression-free survival, overall survival, and adverse events. Comprehensive translational research is conducted using stool, blood, and tissue samples to characterize immune responses and identify biomarkers associated with A-FMT and ICI efficacy.Trial registration: jRCTs031240170.The study is ongoing, and patients are currently being enrolled. Enrollment started in June 2024. A total of 7 patients have been enrolled as of August 2025. This protocol is version 3.2.},
}

@article {pmid41402129,
year = {2025},
author = {Wang, J and Li, J and Li, Y and Huang, W and Huang, C and Xu, Q and Sun, J and Gong, J and Ma, X and Wang, G and Meng, Y and Li, X},
title = {Angiotensin-(1-7) alleviates intestinal barrier dysfunction and dysbiosis in mice with polymicrobial sepsis.},
journal = {British journal of pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bph.70248},
pmid = {41402129},
issn = {1476-5381},
support = {82170641//National Natural Science Foundation of China/ ; 82470663//National Natural Science Foundation of China/ ; 82270089//National Natural Science Foundation of China/ ; 81873583//National Natural Science Foundation of China/ ; 2021A1515012595//Guangdong Provincial Science and Technology Projects under Grant/ ; 2024A1515220136//Guangdong Provincial Science and Technology Projects under Grant/ ; 202312121006//National College Students' Innovation and Entrepreneurship Training Program/ ; S202012121056//Guangdong Provincial Innovation Training Projects under Grant/ ; 2017B020209003//Guangdong Science and Technology Project under Grant/ ; JCYJ20210324112807021//Technical Research and Development Project of Shenzhen/ ; },
abstract = {BACKGROUND AND PURPOSE: The intestine plays a key role in the initiation of sepsis. The gut barrier impedes the translocation of commensal bacteria to the liver in sepsis. Previous studies have reported that angiotensin-(1-7) [Ang-(1-7)] attenuated sepsis-induced organ injury and mortality. However, its role in sepsis-induced intestinal barrier dysfunction remains unclear. Here we have investigated therapeutic effects of Ang-(1-7) on the intestinal barrier dysfunction and dysbiosis in a murine model of sepsis.

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

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

CONCLUSION AND IMPLICATIONS: Ang-(1-7) protected against sepsis-induced intestine barrier dysfunction and liver injury in mice by modulating gut homeostasis and NLRP6 inflammasome. Ang-(1-7) is a promising candidate drug for protecting intestinal homeostasis in sepsis, offering new insights for clinical treatment.},
}

@article {pmid41400824,
year = {2025},
author = {Liu, M and Liu, W and Zhao, K and Zhang, W and Lei, B and Zhang, Y and Li, L and Yuan, W},
title = {Adult duck fecal microbiota transplantation alleviates short beak and dwarfism syndrome in ducklings by inhibiting Th17 cell differentiation.},
journal = {Virulence},
volume = {},
number = {},
pages = {2605745},
doi = {10.1080/21505594.2025.2605745},
pmid = {41400824},
issn = {2150-5608},
abstract = {Novel goose parvovirus (NGPV) infection in ducklings induces short beak and dwarfism syndrome (SBDS), leading to significant economic losses. Since NGPV predominantly infects ducklings, whether reshaping the intestinal flora of ducklings through fecal microbiota transplantation from adult ducks (FMT-A) can alleviate SBDS is an interesting question. This study aimed to investigate the impact of FMT-A on the susceptibility of ducklings to NGPV infection, to elucidate the potential relationship between gut microbiota and viral pathogenicity. The results showed that ducklings were more susceptible to NGPV than adults, and that adult ducks exhibited higher fecal microbiota richness and diversity. FMT-A treatment attenuated NGPV-induced reductions in body weight, beak and tibia length, and muscle mass. Furthermore, FMT-A alleviated gut dysbiosis and intestinal tissue damage, increased glycogen in the intestinal mucosa, upregulated ZO-1 expression, expanded the epiphyseal region, and reduced osteoclast numbers in the tibia of ducklings. Moreover, FMT-A suppressed the expression of the Th17 cell-specific transcription factor retinoic acid receptor-related orphan receptor γt in the ileum and bone, and decreased the expression levels of pro-inflammatory cytokines in the ileum, bone, and serum. These findings indicate that ducklings are more susceptible to NGPV than adult ducks, with significantly lower diversity and abundance of fecal microbiota. FMT-A can stabilize intestinal flora, mitigate intestinal barrier damage, inhibit Th17 cell differentiation, thereby reducing abnormal bone development, and ultimately alleviate SBDS in ducklings. These findings provide a theoretical basis for developing novel strategies targeting gut microbiota modulation to prevent and control SBDS in ducklings.},
}

@article {pmid41400783,
year = {2025},
author = {Wei, Q and Wang, Y and Rui, M and You, JHS},
title = {Health economic evaluations of fecal microbiota transplantation for non-clostridioides difficile related diseases: a systematic review.},
journal = {Health economics review},
volume = {15},
number = {1},
pages = {103},
doi = {10.1186/s13561-025-00698-5},
pmid = {41400783},
issn = {2191-1991},
}

@article {pmid41399570,
year = {2025},
author = {Bheemaneni, RS and Sakarkar, P and Nigam, A and Nwachukwu, EC and Sekar Lakshmisai, S and Mohammed, L},
title = {Unraveling the Association Between Fibromyalgia and Irritable Bowel Syndrome: A Systematic Review.},
journal = {Cureus},
volume = {17},
number = {11},
pages = {e96801},
pmid = {41399570},
issn = {2168-8184},
abstract = {Fibromyalgia (FM) and irritable bowel syndrome (IBS) often occur together. Patients with FM and IBS present similar symptoms, such as pain and fatigue; this leads to a delay in diagnosis and management. This systematic review explored the shared pathophysiology of these conditions in adults, focusing on the roles of immune dysfunction, gut dysbiosis, neurotransmitter imbalances, and disturbances in the gut-brain axis. We searched five databases, PubMed, PubMed Central, Google Scholar, Cochrane, and ScienceDirect, for relevant free full-text English articles from 2015 to 2025. Ten studies were selected after screening, identification, and quality assessment, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Our review found that immune system dysregulation involves mast cells and pro-inflammatory cytokines that damage the gut barrier. The gut microbiome and neurotransmitter levels seem to have a reciprocal influence on each other, and their alteration contributes to pathogenesis, with an increase of certain species showing an association with symptom severity. Serotonin and tryptophan metabolism appear to have a crucial role in pain perception, particularly visceral hypersensitivity. Therapeutic strategies targeting the gut microbiome, such as probiotics and fecal microbiota transplantation, have potential but require further research. Overall, this review identified overlapping mechanisms of FM-IBS comorbidity, which can pave the way to effective and combined treatment approaches. Future research should explore gender distinctions in the mechanisms, medications that act on neurotransmitter receptors (especially serotonergic pathways), and the utility of fecal microbiota transplantation and probiotics.},
}

@article {pmid41399411,
year = {2025},
author = {Li, X and Ji, J and Li, J and Li, S and Luo, Q and Gu, M and Yin, X and Zhang, M and Fan, H and Yao, R},
title = {Gut microbiota-bile acid metabolic disorder involved in the cognitive impairments in epilepsy through HO-1 dependent ferroptosis.},
journal = {Journal of pharmaceutical analysis},
volume = {15},
number = {11},
pages = {101291},
pmid = {41399411},
issn = {2214-0883},
abstract = {Abnormal bile acid (BA) metabolism has been implicated in the pathogenesis of central nervous system (CNS) diseases, but its role in epilepsy remains unclear. In this study, we investigated the relationship between gut microbiota-driven dysregulation of BA metabolism and seizure-induced ferroptotic neuronal death in epilepsy. Our targeted metabolomic analysis revealed elevated levels of deoxycholic acid (DCA) in the serum and cerebrospinal fluid (CSF) of epileptic patients, which correlated with cognitive impairment. In a pentylenetetrazol (PTZ)-induced mouse model of epilepsy, 16S ribosomal RNA (16S rRNA) sequencing showed significant alterations in gut microbiota composition. Importantly, fecal microbiota transplantation (FMT) from healthy mice into epileptic mice significantly reduced seizure activity and improved cognitive function, primarily by normalizing serum and brain levels of secondary bile acids (SBAs), including DCA. Both in vitro and in vivo experiments demonstrated that DCA promotes ferroptosis in hippocampal neurons by activating the farnesoid X receptor (FXR). This activation triggered the nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase-1 (HO-1) signaling pathway, known to be involved in oxidative stress and cell death regulation. Our findings suggest that the upregulation of DCA, through its effects on FXR and HO-1, plays a critical role in the progression of epilepsy by inducing ferroptosis in hippocampal neurons. Targeting the DCA-FXR-HO-1 axis may provide a novel therapeutic strategy for treating seizures and associated cognitive deficits in epilepsy.},
}

@article {pmid41399387,
year = {2026},
author = {Yu, Y and Zhao, W and Yang, M and Wu, B and Yuan, X},
title = {Tumor-Promoting Gut Microbes in Colorectal Cancer: Mechanisms and Translational Perspectives.},
journal = {International journal of medical sciences},
volume = {23},
number = {1},
pages = {63-75},
pmid = {41399387},
issn = {1449-1907},
mesh = {Humans ; *Colorectal Neoplasms/microbiology/therapy/diagnosis/pathology/immunology ; *Gastrointestinal Microbiome/immunology/physiology ; *Dysbiosis/microbiology/complications/therapy/immunology ; Fecal Microbiota Transplantation/methods ; Probiotics/therapeutic use ; Carcinogenesis/immunology ; Translational Research, Biomedical ; },
abstract = {Colorectal cancer (CRC) represents a predominant global malignancy, characterized by increasing incidence and mortality rates. Recent investigations have underscored the gut microbiota as a pivotal element in the pathogenesis and progression of CRC. This review synthesizes current evidence regarding the association between gut microbial dysbiosis and CRC, with a particular emphasis on pathogenic bacteria such as Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, pks[+] Escherichia coli, and Enterococcus faecalis, among others. The mechanisms through which these microbes contribute to tumorigenesis include the induction of DNA damage, the promotion of chronic inflammation, and the induction of immunosuppression, and the production of oncogenic metabolites. Additionally, the review examines the clinical implications of gut microbiota, highlighting their potential as non-invasive biomarkers for early CRC detection and their impact on the efficacy and toxicity of chemotherapy, radiotherapy, and immunotherapy. Furthermore, emerging microbiota-targeted interventions, such as fecal microbiota transplantation, dietary modification, and probiotics, are evaluated for their therapeutic potential. Despite substantial progress, challenges remain in standardizing microbial markers and optimizing individualized microbiota modulation strategies. Future studies integrating multi-omics and machine learning approaches may pave the way for microbiome-based precision medicine in CRC.},
}

Humans
*Colorectal Neoplasms/microbiology/therapy/diagnosis/pathology/immunology
*Gastrointestinal Microbiome/immunology/physiology
*Dysbiosis/microbiology/complications/therapy/immunology
Fecal Microbiota Transplantation/methods
Probiotics/therapeutic use
Carcinogenesis/immunology
Translational Research, Biomedical

@article {pmid41399025,
year = {2025},
author = {Zhao, D and Wang, X and Wang, K and Yang, B and Zhu, H and Xu, Y and Ye, C and Li, L and Lv, X and Zhou, S and Ma, C and Chen, X and Yin, F and Zhu, Y and Cao, Z and Li, N and Zuo, T and Qin, H and Chen, Q},
title = {Recipients' native bacteria determine the outcome of FMT treatment in inflammatory bowel disease.},
journal = {Gut microbes},
volume = {17},
number = {1},
pages = {2600055},
doi = {10.1080/19490976.2025.2600055},
pmid = {41399025},
issn = {1949-0984},
mesh = {Humans ; Male ; Female ; Adult ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/adverse effects ; Middle Aged ; *Bacteria/classification/isolation & purification/genetics ; Treatment Outcome ; Retrospective Studies ; Feces/microbiology ; *Colitis, Ulcerative/therapy/microbiology ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Crohn Disease/therapy/microbiology ; Young Adult ; Prospective Studies ; Aged ; },
abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a promising treatment for inflammatory bowel disease (IBD), achieving clinical response rate of ~50% for ulcerative colitis (UC), and Crohn's disease (CD). While prior research has emphasized donor selection and treatment protocols, the role of the patient's native intestinal microbiota in FMT outcomes remains underexplored.

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

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

CONCLUSION: The patient's native microbiota significantly influences FMT efficacy in IBD, influencing microbiome remodeling and clinical outcomes, highlighting the importance of baseline microbial profiles in predicting FMT responsiveness and optimizing therapy.},
}

Humans
Male
Female
Adult
*Gastrointestinal Microbiome
*Fecal Microbiota Transplantation/adverse effects
Middle Aged
*Bacteria/classification/isolation & purification/genetics
Treatment Outcome
Retrospective Studies
Feces/microbiology
*Colitis, Ulcerative/therapy/microbiology
*Inflammatory Bowel Diseases/therapy/microbiology
*Crohn Disease/therapy/microbiology
Young Adult
Prospective Studies
Aged

@article {pmid41398400,
year = {2025},
author = {Myagmankhuu, S and Tsuji, S and Akagawa, S and Kino, J and Akagawa, Y and Yamanouchi, S and Kaneko, K},
title = {Depletion of gut microbiota alleviates proteinuria in puromycin aminonucleoside-induced nephrosis in rats.},
journal = {Pediatric research},
volume = {},
number = {},
pages = {},
pmid = {41398400},
issn = {1530-0447},
abstract = {BACKGROUND: The gut-kidney axis has been implicated in chronic kidney disease, however its role in minimal change nephrotic syndrome (MCNS) is poorly understood. We investigated the impact of gut microbiota on proteinuria in MCNS.

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

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

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

IMPACT: This study demonstrated that depleting the gut microbiota with antibiotics reduced proteinuria in a rat model of minimal change nephrotic syndrome, suggesting that harmful gut bacteria play a critical role in this disease. This research also identified indoxyl sulfate as a key uremic toxin produced by gut bacteria that worsens proteinuria and kidney damage, highlighting its role in disease progression. These findings could lead to novel treatments that target gut microbiota, including antibiotics or activated charcoal adsorbents that reduce proteinuria in minimal change nephrotic syndrome, and potentially minimize steroid use.},
}

@article {pmid41397827,
year = {2025},
author = {Mei, ZB and Cao, YL and Lv, BB and Wang, SY and Tian, K and Liu, QL and Ma, LZ and Wang, YS and Wei, D},
title = {[Efficacy observation of pelvic floor autologous fascia integrated repair based on membrane anatomy for complete rectal prolapse].},
journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery},
volume = {28},
number = {12},
pages = {1441-1447},
doi = {10.3760/cma.j.cn441530-20250810-00300},
pmid = {41397827},
issn = {1671-0274},
support = {LHGJ20250781//Medical Science and Technology Project of Henan Province/ ; },
mesh = {Humans ; Retrospective Studies ; *Pelvic Floor/surgery ; *Fascia/transplantation ; *Rectal Prolapse/surgery ; Female ; Treatment Outcome ; Male ; Laparoscopy ; Middle Aged ; Aged ; Adult ; Quality of Life ; },
abstract = {Objective: To compare the clinical efficacy of laparoscopic pelvic floor autologous fascia integral repair based on membrane anatomy versus transperineal proctosigmoidectomy (Altemeier procedure) in the treatment of patients with complete rectal prolapse (CRP). Methods: This study employed a retrospective observational cohort design. Clinical data were collected from a total of 55 CRP patients who underwent surgical treatment between January 2018 and July 2023, including 25 patients from Luoyang Central Hospital, affiliated with Zhengzhou University, and 30 patients from the 989th Hospital of the Joint Logistics Support Force & Military Anorectal Surgery Research Institute. All patients undergoing surgery met the following criteria: aged ≥ 18 years, rectal prolapse protruding outside the anus, prolapse length > 5 cm with inability to self-reduce, conforming to the diagnostic criteria for CRP, and being first-time treated patients. Twenty-seven patients who underwent the Altemeier procedure between January 2018 and March 2021 were assigned to the Altemeier group; 28 patients who underwent laparoscopic pelvic floor autologous fascia integral repair based on membrane anatomy between April 2021 and July 2023 were assigned to the integral repair group. The therapeutic efficacy differences between the two groups were analyzed and compared, including the CRP length (DCRP), Wexner Constipation Score, Wexner Fecal Incontinence Score, and Gastrointestinal Quality of Life Index (GIQLI) before surgery and at 6, 12, and 24 months after surgery, as well as postoperative complications and recurrence at 24 months after surgery. Results: There were no statistically significant differences between the two groups in terms of gender distribution, age, preoperative body mass index (BMI), defecation frequency, DCRP, Wexner Constipation Score, Wexner Fecal Incontinence Score, and GIQLI (all P>0.05). All patients completed the surgery. The length of hospital stay and intraoperative blood loss in the integral repair group were significantly less than those in the Altemeier group (both P<0.01). At 6, 12, and 24 months after surgery, the DCRP, Wexner Constipation Score, Wexner Fecal Incontinence Score, and GIQLI in both groups significantly improved compared with the preoperative values (all P<0.001). At 6, 12, and 24 months after surgery, the CRP treatment effect, Wexner Constipation Score, Wexner Fecal Incontinence Score, and GIQLI in the integral repair group were significantly better than those in the Altemeier group (χ[2]=15.821, P<0.001; χ[2]=18.238, P<0.001; χ[2] = 12.558, P=0.001; and χ[2] =22.413, P<0.001, respectively). In the integral repair group, 4 patients (14.3%) developed grade I-III postoperative complications, including 2 cases of urinary retention, 1 case of anastomotic bleeding, and 1 case of anastomotic stenosis. In the Altemeier group, 11 patients (40.7%) developed grade I-III postoperative complications, including 4 cases of urinary retention, 3 cases of anastomotic bleeding, 1 case of anastomotic stenosis, 2 cases of intestinal fistula, and 1 case of fecal incontinence. The difference between the two groups was statistically significant (χ[2]=4.850, P=0.028). There was no recurrence of CRP in the integral repair group at 24 months after surgery, while 7 cases of CRP recurrence were observed in the Altemeier group at 24 months after surgery. The difference between the two groups was statistically significant (χ[2]=6.148, P=0.013). Conclusion: The autologous fascia repair technique based on membrane anatomy and the pelvic floor integral theory is superior to the transperineal Altemeier procedure in the treatment of CRP. Furthermore, it is an effective surgical method for CRP.},
}

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

@article {pmid41397823,
year = {2025},
author = {Huang, YS and Tong, WD and Xiao, GD and Li, Q and Guo, M},
title = {[Transformation and evidence-based progress of chronic constipation treatment mode].},
journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery},
volume = {28},
number = {12},
pages = {1411-1416},
doi = {10.3760/cma.j.cn441530-20251013-00379},
pmid = {41397823},
issn = {1671-0274},
support = {82370547//National Natural Science Foundation of China/ ; CSTB2023NSCQZDJ0012//Key Project of Chongqing Natural Science Foundation/ ; 2022XLC05//Clinical Innovation Research Project of Army Medical University/ ; },
mesh = {Humans ; *Constipation/therapy ; Chronic Disease ; Fecal Microbiota Transplantation ; },
abstract = {In recent years, significant progress has been made in the treatment of chronic constipation, with high-quality studies emerging in areas such as fecal microbiota transplantation (FMT), sacral neuromodulation (SNM), acupuncture, and surgical techniques. The therapeutic approach is shifting from a traditional "medication and surgery" model toward an integrated strategy that includes dietary and defecation habit adjustment, FMT, SNM, acupuncture, pharmacotherapy, and surgery. Although FMT can partially improve stool frequency and consistency, its standardization and long-term efficacy require further validation. SNM demonstrates limited effectiveness in treating chronic constipation and is relatively cost-inefficient. Electroacupuncture remains controversial, though some studies support its value. Biofeedback therapy is recommended by multiple guidelines as the first-line treatment for dyssynergic defecation (DD), with portable home-based biofeedback systems showing considerable potential. For internal rectal prolapse (IRP) and rectocele (RC), various surgical options exist without a clear superiority, though laparoscopic ventral rectopexy (VMR) is increasingly favored due to its low recurrence rate and high patient satisfaction. In the surgical management of slow transit constipation (STC), total colectomy with ileorectal anastomosis remains the mainstream approach, while subtotal colectomy is gaining attention as an alternative.},
}

Humans
*Constipation/therapy
Chronic Disease
Fecal Microbiota Transplantation

@article {pmid41397742,
year = {2025},
author = {Kragsnaes, MS and Gilbert, BTP and Sofíudóttir, BK and Rooney, CM and Hansen, SM and Mauro, D and Mullish, BH and Bergot, AS and Mankia, KS and Goel, N and Bakland, G and Johnsen, PH and Miguens Blanco, J and Li, S and Dumas, E and Lage-Hansen, PR and Wagenaar, C and Bakdash, G and Robinson, M and Kristiansen, K and Marchesi, JR and Schett, G and Zaiss, MM and Orlu, M and van Schaadenburg, D and Scher, JU and McGonagle, D and Elewaut, D and Breban, M and Tugwell, P and Finckh, A and Ciccia, F and Kriegel, MA and Daien, C and Ellingsen, T and Christensen, R and , },
title = {Efficacy and safety of microbiota-targeted therapeutics in autoimmune and inflammatory rheumatic diseases: protocol for a systematic review and meta-analysis of randomised controlled trials.},
journal = {BMJ open},
volume = {15},
number = {12},
pages = {e101593},
doi = {10.1136/bmjopen-2025-101593},
pmid = {41397742},
issn = {2044-6055},
mesh = {Humans ; Systematic Reviews as Topic ; Meta-Analysis as Topic ; Randomized Controlled Trials as Topic ; *Gastrointestinal Microbiome ; *Rheumatic Diseases/therapy/microbiology ; *Autoimmune Diseases/therapy/microbiology ; Probiotics/therapeutic use ; Research Design ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use ; },
abstract = {INTRODUCTION: An abnormal composition of gut bacteria along with alterations in microbial metabolites and reduced gut barrier integrity has been associated with the pathogenesis of chronic autoimmune and inflammatory rheumatic diseases (AIRDs). The aim of the systematic review, for which this protocol is presented, is to evaluate the clinical benefits and potential harms of therapies targeting the intestinal microbiota and/or gut barrier function in AIRDs to inform clinical practice and future research.

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

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

PROSPERO REGISTRATION NUMBER: CRD42025644244.},
}

Humans
Systematic Reviews as Topic
Meta-Analysis as Topic
Randomized Controlled Trials as Topic
*Gastrointestinal Microbiome
*Rheumatic Diseases/therapy/microbiology
*Autoimmune Diseases/therapy/microbiology
Probiotics/therapeutic use
Research Design
Fecal Microbiota Transplantation
Anti-Bacterial Agents/therapeutic use

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

*Diabetes Mellitus, Type 2/therapy/microbiology
*Gastrointestinal Microbiome/drug effects
Humans
*Fecal Microbiota Transplantation/methods
Probiotics/administration & dosage/therapeutic use
Prebiotics/administration & dosage
Synbiotics/administration & dosage
Animals

@article {pmid41395487,
year = {2025},
author = {Bai, Z and Wang, Y and Li, Y and Xu, J and Lai, Z},
title = {The gut microbiota in liver transplantation recipients during the perioperative and postoperative recovery period.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1684303},
pmid = {41395487},
issn = {1664-302X},
abstract = {BACKGROUND: Chronic Liver Disease (CLD) is one of the frequent causes of death, especially in the developing world. Liver transplantation (LT) is an effective modality to treat end-stage liver disease. Perioperative management of liver transplantation patients and prevention of postoperative complications are the key to improving patient prognosis and quality of life, and the intestinal flora of these patients can affect postoperative complications and overall prognosis.

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

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

CONCLUSION: The diversity of intestinal flora in the perioperative period of LT patients decreased first and then increased, and the turning point of intestinal flora recovery was 1 month after LT surgery.},
}

@article {pmid41395479,
year = {2025},
author = {Yang, J and Wang, J and Li, J and Yang, S},
title = {Lung-gut axis, intestinal microbiota, and pulmonary fibrosis: mechanisms and therapeutic potential.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1711299},
pmid = {41395479},
issn = {1664-302X},
abstract = {Pulmonary fibrosis (PF) is a progressive and life-threatening interstitial lung disease with irreversible lung function loss. The bidirectional interaction between respiratory and gut microbiota mediated by the "lung-gut axis" has emerged as a core regulatory link in PF pathogenesis. This review integrates clinical and preclinical data to systematically clarify the association between microbiota dysbiosis and PF. Clinical evidence shows that PF patients (including idiopathic pulmonary fibrosis, silicosis, and coal workers' pneumoconiosis) exhibit reduced pulmonary microbiota diversity, increased pro-inflammatory microbial abundance, and altered gut microbiota composition. Preclinical studies using bleomycin or silica-induced PF models confirm consistent microbiota changes and abnormal metabolites. Further, five core pathophysiological mechanisms (immune dysregulation, gut-lung barrier dysfunction, sustained activation of Type 2 epithelial-mesenchymal transition, autophagy modulation, and alveolar epithelial cell apoptosis mediated by microbial peptides) explain how microbiota alterations drive PF progression. Key microbial mediators (e.g., tryptophan metabolites, short-chain fatty acids, lipopolysaccharide, bile acid metabolites) exert bidirectional regulatory effects on PF through synergistic or antagonistic interactions. Additionally, microbiota-targeted strategies such as probiotic/prebiotic intervention, fecal microbiota transplantation, dietary adjustment, and antibiotics have shown experimental anti-fibrotic efficacy. This review highlights the gut microbiota as a potential therapeutic target for PF, while discussing current challenges (e.g., unclear causal relationship, lack of standardized intervention protocols) and future research directions, providing a new framework for PF mechanism research and clinical intervention.},
}

@article {pmid41395459,
year = {2025},
author = {Li, Q and Liu, Y},
title = {Analyzing the gut liver axis: a dual role of the microbiome in the genesis, progression, and treatment of liver cell carcinoma.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1701101},
pmid = {41395459},
issn = {1664-302X},
abstract = {Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, and the poor prognosis highlights the pressing need for innovative therapeutic strategies. The gut-liver axis, a critical bidirectional pathway linking the gut microbiota to the liver, plays a pivotal role in HCC pathogenesis. This review systematically delineates current evidence on how gut dysbiosis, compromised intestinal barrier function, and resultant microbial metabolites (e.g., bacterially metabolized bile acids) drive hepatocarcinogenesis via specific signaling pathways, while also addressing the loss of protective effects due to the depletion of beneficial microbes. Moving beyond descriptive summaries, this article focuses on elucidating the core molecular mechanisms of microbiome-regulated HCC-a key knowledge gap that remains unaddressed-and reconciles conflicting findings into a unified framework. We further explore the translational potential of microbiome signatures as non-invasive biomarkers and evaluate microbiota-targeting interventions (e.g., probiotics, dietary modulation, fecal microbiota transplantation) for enhancing treatment efficacy. Ultimately, this review aims to provide a clear roadmap for developing microbiome-based precision medicine in HCC, with the goal of improving clinical management and patient outcomes.},
}

@article {pmid41395292,
year = {2025},
author = {Ren, H and Wen, J and Liu, J and Wang, L},
title = {Gut microbiota in immunomodulation and infection prevention among multiple myeloma patients after chemotherapy: current evidence and clinical prospects.},
journal = {American journal of cancer research},
volume = {15},
number = {11},
pages = {4621-4638},
pmid = {41395292},
issn = {2156-6976},
abstract = {Multiple Myeloma (MM) is the second most common hematological malignancy, with its pathogenesis involving complex cytogenetic variations, tumor clonal evolution, and dynamic interactions between tumor cells and bone marrow stromal microenvironment. Recent studies highlight the role of the intestinal microbiota, a key component of the tumor-associated microenvironment, in regulates MM occurrence, progression, and treatment response via the "gut-bone marrow axis". Under physiological conditions, it protects the local microenvironment by regulating host metabolism and maintaining immune homeostasis. However, intestinal dysbiosis causes metabolic disorders and immune surveillance defects, promoting tumor growth, drug resistance, and poor prognosis. Though traditional treatments such as chemotherapy and hematopoietic stem cell transplantation have been optimized, chemotherapy disrupts intestinal mucosal integrity and impairs immunity, significantly increasing post-chemotherapy infections. These infections can interrupt treatment, worsen conditions, and reduce quality of life, leaving MM still intractable. Notably, microbiota-targeted interventions (e.g., probiotics, fecal microbiota transplantation [FMT]) have shown potential to reduce infection risk by restoring microbiota balance and repairing intestinal barriers. These interventions may also exert potential anti-tumor effects through immune microenvironment regulation and alleviate chemo/radiotherapy-related adverse reactions (e.g., nausea, diarrhea), offering a new direction for relapsed/refractory MM. This article summarizes the molecular regulatory network of the intestinal microbiota in the pathogenesis of MM and the research progress of microbiota-based interventions, aiming to provide a foundation for developing novel microbiome-oriented precision treatment regimens and improving chemotherapy tolerance and patient prognosis.},
}

@article {pmid41393538,
year = {2025},
author = {Manoria, PC},
title = {The Obesity Drug Revolution: New Frontiers in Pharmacotherapy.},
journal = {Cureus},
volume = {17},
number = {11},
pages = {e96713},
pmid = {41393538},
issn = {2168-8184},
abstract = {Obesity is the most prevalent condition in high-income nations, primarily associated with increased risk of diabetes, cardiovascular disease (CVD), hypertension, and hyperlipidemia. Lifestyle modifications are a key determinant in non-pharmacological management that includes a combination of nutritional therapy, a low-calorie diet, and exercise. Earlier, anti-obesity drugs had been withdrawn from the market due to their safety profiles with cardiovascular and neuropsychiatric toxicity. The current FDA-approved pharmacotherapy consists of orlistat, setmelanotide, phentermine-topiramate, naltrexone-bupropion, liraglutide, semaglutide, and tirzepatide. Among these, semaglutide has a better clinical and regulatory profile with the feasibility of dosing and frequency. Orforglipron, a non-peptide oral glucagon-like peptide-1 receptor agonist, offers parenteral efficacy with convenient dosing. Probiotics, prebiotics, and fecal microbiota transplantation promote moderate weight loss by regulating metabolism and inflammation. Mitochondrial uncouplers help energy utilization rather than appetite regulation, which focuses on metabolic efficiency. A few challenges in obesity management are financial barriers, weight-promoting medications, inadequate obesity training, discomfort with prescribing, and lack of reimbursement. Innovative therapeutic approaches, multidisciplinary care, and a patient-centered plan are required for better clinical outcomes. This review highlights the current and emerging therapies designed to enhance long-term outcomes in obesity care.},
}

@article {pmid41393108,
year = {2025},
author = {Sun, Y and Yang, H and Zhang, J and Cong, S and Wang, L and Yu, T},
title = {Development and emerging trends in gastrointestinal dysfunction of Parkinson's disease: a decade-long bibliometric analysis.},
journal = {Frontiers in aging neuroscience},
volume = {17},
number = {},
pages = {1712302},
pmid = {41393108},
issn = {1663-4365},
abstract = {Gastrointestinal (GI) dysfunction represents a prevalent non-motor symptom of Parkinson's disease (PD) that not only contributes significantly to disease progression but also substantially compromises patients' quality of life. Over the past decade, research in this domain has expanded considerably. To systematically delineate the knowledge framework and evolving trends, we performed a bibliometric analysis of publications on GI and PD from 2015 to 2025. A total of 924 articles were retrieved from the Web of Science Core Collection (WoSCC). Co-occurrence, clustering, and collaboration network analyses were performed using VOSviewer, CiteSpace, and the R package Bibliometrix. For findings validation, the PubMed database was incorporated as an independent external validation dataset, providing complementary verification of keyword analyses derived from WoSCC. Our analysis revealed a steady annual increase in publication output. China and the United States emerged as the most prolific contributors globally, with the latter attaining the highest total citation count. At the institutional level, Capital Medical University led in publication output, whereas the University of Helsinki ranked highest in both total and average citations. Among journals, Parkinsonism & Related Disorders published the most papers on this topic, while Movement Disorders received the most citations. Keyword cluster analyses identified three primary research frontiers: (1) pathogenesis, focusing on α-synuclein (α-syn), the brain-gut-microbiome axis, and the enteric nervous system; (2) clinical manifestations, especially dysphagia and constipation; and (3) therapeutic interventions, particularly fecal microbiota transplantation and probiotics. By integrating established knowledge and highlighting emerging trends, this review aims to inform and guide future research and clinical practice in the field of gastrointestinal dysfunction in PD.},
}

@article {pmid41392314,
year = {2025},
author = {Abahussin, HM and Alotaibi, MS and Alhazzaa, OA and Alotaibi, AG and Alsaab, SM and Aljawini, NA and Alawad, AO},
title = {Exploring the intricate link between gut microbiota dysbiosis and the aging process: implications for age-related diseases.},
journal = {Gut pathogens},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13099-025-00788-z},
pmid = {41392314},
issn = {1757-4749},
abstract = {Aging is a complex process marked by the gradual accumulation of impairments in molecules and tissues, leading to frailty and dysfunction. This decline is a significant risk factor for many debilitating conditions. Recently, gut microbiota dysbiosis has been identified as one of the hallmarks of aging. This review sheds light on the role of gut microbiota dysbiosis in accelerating aging and its relation to age-associated diseases, including neurodegenerative disorders, cardiovascular diseases, cancer and diabetes. Emerging research demonstrates a strong link between the gut microbiome and the aging process, although the underlying mechanisms remain under investigation. Animal studies suggest that targeting the gut microbiome may offer a promising approach to mitigate aging and related diseases. However, further human studies are needed to confirm these findings.},
}

@article {pmid41109531,
year = {2025},
author = {Kapoor, HK and Appolon, CB and Bardsley, CA and Kharel, K and Schneider, KR and Sharma, M and Mishra, AK and Dev Kumar, G and Pires, AFA and Dunn, LL and Mishra, A},
title = {Temporal and Environmental Drivers for Survival of Escherichia coli in Florida Soils Amended with Heat-Treated Poultry Pellets and Composted Poultry Litter.},
journal = {Journal of food protection},
volume = {88},
number = {12},
pages = {100639},
doi = {10.1016/j.jfp.2025.100639},
pmid = {41109531},
issn = {1944-9097},
mesh = {*Escherichia coli/growth & development/isolation & purification ; *Soil Microbiology ; Random Allocation ; Onions/growth & development/microbiology ; Colony Count, Microbial ; Florida ; *Fertilizers/microbiology ; Composting ; Poultry/microbiology ; Feces/microbiology ; Hot Temperature ; Soil/chemistry ; Linear Models ; Models, Biological ; Time Factors ; Humidity ; },
abstract = {Previous studies have shown that field environmental conditions influence pathogen survival in the soils amended with biological soil amendments of animal origin (BSAAOs). To address this, a two-year completely randomized design field study in Florida was conducted with plots amended with heat-treated poultry pellets (HTPPs), composted poultry litter (PL), and unamended (UN), all inoculated with E. coli. Onion bulbs were transplanted into selected HTPP plots (O-HTPP) and field cured after harvesting. Soil samples were enumerated for E. coli on days 0, 1, 3, 7, 14, 28, 56, 84, 112, 140, 147 (harvest day), and 161 (after curing). The E. coli data were used to fit a linear mixed effect model (LME) with five weather variables: cumulative rainfall (cmrain4), average air temperature (at601234), relative humidity (RH1234), wind speed (W1), soil temperature (ast1). Overall, E. coli levels were 1.8 and 1.6 log10CFU or MPN/g higher in HTPP than UN plots in Year 1 and Year 2. The LME for soil amendment plots identified weather parameters that significantly influenced E. coli survival; cmrain4 and W1 increased and decreased survival by 0.698 and 0.712 log10CFU or MPN/g (p < 0.01), in Year 1. In the LME that compared plots with and without onions, W1 significantly increased survival in soils by 0.504 log10CFU or MPN/g (p < 0.05) in Year 1 (p < 0.05). These robust LME models (R[2]: 0.88-0.92) can predict the E. coli population in soils amended with poultry-litter-based amendments with or without onions. However, future studies will benefit from frequent samplings at later time points.},
}

*Escherichia coli/growth & development/isolation & purification
*Soil Microbiology
Random Allocation
Onions/growth & development/microbiology
Colony Count, Microbial
Florida
*Fertilizers/microbiology
Composting
Poultry/microbiology
Feces/microbiology
Hot Temperature
Soil/chemistry
Linear Models
Models, Biological
Time Factors
Humidity

@article {pmid41391369,
year = {2025},
author = {Wang, S and Wu, J and Xu, L and Wu, S and Pei, X and Wang, H and Deng, L and Xu, H and Chen, X},
title = {WenDan Decoction activates neuronal autophagy in the hippocampus via the gut-brain axis to improve depressive-like behavior in HFD mice.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {150},
number = {},
pages = {157686},
doi = {10.1016/j.phymed.2025.157686},
pmid = {41391369},
issn = {1618-095X},
abstract = {BACKGROUND: High-fat diet (HFD) is implicated in depression pathogenesis. WenDan Decoction (WDD), a classical traditional Chinese medicine formula, shows promise for metabolic and psychiatric disorders, but its precise mechanisms require elucidation.

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

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

CONCLUSION: WDD ameliorates depressive-like behaviors in HFD mice by modulating the gut microbiota and metabolism to suppress PI3K/AKT/mTOR pathway activation and restore autophagic flux. This study provides crucial mechanistic insights into WDD's effects against depression.},
}

@article {pmid41391320,
year = {2025},
author = {Tang, N and Deng, G and Jin, Z and Chen, J and Wang, D and Luo, Y and Luo, Y and Zhang, G},
title = {Bacillus sp. S361 isolated from bioaerosols in pharmaceutical wastewater treatment plants aggravates Klebsiella pneumoniae-induced lung injury in rats by modulating the gut microbiota.},
journal = {Journal of hazardous materials},
volume = {501},
number = {},
pages = {140669},
doi = {10.1016/j.jhazmat.2025.140669},
pmid = {41391320},
issn = {1873-3336},
abstract = {Current research on bioaerosol diversity in pharmaceutical wastewater treatment plants (PWWTPs) remains limited, especially concerning pulmonary injury mechanisms. Bacterial diversity in two PWWTPs was investigated via high-throughput sequencing and culture-based isolation, revealing functional interactions with pathogenic Klebsiella pneumoniae (Kpn). Emissions showed bimodal size distributions: Plant A dominated by ≥ 7μm particles, Plant B by 0.65-1.1μm submicron fractions enriched with Pseudomonadota (formerly Proteobacteria). Strain S361 (Bacillus sp., Bacillota) isolated from AeT1 exhibited significant synergistic pathogenicity with Kpn. Whole-genome sequencing identified 51 antibiotic resistance genes (ARGs) across 12 resistance mechanisms and 86 virulence factors in Bacillus sp. S361. Mechanistically, Bacillus sp. S361 synergistically enhances pulmonary colonization and pathogenicity of Kpn via distinctive metabolic crosstalk. Co-exposure to S361 and Kpn disrupts gut microbiota homeostasis, inducing dysregulated short-chain fatty acid (SCFA) metabolism and intestinal barrier impairment. This gut-derived dysfunction mediates systemic inflammation through the gut-lung axis, ultimately amplifying Kpn-induced lung injury. Fecal microbiota transplantation (FMT) experiments confirmed gut microbiota's mediating role, as recipient rats developed pathological changes (alveolar septal thickening, inflammatory infiltration) mirroring co-infected groups. Notably, microbiota-depleted rats suffered more severe lung injury than protected counterparts, establishing gut dysbiosis as a critical determinant of pulmonary damage. These findings implicate PWWTP bioaerosols in driving Kpn pathogenicity via Bacillus sp. S361-mediated synergy and gut-lung dysregulation, necessitating targeted interventions for occupational risk mitigation.},
}

@article {pmid41390868,
year = {2025},
author = {Iskander, O and Michot, N and Courtot, L and Bourbao-Tournois, C and Artus, A and Thiery, J and Deffain, A and Proutheau, G and Bouayed, A and Salame, E and Demtröder, CR and Giger-Pabst, U and Ouaïssi, M},
title = {Evaluating the influence of metabolic bariatric surgery on urinary and fecal incontinence outcomes: a one-year postoperative analysis.},
journal = {Langenbeck's archives of surgery},
volume = {},
number = {},
pages = {},
doi = {10.1007/s00423-025-03947-7},
pmid = {41390868},
issn = {1435-2451},
}

@article {pmid41390455,
year = {2025},
author = {Isnard, S and Berini, CA and Parvathy, SN and Feng, H and Aiyana, O and Royston, L and Mabanga, T and Lakatos, PL and Bessissow, T and Klein, MB and Lebouché, B and Costiniuk, CT and Routy, B and Silverman, MS and Routy, JP},
title = {Fecal microbiota transplantation to reduce immune activation in ART-treated people with HIV with low CD4/CD8 ratio: protocol for the single-blind, randomized, placebo-controlled Gutsy study (CIHR/CTN PT038).},
journal = {Trials},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13063-025-09345-0},
pmid = {41390455},
issn = {1745-6215},
support = {CTN PT038//Canadian HIV Trials Network, Canadian Institutes of Health Research/ ; Cell Therapy network//Fonds de Recherche du Québec - Santé/ ; },
abstract = {BACKGROUND: Despite antiretroviral therapy (ART) controlling HIV viral replication, people with HIV (PWH) remain at risk for inflammatory non-AIDS comorbidities. Factors contributing to comorbidities in PWH on ART include spontaneous release of HIV products, CMV co-infection, microbial translocation, and gut dysbiosis, each driving systemic T-cell activation. In addition to ART, novel gut microbiota-modulating therapies could reduce epithelial gut permeability, microbial translocation, and immune activation. Fecal microbiota transplantation (FMT) from healthy volunteer is a promising therapy to counteract dysbiosis, protect from gut barrier damage, and lower systemic immune activation.

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

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

TRIAL REGISTRATION: ClinicalTrials.gov NCT06022406. Registered on 2024-08-01. https://clinicaltrials.gov/study/NCT06022406?cond=HIV&term=Gutsy&rank=1.},
}

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

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

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

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

CONCLUSIONS: Grain proteins diet-induced alleviate glucose metabolic disorders by enriching gut microbiota-derived indole metabolites, which improve intestinal homeostasis and inhibit hepatic gluconeogenesis through AhR and NLK/FOXO1 signaling. These findings highlight the therapeutic potential of grain proteins for T2D prevention and management.},
}

@article {pmid41389504,
year = {2025},
author = {Meenakshi, S and Amrutha, TV and Abubakar, M and Prakash, V and Kumar, N and Murti, K},
title = {Fluoride-induced gut dysbiosis in metabolic disorders: Mechanisms and public health implications.},
journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)},
volume = {93},
number = {},
pages = {127806},
doi = {10.1016/j.jtemb.2025.127806},
pmid = {41389504},
issn = {1878-3252},
abstract = {AIM: This review explores the effects of fluoride exposure and metabolic alterations linked to obesity and diabetes, and highlights preventive and therapeutic approaches to mitigate fluoride-driven metabolic risks.

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

CONCLUSION: Since fluoride contaminates drinking water in areas with an endemic tendency, defluoridation, exposure monitoring, and public awareness are essential preventive strategies. Future mechanistic and clinical studies are necessary to elucidate the pathways linking fluoride metabolic disease progression.},
}

@article {pmid41389450,
year = {2025},
author = {Mittal, A and Sharma, S},
title = {Gut microbiota and nutritional interventions in alcohol-associated liver disease: Mechanisms and therapeutic advances.},
journal = {Nutrition research (New York, N.Y.)},
volume = {145},
number = {},
pages = {8-24},
doi = {10.1016/j.nutres.2025.11.004},
pmid = {41389450},
issn = {1879-0739},
abstract = {Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality worldwide. Despite growing awareness of its burden, treatment options remain limited, with abstinence as the only widely accepted intervention. Recent research underscores the critical role of the gut-liver axis and nutritional status, particularly dietary protein, in modulating ALD pathogenesis and progression. This review aims to integrate current knowledge on the interplay between gut microbiota, dietary protein, and alcohol-induced liver injury, and to evaluate microbiota-targeted therapeutic strategies, including fecal microbiota transplantation (FMT), within this context. We examine how chronic alcohol intake reshapes the gut microbiome, impairs barrier function, and alters microbial metabolism. We discuss how dietary protein, based on source, quantity, and amino acid composition, influences microbial ecology and metabolite profiles, with plant and dairy proteins emerging as beneficial. The review also highlights advances in FMT, which shows promise in improving outcomes in severe alcoholic hepatitis. However, its efficacy is modulated by donor microbial composition and recipient compatibility, both of which may be influenced by diet. Furthermore, we address emerging evidence on the role of fungal and viral communities, which remain understudied contributors to ALD. Despite substantial progress, significant knowledge gaps persist. These include the need for clinical validation of preclinical findings, deeper exploration of nonbacterial microbiota, and a lack of personalized, nutrition-based interventions. Addressing these gaps through integrative, multiomic approaches will be essential to advancing precision therapeutics in ALD.},
}

@article {pmid41388767,
year = {2025},
author = {Hou, B and Shao, H and Yuan, D and Tham, EH},
title = {Skin and gut microbiome in atopic dermatitis: Mechanisms and therapeutic opportunities.},
journal = {Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology},
volume = {36},
number = {12},
pages = {e70265},
doi = {10.1111/pai.70265},
pmid = {41388767},
issn = {1399-3038},
support = {//National Medical Research Council/ ; },
mesh = {Humans ; *Dermatitis, Atopic/therapy/microbiology/immunology ; *Gastrointestinal Microbiome/immunology ; *Skin/microbiology/immunology ; *Dysbiosis/immunology/therapy ; Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; },
abstract = {The pathogenesis of atopic dermatitis (AD) comprises a combination of genetic, immune, and microbial factors. An imbalance in skin and gut microbiota composition, termed dysbiosis, may contribute to AD pathogenesis and severity through overgrowth of pathogenic microbes and suppression of healthy commensal colonization. These, in turn, promote barrier disruption and pro-inflammatory responses. The skin and gut microbiota composition plays crucial roles in AD, namely as early predictive biomarkers of AD onset; indicators of treatment response; and as future novel therapeutics such as probiotics, fecal, and skin microbiota transplantation. Such interventions aim to directly "reset" and restore a healthy microbial equilibrium, thereby fundamentally repairing barrier function, regulating immune homeostasis, and establishing new adjunctive pathways for the long-term management of AD.},
}

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

@article {pmid41387927,
year = {2025},
author = {Shi, F and Yang, Z and Zhang, L and Zou, D and Yu, J and Guo, N and Ren, S and Tang, X and Gu, C and Xu, R and Ru, Y and Zhang, Y and Wang, D},
title = {Deoxycholic acid derived from the gut microbiota involved in the regulation of adaptive thermogenesis in response to dietary protein restriction in plateau pika.},
journal = {Microbiome},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40168-025-02233-4},
pmid = {41387927},
issn = {2049-2618},
support = {32301301//National Natural Science Foundation of China/ ; 32330012//National Natural Science Foundation of China/ ; 23-2-1-26-zyyd-jch//Natural Science Foundation of Qingdao/ ; ZR2024QC355//Natural Science Foundation of Shandong/ ; },
abstract = {BACKGROUND: Most winter-active mammals experience protein restriction. Gut microbiota is a key regulator of host energy homeostasis during nutrient deficiency, yet cross talk between microbiota and factors (e.g., hormones, signaling molecules) that regulate host energy metabolism in a low-protein (LP) context has not been studied sufficiently.

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

CONCLUSIONS: Our study reveals an association between the gut microbiota and LP diet-associated regulation of FGF21 signaling and thermogenesis and further demonstrates that this relationship is influenced by interspecies microbial transfer, indicating a critical mechanism whereby horizontal microbial exchange between sympatric species enhances host energy homeostasis. These findings provide novel insights into our understanding of the adaptations of mammals to high-elevation environments. Video Abstract.},
}

@article {pmid41115624,
year = {2025},
author = {Mishra, R and Harvey, A and Guo, A and Tillotson, G and Feuerstadt, P and Khanna, S and Shannon, WD and Blount, KF},
title = {Microbiome and metabolome changes after fecal microbiota, live-jslm, administration are associated with health-related quality of life improvements.},
journal = {Anaerobe},
volume = {96},
number = {},
pages = {103006},
doi = {10.1016/j.anaerobe.2025.103006},
pmid = {41115624},
issn = {1095-8274},
mesh = {Humans ; *Quality of Life ; *Metabolome ; *Gastrointestinal Microbiome ; Male ; Female ; *Feces/microbiology ; Middle Aged ; *Fecal Microbiota Transplantation/methods ; *Clostridium Infections/prevention & control/therapy/microbiology ; Adult ; Aged ; Clostridioides difficile ; },
abstract = {OBJECTIVES: Increasing evidence indicates a gut microbiome-brain axis, but more robust statistical methods are needed to solidify this connection. In a large phase 3, randomized, placebo-controlled clinical trial (PUNCH CD3; NCT03244644), fecal microbiota, live-jslm (REBYOTA; RBL, previously RBX2660), was effective in preventing recurrent Clostridium difficile infections, and trial participants had significant gut microbiome and metabolome shifts concurrent with significant changes in health-related quality of life (HRQOL). Advanced statistical methods were applied to data from this trial to further explore and demonstrate associations between changing HRQOL and microbiome or metabolome changes.

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

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

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

CLINICAL TRIAL REGISTRATION: NCT03244644.},
}

Humans
*Quality of Life
*Metabolome
*Gastrointestinal Microbiome
Male
Female
*Feces/microbiology
Middle Aged
*Fecal Microbiota Transplantation/methods
*Clostridium Infections/prevention & control/therapy/microbiology
Adult
Aged
Clostridioides difficile

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

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

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

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

CONCLUSION: Our findings highlight that SLBZ is a promising therapeutic agent mitigating obesity-related cognitive impairment via the "gut microbiota-vitamin B6-neuroprotection" axis.},
}