@article {pmid41764851,
year = {2026},
author = {Guo, Q and He, Y and Cao, T and Lin, C and Deng, M and Wu, R and Cai, H},
title = {Tryptophan-kynurenine metabolism: A link between the gut microbiota dysbiosis and cognitive impairment.},
journal = {Microbiological research},
volume = {307},
number = {},
pages = {128481},
doi = {10.1016/j.micres.2026.128481},
pmid = {41764851},
issn = {1618-0623},
abstract = {Cognitive impairment is a central feature of neuropsychiatric and neurodegenerative disorders, significantly diminishing patients' quality of life. Emerging evidence underscores the role of gut microbiota dysbiosis in the progression of cognitive decline. The gut microbiota influences brain function through various mechanisms, with the kynurenine pathway standing out as a key biochemical route linking peripheral metabolism to central nervous system function, thereby impacting cognitive performance. Dysregulation of the kynurenine pathway has been closely associated with neurotransmitter imbalances, exacerbated neuroinflammation, and metabolic dysfunction, all of which contribute to the onset and progression of cognitive impairment. Recent studies suggest that interventions targeting the gut microbiota, such as probiotics, antibiotics, and fecal microbiota transplantation, may improve cognitive function by modulating the kynurenine pathway. This review examines the complex relationship between gut microbiota, the kynurenine pathway, and cognition, highlighting the potential of targeting kynurenine pathway-related enzymes and microbiota modulation as therapeutic strategies. Despite promising findings, the precise mechanisms and therapeutic potential of these interventions remain under investigation, offering new avenues for the treatment of cognitive disorders.},
}

@article {pmid41764528,
year = {2026},
author = {Zhang, W and Su, Q and Shi, H and Sun, Y and Li, X and Li, M and Wang, H and Yu, J and Wong, N and Chan, FKL and Zhang, J and Ng, SC},
title = {Discovery and characterization of Christensenella hongkongensis as a novel bacterium in the adenoma-carcinoma progression.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-07886-9},
pmid = {41764528},
issn = {1479-5876},
}

@article {pmid41763794,
year = {2026},
author = {Wei, K and Peng, L and Wei, Q and Wei, Y and Wang, L and Zhu, Y and Wei, Y and Wei, X},
title = {Amelioration of colitis by donor microbiota modulated with tea active ingredients: A fecal microbiota transplantation study.},
journal = {Food research international (Ottawa, Ont.)},
volume = {229},
number = {},
pages = {118473},
doi = {10.1016/j.foodres.2026.118473},
pmid = {41763794},
issn = {1873-7145},
abstract = {Fecal microbiota transplantation (FMT) using donor microbiota modulated by tea represents an emerging approach to ameliorate ulcerative colitis (UC). This study aims to demonstrate the amelioration of dextran sulfate sodium (DSS)-induced colitis by donor microbiota modulated with tea-derived bioactive ingredients-tea polyphenols (TPP), tea polysaccharides (TPS), or theabrownin (TB). Following transplantation of fecal microbiota modulated by TPP, TPS, or TB from donors into colitis mice, significant reductions in Disease Activity Index (DAI) were observed, alongside attenuated intestinal histopathological damage. Additionally, gut barrier integrity was enhanced, as indicated by upregulated expression of occludin and Muc2. Fecal microbiota modulated by TPP and TPS showed superior efficacy in alleviating colitis compared with TB-modulated microbiota. The mechanism involved that marked enrichment of beneficial genera, including Akkermansia (TPP-enriched) and Allobaculum/Lactobacillus (TPS-enriched), which promoted the biosynthesis of short-chain fatty acids (SCFAs) and secondary bile acids, while reducing primary bile acids levels. These metabolic changes enhanced intestinal barrier function and suppressed suppressing pro-inflammatory cytokines through the modulation of TLR4/NF-κB p65 and Nrf2/ARE signaling pathways. This study not only elucidates the mechanism of tea bioactive ingredients-modulated donor microbiota alleviates colitis through regulation of the gut-microbiota-metabolite axis, but also provides a foundation for FMT-based strategies in colitis intervention.},
}

@article {pmid41763137,
year = {2026},
author = {Zhou, S and Su, F and Gao, Q and Wang, M and Duan, J and Li, J},
title = {Cordyceps cicadae polysaccharides ameliorate ulcerative colitis by modulating the gut microbiota and regulating the bile acid/FXR/NF-κB signaling pathway.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {153},
number = {},
pages = {158007},
doi = {10.1016/j.phymed.2026.158007},
pmid = {41763137},
issn = {1618-095X},
abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease, closely linked to dysbiosis of the intestinal microbiota and abnormal bile acid homeostasis. Polysaccharides derived from Paecilomyces cicadae (CCP) exhibit immunomodulatory and anti-inflammatory effects. However, their therapeutic potential and underlying mechanisms in UC remain poorly elucidated.

PURPOSE: This research seeks to evaluate the therapeutic efficacy of CCP in the treatment of UC and utilizing the "microbiota-bile acid metabolism-immunity" axis, elucidates the mechanisms by which CCP enhances intestinal barrier integrity and ameliorates inflammation via modulation of the gut microbiota-mediated farnesoid X receptor (FXR)/NF-κB signaling pathway.

METHODS: The physicochemical properties of CCP were characterized by FTIR spectroscopy, HPLC, and SEM analyses. A dextran sulfate sodium (DSS)-induced colitis mouse model was used to evaluate the ameliorative effects of CCP. Gut microbial alterations were profiled by 16S rDNA sequencing, while targeted metabolomics enabled comprehensive quantification of bile acid profiles in serum and fecal samples. Fecal microbiota transplantation (FMT) was conducted to validate the microbiota-mediated actions of CCP. Downstream molecular mechanisms were examined using Western blotting and immunofluorescence assays to assess modulation along the microbiota-bile acid axis.

RESULTS: CCP is primarily composed of glucose, mannose, and galactose, exhibiting a characteristic polysaccharide structure with a uniform molecular weight distribution. Treatment with CCP significantly ameliorated DSS-induced colitis in mice, as evidenced by reduced weight loss, preserved colon length, and decreased histopathological damage. 16S rDNA analysis demonstrated CCP-driven restoration of intestinal microbial diversity and a marked increase in Clostridium Kas107-2 (cluster XIVa). Metabolomics revealed normalization of bile acid metabolism, with elevated synthesis of secondary bile acids (deoxycholic acid, lithocholic acid, 12-keto LCA) and reduced levels of primary bile acids (α/β-MCA). Mechanistically, CCP activated FXR signaling, suppressed IκBα phosphorylation, downregulated NF-κB signaling, and reduced production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). Enhanced expression of tight junction proteins (ZO-1, Occludin, Claudin-1) indicated improved epithelial barrier function. Notably, FMT from CCP-treated donors replicated these protective effects, confirming colitis attenuation, bile acid restoration, and inhibition of FXR/NF-κB signaling.

CONCLUSIONS: CCP ameliorate experimental UC by promoting the proliferation of Clostridium cluster XIVa, modulating bile acid metabolism to facilitate secondary bile acid biosynthesis, activating FXR pathways, and suppressing NF-κB-driven inflammatory responses, thereby reinforcing intestinal epithelial barrier integrity.},
}

@article {pmid41763136,
year = {2026},
author = {Guo, Y and Xu, X and Han, A and Song, F and Zhang, Y and Jiang, X and Yu, W},
title = {Isorhamnetin alleviates diet induced MASLD in mice by modulating gut microbiota and bile acid metabolism.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {153},
number = {},
pages = {157987},
doi = {10.1016/j.phymed.2026.157987},
pmid = {41763136},
issn = {1618-095X},
abstract = {BACKGROUND: With the increasing prevalence of sedentary lifestyles and high-fat, high-sugar diets, the incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) has continued to rise. Although the natural flavonoid compound isorhamnetin (ISO) has been shown to improve dyslipidemia in MASLD mice, its mechanism of action in regulating lipid metabolism via the gut microbiota and its metabolites remains unclear.

OBJECTIVE: This study investigates whether ISO can ameliorate high-fat diet-induced MASLD in mice in a dose-dependent manner and explores the mediating role of the gut microbiota in this process.

METHODS: Physiological monitoring, biochemical markers assessment, tissue section analysis, 16S rRNA sequencing, bile acid (BA) targeted metabolomics, and molecular analysis were performed on mouse tissues. In addition, fecal microbiota transplantation (FMT) from mice fed a high-dose of ISO further validated the regulatory role of the gut microbiota in MASLD mice. Molecular dynamics simulations and in vitro assays were performed to evaluate the interaction between ISO and FXR.

RESULTS: ISO dose-dependently reduced body weight and hepatic lipid content, inhibited lipid synthesis and promoted lipid oxidation. ISO reshaped the gut microbiota, increasing the relative abundance of Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae. These changes altered the BA pool composition by increasing the proportion of primary and conjugated BAs, activated the hepatic-ileal Farnesoid X Receptor (FXR) signaling axis, accelerated enterohepatic BA circulation, and reduced dietary fat absorption. Concurrently, ISO enhanced intestinal barrier integrity and alleviated hepatic inflammation. Fecal microbiota transplantation from ISO-treated mice partially reproduced these metabolic benefits. Molecular dynamics simulations and in vitro experiments further verified that ISO interacts with FXR and consequently enhances FXR signaling.

CONCLUSION: ISO alleviates MASLD by synergistically regulating gut microbiota and FXR signaling, highlighting its potential as a mild, multi-target natural therapeutic candidate for MASLD therapy.},
}

@article {pmid41762381,
year = {2026},
author = {Sasidharan Pillai, S and Ashraf, AP},
title = {Gut Microbiota and Metabolic Health: From Dysbiosis to Therapeutics.},
journal = {Diabetes therapy : research, treatment and education of diabetes and related disorders},
volume = {},
number = {},
pages = {},
pmid = {41762381},
issn = {1869-6953},
abstract = {The gut microbiota (GM) is a pivotal regulator of host metabolism and a contributor to the pathophysiology of obesity, type 2 diabetes (T2D), and metabolic syndrome (MS). Disruptions in GM composition and function are collectively termed dysbiosis. This review synthesizes current evidence on GM dysbiosis, moving beyond simple taxonomic associations, to examine functional drivers of metabolic dysfunction. Dysbiosis impairs metabolic health through several interconnected pathways: enhanced dietary energy extraction, compromised intestinal barrier integrity leading to metabolic endotoxemia, chronic low-grade "meta-inflammation," and the disruption of circadian rhythms and neuro-immune signaling. Beyond bacteria, dysbiosis of the gut virome and mycobiota may further modulate metabolic risk. Animal and emerging human studies indicate that reduced virome diversity and altered phage-bacteria interactions can amplify dysbiosis, promote inflammatory signaling, and impair metabolic homeostasis. Recognition of GM dysbiosis as a contributor to metabolic disease has prompted development of therapeutic strategies aimed at restoring microbial balance and function. These interventions span a spectrum from established clinical approaches with indirect microbiota effects to experimental therapies designed to directly manipulate microbial composition or activity. We evaluate the clinical readiness of GM-targeted therapies, including dietary patterns, prebiotics, probiotics, and fecal microbiota transplantation. While established metabolic treatments such as glucagon-like peptide-1 (GLP-1) receptor agonists and bariatric surgery significantly reshape the GM, direct microbial manipulations often yield variable results in human trials. We conclude that the future of metabolic management lies in personalized microbiomics, utilizing artificial intelligence and precision-based interventions to restore specific functional microbial deficits tailored to the individual host profile.},
}

@article {pmid41761979,
year = {2026},
author = {Guo, Z and Gao, Z and Zhao, Y and Ni, X and Zhang, W and Li, L and Ren, S and Li, Q and Guo, D and Yue, L and Liu, Y and Lin, L and Fan, S and Hai, X},
title = {Administering Bifidobacterium pseudolongum With Arsenic Trioxide Attenuates Acute Promyelocytic Leukemia in Mice by Restoring Immune Microenvironment and Intestinal Homeostasis.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {31},
number = {2},
pages = {48584},
doi = {10.31083/FBL48584},
pmid = {41761979},
issn = {2768-6698},
support = {82274028//National Natural Science Foundation of China/ ; 2022ZX02C09//Heilongjiang Key R&D Program/ ; //Fundamental Research Funds for the Provincial Universities in Heilongjiang Province (2025)/ ; JJ2025PL0189//Natural Science Foundation of Heilongjiang Province/ ; 2024M10//Innovation Fund of the First Affiliated Hospital of Harbin Medical University/ ; 2024M25//Innovation Fund of the First Affiliated Hospital of Harbin Medical University/ ; 230000253533210000086//2025 Central Government Fiscal Subsidy Fund for Medical Care Compliance and Capacity Enhancement (Traditional Chinese Medicine Undertakings and Inheritance and Development Component)/ ; },
abstract = {OBJECTIVE: Arsenic trioxide (ATO) is a cornerstone of acute promyelocytic leukemia (APL) therapy but induces severe gut microbiota dysbiosis, limiting its efficacy and safety. This study investigated whether adjunctive Bifidobacterium pseudolongum (BP) could mitigate these adverse effects and enhance therapeutic outcomes.

METHODS: 16S rRNA gene sequencing data of gut microbiota were obtained from a cohort of 22 APL patients treated with ATO-based regimens (20 of 22 data were obtained and analysis further), accessible under BioProject ID PRJNA935705. To evaluate the within-sample microbial community richness and evenness, alpha and beta diversity indices were calculated. Using a murine APL model, we compared ATO monotherapy with ATO+BP co-treatment. Analyses included fecal metagenomic sequencing, single-cell RNA sequencing (sc-RNA-seq), flow cytometric immune profiling, and assessment of intestinal tight junction proteins (claudin-1, occludin, and ZO-1) via immunofluorescence.

RESULTS: ATO treatment significantly reduced gut microbial diversity and depleted beneficial taxa. Sc-RNA-seq data showed that ATO could orchestrate the APL immune microenvironment mainly through functional activation of CD8+ T cells and monocytes. BP supplementation restored microbial homeostasis and synergistically enhanced ATO's antileukemic effect, reducing the leukemic burden in peripheral blood by 72% and in bone marrow by 64% compared to ATO alone. Mechanistically, BP preserved intestinal barrier integrity by upregulating tight junction protein expression and modulated anti-tumor immunity, notably increasing bone marrow CD8+ T cells by 2.21-fold.

CONCLUSIONS: BP is an effective adjunct to ATO therapy, counteracting gut dysbiosis, intestinal damage, and the immune microenvironment while synergistically improving antileukemic efficacy. Targeting the gut-leukemia axis with BP represents a promising strategy for improving the precision and safety of APL treatment.},
}

@article {pmid41761700,
year = {2026},
author = {Pepke, ML and Hansen, SB and Limborg, MT},
title = {The ageing holobiont: crosstalk between telomere dynamics, oxidative stress and the gut microbiome.},
journal = {Biological reviews of the Cambridge Philosophical Society},
volume = {},
number = {},
pages = {},
doi = {10.1002/brv.70152},
pmid = {41761700},
issn = {1469-185X},
support = {DNRF143//Danmarks Grundforskningsfond/ ; CF21-0356//Carlsbergfondet/ ; },
abstract = {The gut tissue is at the frontline of early onset of ageing. It exhibits high cell turnover rates and rapid telomere shortening, which can have systemic effects on the developing or senescing organism. We conducted a literature review of studies on the crosstalk between telomere length dynamics, telomerase activity, oxidative stress, and gut microbiota composition and activity in animals. Studies mainly on humans and animal models include correlations between telomere dynamics and gut microbiome components, particularly under pathogenic conditions, but also manipulations of either the gut microbiome through faecal microbiota transplantations or of telomere dynamics using telomerase knockout models. This synthesis reveals that components of the gut microbiome including microbial metabolites and pathogenic bacteria can affect telomere dynamics through oxidative-stress-inducing processes, and that telomere maintenance is critical in maintaining gut barrier and tissue integrity, which link inflammation and gut dysbiosis. Some of the interactions between the gut microbiome and host telomere dynamics are bidirectional and important in maintaining intestinal homeostasis. However, many of the causal molecular or cellular mechanisms - and how they translate into organismal senescence - remain to be identified. Furthermore, we highlight how recent advances in whole genome sequencing capacities and bioinformatic tools represent an often-unexploited resource for measuring telomere lengths and may be particularly valuable tools within the hologenomic framework outlined here. Investigating the role of telomere dynamics in mediating gut microbiota-host interactions in different species will improve our understanding of how crosstalk between these hallmarks of ageing shape holobiont physiology in general and the ageing phenotype in particular.},
}

@article {pmid41761646,
year = {2026},
author = {Chen, Y and Jie, W and Xu, Y and Chen, X and Zhu, S and Ma, Y and Hu, L and Chen, C and Liu, B and Xu, D and Cai, D and Liu, Z},
title = {Correlation study between gut microbiota and intestinal permeability in cerebral small vessel disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261418554},
doi = {10.1177/13872877261418554},
pmid = {41761646},
issn = {1875-8908},
abstract = {BackgroundDysbiosis of gut microbiota and increased intestinal permeability are associated with various diseases, and their relationship with cognitive dysfunction such as cerebral small vessel disease (CSVD) and Alzheimer's disease remains to be elucidated.ObjectiveThis study investigates the role of gut microbiota dysbiosis and its relationship with intestinal permeability in patients with cognitive impairment associated with CSVD (CSVD-CI).MethodsIntestinal permeability was detected in 21 patients with CSVD-CI and 20 healthy controls by testing urine lactulose/mannitol, and correlation analysis was performed between the test results and cognitive function assessment. 16S rRNA sequencing was used to analyze the different combination of gut microbiota. Feces of the patients or controls were gavaged into C57 mice, and gut barrier function, behavior, and metabolites were assessed.ResultsPatients with CSVD-CI have a higher incidence of hypertension, higher homocysteine levels, higher scores for white matter hyperintensities, and worse cognitive function. Their urinary mannitol recovery rate is higher, which is correlated with lower scores of cognitive function assessment. Alterations in the gut microbiota involve a reduction in Prevotella-9 alongside increases in Proteobacteria and Fusobacteria. Fecal microbiota transplantation (FMT) from patients with CSVD-CI increases intestinal permeability in mice, but does not change their cognitive function; meanwhile, fecal metabolomics analysis has identified alterations in bile acids and vitamins, which are associated with shifts in the gut microbiota.ConclusionsPatients with CSVD-CI have gut microbiota imbalance and increased intestinal permeability, which are associated with cognitive decline. FMT from these patients can cause intestinal leakage and the production of harmful metabolites in mice.},
}

@article {pmid41761296,
year = {2026},
author = {Ye, H and Yang, X and Zheng, M and Dong, W and Chen, X and Chen, J and Hu, M and Zhou, M and Zheng, P and Shen, L and Wu, Y and Zheng, K and Huang, XF and Yu, Y},
title = {Early risperidone exposure impairs cognitive function by perturbation of the gut microbiome and bile acids/tyrosine-PTP1B axis.},
journal = {Microbiome},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40168-026-02358-0},
pmid = {41761296},
issn = {2049-2618},
abstract = {BACKGROUND: Second-generation antipsychotics (SGAs) are increasingly being utilized in children and adolescents. Risperidone, one of the most commonly prescribed SGAs in this population, has been found to adversely affect cognitive function; however, limited knowledge exists regarding the impact of risperidone on the gut microbiome-brain axis. We hypothesized that the cognitive impairment induced by risperidone is mediated by alterations in the gut microbiome and its metabolites.

RESULTS: In this study, we found that early-life risperidone exposure impaired cognition in mice, including deficits in behavior tests and hippocampal dendritic architecture. The risperidone-exposed mice also exhibited gut microbiota dysbiosis along with damage to the intestinal barrier. Fecal microbiota transplantation (FMT) from treated donors to recipients demonstrated the causal role of the gut microbiome in risperidone-induced cognitive deficits. Of note, risperidone increased the abundance of species Escherichia coli, Eggerthella lenta, Ruminococcus gnavus, Clostridium perfringens, Clostridium difficile, and Blautia hydrogenotrophica. These altered species are identified to encode 7α-HSDH, 3β/α-HSDH, TyrB, and porA, the key enzymes in secondary bile acid metabolism and tyrosine metabolism. Furthermore, a significant reduction in tauroursodeoxycholic acid (TUDCA, the metabolite of bile acid metabolism) and accumulation of p-cresol (the metabolite of tyrosine metabolism) were observed in the brains of mice exposed to risperidone. Mechanically, TUDCA prevented cognitive impairment and endoplasmic reticulum (ER) stress in the hippocampus induced by risperidone, while p-cresol induced neuronal ER stress. Knockout of protein tyrosine phosphatase 1B (PTP1B, ER stress-associated protein) in neurons ameliorated cognitive impairment and neurological damage induced by risperidone.

CONCLUSIONS: This study, for the first time, reveals that early risperidone exposure induces gut microbiome dysbiosis and disturbs the bile acids/tyrosine-PTP1B axis to impair cognitive function. These findings alert the risk of gut and neurological side effects of SGAs treatment and highlight that it is crucial to maintain gut homeostasis during the brain developmental phases of children and adolescents with SGAs exposure. Video Abstract.},
}

@article {pmid41761083,
year = {2026},
author = {Mo, C and Shao, R and Shi, Z and Lou, X and Xue, J and Ning, D and Liu, Y and Jiang, W and Wei, X and Xiao, J and Wang, F and Chen, G},
title = {Fecal microbiota transplantation reduces susceptibility to post-antibiotic CLP-induced sepsis by modulating the gut microbiota and its metabolites.},
journal = {BMC microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12866-026-04858-3},
pmid = {41761083},
issn = {1471-2180},
support = {202401AS070017//Yunnan Provincial Basic Research Program/ ; 202302AA310042//The Yunnan Provincial Major Program in Biomedicine/ ; 8256080235//National Natural Science Foundation of China/ ; },
abstract = {Sepsis remains a leading cause of mortality in intensive care units, and antibiotics continue to serve as the cornerstone of treatment. However, their potentially detrimental effects on gut health are often overlooked. Although antibiotic exposure may increase susceptibility to disease, its contribution to the progression of sepsis has not been fully elucidated. In this study, we investigated the effects of antibiotics on the gut microbiota, microbial metabolites, and intestinal barrier integrity in healthy mice, and further evaluated their impact on subsequent sepsis outcomes. Using a cecal ligation and puncture (CLP)-induced sepsis model, we demonstrated that antibiotic-induced gut dysbiosis exacerbated intestinal barrier damage and significantly increased mortality. In contrast, fecal microbiota transplantation (FMT) markedly improved survival and restored intestinal barrier function. Mechanistically, the protective effects of FMT were associated with modulation of the Hippo signaling pathway, which was accompanied by reduced intestinal permeability. Collectively, these findings highlight the critical role of antibiotic-induced gut dysbiosis in the pathogenesis of sepsis and support FMT as a potential therapeutic strategy to alleviate intestinal barrier damage and improve survival in sepsis.},
}

@article {pmid41760447,
year = {2026},
author = {Martin, M and Nguyen, VM and Puyade, M and Broca, F and Roblot, P},
title = {Faecal incontinence in systemic sclerosis: A narrative review.},
journal = {La Revue de medecine interne},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.revmed.2026.02.001},
pmid = {41760447},
issn = {1768-3122},
abstract = {Although associated with impaired health-related quality of life, faecal incontinence (FI) is underscreened in cases of systemic sclerosis (SSc). Its pathophysiology is complex and multifactorial, encompassing vasculopathy, fibrosis and probably (autoimmune) neuropathy. FI prevalence in SSc seems to be 5-6-fold higher than in the age- and sex-matched general population and is severe in nearly 15% of cases. FI is associated with diarrhoea, small intestinal bacterial overgrowth, constipation, urinary incontinence, anticentromere positivity and some features of vasculopathy. FI should be regularly screened in all SSc patients. Simple self-questionnaires are useful tools, completed by meticulous digital rectal exam for anal and puborectalis tone and by neurological examination. In case of unexplained chronic constipation or diarrhoea, endoscopic explorations are mandatory first to search for organic cause. Anorectal manometry is recommended in case of suspected anorectal dysfunction. Management should be multidisciplinary and, in general, follows the recommendations applied to the general population. It consists mainly in diet and lifestyle modifications and biofeedback therapy. Loperamide or laxative/transanal irrigation could be proposed as options in case of chronic diarrhoea or terminal constipation respectively. Nerve stimulation and faecal microbiota transplantation require further studies before conclusions can be drawn.},
}

@article {pmid41759744,
year = {2026},
author = {Waghmare, PV and Kolekar, KA and Bashir, B and Kumbhar, PS and Patil, KS and Gupta, G and Prasher, P and Jha, SK and Disouza, J and Gurav, SS and Dua, K and Singh, SK},
title = {Advocating gut-retina connection and microbiota mediated pathways in management of age-related macular degeneration: Preclinical to clinical perspective.},
journal = {Ageing research reviews},
volume = {117},
number = {},
pages = {103071},
doi = {10.1016/j.arr.2026.103071},
pmid = {41759744},
issn = {1872-9649},
abstract = {Age-related macular degeneration (ARMD) is the primary manifestation of permanent vision loss internationally. Different factors that contribute to ARMD involve ageing, genetic predisposition, oxidative stress, immunological imbalances, aberrations in the breakdown of lipids, and persistent inflammation. Gut microbiota has emerged as the significant cause of ARMD by disrupting systemic immune and inflammatory responses and metabolic homeostasis. Age-related changes in gut microbiota (dysbiosis) cause lowered microbial diversity, enhanced gut permeability, and pro-inflammatory species, leading to macular damage. The healthy gut microbiota containing Lactobacillus casei, Lactobacillus plantarum, Lactobacillus rhamnosus, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, and Faecalibacterium prausnitzii, are responsible for maintaining gut homeostasis, protecting the retina, and preventing ARMD progression. In contrast, the elevated population of pathogenic species such as Escherichia coli, Prevotella, Desulfovibrio, Enterococcus faecalis, and Streptococcus salivarius in gut dysbiosis is involved in ARMD progression. This review explores gut microbiota and their dynamics in ageing. The age-dependent gut microbiota variations and potential biological implications for the progression of ARMD are discussed. The review also discusses observations from experimental animals and explores potential microbiome-centered treatment avenues, covering probiotics, synbiotics, dietary remedies, metabolite-based treatment, and fecal microbiota transplantation for managing ARMD. Furthermore, various challenges in the management of gut microbiota-driven ARMD are also briefed with future directions. Thus, a gut microbiota-focused paradigm can offer novel choices for ARMD prevention and treatment.},
}

@article {pmid41759374,
year = {2026},
author = {Zhou, H and Huang, Y and Chen, C and Song, M and Hylemon, PB},
title = {Gut microbiome and bile acid metabolism in liver disease: Mechanisms, clinical implications, and therapeutic opportunities.},
journal = {Pharmacological reviews},
volume = {78},
number = {2},
pages = {100120},
doi = {10.1016/j.pharmr.2026.100120},
pmid = {41759374},
issn = {1521-0081},
abstract = {The intricate interplay between the gut microbiome and bile acid metabolism via the gut-liver axis is fundamental to hepatic homeostasis. Perturbations in this axis are increasingly implicated in the pathogenesis of diverse liver diseases, including metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, cholestatic liver diseases, and hepatocellular carcinoma. This review integrates current understanding of hepatic bile acid synthesis, enterohepatic circulation, and gut microbial bile acid transformations, detailing how bile acids function as signaling molecules through nuclear receptors including farnesoid X receptor, pregnane X receptor, vitamin D receptor, constitutive androstane receptor, and G-protein-coupled receptors; G protein-coupled bile acid receptor 1 (also known as Takeda G protein-coupled receptor 5), and sphingosine-1-phosphate receptor 2. We explore disease-specific alterations in gut microbiota composition and bile acid profiles in metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, cholestatic liver diseases, and liver cancers, focusing on mechanisms linking gut dysbiosis, impaired intestinal barrier function, altered bile acid signaling, inflammation, and immune modulation to liver injury and progression. Furthermore, we discuss the clinical implications, highlighting the potential of microbiome signatures and bile acid profiles as diagnostic and prognostic biomarkers. Therapeutic strategies targeting the gut-liver axis, including probiotics, fecal microbiota transplantation, farnesoid X receptor agonists, and fibroblast growth factor 19 analogs, are reviewed. Finally, we address current challenges and future directions, emphasizing the need for multiomics integration, functional studies, and personalized medicine approaches to leverage the gut-liver axis for improved liver disease management. SIGNIFICANCE STATEMENT: Disruption of the gut microbiome-bile acid-liver axis is now recognized as a unifying mechanism driving multiple liver diseases, including metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, cholestatic liver diseases, and hepatocellular carcinoma. Unraveling the molecular and microbial interactions within this axis offers fundamental insights into disease pathogenesis and reveals novel therapeutic opportunities. Integrating multiomics technologies with artificial intelligence-based analytics will accelerate the discovery of predictive biomarkers and personalized interventions, advancing the field toward precision-based liver disease treatment protocols.},
}

@article {pmid41759265,
year = {2026},
author = {Qu, Y and Wang, P and Wang, D and Li, B and Yang, F},
title = {Intermittent fasting protects MPTP-induced Parkinson's disease mouse model through regulating gut microbiota dysbiosis.},
journal = {International immunopharmacology},
volume = {175},
number = {},
pages = {116447},
doi = {10.1016/j.intimp.2026.116447},
pmid = {41759265},
issn = {1878-1705},
abstract = {Parkinson's disease (PD) is a neurodegenerative disorder characterized by gut microbiota dysbiosis and excessive inflammatory responses. Intermittent fasting (IF) exerts neuroprotective effects on neurodegenerative diseases. However, the impact of IF on PD and its mechanisms still need to be elucidated. In the present study, we found that 13-week IF regimen (designed as alternate-day fasting) mitigated motor impairment, α-synuclein aggregation, and loss of dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Meanwhile, IF attenuated intestinal dysfunctions, intestinal pro-inflammatory cytokines (tumor necrosis factor-αlphα (TNF-α) and interleukin-1 beta (IL-1β)) levels, and gut barrier destruction. Furthermore, IF alleviated brain barrier impairment and suppressed the activation of astrocytes and microglia. Mechanistic studies revealed that IF suppressed the toll-like receptor 4 (TLR4)/NF-κB signaling pathway both in the colon and substantia nigra. 16S rRNA sequencing demonstrated that IF alleviated MPTP-induced microbiota dysbiosis, decreasing harmful bacteria abundances (Proteobacteria, Burkholderiales, Sutterellaceae, Parasutterella, Burkholderiales_bacterium, and Desulfovibrio_fairfieldensis) while increasing probiotic bacteria abundances (Oscillospirales, Rikenellaceae, and Lactobacillus_murinus), which were significantly correlated with the anti-inflammatory effects of IF. Gas chromatography-mass spectrometry (GC-MS) revealed that IF induced the levels of fecal short chain fatty acids (SCFAs). Antibiotics intervention abolished the beneficial effects of IF, suggesting that gut microbiota contributed to the neuroprotection of IF for PD. These findings suggest that IF regimen may serve as a novel therapeutic strategy for PD, likely linked to its regulation of gut microbiota to inhibit gut-brain axis inflammation.},
}

@article {pmid41757041,
year = {2026},
author = {Tschang, MA and Vuong, RD and Eilers, B and Chac, D and Waalkes, A and Penewit, K and Easton, A and Schuessler, B and Daniels, R and Weil, AA and Salipante, SJ and Gibbons, SM and Schindler, AG},
title = {If you give a mouse a poopsicle: a novel fecal microbiota transplant method for exploring the role of the gut microbiome in stress-related outcomes in mice.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.16.705192},
pmid = {41757041},
issn = {2692-8205},
abstract = {The microbiome-gut-brain axis is a mediator of stress-related disorders. The number of preclinical studies exploring the potential causal mechanism of this connection using fecal microbiota transplantation (FMT) is growing. However, the most common method for delivering fecal transplants in rodent models is still oral gavage, which creates an adverse experience that may confound stress-related outcomes. Here, we establish an alternative methodology for FMT that decreases stress induced by traditional experimental procedures. We first used preference and anxiety behavior assays to identify antibiotic therapies having maximal tolerability and minimal anxiolytic properties. We then collected feces from donor mice and homogenized them with a microbe-stabilizing buffer to create a slurry, which was frozen into pellets ("poopsicles") for subsequent FMT. Recipient mice voluntarily consumed the pellets, and blood was collected to compare corticosterone levels relative to traditional gavage FMT. Plasma corticosterone levels were found to be significantly lower in mice receiving FMT via pellets compared to oral gavage. Furthermore, relative to gavage FMT, microbial signatures of mice receiving FMT via pellets were more similar to those of the donor pellets at one week following final FMT and were sustained for up to six weeks, as assessed by comparing Bray-Curtis beta-diversity distances. Together, these results establish effective antibiotic and FMT methods that minimize treatment-induced stress, while effectively transplanting fecal microbes between murine conspecifics.},
}

@article {pmid41754939,
year = {2026},
author = {Cosimato, I and Brescia, A and Franci, G and Casolaro, V and Folliero, V},
title = {Emerging Therapeutic Approaches for Modulating the Intestinal Microbiota.},
journal = {Pharmaceutics},
volume = {18},
number = {2},
pages = {},
pmid = {41754939},
issn = {1999-4923},
abstract = {Background/Objectives: The gut microbiota is increasingly recognized as a key determinant of human health, playing a vital role in metabolism, immunity, and disease susceptibility. Dysbiosis, or microbial imbalance, is associated with gastrointestinal disorders such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and Clostridioides difficile infection (CDI), as well as extraintestinal conditions, including obesity, cardiovascular disease, and neuropsychiatric disorders. This review aims to provide an updated overview of emerging therapeutic strategies to modulate the gut microbiota to restore eubiosis and improve health outcomes. Methods: A narrative review of recent literature was conducted, focusing on preclinical and clinical studies investigating microbiota-targeted therapies. The review primarily covers innovative interventional approaches, including fecal microbiota transplantation (FMT), bacterial consortium transplantation (BCT), bacteriophage therapy and outer membrane vesicles (OMVs). Results: Evidence supports the role of probiotics, prebiotics, and synbiotics in remodeling microbial communities and improving host health, although their effects may be strain- and context-dependent. FMT has demonstrated high efficacy in the treatment of recurrent Clostridium difficile infections and is being studied for IBD, IBS and extraintestinal diseases, following the recent Food and Drug Administration approval of the first commercial FMT products. BCT offers a standardized alternative to donor-derived material, with early clinical successes such as FDA-approved SER-109. Phage therapy and OMVs represent promising frontiers, offering targeted microbial modulation and interactions with the immune system, although clinical data remain limited. Conclusions: Emerging gut microbiota modulation strategies offer new perspectives for precision medicine and could transform the prevention and treatment of many diseases, but further studies are needed to ensure their safety, standardization, and clinical application.},
}

@article {pmid41754110,
year = {2026},
author = {Singh, N and Hosein, E and Virkud, YV and Keet, C and Kulis, M},
title = {The Gut Microbiome in the IgE-Mediated Food-Allergic Patient-A Narrative Review.},
journal = {Nutrients},
volume = {18},
number = {4},
pages = {},
pmid = {41754110},
issn = {2072-6643},
abstract = {Food allergies (FA) are a major public health concern in both children and adults. Immunoglobulin E (IgE)-mediated FA is characterized by allergic reactions driven by allergen-specific IgE and the subsequent degranulation of mast cells and basophils. Current FA management primarily involves avoidance of allergen-containing food, and more recently, therapies such as oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and the anti-IgE biologic omalizumab. However, these interventions are not curative. The gut microbiome has been implicated in the development and regulation of oral tolerance to food antigens. This narrative review explores the role of probiotics, fecal microbiota transplantation (FMT), dietary interventions, and the interaction between the microbiome and OIT as potential strategies to manage established FA. We also explore barriers to their proliferation as part of regular clinical care. We conclude that future research should (1) address how the microbiome interacts with immunotherapies other than OIT, (2) explore the role of novel microbiome-based treatments like FMT as potential adjuvants to existing food allergy therapeutics, and (3) focus on developing standardized protocols and endpoints for microbiome-based therapeutics.},
}

@article {pmid41754077,
year = {2026},
author = {Ashkanani, G and Rob, M and Yousef, M and Ashkanani, A and Al-Najjar, YA and Laws, S and Chaari, A},
title = {The Effects of Microbiome Modulating Therapies on Inflammatory Markers in Autoimmune Disease: A Systematic Review and Meta-Analysis.},
journal = {Nutrients},
volume = {18},
number = {4},
pages = {},
pmid = {41754077},
issn = {2072-6643},
abstract = {BACKGROUND: Autoimmune diseases (ADs) are a growing global health burden, driven by chronic inflammation and immune dysregulation. The gut-immune axis plays a central role in their pathogenesis, with dysbiosis linked to several conditions. This has prompted investigation into nutraceuticals such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation as adjunctive therapies.

METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines, searching PubMed, Embase, and Web of Science for randomized controlled trials evaluating these interventions in autoimmune diseases.

RESULTS: Twenty-eight randomized control trials (RCTs) involving 2002 patients across 11 countries met inclusion criteria. Across the included RCTs, pooled analyses demonstrated significant reductions in c-reactive protein (CRP) (SMD -0.67, 95% CI -1.00 to -0.33; I[2] = 80.8%) and Tumor necrosis factor-alpha (TNF-α) (SMD -1.81, 95% CI -2.67 to -0.94; I[2] = 96%), a significant increase in Interleukin-10 (IL-10) (SMD 2.65, 95% CI 0.64 to 4.66; I[2] = 98%), and no overall significant effect on Interleukin-6 (IL-6) (SMD -0.89, 95% CI -1.99 to 0.22; p = 0.12). The strongest evidence of benefit was observed in rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. Pooled effects are limited by extreme between-study heterogeneity (I[2] 80-98%), leaving interpretation as exploratory rather than definitive. More limited or inconsistent findings were reported for systemic lupus erythematosus, hypothyroidism, axial spondylarthritis, and juvenile idiopathic arthritis. Heterogeneity in study design, probiotic strain selection, dosage, and treatment duration limited comparability across trials.

CONCLUSIONS: Overall, microbiome-targeted nutraceuticals appear promising for attenuating systemic inflammation in select autoimmune conditions, but results remain mixed. Larger, rigorously designed RCTs with standardized endpoints are needed to clarify efficacy, identify optimal formulations, and define patient populations most likely to benefit.},
}

@article {pmid41753607,
year = {2026},
author = {Yuan, H and Yi, L and Jia, H and Song, G and Cheng, W and Xie, Y and Zhu, J and Zhao, S},
title = {Gut Microbiota-Derived Metabolites to Regulate Intramuscular Fat Deposition in Pigs.},
journal = {Microorganisms},
volume = {14},
number = {2},
pages = {},
pmid = {41753607},
issn = {2076-2607},
support = {2024YFD1800404//National Key Research and Development Program of China/ ; 32360808//National Natural Science Foundation of China/ ; 31760645//National Natural Science Foundation of China/ ; 31260592//National Natural Science Foundation of China/ ; 31060331//National Natural Science Foundation of China/ ; 32560790//National Natural Science Foundation of China/ ; 202202AE090032//Major Science and Technology Project of Yunnan Province/ ; 202501AS070086//Major Science and Technology Projects of Yunnan Province/ ; },
abstract = {Intramuscular fat (IMF) is a crucial determinant of pork quality, influencing tenderness, flavor, and consumer preferences, yet selective breeding has reduced its levels in modern pigs. This review explores the molecular and cellular mechanisms of IMF deposition, including progenitor cell differentiation via pathways like Wnt/β-catenin and PPARγ, and advances in non-invasive detection methods such as hyperspectral imaging and Raman spectroscopy. It highlights correlations and causal links between the gut microbiota composition and IMF, established through omics analyses, fecal microbiota transplantation, and germ-free models. Key microbial metabolites, including short-chain fatty acids (SCFAs) and bile acids, modulate lipid metabolism bidirectionally via signaling receptors like GPR43, FXR, and TGR5. Future research should integrate multi-omics and develop probiotics to enhance IMF efficiency for sustainable pork production.},
}

@article {pmid41752141,
year = {2026},
author = {Wu, Y and Wong, OWH and Chen, S and Wang, Y and Zhang, G and Gao, Y and Chan, FKL and Ng, SC and Su, Q},
title = {Gut Microbiome Mediates the Causal Link Between Autism Spectrum Disorder and Dietary Preferences: A Mendelian Randomization Study.},
journal = {International journal of molecular sciences},
volume = {27},
number = {4},
pages = {},
pmid = {41752141},
issn = {1422-0067},
abstract = {Autism spectrum disorder (ASD) frequently co-occurs with malnutrition and gut dysbiosis, yet the underlying mechanisms remain poorly understood. Herein, this cross-sectional study first profiles dietary intake differences using dietary records from 210,874 participants (ASD = 232; non-ASD = 210,642; median age = 56.18) from the UK Biobank (UKB). Second, a bi-directional Mendelian Randomization (MR) approach serves to dissect relationships between ASD genetic susceptibility and dietary preferences by leveraging genome-wide association metadata from the iPSYCH-PGC (ASD) and UKB (dietary intake/food-liking traits). The same strategy is implemented to identify ASD-associated gut microbial species. Mediation analyses further assess the role of gut microbiota in the association between ASD and dietary preferences. Subjects with ASD exhibit higher consumption of cheese, processed meat, and oily fish, alongside lower intake of fruits, and demonstrate a preference for high-fat/salt and energy-dense foods. Additionally, the depletion of Turicibacter, Streptococcus, and Lachnospiraceae NK4A136 was causally related with ASD (all false discovery rate < 0.05; β = -0.15, β = -0.10, β = -0.093, respectively), which significantly mediates the ASD-associated elevated preference for high-fat/salt foods. In conclusion, ASD is associated with specific dietary preferences, likely mediated via gut microbiota, highlighting the future potential of gut microbiome-based therapeutics to modify eating disorders for ASD.},
}

@article {pmid41752122,
year = {2026},
author = {Wang, SJ and Nian, HY and Chen, ZH and Cui, L},
title = {Human Microbiota-Associated Pig Models for Translational Microbiome Research: A Scoping Review.},
journal = {International journal of molecular sciences},
volume = {27},
number = {4},
pages = {},
pmid = {41752122},
issn = {1422-0067},
support = {23141900100//Science and Technology Commission of Shanghai Municipality/ ; },
abstract = {The human microbiota-associated (HMA) pig model provides a physiologically relevant platform that bridges preclinical and translational research. However, its use remains limited, with existing studies showing considerable variation in establishment methods. This scoping review systematically evaluates methodological frameworks, engraftment outcomes, and research applications of HMA pig models. Additionally, it highlights their strengths, limitations, and implications for future studies. We conducted a comprehensive literature search in PubMed, Web of Science, Scopus, and Directory of Open Access Journals, following PRISMA guidelines for Scoping Reviews. The review examines the methodological foundations of HMA pig model generation and proposes a minimal reporting framework to promote standardization. It synthesizes studies on human microbiota engraftment in pigs, identifying factors that influence colonization efficiency. Finally, it summarizes current applications, discusses persistent limitations and translational challenges, and outlines opportunities for future research. Overall, these integrated insights aim to foster standardized, reproducible protocols for HMA pig model preparation and guide advancements in the field.},
}

@article {pmid41752118,
year = {2026},
author = {Kurdi, MA and Alotaibi, H and Alkhuraymi, AT and Aldahery, LN and Alhawaj, AF and Aldali, HJ},
title = {Amyotrophic Lateral Sclerosis (ALS) Genetics and Microbiota: A Comprehensive Review.},
journal = {International journal of molecular sciences},
volume = {27},
number = {4},
pages = {},
pmid = {41752118},
issn = {1422-0067},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a severe, progressive neurodegenerative disorder characterized by the loss of upper and lower motor neurons, affecting 0.5 to 2.6 per 100,000 people, with a median survival of 2 to 5 years. It is increasingly seen as a multisystem disorder, sharing essential clinicopathological features with Frontotemporal Dementia (FTD). This convergence arises from overlapping molecular processes, including severe oxidative stress, glutamate-mediated excitotoxicity, mitochondrial dysfunction, and widespread aggregated TDP-43 proteinopathy in both sporadic and familial cases. Several key genetic factors have been identified, particularly mutations in C9orf72, SOD1, TARDBP, and FUS, which serve as important targets for novel treatments, such as Tofersen, a recently approved SOD1-specific antisense oligonucleotide (ASO) gene therapy. Additionally, there is increasing evidence of the gut-brain connection. Dysbiosis, involving species such as Akkermansia muciniphila, and lower levels of neuroprotective metabolites, such as nicotinamide, may affect the course of the disease. As a result, treatment strategies are shifting toward a personalized approach. This includes using gene therapy, ranging from ASOs and RNA interference (RNAi) to new CRISPR-based genome editing. It also involves exploring microbiome-modulating treatments, such as specific probiotics and Fecal Microbiota Transplantation (FMT). While microbiome and gene therapies remain largely experimental, their potential is promising, as highlighted by the recent approval of Tofersen. These novel approaches could be further enhanced and guided by more robust diagnostic criteria and by investigating early multimodal treatment strategies to slow the progression of this complex disease.},
}

@article {pmid41751793,
year = {2026},
author = {Ptáček, O and Musil, Z and Guarnieri, G and Vrbacká, A and Moudrá, P and Zlámalová, A and Röszlerová, P and Tonhajzer, M and Musil, V and Morelli, A and Zach, P},
title = {Amyotrophic Lateral Sclerosis: The State of the Art on Treatments and the Therapeutic Role of the Intestinal Microbiome in Human Studies.},
journal = {International journal of molecular sciences},
volume = {27},
number = {4},
pages = {},
pmid = {41751793},
issn = {1422-0067},
support = {Cooperatio 39 - Oncology and Haematology//Charles University/ ; Cooperatio 33-Intensive Care Medicine//Charles University/ ; Cooperatio 36-Medical Diagnostics and Basic Medical Sciences//Charles University/ ; #NEXTGENERATIONEU//European Commission/ ; MNESYS (PE0000006) - A Multiscale integrated approach to the study of the nervous system in health and disease (DR. 1553 11.10.2022)//Ministry of University and Research (MUR), National Recovery and Resilience Plan (NRRP)/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disorder; to date, there is no long-term effective treatment. Recently, a relationship has been discovered between the human intestinal microbiome and the pathogenesis of ALS, on which basis faecal microbiota transplantation (FMT) has been proposed as a potential treatment for ALS. In this review, we compare three existing case studies examining the effect of FMT on the course of ALS, highlighting differences in methodology and results. In two of the studies, a halt in the progression of ALS symptoms was observed following FMT, accompanied by improvement in patient health. However, in the third and largest study, no significant effect of FMT was observed. The possible explanation for this discrepancy may be the intentional depletion of intestinal microorganisms using antibiotics prior to FMT in the third study. Future studies and/or completion of the ongoing clinical studies will help clarify the therapeutic effectiveness of FMT in ALS patients.},
}

@article {pmid41749649,
year = {2026},
author = {Pawłowski, P and Zaj, N and Iwaniszczuk, K and Grzelka, I and Makuch, W and Samardakiewicz-Kirol, E and Kościołek, A and Samardakiewicz, M},
title = {Personalizing Nutritional Therapy in Pediatric Oncology: The Role of Gut Microbiome Profiling and Metabolomics in Mitigating Mucositis and Enhancing Immune Response to Chemotherapy.},
journal = {Children (Basel, Switzerland)},
volume = {13},
number = {2},
pages = {},
pmid = {41749649},
issn = {2227-9067},
abstract = {INTRODUCTION: Intensive chemotherapy protocols and hematopoietic stem cell transplantation (HSCT) in children with cancer frequently lead to severe complications, such as mucositis and immune dysfunction. A growing body of evidence indicates that these complications are closely associated with the patient's nutritional status and the composition of the gut microbiome, which becomes profoundly destabilized as a result of cytotoxic therapy and antibiotic use.

BACKGROUND: The aim of this review is to critically evaluate the current state of knowledge on the interplay between gut dysbiosis, metabolomic profiles-with particular emphasis on short-chain fatty acids (SCFAs)-and treatment-related toxicity in pediatric patients, as well as to delineate pathways toward personalized nutritional therapy.

METHODS: A narrative review was conducted, including clinical and preclinical studies published between January 2015 and October 2025. PubMed/MEDLINE, Embase, Cochrane Library, and other databases were searched, focusing on changes in microbiome composition, correlations between gut-derived metabolites and the severity of complications (sepsis, graft-versus-host disease [GvHD], mucositis), and the effects of targeted nutritional interventions (probiotics, prebiotics, postbiotics, and fecal microbiota transplantation [FMT]) on microbiome modulation during anticancer therapy.

RESULTS: The analysis demonstrates that pediatric oncologic treatment leads to a marked reduction in microbial diversity, including the loss of protective Clostridiales taxa (e.g., Faecalibacterium), accompanied by an overgrowth of Proteobacteria pathobionts. Metabolomic profiling indicates that low SCFA levels (e.g., butyrate < 20-50 µmol/g) are a strong predictor of severe mucositis, prolonged neutropenia, and an increased risk of sepsis. Interventions aimed at restoring eubiosis and enhancing SCFA production show potential in strengthening the intestinal barrier, modulating immune responses, and enabling maintenance of the planned relative dose intensity (RDI) of chemotherapy by reducing treatment-related toxicity.

CONCLUSIONS: Gut microbiome profiling and fecal metabolomics represent promising prognostic tools in pediatric oncology. There is an urgent need for further research employing "omics"-based approaches to develop precise, individually tailored nutritional protocols. Such strategies, including postbiotics and FMT, may minimize treatment-related adverse effects and improve long-term clinical outcomes in pediatric patients.},
}

@article {pmid41749264,
year = {2026},
author = {Li, L and Cai, F and Liu, Z and Mo, W and Zhang, J and Qin, J and Liang, C and Xu, H and Liu, S and Tang, S and Peng, P and Liang, J and Ruan, H and Qin, R and Luo, F and Xiong, G and Yang, C and Zou, J and Liu, S and Geng, Y and Huang, J},
title = {Cross-kingdom microbial interactions in the gut during inflammatory bowel disease.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-07692-3},
pmid = {41749264},
issn = {1479-5876},
abstract = {BACKGROUND: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic, relapsing inflammation of the gastrointestinal tract. Recent studies emphasize the importance of gut microbiome dysbiosis in IBD pathogenesis, where interactions among bacteria, fungi, protozoa, and viruses contribute to inflammation, immune modulation, and epithelial barrier disruption.

METHODS: A comprehensive narrative literature review was conducted, focusing on human data and preclinical studies. Biomedical databases were searched for research related to microbial communities and their role in IBD development, specifically targeting microbial metabolites, gut fungi, protozoa, and viruses. Relevant studies were analyzed to assess their impact on immune pathways and microbial interactions.

RESULTS: The review reveals how different microbial kingdoms collaborate through bacteria-fungi, bacteria-protozoa, and phage-bacteria interactions, influencing metabolite production and immune system function. Specific microbial metabolites like short-chain fatty acids (SCFAs), indoles, bile acids, and others play significant roles in regulating mucosal immunity and barrier function. Disruptions in these interactions lead to chronic inflammation and contribute to disease progression. Multi-kingdom therapies, including probiotics, yeast-based treatments, and fecal microbiota transplantation (FMT), show promise but face challenges due to clinical variability.

CONCLUSION: Understanding IBD as a disruption of microbial ecosystems enables the development of personalized treatment strategies. Multi-omics studies and microbiome-based interventions targeting specific microbial interactions hold potential for more effective, individualized therapies in IBD management. However, further research and larger clinical trials are necessary for translating these findings into routine clinical practice.},
}

@article {pmid41747917,
year = {2026},
author = {Liu, X and Wang, Y and Medina, AA and Liu, D and Liu, J and Tang, W and Wang, M and Chen, X and Huang, K and Liu, M and Wang, C and Liu, Y},
title = {Probiotic-derived extracellular vesicles attenuate cholestatic liver damage via gut-liver axis.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {108152},
doi = {10.1016/j.phrs.2026.108152},
pmid = {41747917},
issn = {1096-1186},
abstract = {Gut-liver axis disturbance is the unifying pathogenesis of cholestatic liver diseases. The purpose of this study was to explore the underlying mechanisms of the probiotic Lactobacillus amylovorus (LA) and its secreted extracellular vesicles (EVs) on liver damage and fibrosis in 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed and multidrug resistance protein 2 knockout (Mdr2[-/-]) mice. Direct replenishment of LA is sufficient to correct the DDC-fed and Mdr2[-/-]-induced liver damage and fibrosis. Mechanistic studies show that the secretion of EVs is required for the LA-induced liver protective effects. RNA sequencing results demonstrated that the enrichment of differentially expressed genes was associated with glutathione metabolism, microbial metabolism in diverse environments and inflammatory mediator regulation of TRP channels in DDC-fed mice. Our findings revealed that LAEVs reshaped the gut microbiota, which was associated with increased bile acids (BAs) deconjugation and fecal BAs excretion, repaired gut barrier function, activated intestinal Farnesoid X receptor/Fibroblast growth factor 15 (FXR/FGF-15) axis, reduced liver BAs and oxidative stress level, which ultimately mitigated liver damage and fibrosis in both DDC-fed and Mdr2[-/-] mice. Notably, LAEVs did not ameliorate DDC-induced liver damage or fibrosis in antibiotic-treated mice. Furthermore, LAEVs provided protection against DDC-induced liver injury and fibrosis in fecal microbiota transplantation mice. LAEVs did not ameliorate DDC-induced liver damage or fibrosis in BSH inhibitor (CAPE)-treated mice. LAEVs also failed to improve liver damage and fibrosis in DDC-induced intestinal epithelial cell-specific FXR knockout (Fxr[△IE]) mice. This study revealed that LAEVs mitigated cholestatic liver fibrosis via regulating gut microbiota-bile acid-ROS axis in mice.},
}

@article {pmid41747877,
year = {2026},
author = {Waghmare, A and Rahangadale, S and Khare, K and Taksande, B and Umekar, M and Mangrulkar, S},
title = {Interweaving microglial senescence and gut microbiome dynamics in Alzheimer's disease - Mechanisms and therapeutic frontiers.},
journal = {Molecular and cellular neurosciences},
volume = {},
number = {},
pages = {104075},
doi = {10.1016/j.mcn.2026.104075},
pmid = {41747877},
issn = {1095-9327},
abstract = {Alzheimer's disease (AD), a prevalent neurodegenerative disorder characterized by cognitive impairment and neuronal degeneration, is increasingly recognized as being driven not only by the traditional amyloid-beta and tau pathologies but also by persistent neuroinflammation and systemic immune dysregulation. Emerging evidence implicates microglia senescence and gut microbiota dysbiosis is critical contributors to the neuroinflammatory landscape. Senescent microglia marked by reduced phagocytic ability and a pro-inflammatory secretory profile, are unable to clear pathogenic stimuli, thereby intensifying neuronal damage. Simultaneously, gut dysbiosis, characterized by a reduction in beneficial bacteria and an increase in endotoxin-producing species, elevates systemic inflammation and compromises the intestinal and blood brain barrier. Microbial metabolites, such as short-chain fatty acids (SCFAs) and lipopolysaccharides (LPS), affect microglial activation through the gut-brain axis, primarily via the TLR4/NF-κB and NLRP3 inflammasome pathways, thus promoting microglial senescence and exacerbating AD pathology. Therapeutic approaches that target these interacting pathways are rejuvenation of microglia with senolytics and stimulation of TREM2; regulation of gut microbiota with probiotics, prebiotics, lifestyle modification, dietary intervention; and fecal microbiota transplantation. Precision medicine approaches incorporating microbiome profiling and immunogenetic analysis will enhance these treatments. This review combines mechanistic insight into microglial aging and gut-brain interaction, emphasizes their synergistic role in AD pathogenesis, and delineates integrated therapeutic strategies. Dissection of the gut-microglia axis can reveal novel targets for early intervention to counteract neuroinflammation, improve cognitive function, and slow disease progression in AD.},
}

@article {pmid41747725,
year = {2026},
author = {Chen, K and Liu, Y and Rong, J and Dai, N and Xu, C and Li, H and Zhong, L and Wang, B and Ji, Z and Xie, S and Xu, Y and Yang, F and Wang, J and Li, D and Gu, Y and Zhou, X and Li, Y and Chen, M and Chen, Y and Li, W and Tang, Z and Cai, J and Xu, J and Xia, S and Zhan, Q and Zhou, Z},
title = {Strain-level genetic heterogeneity and colonization dynamics drive microbiome therapeutic efficacy.},
journal = {Cell host & microbe},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.chom.2026.02.002},
pmid = {41747725},
issn = {1934-6069},
abstract = {Fecal microbiota transplantation (FMT) has shown immunotherapeutic promise, yet its efficacy in non-small-cell lung cancer (NSCLC) remains unclear. We demonstrate that FMT improves anti-PD-1 efficacy and progression-free survival in a single-arm trial of advanced PD-L1-negative NSCLC. Analyzing over 2,000 metagenomes from diverse disease cohorts and healthy controls via a high-resolution strain-tracking framework, we reveal that phylogenetically distinct strains within identical species exert opposing therapeutic effects, resolving prior inconsistencies. We identify conserved ecological principles where engraftment relies on species-intrinsic metabolic and immune evasion traits. Crucially, successful colonization by specific beneficial strain variants correlates with positive clinical outcomes. Finally, we identify 38 priority species with robust engraftment potential and significant heterogeneity as candidates for precision therapeutics. These findings establish a strain-function-efficacy paradigm, elucidating the mechanistic basis of variable outcomes and guiding next-generation microbiome drug development.},
}

@article {pmid41746975,
year = {2026},
author = {Wang, G and Liu, L and Zhang, H and Mao, P and Lu, S and Zhang, X and Li, X and Song, C},
title = {Effects of tacrolimus treatment on the gut microbiota and metabolites in liver transplant recipients.},
journal = {PloS one},
volume = {21},
number = {2},
pages = {e0343817},
pmid = {41746975},
issn = {1932-6203},
abstract = {BACKGROUND: Liver transplantation (LT) is an effective treatment for patients with end-stage liver disease. In recent years, more and more evidence has supported the association between gut microbiota dysbiosis and the pathogenesis and progression of liver diseases.

METHODS: The study included 36 patients who received tacrolimus treatment after liver transplantation. Patients were stratified into subgroups according to three key variables: tacrolimus treatment duration, whole-blood tacrolimus concentration, and tacrolimus concentration-to-dose (C/D) ratio. Fecal samples and whole-blood specimens were collected from all participants. The Illumina HiSeq X platform was used to detect the gut metagenome, analyzing the composition and characteristics of the gut microbiota. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology was employed to detect metabolites of the gut microbiota, revealing their metabolic profiles.

RESULTS: As the duration of tacrolimus use increased, the diversity of the gut microbiota also increased, and the abundance of Escherichia coli_D and Bacteroides stercoris rose. Additionally, the abundance of Brunovirus and Uetakevirus tended to decrease. The abundance of gene functions related to chemical carcinogenesis and bacterial invasion of epithelial cells significantly decreased. In the gut microbiota metabolites, 16 substances like Astragaloside A and Acetyl-L-carnitine significantly increased, while 108 substances like Capsaicin and TLK significantly decreased. Within a certain range, as the concentration of tacrolimus in whole blood increased, the diversity of the gut microbiota increased. The abundance of Phocaeicola and Klebsiella increased, and the abundance of Peduovirus among viruses also rose. However, excessively high concentrations may lead to a decrease in the diversity of the gut microbiota and a decrease in the abundance of Phocaeicola. With respect to the C/D ratio, increased ratios were linked to significantly higher levels of 57 fecal metabolites (e.g., PC 34:2, 5-Methyl-2'-deoxycytidine), whereas 13 metabolites (e.g., FAHFA 2:0/16:0) showed substantial declines.

CONCLUSIONS: Tacrolimus treatment is associated with distinct alterations in gut microbiota and metabolites among LT recipients. These findings provide a preliminary framework for future investigations aimed at optimizing immunosuppressive regimens, although their clinical translational potential requires validation in larger-scale, prospective cohort studies.},
}

@article {pmid41745976,
year = {2026},
author = {Németh, K and Tóth, I and Lányi, K and Schilling-Tóth, BM and Csorba, S and Žura Žaja, I and Sterczer, Á},
title = {The Collaborative Collapse: Bile Acid Dysmetabolism as a Central Pathogenic Driver in Canine and Feline Multi-Systemic Disorders-From Mechanisms to Precision Therapeutics.},
journal = {Veterinary sciences},
volume = {13},
number = {2},
pages = {},
pmid = {41745976},
issn = {2306-7381},
support = {SRF-003//University of Veterinary Medicine Budapest/ ; 2025-2.1.1-EKÖP-2025-00022//Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund/ ; },
abstract = {Veterinary metabolomics has redefined bile acids (BAs) from simple digestive surfactants to systemic endocrine signals within a microbial-host metabolic axis. This review aims to evaluate how BA dysmetabolism acts as a central pathogenic factor in canine and feline disease. We analyze the BA pool's integrity, which depends on a specialized functional guild, primarily Peptacetobacter hiranonis, responsible for 7α-dehydroxylation. We delineate two principal pathological profiles: (1) microbial collapse, characterized by secondary bile acid (SBA) depletion and compromised farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) signaling, which exacerbates inflammation in chronic enteropathy (CE), protein-losing enteropathy (PLE), and exocrine pancreatic insufficiency (EPI); and (2) hepato-biliary spillover, wherein host-induced dysfunction results in primary bile acid (PBA) excess. Recent data have linked these disruptions to skeletal health, feline renal fibrosis, cardiac remodeling in myxomatous mitral valve disease (MMVD), and neuroinflammation in epilepsy and hepatic encephalopathy. The discovery of microbially conjugated bile acids (MCBAs) and microbial extracellular vesicles (MEVs) reveals highly specific, vesicle-mediated communication pathways impacting systemic health. Diagnostic protocols should prioritize functional profiling, including the dysbiosis index (DI), serum conjugated BA analysis, and SBA/PBA ratios. Clinical management is moving beyond empirical fecal microbiota transplantation (FMT), towards precision synthetic microbial consortia (SynComs), neuroprotective BAs like tauroursodeoxycholic acid (TUDCA), and molecular postbiotics to restore the collaborative metabolome.},
}

@article {pmid41745910,
year = {2026},
author = {Cao, X and Zhou, L and Ding, Y and Ma, C and Chen, Q and Li, N and Ren, H and Yan, P and Jia, J},
title = {Study of Fecal Microbiota Transplantation Ameliorates Colon Morphology and Microbiota Function in High-Fat Diet Mice.},
journal = {Veterinary sciences},
volume = {13},
number = {2},
pages = {},
pmid = {41745910},
issn = {2306-7381},
support = {ZR2023MC164//the Natural Science Foundation of Shandong Province/ ; 2022KJ137//the Youth Innovation Team Project Program of Shandong Provincial Education Department/ ; },
abstract = {This study investigates whether fecal microbiota transplantation (FMT) can alleviate gut microbiota dysbiosis induced by a high-fat diet (HFD) through modulation of fatty acid metabolism, competition for nutrients, production of short-chain fatty acids (SCFAs), and restoration of mucus layer integrity. To elucidate the mechanisms by which FMT regulates colonic microbial function and host metabolic responses, 80 male Bal b/c mice were randomly assigned to four experimental groups (n = 20 per group): Normal Diet Group (NDG), High-Fat Diet Group (HDG), Restrictive Diet Group (RDG), and HDG recipients of NDG-derived fecal microbiota (FMT group). The intervention lasted for 12 weeks, during which body weight was monitored biweekly. At the end of the experiment, tissue and fecal samples were collected to assess digestive enzyme activities, intestinal histomorphology, gene expression related to gut barrier function, and gut microbiota composition via 16S rRNA gene sequencing. Results showed that mice in the HDG exhibited significantly higher final body weight and greater weight gain compared to those in the NDG and RDG (p < 0.05). Notably, FMT treatment markedly attenuated HFD-induced weight gain (p < 0.05), reducing it to levels comparable with the NDG (p > 0.05). While HFD significantly elevated the activities of α-amylase and trypsin (p < 0.05), FMT supplementation effectively suppressed these enzymatic activities (p < 0.05). Moreover, FMT ameliorated HFD-induced intestinal architectural damage, as evidenced by significant increases in villus height and the villus height-to-crypt depth ratio (V/C) (p < 0.05). At the molecular level, FMT significantly downregulated the expression of pro-inflammatory cytokines (IL-1β, IL-1α, TNF-α) and upregulated key tight junction proteins (Occludin, Claudin-1, ZO-1) and mucin-2 (MUC2) relative to the HDG (p < 0.05). 16S rRNA analysis demonstrated that FMT substantially increased the abundance of beneficial genera such as Lactobacillus and Bifidobacterium while reducing opportunistic pathogens including Romboutsia (p < 0.05). Furthermore, alpha diversity indices (Chao1 and ACE) were significantly higher in the FMT group than in all other groups (p < 0.05), indicating enhanced microbial richness and community stability. Functional prediction using PICRUSt2 revealed that FMT-enriched metabolic pathways (particularly those associated with SCFA production) and enhanced gut barrier-related functions. Collectively, this study deepens our understanding of host-microbe interactions under HFD-induced metabolic stress and provides mechanistic insights into how FMT restores gut homeostasis, highlighting its potential as a therapeutic strategy for diet-induced dysbiosis and associated metabolic disorders.},
}

@article {pmid41745224,
year = {2026},
author = {Spaggiari, L and Tedeschi, G and Benatti, G and De Benedittis, M and Franzè, MT and Pinetti, D and Pericolini, E and Ardizzoni, A},
title = {Untargeted Metabolomic Analysis of Cell-Free Supernatants (CFSs) from Different Clinical Isolates of Saccharomyces cerevisiae and Their Effects on Candida albicans Virulence.},
journal = {Journal of fungi (Basel, Switzerland)},
volume = {12},
number = {2},
pages = {},
pmid = {41745224},
issn = {2309-608X},
support = {not applicable//FAR Dipartimentale 2024 (Ardizzoni) and FAR Dipartimentale 2025 (Pericolini)/ ; },
abstract = {Saccharomyces cerevisiae probiotic properties are effective for the treatment of infections by the opportunistic pathogen Candida albicans. Here, we assessed the anti-Candida effect of cell-free supernatants (CFSs) from three different fecal isolates and one ATCC strain of S. cerevisiae. We evaluated C. albicans growth inhibition through CFUs, and the impairment of virulence factors (adhesion, biofilm formation, and metabolic activity) by crystal violet and XTT assays. An untargeted metabolomic analysis of the CFSs was also performed. The CFSs moderately reduced C. albicans growth, but they could impair C. albicans virulence by reducing its capacity to adhere and to form a biofilm, and by decreasing the metabolic activity of biofilm-embedded fungal cells. The untargeted metabolomic analysis indicated an overexpression of N-acetyl-DL-tryptophan and other molecules derived from its metabolism (kynurenic acid and indole-3-acrylic acid), the dipeptides glycyl-L-leucine, prolyl-leucine, and γ-L-glutamyl-L-leucine, and the unconventional nucleotide inosine in the CFSs from fecal isolates, as compared to the reference strain. Further studies are warranted to better characterize the metabolome of these CFSs. Should the effects described here also be confirmed in vivo, the possible future employment of S. cerevisiae CFSs as a postbiotic aid to the current antifungal therapy may be considered.},
}

@article {pmid41745080,
year = {2026},
author = {Kumar, S and Himanshu, and Gaur, P and Ahmad, S and Puri, P and Raj, VS and Pandey, RP},
title = {Microbiota Transplantation as a Future Novel Therapeutic Strategy Approach.},
journal = {Diseases (Basel, Switzerland)},
volume = {14},
number = {2},
pages = {},
pmid = {41745080},
issn = {2079-9721},
abstract = {Bacterial vaginosis (BV) is a leading cause of genital discomfort among women globally, and it arises from dysbiosis of the vaginal ecosystem characterized by the overgrowth of pathogenic bacteria. Current therapeutic strategies primarily rely on antibiotics and/or probiotics, which demonstrate clinical efficacy but are frequently associated with limitations such as antimicrobial resistance, high recurrence rates, and incomplete restoration of a healthy vaginal microbiota. Inspired by the success of fecal microbiota transplantation in gastrointestinal disorders, vaginal microbiome transplantation (VMT) from healthy donors has emerged as a potential alternative therapeutic approach for BV. However, experimental and early clinical studies indicate that VMT efficacy is not uniform across individuals, with considerable inter-individual variability in treatment outcomes. Host genetic factors, baseline vaginal microbial composition, immune status, and environmental influences are likely to modulate therapeutic success, underscoring the need for personalized interventions. This article critically evaluates the shortcomings of existing standardized treatments, highlights the potential advantages and challenges of VMT, and discusses emerging, precision-based therapeutic strategies for BV in light of recent research advances and ongoing clinical trials worldwide.},
}

@article {pmid41744425,
year = {2026},
author = {Sandeep, G and Pahari, S and Nayak, V and Gundamaraju, R and Mishra, P and Misra, A},
title = {The Gut-Prostate Axis: Decoding the Interplay of Environmental Factors, Microbial Metabolites, and Hormonal Regulation in Prostate Cancer Pathogenesis.},
journal = {Technology in cancer research & treatment},
volume = {25},
number = {},
pages = {15330338261424322},
pmid = {41744425},
issn = {1533-0338},
abstract = {Prostate cancer remains one of the most common malignancies in men, with its progression strongly influenced by androgen signaling. While genetic alterations are well-documented in prostate cancer, growing evidence highlights the contribution of environmental factors, particularly diet and the gut microbiome, in modulating disease risk and therapy response. The gut microbiota plays a crucial role in regulating host metabolism, immune responses, and hormone activity. Recent findings suggest that specific microbial communities influence androgen biosynthesis and metabolism through enzymes such as β-glucuronidase, altering systemic androgen availability and imp acting tumor progression. Additionally, microbial metabolites, including short-chain fatty acids, secondary bile acids, and bacterial genotoxins, can affect inflammatory pathways and cellular signaling relevant to prostate tumorigenesis. Experimental studies also indicate that modifying the gut microbiota through dietary interventions, probiotics, or fecal microbiota transplantation can influence tumor growth and improve responses to immunotherapy and hormone-based treatments. In this review we present the current knowledge on gut-prostate axis, examine the mechanistic links between microbial activity and prostate cancer biology, and discuss emerging microbiome-based strategies as potential therapies. A deeper understanding of this bidirectional crosstalk could pave the way for microbiome-informed approaches to prevention, diagnosis, and personalized treatment of prostate cancer.},
}

@article {pmid41743894,
year = {2026},
author = {Jayathilaka, NS and Wijekoon, KJ and Sachinthani, SDD and Weththasinghe, AV and Ganamurali, N and Sabarathinam, S},
title = {Enteroendocrine hormones and gut microbiota in obesity: a systematic review from mechanistic insight to precision metabolic care.},
journal = {Journal of diabetes and metabolic disorders},
volume = {25},
number = {1},
pages = {73},
pmid = {41743894},
issn = {2251-6581},
abstract = {PURPOSE: This systematic review aims to synthesize current evidence on enteroendocrine cell alterations in obesity, elucidate the mechanisms by which gut microbial taxa and metabolites regulate gut hormone release, and assess therapeutic innovations targeting the microbiota-enteroendocrine axis for precision metabolic care.

METHODS: A systematic search of PubMed, Web of Science, Scopus, and Embase was conducted from January 2015 to July 2025 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Studies examining enteroendocrine cell function, gut microbiota composition, and their metabolic interactions in human obesity, animal models, and cellular systems were included. Data were extracted on gut hormone levels, microbial community structure, short-chain fatty acid production, and therapeutic interventions. Quality assessment was performed using the Cochrane Risk of Bias tool for randomized controlled trials and Newcastle-Ottawa Scale for observational studies.

RESULTS: Microbial dysbiosis characterized by depletion of short-chain fatty acid-producing bacteria is associated with impaired gut hormone release and altered free fatty acid receptor signaling. Therapeutic strategies including glucagon-like peptide-1 receptor agonists are associated with substantial weight loss, whereas probiotics, prebiotics, and fecal microbiota transplantation show variable and generally modest metabolic effects in human studies.

CONCLUSION: The microbiota-enteroendocrine axis represents a promising therapeutic target for obesity management, supported by mechanistic and associative evidence.Multi-modal precision approaches integrating hormonal pharmacotherapy with microbiota modulation may enable more durable metabolic benefits and personalized obesity treatment.},
}

@article {pmid41743795,
year = {2026},
author = {Zhang, J and Ji, J and Dai, X and Li, B and Liu, T and Zhang, S and Yu, Y},
title = {Microplastics and Nanoplastics Cause Thyroid Dysfunction in Adolescent Mice through the Intestinal Microbiota-Mediated Hypothalamus-Pituitary-Thyroid Axis.},
journal = {Environment & health (Washington, D.C.)},
volume = {4},
number = {2},
pages = {313-323},
pmid = {41743795},
issn = {2833-8278},
abstract = {Polypropylene (PP) and poly-(ethylene terephthalate) (PET) plastic products are widely used in diet packaging and may generate microplastics (MPs) and nanoplastics (NPs) during use. However, their effects and mechanisms on causing endocrine system diseases remain unclear. Here, we established a dietary exposure mouse model using micro and nanoplastics (MNPs) and found that MNPs caused a decrease in thyroid function in adolescent mice. Fecal microbiota transplantation (FMT) was used to reconstruct the intestinal microbiota of mice to reveal the mechanisms of thyroid dysfunction. The abundance of Bacteroides in the intestinal tract significantly changed after FMT. PP-MPs and NPs affected the levels of lysophosphatidylethanolamine and fatty acid esters of hydroxy fatty acids, respectively, which competitively bound to thyrotropin receptor (TSHR) on the thyroid gland, thus affecting the thyroid function. PET-MNPs affected the level of 4-hydroxy-3-methoxyphenylglycol sulfate, which regulated the activity of sympathetic nervous system by acting on the thyrotropin-releasing hormone receptor and TSHR in mice, thereby interfering with the regulatory function of the hypothalamus-pituitary-thyroid (HPT) axis on the synthesis and secretion of thyroid hormones. This study emphasizes the key role of intestinal microbiota-mediated HPT axis in thyroid dysfunction caused by MNP exposure and provides theoretical basis for the prevention of endocrine-related diseases during adolescence caused by MNPs.},
}

@article {pmid41743374,
year = {2026},
author = {Marasco, G and Meacci, D and Sarnelli, G and Tosetti, C and Cremon, C and Savarino, EV and Barbara, G},
title = {Diarrhea management: from pathophysiology to microbiota modulation.},
journal = {Therapeutic advances in gastroenterology},
volume = {19},
number = {},
pages = {17562848261424324},
pmid = {41743374},
issn = {1756-283X},
abstract = {Diarrhea, whether acute or chronic, is a common clinical condition with numerous causes that collectively impose significant health, economic, social, and psychological burdens worldwide. Based on its duration, diarrhea is classified as acute when lasting less than 2 weeks and chronic when persisting for more than 4 weeks. From a pathophysiological standpoint, diarrhea can be categorized into four main types: osmotic, secretory, inflammatory, and motility-related. Acute diarrhea is most commonly caused by infectious gastroenteritis and tends to have a self-limited course. In contrast, chronic diarrhea presents a more complex diagnostic challenge due to its varied etiologies and clinical presentations. A shared feature among many causes of both acute and chronic diarrhea is an alteration in the gut microbiota, a condition referred to as dysbiosis. While acute infections often result in temporary microbial imbalance, chronic conditions such as irritable bowel syndrome and symptomatic uncomplicated diverticular disease are associated with persistent dysbiosis. This review aims to explore the most prevalent causes and underlying mechanisms of acute and chronic diarrhea, with a particular focus on the role of the gut microbiota. It will also examine the principal therapeutic strategies aimed at modulating intestinal microbiota, including prebiotics, probiotics, antibiotics, and fecal microbiota transplantation.},
}

@article {pmid41743065,
year = {2026},
author = {Ren, D and Chai, X and Xiang, C and Zhao, Y and Sun, P and Wang, M and Li, J and Wu, J and Yi, C and Chen, S and Li, E and Zhao, S},
title = {Acer truncatum Bunge seed oil attenuates learning and memory impairment in AD mouse model via modulating gut microbiota and metabolism.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1757330},
pmid = {41743065},
issn = {2296-861X},
abstract = {This study aimed to clarify the neuroprotective effect of Acer truncatum Bunge seed oil (ASO) and its interactions with the gut microbiota in transgenic mice with 5 × Familial Alzheimer's disease (5 × FAD). The AD-transgenic mice were fed with standard diet supplemented with 4% ASO from one to six months of age. The result show that ASO intervention can alleviate learning and memory impairment, enhance motor coordination and endurance, and reduce Aβ deposition in the brains. It also inhibit the proliferation of microglia and astrocytes, decrease the levels of IL-1β, IL-6, and TNF-α in the hippocampus and serum. Then, ASO could increase the Chao1 index and Shannon index, alter the gut microbiota composition, specifically, enhance the growth of gut bacteria correlated with the production of SCFAs, including Ruminococcaceae, Butyricicoccus, Sutterella and others, particularly those related to butyrate production. Additionally, ASO can increase the concentrations of SCFAs in fresh feces and serum, particularly butyric acid. ASO could primarily modulate the biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, and sphingolipids metabolism in serum. At the same time, Fecal microbiota transplantation (FMT) could reduce Aβ deposition, enhance learning and memory. Finally, Supplementation of sodium Buty also mitigate learning and memory impairments. This study highlights the gut microbiota might be a potential therapeutic target for AD and provides a scientific foundation for developing novel pharmaceuticals or nutraceuticals.},
}

@article {pmid41741396,
year = {2026},
author = {Garcia-Guevara, F and Resink, T and Clasen, F and Uhlén, M and Achour, A and Shoaie, S},
title = {Temporal dynamics of gut biosynthetic gene clusters link persistent colonization and engraftment in fecal microbiota transplantation.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2634469},
pmid = {41741396},
issn = {1949-0984},
abstract = {The human gut microbiome carries a large array of biosynthetic gene clusters (BGCs) that encode the production of secondary metabolites, yet their temporal dynamics and role during microbial colonization remain largely unexplored. Here, we tracked BGCs profile over time in a cohort of healthy adults, and identified two distinct groups: persistent, which are stable over time, and transient, which are more sporadic. Functional annotations indicated persistent gene clusters are enriched in antibiotic resistance mechanisms, while transient ones more frequently carry virulence-associated genes. We then examined colonization of these two groups in the context of fecal microbiome transplantation. Our results show that persistent gene clusters exhibit higher colonization rates than transient ones. These findings contribute to our understanding of how microbial metabolites influence host health, potentially guiding future therapeutic strategies targeting the microbiome.},
}

@article {pmid41738638,
year = {2026},
author = {Eriksen, LL and Støy, S and Hansen, MM and Gatten, EP and Erikstrup, C and Kelsen, J and Mullish, BH and Marchesi, JR and Thomsen, KL and Dahlerup, JF and Dahl Baumwall, SM and Hvas, CL},
title = {Dynamics in circulating immune cell subsets after faecal microbiota transplantation for recurrent Clostridioides difficile infection.},
journal = {Clinical and translational gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.14309/ctg.0000000000001008},
pmid = {41738638},
issn = {2155-384X},
abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile infection (rCDI). Adverse reactions to FMT occur early, and cellular immune responses after FMT may contribute to effects and reactions. We compared early changes in peripheral immune cell subsets and clinical outcomes in patients with rCDI who received either FMT and antibiotics or antibiotics alone in a randomized trial.

METHODS: Thirty-five patients with rCDI were randomized to vancomycin and FMT (n=20) or vancomycin alone (n=15). Blood samples were drawn before (wk0) and one week (wk1) after treatment. In three additional patients, blood samples were drawn before, and 24 hours and wk1 after FMT. Adaptive and innate immune cell subsets and gut-homing memory (CD45RO+integrinβ7+) and effector (CD45RO-integrinβ7+) T cells were analysed by flow cytometry.

RESULTS: FMT induced subtle changes in immune cell subsets with no clear pattern from wk0 to wk1. The Treg fraction tended to decrease after FMT, and a similar decrease at 24 hours indicated rapid Tregs dynamics. NKT cells increased during the first 24 hours and returned to baseline level at wk1. Regardless of FMT, patients with clinical resolution from rCDI had a decrease in non-classical monocytes and a shift in gut-homing memory to effector cells at wk1.

CONCLUSION: In rCDI, FMT induced subtle and transient dynamics in peripheral immune cell subsets. Tregs and NKT cells seemed responsive and should be further studied. Cure of CDI may be associated with an increase in circulating gut-homing T cells.},
}

@article {pmid41737395,
year = {2026},
author = {Wen, D and Liu, S and Wu, Y and Zhang, H and Zhang, K},
title = {Fecal microbiota transplantation improves functional constipation through the gut microbiome-bile acid-receptor axis.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1751593},
pmid = {41737395},
issn = {2296-858X},
abstract = {Functional Constipation (FC) is a prevalent gastrointestinal motility disorder worldwide that markedly impairs patients' quality of life, yet the currently available treatment options often show limited efficacy. In recent years, research has gradually revealed the critical role of the gut microbiota and bile acid metabolism in the pathogenesis of FC. Fecal Microbiota Transplantation (FMT), which restores the intestinal microecological balance by transferring gut microbiota from healthy donors, has demonstrated clinical efficacy in promoting bowel movements, improving stool consistency, and enhancing patients' quality of life. However, its underlying mechanisms remain incompletely understood. Current evidence indicates that FMT restores microbial diversity, increases beneficial taxa, and partially reconstructs the bile acids (BAs) profile, thereby modulating Farnesoid X Receptor (FXR) and Takeda G Protein-Coupled Receptor 5 (TGR5) mediated signaling pathways to enhance intestinal secretion and alleviate constipation-related symptoms. The resulting microbiota-bile acid-receptor pathway elucidates the mechanistic link between microbial remodeling and host gastrointestinal motility, thereby offering theoretical support for the therapeutic application of FMT in functional constipation.},
}

@article {pmid41736135,
year = {2026},
author = {Huang, H and Peng, S and Liu, Y and Chen, L and Wu, F},
title = {Fecal microbiota transplantation for advanced non-small cell lung cancer with secondary PD-1 resistance efficacy prognostic factors and microbiome diversity analysis.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-07885-w},
pmid = {41736135},
issn = {1479-5876},
support = {2025YLCE0054//Talent Program of Ganzhou Sci-Tech and Medical Joint Program/ ; 82560474//Regional Programs of the National Natural Science Foundation of China/ ; 82560461//Regional Programs of the National Natural Science Foundation of China/ ; 82360507//Regional Programs of the National Natural Science Foundation of China/ ; },
}

@article {pmid41735123,
year = {2026},
author = {D'Arcangelo, G and Paparella, R and Gravina, A and Tarani, F and Tarani, L and Aloi, M and Petrella, C},
title = {Exploring novel biomarkers in pediatric ulcerative colitis: The role of Lipocalin-2, MMP-9, and MMP-9/LCN-2 complex.},
journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.dld.2026.01.224},
pmid = {41735123},
issn = {1878-3562},
abstract = {BACKGROUND AND AIMS: Lipocalin-2 (LCN-2), Matrix Metalloproteinase-9 (MMP-9), and the MMP-9/LCN-2 complex are emerging biomarkers for ulcerative colitis (UC). While extensively studied in adults, data in children are limited. This study aimed to evaluate their serum levels in children with newly diagnosed UC, compare them with healthy controls, and assess correlations with disease severity and extent.

METHODS: In this prospective case-control study, 32 children with UC (6-18 years) and 38 healthy controls were enrolled. Baseline clinical (Pediatric Ulcerative Colitis Activity Index/ PUCAI), laboratory (albumin, hemoglobin, Erythrocyte Sedimentation Rate, C-reactive protein/CRP, fecal calprotectin), and endoscopic (extent, Ulcerative Colitis Endoscopic Index of Severity/UCEIS) data were collected. Serum LCN-2, MMP-9, and MMP-9/LCN-2 complex levels were measured by ELISA.

RESULTS: Serum LCN-2, MMP-9, and MMP-9/LCN-2 levels were significantly higher in UC patients than controls. ROC analysis indicated LCN-2 had the best diagnostic performance. Higher LCN-2 and MMP-9 levels were observed in children with more severe endoscopic disease (UCEIS > 4) or pancolitis. LCN-2 levels inversely correlated with albumin, whereas MMP-9 positively correlated with CRP and UCEIS.

CONCLUSIONS: LCN-2 and MMP-9 are promising biomarkers in pediatric UC, reflecting disease severity and extent. Their measurement may have clinical utility in monitoring disease progression and guiding management in children.},
}

@article {pmid41735080,
year = {2026},
author = {Yu, Y and Lu, L and Ji, G and Xu, H},
title = {Ecological battle of gut microbiota under drug intervention.},
journal = {Trends in microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tim.2026.01.002},
pmid = {41735080},
issn = {1878-4380},
abstract = {Ecological consequences of drug exposure in the gut microbiota remain difficult to predict. In a recent Cell study, Shi et al. have demonstrated that nutrient competition and interspecies antagonism drive drug-induced microbiome restructuring. Their predictive framework advances mechanistic understanding of drug-microbiome interactions and fecal microbiota transplantation.},
}

@article {pmid41734860,
year = {2026},
author = {Wu, QL and Zhou, YR and Chen, ZR and Liu, MX and Liu, MX and Liu, YF and Li, ZS and Zhao, QR and Zhang, YQ and Zhang, GQ and Zhang, Z and Gong, YT and Tang, C and Yang, T and Du, ZC},
title = {Roles of the gut microbiota in cancer immunotherapy: Mechanistic foundations and therapeutic opportunities.},
journal = {Critical reviews in oncology/hematology},
volume = {221},
number = {},
pages = {105230},
doi = {10.1016/j.critrevonc.2026.105230},
pmid = {41734860},
issn = {1879-0461},
abstract = {Cancer immunotherapy has revolutionized oncological treatment through diverse modalities including immune checkpoint blockade, adoptive cell therapy, therapeutic vaccines, and cytokine-based approaches. Despite these advances, clinical responses remain heterogeneous, with sustained benefit limited to a minority of patients. Emerging evidence now implicates gut microbiota as a critical systemic regulator of immunotherapy efficacy across multiple treatment platforms, mechanistically linking intestinal dysbiosis to antitumor immunity through the gut-immune-tumor axis. Specific commensal taxa and their metabolites, including short-chain fatty acids and tryptophan derivatives, regulate anti-tumor immunity through effector T cell enhancement, dendritic cell activation, and regulatory T cell suppression. This review systematically examines the microbial-metabolite-immune axis, elucidating mechanisms whereby intestinal microbes and metabolites mediate immunotherapy responses. We comprehensively evaluate microbiota-targeting strategies including dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation, providing mechanistic insights and translational frameworks. We further discuss current challenges in transitioning from associative microbiome studies to mechanistic causality, standardizing intervention protocols, and integrating multi-modal microecological data, proposing future directions for engineered probiotics and precision microbial therapeutics to optimize outcomes under current immunotherapy.},
}

@article {pmid41732311,
year = {2026},
author = {Makkieh, Y and Shah, HH and Imran, SB and Pathan, SMK and Saju, AC and Majooju, M and Garg, A and Naag, T and Islam, R and Fahima, C and Ali, R},
title = {The gut-heart axis: Exploring the role of the gut microbiome in cardiovascular health - A focused systematic review.},
journal = {American heart journal plus : cardiology research and practice},
volume = {61},
number = {},
pages = {100687},
pmid = {41732311},
issn = {2666-6022},
abstract = {This focused systematic review examines the role of the gut microbiota in cardiovascular disease (CVD). The review explores mechanisms linking gut dysbiosis with CVD via microbial metabolites such as trimethylamine-N-oxide (TMAO) and short-chain fatty acids (SCFAs), which affect inflammation, endothelial function, and lipid metabolism. Interventions including dietary modifications, probiotics, prebiotics, fecal microbiota transplantation, and pharmacological agents such as statins, rifaximin, and empagliflozin are evaluated for their impact on microbial composition and cardiovascular outcomes. Probiotic strains and fiber-rich diets demonstrated modest improvements in blood pressure, lipid profiles, and inflammatory markers. Studies revealed that gut microbiome alterations influence drug metabolism and bleeding risk in patients taking oral anticoagulants. Limited evidence suggests that modulation of the microbiota may reduce chemotherapy-induced cardiotoxicity. However, only nine eligible studies met the inclusion criteria, reflecting the early and heterogeneous nature of this research area. Consequently, these findings should be interpreted as exploratory and hypothesis-generating. The focused review emphasizes the need for large-scale trials to validate microbiome-targeted strategies in CVD prevention and management. This focused systematic review is registered with PROSPERO (ID: CRD420251022190).},
}

@article {pmid41731480,
year = {2026},
author = {Liu, P and Hu, P and Jin, M and Wan, Y and Wu, J and Sun, W and Tang, Y and Huang, L and Zhang, D and Shi, D and Xie, T and Tong, Y and Zheng, H and Wang, L and He, H and Xu, X},
title = {Gut microbiota dysbiosis contributes to diabetic nephropathy via affecting renal lipid deposition and inflammatory responses.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-07832-9},
pmid = {41731480},
issn = {1479-5876},
support = {82304948//National Natural Science Foundation of China/ ; No.2022MHCX01//School-level Project Innovation Project of Minhang Hospital Affiliated to Fudan University/ ; 24ZR1461700//Shanghai Natural Science Foundation/ ; 2024MZYS07//High-Level Specialist Physician Training Program under the Collaborative Health Service System of Medical Education and Research in Minhang District/ ; 2023MHBJ04//Minhang District Central Hospital Topnotch Project/ ; 2025MHZ035//Natural Science Research Project in Minhang District/ ; },
}

@article {pmid41729099,
year = {2026},
author = {Zhang, B and Si, Y and Liu, Y and Wei, J and Li, M and Si, D and Li, H and Wang, X and Han, P and Wang, W and Bao, J and Cheng, L and Lei, Y and Ma, H and Liu, Y},
title = {Simulated microgravity induces cerebral dysfunction by disturbing protective microbiota-metabolite-microglia signaling across the gut‒brain axis.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2635820},
pmid = {41729099},
issn = {1949-0984},
mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Rats ; *Weightlessness Simulation/adverse effects ; Male ; Fecal Microbiota Transplantation ; *Microglia/metabolism ; Hippocampus/metabolism ; Rats, Sprague-Dawley ; Signal Transduction ; *Brain/metabolism ; },
abstract = {Long-duration spaceflight characterized by microgravity adversely affects operator proficiency postlanding, yet the mechanisms by which microgravity induces cerebral dysfunction refractory to short-term recovery among astronauts remain poorly defined. Here, we demonstrate that simulated microgravity (SMG) leads to chronic behavior disorders and cognitive deficits via a microbiota-metabolite-brain axis. Fecal microbiota transplantation (FMT) from long-term SMG-treated donor rats to recipients (n = 5 per group) under normal gravity (NG) induces anxiety-like behaviors and spatial working memory disturbances by impairing synaptic plasticity in the hippocampus, reproducing the phenotype of SMG-exposed rats. SMG destroys intestinal barriers and alters the gut microbiota to a proinflammatory state with an increased abundance of Proteobacteria but decreased production of linoleic acid (LA) and LA-derived metabolites, which is highly associated with neuroinflammation in the hippocampus. Mechanistically, LA can be taken up by the hippocampus under NG conditions, and then block inflammatory microglial activation by interacting with signal transducer and activator of transcription 1 (STAT1) and inhibiting its phosphorylation at Tyr 701 and Ser 727. However, the Proteobacteria, especially Pseudomonas aeruginosa, tend to be the dominant phylum in gut microbiota under SMG conditions and consume large amounts of LA, breaking LA-dependent immune homeostasis in the central nervous system (CNS). Dietary supplementation with LA significantly mitigated SMG-induced neuroinflammation and cognitive impairment. Taken together, our findings in SD rats models reveal a critical role for gut microbiota dysbiosis in simulated microgravity-associated encephalopathy, offering a novel strategy for LA replenishment to improve brain function during spaceflight.},
}

Animals
*Gastrointestinal Microbiome/physiology
Rats
*Weightlessness Simulation/adverse effects
Male
Fecal Microbiota Transplantation
*Microglia/metabolism
Hippocampus/metabolism
Rats, Sprague-Dawley
Signal Transduction
*Brain/metabolism

@article {pmid41727680,
year = {2026},
author = {Su, B and Cao, Y and Ma, L and Huang, J},
title = {BMI-stratified phenotypes of polycystic ovary syndrome: advances in gut microbiota research and personalized management strategies.},
journal = {Frontiers in endocrinology},
volume = {17},
number = {},
pages = {1734041},
pmid = {41727680},
issn = {1664-2392},
mesh = {Humans ; *Polycystic Ovary Syndrome/microbiology/therapy/pathology ; *Gastrointestinal Microbiome/physiology ; Female ; *Body Mass Index ; *Precision Medicine/methods ; *Obesity/complications/microbiology ; Phenotype ; Dysbiosis ; },
abstract = {Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine-metabolic disorder affecting 11%-13% of women of reproductive age. Based on body mass index (BMI), patients can be phenotypically classified into obese and non-obese subgroups: the obese PCOS is characterized by insulin resistance, hyperandrogenemia, and metabolic syndrome, with more pronounced metabolic risks; non-obese PCOS primarily manifests as reproductive endocrine dysfunction. In recent years, studies have shown that the Gut microbiota plays a key role in the pathogenesis of PCOS, and dysbiosis in the obese subgroup is generally more pronounced, potentially amplifying metabolic abnormalities through pathways such as short-chain fatty acids, bile acid disturbances, and endotoxin-related low-grade inflammation. This review systematically summarizes the clinically heterogeneous features of BMI-stratified PCOS and its gut microbiota characteristics, with a focus on elucidating the mechanistic differences between obese and non-obese individuals in terms of inflammation, metabolites, and endocrine regulatory pathways. Based on current evidence, individualized intervention strategies targeting different BMI subtypes are proposed, including dietary and lifestyle modifications, interventions with probiotics/prebiotics/synbiotics, and exploration of emerging precision microbiome therapies such as fecal microbiota transplantation. The interaction between BMI and gut microbiota provides new directions for stratified management and personalized treatment of PCOS; however, high-quality longitudinal and interventional studies are still needed to clarify causal relationships and optimize microbiota-targeted strategies.},
}

Humans
*Polycystic Ovary Syndrome/microbiology/therapy/pathology
*Gastrointestinal Microbiome/physiology
Female
*Body Mass Index
*Precision Medicine/methods
*Obesity/complications/microbiology
Phenotype
Dysbiosis

@article {pmid41727556,
year = {2026},
author = {Millar, BC and Cates, MJ and Torrisi, MS and Round, AJ and Warde, A and Lowery, CJ and Moore, JE},
title = {Antimicrobial Resistance: The Answers.},
journal = {British journal of biomedical science},
volume = {83},
number = {},
pages = {15559},
pmid = {41727556},
issn = {2474-0896},
mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use/pharmacology ; *Drug Resistance, Bacterial ; COVID-19/epidemiology ; SARS-CoV-2 ; },
abstract = {Antimicrobial resistance (AMR) has caused a global public health crisis, contributing to approximately five million deaths in 2019 and predicted deaths of approximately ten million annually by 2050. This equates to approximately 1.4-fold more deaths annually from AMR in 2050 than the entire COVID-19 pandemic to date. To tackle this AMR pandemic, regulatory and policy frameworks have been prepared at local, national and international levels with multi-faceted proposals and advances encompassing surveillance, diagnostics, infection prevention, antibiotic prescribing and variation of existing and novel treatment approaches. This narrative review primarily focuses on research and development which have been documented over the last five years in relation to therapeutic approaches at various stages in clinical development and the potential role that vaccines can play in the fight against AMR. This review provides an overview on antibacterial drugs, including novel classes of antibiotics, which have been recently approved, as well as combination antibiotic therapy and the potential of repurposed drugs. The potential role of novel antimicrobial, antibiofilm and quorum sensing inhibitors, such as antimicrobial peptides, nanomaterials and compounds from the extreme and natural environments, as well as ethnopharmacology including the antimicrobial effects of plants, spices, honey and venoms are explored. Novel therapeutic approaches are critically discussed in terms of their realistic clinical potential, detailing recent and ongoing trials to highlight the current interest of these approaches, including immunotherapy, bacteriophage therapy, antimicrobial photodynamic therapy (aPDT), antimicrobial sonodynamic therapy (aSDT), nitric oxide therapy and microbiome manipulation including faecal microbiota transplantation (FMT). The potential of predatory bacteria as living antimicrobial agents is also discussed. Importantly, there have been many technological developments which have enhanced bioprospecting and research and development of novel antimicrobials which this review draws attention to, including artificial intelligence, machine learning and Organ-on-a-Chip devices. Finally, key messages from the recent World Health Organization report into the role of vaccines against AMR provides an interesting perspective relating to prevention which can be of significance in tackling the AMR burden.},
}

Humans
*Anti-Bacterial Agents/therapeutic use/pharmacology
*Drug Resistance, Bacterial
COVID-19/epidemiology
SARS-CoV-2

@article {pmid41727337,
year = {2026},
author = {Toumazi, D and Charalambous, C and Constantinou, C and Nicolaou, N},
title = {From the gut to the brain: The involvement of the gut microbiota in the development and progression of glioblastoma.},
journal = {Neuro-oncology advances},
volume = {8},
number = {1},
pages = {vdaf267},
pmid = {41727337},
issn = {2632-2498},
abstract = {Glioblastoma (GB) is the most malignant tumor in the adult central nervous system (CNS), presenting substantial treatment challenges due to its infiltrative nature, heterogeneity and immunosuppressive environment it creates. Current therapeutic efforts are focused on enhancing our understanding of GB and developing effective therapies. An emerging area of interest is the bidirectional gut-brain axis, which mediates communication between gut microbiota and CNS. The gut-brain axis allows the microbiota to modulate the immune system and inflammatory pathways through microbial metabolites, such as short-chain fatty acids (SCFAs) and tryptophan derivatives, promoting or suppressing GB progression. Understanding these interactions can lead to microbiota-targeted therapies for GB patients. Novel therapies, such as fecal microbiota transplantation to enhance immunotherapy response and using bacterial toxins to cross the blood-brain barrier, show promise in improving treatment-resistant GB treatment. Additionally, the role of probiotics and antibiotics on GB prognosis is being investigated. While more research is needed to understand the gut microbiota's role in GB, recent findings suggest promising directions for future therapies. This review examines the interplay between key immune system components and the microbiota in GB development and explores how this understanding could facilitate the development of novel therapeutic interventions.},
}

@article {pmid41725847,
year = {2026},
author = {Liu, G and Chen, L and Guan, M and Xiao, N},
title = {Global trends and future perspectives in autism spectrum disorder and gut microbiota research: a comprehensive bibliometric analysis.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1607951},
pmid = {41725847},
issn = {1662-4548},
abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition. Increasing studies examine whether gut microbiota alterations and the gut-brain axis are linked to ASD-relevant phenotypes. As the literature expands rapidly, a quantitative mapping is needed to clarify influential work and evolving themes.

OBJECTIVE: To map global research on ASD and the gut microbiota, identify major contributors and knowledge bases, and characterize thematic evolution and emerging fronts.

METHODS: We analyzed 1,391 English-language articles and reviews indexed in the Web of Science Core Collection (1999-2024). CiteSpace, VOSviewer, and R were used to evaluate publication trends, collaboration networks, co-citation structure, keyword clustering, and burst detection.

RESULTS: Publication output increased slowly before 2010 and accelerated after 2018. The United States and China were leading contributors and key collaboration hubs. The co-citation core was anchored by landmark experimental and translational studies, including work on microbiome-to-behavior links and microbiome-targeted interventions. Keyword clustering and timeline views highlighted three prominent thematic directions: fecal microbiota transplantation, Rett syndrome, and maternal immune activation. Recurrent and burst keywords emphasized the gut-brain axis, short-chain fatty acids, gastrointestinal symptoms, and oxidative stress. Recent burst terms, including obesity, major depressive disorder, and glutamate, suggest increasing connections to metabolic and broader psychiatric dimensions.

CONCLUSION: ASD-microbiome research has shifted from descriptive comparisons toward mechanism-oriented and intervention-relevant questions. Future progress will benefit from standardized protocols, longitudinal designs, and multi-omics integration, together with rigorously designed trials to evaluate microbiome-targeted strategies.},
}

@article {pmid41724232,
year = {2026},
author = {Tang, H and Sulaiman, JE and Zhang, Y and Yang, Y and Wang, J and Zhong, W and Lei, H and Liu, Y},
title = {Cyanidin-3-O-glucoside alleviates aflatoxin B1-induced splenic immunotoxicity via gut microbiota remodeling.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {396},
number = {},
pages = {127856},
doi = {10.1016/j.envpol.2026.127856},
pmid = {41724232},
issn = {1873-6424},
abstract = {While the hepatotoxicity of aflatoxin B1 (AFB1) is well characterized, its immunotoxicity remains overlooked. This study investigates whether cyanidin-3-O-glucoside (C3G), a bioactive polyphenolic flavonoid, can alleviate AFB1-induced immunotoxicity. Our results demonstrated that C3G significantly ameliorated AFB1-induced splenic injury, which was associated with the suppression of the NLRP3/caspase-1/GSDMD pyroptosis pathway and reduced expression of IL-1β and IL-18. Furthermore, C3G modulated the gut microbiota by enriching specific beneficial bacteria (e.g., Alistipes and Candidatus Saccharimonas) and reversed AFB1-induced metabolic disorders. Transplantation of fecal microbiota from C3G-pretreated donor mice reproduced the protective effect of C3G in mice exposed to AFB1, whereas sterile fecal filtrate transplantation only offered partial relief, indicating that the core mechanism depends on viable microbiota. In summary, C3G alleviates AFB1-induced splenic injury by restructuring the dysbiotic gut microbiota into a more enriched community. This remodeling restores metabolic homeostasis and inhibits NLRP3-mediated pyroptosis via the gut-spleen axis. Our findings demonstrate that C3G alleviates AFB1-induced splenic immunotoxicity by remodeling the gut microbiota via the gut-spleen axis, establishing a novel microbiota-dependent strategy mediated by natural polyphenols.},
}

@article {pmid41724218,
year = {2026},
author = {Liu, J and Liu, T and Nie, L and Zhou, L and Luo, J and Guo, L and Zhang, X and Gong, M and Chen, Z and Li, X and Fan, X},
title = {Semaglutide attenuates autistic-like behaviors in BTBR mice through the shaping of gut microbiota.},
journal = {Pharmacological research},
volume = {225},
number = {},
pages = {108149},
doi = {10.1016/j.phrs.2026.108149},
pmid = {41724218},
issn = {1096-1186},
abstract = {Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental condition characterized by deficits in social communication and the presence of repetitive behaviors. The significance of the gut-brain axis in the pathogenesis of ASD often points to a relationship with gut dysbiosis and metabolic disruptions in affected individuals. This study investigates the potential of the glucagon-like peptide-1 receptor agonist, semaglutide, to modulate gut microbiota, metabolic pathways, and neurodevelopmental outcomes using the BTBR T(+) Itpr3(tf)/J (BTBR) mouse model of ASD. Our findings indicate that administration of semaglutide during an early neurodevelopmental stage leads to significant improvements in social behavior, cognitive function, and repetitive behaviors in BTBR mice. This therapeutic effect is associated with the restoration of gut microbiota, as demonstrated by fecal microbiota transplantation from C57BL/6 J controls and semaglutide-treated BTBR mice, which ameliorated the ASD behaviors in BTBR mice. Metabolomic profiling identified adrenic acid (AdA) as a crucial mediator; AdA levels in BTBR mice were lower but returned to normal following semaglutide treatment. Additionally, RNA sequencing revealed that hippocampal neurogenesis is associated with semaglutide treatment, and AdA supplementation restored social behaviors and hippocampal neurogenesis. These results highlight the critical role of the gut microbiota-brain axis in the therapeutic effects of semaglutide on ASD and suggest that targeting this axis alongside AdA may represent a promising strategy for ASD.},
}

@article {pmid41723574,
year = {2026},
author = {Benedé-Ubieto, R and Estévez-Vázquez, O and Acar, R and Leal-Lassalle, H and Gutierrez, AH and Redondo-Urzainqui, A and Iborra, S and Odintsova, VE and Tyakht, A and Herranz, JM and Firat, Z and Basol, M and Korkmaz, B and Sanz-García, C and Juanola, O and Caparrós, E and Francés, R and Ciudin, A and Pericàs, JM and Gómez-Santos, B and Aspichueta, P and Treichel, N and Clavel, T and Reißing, J and Bruns, T and Bartneck, M and Mazariegos, MS and Wolters, JC and Jorquera, G and Liedtke, C and Vaquero, J and Bañares, R and Cakan-Akdogan, G and Ávila, MA and Konu, O and Cubero, FJ and Nevzorova, YA},
title = {Alcohol consumption in metabolic dysfunction-associated steatotic liver disease (MASLD): understanding the gut-liver crosstalk for clinical translation.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2631834},
pmid = {41723574},
issn = {1949-0984},
mesh = {Animals ; Humans ; *Gastrointestinal Microbiome/drug effects ; Mice ; Male ; *Liver/metabolism/pathology/drug effects ; Disease Models, Animal ; *Alcohol Drinking/adverse effects ; Zebrafish ; Mice, Inbred C57BL ; Diet, High-Fat/adverse effects ; *Fatty Liver/microbiology/metabolism/etiology ; Hep G2 Cells ; Fecal Microbiota Transplantation ; Female ; Diet, Western/adverse effects ; Hepatocytes/metabolism ; Dysbiosis ; Middle Aged ; },
abstract = {OBJECTIVE: In the present study, we investigated the role of the gut-liver crosstalk in the pathogenesis of steatotic liver disease (SLD) induced by the compounding and deleterious effects of alcohol and metabolic risk factors, and explored the potential translational aspects of microbiome-based interventions.

DESIGN: The effects of combined exposure to alcohol and a high-fat, high-cholesterol diet (HFHC) Western diet (WD) were tested in a dietary mouse DUAL model and compared to mice fed only with WD. Liver and gut phenotypes were evaluated via histochemistry, flow cytometry, gene expression, proteomic, and metabolomic analyses. The effects on the gut microbiota were studied in both DUAL mice and MASLD patients with a history of alcohol consumption. Antibiotic-induced microbiota depletion (AIMD) and microbiota modulation therapies (probiotics and fecal microbiota transplant (FMT)) were performed in mice. Primary human hepatocytes and HepG2 cells were used to study the underlying mechanisms. Zebrafish larvae exposed to alcohol and a HFHC diet were used as a validation model.

RESULTS: Alcohol in combination with WD synergistically exacerbated SLD. DUAL-diet-induced disruption of the intestinal barrier led to LPS leakage into the bloodstream and subsequent TLR4-mediated hepatic inflammation. This, together with enhanced intestinal fat absorption, and impaired intrahepatic lipid oxidation - particularly due to insufficient CPT-1 activity - contributed to prominent steatohepatitis. The DUAL-induced changes in the gut microbiota showed similarities to human dysbiosis in MASLD patients who consumed alcohol, including an increase in Bacteroides and Alistipes. AIMD improved pathology, indicating a causal role of the microbiota in the pathophysiology of DUAL steatohepatitis, whilst early microbiome modulation via FMT induced mild improvements in liver and gut physiology.

CONCLUSIONS: These results indicated that the microbiota‒gut‒liver axis plays a crucial role in the progression of SLD intensified by alcohol and concurrent metabolic risk factors, thus providing a promising translational target for potential therapeutic interventions.},
}

Animals
Humans
*Gastrointestinal Microbiome/drug effects
Mice
Male
*Liver/metabolism/pathology/drug effects
Disease Models, Animal
*Alcohol Drinking/adverse effects
Zebrafish
Mice, Inbred C57BL
Diet, High-Fat/adverse effects
*Fatty Liver/microbiology/metabolism/etiology
Hep G2 Cells
Fecal Microbiota Transplantation
Female
Diet, Western/adverse effects
Hepatocytes/metabolism
Dysbiosis
Middle Aged

@article {pmid41723572,
year = {2026},
author = {Liang, H and Ding, X and Liu, S and Tong, S and Wang, X and Zhang, Z and Wang, W and Zhang, X and Yuan, Y and Jiang, Y and Sun, T},
title = {Aging-caused the changes of the gut microbiota drive intestinal barrier dysfunction and increase sepsis susceptibility.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2630475},
pmid = {41723572},
issn = {1949-0984},
mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; Mice ; *Sepsis/microbiology/metabolism ; Humans ; *Aging ; Male ; Feces/microbiology ; Mice, Inbred C57BL ; Histamine/metabolism ; *Intestinal Mucosa/metabolism/microbiology ; Female ; Bacteria/classification/genetics/isolation & purification/metabolism ; Fecal Microbiota Transplantation ; Aged ; Disease Susceptibility ; Disease Models, Animal ; Middle Aged ; },
abstract = {Physiological and pathological changes associated with aging contribute to deteriorating disease prognosis in sepsis. However, the mechanisms by which these disturbances exacerbate inflammation remain underexplored. In this study, fecal samples were collected from aged and young septic patients and mice and subsequently transplanted into young pseudo-germ-free mice via fecal microbiota transplantation. Fecal, colon tissue, and blood samples were collected to be used 16S rDNA sequencing to characterize the gut microbiota, histopathological examination, enzyme-linked immunosorbent assay and FITC-dextran intestinal permeability assay to assess gut injury and gut barrier function. Additionally, nontargeted and targeted metabolomics were used to identify differential metabolites in the feces of aged and young septic mice. To further validate the roles of specific bacterial strains and their metabolites in sepsis, genetically engineered bacteria were used in both in vivo and in vitro experiments. The results showed that an increased abundance of Klebsiella aerogenes (K. aero) in aged hosts, which led to elevated histamine (HA) production and exacerbated intestinal barrier dysfunction. Importantly, K. aero strains carrying a histidine decarboxylase gene variant were identified as major HA producers. Mechanistically, HA was shown to drive intestinal barrier dysfunction by inhibiting Nlrp6 expression and its subsequent binding to LC3, thereby impairing autophagy. Treatments that modulated HA levels or overexpressed Nlrp6 ameliorated inflammation in septic mice. These findings suggest that targeting the HA-Nlrp6-LC3 axis could offer a novel therapeutic approach for managing sepsis, particularly in aged populations.},
}

*Gastrointestinal Microbiome/physiology
Animals
Mice
*Sepsis/microbiology/metabolism
Humans
*Aging
Male
Feces/microbiology
Mice, Inbred C57BL
Histamine/metabolism
*Intestinal Mucosa/metabolism/microbiology
Female
Bacteria/classification/genetics/isolation & purification/metabolism
Fecal Microbiota Transplantation
Aged
Disease Susceptibility
Disease Models, Animal
Middle Aged

@article {pmid41722712,
year = {2026},
author = {Beales, JT and Mohanty, V and Seng, MM and Tapp, ZM and Sardesai, SD and Williams, NO and Gatti-Mays, ME and Stover, DG and Sudheendra, PK and Wesolowski, R and Bailey, MT and Ni, A and Cologna, SM and Pyter, LM},
title = {Gut microbiota and metabolite disruption during breast cancer chemotherapy is associated with peripheral neuropathy sensory symptoms and pain.},
journal = {Brain, behavior, and immunity},
volume = {135},
number = {},
pages = {106489},
doi = {10.1016/j.bbi.2026.106489},
pmid = {41722712},
issn = {1090-2139},
abstract = {Chemotherapy-induced peripheral neuropathy (CIPN) is a common and serious adverse effect of chemotherapeutic agents such as taxanes, platinum compounds, and vinca alkaloids. Efforts to prevent and treat CIPN are impeded by an incomplete understanding of its pathogenesis. Recently, the gut microbiota has been causally linked to CIPN in rodent models. However, human studies exploring this connection are limited. Here, in a cohort of 70 patients with early-stage breast cancer, relationships between disruptions in the gut microbiota during chemotherapy and both participant CIPN symptoms and general pain symptoms were investigated. Study participants provided fecal samples (for 16S rRNA sequencing and targeted metabolomics), blood samples, and sensory symptom information during the three days prior to their first and their final chemotherapy (including a taxane drug) infusions. Sensory neuropathy symptoms increased during treatment, as did circulating levels of neurofilament light chain (NFL), a putative biomarker of CIPN. Decreases in microbiota alpha diversity during chemotherapy were associated with worse neuropathy symptoms during treatment, along with worsening of general pain, after controlling for pre-treatment baseline symptoms. Larger shifts in beta diversity from baseline to last infusion also coincided with more severe neuropathy symptoms. Bacterial producers of short-chain fatty acids were decreased in participants with neuropathy symptoms at the final chemotherapy infusion. Furthermore, decreases in fecal levels of short-chain fatty acids during treatment were related to worse neuropathy symptoms, suggesting a potential mechanism by which gut microbiota alterations could influence CIPN. Collectively, these findings corroborate preclinical work linking the gut microbiota to CIPN and provide evidence of potential microbiota involvement in general pain symptoms as well. Larger confirmatory studies in the future could support microbiota-targeted interventions for CIPN, such as fecal microbiota transplants or dietary interventions.},
}

@article {pmid41722699,
year = {2026},
author = {Shang, A and Shen, J},
title = {Gut microbiota and their metabolites in stroke: From mechanistic study toward therapeutic perspectives.},
journal = {Pharmacological research},
volume = {225},
number = {},
pages = {108147},
doi = {10.1016/j.phrs.2026.108147},
pmid = {41722699},
issn = {1096-1186},
abstract = {Stroke is a medical emergency with high incidence, mortality, disability rate, and multiple complications, which place a serious burden on families and society. Clinically, gastrointestinal dysfunction has been observed in a significant percentage of stroke patients, suggesting that gut microbiota may be a viable target for stroke prevention and therapy. In this review, we summarized the alterations in the intestinal environment following stroke across clinical and preclinical models, highlighting the changes in the major bacterial communities, including Bacteroidetes, Firmicutes, Proteobacteria and Actinomycetota, etc. Considering the connection between the brain-gut axis, we discussed the therapeutic potential for treating ischemic stroke by modulating the gut microbiota, including protection of the blood-brain barrier (BBB) and the intestinal barrier, as well as the application of fecal microbiota transplantation (FMT). Furthermore, we highlighted the main mechanisms of regulating gut microbiota to improve stroke outcomes, involving intestinal metabolites such as short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), and phenylacetylglutamine (PAGln), endotoxin, hormones, and amino acids, as well as factors related to immunity, inflammation, and oxidative stress. Finally, we summarized potential targeted therapeutic approaches, such as natural small molecules, engineered probiotics, and bile acid-nanoparticles, etc. Collectively, these insights support the gut microbiota as a promising target for mitigating stroke risk, attenuating acute injury, and enhancing recovery.},
}

@article {pmid41722622,
year = {2026},
author = {Allen, SL and Breen, L and Lord, JM and Duggal, NA},
title = {Age-related sarcopenia and the gut microbiome: mechanistic insights into the gut-muscle axis and potential microbiome based therapeutic interventions.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103065},
doi = {10.1016/j.arr.2026.103065},
pmid = {41722622},
issn = {1872-9649},
abstract = {Ageing is associated with a loss of skeletal muscle mass, strength and function, termed sarcopenia. The presence of sarcopenia is known to be problematic leading to an increased risk of falls, fractures and mortality. Age-related changes in the gut microbiome, characterized by reduced diversity and altered metabolite production, may compromise intestinal barrier function, leading to increased permeability. These age-associated changes in the gut microbiome led to changes in circulating microbial metabolites and toxins, such as a decrease in short-chain fatty acids, an increase in lipopolysaccharides and an imbalance in bile acid production. Together these alterations may contribute to the development of sarcopenia through impairments in muscle protein turnover. Currently, lifestyle-based approaches e.g., exercise and diet, alongside the use of pre-, pro- and post-biotics have been proposed as strategies to target the gut-muscle axis and combat the risk of sarcopenia in the expanding ageing population. However, little evidence is available to support their use within clinical settings. Several new strategies including the nutraceutical Urolithin A and faecal microbiome transplants (FMT) have been suggested to treat age-related sarcopenia. This review provides insight into the potential interactions of the gut microbiome and skeletal muscle with ageing and sarcopenia development, alongside potential new and existing countermeasures.},
}

@article {pmid41721978,
year = {2026},
author = {Mokhtari, H and Hoseini, MHM and Hashemi, SM and Tahvildari, S and Yeganeh, F},
title = {Intrarectal delivery of chitosan hydrogel-encapsulated mesenchymal stem cell-conditioned media attenuates disease severity in experimental ulcerative colitis.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41721978},
issn = {1568-5608},
support = {43002260//Deputy of Research, Faculty of Medicine, Shahid Beheshti University of Medical Sciences/ ; },
abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease characterized by mucosal immune dysregulation and epithelial injury. While mesenchymal stem cells (MSCs) hold regenerative and immunomodulatory promise, their use entails safety and logistical challenges. MSC-derived conditioned medium (MSC-CM) may offer a safer, cell-free alternative. Here, we present a novel intrarectal delivery strategy that pairs MSC-CM with a mucoadhesive chitosan hydrogel (Cs-Hyd), aiming for localized mucosal therapy in colitis.

METHODS: Experimental colitis was induced in mice via DSS exposure. Human MSCs were cultured under standardized conditions to generate CM enriched in immunoregulatory factors. This CM was loaded into a chitosan hydrogel, validated for mucoadhesion and release kinetics, and administered intrarectally. Clinical metrics (weight loss, stool consistency, fecal blood), colon length, histopathology, cytokine profiles, and myeloperoxidase (MPO) activity were assessed. Data were analyzed via ANOVA with post hoc Tukey correction; significance was set at p < 0.05.

RESULTS: In the DSS model, 60% mortality was observed by day 10, whereas the Cs-Hyd containing MSC-CM (Cs-Hyd-CM) group achieved 100% survival (n = 4-6, log-rank p = 0.034). Cs-Hyd-CM-treated mice exhibited substantially less weight loss (- 5.2 ± 1.3% vs. - 15.1 ± 2.2%; repeated-measures ANOVA, p = 0.008), lower Disease Activity Index (DAI: 2.1 ± 0.6 vs. 8.0 ± 0.9; p = 3.2 × 10[-4]), and preserved colon length (7.5 ± 0.4 cm vs. 6.0 ± 0.3 cm; p = 6.2 × 10[-3]). Histology scores decreased by ~ 70% (4.0 ± 0.7 vs. 12.1 ± 0.8; p = 3.1 × 10[-6]), confirming mitigation of ulceration and inflammation. Treatment with Cs-Hyd-CM reduced TNF-α by ~ 40% vs DSS-only (104.5 ± 6.8 → 63.8 ± 8.7 pg/mg; p = 4.6 × 10[-4]) while restoring IL-10 toward normal levels (p = 3.0 × 10[-3]). MPO activity dropped ~ 52% (76.5 ± 3.4 → 36.8 ± 5.3 U/mg; p = 8.4 × 10[-4]). Collectively, Cs-Hyd-CM significantly attenuated disease severity and promoted mucosal healing in DSS colitis.

CONCLUSIONS: Local intrarectal delivery of MSC-CM via chitosan hydrogel substantially alleviates experimental UC. This cell-free platform leverages MSC secretome functions, immunomodulation, barrier restoration, and controlled retention, while avoiding the complexities and risks of cell transplantation.},
}

@article {pmid41720783,
year = {2026},
author = {Lee, JM and Kim, MJ and Lee, H and Hyun, Y and Nam, SW and Jeon, DG and Shin, JH and Kim, ES},
title = {Maternal gut microbial legacy shapes intestinal health and susceptibility of offspring to colitis.},
journal = {NPJ biofilms and microbiomes},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41522-026-00938-4},
pmid = {41720783},
issn = {2055-5008},
support = {RS-2021-NR060094//National Research Foundation of Korea/ ; 2023R1A2C2005817//National Research Foundation of Korea/ ; 2021R1A6C101A416//Ministry of Education/ ; 2021R1A6C101A416//Ministry of Education/ ; 2021R1A6C101A416//Ministry of Education/ ; },
abstract = {Maternal gut dysbiosis caused by inflammatory bowel disease during pregnancy can affect the gut health of the offspring by altering the composition of the gut microbiota, as well as immune function; however, the underlying mechanisms and potential for therapeutic intervention remain unclear. This study investigated the impact of maternal colitis on the gut health of offspring, and assessed the therapeutic potential of microbial manipulation. Offspring born to mothers with colitis exhibited gut microbial dysbiosis characterized by Lactobacillus spp. depletion, impaired barrier function, low-grade intestinal inflammation, compromised Wnt signaling, reduced crypt cell proliferation and diminished organoid-forming capacity, all of which increased their susceptibility to colitis in adulthood. Notably, early-life interventions such as fecal microbiota transplantation (FMT), targeted supplementation with Lactobacillus and cross-fostering during the postnatal period effectively reshaped the gut microbiota and reduced the risk of developing colitis later in life. These findings underscore the critical impact of the prenatal maternal gut microbial community on programming offspring intestinal barrier function and immune homeostasis, thereby influencing lifelong disease susceptibility. Moreover, the early-postnatal period represents a crucial therapeutic window in which microbial interventions like FMT can effectively mitigate gut dysbiosis and confer long-term protection against colitis.},
}

@article {pmid41719127,
year = {2026},
author = {Wang, S and Su, LY and Lan, D and Pan, H and Xiong, M and Yao, M and Deng, Y and Fan, Z and Cao, Y and Zhou, H},
title = {Adenosine signaling driven by the gut microbiota underlies chronic alcohol-induced anesthetic resistance.},
journal = {Cell reports},
volume = {45},
number = {3},
pages = {117015},
doi = {10.1016/j.celrep.2026.117015},
pmid = {41719127},
issn = {2211-1247},
abstract = {Chronic alcohol consumption increases anesthetic tolerance, yet the underlying in vivo mechanisms remain unclear. Here, we demonstrate that long-term alcohol exposure reduces anesthetic efficacy in both humans and mice, prolonging induction and shortening maintenance. Fecal microbiota transplantation from alcohol-exposed donors recapitulated this phenotype in naive mice, indicating a causal role of gut microbiome alterations. Metagenomic and metabolomic analyses identified elevated adenosine as a key microbiota-derived metabolite. Adenosine supplementation decreased anesthetic sensitivity, likely via downregulation of gamma-aminobutyric acid (GABA) receptors. Our findings reveal a gut microbiota-adenosine pathway mediating alcohol-induced anesthetic resistance.},
}

@article {pmid41718442,
year = {2026},
author = {Stafford, WH and McArthur, J and Ghafoor, S},
title = {Critical Intestinal Perforations in Pediatric Immunocompromised Patients: A Case-Based Review.},
journal = {Pediatric reports},
volume = {18},
number = {1},
pages = {},
pmid = {41718442},
issn = {2036-749X},
abstract = {As survival rates for children with cancer and immune disorders have improved, clinical focus has shifted toward managing serious treatment-related complications. Intestinal perforation remains life-threatening and is typically diagnosed by signs of peritonitis and inflammation. This report presents three high-risk pediatric patients who developed severe intestinal perforation without the usual clinical symptoms. Each patient was receiving high-dose corticosteroids and/or targeted biologic immunomodulators (ruxolitinib, anakinra, tocilizumab, eculizumab). Classic indicators such as fever, leukocytosis, hemodynamic instability, and abdominal pain were absent, despite surgical findings of fecal contamination and bowel necrosis. All three patients survived to hospital discharge. These cases demonstrate that potent immunomodulatory therapies can mask the physiological response to perforation. Relying solely on traditional clinical signs may delay diagnosis. In this population, subtle findings such as persistent gastrointestinal bleeding, feeding intolerance, or minor imaging abnormalities should prompt consideration of perforation. Early imaging and multidisciplinary review are essential for timely intervention and improved outcomes.},
}

@article {pmid41716824,
year = {2026},
author = {Ge, C and Zou, C and Lv, Y and Huang, W and Luo, X and Wu, L and Hu, Z and Zhan, S and Shen, X and Lin, G and Yu, D and Liu, B},
title = {Trace mineral sources affect oxidized oil induced intestinal damage in chickens by modulation of gut microbiota and short-chain fatty acid metabolism.},
journal = {Animal nutrition (Zhongguo xu mu shou yi xue hui)},
volume = {24},
number = {},
pages = {522-533},
pmid = {41716824},
issn = {2405-6383},
abstract = {This study investigated in vivo interactions between oil quality and trace mineral sources (organic vs. inorganic) on oxidative stress and intestinal damage in chickens. A total of 360 one-day-old male Lingnan yellow-feathered chickens with similar initial body weight (40 ± 2 g) were randomly assigned to four treatments in a 2 × 2 factorial design, with two oil qualities (fresh or oxidized) and two trace mineral sources (inorganic or organic). The experiment lasted for 21 days, with 6 replicates per treatment and 15 birds per replicate. Results showed that oxidized soybean oil (OSO) impaired jejunal barrier function (damaged morphology, downregulated tight junction genes), associated with reduced antioxidant capacity, elevated proinflammatory cytokines, and altered gut microbiota/short-chain fatty acid (SCFA) metabolism. Significant interactions were observed between oil quality and trace mineral sources (P < 0.05): only in the OSO group, organic trace minerals (OTM) outperformed inorganic ones (ITM) in enhancing total antioxidant capacity (P = 0.005) and glutathione peroxidase activity (P = 0.001), suppressing proinflammatory cytokines (e.g., interleukin-1β, P = 0.019; interleukin-2, P = 0.019; interleukin-6, P = 0.014; tumor necrosis factor-α, P = 0.001), increasing SCFA-producing bacteria (e.g., Lactobacillus and Butyricicoccus) while reducing pathogens (e.g., Helicobacter), and elevating SCFAs (P = 0.030). Furthermore, targeted metabolomic analysis revealed that OTM significantly increased the production of SCFAs, especially butyric acid (P = 0.001), which were positively correlated with the OTM-enriched microbiota. Mantel-test analysis revealed that the altered microbiota and metabolites showed strong correlations with specific parameters of intestinal health. The fecal microbiota transplantation experiment further confirmed that the intestinal protective effect is likely mediated by OTM-altered gut microbiota and their metabolites. In summary, the replacement of ITM by OTM in chicken diets can minimize the negative impact on OSO induced intestinal damage by improving intestinal barrier function and alleviating inflammatory responses mediated by gut microbiota modulation and SCFA metabolism.},
}

@article {pmid41716676,
year = {2026},
author = {Wang, R and Tong, A and Jin, K and Yu, R and Lin, D and Yang, D and Liu, X and Cui, J and Niu, J and Cui, Y and Zhu, H and Zhou, M},
title = {Harnessing the gut-immune-joint axis: Oral microalgae-based thermoresponsive microspheres enhance intra-articular therapy for rheumatoid arthritis.},
journal = {Bioactive materials},
volume = {61},
number = {},
pages = {72-91},
pmid = {41716676},
issn = {2452-199X},
abstract = {Rheumatoid arthritis (RA) is a chronic autoimmune disease primarily caused by an aberrant immune response that erroneously attacks the synovial joints, leading to inflammation and joint damage. Emerging evidence suggests that impaired intestinal barrier integrity and imbalanced gut microbiota play crucial roles in driving RA development, promoting systemic inflammation, and exacerbating joint pathology. Here we propose a synergistic therapeutic strategy that concurrently addresses both the systemic gut-immune axis and local joint inflammation. This approach integrates intra-articular injection of triamcinolone acetonide (TAA) with oral administration of thermoresponsive microspheres encapsulating Chlorella vulgaris (CV) and ginseng polysaccharides (GPS), designated as CG@GelMA. The microspheres undergo temperature-induced gelation at body temperature, thereby facilitating gastric transit and enabling prolonged drug release in the intestinal tract. Oral administration of CG@GelMA restored intestinal barrier function by enhancing tight junction protein expression and exerting anti-inflammatory effects, while intra-articular TAA synergistically alleviated synovial inflammation, improved locomotor function, and preserved bone and cartilage integrity. Moreover, the combination therapy elicited superior immune modulation, characterized by increased regulatory T cells, reduced Th17 cells, and a systemic cytokine shift toward elevated interleukin-10 and reduced interleukin-17. Notably, this systemic immunomodulation was driven by CG@GelMA-mediated remodeling of the gut ecosystem, which enriched beneficial taxa (e.g., Lactobacillus), reduced potentially pathogenic genera (e.g., Escherichia-Shigella), and, importantly, led to a significant increase in the intestinal levels of immunomodulatory metabolites, including several short-chain fatty acids (SCFAs). Fecal microbiota transplantation (FMT) and depletion studies definitively established the gut microbiota as the central mediator of these therapeutic effects. Together, these findings highlight a synergistic combinatorial strategy that couples microbiota-driven systemic immunomodulation with potent local anti-inflammatory effects, offering a promising avenue for the treatment of RA and other systemic inflammatory disorders.},
}

@article {pmid41716460,
year = {2026},
author = {Guo, Y and Wang, X and Wu, Y and Li, Y and Wei, X},
title = {The role of the microbial-immune-bone axis in bone tumor development: mechanistic integration, systems modeling, and intervention prospects.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1762046},
pmid = {41716460},
issn = {2235-2988},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; Animals ; *Bone Neoplasms/immunology/pathology/microbiology ; Tumor Microenvironment/immunology ; *Bone and Bones/immunology/pathology ; Bone Remodeling ; },
abstract = {The emergence and development of bone tumors stem from a combination of intrinsic genetic alterations in tumor cells, remodeling of the bone marrow microenvironment, and shifts in the host's systemic immune-metabolic state. In recent years, gut microorganisms have been shown not only to influence bone mass regulation and conditions involving disrupted bone homeostasis, such as osteoporosis, but also to substantially affect the formation of primary bone tumors and metastatic lesions by modulating immune cell differentiation, inflammatory activity, and the coupling of bone remodeling. Focusing on the "Microbiota-Immune-Bone axis" (MIB), a growing body of fundamental and translational research indicates that alterations in gut microbial composition and function can reshape metabolite profiles-including short-chain fatty acids, bile acids, indole derivatives-and pathogen-associated molecular patterns (PAMPs). These signals act on the intestinal barrier and bone marrow immunity through G-protein-coupled receptors, nuclear receptors, and pattern-recognition receptors, thereby shifting the balance between bone resorption and formation and modifying the immune characteristics of the bone microenvironment, ultimately facilitating bone tumor cell colonization, proliferation, and immune escape. This review takes the MIB axis as its central framework to integrate the major pathways through which gut microbes and their metabolites regulate intestinal and myeloid immunity, bone remodeling, and bone tumor biology, to construct a systems-level model of tumor initiation and progression, to identify druggable signaling nodes, and to assess the potential and challenges of microbiota-modulating approaches-including antibiotics, probiotics, dietary strategies, and fecal microbiota transplantation-in preventing and treating bone tumors, thereby offering a theoretical foundation for developing integrated interventions targeting the gut microbiota and the MIB axis.},
}

Humans
*Gastrointestinal Microbiome/immunology
Animals
*Bone Neoplasms/immunology/pathology/microbiology
Tumor Microenvironment/immunology
*Bone and Bones/immunology/pathology
Bone Remodeling

@article {pmid41716434,
year = {2026},
author = {Mohiuddin, M},
title = {Chronic Antibiotic Use, Gut Microbiota Dysbiosis, and Increased Risk of Colorectal Cancer: An Emerging Threat.},
journal = {Health science reports},
volume = {9},
number = {2},
pages = {e71866},
pmid = {41716434},
issn = {2398-8835},
abstract = {BACKGROUND AND AIMS: The gut microbiota plays a vital role in host health by regulating metabolic processes, immune function, and epithelial barrier functions. Chronic use of antibiotics can alter this environment and introduce gut dysbiosis, which is defined as an alteration of microbial communities characterized by a loss of beneficial microbes and overgrowth of pathogenic microbes. Gut dysbiosis is increasingly associated with the development and progression of colorectal cancer (CRC). We explored the relationship between long-term antibiotic exposure, gut microbiota dysbiosis, and CRC risk, as well as strategies for preventing and restoring gut microbiomes.

METHODS: Relevant information was extracted from published articles available in PubMed, Scopus, and Google Scholar. The keywords "Gut," "Dysbiosis," "Antibiotic," "Colorectal," and "Microbiota" were used to search for relevant information.

RESULTS: Studies have demonstrated that chronic antibiotic exposure significantly reduces microbial diversity, particularly by decreasing beneficial species (e.g., Lactobacillus, Bifidobacterium, and Faecalibacterium), while favoring pathogenic species (e.g., Klebsiella pneumoniae and Enterococcus faecium). Antibiotic-induced dysbiosis reduces the production of microbial metabolites, including short-chain fatty acids, which are essential for supporting epithelial integrity and immune homeostasis. Prior antibiotic use is associated with a 13% increased risk of CRC, with antibiotic-induced microbiota alterations lasting for months to years. Several factors, including diet, pollution, and over-the-counter access to antibiotics in low-and middle-income countries, may contribute to an increased risk of dysbiosis and CRC. Additionally, interventions such as dietary fiber, probiotic supplementation, fecal microbiota transplantation, next-generation probiotics, and phage therapy may be potential strategies to restore the microbiome and achieve gut health.

CONCLUSION: Substantial use of antibiotics may alter the gut microbiota and increase the risk of CRC. To mitigate this risk, it is essential to practice prudent antibiotic use and adopt dietary, probiotic, and microbiome-restoring practices to support the health of the gut microbiome.},
}

@article {pmid41716280,
year = {2026},
author = {Jiang, HB and Zhang, JQ and Liang, H and Sun, LY and Deng, CQ and Yang, SF},
title = {Exploring osteosarcopenia from the gut microbiota perspective: mechanistic insights and therapeutic potentials based on the gut-muscle-bone Axis.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1729870},
pmid = {41716280},
issn = {1664-302X},
abstract = {The aging society presents a growing challenge in the form of osteosarcopenia (OS). This syndrome is marked by the concomitant deterioration of bone (osteoporosis) and muscle (sarcopenia), and significantly elevates the risks of fractures, disability, and mortality. Despite its clinical relevance, the shared pathophysiology and effective interventions for OS remain elusive. Emerging evidence highlights the gut microbiota (GM) as a critical modulator of musculoskeletal health. This review integrates current evidence to delineate "gut-muscle-bone Axis" framework, summarizing current evidence on how GM dysbiosis may be involved in OS through multifaceted mechanisms, including intestinal barrier disruption, chronic inflammation, endocrine dysregulation, impaired nutrient absorption, and disrupted muscle-bone crosstalk. GM-derived metabolites, such as short-chain fatty acids (SCFAs), interact with immune, metabolic, and hormonal pathways to influence osteoblast/osteoclast activity and muscle protein synthesis. Furthermore, systemic inflammation triggered by GM imbalance exacerbates bone resorption and muscle atrophy. The axis also highlights bidirectional feedback between muscle and bone, mediated by myokines (e.g., irisin) and osteokines (e.g., osteocalcin), which synergistically regulate musculoskeletal homeostasis. Therapeutic strategies targeting GM modulation-such as dietary optimization (plant-based proteins, high-fiber diets), probiotics/prebiotics, exercise, and fecal microbiota transplantation (FMT)-suggest a potential capacity to modulate gut-muscle-bone interactions, which may be relevant to osteosarcopenia-related pathophysiological processes. This review proposes an integrative conceptual framework for understanding the pathogenesis of OS, synthesizing evidence primarily derived from osteoporosis and sarcopenia research, as well as animal and mechanistic studies. While direct clinical evidence in OS remains limited, emerging findings suggest that microbiota-centered strategies may hold potential for future preventive and therapeutic exploration.},
}

@article {pmid41716272,
year = {2026},
author = {Li, M and Xiao, S and Wang, Y and Li, T and Hu, Q and Dong, L and Guo, Y and Shi, Z and Yang, Q and Cai, W and Li, Q and Peng, B and Li, P and Weng, X and Wang, Y and Li, Y and Dong, Y and Zhu, X and Gong, Z and Chen, Y},
title = {Wuji Pill and Akkermansia muciniphila alleviates intestinal dysfunction and depression-like behavior in irritable bowel syndrome through the microbiota-gut-brain axis.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1739408},
pmid = {41716272},
issn = {1664-302X},
abstract = {INTRODUCTION: Irritable bowel syndrome (IBS) is a typical disorder of gut-brain interaction (DGBI). The microbiota-gut-brain (MGB) axis is pivotal in preventing and treating IBS. Wuji Pill is a traditional Chinese medicine commonly used to treat IBS. This study aimed to investigate the mechanism by which Wuji Pill improves IBS via the MGB axis.

METHODS: The visceral sensitivity and colonic motor function were evaluated using the abdominal wall withdrawal reflex test and the colonic motility curve. Depression-like behavior were evaluated using sucrose preference test, open field test, novelty-suppressed feeding test, and forced swimming tests. The intestinal mucus secretion and the activation status of microglia was detected using AB-PAS staining and immunofluorescence staining, respectively. The species composition and abundance of gut microbiota were detected through 16S rRNA sequencing and RT-qPCR. Targeted metabonomics and RT-qPCR were used for metabolites and metabolic enzymes analysis.

RESULTS: In this study, Wuji Pill improved the symptoms of IBS rats and increased the relative abundance of Akkermansia muciniphila in feces. Additionally, antibiotics affected the repair of intestinal mucus secretion and significantly reduced the level of short-chain fatty acids. Subsequently, fecal microbiota transplantation and A. muciniphila transplantation can improve the symptoms of IBS rat by increasing intestinal mucus secretion, elevating the levels of acetic acid and butyric acid in feces. Additionally, the microglia in the cortex were suppressed, and the tryptophan-kynurenine pathway in the hippocampus was inhibited, leading to the conversion of tryptophan into 5-HT.

DISCUSSION: This study highlights the Wuji Pill may alleviate IBS symptoms by modulating A. muciniphila and regulating the tryptophan metabolism pathway through MGB axis.},
}

@article {pmid41715264,
year = {2026},
author = {Kumar, R and Elangovan, S and Asrani, S},
title = {Emerging Therapeutic Regimens as Alternatives to Glucocorticoids for Severe Alcohol-Associated Hepatitis: A Comprehensive Review.},
journal = {Clinical and molecular hepatology},
volume = {},
number = {},
pages = {},
doi = {10.3350/cmh.2025.1163},
pmid = {41715264},
issn = {2287-285X},
abstract = {Severe alcohol-associated hepatitis (SAH) is the most aggressive form of alcohol-associated liver disease and is associated with very high short-term mortality. It is characterized by the acute onset of jaundice in the context of ongoing alcohol use, most commonly defined by a Maddrey Discriminant Function ≥32 or a Model for End-Stage Liver Disease score ≥ 20. Despite its increasing global burden and substantial healthcare costs, therapeutic options remain limited, and outcomes are poor. The severity of liver failure, systemic inflammation, infectious complications, and extrahepatic organ dysfunction determines the prognosis in SAH. The pathophysiology of SAH is multifactorial, involving direct hepatotoxicity from alcohol metabolites, oxidative stress, dysregulated immune activation, gut dysbiosis with increased intestinal permeability, impaired hepatic regeneration, and genetic susceptibility. These interrelated mechanisms culminate in an exaggerated inflammatory response driven by macrophage activation and cytokine release, resulting in hepatocellular injury and multi-organ failure. Glucocorticoids remain the guideline-recommended standard of care for selected patients; however, their benefit is limited to modest short-term survival gains, with high rates of non-response and infection. Numerous investigational therapies targeting inflammation, oxidative stress, liver regeneration, bile acid signaling, epigenetic regulation, and the gut-liver axis have been evaluated, with largely disappointing results. Emerging approaches, including interleukin-22 agonists and epigenetic modulators such as larsucosterol, show promise but require validation in well-designed trials. This review synthesizes current evidence on the definition, prognostic assessment, and pathophysiology of SAH, critically appraises existing and emerging therapies, and highlights the need for combination strategies, improved patient stratification, and personalized treatment approaches.},
}

@article {pmid41714082,
year = {2026},
author = {Mahajan, S and Nk, A and Banerjee, SK},
title = {Recent advances of microbial medicine to prevent and treat cardiovascular disease.},
journal = {Progress in molecular biology and translational science},
volume = {220},
number = {},
pages = {305-337},
doi = {10.1016/bs.pmbts.2026.01.028},
pmid = {41714082},
issn = {1878-0814},
mesh = {Humans ; *Cardiovascular Diseases/therapy/prevention & control/microbiology ; Animals ; Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; },
abstract = {Cardiovascular diseases (CVDs) remain the leading cause of global mortality, with standard pharmacological interventions often failing to fully address their complex pathophysiology. Recent advances in microbial medicine highlight the human gut microbiome as a critical regulator of cardiovascular health. Gut microbial metabolites such as short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), and indole derivatives play pivotal roles in modulating inflammation, lipid metabolism, immune function, and vascular homeostasis. Dysbiosis, or microbial imbalance, has been strongly associated with atherosclerosis, hypertension, and heart failure. Consequently, therapies targeting the gut microbiota including probiotics, prebiotics, synbiotics, and postbiotics have emerged as promising adjuncts in CVD prevention and treatment. Moreover, fecal microbiota transplantation (FMT) and synthetic biology approaches using engineered microbes offer novel strategies to restore microbial balance and deliver therapeutic molecules. Dietary interventions, particularly Mediterranean and fiber-rich diets, further support cardiovascular health through microbiota modulation. While preclinical and clinical studies underscore the potential of microbiome-based interventions, challenges related to strain specificity, delivery systems, and regulatory frameworks remain. Nonetheless, integrating microbial medicine into cardiovascular care represents a transformative shift toward precision, holistic, and personalized treatment paradigms. This chapter explores these cutting-edge therapeutic interventions and their implications for reshaping the future landscape of cardiovascular disease management.},
}

Humans
*Cardiovascular Diseases/therapy/prevention & control/microbiology
Animals
Gastrointestinal Microbiome
Fecal Microbiota Transplantation
Probiotics/therapeutic use

@article {pmid41714079,
year = {2026},
author = {Bhowmick, J and Bagchi, A},
title = {Fecal microbiota transplantation in liver diseases: Therapeutic potential and associated risks.},
journal = {Progress in molecular biology and translational science},
volume = {220},
number = {},
pages = {229-246},
doi = {10.1016/bs.pmbts.2026.01.001},
pmid = {41714079},
issn = {1878-0814},
mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects ; *Liver Diseases/therapy/microbiology ; Risk Factors ; Animals ; },
abstract = {Fecal microbiota transplantation (FMT) is a biologically coherent strategy to modulate the gut-liver axis by restoring ecosystem structure and function. This chapter synthesizes current evidence and practice of FMT in various liver disease conditions. In cirrhosis with recurrent hepatic encephalopathy (HE), randomized trials demonstrate adjunctive benefits of FMT, reducing recurrence and hospitalizations as well as improving cognition, with route flexibility (lower-GI infusions or oral capsules) and emerging microbiome predictors of response. In severe alcohol-associated hepatitis and ACLF, early single-center trials suggest fewer infections and short-term survival gains, warranting confirmation in multicenter, blinded studies for further outcomes. For MASLD/MASH, FMT consistently shifts intestinal permeability, bile-acid signatures, and hepatic transcriptomics, although it has not reliably improved MRI-PDFF or insulin resistance in unselected cohorts; future success likely requires phenotype enrichment and function-matched donors or defined consortia. Data in chronic hepatitis B remain exploratory, positioning FMT, if at all, as an adjunct to antivirals. Methods are standardized around rigorous donor screening, controlled manufacturing, indication-specific endpoints, and strain-resolved engraftment analytics linking mechanism to outcome. Refractory Clostridium difficile is the only FDA-approved indication of FMT. Use of FMT in hepatology use should remain protocolled and regulated. Priorities include precision donor matching, next-generation consortia, platform trials, and long-term safety registries.},
}

Humans
*Fecal Microbiota Transplantation/adverse effects
*Liver Diseases/therapy/microbiology
Risk Factors
Animals

@article {pmid41714075,
year = {2026},
author = {Konar, D},
title = {Clinical applications of live biotherapeutics: Current trends and future prospects.},
journal = {Progress in molecular biology and translational science},
volume = {220},
number = {},
pages = {103-138},
doi = {10.1016/bs.pmbts.2026.01.003},
pmid = {41714075},
issn = {1878-0814},
mesh = {Humans ; Animals ; *Biological Therapy/trends/methods ; *Biological Products/therapeutic use ; },
abstract = {Live biotherapeutic (LBP) is defined by the FDA as a biological product that: (1) contains live organisms, such as bacteria; (2) applies to the prevention, treatment, or cure of a disease or condition of human beings; and (3) is not a vaccine. Progress in microbiome science and the limitations of antibiotics have necessitated the use of LBPs to complement or replace conventional therapies across multiple medical disciplines. The most important advancement is in the infectious disease domain, where fecal microbiota transplantation validated ecological restoration for recurrent Clostridioides difficile infection and paved the way for the first approved LBPs (REBYOTA® and VOWST™/SER-109). Constructing rational microbial consortia and strain-level strategies aim to induce commensal resilience and prevent the establishment of multidrug-resistant organisms. In oncology, gut microbial composition modulates response to immune checkpoint inhibitors. So, defined microbial consortia and engineered E. coli Nissle are being developed to enhance antitumor immunity and localize payloads. Early studies in animals and humans also support the application of this approach in metabolic disease, allergy, and oral health. Translation from benchside to bedside, however, is fraught with hurdles-variable patient response, manufacturing consistency, safety standards, cost, and ethics-exacerbated by heterogeneous global regulations, underscoring the need for harmonization. Precision microbial consortia, programmable "living medicines," and biohybrid formulations could extend LBPs into broader indications and global health, shifting practice toward an ecological model of therapeutics.},
}

Humans
Animals
*Biological Therapy/trends/methods
*Biological Products/therapeutic use

@article {pmid41713826,
year = {2026},
author = {Yerushalmy-Feler, A and Spencer, EA and Dubinsky, MC and Suskind, DL and Mitrova, K and Hradsky, O and Conrad, MA and Kelsen, JR and Sladek, M and Yeh, PJ and Tzivinikos, C and Henderson, P and Wlazlo, M and Hackl, L and Shouval, DS and Mouratidou, N and Bramuzzo, M and Urlep, D and Olbjørn, C and Mancuso, G and Schneider, AM and Pujol-Muncunill, G and Yogev, D and Kang, B and Gasparetto, M and Rungø, C and Romano, C and Martinelli, M and Kolho, KL and Hojsak, I and Norsa, L and Rinawi, F and Sansotta, N and Rimon, RM and Granot, M and Scarallo, L and Trindade, E and Rodríguez-Belvís, MV and Turner, D and Cohen, S},
title = {Upadacitinib Maintenance Therapy in Pediatric Ulcerative Colitis: 52-week Multicenter Study from the Porto Group of ESPGHAN.},
journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cgh.2026.02.012},
pmid = {41713826},
issn = {1542-7714},
abstract = {BACKGROUND AND AIMS: Data on upadacitinib therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBD-U) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as a maintenance therapy in pediatric UC.

METHODS: Children treated with upadacitinib for maintenance of remission of active UC or IBD-U from 35 centers affiliated with the Porto group of ESPGHAN were enrolled in this retrospective study. Data on demographic, clinical, laboratory, endoscopic, imaging and adverse events (AEs) data were recorded over 52 weeks of follow-up.

RESULTS: A total of 105 children were included (95 UC and 10 IBD-U, mean age 14.6±3.3 years). Prior to upadacitinib, 103/105 (98%) children were treated with biologic therapies and 79 (75%) with ≥2 biologics. Clinical remission and corticosteroid-free clinical remission (CFR) were observed after 8 weeks in 61 (58%) and 53 (51%) children, respectively. By week 52, 75 (71%) children achieved clinical remission and 73 (70%) CFR. Sustained CFR was recorded in 63 (60%) children. CFR with normal C-reactive protein was observed in 56% of children, and CFR with fecal calprotectin levels <150 mcg/g was observed in 38%, by week 52. Fifty-two (50%) children experienced AEs, two of which were serious (an appendiceal neuroendocrine tumor and cytomegalovirus colitis). The most frequent AEs were hyperlipidemia (n=20), infections (n=18), and acne (n=14).

CONCLUSION: Upadacitinib is an effective induction and maintenance therapy for refractory pediatric UC and IBD-U. Effectiveness should be weighed against the potential risks of AEs.},
}

@article {pmid41713817,
year = {2026},
author = {Zhao, Q and Cao, Y and Zhang, Z and Yang, Y and Wang, L and Xu, M and Mao, Y and Zhang, X and Zeng, M and Yang, P and Chen, Q and Yan, H and Yang, G},
title = {Xiao-Chaihu-Tang preserves intestinal barrier and ameliorates irinotecan-evoked delayed diarrhea by anchoring endogenous tryptophol to modulate inflammation and oxidation dependent on AhR-UGT1A1-microbiota axis.},
journal = {Journal of ethnopharmacology},
volume = {363},
number = {},
pages = {121380},
doi = {10.1016/j.jep.2026.121380},
pmid = {41713817},
issn = {1872-7573},
abstract = {Xiao-Chaihu-Tang (XCHT), a well-known traditional formula, is commonly used to treat various types of diarrhea. It also exhibits promising efficacy against chemotherapy irinotecan (CPT-11)-induced delayed diarrhea (DD). However, its underlying mechanisms, specifically concerning endogenous metabolites, key pathways, and functional gut bacteria at the species level, remain unclear, severely restricting its clinical application.

AIM OF THE STUDY: This study aimed to elucidate the biomarkers, pathways, and functional bacteria involved in XCHT's alleviating CPT-11-evoked DD using multi-omics approaches, antagonists, and fecal microbiota transplantation (FMT).

MATERIALS AND METHODS: First, the ingredients of XCHT and absorbed compounds in rat plasma were identified using liquid chromatography-mass spectrometry (LC-MS). Next, the therapeutic effects of XCHT were assessed by monitoring perianal status, body weight, disease activity index, food and water intake, and histopathological changes in the colon (hematoxylin and eosin, alcian blue-periodic acid-schiff staining). The underlying mechanisms were studied using metabolomics and network pharmacology, which highlighted the role of endogenous biomarkers and associated pathways. Tryptophol was identified as a key correlate, and its efficacy was further validated in rat and Caco-2 models using antagonists of potential targets (AhR and UGT1A1). The levels of inflammatory cytokines, and oxidative stress markers, intestinal barrier proteins, and mucins were detected by enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunofluorescence. Furthermore, functional gut bacteria were identified using metagenomic sequencing and validated using FMT, while gut leakage was detected using fluorescence in situ hybridization (FISH). Finally, the interactions between tryptophol with targets of AhR and UGT1A1 were examined using molecular docking, molecular dynamics, and surface plasmon resonance.

RESULTS: LC-MS analysis identified 43 phytochemicals in XCHT and 17 compounds absorbed in plasma. XCHT, similar to tryptophol, attenuated DD by improving perianal status, disease activity index, and colon pathology, while increasing body weight, food intake, and water intake. Metabolomics analysis revealed 33 potential endogenous biomarkers, including PGB3, LysoPA, and so on. Integrated with network pharmacology, the results indicated that the therapeutic effect of XCHT involved the regulation of tryptophan metabolism, arachidonic acid metabolism, inflammation, and oxidative stress. Tryptophol, which exhibited a strong correlation with efficacy indices, reduced inflammation and oxidation in vivo/vitro, and enhanced intestinal barrier protein and mucin expression in an AhR-UGT1A1-dependent manner. Furthermore, metagenomic sequencing and FISH demonstrated that both XCHT and tryptophol normalized the abundance of 10 gut bacterial species (for example, Lactobacillaceae bacterium, Massiliimalia timonensis, and Limosilactobacillus reuteri) and inhibited bacterial invasion. Molecular interaction studies confirmed the strong binding between tryptophol with AhR and UGT1A1.

CONCLUSION: This study demonstrates that XCHT preserves intestinal barrier integrity in rats and alleviates CPT-11-induced DD. This protective effect is mediated by modulating inflammation and oxidative stress via the tryptophol- AhR-UGT1A1-microbiota axis, providing a novel paradigm for mechanistic studies on toxicity reduction in clinical chemotherapy drugs.},
}

@article {pmid41713731,
year = {2026},
author = {Xu, J and Hu, R and Zheng, J and Ju, Q and Liu, Y and Chen, S and Liu, Z and Lei, Y and Yang, J and Zhang, D and Shen, W},
title = {Modulation of the intestinal microbiome and reversal of the immunosuppressive microenvironment by nanoparticles for chemoimmunotherapy in prostate cancer.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2026.02.027},
pmid = {41713731},
issn = {2090-1224},
abstract = {INTRODUCTION: Prostate cancer (PCa), a "cold" tumor with an immunosuppressive microenvironment, exhibits poor sensitivity to immunotherapies, limiting treatment efficacy. Chemotherapeutics often cause intestinal injury and disrupt gut microbiota, further impairing chemoimmunotherapy outcomes. Modulating gut microbiota to reverse immunosuppression represents a potential strategy to enhance PCa treatment.

OBJECTIVES: To develop a novel therapeutic strategy using nanomedicine to regulate intestinal flora, thereby reversing the immunosuppressive microenvironment and improving chemoimmunotherapy efficacy in PCa.

METHODS: Cabazitaxel (CBZ)-loaded, folic acid (FA)-modified pH/ROS dual-responsive nanoparticles (CBZ/FA-CA-OCD NPs) were fabricated. In vitro and in vivo experiments evaluated NPs accumulation, cellular internalization (via FA-mediated endocytosis), drug release, intestinal mucosal injury, and tumor growth inhibition. Gut microbiota modulation (e.g., Lachnospiraceae, Firmicutes, Muribaculaceae, Bacteroidota) and CD4[+]/CD8[+] T-cell infiltration were assessed. Fecal microbiota transplantation (FMT) validated microbiota-mediated immune effects.

RESULTS: The CBZ/FA-CA-OCD NPs accumulated in PCa tissues were internalized by PC-3/LNCaP cells and released CBZ in acid/ROS microenvironments to inhibit tumor growth. Compared to free CBZ, NPs attenuated intestinal injury, modulated microbiota (increased Lachnospiraceae/Firmicutes, decreased Muribaculaceae/Bacteroidota), and enhanced anti-PD-1 efficacy by increasing CD4[+]/CD8[+] T-cell infiltration. FMT confirmed that microbiota from NP-treated mice promoted T-cell infiltration in tumors.

CONCLUSION: CBZ/FA-CA-OCD NPs improve PCa chemoimmunotherapy by regulating gut microbiota, reversing immunosuppression, and enhancing T-cell infiltration. This nanomedicine-based strategy provides a promising approach to boost PCa treatment outcomes.},
}

@article {pmid41713730,
year = {2026},
author = {Li, Y and Zhang, Y and Liu, T and Tuo, Y and Zhang, Y and You, H and Peng, S and Wu, T and Cai, T and Lin, Z and Feng, Z and Liu, Z and Wu, J and Liu, X and Ding, L},
title = {Alleviation of high-fat diet-induced lipid metabolism disorders: role of quinoa peptides in reducing high-activity BSH-producing gut microbiota abundance and modulating BA-FXR/TGR5 signaling.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2026.02.040},
pmid = {41713730},
issn = {2090-1224},
abstract = {INTRODUCTION: Lipid metabolism disorders contribute significantly to various metabolic diseases and are closely related to gut microbiota dysbiosis. Quinoa intake has been increasingly linked to improved metabolic regulation and body weight control. In our earlier work, oral administration of quinoa-derived peptides (QPep) modulated gut microbiota composition and mitigated hepatic lipid dysregulation in high-fat diet (HFD)-induced obese mice. Nevertheless, the specific mechanisms responsible for these effects remain incompletely understood.

OBJECTIVES: This study aimed to elucidate the mechanisms by which QPep alleviates lipid metabolic disorders in HFD-induced obese mice.

METHODS: Mice were fed a HFD with or without oral QPep intervention. Both antibiotic treatment and fecal microbiota transplantation were employed to assess the microbiota-dependent effects of QPep. Comprehensive multi-omics and molecular analyses were conducted to characterize metabolic phenotypes alongside gut microbial composition, bile acids (BAs) metabolism, and host signaling pathways in the liver, ileum, and adipose tissues.

RESULTS: QPep administration alleviated HFD-induced metabolic disorders, leading to reductions in body weight and adiposity, improvements in serum lipid profiles and hepatic steatosis, and restoration of glucose homeostasis. Microbiota depletion and transplantation experiments suggested a microbiota-dependent contribution to the observed effects. Mechanistically, QPep selectively reduced high-activity bile salt hydrolase (BSH)-producing bacteria abundance, reduced intestinal BSH activity, and preserved conjugated BAs, thereby suppressing ileal FXR-FGF15 signaling, enhancing hepatic BAs synthesis, and activating TGR5 in adipose and ileum tissues to restore systemic lipid metabolism.

CONCLUSION: These findings demonstrate that QPep modulate gut microbiota-BAs signaling to restore lipid homeostasis, highlighting their potential as a dietary intervention for the prevention and management of obesity-related metabolic disorders.},
}

@article {pmid41713032,
year = {2026},
author = {Park, J and Choi, Y and Lee, W and Kang, A and Seo, E and Kim, MG and Jang, KB and Song, M and Oh, S and Kim, Y},
title = {Heat-killed Bacteroides fragilis SLAM_BAF01 alleviates weaning-induced stress responses and cognitive impairments by modulating the gut-brain-microbiome axis.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {196},
number = {},
pages = {119121},
doi = {10.1016/j.biopha.2026.119121},
pmid = {41713032},
issn = {1950-6007},
abstract = {Weaning transition in porcine industry is marked by nutritional, microbial, and psychological stresses that can impair growth and development. Accumulating evidence indicates that weaning-related stress not only disrupts gut microbial homeostasis but impairs gut-brain axis signaling through activation of stress-related neuroendocrine pathways. However, current interventions have largely focused on improving growth performance or enteric symptoms, while integrated strategies targeting the gut-brain-microbiome axis remain limited. Next-generation probiotics (NGPs) such as Bacteroides fragilis have been reported to exert beneficial effects on both intestinal health and brain function, positioning them as promising candidates for alleviating weaning stress. However, their practical application remains challenging due to the strict anaerobic nature. In this study, we investigated that a porcine-derived heat-killed B. fragilis SLAM_BAF01 exerts beneficial effects under weaning stress through gut-brain-microbiome modulation, thereby enabling a more stable and scalable application. First, to investigate the relationship within the gut-brain-microbiome axis under weaning stress conditions, we employed a fecal microbiota transplantation (FMT)-based mouse model and a physiologically relevant weaning pig model. Multi-omics analyses were conducted to characterize microbial and host responses. B. fragilis SLAM_BAF01 exhibited acid and bile tolerance, preserved structural integrity, and lacked enterotoxicity. In the mouse FMT model, heat-killed SLAM_BAF01 positively modulated gut microbial composition, reinforced intestinal barrier function, and attenuated stress-related responses. Especially, brain γ-aminobutyric acid (GABA) levels increased by 150 %, while serum corticosterone levels were reduced by 17 % compared with the control. In the weaning pig model, heat-killed SLAM_BAF01 improved growth performance by 7 % and significantly reduced inflammation and stress markers. These findings demonstrate that heat-killed postbiotic B. fragilis SLAM_BAF01 as a promising candidate capable of mitigating weaning-associated stress through enhancing gut-brain-microbiome axis function in porcine industry.},
}

@article {pmid41711677,
year = {2026},
author = {Rinderknecht, S and Bertolo, A and Valido, E and Stojic, S and Wong, S and Farkas, GJ and Iyer, P and Jaric, I and Stoyanov, J and Glisic, M},
title = {The role of short-chain fatty acids in spinal cord injury: A systematic review of human and animal evidence.},
journal = {The journal of spinal cord medicine},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/10790268.2025.2607831},
pmid = {41711677},
issn = {2045-7723},
abstract = {CONTEXT: Spinal cord injury (SCI) disrupts gut microbiota composition, resulting in dysbiosis that can worsen neuroinflammation and impede post-injury recovery. Short-chain fatty acids (SCFA), metabolites produced by the gut microbiome with anti-inflammatory properties, offer a promising avenue for improving recovery and rehabilitation outcomes.

OBJECTIVE: We aimed to compile a summary of the human and animal evidence on the potential benefits of SCFA or SCFA  - producing bacteria in individuals with SCI.

METHODS: Three databases (EMBASE, Medline (Ovid) and Web of Science) were searched from inception until 19 October 2023. No language restrictions were applied. Title and abstract screening, data extraction and risk of bias assessments were done independently by two reviewers.

RESULTS: A total of 2492 studies were retrieved, 69 full-text studies were reviewed, and 13 studies were included (11 animal and 2 human). Human studies, which involved participants with chronic SCI, linked gut dysbiosis (a proxy for low SCFA production) and human metabolic profiles, suggesting a potential role for microbiome-targeted interventions even in later stages of injury. Evidence from animal studies, predominantly in acute and sub-acute models of SCI, consistently associated SCFA interventions with improved motor function, reduced tissue damage and favorable changes in inflammatory and oxidative stress markers. Fecal microbiota transplantation and probiotics improved motor function and reduced lesion size in animal models. Gut microbiome modulations through treatments such as melatonin, moxibustion, and intermittent fasting was correlated with improved motor outcomes and increased abundance of SCFA-producing bacteria.

CONCLUSIONS: This review highlights the potential of targeting the gut microbiota and SCFAs as therapeutic strategies for SCI recovery. However, despite promising results in animal models, human evidence remains limited.},
}

@article {pmid41710924,
year = {2026},
author = {Liu, X and Chen, Z and Lu, Y and Wu, Y and Huang, Y and Zhang, Y and Li, M and Feng, N},
title = {Fecal microbiota transplantation: a novel strategy and challenges in the adjuvant treatment of bladder Cancer.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1756107},
pmid = {41710924},
issn = {1664-302X},
abstract = {The clinical management of bladder cancer faces major challenges due to treatment resistance and recurrence, which require the development of new adjuvant strategies. The role of the gut microbiome in influencing bladder cancer progression and treatment response through the "gut-bladder axis" is gaining recognition. This understanding provides a theoretical rationale for exploring microbiota-targeting interventions, such as fecal microbiota transplantation (FMT). As a method capable of thoroughly reshaping the gut microbiota, FMT may have broad clinical potential. This review systematically explores the possible role of FMT in treating bladder cancer. It begins by summarizing the observational and causal evidence linking gut microbiota dysbiosis to bladder cancer, which forms the rationale for considering FMT as an intervention. Then, it discusses how FMT might improve therapeutic effectiveness, including regulation of microbial metabolites (such as short-chain fatty acids, tryptophan, and bile acids), repair of the intestinal barrier, induction of epigenetic reprogramming and modulation of the urinary microbiota. The review also considers potential scenarios for combining FMT with existing adjuvant therapies, including immunotherapy, chemotherapy, and radiotherapy. Finally, it objectively evaluates the key challenges in translating FMT into clinical practice, including effectiveness, safety, standardization, and regulatory or ethical issues, and outlines future directions. By synthesizing current evidence, this review highlights FMT as a potentially promising and innovative adjuvant strategy worthy of further investigation, which, if validated, could contribute to overcoming current therapeutic challenges in bladder cancer.},
}

@article {pmid41709304,
year = {2026},
author = {Zhang, Q and Zhu, Q and Xiao, Y and Liao, S and Liu, S and Shi, S},
title = {Microbiota-derived propionate suppresses Salmonella virulence gene expression via LuxS quorum sensing.},
journal = {Microbiome},
volume = {14},
number = {1},
pages = {70},
pmid = {41709304},
issn = {2049-2618},
support = {32573258//National Natural Science Foundation of China/ ; YZ2024242//Yangzhou Science and Technology Program/ ; CARS-41-G01//Agriculture Research System of China/ ; },
mesh = {Animals ; *Quorum Sensing/drug effects ; Chickens/microbiology ; *Carbon-Sulfur Lyases/genetics/metabolism ; *Bacterial Proteins/genetics/metabolism ; *Propionates/metabolism/pharmacology ; Virulence/genetics ; *Gastrointestinal Microbiome ; Gene Expression Regulation, Bacterial/drug effects ; *Salmonella Infections, Animal/microbiology ; Lactones/metabolism ; Homoserine/analogs & derivatives/metabolism ; Biofilms/drug effects/growth & development ; RNA, Ribosomal, 16S/genetics ; Cecum/microbiology ; Virulence Factors/genetics ; *Salmonella/pathogenicity/genetics/drug effects ; Feces/microbiology ; },
abstract = {BACKGROUND: Despite mounting evidence that commensal microbes enhance host defenses, whether and how they directly suppress pathogen virulence remains elusive. Here, we investigate metabolites from the gut microbiota of infection‑resistant Tibetan chickens for their ability to reduce Salmonella virulence gene expression and elucidate the molecular mechanism by which these compounds inhibit the LuxS/AI‑2 quorum‑sensing system.

RESULTS: Initially, we compared the expression of the quorum‑sensing gene luxS and biofilm-associated virulence genes in Tibetan chickens and broiler chickens post-Salmonella infection. Notably, Tibetan chickens exhibited significantly lower virulence gene expression than broiler chickens. Subsequently, fecal microbiota transplantation (FMT) from Tibetan chickens to broiler chickens reduced virulence gene expression in infected recipients. Further, 16S rRNA gene sequencing of cecal contents revealed that FMT enhanced microbial diversity and altered composition in infected broiler chickens, specifically enriching short-chain fatty acids (SCFA)-producing beneficial bacteria (e.g., Bacteroides, Rikenellaceae_RC9_gut_group, Phascolarctobacterium, Desulfovibrio). Critically, using Transwell chambers to separate microbes and metabolites, we identified metabolites as mediators of this effect. Subsequent liquid chromatography-mass spectrometry (LC-MS) quantification demonstrated significantly elevated propionate concentrations in both uninfected and infected Tibetan chickens, and FMT-recipient broiler chickens. Propionate levels correlated negatively with key virulence factor expression. Moreover, in vitro experiments showed that propionate inhibited Salmonella biofilm formation, reduced autoinducer-2 (AI-2) activity, and downregulated the expression of virulence genes. In vivo, we further confirmed that propionate decreased the expression of Salmonella virulence genes. Taken together, these results support that propionate suppresses Salmonella virulence gene expression by targeting the LuxS/AI-2 quorum-sensing pathway. To validate this mechanism, we generated a luxS knockout strain by homologous recombination; strikingly, propionate failed to attenuate virulence gene expression in this mutant, thereby establishing the essential role of LuxS/AI-2. Finally, molecular docking identified propionate-LuxS binding sites (Ile53), and site-directed mutagenesis validated critical functional residues, highlighting structural determinants for virulence gene expression regulation.

CONCLUSION: These findings underscore the role of the gut-derived metabolite propionate in directly modulating pathogen virulence gene expression by targeting the LuxS/AI-2 quorum‑sensing system, offering novel insights into microbiota-based strategies for infectious disease management.},
}

Animals
*Quorum Sensing/drug effects
Chickens/microbiology
*Carbon-Sulfur Lyases/genetics/metabolism
*Bacterial Proteins/genetics/metabolism
*Propionates/metabolism/pharmacology
Virulence/genetics
*Gastrointestinal Microbiome
Gene Expression Regulation, Bacterial/drug effects
*Salmonella Infections, Animal/microbiology
Lactones/metabolism
Homoserine/analogs & derivatives/metabolism
Biofilms/drug effects/growth & development
RNA, Ribosomal, 16S/genetics
Cecum/microbiology
Virulence Factors/genetics
*Salmonella/pathogenicity/genetics/drug effects
Feces/microbiology

@article {pmid41708595,
year = {2026},
author = {Moses, AB and Yeh, AC},
title = {The gut microbiome in graft-versus-host disease: mechanisms of immune modulation and therapeutic approaches.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2631224},
pmid = {41708595},
issn = {1949-0984},
mesh = {*Graft vs Host Disease/immunology/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome/immunology ; Animals ; Hematopoietic Stem Cell Transplantation/adverse effects ; Immunity, Innate ; T-Lymphocytes/immunology ; Gastrointestinal Tract/microbiology/immunology ; Adaptive Immunity ; Probiotics/administration & dosage ; },
abstract = {Graft-versus-host disease (GvHD) remains a major complication of allogeneic hematopoietic stem cell transplantation and occurs when T cells from the donor graft target recipient-derived antigen on host tissue. The involvement of the gastrointestinal (GI) tract drives morbidity and mortality-not coincidentally, the GI tract also harbors the most complex and abundant human microbial reservoir. In this review, we first revisit how the microbiota initiates, propagates, and protects against GvHD in the context of both innate and adaptive immunity. Historically, the impact of the microbiota on GvHD has been ascribed primarily to the activation of innate immunity, setting the stage for donor alloreactivity. Although established models of GvHD focus on donor-host genetic disparity as the principal driver of donor T-cell activation, commensal microbes in the GI tract, whose collective gene content exceeds that of the human genome by more than two orders of magnitude, constitutes an immense and poorly understood source of potential T-cell antigens. We next discuss the evolution of therapeutic approaches aimed at modifying the microbiota to improve GvHD outcomes, incorporating over 40 clinical studies spanning the last 40 years, from broad decontamination strategies to pre/probiotic approaches and targeted ecosystem replacement, including fecal microbiota transplantation.},
}

*Graft vs Host Disease/immunology/therapy/microbiology
Humans
*Gastrointestinal Microbiome/immunology
Animals
Hematopoietic Stem Cell Transplantation/adverse effects
Immunity, Innate
T-Lymphocytes/immunology
Gastrointestinal Tract/microbiology/immunology
Adaptive Immunity
Probiotics/administration & dosage

@article {pmid41708473,
year = {2026},
author = {Liss, MA and White, JR and Doris, M and Lai, Z and Johnson-Pais, TL and Leach, RJ and Goros, M and Gelfond, J and Wickes, B},
title = {Gut Microbiome as a Lifestyle Risk Factor Associated with Prostate Cancer.},
journal = {European urology focus},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.euf.2026.01.001},
pmid = {41708473},
issn = {2405-4569},
abstract = {BACKGROUND AND OBJECTIVE: Most prostate cancer prevention strategies suggest lifestyle modifications, which lack personalization. Gut microbiome is increasingly recognized as an influencing factor in nongastrointestinal cancers, including prostate cancer. The use of gut microbiome as a lifestyle biomarker could help identify individuals with lifestyle more prone to prostate cancer and allow for modification. We aimed to develop a gut microbiome-based biomarker derived from patients undergoing prostate cancer screening.

METHODS: We assessed whether the future cancer risk can be evaluated based on a microbiome risk analysis. After extracting DNA, sequencing, and performing a bioinformatics analysis, we identified 39 unique microbial genera of importance. We utilized an artificial intelligence model to calculate their presence, abundance, and weighted significance, generating a microbiome score (Prostate Cancer Risk Insight using Microbiome UnderStanding [PRIMUS]) that ranges from 0 to 1.

KEY FINDINGS AND LIMITATIONS: Men with an increasing PRIMUS signature showed a sequential increase in prostate cancer risk. The prostate cancer risk persisted after a median follow-up of 4.5 yr. As a risk-assessment tool, the microbiome score compared favorably with prostate cancer risk calculators. Study limitations include the use of two patient groups to diversify the population for both a screening and a prebiopsy scenario; however, the cohorts used different collection methods, including stool, rectal swabs, and glove tip samples, but the same DNA isolation and sequencing. We relied on the longitudinal approach to help reduce these initial differences.

The gut microbiome may serve as a lifestyle risk factor for prostate cancer, but it is not intended to guide biopsy decisions. The implications of this study hinge on the potential for modifiability of the microbiome that could be tested in future clinical trials on prostate cancer risk reduction.},
}

@article {pmid41708187,
year = {2026},
author = {Fang, M and He, J and Zhou, S and Hong, P and Ke, L and Wu, H and Shu, Y},
title = {Pleurotus ostreatus polysaccharides improve microcystin-LR-induced intestinal damage in tadpoles by regulating the interaction between microbiota and intestine.},
journal = {Harmful algae},
volume = {153},
number = {},
pages = {103056},
doi = {10.1016/j.hal.2026.103056},
pmid = {41708187},
issn = {1878-1470},
mesh = {Animals ; *Intestines/drug effects/microbiology ; *Microcystins/toxicity ; *Gastrointestinal Microbiome/drug effects ; *Pleurotus/chemistry ; *Polysaccharides/pharmacology ; Larva/drug effects/microbiology ; *Ranidae ; Marine Toxins ; Oxidative Stress/drug effects ; },
abstract = {Exposure to microcystins (MCs) can cause severe intestinal damage. This study aimed to assess the efficacy of Pleurotus ostreatus polysaccharide in alleviating intestinal damage induced by microcystin-leucine-arginine (MC-LR) in tadpoles. Over a 30-day period, tadpoles (Pelophylax nigromaculatus) received daily exposures to MC-LR and were provided with diets either supplemented with or devoid of P. ostreatus polysaccharide. Results revealed that feeding P. ostreatus polysaccharide conferred protection against MC-LR-induced intestinal damage by mitigating barrier damage, lowering intestinal permeability, and reducing the tissue burden of MC-LR. The LPS/TLR4 pathway response was attenuated, reducing inflammation, and oxidative stress-mediated apoptosis response was also diminished. Gram-negative bacteria (e.g., Bacteroides) in the intestine show a positive correlation with LPS content and the transcription of key genes in the LPS/TLR4 pathway. Metagenomic and metabolite analysis of intestinal contents revealed increased abundance of the alanine-glyoxylate aminotransferase gene (agxt)-the key enzyme converting glyoxylic acid to glycine-and elevated glycine content in the MC-LR-exposed group fed polysaccharide. Results from the corresponding fecal microbiota transplantation experiment aligned with the trends observed in the exposure experiment. Therefore, polysaccharide alleviates MC-LR-induced intestinal damage by enhancing intestinal microbiota-mediated glycine synthesis, supplying raw materials for intestinal GSH production, reducing oxidative stress levels, and simultaneously dampening the LPS/TLR4 pathway response. Moreover, feeding polysaccharides might also regulate the intestine's defense against pathogens after MC-LR exposure by enhancing lysozyme activity. There is no evidence of intestinal damage in the P. ostreatus exopolysaccharide group. This study highlights for the first time the role of P. ostreatus polysaccharides in mitigating MC-LR-induced intestinal tissue damage, potentially offering novel insights for their application in aquaculture.},
}

Animals
*Intestines/drug effects/microbiology
*Microcystins/toxicity
*Gastrointestinal Microbiome/drug effects
*Pleurotus/chemistry
*Polysaccharides/pharmacology
Larva/drug effects/microbiology
*Ranidae
Marine Toxins
Oxidative Stress/drug effects

@article {pmid41707756,
year = {2026},
author = {Lou, S and Li, W and Wang, G and Qian, H and Zhou, J},
title = {Microbiome-gut-liver axis in chronic inflammation and cancer immunotherapy: Multi-omics Insights and a translational roadmap toward personalized medicine.},
journal = {Critical reviews in oncology/hematology},
volume = {221},
number = {},
pages = {105217},
doi = {10.1016/j.critrevonc.2026.105217},
pmid = {41707756},
issn = {1879-0461},
abstract = {Gut-liver axis is critical to integrate microbial, metabolic, and immune signaling networks to control hepatic homeostasis and carcinogenesis. Gut microbial balance disruption (dysbiosis) stimulates chronic inflammation, metabolic disorders, and transition from non-alcoholic fatty liver disease (NAFLD) to hepatocellular carcinoma (HCC). Latest evidence points to the gut and intratumoral microbiota's roles in shaping immune regulation and responsiveness to immunotherapy against cancer. This review encapsulates the latest evidence on the microbiome-gut-liver axis in chronic liver disease and cancer, highlighting multi-omics evidence, mechanisms of immune modulation, and translational avenues to microbiome-informed precision medicine in HCC. Comprehensive literature search on PubMed, Scopus, Web of Science, and Embase (until September 2025) focused on the gut-liver axis, microbiome, immune checkpoint inhibitors (ICIs), and multi-omics integration. Only mechanistically and translationally relevant peer-reviewed studies were included. Dysbiosis disrupts the permeability of the intestines and metabolism of bile acids and affects immune signaling to induce hepatic inflammation and fibrogenesis. Multi-omic studies identify key microbial metabolites, short-chain fatty acids, secondary bile acids, and tryptophan derivatives to govern the function of T-cell and responsiveness to checkpoint. Clinical research demonstrates that increased abundance of taxa like Akkermansia muciniphila, Bifidobacterium longum, and Faecalibacterium prausnitzii improves ICI efficacy but antibiotic exposure decreases therapeutic efficacy. Tumor-residing microbiomes further determine immune infiltration and risk of recurrence. Multi-omic and computational integration of gut and tumor microbiome data provides mechanistic insight to microbial-informed immunotherapy. Standardization, regulatory convergence, and ethical guidelines are critical to translate microbiome therapeutics, namely fecal microbiota transplantation, engineered probiotics, and metabolite-directed interventions to safe and individualized strategies to treat liver cancer.},
}

@article {pmid41707754,
year = {2026},
author = {Zhang, N and Shi, J and Zhang, H and Zhou, Z and Liu, M and Liang, X and Zhou, Y and Zhang, K and Cui, Z and Xue, M and Liang, H},
title = {Folic acid mitigation of alcohol-induced sarcopenia via gut-muscle axis modulation.},
journal = {Metabolism: clinical and experimental},
volume = {178},
number = {},
pages = {156567},
doi = {10.1016/j.metabol.2026.156567},
pmid = {41707754},
issn = {1532-8600},
abstract = {BACKGROUND: Alcohol-related muscle dysfunction is highly prevalent and substantially impairs the quality of life in individuals with alcohol use disorders. Chronic alcohol consumption-induced folic acid (FA) deficiency, potentially worsening alcohol-related diseases, and has been reported to FA exert protective effects on muscle health. However, the precise mechanisms by which FA may protect skeletal muscle via the gut-muscle axis in alcohol-induced sarcopenia remain insufficiently elucidated. This study aims to investigate whether FA can prevent alcohol-induced sarcopenia and to elucidate the underlying mechanisms of the gut-muscle axis.

METHODS: In vivo, eight-week-old male C57BL/6 J mice were given a Lieber-DeCarli alcohol diet for 12 weeks and administered either FA (2.5 or 5 mg/kg) or idebenone (2.5 mg/kg). To further elucidate the role of the gut-muscle axis, we conducted in vivo myostatin (MSTN) manipulation and fecal microbiota transplantation (FMT) experiments. Evaluations included muscle mass and strength, histology, mitochondrial function, markers of oxidative stress and inflammation, gut microbiota, and serum metabolomics. In vitro, C2C12 myoblasts were treated with ethanol or indoxyl sulfate (IS) and then supplemented with FA to assess the mechanism of their action.

RESULTS: FA intervention effectively restored muscle mass and strength, reduced homocysteine levels, and improved mitochondrial function (P < 0.05). Mechanistically, FA downregulated MSTN signaling, resulting in decreased protein degradation and increased protein synthesis (P < 0.05). In vivo gain- and loss-of-function experiments, confirming MSTN's critical mediation of FA's protective effects. Concurrently, integrated multi-omic analysis identified that FA rebalanced the gut microbiota-metabolite network, with IS identified as a key gut-derived mediator. FMT from high-dose FA-treated donors replicated the muscle-protective effects, confirming the critical causal role of gut microbiota in FA's therapeutic efficacy. In vitro, FA (40 μM) improved mitochondrial membrane potential and increased the myotube fusion index while suppressing MSTN pathway activation (P < 0.05).

CONCLUSIONS: FA significantly attenuated alcoholic sarcopenia by modulating the gut-muscle axis. Specifically, FA corrected the dysregulation of the alcohol-Hcy axis, and enhanced mitochondrial function. Additionally, FA rebalanced to the intestinal microbiota-metabolite network and inhibited MSTN-mediated excessive protein degradation, collectively restoring muscle protein homeostasis.},
}

@article {pmid41705405,
year = {2026},
author = {Wetthasinghe, L and Ng, HF and Chew, KS and Ranai, NM and Ngeow, YF and Lee, WS},
title = {Paediatric Crohn's Disease Management: A Mini Review Exploring Conventional and Innovative Therapies With Promising Potential.},
journal = {Journal of gastroenterology and hepatology},
volume = {},
number = {},
pages = {},
doi = {10.1111/jgh.70307},
pmid = {41705405},
issn = {1440-1746},
support = {//UTAR Research Scholarship Scheme/ ; 6274/0016//UTAR Research Fund/ ; 6555/1L02//UTAR Research Fund/ ; 4417/0004//Toray Science Foundation Japan/ ; },
abstract = {Pediatric Crohn's disease (pCD) is a chronic, relapsing inflammatory bowel disease with increasing incidence worldwide, including in Asia where it was once rare. Affected children often experience gastrointestinal symptoms, growth failure, malnutrition, and psychosocial impacts that significantly impair quality of life. This review summarizes current knowledge on the epidemiology and pathogenesis of pCD, highlighting the role of dysbiosis, environmental triggers, and immune dysregulation. Conventional management strategies, including aminosalicylates, corticosteroids, immunomodulators, biologics, surgery, and nutritional interventions such as exclusive enteral nutrition, are discussed, alongside their limitations in efficacy, tolerability, or long-term safety. The paper further explores emerging therapeutic approaches, including helminthic therapy, fecal microbiota transplantation, and synthetic biotics, which aim to modulate the gut microbiome or immune response more precisely. Although early data from clinical trials are promising, these novel modalities require further investigation, particularly in pediatric populations, to establish optimal protocols, safety profiles, and long-term outcomes. The integration of established and innovative strategies, informed by ongoing research, offers the potential for more personalized and effective care in managing pCD.},
}

@article {pmid41705053,
year = {2026},
author = {Chen, L and Xinxin, Z and Yue, Z and Qianlei, X and Huijun, G and Xuewei, L},
title = {Intestinal microecology: a crucial factor influencing incomplete immune reconstitution after antiretroviral therapy in people living with HIV-1.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1729968},
pmid = {41705053},
issn = {2296-2565},
mesh = {Humans ; *HIV Infections/drug therapy/immunology ; *Gastrointestinal Microbiome/immunology ; *HIV-1 ; *Anti-Retroviral Agents/therapeutic use ; *Immune Reconstitution ; Quality of Life ; CD4 Lymphocyte Count ; },
abstract = {Some people living with HIV-1 (PLWH) experience insufficient increases in CD4 + T cell counts after antiretroviral therapy (ART), a clinical manifestation referred to as incomplete immune reconstitution (INR). INR significantly increases in the incidence of AIDS and non-AIDS events and profoundly affects the life expectancy and quality of life of PLWH. Recent studies have indicated that intestinal microecology plays a crucial role in immune reconstitution through multiple pathways. This review summarizes several mechanisms through which intestinal microecology contributes to impaired immune reconstitution in PLWH, including changes in microbiota composition, variations in intestinal metabolic products, and damage to the intestinal mucosal barrier. Additionally, intervention strategies such as fecal microbiota transplantation, probiotics, and traditional Chinese medicine are proposed. These innovative therapeutic approaches hold promise for overcoming the limitations of conventional treatments, providing clinicians with a scientific basis for personalized therapeutic strategies and researchers with theoretical guidance for exploring novel mechanisms and research methods. Ultimately, these efforts aim to improve the prognosis and quality of life for PLWH and reduce the global public health burden posed by HIV-1 infection.},
}

Humans
*HIV Infections/drug therapy/immunology
*Gastrointestinal Microbiome/immunology
*HIV-1
*Anti-Retroviral Agents/therapeutic use
*Immune Reconstitution
Quality of Life
CD4 Lymphocyte Count

@article {pmid41704851,
year = {2025},
author = {Soriano, S and Marshall, A and Holcomb, M and Flinn, H and Burke, M and Kara, G and Scalzo, P and Villapol, S},
title = {Sex-specific effects of fecal microbiota transplantation on TBI-exacerbated Alzheimer's disease pathology in mice.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1703708},
pmid = {41704851},
issn = {1664-302X},
abstract = {BACKGROUND: Traumatic brain injury (TBI) accelerates Alzheimer's disease (AD) pathology and neuroinflammation, potentially via gut-brain axis disruptions. Whether restoring gut microbial homeostasis mitigates TBI-exacerbated AD features remains unclear, particularly with respect to sex differences.

OBJECTIVE: The goal of our study was to test whether fecal microbiota transplantation (FMT) modifies amyloid pathology, neuroinflammation, gut microbial composition, metabolites, and motor outcomes in male and female 5xFAD mice subjected to TBI.

METHODS: Male and female 5xFAD mice received sham treatments or controlled cortical impact, followed 24 h later by vehicle (VH) or sex-matched FMT from C57BL/6 donors. Assessments at baseline, 1-, and 3-days post-injury (dpi) included Thioflavin-S and 6E10 immunostaining for Aβ, Iba-1 and GFAP for glial activation, lesion volume, rotarod performance, 16S rRNA sequencing for microbiome profiling, serum short-chain fatty acids (SCFAs), and gut histology.

RESULTS: TBI increased cortical and dentate gyrus Aβ burden, with females showing greater vulnerability. FMT reduced Aβ deposition in sham animals and shifted plaque morphology but did not attenuate TBI-induced amyloid escalation. FMT differentially modulated glial responses by sex and region (reduced microgliosis in males) without altering lesion volume at 3 dpi. Rotarod performance was better in sham females compared to males and declined in FMT-treated TBI females. Fecal microbiome alpha diversity and richness were unchanged, while beta diversity revealed marked, time-dependent community shifts after TBI that were slightly altered by FMT. Gut morphology remained broadly intact, but crypt width increased after TBI, particularly in males.

CONCLUSION: In 5xFAD mice, TBI drives sex-dependent worsening of amyloid pathology, neuroinflammation, and dysbiosis. Acute FMT partially restores microbial composition and plaque features in sham animals but fails to reverse TBI-induced neuroinflammation or motor deficits. These findings underscore the context- and sex-dependence of microbiome interventions and support longer-term, sex-specific strategies for AD with comorbid TBI.},
}

@article {pmid41704316,
year = {2026},
author = {Wang, Y and Yang, Z and Liu, C and Liu, Y and Bai, Z and Miao, W and Zhang, T and Wang, Y and Li, X and Lai, Z and Xu, J},
title = {Gut microbial signatures of advanced hepatocellular carcinoma and their potential diagnostic value.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1760859},
pmid = {41704316},
issn = {1664-302X},
abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) is a prevalent and lethal malignancy worldwide. Gut microbiota play crucial roles in liver disease progression and may offer noninvasive diagnostic value, yet microbial signatures specific to advanced HCC remain unclear.

METHODS: Seventy-six participants, including early-stage HCC (HCC12), advanced HCC (HCC34), liver cirrhosis (LC), and healthy controls (CG), were prospectively enrolled. Fecal samples underwent 16S rRNA sequencing to characterize microbial diversity and community composition. Differential taxa were identified using Kruskal-Wallis tests, linear discriminant analysis effect size (LEfSe), and zero-inflated negative binomial regression (ZINB). Machine learning models were constructed using clinical features, representative microbiota, and their combination. External validation was performed using 74 published HCC cases.

RESULTS: Advanced HCC exhibited reduced microbial richness and diversity, accompanied by substantial community structure alterations. Enterococcus, Enterococcaceae, Enterobacteriaceae, and Escherichia-Shigella were enriched in HCC34, whereas Ruminococcus and Blautia were depleted. These taxa correlated strongly with liver injury markers and HCC-specific biomarkers. The extreme gradient boosting model showed high diagnostic potential when using either clinical or microbial features alone, while the combined model achieved improved accuracy (AUC = 1.0 in the primary test set). External validation supported the good generalizability of the model (AUC = 1.0 in the external cohort). Feature importance analysis identified Enterococcus as the most influential discriminator of advanced HCC.

CONCLUSION: This study reveals distinct gut microbial signatures associated with advanced HCC and suggests that Enterococcus may serve as a potentially important microbial marker linked to disease severity. Integrating gut microbiota profiling with clinical features may offer a promising noninvasive strategy for the accurate identification of advanced HCC and provides hypothesis-generating insights for microbiome-based therapeutic interventions.},
}

@article {pmid41702649,
year = {2026},
author = {Qi, X and Yang, M and Liu, X and Ma, L and Kaifi, JT and Ericsson, AC and Kimchi, ET and Staveley-O'Carroll, KF and Li, G},
title = {Modulating Bacteroides to boost anti-PD-1 immunotherapy in HCC.},
journal = {Journal for immunotherapy of cancer},
volume = {14},
number = {2},
pages = {},
pmid = {41702649},
issn = {2051-1426},
mesh = {*Carcinoma, Hepatocellular/drug therapy/immunology/therapy ; Animals ; Mice ; *Liver Neoplasms/drug therapy/immunology ; Humans ; *Immunotherapy/methods ; *Gastrointestinal Microbiome/immunology ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors ; *Bacteroides ; *Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Male ; },
abstract = {BACKGROUND: The gut microbiota is increasingly recognized as a critical external regulator along the gut-liver axis, influencing hepatocarcinogenesis and modulating responses to immunotherapy. However, the specific microbial determinants, underlying mechanisms, and potential clinical applications remain incompletely elucidated.

METHODS: Building on the observed association between gut microbiota and anti-programmed cell death protein-1 (PD-1) immunotherapeutic efficacy in patients with hepatocellular carcinoma (HCC), we leveraged a suite of clinically relevant murine HCC models to comprehensively characterize tumor-associated microbial signatures using 16S ribosomal RNA gene sequencing. By precisely manipulating microbial composition through a non-hepatotoxic antibiotic cocktail 3 (ABX-3), targeted microbial supplementation, human fecal microbiota transplant (FMT), and controlled Bacteroides thetaiotaomicron (B.th) repopulation following gut sterilization with ABX-5, we demonstrated a direct causal relationship between microbiota modulation and intrahepatic immune activation. Single-cell RNA sequencing of hepatic non-parenchymal cells, together with functional validation experiments, was performed to elucidate the underlying immune mechanisms.

RESULTS: Bacteroides-enriched gut microbiota derived from anti-PD-1-responsive patients with HCC significantly suppressed tumor growth in murine HCC models. In parallel, within our murine HCC system, ABX-3 administration, implemented as both a preventive and therapeutic intervention, attenuated tumor initiation and progression by selectively enriching Bacteroides within the gut microbial community. Functionally, ABX-3 enhanced the capacity of tumor antigen-specific T-cell receptor-I T cells to mount robust immune responses, culminating in targeted tumor regression following antigen-specific immunization. Among the Bacteroides species, B.th emerged as a critical mediator that potentiated αPD-1 immunotherapy in HCC by relieving Krüppel-like factor 2 (KLF2)-dependent suppression in dendritic cells (DCs). Mechanistically, the KLF2-toll-like receptor 9 (TLR9) signaling axis in DCs governed the activation of antigen-specific CD8[+] T cells, thereby amplifying antitumor immunity within the HCC microenvironment.

CONCLUSIONS: B.th is identified as a key immunomodulatory species that enhances anti-PD-1 efficacy by reprogramming DCs through the KLF2/TLR9 signaling pathway. These findings reveal a novel microbiota-informed strategy to improve immunotherapeutic outcomes in HCC.},
}

*Carcinoma, Hepatocellular/drug therapy/immunology/therapy
Animals
Mice
*Liver Neoplasms/drug therapy/immunology
Humans
*Immunotherapy/methods
*Gastrointestinal Microbiome/immunology
*Programmed Cell Death 1 Receptor/antagonists & inhibitors
*Bacteroides
*Immune Checkpoint Inhibitors/pharmacology/therapeutic use
Male

@article {pmid41699414,
year = {2026},
author = {Karlović, D and Kršul, D and Fučkar Čupić, D and Zelić, M},
title = {Autologous skin graft intersphincteric implantation in anal fistula treatment (ASGIIFT) - A novel surgical technique in the treatment of complex transsphincteric anal fistulas.},
journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland},
volume = {28},
number = {2},
pages = {e70407},
pmid = {41699414},
issn = {1463-1318},
mesh = {Humans ; *Rectal Fistula/surgery ; Female ; Male ; Middle Aged ; Prospective Studies ; Adult ; *Skin Transplantation/methods ; *Anal Canal/surgery ; Treatment Outcome ; Postoperative Complications/etiology/epidemiology ; Wound Healing ; Transplantation, Autologous/methods ; Aged ; Fecal Incontinence/etiology ; },
abstract = {AIM: This study aimed to evaluate whether implantation of an autologous skin graft in the intersphincteric space, as part of the ASGIIFT procedure, improves the primary healing of complex transsphincteric cryptoglandular anal fistulas.

METHODS: A prospective observational IDEAL stage 2a study was conducted at a tertiary referral centre for minimally invasive colorectal surgery and proctology in Croatia between September 2021 and January 2023, with an 18-month follow-up. Preoperative pelvic MRI was performed in all cases, and 40 adult patients who met the inclusion criteria were included in the study. The primary outcome was the postoperative primary healing rate which was defined clinically. Secondary outcomes included postoperative continence disturbance, postoperative pain, time of healing and other postoperative complications (Wexner score and VAS - Visual Analogue Scale were used). The ASGIIFT procedure includes all standard steps of the LIFT technique (ligation of the intersphincteric fistula tract), with the addition of a pre-prepared autologous dermal graft placed into the intersphincteric space. The study was approved by the institutional ethics committee.

RESULTS: Primary clinical healing was achieved in 35 patients (87.5%) within a median of 4 weeks postoperatively (range 3-6 weeks). Five initially unhealed patients showed conversion from transsphincteric to intersphincteric fistula during the follow-up period and were subsequently treated by fistulotomy without complications. No patient experienced worsening continence, and no serious postoperative complications occurred.

CONCLUSION: ASGIIFT appears to be a safe and feasible technique for treating transsphincteric anal fistulas, showing promising early results in this single-centre IDEAL 2a study. Further prospective comparative studies are warranted to validate these initial findings.},
}

Humans
*Rectal Fistula/surgery
Female
Male
Middle Aged
Prospective Studies
Adult
*Skin Transplantation/methods
*Anal Canal/surgery
Treatment Outcome
Postoperative Complications/etiology/epidemiology
Wound Healing
Transplantation, Autologous/methods
Aged
Fecal Incontinence/etiology

@article {pmid41699270,
year = {2026},
author = {Bashiardes, S and Heinemann, M and Adlung, L and Valdés-Mas, R and Mahdi, JA and Nobs, SP and Tuganbaev, T and Yamada, T and Horn, M and Mor, U and Cohen, Y and Israel, S and Korem, M and Oster, Y and Olshtain-Pops, K and Orenbuch-Harroch, E and Arslan, MD and Molina, S and Zur, M and Eliyahu-Miller, S and Bukimer, A and Federici, S and Dori-Bachash, M and Amar, N and Elbirt, D and Cohen-Poradosu, R and Turner, D and Hershcovici, T and Vainer, E and Stettner, N and Harmelin, A and Gebremeskel, H and Kebede, Y and Schmidt, S and Zmora, N and Dhamodaran, A and Puschhof, J and Bentwich, Z and Shapiro, H and Amit, I and Elinav, H and Elinav, E},
title = {Human immunodeficiency virus-associated gut microbiome impacts systemic immunodeficiency and susceptibility to opportunistic gut infection.},
journal = {Nature microbiology},
volume = {},
number = {},
pages = {},
pmid = {41699270},
issn = {2058-5276},
abstract = {The gut microbiome of people living with human immunodeficiency virus (PLWH) has been characterized, but its role in influencing host immunity and associated clinical features are unclear. Here we used shotgun metagenomics to characterize the faecal microbiome of two geographically distinct cohorts of PLWH and healthy controls in Israel and Ethiopia. We uncovered disease-specific, geographically divergent microbial patterns including a shift from Bacteroides to Prevotella species in an Israeli cohort and multiple Enterobacteriaceae species including Escherichia coli and Klebsiella quasivariicola in an Ethiopian cohort. We identified correlations between human immunodeficiency virus-related dysbiosis and the extent of systemic immunodeficiency, as proxied by peripheral CD4[+] T cell counts. Faecal microbiome transplantation from PLWH with high peripheral CD4[+] T cell counts induced colonic epithelium-associated CD4[+] T cells in germ-free or antibiotic-treated recipient mice. Impaired epithelium-associated lymphocyte induction in recipients of faecal microbiome transplantation from severely immunodeficient PLWH donors was associated with altered protection from Cryptosporidium parvum infection. Collectively, our results suggest a link between systemic immunodeficiency and associated intestinal dysbiosis in PLWH, resulting in impaired gut mucosal immunity.},
}

@article {pmid41698951,
year = {2026},
author = {Guo, L and Pei, X and Tan, J and Sun, H and Jiang, S and Wei, H and Peng, J},
title = {From association to intervention: Muribaculaceae driven SCFAs production enhances boar semen quality via inflammation alleviation.},
journal = {NPJ biofilms and microbiomes},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41522-026-00933-9},
pmid = {41698951},
issn = {2055-5008},
support = {CARS-35//Agriculture Research System of China/ ; 32430099//Key Program of the National Natural Science Foundation of China/ ; 2662023DKPY002//the Fundamental Research Funds for the Central Universities/ ; },
abstract = {The gut microbiota plays a vital role in host reproduction, yet its contribution to semen quality in boars remains unclear. In this study, we analyzed 556 boars from three commercial breeds and identified Muribaculaceae as a key microbial taxon positively associated with sperm quality, with the effect mediated by short-chain fatty acids (SCFAs). This association was validated in Yorkshire boars with extreme semen phenotypes. Fecal microbiota transplantation in mice confirmed that enrichment of Muribaculaceae improved semen quality, likely through enhanced SCFA production and reduced inflammation in the gut and reproductive tract. Furthermore, in vitro fermentation and mouse experiments demonstrated that a designed functional fiber selectively promoted Muribaculaceae, increased SCFA levels, and improved sperm quality. These findings suggest a functionally supported and potentially translational association between gut microbiota and boar fertility, suggesting that targeted dietary modulation of Muribaculaceae may represent a novel strategy to enhance reproductive performance in livestock.},
}

@article {pmid41698880,
year = {2026},
author = {Huang, T and Yang, H and Zhang, L and Wang, X and Chen, Y and Dai, H and Hashimoto, K and Luo, Y and Pu, Y and Liu, Y},
title = {HLA-B27-associated gut microbiota and amino acid perturbations promote ankylosing spondylitis through M1 macrophage activation.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2630561},
pmid = {41698880},
issn = {1949-0984},
mesh = {*Gastrointestinal Microbiome ; Humans ; *HLA-B27 Antigen/genetics/immunology/metabolism ; *Spondylitis, Ankylosing/microbiology/immunology/metabolism/genetics ; Animals ; Mice ; Male ; Female ; *Amino Acids/metabolism ; *Macrophage Activation ; Fecal Microbiota Transplantation ; Adult ; Middle Aged ; *Macrophages/immunology ; Bacteria/classification/genetics/isolation & purification/metabolism ; Feces/microbiology ; Metabolomics ; Dysbiosis ; },
abstract = {Ankylosing spondylitis (AS) is strongly associated with the human leukocyte antigen B27 (HLA-B27), yet how this genetic risk factor interacts with the gut microbiome remains unclear. We integrated fecal gut microbiota analysis, untargeted metabolomics, and clinical phenotyping in 88 participants, including HLA-B27-positive patients with AS (n = 28), HLA-B27-positive healthy controls (n = 30), and HLA-B27-negative healthy controls (n = 30). HLA-B27 positivity, particularly in AS, was associated with marked alterations in gut microbial composition and metabolic profiles, with forty bacterial species showing progressive disease-related shifts across cohorts. Integrated pathway and metabolomic analyses identified three amino acid-related pathways consistently disrupted in AS: tryptophan metabolism, cysteine metabolism, and pyruvate-centered biosynthesis of branched-chain amino acids, ornithine, and lysine. Correlation network analyses linking differential taxa, metabolites, and clinical indices revealed previously unrecognized microbial and metabolic signatures that robustly distinguished AS from both control groups. To explore causality, fecal microbiota transplantation (FMT) from clinical donors into antibiotic-treated mice recapitulated key disease-relevant features, including impaired intestinal barrier function, systemic inflammation, trabecular bone loss, and polarization of macrophages toward a proinflammatory M1 phenotype. Mechanistic validation identified cinnabarinic acid as a critical microbial-derived metabolite that suppresses M1 macrophage polarization via activation of the aryl hydrocarbon receptor (AhR) pathway and confers protection in the FMT model. Together, these findings support a model in which HLA-B27-associated gut dysbiosis and metabolic reprogramming promote AS pathogenesis through macrophage-mediated inflammation and osteocatabolic signaling, highlighting microbial-metabolic pathways as potential therapeutic targets.},
}

*Gastrointestinal Microbiome
Humans
*HLA-B27 Antigen/genetics/immunology/metabolism
*Spondylitis, Ankylosing/microbiology/immunology/metabolism/genetics
Animals
Mice
Male
Female
*Amino Acids/metabolism
*Macrophage Activation
Fecal Microbiota Transplantation
Adult
Middle Aged
*Macrophages/immunology
Bacteria/classification/genetics/isolation & purification/metabolism
Feces/microbiology
Metabolomics
Dysbiosis

@article {pmid41697021,
year = {2026},
author = {Han, B and Wen, H and Li, Y and Wang, Y and Lv, X and Kang, M and Huang, W and Lan, Y and Tong, S and Zhang, M and Chen, D and Zhu, C and Jiang, Y and Tang, D},
title = {Gut microbial production of lithocholic acid reprograms pro-resolutive macrophages to enhance vedolizumab responsiveness via the TGR5/FXR-NF-κB axis.},
journal = {The ISME journal},
volume = {},
number = {},
pages = {},
doi = {10.1093/ismejo/wrag028},
pmid = {41697021},
issn = {1751-7370},
abstract = {Crohn's disease (CD) is a complex chronic transmural inflammatory bowel disease. Although vedolizumab (VDZ) markedly improves clinical outcomes in CD, treatment non-response remains a significant limitation, constraining its broader utility. Elucidating the mechanisms underlying VDZ responsiveness is thus critically needed. In this research, we employed a humanized mouse model of 2,4,6-trinitrobenzene sulfonic acid-induced colitis to investigate VDZ treatment response in CD. Our findings indicate that VDZ significantly alleviated disease phenotypes in a portion of CD mice. Integrated metagenomic and metabolomic profiling identified baseline gut microbiota-derived secondary bile acids as potential predictors of VDZ efficacy. Subsequent fecal microbiota transplantation from clinical donors into pseudo-germ-free mice confirmed that gut microbial composition critically influences VDZ responsiveness. Targeted metabolomics further pinpointed lithocholic acid (LCA) as a key microbially derived metabolite correlated with therapeutic remission. Single-cell RNA sequencing also revealed that intestinal macrophages serve as pivotal mediators of LCA-driven modulation of treatment outcomes. Furthermore, transcriptomic analyses demonstrated that LCA polarizes macrophages toward an M2-resolutive phenotype via concurrent engagement of the TGR5/FXR and their downstream NF-κB pathways. Ultimately, using a conditioned medium co-culture system, we established that the regulatory effects of pro-resolutive macrophage niche on treatment response in a manner dependent on the TGR5/FXR-NF-κB axis. Taken together, our study elucidates a microbiota-immune circuit in which gut microbial metabolite LCA augments VDZ responsiveness in CD by reprogramming macrophages toward a pro-resolutive phenotype via the TGR5/FXR-NF-κB signaling network. These insights provide a mechanistic foundation for biomarker development and personalized therapeutic strategies in inflammatory bowel disease.},
}

@article {pmid41695956,
year = {2026},
author = {Ali, A and AlHussaini, KI},
title = {Diagnostic challenges and treatment approaches for Clostridioides difficile infection in IBD patients.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1740387},
pmid = {41695956},
issn = {1664-302X},
abstract = {BACKGROUND: Clostridioides difficile infection (CDI) poses a major clinical challenge in patients with inflammatory bowel disease (IBD) due to overlapping symptoms, diagnostic complexities, and distinct therapeutic considerations. The interaction between CDI and IBD involves disrupted gut microbiota, immune dysregulation, and disease-specific risk factors.

METHODS: This review critically examines the current evidence on the diagnosis and management of CDI in patients with IBD. Literature sources discussing diagnostic methodologies, therapeutic strategies, and preventive interventions were analyzed, with a focus on recent advances and their clinical applicability.

RESULTS: Diagnosing CDI in IBD remains difficult due to similar clinical presentations between infectious colitis and IBD flares, alongside limitations of stool assays, molecular tests, and endoscopic evaluations. Emerging diagnostic tools may enhance the accuracy and timeliness of detection. Standard therapies, antibiotics, and fecal microbiota transplantation (FMT) remain essential; however, their application requires individualization, taking into account immunosuppressive therapy, drug interactions, and the risk of recurrence. Treatment outcomes are further influenced by disease severity and patterns of antimicrobial resistance. Preventive strategies, including antimicrobial stewardship, probiotics, and vaccination, may help reduce the incidence of CDI among patients with IBD.

CONCLUSION: CDI in IBD necessitates a personalized management approach that incorporates accurate diagnostics, targeted therapy, and preventive measures. Despite therapeutic advances, significant knowledge gaps persist regarding host microbiome interactions and the optimization of individualized treatment. Future research should focus on improving diagnostic precision and developing personalized medicine strategies to enhance outcomes for IBD patients affected by CDI.},
}

@article {pmid41695578,
year = {2026},
author = {Ni, S and Fu, W and Zhang, L and Zhang, Z and Li, X},
title = {Circadian rhythms regulate osteoclast recycling through gut microbiota-dependent Th17 cell expansion.},
journal = {Current research in microbial sciences},
volume = {10},
number = {},
pages = {100561},
pmid = {41695578},
issn = {2666-5174},
abstract = {The circadian clock coordinates diverse biological processes to maintain physiological function and homeostasis in mammals under the day-night light cycle. Disruption of circadian rhythms impairs immune and metabolic functions and increases susceptibility to various diseases. Here, we demonstrate that long-term rest-phase time-restricted feeding (TRF), which disrupts circadian rhythmicity, induces bone loss and gut microbiota dysbiosis in male mice. Fecal microbiota transplantation (FMT) from circadian-misaligned feeding donors to germ-free recipients increased Th17 cell populations, thereby promoting the fusion of osteomorphs-a recently identified osteoclast precursor-into mature osteoclasts through the RANKL-RANK-OPG signaling pathway. Collectively, our findings identify a gut microbiota-Th17-osteomorph axis as a critical mediator of circadian disruption-induced bone loss, uncovering a previously unrecognized mechanism by which circadian rhythms regulate skeletal homeostasis.},
}

@article {pmid41695569,
year = {2025},
author = {Yang, J and Dai, Y and Li, J},
title = {Gut microbiota-immunity cascade in hepatocellular carcinoma: mechanisms and therapeutic opportunities.},
journal = {Oncology reviews},
volume = {19},
number = {},
pages = {1687901},
pmid = {41695569},
issn = {1970-5565},
abstract = {Hepatocellular carcinoma (HCC) constitutes a major global health burden, with limited responsiveness to current immunotherapeutic regimens. Accumulating evidence underscores the gut microbiota as a crucial regulator of the gut-liver axis, modulating tumor initiation, immune evasion, and the outcomes of immunotherapeutic interventions-and notably, it concurrently exhibits both potential diagnostic biomarker value and actionable therapeutic target properties. In the present review, we synthesize the characteristic features of gut dysbiosis in HCC, delineate the mechanisms by which microbial metabolites-including short-chain fatty acids (SCFAs), bile acids, and indoles-modulate the tumor immune microenvironment (TME), and elaborate on their dual roles in promoting anti-tumor immunity while concomitantly mediating immune suppression. We further examine the clinical correlations between specific microbial taxa and the efficacy of immune checkpoint inhibitors (ICIs)-findings that support the utility of gut microbiota signatures as predictive or diagnostic biomarkers-and explore emerging microbiota-targeted strategies, such as fecal microbiota transplantation (FMT), probiotic supplementation, phage therapy, and dietary modulation, which validate the gut microbiota as a viable therapeutic target.},
}