@article {pmid42506336,
year = {2026},
author = {Esparza-Sánchez, J and Garibi-Miranda, DA and Chávez-Tinoco, M and Mejía-Méndez, JL and Sepulveda-Villegas, M and Sanchez-Ante, G and Sánchez-López, AL},
title = {The Gut Microbiota in Addiction Biology: A Systematic Review of Substance-Induced Dysbiosis and Gut-Brain Axis Alterations.},
journal = {Medical sciences (Basel, Switzerland)},
volume = {14},
number = {3},
pages = {},
doi = {10.3390/medsci14030367},
pmid = {42506336},
issn = {2076-3271},
support = {IJST070-23EG71001//Monterrey Institute of Technology/ ; },
mesh = {*Dysbiosis/chemically induced/microbiology ; *Gastrointestinal Microbiome/drug effects/physiology ; Humans ; Animals ; *Substance-Related Disorders/microbiology ; *Brain-Gut Axis ; *Brain ; },
abstract = {BACKGROUND: Growing evidence suggests that chronic substance use disrupts the gut microbiota composition and function, which can contribute to intestinal dysfunction, systemic inflammation, and gut-brain axis dysregulation. However, current evidence remains fragmented and heterogenous, with most studies focusing on individual substances rather than substance-specific microbial signatures.

OBJECTIVE: Therefore, this systematic review synthesizes recent evidence (2019-2025) to characterize the impact of chronic substance use, including alcohol, nicotine, opioids, cocaine, and methamphetamine, on the gut microbiota composition and functional integrity.

METHODS: Following the PRISMA 2020 guidelines, a total of 91,421 records were identified before screening through searches conducted across electronic databases and publisher platforms, including PubMed, Web of Science, ProQuest, and BSCOhost, among others. After duplication removal and application of the predefined eligibility criteria, 60 studies were selected for qualitative analysis.

RESULTS: The findings revealed an interspecies similarity in which chronic substance exposure generally induced dysbiosis characterized by a depletion of beneficial short-chain fatty acid (SCFA)-producing taxa, such as Lactobacillus, Akkermansia, and Faecalibacterium, alongside the enrichment of opportunistic pathogens such as Escherichia-Shigella. Alcohol emerged as a particularly potent ecological driver, consistently reducing the richness and diversity of the microbial community. Mechanistically, these alterations are linked to impaired intestinal barrier function, increased lipopolysaccharide translocation, and the activation of systemic inflammatory pathways. Furthermore, substance-specific metabolic fingerprints were identified, including disruptions in glutamate pathways for cocaine and trimethylamine N-oxide precursors for methamphetamine. Preclinical evidence from fecal microbiota transplantation and germ-free models suggests that these microbial shifts actively modulate reward sensitivity and neuroplasticity through the gut-brain axis.

CONCLUSION: Collectively, the data presented in this study support a shift from reductionist addiction models toward a systems-level framework, positioning the gut microbiome as a pivotal, modifiable component of addiction biology and a promising target for novel therapeutic interventions.},
}

*Dysbiosis/chemically induced/microbiology
*Gastrointestinal Microbiome/drug effects/physiology
Humans
Animals
*Substance-Related Disorders/microbiology
*Brain-Gut Axis
*Brain

@article {pmid42507333,
year = {2026},
author = {Amin, I and Elgebaly, AS and Mohamed, HH and Abuelhaded, K and Alam-ElDein, KM and Ibrahim, AK and Farag, SA and Adel, A and Hamdy, M and Elkhawanky, M and Mahdy, A},
title = {Microbiome-guided cancer immunotherapy: immune mechanisms, resistance pathways, and translational opportunities for precision oncology.},
journal = {Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico},
volume = {},
number = {},
pages = {},
pmid = {42507333},
issn = {1699-3055},
abstract = {The gut microbiome is increasingly recognized as a modulator of tumor-immune interactions and has been associated with cancer development, progression, and therapeutic response, while direct causal evidence remains strongest in mechanistic and interventional models. Microbial composition and metabolites, including SCFAs, bile acids, inosine, and tryptophan-derived products, may shape host immunity by influencing the tumor microenvironment (TME) and systemic immune responses, although the strength of evidence varies by model system and clinical context. These microbial signals have been linked to changes in T cells, B cells, NK cells, and MDSCs, with mechanistic studies supporting effects on cytokine networks, immune checkpoint signaling, inflammation, and antitumor immunity. Emerging translational evidence indicates that specific microbial signatures may serve as predictive biomarkers for immunotherapy efficacy, resistance, and treatment-related toxicity. In parallel, microbiome-targeted strategies, including FMT, probiotics, prebiotics, dietary modulation, and engineered microbial therapeutics, are being investigated as adjunctive approaches to improve cancer therapy, but their clinical efficacy remains incompletely validated. Understanding microbiome-immune crosstalk may therefore support precision oncology by identifying tractable microbial targets for improving therapeutic outcomes, overcoming immune-mediated treatment resistance, and guiding patient stratification across diverse cancer types and settings in clinical oncology practice.},
}

@article {pmid42510952,
year = {2026},
author = {H Navia, S and Illescas, O and Silva-Magaña, MA and Juárez-Avelar, I and Terrazas-Rodriguez, M and Vaca-Paniagua, F and Díaz Velásquez, CE and Vega, L and Terrazas, LI and Rodríguez-Sosa, M},
title = {MIF Deficiency Modulates Gut Microbiota Composition and Promotes Colitis-Associated Colorectal Cancer in a Murine Model.},
journal = {Current issues in molecular biology},
volume = {48},
number = {7},
pages = {},
doi = {10.3390/cimb48070712},
pmid = {42510952},
issn = {1467-3045},
support = {CIKAS-FICDTEM25-019//Mexico State Council for Science and Technology (COMECyT)/ ; IN208126//Programa Académico de Investigación e Innovación Tecnológica (PAPIIT)-UNAM/ ; IV200425//Programa Académico de Investigación e Innovación Tecnológica (PAPIIT)-UNAM/ ; },
abstract = {Intestinal dysbiosis is a hallmark of both inflammatory bowel conditions and colorectal cancer, yet the mechanisms by which inflammatory mediators alter microbial communities and may contribute to tumor development remain poorly understood. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in innate immunity and the progression of inflammatory and neoplastic disorders. In this study, sequencing of the microbial 16S rRNA gene was performed to characterize the fecal microbiota profiles of wild-type (WT) and MIF-knockout (MIF-KO) BALB/c mice subjected to AOM/DSS-induced colitis-associated colorectal cancer (CAC). CAC induction resulted in marked microbial shifts, including increases in Muribaculaceae and Bacteroidota, in both WT and MIF-KO mice. Notably, MIF-KO CAC mice developed more severe disease compared with WT CAC mice. Furthermore, FMT experiments revealed that the fecal microbiota from MIF-KO donors was associated with increased tumor burden in WT recipients under CAC-inducing conditions compared with that in recipients colonized with WT-derived microbiota. Together, these findings suggest that MIF deficiency is associated with gut microbiota remodeling during CAC and support a potential relationship between the MIF-dependent host context, microbial composition and colorectal cancer severity.},
}

@article {pmid42511198,
year = {2026},
author = {Zhang, S and Wu, Y and Wang, F and Li, H and Zheng, N and Chen, H and Zhao, Y},
title = {Camel Milk Alleviates Chronic Fatigue Syndrome-like Symptoms in Mice by Modulating the Small Intestinal Microbiota and Inflammation.},
journal = {Foods (Basel, Switzerland)},
volume = {15},
number = {14},
pages = {},
pmid = {42511198},
issn = {2304-8158},
support = {2025D01B138//Science and Technology Department of Xinjiang Uyghur Autonomous Region/ ; },
abstract = {This study aimed to investigate the therapeutic effects of camel milk (CM) on chronic fatigue syndrome (CFS) and elucidate the mechanisms underlying the microbiota-gut-brain axis. Using a murine model of CFS induced by chronic restraint and forced swimming stress, we administered lyophilized CM (1500 mg/kg/day, equivalent to approximately 121.5 mg/kg/day in humans based on body surface area conversion using the standard allometric scaling formula) orally. CM supplementation was significantly associated with ameliorated fatigue-like behaviors, as evidenced by prolonged swimming endurance and reduced immobility time. Metagenomic analysis revealed that CM was associated with reshaping of the small intestinal microbiota, including enrichment of beneficial Lactococcus lactis and suppression of pathobionts (H. hepaticus and H. typhlonius). These microbial shifts correlated with increased luminal lactic acid, improved intestinal barrier integrity (increased villus height, reduced crypt depth), and attenuated local inflammation (reduced TNF-α and IL-6, elevated IL-10). Consequently, CM was associated with reduced bacterial translocation and systemic inflammation, and normalization of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. We conclude that CM is associated with prevention of CFS-like symptoms through modulation of the gut ecosystem and strengthening of the intestinal barrier, potentially breaking the vicious cycle of gut inflammation and HPA axis dysfunction, although causality remains to be established through fecal microbiota transplantation or similar mechanistic studies.},
}

@article {pmid42511589,
year = {2026},
author = {Ciaușu-Sliwa, D and Capotă, R and Bostănaru-Iliescu, AC and Năstasă, V and Mareș, M},
title = {Molecular Mechanisms of Gut Microbiota-Immune System Crosstalk: From Mucosal Architecture to Adaptive Immunity Programming.},
journal = {International journal of molecular sciences},
volume = {27},
number = {14},
pages = {},
pmid = {42511589},
issn = {1422-0067},
abstract = {The mammalian gut microbiome functions as a metabolically active immunological organ and has co-evolved with its host to maintain systemic homeostasis. This review integrates current evidence on the molecular mechanisms governing bidirectional microbiota-immune communication, emphasizing evolutionary conservation, receptor-mediated signaling, and translational implications. Microbial structural ligands and metabolites-including short-chain fatty acids, bile-acid derivatives, and tryptophan catabolites-engage host receptors such as G-protein-coupled receptors, FXR/TGR5, and the aryl hydrocarbon receptor (AhR), thereby regulating epithelial barrier integrity, regulatory T-cell differentiation, Th17 polarization, mucosal IgA production, and systemic immune tone. Riboflavin-derived metabolites presented via major histocompatibility complex class-I-related molecule (MR1) further shape mucosal-associated invariant T-cell development (MAIT), illustrating metabolite-driven immune system programming. Dysbiosis induced by antibiotics, dietary perturbation, or aging disrupts these molecular networks, promoting chronic inflammatory, metabolic, autoimmune, and neuroimmune disorders. Comparative analyses across mammalian systems underscore conserved pathways of host-microbe coadaptation and immune education. Therapeutically, microbiota-modulating strategies-including probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), postbiotics, and IgY-based passive immunotherapy-aim to restore immunometabolic signaling. Emerging in vitro and in silico platforms further provide mechanistic precision while supporting ethically aligned translational research. Collectively, these insights position microbiota-derived molecular signaling as a central determinant of adaptive immune architecture and a targetable axis in precision immunotherapy.},
}

@article {pmid42511843,
year = {2026},
author = {Rajarathinam, B and Nair, PV and Murali, N and Lekshmi, G and Sajeev, AK and Pillai, AB and Thomas, A and Hely, S and Arun, K and Prakash, V and Nair, BG and Venugopal, P and Aradhya, R},
title = {Antibiotic Class-Specific Effects on Inflammatory Bowel Disease: Microbiome Disruption, Risk, and Recovery.},
journal = {International journal of molecular sciences},
volume = {27},
number = {14},
pages = {},
pmid = {42511843},
issn = {1422-0067},
abstract = {Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory diseases resulting from complex interactions between host genetics, environmental factors, immune dysregulation, and the gut microbiome. Among environmental exposures, antibiotics have emerged as important factors of IBD risk and disease course because of their profound effects on intestinal microbial communities. This review synthesizes current evidence on the class-specific effects of antibiotics on IBD, integrating epidemiological, mechanistic, and clinical studies to examine how different antibiotic classes influence disease susceptibility, progression, and microbiome recovery. Current evidence indicates that antibiotic-associated IBD risk varies according to antibiotic class, cumulative exposure, age at exposure, and antimicrobial spectrum, with broad-spectrum and anti-anaerobic agents showing the strongest associations. Mechanistically, antibiotics promote dysbiosis by depleting beneficial commensal bacteria, disrupting microbial metabolite production, expanding pathobionts and the intestinal resistome, and impairing epithelial barrier integrity and immune homeostasis. The review also discusses microbiome-preserving and microbiome-restorative approaches, including antimicrobial stewardship, fecal microbiota transplantation, prebiotics, probiotics, synbiotics, postbiotics, and dietary interventions, as potential strategies to mitigate antibiotic-associated dysbiosis. Overall, the evidence highlights the class-specific effects of antibiotics in IBD and underscores the importance of microbiome-informed antimicrobial stewardship and precision therapeutic strategies to optimize patient outcomes while minimizing long-term disruptions of host-microbiome homeostasis.},
}

@article {pmid42513562,
year = {2026},
author = {Hau, HM and Jahn, N and Karitnig, R and Hasenhütl, SM and Sucher, R and Stiegler, P and Laudi, S},
title = {Microbiome-Targeted Modulation in Renal Transplantation.},
journal = {Journal of clinical medicine},
volume = {15},
number = {14},
pages = {},
doi = {10.3390/jcm15145648},
pmid = {42513562},
issn = {2077-0383},
abstract = {The gut microbiome has emerged as a critical determinant of health and disease across virtually all organ systems. In the context of chronic kidney disease (CKD) and renal transplantation, mounting evidence reveals a complex bidirectional relationship between the intestinal microbiota and kidney function-commonly referred to as the gut-kidney axis. Patients with CKD harbor a profoundly altered gut microbial ecosystem characterized by reduced diversity, depletion of beneficial commensal organisms, and expansion of pathobiont taxa capable of generating uremic toxins and pro-inflammatory mediators. These perturbations are further compounded by the uremic milieu itself, dietary restrictions, frequent antibiotic exposure, and the use of immunosuppressive agents following transplantation. The gut-liver-kidney axis adds an additional layer of complexity, linking hepatic metabolism, bile acid signaling, endotoxemia, and systemic immune activation to the progression of renal disease. Gut-derived metabolites-including short-chain fatty acids (SCFAs), bile acids, trimethylamine N-oxide (TMAO), and tryptophan-derived uremic solutes such as indoxyl sulfate and p-cresyl sulfate-serve as molecular mediators of inter-organ crosstalk and have been identified as both biomarkers and therapeutic targets. A growing body of literature supports the diagnostic and prognostic utility of microbiome composition and its metabolic signatures in patients with CKD and those undergoing renal replacement therapy. Therapeutic strategies aimed at restoring microbial homeostasis-encompassing dietary interventions, prebiotics, probiotics, synbiotics, fecal microbiota transplantation (FMT), bile acid-based therapies, and novel pharmacological approaches-hold considerable promise for improving outcomes in CKD and transplant recipients. Importantly, the bidirectional relationship between immunosuppressive drugs and the gut microbiota has emerged as a clinically significant determinant of both microbial ecology and drug pharmacokinetics: each major immunosuppressive agent class-corticosteroids, calcineurin inhibitors, mycophenolate mofetil, and mTOR inhibitors-induces characteristic dysbiotic patterns, while in turn, the microbiota modulates drug bioavailability through enzymatic biotransformation (notably bacterial beta-glucuronidase activity affecting mycophenolic acid enterohepatic recirculation) and modulation of host drug-metabolizing enzymes. This narrative review provides a comprehensive overview of the current understanding of microbiome dysbiosis in the setting of renal disease and transplantation, examines the mechanistic underpinnings of the gut-liver-kidney axis, details the multifaceted impact of dysbiosis on transplant outcomes-including allograft function and rejection, infection, post-transplant diabetes, and cardiovascular complications-and critically appraises the translational potential of microbiome-targeted interventions. We conclude by highlighting ongoing challenges and future directions toward personalized, microbiome-informed clinical care.},
}

@article {pmid42513975,
year = {2026},
author = {Tan, Y and Hu, Y and Cao, Z and Wang, X and Yuan, Y and Chu, H},
title = {Gut Microbiota and Ageing: A Critical Crosstalk in Alcohol-Related Liver Disease.},
journal = {Microorganisms},
volume = {14},
number = {7},
pages = {},
doi = {10.3390/microorganisms14071469},
pmid = {42513975},
issn = {2076-2607},
support = {No.2022YFA1305600//the National Key R&D Program of China/ ; No. 82470584//National Natural Science Foundation of China/ ; No.82000561//National Natural Science Foundation of China/ ; No.2021xhyn005//the Science foundation of union hospital/ ; },
abstract = {Alcohol-related liver disease (ALD) poses a significant global health burden, driven by complex mechanisms including oxidative stress, inflammation, and gut-liver axis disruption. While the individual roles of gut microbiota dysbiosis and ageing in ALD pathogenesis are increasingly recognized, their synergistic interaction remains poorly understood. This review synthesizes current evidence to argue that there is an interaction between ageing and the gut microbiota that collectively amplifies progression of ALD. Specifically, ageing promotes gut dysbiosis through immunosenescence (e.g., reduced IgA diversification and antimicrobial peptide decline), intestinal barrier failure, and altered microbial metabolite profiles (e.g., decreased short-chain fatty acids and dysregulated bile acid metabolism). Conversely, dysbiosis-derived metabolites and endotoxins modulate ageing-related signaling pathways, including SIRT1, FOXO, and Nrf2, thereby accelerating hepatic cellular senescence, inflammation, and fibrogenesis. Furthermore, we also discussed the typical microbial changes in ALD. These include an increase in the Proteobacteria, a decrease in the Bacteroidetes, as well as imbalances in fungi and viruses. In ageing, similar but distinct shifts occur, such as reduced microbial diversity, decreased short-chain fatty acid producers, and increased intestinal permeability. Therapeutic strategies targeting the gut microbiota (probiotics, fecal microbiota transplantation) or ageing-related pathways (SIRT1 activators) hold promise. Future research priorities include validating ageing-associated microbial signatures as predictors of ALD progression and testing microbiota-targeted interventions in aged preclinical models. Collectively, this review identifies the microbiota-ageing axis as a tractable therapeutic target for ALD and provides a framework for future mechanistic and translational studies.},
}

@article {pmid42514045,
year = {2026},
author = {Wang, M and He, Q and Qiu, Y and Huang, L and Zhang, Y and Ye, D and He, Z and Wen, C},
title = {High Humidity Exacerbates Rheumatoid Arthritis in Mice via Prevotella stercorea-Mediated Chondroitin Sulfate Degradation.},
journal = {Microorganisms},
volume = {14},
number = {7},
pages = {},
doi = {10.3390/microorganisms14071540},
pmid = {42514045},
issn = {2076-2607},
support = {82405212//National Natural Science Foundation of China/ ; 82274382//National Natural Science Foundation of China/ ; 82474147//National Natural Science Foundation of China/ ; },
abstract = {Background: Rheumatoid arthritis (RA) is influenced by environmental exposures. High humidity has been clinically associated with worsened joint symptoms, but the microbial and metabolic mechanisms remain unclear. We investigated whether a gut microbiota-metabolism axis contributes to humidity-associated aggravation of collagen-induced arthritis (CIA). Methods: CIA mice were maintained under normal or high relative humidity. We integrated 16S rRNA and metagenomic sequencing, liquid chromatography-tandem mass spectrometry metabolomics, and intestinal barrier assessments. Fecal microbiota transplantation (FMT) was performed to evaluate microbiota dependency. Based on multi-omics findings, we quantified chondroitin sulfate (CS) and conducted functional experiments involving Prevotella stercorea (P. stercorea) supplementation, CS administration, and in vitro degradation assays. Results: High humidity aggravated arthritis severity and systemic inflammation, including increased interleukin-6, interleukin-17A, and granulocyte colony-stimulating factor, and was accompanied by impaired intestinal barrier integrity. FMT supported a microbiota-dependent contribution. Metagenomic analysis identified enrichment of P. stercorea and glycosaminoglycan degradation pathways under high humidity. CS abundance was reduced in articular cartilage, P. stercorea degraded CS in vitro and was associated with cartilage CS loss in vivo, and CS supplementation attenuated arthritis under high humidity and reduced the arthritis-promoting effects associated with P. stercorea. Conclusions: High humidity is associated with microbiota-dependent functional remodeling, enhanced CS degradation, and aggravated arthritis in CIA mice. These findings suggest that humidity-associated alterations in microbial CS metabolism may link environmental exposure to cartilage disruption and joint inflammation.},
}

@article {pmid42514077,
year = {2026},
author = {Liu, A and Ran, D and Shen, Z and Rojba, M and Zhang, J},
title = {The Gut-Lung Microbiome Axis in Alveolar Stem Cell Regeneration and Lung Repair.},
journal = {Microorganisms},
volume = {14},
number = {7},
pages = {},
doi = {10.3390/microorganisms14071572},
pmid = {42514077},
issn = {2076-2607},
abstract = {The mammalian respiratory system stands as a frontline barrier, constantly exposed to environmental insults, balancing defensive immunity with gas exchange. Historically considered sterile, the lung harbors a dynamic, low-biomass microbiome that evolves continuously in response to pulmonary pathologies. Accumulating evidence underscores that respiratory health and structural recovery are not autonomous but are critically integrated with distal microbial systems, especially the intestinal tract, through the gut-lung axis (GLA). This review characterizes the GLA as a bidirectional communication highway fueled by immune pathways, microbial metabolites, and direct microbial translocations. During acute or chronic injuries, such as COVID-19, COPD, asthma, idiopathic pulmonary fibrosis (IPF) and lung cancer, the gut microbiota serves as a remote metabolic "rheostat". It delivers pivotal signaling molecules, such as short-chain fatty acids (SCFAs) and tryptophan metabolites (indoles), that could shape the local microenvironment in which the respiratory epithelium undergoes functional repair or maladaptive, fibrotic remodeling. Mechanistically, gut-derived butyrate enhances mitochondrial activity in alveolar epithelial cells, while resident progenitors, such as Alveolar Type 2 (AT2) cells, depend on intact mitochondrial fatty acid oxidation for proper regenerative differentiation. Conversely, critical lung illness disrupts this homeostasis via a "pathological circuit," where severe pulmonary inflammation drives gut permeability, fecal dysbiosis, and the subsequent translocation of pathogen-associated molecular patterns (PAMPs, such as LPS) or gut-associated bacteria back into the pulmonary circulation. This review highlights the systemic nature of lung regeneration, which likely depends heavily on intestinal health through the GLA. Ultimately, leveraging these remote microbial networks through precision postbiotic supplementation, dietary priming, or microbiota transplantation represents a crucial frontier in precision medicine to promote definitive alveolar repair.},
}

@article {pmid42514326,
year = {2026},
author = {Borruel Sainz, N and Serra-Ruiz, X and Guarner Aguilar, F and Castiglione, F and Nardone, OM and Laterza, L and Cascella, F and Gasbarrini, A and Dobrowolska, A and Kanikowska, A and Miheller, P and Menyhárt, O and Noviello, D and Caprioli, F},
title = {VSL#3[®] May Reduce Abdominal Pain and Bloating in Ulcerative Colitis Remission with IBS-like Symptoms: An Exploratory Randomized, Double-Blind Placebo-Controlled Trial.},
journal = {Nutrients},
volume = {18},
number = {14},
pages = {},
doi = {10.3390/nu18142257},
pmid = {42514326},
issn = {2072-6643},
support = {This research was funded by Actial Farmaceutica Srl (Italy).//Actial Farmaceutica Srl/ ; },
abstract = {Background: Irritable bowel syndrome (IBS)-like symptoms are common in patients with ulcerative colitis (UC) in sustained clinical and endoscopic remission and are associated with impaired quality of life. Evidence for targeted treatments in this setting remains limited. Objective: To evaluate the efficacy of the multistrain probiotic VSL#3[®] in patients with UC in stable remission and IBS-like symptoms. Methods: In this randomized, double-blind, explorative, placebo-controlled trial, adults with UC in stable remission for ≥6 months and Rome IV C1 or C4 symptoms received VSL#3[®] 450 billion colony-forming units or placebo twice daily for 8 weeks. The primary endpoint was symptom relief at week 8 assessed by the 5-point Subject's Global Assessment of Relief scale. Secondary endpoints included Irritable Bowel Syndrome Symptom Severity Scale scores (IBS-SSS), bowel habits, biochemical remission assessed through fecal calprotectin, IBS-QoL, and IBDQ. Results: Fifty-five patients were randomized. The primary endpoint did not differ significantly between groups. Between-group differences in IBS-SSS total score were not statistically significant at week 8; however, numerically greater and directionally consistent reductions in symptom severity and abdominal pain were observed with VSL#3[®] across visits, persisting at follow-up. In exploratory subgroup analyses, restricted to patients with higher abdominal pain and bloating scores at baseline, significant intragroup improvements in abdominal pain and bloating were observed with VSL#3[®] but not with placebo. Quality of life improvements were numerically greater and more sustained with VSL#3[®]. Conclusions: Within the limitations of the small sample size, these results show a signal of benefit in the quality of life of UC patients with IBS-like symptoms and suggest a potential complementary role for VSL#3[®] in symptom-oriented management, particularly for abdominal pain and bloating. Larger, adequately powered randomized trials are warranted to confirm these exploratory findings.},
}

@article {pmid42514986,
year = {2026},
author = {Ziaka, M},
title = {A Comprehensive Review of the Gut-Microbiota-Brain Axis in Alzheimer's Disease: From Pathophysiology to Potential Therapies.},
journal = {Pathogens (Basel, Switzerland)},
volume = {15},
number = {7},
pages = {},
doi = {10.3390/pathogens15070659},
pmid = {42514986},
issn = {2076-0817},
abstract = {The gut-microbiota-brain axis (GMBA), an intricate network connecting the gastrointestinal (GI) tract and the brain, plays a pivotal role in maintaining overall health and influencing disease processes. The human gut microbiota, comprising over 3000 bacterial species, regulates immune responses, hormonal signals, and metabolite production, maintaining homeostasis under normal conditions. Dysbiosis, or microbial imbalance, has been linked to various central nervous system (CNS) disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and autism spectrum disorder (ASD). Given the growing interest in this topic and the limited effectiveness of current therapeutic strategies for managing patients with AD, the purpose of the current narrative review is to analyze the pathophysiological role of the GMBA in the pathogenesis of AD and assess potential therapeutic strategies targeting the GMBA, particularly the microbiome and its metabolites. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science to identify clinical studies, experimental research, and review articles examining the GMBA in health and AD, as well as related therapeutic strategies. The search terms included "Alzheimer's disease", "neuroinflammation", "amyloid-beta", "tau", "gut-brain axis", "microbiome", "short-chain fatty acids", "probiotics", "prebiotics", and "fecal microbiota transplantation". In AD, altered gut microbiota composition is associated with neuroinflammation, neurodegeneration, and exacerbation of disease progression. Probiotics have shown potential in enhancing cognitive function and reducing neuroinflammation by modulating microbiota composition and influencing brain-derived neurotrophic factor (BDNF) levels. Prebiotics, through their impact on gut microbiota and metabolite production, also offer therapeutic promise by improving cognitive function and mitigating neuroinflammation. With its historical and modern applications, fecal microbiota transplantation (FMT) may represent a potential strategy for addressing dysbiosis and its neurological implications. This manuscript focuses on GMBA and its effects on neuroinflammation, neurodegeneration, and CNS health while emphasizing the need for further research into microbiome-based therapies and the gut-brain relationship in patients with AD.},
}

@article {pmid42515711,
year = {2026},
author = {Wang, M and Xue, B and Cui, H and Cheng, M and Li, J and Ren, Z and Liang, T and Nie, W and Song, L and Ban, C},
title = {Kai-Bi-Bu-Fei Decoction Protects Mice Against Influenza Virus-Induced Severe Pneumonia via Gut Microbiota-Short Chain Fatty Acid Axis.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {19},
number = {7},
pages = {},
doi = {10.3390/ph19071029},
pmid = {42515711},
issn = {1424-8247},
support = {81973784//National Natural Science Foundation of China/ ; 82474438//National Natural Science Foundation of China/ ; DZMKJCX-2024-012//Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine/ ; DZMG-QNHB0001//Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine/ ; },
abstract = {Background: Kai-Bi-Bu-Fei Decoction (KBD) is derived from the canonical Traditional Chinese Medicine formulas Xuan-Bai-Cheng-Qi and Ma-Xing-Shi-Gan. It has been employed for decades in the treatment of severe pneumonia with significant clinical efficacy. This study aimed to evaluate the protective effects of KBD against influenza virus-induced severe pneumonia in a murine model and to elucidate the underlying molecular mechanisms. Methods: The chemical profile of KBD was characterized using UPLC-Q-TOF-MS. A severe pneumonia model was established in C57BL/6J mice via intranasal infection with influenza A/Puerto Rico/8/34 (H1N1, PR8). Multiple parameters, including 14-day survival rate, body weight, lung index, histopathological changes, viral load, and pulmonary cytokine/chemokine levels, were assessed. Furthermore, multi-omics analyses were integrated to characterize the gut microbiota and metabolic profiles. Fecal microbiota transplantation (FMT) was subsequently performed to validate the functional role of the gut microbiota and its metabolites. Results: KBD treatment significantly improved the survival rate by 40%, reduced the lung index by 27.85%, and alleviated lung injury. It also markedly lowered the viral load by 80.88%, suppressed pro-inflammatory cytokine levels, and restored intestinal barrier integrity. Mechanistically, KBD restored gut microbiota diversity by increasing the abundance of Firmicutes and Bacteroidetes, enriching beneficial genera such as Bifidobacterium and Faecalibaculum, and reducing Verrucomicrobiota. Integrated transcriptomic and metabolomic analyses revealed that KBD enhanced short-chain fatty acid (SCFA) metabolism and up-regulated pyruvate metabolism. Finally, FMT confirmed that the therapeutic benefits of KBD were transferable via the microbiota to microbiota-depleted mice. Conclusions: KBD exerts robust protection against severe influenza pneumonia, a process primarily mediated by the gut microbiota-SCFA axis. The enhancement of mitochondrial energy metabolism also appears to play a critical role in its therapeutic mechanism.},
}

@article {pmid42516368,
year = {2026},
author = {Zhang, Y and Wang, S and Chang, S and Li, Y and Dang, Y and Wang, Z},
title = {Navigating the gut-metabolite-immune axis: enhancing efficacy and mitigating toxicity of immune checkpoint inhibitors.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1803970},
pmid = {42516368},
issn = {1664-3224},
abstract = {Immune checkpoint inhibitors (ICIs) have revolutionized the oncological landscape by disrupting inhibitory pathways, notably programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) pathways, thereby reinvigorating host antitumor immunity. Although these agents have emerged as frontline standard therapies for malignancies, their clinical utility remains limited. Interpatient therapeutic variability is inextricably linked to the composition and functional capacity of the gut microbiome. The underlying mechanisms appear to involve a complex dialogue between the microbiota and host immune system, where microbial metabolites serve as critical mediators in remodeling the tumor microenvironment. Despite these insights, progression in the field remains constrained due to heterogeneity in study cohorts and sample-processing methodologies, hindering the establishment of reproducible individualized predictive models and clinical intervention strategies. Consequently, there is an urgent need to systematically delineate the microbiome-metabolite-immune axis to optimize the balance between ICI efficacy and systemic toxicity. By synthesizing the latest evidence, this review aimed to highlight the pivotal roles of specific taxa, including Bacteroides, Bifidobacterium, and Akkermansia muciniphila, in ICI efficacy. These microbes and their metabolic byproducts potentiate therapeutic responses by enhancing dendritic cell cross-presentation and promoting CD[8+] T-cell infiltration, often via activation of the cyclic GMP-AMP synthase-stimulator of interferon genes or nucleotide-binding oligomerization domain-containing protein 2 signaling pathways. Furthermore, these microbial components demonstrate the ability to protect the heart and colon against inflammation and barrier disruption, thereby mitigating immune-related adverse events. Although the feasibility and safety of interventions such as fecal microbiota transplantation and supplementation with next-generation encapsulated probiotics, postbiotics, or dietary fiber have been demonstrated in preclinical and Phase I trials, substantial hurdles remain. Future progress requires large-scale, multicenter, standardized, longitudinal studies integrating metagenomics and metabolomics to construct robust cross-cancer and cross-population predictive models. Such rigorous validation would enable the development of precise microbial interventions that maximize therapeutic gains while minimizing the incidence of adverse reactions.},
}

@article {pmid42516373,
year = {2026},
author = {Atta, A and Naveed, M and Liu, J and Ansari, I and Ma, R and Wang, X and Feng, B},
title = {Agrocybe cylindracea polysaccharides and polysaccharides-conditioned fecal microbiota transplantation similarly restore ciprofloxacin-induced microbial dysbiosis and improve intestinal barrier function: a comparative study.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1841989},
pmid = {42516373},
issn = {1664-3224},
abstract = {INTRODUCTION: Mushroom consumption has been associated with various health benefits due to their recognized nutritional value. This study examines the ability of Agrocybe cylindracea polysaccharides (ACP) to reverse antibiotic-induced intestinal dysbiosis and evaluates their prebiotic potential in mitigating antibiotic-associated diarrhea.

METHODS: Male BALB/c mice aged 4-5 weeks were divided into five groups: normal control, ciprofloxacin (CIP)-treated, natural recovery, ACP treatment, and ACP-derived fecal microbiota transplantation (ACP-FMT). All intervention groups received CIP for 14 days, followed by their respective treatments for a further 14 days. Gut microbiota modifications were investigated using the Illumina MiSeq platform.

RESULTS: CIP administration markedly decreased bacterial diversity and richness, elevating pathogenic bacteria (Proteobacteria, Enterococcus, and Bacteroides) that persisted in the natural recovery group. Both ACP and ACP-FMT effectively counteracted dysbiosis, increasing beneficial genera including Ruminococcaceae, Lachnospiraceae_NK4A136, and Firmicutes. ACP and ACP-FMT restored mucin-2 biosynthesis and tight junction protein expression. ACP also reduced pro-inflammatory mediators including IL-6, IL-17, TNF-α, and IL-1β.

DISCUSSION: These findings highlight the prebiotic potential of ACP in restoring intestinal health, with therapeutic effects transferable via fecal microbiota transplantation, supporting their application as functional food ingredients for gut microbiota restoration.},
}

@article {pmid42516735,
year = {2026},
author = {McCarney, D and Chen, P and Simes, J and Kahn, SA},
title = {Pediatric Clostridiodes difficile infection with toxic megacolon successfully treated with fecal microbiota transplantation.},
journal = {JPGN reports},
volume = {},
number = {},
pages = {},
pmid = {42516735},
issn = {2691-171X},
abstract = {The rising incidence of pediatric Clostridioides difficile infection (CDI), particularly in medically complex patients, calls for novel, individualized treatments. While fecal microbiota transplantation (FMT) is well-described for recurrent CDI, this report describes the first pediatric case of fulminant CDI with toxic megacolon successfully treated with FMT. This critically ill patient experienced failure of standard-of-care antibiotics and was a poor surgical candidate due to neutropenia and abdominal radiation for rhabdomyosarcoma. Ultimately, FMT rapidly resolved the patient's symptoms without adverse events. FMT should be considered for pediatric fulminant CDI.},
}

@article {pmid42517442,
year = {2026},
author = {Ágreda Fernández, M and Rodríguez-Goncer, I and Aguado, JM and Origüen, J and Fernández-Ruiz, M},
title = {Solid Organ Transplant Recipients With Clostridioides difficile Infection Had Lower Fecal Calprotectin and Lactoferrin Levels Compared to Immunocompetent Patients: Implications for Biomarker Interpretation.},
journal = {Transplant infectious disease : an official journal of the Transplantation Society},
volume = {},
number = {},
pages = {e70288},
doi = {10.1111/tid.70288},
pmid = {42517442},
issn = {1399-3062},
support = {//Merck Sharp & Dohme (MSD/ ; },
}

@article {pmid42518858,
year = {2026},
author = {Zhang, Z and Liao, D and Zhao, L and Lu, X},
title = {Gut-ocular surface axis in dry eye disease: phenotype-specific mechanisms, evidence, and microbiome-targeted interventions.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1873050},
doi = {10.3389/fcimb.2026.1873050},
pmid = {42518858},
issn = {2235-2988},
abstract = {Dry eye disease is a multifactorial, heterogeneous ocular surface disorder characterized primarily by an imbalance in tear film homeostasis. The traditional classification into "aqueous deficiency" and "evaporative" types fails to fully account for the differences in its inflammatory biology, clinical manifestations, and treatment responses. In recent years, the gut microbiota has been implicated in influencing ocular surface homeostasis through immune-inflammatory, metabolic-barrier, and neuroimmune pathways; however, the magnitude of its effects and their biological significance may vary depending on the specific phenotype of dry eye disease (DED). This article reviews the current evidence regarding the gut-ocular surface axis in dry eye disease from a phenotype-specific perspective, categorizing it into direct clinical evidence, animal and mechanistic evidence, indirect and inferential evidence, and hypothesis-generating evidence based on the source and directness of the evidence. The existing evidence is primarily focused on Sjögren syndrome-associated and other immune-mediated forms of dry eye disease. Clinical microbiome studies, germ-free animal models, antibiotic-induced dysbiosis models, and patient-derived microbiota transplantation experiments all suggest that gut microbiota dysbiosis may contribute to systemic immune remodeling and lacrimal-ocular surface inflammatory responses. In contrast, for dry eye syndromes dominated by meibomian gland dysfunction or evaporative dry eye, as well as non-Sjögren aqueous-deficient dry eye, current evidence is primarily supported indirectly by studies on metabolic susceptibility, local microbiome, and animal mechanisms; whereas postoperative, environment-related, and symptom-sign incongruence types of dry eye are more often characterized by early clues or research hypotheses related to host inflammatory thresholds, ocular surface repair capacity, and neuroimmune regulation. Although microbiome-targeted interventions (including probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation) have demonstrated some translational potential, they remain limited by small sample sizes, high heterogeneity in study designs, short follow-up periods, and a lack of validation through phenotypic stratification. Future research should shift from general descriptions of microbial differences to stratified cohorts, causal validation, functional multi-omics analysis, and mechanism-driven intervention trials to clarify the true role of the gut microbiota in different DED phenotypes and to advance the development of precision adjunctive treatment strategies.},
}

@article {pmid42503576,
year = {2026},
author = {Mansour, RM and Alam-ElDein, KM and Abdel Mageed, SS and El-Sayyad, GS and Ghanem, A and Shaker, AAS and Mohammed, OA and Farag, DAA and Abdelnaby, M and Hathout, A and Adelaziz, RY and Ahmed, NE and Mohamed, MYA and Doghish, AS},
title = {Targeting the Microbiota-Gut-Brain Axis: Emerging Nanomedicine Approaches for Neurodegenerative Diseases.},
journal = {The European journal of neuroscience},
volume = {64},
number = {2},
pages = {e70606},
doi = {10.1111/ejn.70606},
pmid = {42503576},
issn = {1460-9568},
mesh = {Humans ; *Neurodegenerative Diseases/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; Animals ; *Dysbiosis/therapy/microbiology ; *Brain/metabolism ; *Nanomedicine/methods ; Fecal Microbiota Transplantation/methods ; *Brain-Gut Axis/physiology ; Probiotics/therapeutic use ; },
abstract = {The microbiota-gut-brain axis (MGBA) is a bidirectional relationship between the gut microbiota (GM) and the brain, where the GM affects the gastrointestinal tract (GIT) and the central nervous system (CNS), and vice versa. Microbiotas are important for several vital body processes, including metabolism, immunity, and homeostasis. The MGBA has three main pathways: the vagal nerve mechanism, the immune-related mechanism, and the neuroendocrine mechanism. GM imbalance, known as dysbiosis, affects the GIT, the brain, and the CNS. Furthermore, dysbiosis is linked to several neurological disorders such as Alzheimer's (AD), Parkinson's (PD), depression, autism spectrum disorder (ASD), and multiple sclerosis (MS). Studying MGBA gives researchers new therapeutic ideas using microbiota. Using special diets rich in fiber and probiotics, in addition to fecal microbiota transplantation (FMT), is being studied as a new therapy for MGBA. From the point of view that these therapeutic interventions maintain microbiota imbalance, which in turn will affect the brain and can relieve the neurological disorders caused by dysbiosis and MGBA.},
}

Humans
*Neurodegenerative Diseases/microbiology/therapy
*Gastrointestinal Microbiome/physiology
Animals
*Dysbiosis/therapy/microbiology
*Brain/metabolism
*Nanomedicine/methods
Fecal Microbiota Transplantation/methods
*Brain-Gut Axis/physiology
Probiotics/therapeutic use

@article {pmid42503584,
year = {2026},
author = {Herz, J and Bendix, I and Orywal, F and Härtel, C and Felderhoff-Müser, U},
title = {Gut-brain-immune interactions in neonatal hypoxic-ischemic brain injury.},
journal = {Molecular and cellular pediatrics},
volume = {13},
number = {1},
pages = {},
pmid = {42503584},
issn = {2194-7791},
abstract = {BACKGROUND: Neonatal hypoxia-ischemia (HI) is the leading cause of childhood mortality and neurodevelopmental disability. Despite therapeutic hypothermia as the only clinically established treatment to date, outcomes remain poor for a significant proportion of affected infants. Mechanistic understanding has been brain-oriented in the past, however the gut and immune system are increasingly recognized as active modulators of brain injury, recovery and neurodevelopment.

MAIN BODY: Gut microbiota regulate microglial maturation, myelination and blood-brain barrier integrity. Neonatal HI induces gut dysbiosis and barrier failure, associated with neuroinflammation. First, faecal microbiota transplantation experiments in animal models suggest a causal relationship. Clinical data corroborate microbial perturbations in HIE infants, though antibiotic exposure and the NICU environment represent potential confounders. At the level of the immune system, dysregulated peripheral innate and adaptive immune responses are well documented in HI-affected neonates, with some alterations persisting into school age. The microbiota dimension of these immune responses remains largely unexplored, despite well-characterized microbiota-immune interactions in models of adult stroke. Therapeutic candidates include probiotics, human milk oligosaccharides and butyrate, each with preliminary preclinical support but no completed clinical trials in HIE.

CONCLUSION: Reframing neonatal HI as a systemic gut-brain-immune disease opens up new possibilities for adjunctive therapy and biomarker discovery. Progress requires longitudinal multi-omic clinical cohorts, sex-stratified and disease-phase-resolved preclinical analyses and rigorous evaluation of microbiome-targeted interventions.},
}

@article {pmid42504648,
year = {2026},
author = {Kim, YS and Choi, SC},
title = {Beyond Dysbiosis Restoration: Does the Success of Fecal Microbiota Transplantation for Irritable Bowel Syndrome Lie in Repairing the Intestinal Stem Cell Niche?.},
journal = {Journal of neurogastroenterology and motility},
volume = {32},
number = {3},
pages = {307-309},
doi = {10.5056/jnm26132},
pmid = {42504648},
issn = {2093-0879},
}

@article {pmid42504661,
year = {2026},
author = {El-Salhy, M and Skarvatun, T and Hoff, DAL and Lunding, J and Kjelsvik Steinsvik, E and Gilja, OH and Hatlebakk, JG},
title = {Possible Mechanisms Underlying the Effects of Fecal Microbiota Transplantation in Patients With Irritable Bowel Syndrome.},
journal = {Journal of neurogastroenterology and motility},
volume = {32},
number = {3},
pages = {449-463},
doi = {10.5056/jnm26028},
pmid = {42504661},
issn = {2093-0879},
abstract = {BACKGROUND/AIMS: : This study aims to identify the mechanisms underlying the effects of fecal microbiota transplantation (FMT).

METHODS: : This study investigated 93 patients included in our previous clinical trial: 24 received 30 g of their own feces (placebo group), while 47 and 22 received 30 g and 60 g of donor feces, respectively. The patients underwent sigmoidoscopy with biopsies, provided fecal samples, and completed questionnaires to assess irritable bowel syndrome (IBS) symptoms, fatigue, and quality of life at the baseline and at 1 month following FMT. The biopsy samples were immunostained for Musashi-1, neurogenin-3, and enteroendocrine and immune cells. The cell densities were quantified by computerized image analysis. Fecal short-chain fatty acids (SCFAs) were measured by gas chromatography, and fecal bacteria were measured by 16S ribosomal RNA polymerase chain reaction DNA amplification.

RESULTS: : The densities of stem cells, enteroendocrine cell progenitors, serotonin, glucagon-like peptide 1, and peptide YY (PYY) cells increased following FMT in the 30-g and 60-g treated groups but not in the placebo group, and they were inversely correlated with both IBS symptoms and fatigue. The densities of submucosal immune cells and mast cells decreased following FMT in the 30-g and 60-g treated groups but not in the placebo group, and they were correlated with IBS symptoms and fatigue. The fecal level of butyric acid increased in patients treated with donor feces, and this was inversely correlated with IBS symptoms and fatigue.

CONCLUSIONS: : Stem cells, enteroendocrine progenitors, serotonin, and glucagon-like peptide 1 as well as low-grade inflammation may play roles in IBS symptom manifestations. The effects of FMT are probably due to the amelioration of these abnormalities.},
}

@article {pmid42504914,
year = {2026},
author = {Szabó, BG and Korózs, D and Bator, M and Jeszenszky, K and Lakatos, V and Gopcsa, L and Reményi, P and Sinkó, J},
title = {Fecal Microbiota Transplantation and Microbiota-Based Therapeutics in Allogeneic Hematopoietic Stem Cell Transplantation: Current Evidence and Future Directions.},
journal = {Clinical pharmacology and therapeutics},
volume = {},
number = {},
pages = {},
doi = {10.1002/cpt.70408},
pmid = {42504914},
issn = {1532-6535},
abstract = {The intestinal microbiome is a key regulator of immune homeostasis, metabolism, and epithelial barrier integrity. In patients with malignant hematological diseases, particularly those undergoing hematopoietic stem cell transplantation, microbiome perturbations by reduced diversity, pathobiont expansion, and loss of beneficial metabolites are common as a consequence of exposure to cytotoxic therapy and broad-spectrum antimicrobials. Accordingly, enteral microbiome manipulation has emerged as a promising strategy. We performed a narrative review of the literature in PubMed/MEDLINE, Embase, and the Web of Science from inception to October 2025. We focused on adult hematology and HSCT populations and synthesized evidence across microbiome-directed interventions, including fecal microbiota transplantation (FMT) and emerging standardized microbiota products, as well as adjunctive strategies such as pre-, pro-, and postbiotics, dietary modulation, and microbiome-sparing antimicrobial practices. Available clinical evidence, predominantly from case series, small cohorts and a limited number of randomized trials, suggests that FMT is feasible in selected immunocompromised patients and may be beneficial for recurrent Clostridioides difficile infection, multidrug-resistant organism decolonization and steroid-refractory gastrointestinal GvHD. Mechanistic data support pleiotropic effects of microbiome restoration, including replenishment of immunoregulatory metabolites, improved colonization resistance and reinforcement of mucosal function. While most reported adverse events are mild, rare transmission events and product variability necessitate for rigorous donor screening, standardized manufacturing and regulatory oversight. Key knowledge gaps include patient selection, optimal timing, dosing strategies, durability of benefit and integration with concurrent medications. In conclusion, microbiome-based interventions may transition from rescue therapy toward a structured component of supportive care in hematologic malignancy management.},
}

@article {pmid42505651,
year = {2026},
author = {Niculescu, AG and Iacob, CM and Brătilă, E and Tocariu, R and Coroleucă, CA and Corcionivoschi, N and Vrancianu, CO and Popescu, DL and Popa, GL and Popa, MI and Cristian, RE and Grigore, GA},
title = {Antibiotic-Driven Gut Microbiome Dysbiosis: Resistome Dynamics, Metabolic Disruption, and Paths to Restoration.},
journal = {Antibiotics (Basel, Switzerland)},
volume = {15},
number = {7},
pages = {},
doi = {10.3390/antibiotics15070688},
pmid = {42505651},
issn = {2079-6382},
support = {PN-IV-P2-2.1-TE-2023-1449//Executive Unit for Financing Higher Education, Research, Development and Innovation/ ; Component C9/Investment no. 8 (I8), PNRR-III-C9-2023-I8, contract no 760231, ID proiect - CF 53/28.12.2023//Ministry of Research and Innovation/ ; },
abstract = {The gut microbiome is a dynamic ecosystem that plays essential roles in host metabolism, immune regulation, colonization resistance, and maintenance of intestinal homeostasis. Antibiotic exposure profoundly disrupts this ecosystem by reducing microbial diversity, depleting beneficial commensals, reshaping microbial metabolic functions, and remodeling the gut resistome through the selection and dissemination of antibiotic resistance genes (ARGs). Increasing evidence from longitudinal metagenomic, multi-omics, and experimental studies indicates that these perturbations may persist long after antibiotic withdrawal due to incomplete ecological recovery, sustained mobile genetic element-mediated ARG dissemination, and altered microbiome resilience. Beyond antimicrobial resistance, antibiotic-induced dysbiosis has been associated with reduced short-chain fatty acid production, altered bile acid metabolism, impaired epithelial barrier function, and broader disturbances in host metabolic homeostasis, although many of these relationships remain associative rather than causal. This review provides an integrated overview of antibiotic-driven gut microbiome dysbiosis, emphasizing the ecological, functional, metabolic, and resistome-level consequences of antibiotic exposure together with the mechanisms governing microbiome recovery. Current microbiome-targeted restoration strategies, including probiotics, phage therapy, fecal microbiota transplantation, and next-generation microbiome therapeutics, are critically evaluated with particular attention to their evidence maturity, limitations, and translational potential. Finally, key knowledge gaps and future research priorities are discussed to support the development of more effective microbiome-preserving antimicrobial strategies and to limit the long-term dissemination of antimicrobial resistance.},
}

@article {pmid42501925,
year = {2026},
author = {Hu, J and Ma, X and Wang, Y and Liu, L and Tang, M and Tian, X and Liu, H and Gao, Y and Lv, J},
title = {Mechanistic insights into Cistanche deserticola aqueous extract in alleviating functional constipation: Integration of gut microbiota remodeling and focal adhesion-associated mucosal repair.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {122240},
doi = {10.1016/j.jep.2026.122240},
pmid = {42501925},
issn = {1872-7573},
abstract = {Cistanche deserticola Ma (Orobanchaceae), a widely used botanical drug in Traditional Chinese Medicine, is traditionally utilized to moisten the intestines and relieve constipation, particularly for senile and deficiency-induced constipation.

AIM OF THE STUDY: To evaluate the restorative effects of C. deserticola (CD) aqueous extract on functional constipation (FC) and elucidate its multi-omic mechanisms mediated by the gut microbiota-short-chain fatty acid (SCFA)-host axis.

MATERIALS AND METHODS: The CD extract was phytochemically characterized via UPLC-Q-TOF-MS/MS. Loperamide induced FC mice were treated with physiologically relevant doses of CD extract (369 and 615 mg/kg/day). Efficacy was assessed via phenotypic, biochemical, and histopathological evaluations. Mechanisms were explored integrating 16S rRNA sequencing, targeted SCFA metabolomics, and colonic transcriptomics. Fecal microbiota transplantation (FMT) was conducted to verify microbiota dependency. Key signaling networks were validated using Western blotting and immunofluorescence.

RESULTS: CD administration significantly accelerated intestinal transit, repaired mucosal barriers, restored gastrointestinal hormones, and mitigated oxidative and inflammatory stress. Microbiome profiling demonstrated CD reversed dysbiosis by enriching beneficial SCFA-producers (e.g., Lachnospiraceae NK4A136 group), correspondingly elevating colonic propionate and butyrate. FMT confirmed these therapeutic effects were microbiota-driven. Transcriptomic and molecular validations revealed that CD-mediated microecological restoration reactivated the Integrin αL/p-FAK/Filamin C mechanotransduction cascade and PDGFC/SGK1 signaling pathways, thereby promoting focal adhesion and structural mucosal repair.

CONCLUSIONS: CD alleviates FC by concurrently remodeling the gut microbiota, enhancing SCFA production, and reactivating colonic mechanotransductive tissue repair networks. This provides a robust scientific rationale for its traditional ethnopharmacological use in constipation management.},
}

@article {pmid42501995,
year = {2026},
author = {Diaz Fernandez, W and Salolin Vargas, VP and Padilla-Zambrano, HS and Cerino-Penaloza, MS and Saldaña Ruiz, MA and Leggett, C},
title = {[Microbiome-Gut-Brain Axis in Irritable Bowel Syndrome: Pathophysiology and Therapeutic Approaches].},
journal = {Revista de gastroenterologia del Peru : organo oficial de la Sociedad de Gastroenterologia del Peru},
volume = {46},
number = {2},
pages = {175-187},
pmid = {42501995},
issn = {1609-722X},
mesh = {Humans ; *Irritable Bowel Syndrome/therapy/physiopathology/microbiology ; *Gastrointestinal Microbiome/physiology ; Probiotics/therapeutic use ; *Brain-Gut Axis/physiology ; Prebiotics ; Dysbiosis/physiopathology ; FODMAP Diet ; Fecal Microbiota Transplantation ; },
abstract = {Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder characterized by chronic abdominal pain, bloating, and altered bowel habits, with a substantial impact on quality of life and healthcare systems. In recent years, the gut microbiota has emerged as a central component in its pathophysiology. Patients with IBS exhibit alterations in microbial diversity and composition -known as dysbiosis- that vary according to clinical subtype: diarrhea-predominant, constipation-predominant, or mixed. These alterations are associated with intestinal epithelial barrier dysfunction, low-grade inflammation mediated by mast cells and proinflammatory cytokines, disturbances in fermentation and gas production, and dysregulation of the microbiota-gut-brain axis, a multidirectional communication system integrating the central nervous system, the enteric nervous system, and the gut microbiota. Microbial metabolites -including short-chain fatty acids, serotonin, tryptamine, and histamine- actively participate in the modulation of motility, visceral sensitivity, and neuroimmunoendocrine responses. In this context, microbiota-targeted therapeutic strategies have emerged, including probiotics, prebiotics, synbiotics, a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet, rifaximin, and fecal microbiota transplantation, showing promising but heterogeneous results. Emerging therapies such as postbiotics and phage therapy open new perspectives. This review analyzes the pathophysiological mechanisms linking dysbiosis to IBS and evaluates the main microbiota-directed therapeutic interventions.},
}

Humans
*Irritable Bowel Syndrome/therapy/physiopathology/microbiology
*Gastrointestinal Microbiome/physiology
Probiotics/therapeutic use
*Brain-Gut Axis/physiology
Prebiotics
Dysbiosis/physiopathology
FODMAP Diet
Fecal Microbiota Transplantation

@article {pmid42497111,
year = {2026},
author = {Dubey, I and Yadav, M and Kushwaha, S},
title = {Irisin-treated microbiota restore blood-testis barrier integrity and spermatogenesis in chronically stressed rats.},
journal = {Tissue barriers},
volume = {},
number = {},
pages = {2700679},
doi = {10.1080/21688370.2026.2700679},
pmid = {42497111},
issn = {2168-8370},
abstract = {Chronic psychological stress impairs male fertility by disrupting spermatogenesis and the blood-testis barrier (BTB), which is essential for testicular function. Irisin, a myokine/adipokine involved in metabolic regulation, protects against testicular dysfunction and may beneficially modulate gut microbiota, highlighting its potential in the gut-testis axis. This study investigated the effect of fecal microbiota transplantation (FMT) from irisin-treated rats in restoring BTB integrity in a chronic unpredictable stress (CUS) rat model. Male Sprague-Dawley rats were randomized into four groups: Control, CUS, CUS + Control-FMT, and CUS + Irisin-FMT. CUS-exposed rats received FMT (5 mL, intra-rectally, on alternate days for 2 weeks) from donors treated with either irisin (100 ng/kg, subcutaneously, 4 weeks) or vehicle. The CUS + Irisin-FMT group showed marked improvements in sperm quality, and hormonal profiles, including testosterone, LH, FSH, and irisin. Irisin-FMT increased crypt length, goblet cells, and histological scores, and improved the testicular histological structure and Johnsen's index. These effects were accompanied by upregulation of BTB proteins, E- and N-cadherin, spermatogonia markers, suppression of inflammatory markers (NF-κB, IL-1β, IL-6), and activation of integrin-FAK/Akt/mTOR signaling. Microbiota analysis revealed an increase in beneficial genera, including Lactobacillus and Blautia, as well as the restoration of key families and phyla. Dysbiosis promotes systemic inflammation by altering butyrate and acetate, impairing BTB integrity and testicular function via immune activation, oxidative stress, and endocrine disruption. Irisin-FMT mitigates stress-induced testicular dysfunction by modulating gut microbiota and activating protective signaling pathways, highlighting a novel microbiome-based strategy for male infertility.},
}

@article {pmid42498089,
year = {2026},
author = {Gao, HQ and Zhang, N and Li, GN and Wen, L and Li, Y and Li, M and Dong, TW and Zhong, L and Wei, DN and Zhang, MM and Ou, L},
title = {Da-Jian-Zhong decoction restores the gut-brain balance in diarrhea-predominant irritable bowel syndrome rats via gut microbiota-bile acid axis.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {122224},
doi = {10.1016/j.jep.2026.122224},
pmid = {42498089},
issn = {1872-7573},
abstract = {Da-Jian-Zhong decoction (DJZD), a Chinese medicinal formula, exhibits therapeutic effects in the clinical management of diarrhea-predominant irritable bowel syndrome (IBS-D). Accumulating studies have demonstrated that DJZD can regulate the gut-brain balance in IBS-D model rats; however, its underlying molecular mechanism remains unclear.

AIM OF THE STUDY: To explore the potential mechanism by which DJZD restores the gut-brain axis in IBS-D model rats.

MATERIALS AND METHODS: Firstly, the therapeutic effects of DJZD in IBS-D model rats were evaluated based on the Bristol stool scale, abdominal withdrawal reflex (AWR) score, open field test (OFT) behavior, intestinal barrier function, and brain-gut peptide levels. Moreover, alterations in gut microbiota was detected using sequencing of the whole microbial genome. Subsequently, fecal microbiota transplantation (FMT) was performed to explore whether the regulatory effect of DJZD on the gut-brain axis against IBS-D was dependent on gut microbiota. The UHPLC-QTRAP-MS/MS was utilized to analyze bile acids (BAs) profiles and identify gut microbiota-derived BAs metabolites responsible for the beneficial effects of DJZD. Finally, the role of BAs metabolites in restoring the gut-brain axis was further verified using the IBS-D model rats.

RESULTS: Treatment with DJZD not only decreased AWR scores, improved stool score and intestinal barrier function, but also enhanced sucrose preference and changed OFT performance of IBS-D rats. Meanwhile, DJZD normalized the levels of 5-hydroxytryptamine (5-HT) and substance P (SP) in both the colon and hippocampus. Fecal microbiota harvested from DJZD-treated rats also reversed these IBS-D-associated pathological manifestations. Moreover, DJZD notably elevated the contents of secondary BAs (SBAs) in IBS-D rats, particularly norchenodeoxycholic acid (NorDCA), lithocholic acid (LCA), deoxycholic acid (DCA), and 3β-ursodeoxycholic acid (3β-UDCA). The elevated SBAs were positively correlated with the relative abundances of Akkermansia sp., Ruminococcus sp., and Clostridium sp. This could be attributed to the ability of these bacteria to produce bile salt hydrolases (BSH) and 7α-hydroxysteroid dehydrogenases (7α-HSDH). Additionally, administration with an LCA and DCA mixture was found to improve intestinal and brain dysfunction and restored abnormal 5-HT and SP levels.

CONCLUSION: DJZD restores gut-brain balance in IBS-D rats by regulating gut microbiota-bile acid axis, which provides a promising therapeutic strategy for IBS-D via targeting bile acid metabolites and intestinal bacteria.},
}

@article {pmid42501555,
year = {2026},
author = {Zhu, T and Sha, Y and Wang, Q and Yang, H and Liu, T},
title = {Gut microbiota and polycystic ovary syndrome: Pathogenesis and novel therapeutic approaches.},
journal = {Microbiological research},
volume = {312},
number = {},
pages = {128643},
doi = {10.1016/j.micres.2026.128643},
pmid = {42501555},
issn = {1618-0623},
abstract = {Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women that is characterized by a complex pathogenesis involving multiple mechanisms, including hyperandrogenism, ovulatory dysfunction, insulin resistance (IR), and chronic inflammation. Recent studies have demonstrated that the gut microbiota acts as an important metabolic regulator and may play a pivotal role in the onset and progression of PCOS. Patients with PCOS frequently exhibit gut microbiota dysbiosis, which is characterized by reduced microbial diversity, decreased levels of beneficial bacteria, increased levels of pathogenic bacteria, and altered metabolic byproducts. This imbalance may contribute to IR and ovarian dysfunction by activating the toll-like receptor 4/nuclear factor kappa B inflammatory pathway, inducing oxidative stress, and disrupting Wnt/β-catenin signaling. The Wnt/β-catenin signaling pathway, a key regulator of follicular development, is frequently aberrantly activated in PCOS. In this narrative review, we summarize the recent advances in understanding the roles of the gut microbiota and the Wnt/β-catenin signaling pathway in the pathogenesis of PCOS. To this end, we conducted a comprehensive literature search across PubMed, Web of Science, Embase, and Cochrane Library databases, covering publications from January 2012 to March 2026. Ninety-eight articles were included after screening. We further explored therapeutic strategies based on microbiome modulation and signaling pathway targeting, including probiotics, traditional Chinese medicine, ginsenosides, puerarin, fecal microbiota transplantation, and nanoparticle-based ginseng-derived exosomes, thereby providing novel insights into potential therapies for PCOS.},
}

@article {pmid42492261,
year = {2026},
author = {Zhu, Y and Ding, X and Wang, X and Zhou, C and Sheng, Y and Li, M and Yu, Y and Zhu, F and Zhang, Y},
title = {A water-soluble Dendrobium officinale polysaccharide (DOPW) attenuates hepatic fibrosis via gut microbiota-mediated autophagy activation.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {159},
number = {},
pages = {158582},
doi = {10.1016/j.phymed.2026.158582},
pmid = {42492261},
issn = {1618-095X},
abstract = {BACKGROUND: Hepatic fibrosis currently lacks effective therapies. DOPW, a water-soluble polysaccharide isolated from Dendrobium officinale, exerts anti-fibrotic effects, but its underlying mechanisms remain unclear.

PURPOSE: This study investigates whether DOPW attenuates fibrosis through a gut microbiota-dependent mechanism involving key microbial metabolites and the hepatic ERK1/2-autophagy signaling pathway.

METHODS: DOPW was structurally characterized. Its anti-fibrotic efficacy was evaluated in a mouse model of CCl₄-induced hepatic fibrosis and in TGF-β1-induced LX-2 cells. Mechanistic investigations integrated transcriptomic analysis (RNA‑seq) with pharmacological targeting of ERK1/2 signaling and autophagy, combined with 16S rRNA sequencing and fecal microbiota transplantation (FMT) to assess the role of the gut microbiota. The key microbial metabolite butyrate was quantified in both colonic and hepatic tissues.

RESULTS: DOPW is a polysaccharide (256 kDa) composed of glucose and mannose in a 5:1 molar ratio. DOPW dose-dependently alleviated hepatic fibrosis, reducing liver injury, inflammation, and collagen deposition (all p < 0.001). Mechanistically, DOPW activated hepatic stellate cell autophagy by inhibiting ERK1/2 signaling, as confirmed by rescue experiments with ERK1/2 modulators (all p < 0.05). Notably, DOPW enriched short-chain fatty acid-producing gut microbiota (Parabacteroides, Bifidobacterium, and Prevotella), elevated fecal butyrate by 2.11-fold (p = 0.0443), and reinforced intestinal barrier integrity (all p < 0.05). These microbiota and metabolite changes were associated with suppression of hepatic ERK1/2 phosphorylation. Antibiotic depletion abolished these effects, while FMT with DOPW-modified microbiota reproduced the anti-fibrotic benefits (all p < 0.05).

CONCLUSION: DOPW attenuates hepatic fibrosis by remodeling gut microbiota to enhance short-chain fatty acid production and intestinal barrier integrity, with butyrate and ERK1/2-dependent autophagy emerging as key mediators of this gut-liver crosstalk. These findings position DOPW as a promising microbiota-targeted anti-fibrotic candidate.},
}

@article {pmid42493518,
year = {2026},
author = {Ninkov, M and Maleki Vareki, S},
title = {Microbial engraftment and immune regulation during fecal microbiota transplantation and immune checkpoint inhibitor therapy.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {42493518},
issn = {2041-1723},
mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Immune Checkpoint Inhibitors/therapeutic use ; *Gastrointestinal Microbiome/immunology ; *Neoplasms/therapy/immunology/microbiology ; Animals ; Immunotherapy/methods ; },
abstract = {The gut microbiota is a critical determinant of both therapeutic efficacy and immune-related toxicity during cancer immunotherapy with immune checkpoint inhibitors (ICIs). Fecal microbiota transplantation (FMT) has emerged as a strategy to introduce beneficial microbial functions, yet clinical outcomes remain variable. In this Review, we integrate evidence from recent clinical trials combining FMT with ICIs in a mechanism-based framework for understanding this variability and to guide safer clinical applications. We discuss how specific microbial functional programs can either buffer or lower thresholds for immune dysregulation and outline implications for donor selection, longitudinal monitoring, and trial design in oncology.},
}

*Fecal Microbiota Transplantation/methods
Humans
*Immune Checkpoint Inhibitors/therapeutic use
*Gastrointestinal Microbiome/immunology
*Neoplasms/therapy/immunology/microbiology
Animals
Immunotherapy/methods

@article {pmid42494851,
year = {2026},
author = {Zeng, L and Xue, B and Ren, X and Gong, S and Yan, J},
title = {Gut microbiota in acute lung injury/acute respiratory distress syndrome: mechanistic insights and therapeutic opportunities via the gut-lung axis.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1781229},
pmid = {42494851},
issn = {2235-2988},
mesh = {Humans ; *Respiratory Distress Syndrome/therapy/microbiology ; *Acute Lung Injury/therapy/microbiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; *Gastrointestinal Microbiome ; Prebiotics/administration & dosage ; *Lung/microbiology/immunology ; Drugs, Chinese Herbal/therapeutic use ; Animals ; Medicine, Chinese Traditional ; },
abstract = {Acute lung injury (ALI) is a severe clinical syndrome involving inflammatory damage to pulmonary cells, often progressing to acute respiratory distress syndrome (ARDS) with a crude incidence and mortality rate. Despite advances in supportive care, no definitive pharmacological treatment exists. The role of the gut microbiota in immune homeostasis and the gut-lung axis have motivated research into its association with ALI/ARDS. Probiotics, prebiotics, and traditional Chinese herbal medicines have been shown to alleviate ALI/ARDS by modulating gut microbiota. However, the variability among individuals and the complexity of the microbial ecosystem present significant challenges to research and drug development. The integration of multi-omics with artificial intelligence (AI) holds considerable potential for identifying therapeutic targets. This review summarizes the interactions between the gut microbiota and the gut-lung axis in cases of ALI and ARDS. It also discusses the mechanisms through which probiotics, prebiotics, fecal microbiota transplantation (FMT), and traditional Chinese herbal medicines (TCHMs) can intervene, with the aim of developing safer and more effective therapeutic strategies.},
}

Humans
*Respiratory Distress Syndrome/therapy/microbiology
*Acute Lung Injury/therapy/microbiology
Fecal Microbiota Transplantation
Probiotics/therapeutic use
*Gastrointestinal Microbiome
Prebiotics/administration & dosage
*Lung/microbiology/immunology
Drugs, Chinese Herbal/therapeutic use
Animals
Medicine, Chinese Traditional

@article {pmid42495133,
year = {2026},
author = {Joo, MK and Tak, J and Ha, S and Yoon, KS and Namgoong, JM and Kim, HO},
title = {The gut resistome as a potential determinant of immunotherapy response: antibiotics, immunometabolism, and precision oncology.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1835588},
pmid = {42495133},
issn = {1664-302X},
abstract = {Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, yet their efficacy can be compromised by systemic antibiotic exposure and the resulting disruption of the gut microbiome. Across several tumor types, antibiotic use near the initiation of ICI therapy has frequently been associated with reduced progression-free and overall survival. Emerging data suggest that, beyond taxonomic shifts, antibiotic exposure is often accompanied by expansion of the gut resistome, the collective pool of antibiotic resistance genes. Antibiotic-associated dysbiosis and resistome enrichment are linked to alterations in short-chain fatty acid production, bile acid signaling, and microbial purine metabolism, pathways known to shape antigen presentation, T-cell differentiation, and immune tone. Accordingly, gut resistome profiling should be considered an emerging candidate biomarker. Potential strategies to restore a favorable gut ecosystem include dietary modulation, microbiome-based therapies such as probiotics or fecal microbiota transplantation, and emerging anti-resistance approaches designed to limit resistome expansion. Together, these findings support a resistome-centered framework for patient stratification and microbiome-targeted interventions in precision immune-oncology.},
}

@article {pmid42495595,
year = {2026},
author = {Zhang, ZY and Li, ZD and Peng, CW and Peng, H and Zou, XS and Zhu, YX and Liao, WL and Li, TK and Rong, L},
title = {Role of the gut microbiota in hypertriglyceridemic acute pancreatitis: potential mechanisms and therapeutic implications.},
journal = {Therapeutic advances in gastroenterology},
volume = {19},
number = {},
pages = {17562848261467814},
pmid = {42495595},
issn = {1756-283X},
abstract = {Hypertriglyceridemic acute pancreatitis (HTG-AP) is an acute, noninfectious inflammatory disease caused by excessively high levels of serum triglycerides, leading to an overproduction of free fatty acids. This damages the pancreas and disrupts pancreatic microcirculation, leading ultimately to HTG-AP. Clinically, HTG-AP is associated with increasing incidence, multiple complications, and a higher risk of severe disease or adverse outcomes. There is a lack of unified standards, both domestically and internationally, for the clinical management of HTG-AP. This presents challenges for HTG-AP treatment while also offering opportunities to explore more effective interventional approaches. Preliminary research suggests the importance of the gut microbiota in the development and progression of HTG-AP, potentially mediated by influencing lipid metabolism and inflammatory responses. However, little is known of the potential function of the gut microbiota in the etiology of HTG-AP. This review summarizes current evidence on gut microbiota alterations in HTG-AP, with emphasis on lipid metabolism, intestinal barrier injury, and immune-inflammatory pathways. We also discuss microbiota-targeted interventions as investigational strategies that require HTG-AP-specific clinical validation.},
}

@article {pmid42484510,
year = {2026},
author = {Wang, H and Xu, J and Liang, K and Tian, Y and Cui, Z and Zhang, J},
title = {Paecilomyces cicadae-fermented Radix astragali modulates short-chain fatty acids metabolism in the intestine through gut microbiota and ameliorates hyperuricaemia.},
journal = {British journal of pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bph.70565},
pmid = {42484510},
issn = {1476-5381},
abstract = {BACKGROUND AND PURPOSE: Hyperuricaemia, a severe metabolic disorder linked to gout, is increasingly prevalent worldwide. Radix astragali, as a drug-food homologous material, has significantly expanded the market for novel functional foods. The solid-state fermentation products of R. astragali and Paecilomyces cicadae (RPF) promise to be candidates for lowering uric acid. Here, we have investigated the effects of RPF, using a model of hyperuricaemia in rats.

EXPERIMENTAL APPROACH: Hyperuricaemia, and damage to liver and kidney, was induced in male Sprague-Dawley rats receiving a high purine diet. Gut microbiota and short-chain fatty acid metabolism were examined by multi-omics analysis of rat faeces. Faecal microbiota transplantation was used to assess the therapeutic potential of gut microbiota and RPF. Effects of Eubacterium siraeum on uric acid and short-chain fatty acid metabolism were examined, in vitro and in hyperuricaemic rats.

KEY RESULTS: RPF regulated dysbiosis of gut microbiota and restored the relative abundance of Ruminococcus and Eubacterium, which was associated with normalisation of serum levels of uric acid and short chain fatty acids. In vitro, the E. siraeum DSM15702 strain extensively degraded uric acid. In vivo data from probiotic-treated, hyperuricaemic rats, indicated a reduction of circulating uric acid levels.

CONCLUSION AND IMPLICATIONS: Our study suggests that the gut microbiota-short chain fatty acid axis may play a crucial role in maintaining intestinal homeostasis and in modulating the excretion of uric acid. E. siraeum may serve as a potential adjunct therapy for management of hyperuricaemia.},
}

@article {pmid42485503,
year = {2026},
author = {Khanamani Falahatipour, S and Soltani, M},
title = {Targeting the Gut-Brain Axis: Pharmacological Modulation of the Microbiome for Neurological and Behavioural Disorders in Companion Animals.},
journal = {Veterinary medicine and science},
volume = {12},
number = {4},
pages = {e71105},
doi = {10.1002/vms3.71105},
pmid = {42485503},
issn = {2053-1095},
mesh = {Animals ; Dogs ; Cats ; *Gastrointestinal Microbiome/drug effects ; *Cat Diseases/microbiology/drug therapy ; *Dog Diseases/microbiology/drug therapy ; *Nervous System Diseases/veterinary/drug therapy/microbiology ; *Mental Disorders/drug therapy/microbiology ; *Pets ; *Brain ; Prebiotics ; },
abstract = {BACKGROUND: The gut-brain axis (GBA) represents a paradigm shift in veterinary neuropharmacology, offering novel approaches for managing neurological and behavioural disorders in companion animals.

OBJECTIVES: This review synthesizes current evidence on the bidirectional communication between the gut microbiome and the central nervous system, examining the neural, endocrine, immune, and metabolic pathways that facilitate this dialogue. We explore the unique aspects of canine and feline microbiomes and their implications for species-specific drug development and critically evaluate emerging pharmacological strategies, including psychobiotics, prebiotics, synbiotics and faecal microbiota transplantation (FMT), highlighting their clinical applications in conditions ranging from anxiety and aggression to cognitive dysfunction and epilepsy.

METHODS: This narrative review followed established guidelines for evidence synthesis in veterinary medicine. A comprehensive literature search was performed using PubMed, Google Scholar and Scopus databases covering publications from January 2011 to March 2026.

RESULTS: While promising results have been demonstrated with specific strains, such as Bifidobacterium longum BL999 and Lactiplantibacillus plantarum PS128, significant challenges remain. These include methodological limitations in microbiome research, the predominance of correlative over causal evidence and the need for standardized diagnostic tools.

CONCLUSIONS: Future directions must prioritize large-scale longitudinal studies, robust clinical trials and advanced multi-omics approaches to establish causal mechanisms and develop personalized, microbiome-targeted therapies. Realizing this potential requires a shift from correlative data to causal mechanisms, from a one-size-fits-all approach to species-specific therapeutics and from rodent models to rigorous trials in dogs and cats.},
}

Animals
Dogs
Cats
*Gastrointestinal Microbiome/drug effects
*Cat Diseases/microbiology/drug therapy
*Dog Diseases/microbiology/drug therapy
*Nervous System Diseases/veterinary/drug therapy/microbiology
*Mental Disorders/drug therapy/microbiology
*Pets
*Brain
Prebiotics

@article {pmid42486034,
year = {2026},
author = {Xiang, X and Huang, Y and Shen, Y and Wang, D and Huang, Y},
title = {Radix Isatidis polysaccharide-induced gut microbiota alleviates interstitial nephritis caused by infectious bronchitis virus via the gut-kidney axis.},
journal = {Poultry science},
volume = {105},
number = {11},
pages = {107441},
doi = {10.1016/j.psj.2026.107441},
pmid = {42486034},
issn = {1525-3171},
abstract = {Interstitial nephritis caused by Infectious Bronchitis Virus (IBV) is a primary cause of mortality in chickens. To investigate whether gut microbiota mediate this effect, chickens were treated with antibiotics to deplete intestinal flora, which exacerbated IBV infection and abolished RIP's protective effect. It was found that fecal microbiota transplantation (FMT) could reduce IBV copy numbers, decrease the production of metabolites, decrease the expression of NLRP3 pathway-related genes and proteins in the kidneys and intestines and increase the expression of tight intestinal junction proteins, and alleviate enteritis and interstitial nephritis. The 16S rRNA sequencing results indicated a significant increase in the abundance of harmful Escherichia_Shigella bacteria following IBV infection. However, in the RIP prevention group and FMT group, there was an increase in the abundance of probiotics such as Faecalibacterium, Lactobacillus, and Bifidobacterium. Furthermore, Lactobacillus reuteri, isolated from the feces of RIP-administered chickens and combined with sodium acetate (NaAc), alleviated interstitial nephritis and was associated with decreased expression of NLRP3 pathway-related molecules, reduced inflammatory factors, and enhanced intestinal tight junction proteins. This study not only confirms the vital role of gut microbiota in the treatment of IBV-induced nephritis but also opens avenues for the development of targeted probiotic therapies in viral infections and kidney diseases.},
}

@article {pmid42486038,
year = {2026},
author = {Cheng, C and Lu, W and Fan, W and Wu, H and Tian, X and Yang, D and Peng, H},
title = {Galangin ameliorates Salmonella Pullorum-induced enteritis in Danzhou chicks through gut microbiota-derived indole-3-lactic acid-mediated AHR activation.},
journal = {Poultry science},
volume = {105},
number = {11},
pages = {107439},
doi = {10.1016/j.psj.2026.107439},
pmid = {42486038},
issn = {1525-3171},
abstract = {Antibiotic restrictions in poultry production necessitate natural alternatives against Salmonella Pullorum, a pathogen causing severe enteritis and high chick mortality. We show that the dietary flavonoid galangin alleviates S. Pullorum-induced intestinal injury not via direct antimicrobial action, but by modulating gut microbiota to enrich tryptophan-derived indole-3-lactic acid (ILA). Galangin restored growth, preserved barrier integrity, reduced liver bacterial translocation, and suppressed inflammation in infected chicks. Fecal microbiota transplantation from galangin-treated donors recapitulated these benefits, confirming microbiota dependence. ILA activated the aryl hydrocarbon receptor (AHR), concurrently inhibiting NF-κB and HIF-1α pathways-key drivers of Salmonella-exploited inflammation and metabolic reprogramming-thereby enhancing mucosal defense and limiting intracellular bacterial survival. Pharmacological AHR blockade or NF-κB/HIF-1α activation abolished galangin's effects. Collectively, these findings establish that galangin acts as a prebiotic-like agent via the ILA-AHR axis, providing a mechanism-based strategy for antibiotic reduction in sustainable poultry production.},
}

@article {pmid42486172,
year = {2026},
author = {Hanifeh, M and Huhtinen, M and Ganz, HH and Heilmann, RM and Huang, W and Spillmann, T and Suchodolski, JS},
title = {Clinical trial reveals limited clinical and microbiome effects following oral fecal microbiota transplantation in dogs with chronic enteropathy responsive to tylosin.},
journal = {Journal of the American Veterinary Medical Association},
volume = {},
number = {},
pages = {1-11},
doi = {10.2460/javma.26.03.0178},
pmid = {42486172},
issn = {1943-569X},
abstract = {OBJECTIVE: To evaluate clinical response and fecal biomarkers in dogs with tylosin-responsive enteropathy (TRE) treated with oral fecal microbiota transplantation (FMT).

METHODS: In this prospective, randomized, double-blind, placebo-controlled trial (conducted between August 1, 2020, and December 31, 2022), 14 client-owned dogs with confirmed tylosin-responsive enteropathy entered the treatment phase. Dogs received oral FMT (n = 7) or placebo (7) for 4 weeks; 1 placebo-treated dog was excluded (pyometra), leaving 7 FMT-treated and 6 placebo-treated dogs for analysis. Canine Chronic Enteropathy Clinical Activity Index, fecal consistency, and fecal biomarkers (dysbiosis index, core bacteria, bile acids, short-chain fatty acids, lactate, and calprotectin) were assessed at pretreatment and posttreatment visits. Intestinal permeability was evaluated with serum iohexol. Analyses were limited to pre- and posttreatment comparisons.

RESULTS: Relapse occurred in 2 of 7 FMT-treated dogs (28.6%) and 3 of 6 placebo-treated dogs (50.0%). The dysbiosis index decreased over time in both groups, with no treatment effect. Faecalibacterium spp increased, with higher posttreatment values in the FMT group, whereas Turicibacter spp increased in both groups. Peptacetobacter hiranonis increased over time without between-group differences. Bile acid conversion was observed in a subset of dogs without group differences. Other biomarkers showed no consistent treatment-specific effects.

CONCLUSIONS: Oral FMT was associated with variable microbiome changes and inconsistent clinical response, with no clear treatment-specific effects compared with placebo. These findings support further evaluation of optimized microbiome-based therapies in larger studies.

CLINICAL RELEVANCE: Oral FMT may serve as an adjunctive strategy for microbiome modulation in dogs with chronic enteropathy; however, clinical benefits were inconsistent and optimized protocols may be required.},
}

@article {pmid42486573,
year = {2026},
author = {James, S and Wodeyar, AM and Chaurasia, A},
title = {Modulating the head & neck microbiome for cancer- prevention.},
journal = {Advances in immunology},
volume = {170},
number = {},
pages = {127-140},
doi = {10.1016/bs.ai.2026.03.006},
pmid = {42486573},
issn = {1557-8445},
mesh = {Humans ; *Head and Neck Neoplasms/prevention & control/microbiology/immunology ; *Dysbiosis/immunology/microbiology ; *Microbiota/immunology ; Fecal Microbiota Transplantation ; Probiotics ; Animals ; Prebiotics ; *Gastrointestinal Microbiome/immunology ; },
abstract = {The head and neck microbiome plays a critical role in maintaining epithelial homeostasis, regulating immune surveillance, and shaping inflammatory responses that influence carcinogenesis. Increasing evidence suggests that microbial dysbiosis within the oral and gut ecosystems contributes to the initiation and progression of head and neck cancers, particularly oral squamous cell carcinoma. Given that the microbiome is a modifiable risk factor, targeted modulation has emerged as a promising preventive and supportive strategy in HNC. This chapter highlights current knowledge on microbiome-based interventions, including dietary modification, probiotics, prebiotics, postbiotics, synbiotics, fecal microbiota transplantation, and lifestyle changes, with emphasis on their immunomodulatory and anti-inflammatory effects. These approaches aim to restore microbial balance, enhance barrier integrity, reduce chronic inflammation, and strengthen anticancer immune responses. The chapter also discusses mechanistic links between microbial metabolites and immune pathways, the relevance of the oral-gut axis, and emerging evidence connecting microbiome composition with treatment response and toxicity. Finally, key challenges such as inter-individual variability, site-specific microbial niches, safety considerations, and the need for longitudinal and mechanistic studies are addressed. Overall, microbiome modulation represents a promising, precision-oriented avenue for cancer prevention, risk reduction, and survivorship in head and neck oncology, although robust clinical validation is still required.},
}

Humans
*Head and Neck Neoplasms/prevention & control/microbiology/immunology
*Dysbiosis/immunology/microbiology
*Microbiota/immunology
Fecal Microbiota Transplantation
Probiotics
Animals
Prebiotics
*Gastrointestinal Microbiome/immunology

@article {pmid42486574,
year = {2026},
author = {Choudhury, M and Tavassoli, M},
title = {Microbiome-targeted therapeutics in head & neck cancer.},
journal = {Advances in immunology},
volume = {170},
number = {},
pages = {141-161},
doi = {10.1016/bs.ai.2026.03.012},
pmid = {42486574},
issn = {1557-8445},
mesh = {Humans ; *Head and Neck Neoplasms/therapy/microbiology/immunology ; *Microbiota/immunology ; Probiotics/therapeutic use ; Animals ; *Dysbiosis/immunology/therapy/microbiology ; Fecal Microbiota Transplantation ; Prebiotics ; },
abstract = {The oral microbiome is increasingly recognized as a critical factor in the development, progression, and response to therapy of head and neck cancer. Microbial dysbiosis has been associated with chronic inflammation, immune modulation, altered cellular proliferation and apoptosis, and the production of carcinogenic metabolites which collectively shape the tumor microenvironment. Various bacterial species, including Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus mutans, and Treponema denticola, as well as fungal species such as Candida albicans and non-albicans Candida, have been implicated in oral carcinogenesis. These microorganisms promote tumorigenic processes through the generation of carcinogens such as nitrosamines and acetaldehyde, which activate innate immune pathways such as nuclear factor kappa B and Wnt/β-catenin. Conversely, several commensal species, including Neisseriaceae, Kingella, Corynebacterium, Prevotella nanceiensis, Capnocytophaga leadbetteri, and Selenomonas sputigena, have been associated with a reduced prevalence of head and neck cancer, suggesting a potential association between microbial homeostasis and reduced cancer risk. Advances in microbiome research have led to the exploration of microbiome-targeted therapeutic strategies as adjuncts to conventional head and neck cancer treatment. Approaches including probiotics, prebiotics, postbiotics, dietary modulation, and fecal microbiota transplantation aim to restore microbial balance, enhance antitumor immune responses, mitigate therapy-induced toxicities, and improve treatment efficacy. Probiotic formulations containing Lactobacillus and Bifidobacterium species have shown promise in reducing adverse effects and improving patient quality of life and treatment adherence. This chapter summarizes current evidence on microbiome dysbiosis in head and neck cancer and reviews emerging microbiome-targeted interventions with potential clinical relevance.},
}

Humans
*Head and Neck Neoplasms/therapy/microbiology/immunology
*Microbiota/immunology
Probiotics/therapeutic use
Animals
*Dysbiosis/immunology/therapy/microbiology
Fecal Microbiota Transplantation
Prebiotics

@article {pmid42486576,
year = {2026},
author = {Venugopal, DC and Srinivas, KS},
title = {Challenges and future directions in head and neck microbiome research.},
journal = {Advances in immunology},
volume = {170},
number = {},
pages = {189-227},
doi = {10.1016/bs.ai.2026.03.010},
pmid = {42486576},
issn = {1557-8445},
mesh = {Humans ; *Head and Neck Neoplasms/microbiology/therapy/immunology ; *Microbiota/immunology ; Animals ; *Dysbiosis/microbiology/immunology/therapy ; Fecal Microbiota Transplantation ; Metabolomics ; Metagenomics ; Probiotics/therapeutic use ; },
abstract = {The microbial imbalance in head and neck cancer (HNC) is a promising area of research for developing targeted therapies. Maintenance of microbial diversity and balance through prebiotics, probiotics and faecal microbial transplantation (FMT) holds a potential approach in reestablishing the gut health. Preclinical studies and early clinical trials have shown positive results in restoring the favourable microbial environment, thereby minimizing the inflammation and maximizing the positive immune response. However, the link between microbial flora associated with oral dysbiosis, the associated biomarkers and HNC tumorigenesis needs to be further explored. Future research focusses on developing standardised strategies for maintaining the microbial environment, to serve as an adjunct to the standard treatment protocols for HNC. Biomarkers predicting immune response, synthetic genetically engineered beneficial bacteria, integration of metagenomics, metabolomics and meta transcriptomics for intra-tumoral microbial evaluation are the focus areas of emerging research.},
}

Humans
*Head and Neck Neoplasms/microbiology/therapy/immunology
*Microbiota/immunology
Animals
*Dysbiosis/microbiology/immunology/therapy
Fecal Microbiota Transplantation
Metabolomics
Metagenomics
Probiotics/therapeutic use

@article {pmid42486639,
year = {2026},
author = {Li, H and Ban, C and An, J and Yang, J and Ren, J and Wu, Y and Shen, Z and Zhang, J and Gu, X and Liu, H},
title = {Dihydrotanshinone I Attenuates Atherosclerosis via Inhibiting NLRP3 Inflammasome Activation and Modulating Gut Microbiota.},
journal = {Biological & pharmaceutical bulletin},
volume = {49},
number = {7},
pages = {1140-1152},
doi = {10.1248/bpb.b26-00124},
pmid = {42486639},
issn = {1347-5215},
mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/antagonists & inhibitors ; *Atherosclerosis/drug therapy/metabolism/pathology ; *Inflammasomes/metabolism/antagonists & inhibitors ; *Gastrointestinal Microbiome/drug effects ; *Phenanthrenes/pharmacology/therapeutic use ; Male ; Mice, Inbred C57BL ; Mice ; Diet, High-Fat ; *Anti-Inflammatory Agents/therapeutic use/pharmacology ; *Quinones/therapeutic use/pharmacology ; Salvia miltiorrhiza/chemistry ; Humans ; Furans ; },
abstract = {Atherosclerosis (AS), a primary contributor to cardiovascular disease, is driven by hyperlipidemia, chronic inflammation, and gut dysbiosis. Although Salvia miltiorrhiza Bunge (Danshen) has long been used to treat atherosclerotic disorders, its most potent anti-inflammatory constituent remains unclear. Screening 12 constituents from Danshen revealed that dihydrotanshinone I (DHT) was the most potent inhibitor of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in vitro. In an atherosclerotic mouse model, DHT treatment effectively attenuated dyslipidemia and reduced atherosclerotic plaque burden in the aorta and aortic sinus. Mechanistically, DHT significantly downregulated the aortic mRNA expression of key inflammasome components (NLRP3, ASC, Caspase-1, and IL-1β) and significantly suppressed the aortic protein levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1). Furthermore, gut microbiota analysis indicated that DHT alleviated high-fat diet-induced gut dysbiosis by restoring gut microbial diversity. This was characterized by a decrease in pathobionts (Rikenellaceae_RC9_gut_group, Muribaculum, and [Eubacterium]_ventriosum_group) and an increase in beneficial genera (Akkermansia and Allobaculum). Fecal microbiota transplantation (FMT) confirmed that these atheroprotective effects were transferable via the gut microbiota, highlighting the key role of microbial modulation. Collectively, DHT exerts its anti-atherosclerotic effects by simultaneously improving lipid metabolism, inhibiting NLRP3 inflammasome activation, and restoring gut microbial homeostasis.},
}

Animals
*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/antagonists & inhibitors
*Atherosclerosis/drug therapy/metabolism/pathology
*Inflammasomes/metabolism/antagonists & inhibitors
*Gastrointestinal Microbiome/drug effects
*Phenanthrenes/pharmacology/therapeutic use
Male
Mice, Inbred C57BL
Mice
Diet, High-Fat
*Anti-Inflammatory Agents/therapeutic use/pharmacology
*Quinones/therapeutic use/pharmacology
Salvia miltiorrhiza/chemistry
Humans
Furans

@article {pmid42486817,
year = {2026},
author = {Dong, M and Fang, Z and Zhang, Y and Wu, Y and Zheng, H and Liu, Y and Yang, Q and Kong, D and Chen, K and Wang, S},
title = {[Butyrate alleviates Clostridium difficile infection in high-fat diet-induced obese mice].},
journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University},
volume = {46},
number = {7},
pages = {1474-1486},
doi = {10.12122/j.issn.1673-4254.2026.07.02},
pmid = {42486817},
issn = {1673-4254},
support = {82500630//Natural Science Foundation for the Youth (NSFY) of China/ ; },
mesh = {Animals ; Mice ; Diet, High-Fat/adverse effects ; Clostridioides difficile ; *Obesity/complications ; *Butyrates/pharmacology ; Mice, Inbred C57BL ; Male ; *Clostridium Infections/drug therapy ; Gastrointestinal Microbiome ; Mice, Obese ; Humans ; Disease Models, Animal ; Zonula Occludens-1 Protein/metabolism ; },
abstract = {OBJECTIVES: To investigate the mechanism by which obesity exacerbates Clostridium difficile infection (CDI) and explore the value of gut microbiota metabolite butyrate as an alternative therapy.

METHODS: In mouse models of high-fat diet (HFD)-induced obesity and CDI and normal diet-fed mouse models of CDI, the effect of butyrate treatment on hepatic lipid deposition and liver function was assessed using Oil Red O staining and by measuring aspartate aminotransferase and alanine aminotransferase levels. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) of the mice were determined, and colonic injury was evaluated using HE staining. The expression levels of intestinal mucosal barrier proteins ZO-1 and occludin were detected by RT-PCR and immunohistochemistry, and the levels of C. difficile toxins A and B in mouse serum and feces were measured using RT-PCR and ELISA. The concentration of short-chain fatty acids (SCFAs) in mouse feces was determined using gas chromatography-mass spectrometry. In HCT116 cells induced by palmitic acid in the presence or absence of C. difficile, the effect of butyrate expression levels of ZO-1 and occludin were examined by immunofluorescence staining, and cell apoptosis was analyzed with flow cytometry.

RESULTS: Compared with normal diet-fed mice, the HFD-fed mice with CDI had a significantly higher mortality rate and exhibited severer colonic damage, intestinal barrier function impairment and liver injury with significantly reduced fecal SCFAs concentrations. Butyrate replacement therapy markedly alleviated CDI symptoms, improved intestinal barrier function, and reduced the levels of liver injury markers. Fecal microbiota transplantation produced similar effects to butyrate and obviously alleviated CDI symptoms and increased fecal SCFAs concentrations in the mouse models.

CONCLUSIONS: HFD significantly exacerbates the progression of CDI in mice, and butyrate shows the potential as an alternative therapy for improving obesity-associated CDI.},
}

Animals
Mice
Diet, High-Fat/adverse effects
Clostridioides difficile
*Obesity/complications
*Butyrates/pharmacology
Mice, Inbred C57BL
Male
*Clostridium Infections/drug therapy
Gastrointestinal Microbiome
Mice, Obese
Humans
Disease Models, Animal
Zonula Occludens-1 Protein/metabolism

@article {pmid42487704,
year = {2026},
author = {Liu, R and Wang, J},
title = {Gut microbiota dysbiosis in sepsis: mechanisms and the gut-organ axis with a focus on lung and brain interactions.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1797486},
pmid = {42487704},
issn = {1664-302X},
abstract = {Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, with its high mortality closely linked to complex pathophysiological processes. In recent years, the gut microbiota, as the largest human micro-ecosystem, has garnered increasing attention for its critical role in the onset, progression, and prognosis of sepsis. This narrative review summarizes recent research advances, with a particular focus on studies published over the past 3 years, while incorporating selected earlier studies to provide essential mechanistic background. It first delves into the pathophysiological mechanisms underlying sepsis-induced gut microbiota imbalance, highlighting key factors such as intestinal barrier disruption, immune-microbiota interaction disturbances, and alterations in microbial metabolites. Subsequently, the review comprehensively evaluates clinical diagnostic biomarker potentials and therapeutic strategies centered on gut microbiota modulation, including probiotics, prebiotics, fecal microbiota transplantation, and targeted interventions on microbial metabolites. Finally, current research challenges and future translational directions are discussed, aiming to provide novel theoretical foundations and strategic insights for precise prevention and treatment of sepsis. However, most microbiota-targeted therapeutic strategies remain at the preclinical or early clinical stage, and their efficacy and safety in sepsis require further validation.},
}

@article {pmid42487857,
year = {2026},
author = {Farooq, U and Sadiqa, A and Arshad Jarral, S},
title = {Pathophysiological and Therapeutic Association between Brain-Gut Axis and Irritable Bowel Syndrome: A Systematic Review.},
journal = {Pakistan journal of medical sciences},
volume = {42},
number = {7},
pages = {1869-1876},
pmid = {42487857},
issn = {1682-024X},
abstract = {OBJECTIVE: To identify the association among the gut, brain, and related microbiota, to reach the best-suited personalized management plan for Irritable Bowel Syndrome (IBS).

METHODOLOGY: A systematic review was conducted by reviewing studies across multiple Databases, i.e., Scopus, MEDLINE, PubMed, Web of Science, ScienceDirect (Elsevier), Cochrane Library, Embase, and Google Scholar. The timeframe of selected publications was from 2007 to 2025. The results were extracted from 49 selected manuscripts using PRISMA guidelines. The review discussed the pertinent link between the brain-gut axis and IBS, in relation to etiology, clinical features, and underlying pathophysiological mechanisms, and an optimal management plan that aligns with the new concept of personalized health care, alongside evidence-based medicine.

RESULTS: IBS is a multidimensional ailment concerning gut hypersensitivity, hyper-immunity, imbalanced gut flora, and excessive anxiety or derailed psychology, each presented with a particular feature and associated with related etiology. Conventional therapeutic management benefits from reducing fermentation through a suitable diet plan, antibiotics to regulate gut flora, and neuroregulators that augment signaling pathways between visceral (gut-related) and central (brain) nervous systems. Stress-reducing interventions helped to decline the nociception and symptomatic-anxiety bursts. Upcoming advanced techniques such as Fecal microbiota transplantation (FMT), psychedelic-assisted therapy, traditional Chinese medicine, and the use of neuromodulator devices express possibilities to cure.

CONCLUSION: IBS is a multisystem pathology triggered by gut dysbiosis, hyper-immune responses, visceral hypersensitivity, and stress-axis dysregulation. Thus, it is evident that a multimodal personalized management approach, including dietary, microbiome-targeted, pharmacological, and psychological therapies, is recommended for IBS, based on symptomology and etiology.},
}

@article {pmid42487937,
year = {2026},
author = {Jiang, Y and Qin, W and Wei, L and Liao, Y and Wei, G},
title = {Therapeutic effect of modified meridian-guided acupoint pressing on lumbar facet joint osteoarthritis: an integrated microbiomics and metabolomics analysis.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1862397},
pmid = {42487937},
issn = {2296-858X},
abstract = {PURPOSE: To investigate the therapeutic efficacy of Modified Meridian-Guided Acupoint Pressing (MMGAP) in lumbar facet joint osteoarthritis (LFJ OA) and to explore its underlying mechanisms through integrated microbiomics and metabolomics.

METHODS: Animal model study (urokinase-induced LFJ OA in SD rats) with MMGAP intervention, fecal microbiota transplantation (FMT), and mTORC1 inhibitor (rapamycin) validation. Histological, molecular, 16S rRNA sequencing, and UPLC-MS/MS metabolomic analyses were carried out to assess relevant outcomes.

RESULTS: MMGAP significantly reduced inflammatory cell infiltration in lumbar muscles/facet joints, markedly downregulated serum IL-1β and TNF-α (p < 0.05) as well as TRPV1 protein expression by >40% at the mRNA and protein levels. It reshaped gut microbiota (significantly elevated Observed Species, Shannon and Chao1 indices, p < 0.05; distinct β-diversity clustering vs model group) and serum metabolomic profiles, enriching the mTOR signaling pathway. FMT from MMGAP-treated rats recapitulated therapeutic effects, while rapamycin mimicked MMGAP's anti-inflammatory/analgesic actions.

CONCLUSIONS: MMGAP alleviates LFJ OA through gut microbiota reshaping, serum metabolomic reprogramming, and mTORC1 pathway inhibition. These preclinical findings lay preliminary experimental groundwork supporting the research potential of MMGAP as a non-invasive candidate intervention for degenerative joint diseases.},
}

@article {pmid42488001,
year = {2026},
author = {Wang, W and Xu, L and Leng, P and Jiang, M and Xing, X and Cao, M and Jing, F},
title = {"Envbiotics" -- a novel framework for microbiota-targeted therapeutic strategies in type 2 diabetes mellitus.},
journal = {Frontiers in endocrinology},
volume = {17},
number = {},
pages = {1878037},
pmid = {42488001},
issn = {1664-2392},
mesh = {Humans ; *Diabetes Mellitus, Type 2/microbiology/therapy ; *Prebiotics ; *Probiotics/therapeutic use ; *Gastrointestinal Microbiome/physiology ; Animals ; Fecal Microbiota Transplantation ; },
abstract = {Imbalance of the gut microbiota is an important trigger for insulin resistance in type 2 diabetes mellitus(T2DM). Microbiota-targeted therapies have gradually become an emerging research direction for treating T2DM. However, exogenous strain interventions (supplementing probiotics and fecal microbiota transplantation), endogenous optimization of the gut microbiota (supplementing prebiotics, synbiotics, and postbiotics), and phage therapy focus on "directly introducing microorganisms," "feeding microorganisms," or "directly utilizing microbial components." These approaches cannot cover active substances that target the host as the core and regulate the intestinal microenvironment in a non-nutritional manner, presenting conceptual limitations. In this context, this paper proposes the concept of "Envbiotics, " defined as substances that target the host as the core, optimize the intestinal microenvironment through their own or host metabolites, and directly or indirectly regulate the structure and function of the microbiota in a non-nutritional manner, thereby improving host metabolism and health. Typical evidence, including berberine, urolithin A, plant exosomes, and special targeted delivery technologies, is used to elucidate its mechanism of action. Envbiotics not only fill the gaps in the existing classification system but also provide novel insights for the development of new drugs targeting microbial intervention in T2DM.},
}

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

@article {pmid42488571,
year = {2026},
author = {Ripardo de Azevedo, OG and Leitão de Vasconcelos, PR and Soares Rosa, PN and Vieira Ciurleo, GC and Warren, CA and Oriá, RB},
title = {Immune-related mechanisms of fecal microbiota transplantation in the intestinal microenvironment as a potential intervention for autism spectrum disorder patients.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1775104},
pmid = {42488571},
issn = {1663-9812},
abstract = {Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by behavioral, cognitive, and motor impairments. There is increasing evidence linking ASD with an altered composition of the gut microbiota and chronic low-grade inflammation, suggesting a key role of the gut-brain axis (GBA) in the pathophysiological development of this condition. This mini review explores the molecular and immunological mechanisms underlying the associations between ASD and gut dysbiosis, with particular emphasis on the therapeutic potential of fecal microbiota transplantation (FMT). Dysbiosis can compromise the integrity of the intestinal barrier, increasing permeability and the translocation of pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharides (LPS), thereby releasing inflammatory cytokines, including IL-6 and TNF-α. These mediators activate the mucosal immune pathways, such as the NF-κB signaling and NLRP3 inflammasome, thereby contributing to neuroinflammation and elevating intestinal biomarker levels, such as S100B, RANTES, and calprotectin. Emerging evidence suggests that FMT may restore microbial diversity, promote the expansion of beneficial short-chain-fatty-acid-producing taxa, and reinforce intestinal tight junction proteins, thereby improving the integrity of the gut barrier. These effects may attenuate systemic inflammation, modulate central immune responses, regulate neurotransmitter levels, and improve gastrointestinal and behavioral outcomes in individuals with ASD. Despite these promising findings, current evidence remains limited by small sample sizes, methodological heterogeneity, and short follow-up periods. Hence, future research efforts should prioritize well-designed randomized controlled trials and the development of personalized microbial-based interventions to establish FMT as a safe and effective therapeutic strategy for ASD.},
}

@article {pmid42488628,
year = {2026},
author = {Tian, X and Qu, Z and Cao, Y and Wang, Y and Zhang, B},
title = {Gut microbiota and osteoarthritis: mechanisms and translation.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1873110},
pmid = {42488628},
issn = {1664-3224},
mesh = {Humans ; *Osteoarthritis/microbiology/immunology/metabolism/etiology ; *Gastrointestinal Microbiome/immunology ; Animals ; *Dysbiosis/immunology/microbiology ; },
abstract = {Osteoarthritis (OA) is increasingly recognised as a whole-joint disease driven by biomechanical stress, metabolic dysfunction, low-grade inflammation and immune dysregulation, yet effective disease-modifying treatments remain unavailable. Growing evidence suggests that gut microbiota dysbiosis may contribute to OA pathogenesis, giving rise to the concept of a functional and potentially targetable gut-joint axis. In this narrative review, we synthesise current evidence linking gut microbial alterations to OA and highlight the immunological mechanisms through which intestinal dysbiosis may influence joint degeneration. Human studies have identified OA-associated changes in gut microbial composition and microbial metabolites, whereas preclinical models, germ-free experiments and faecal microbiota transplantation studies provide mechanistic support for a contributory role of dysbiosis in cartilage damage, synovitis and subchondral bone remodelling. Gut dysbiosis can impair intestinal barrier integrity, facilitate systemic exposure to microbial products such as lipopolysaccharide, disturb short-chain fatty acid, bile acid and tryptophan-derived metabolite profiles, and alter enteroendocrine and immune signalling. These processes may activate Toll-like receptor, NF-κB, NLRP3 inflammasome, aryl hydrocarbon receptor and JAK/STAT pathways, thereby reshaping macrophage polarisation, Th17/Treg balance, mucosal IgA responses, innate lymphoid cell and γδT-cell activity, immunosenescence and low-grade systemic inflammation. Through these interconnected immune-metabolic pathways, the gut microbiota may influence cartilage catabolism, synovial inflammation, subchondral bone remodelling and inflammation-related pain. Microbiome-derived taxa, metabolites and host-microbe immune signatures might support risk assessment, endotype stratification and therapeutic monitoring; however, causality in humans remains incompletely established, and current findings are limited by heterogeneity in OA phenotypes, microbiome methods, host metabolic status and clinical endpoints. Microbiota-targeted strategies remain promising adjuncts rather than established disease-modifying treatments. Future studies should integrate standardised microbiome profiling, immune phenotyping, multi-omics approaches, longitudinal cohorts and rigorously designed clinical trials to translate gut-joint axis biology into microbiome-informed precision care for OA.},
}

Humans
*Osteoarthritis/microbiology/immunology/metabolism/etiology
*Gastrointestinal Microbiome/immunology
Animals
*Dysbiosis/immunology/microbiology

@article {pmid42490818,
year = {2026},
author = {Lin, Y and Zheng, J and Hu, D and Ying, Y and Zhu, Y and Chen, Z},
title = {Modulating the gut ecosystem dietary, probiotic, and novel interventions for bone health in postmenopausal women.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1814866},
doi = {10.3389/fimmu.2026.1814866},
pmid = {42490818},
issn = {1664-3224},
mesh = {Humans ; Female ; *Probiotics/therapeutic use ; *Osteoporosis, Postmenopausal/metabolism/microbiology/prevention & control/therapy ; *Gastrointestinal Microbiome ; Animals ; *Bone and Bones/metabolism ; *Postmenopause ; Bone Density ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; Diet ; },
abstract = {Postmenopausal osteoporosis (PMO) is a metabolic bone disorder caused by estrogen deficiency, posing significant risks to the skeletal health and quality of life of middle-aged and elderly women. In recent years, the gut microbiota (GM) has emerged as a novel regulatory target in bone metabolism, attracting increasing research interest. Probiotics may modulate bone metabolism by directly introducing beneficial microorganisms (e.g., Lactobacillus, Bifidobacterium) to improve gut microbiota composition. The gut microbiota may influence the onset and progression of osteoporosis by modulating immune-inflammatory responses, endocrine regulation, nutrient absorption, and the production of metabolic byproducts. This review systematically summarizes the mechanisms by which gut microbiota affects postmenopausal osteoporosis, including the neuroendocrine brain-gut-bone axis, immune regulation, metabolic products such as short-chain fatty acids, intestinal barrier function, and their correlations with bone mineral density. Integrating the latest clinical and animal model studies, we further explore gut microbiota-based intervention strategies, such as probiotics, prebiotics, fecal microbiota transplantation, and dietary modulation. These insights may provide a theoretical foundation and practical guidance for the prevention and treatment of postmenopausal osteoporosis, highlighting the promising role of gut microbiota-targeted therapies in improving bone health in postmenopausal women.},
}

Humans
Female
*Probiotics/therapeutic use
*Osteoporosis, Postmenopausal/metabolism/microbiology/prevention & control/therapy
*Gastrointestinal Microbiome
Animals
*Bone and Bones/metabolism
*Postmenopause
Bone Density
Fecal Microbiota Transplantation
Prebiotics/administration & dosage
Diet

@article {pmid42490850,
year = {2026},
author = {Zheng, J and Huang, P and Li, L and Huang, S and Chen, R and Zhang, S},
title = {Assessing the robustness of clinical trials regarding novel therapies in inflammatory bowel disease.},
journal = {Gastroenterology report},
volume = {14},
number = {},
pages = {goag051},
doi = {10.1093/gastro/goag051},
pmid = {42490850},
issn = {2052-0034},
abstract = {BACKGROUND: Increasing randomized clinical trials evaluating novel therapies for inflammatory bowel disease necessitated the scrutiny of statistical robustness. This study aimed to quantify their fragility and identify factors associated with robustness.

METHODS: This cross-sectional analysis included randomized clinical trials studying biologics, small-molecule inhibitors, fecal microbiota transplantation (FMT), and stem cell therapy (SCT), and then the calculated fragility index (FI) and continuous fragility index (CFI) for binary and continuous outcomes, respectively. Factors affecting robustness were analysed through correlation analysis and multiple linear regression.

RESULTS: Among 129 trials from 53 studies, the median FI and CFI were 6 and 14.8, respectively. The FI varied significantly by the treatment type, trial phase, outcome type, and P values. The FI was positively correlated with the sample size (ρ = 0.734, P < 0.001), discontinuations (ρ = 0.479, P < 0.001), publication year (ρ = 0.253, P = 0.017), impact factor (ρ = 0.368, P < 0.001), and events percentage (ρ = 0.299, P = 0.005). The CFI was influenced by the outcome type and was strongly correlated with the sample size. After adjustment for other characteristics, biologics/small-molecule drugs displayed enhanced robustness relative to FMT/SCT (correlation coefficient B with the natural logarithm of FI: B = 0.283, P = 0.011). The primary or co-primary outcome exhibited greater robustness than did the other outcomes (FI: B = 0.288, P = 0.013; CFI: B = 0.459, P = 0.024). The sample size was positively correlated with both the FI (B = 0.001, P = 0.021) and the CFI (B = 0.001, P = 0.019), whereas discontinuation did not significantly affect the robustness.

CONCLUSION: Randomized clinical trials of novel inflammatory bowel disease therapies exhibit varying robustness and are influenced by multiple study characteristics. Trials of biologics or small molecules, those with positive primary outcomes, and larger studies demonstrated greater robustness, supporting that robustness should be considered in future research when interpreting the efficacy.},
}

@article {pmid42490858,
year = {2026},
author = {Lai, Y and Zhang, M and Lang, D and Tao, E},
title = {Microbial metabolites at the nexus of gut-brain communication and neurodevelopmental disorders.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1836981},
doi = {10.3389/fnut.2026.1836981},
pmid = {42490858},
issn = {2296-861X},
abstract = {The microbiota-gut-brain axis (MGBA) has emerged as a critical regulator of neurodevelopment, with microbial metabolites serving as key signaling molecules that bridge the intestinal ecosystem and the central nervous system. This review gathers current evidence that connects disruptions in microbial metabolites to the pathogenesis of neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Our comprehensive overview discusses major neuroactive metabolite classes-short-chain fatty acids (SCFAs), tryptophan derivatives, bile acids, and phenolic compounds-and their established roles functions in affecting neuroinflammation, epigenetic programming, synaptic function, and blood-brain barrier integrity. Converging evidence from human multi-omics studies and preclinical models frequently reported patterns of metabolic dysregulation in NDDs, including reduced SCFA production, altered kynurenine pathway metabolites, and accumulation of neurotoxic compounds such as para-cresol (p-cresol). However, substantial heterogeneity exists across studies, and causal evidence in humans remains predominantly associative. We further examine the critical early-life window during which the metabolite-producing microbiome is shaped by maternal factors, nutrition, and environmental exposures, with lasting consequences for neurodevelopmental trajectories. Finally, we discuss new intervention strategies such as probiotics, dietary substrates, fecal microbiota transplantation, and metabolite-based therapies, and propose a plan to transition from associative findings to causal, personalized approaches using microbial metabolites as biomarkers and therapeutic targets in child neurodevelopment.},
}

@article {pmid42490889,
year = {2026},
author = {And Alternative Medicine, EC},
title = {RETRACTION: Efficacy of Faecal Microbiota Transplantation for the Treatment of Autism in Children: Meta-Analysis of Randomised Controlled Trials.},
journal = {Evidence-based complementary and alternative medicine : eCAM},
volume = {2026},
number = {},
pages = {9826719},
doi = {10.1155/ecam/9826719},
pmid = {42490889},
issn = {1741-427X},
abstract = {[This retracts the article DOI: 10.1155/2023/5993628.].},
}

@article {pmid42490947,
year = {2026},
author = {Kumar, V and Chaudhary, A and Gautam, M and Verma, P and Singh, M},
title = {Microbiome and cancer: mechanistic insights, diagnostic potential, and therapeutic strategies.},
journal = {Frontiers in cell and developmental biology},
volume = {14},
number = {},
pages = {1844436},
doi = {10.3389/fcell.2026.1844436},
pmid = {42490947},
issn = {2296-634X},
abstract = {The human microbiome is now recognized as an active and dynamic participant in cancer biology rather than a passive bystander. Increasing evidence demonstrates that microbial dysbiosis contributes to tumor initiation and progression through chronic inflammation, genotoxic toxin production, metabolic reprogramming, immune modulation, and direct reshaping of the tumor microenvironment. Specific microbial factors including colibactin, Bacteroides fragilis toxin, CagA, and Fusobacterium adhesins intersect with canonical oncogenic pathways. Linking microbial activity to genomic instability and immune evasion. Microbial metabolites such as secondary bile acids, lipopolysaccharide, hydrogen sulfide, and short-chain fatty acids further regulate epithelial integrity, epigenetic remodeling, and immune cell dynamics in a context-dependent manner. Beyond tumorigenesis, the microbiome critically determines therapeutic response. Microbial communities influence chemotherapy and radiotherapy outcomes and shape immune checkpoint blockade efficacy through immune priming, antigen mimicry, and microbiome-metabolite-immune interactions that govern treatment responsiveness. Emerging preclinical studies and early clinical investigations suggest that microbiome modulation, including fecal microbiota transplantation (FMT), may help restore immunotherapy sensitivity in selected patients; however, larger controlled trials are required to establish efficacy, safety, and long-term clinical benefits. This review integrates mechanistic, preclinical, and clinical evidence across microbiome-driven carcinogenesis, tumor microenvironment remodeling, drug metabolism, and biomarker development. Advances in circulating microbial DNA profiling and machine learning-based diagnostics further position the microbiome as both a mechanistic driver and a translational target in precision oncology. We also discuss key challenges, including interindividual variability, standardization of methodologies, and the need for personalized therapeutic strategies. Collectively, understanding and harnessing microbiome-cancer interactions hold significant promise for improving cancer diagnosis, treatment, and patient outcomes.},
}

@article {pmid42490975,
year = {2026},
author = {Zhao, Y and Xie, X},
title = {The role of the gut microbiota in the development of rheumatic diseases: a focus on fibromyalgia.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1845199},
doi = {10.3389/fimmu.2026.1845199},
pmid = {42490975},
issn = {1664-3224},
mesh = {Humans ; *Fibromyalgia/microbiology/etiology/therapy/metabolism/immunology ; *Gastrointestinal Microbiome/immunology ; Animals ; Dysbiosis ; Probiotics/therapeutic use ; *Rheumatic Diseases/microbiology ; },
abstract = {Fibromyalgia (FM) is a chronic widespread pain syndrome affecting 2%-4% of the population whose pathophysiology remains incompletely understood. Growing evidence implicates gut microbiota dysbiosis as a contributing factor, acting through immune, neuroendocrine, and metabolic pathways that may reinforce central sensitization. Consistent findings of reduced microbial diversity and altered metabolite profiles-including short-chain fatty acids, bile acids, and tryptophan derivatives-suggest mechanistic links between the gut and FM symptoms. Microbiota-targeted interventions such as probiotics, dietary modification, and fecal microbiota transplantation have shown preliminary benefits, though evidence remains limited by small sample sizes and methodological heterogeneity. This review synthesizes current knowledge on the role of the gut microbiota in FM within the broader context of rheumatic diseases and discusses future research directions.},
}

Humans
*Fibromyalgia/microbiology/etiology/therapy/metabolism/immunology
*Gastrointestinal Microbiome/immunology
Animals
Dysbiosis
Probiotics/therapeutic use
*Rheumatic Diseases/microbiology

@article {pmid42490980,
year = {2026},
author = {Zhang, L and Ni, L and Pan, L and Cao, R and Han, L and Long, L},
title = {Psychological stress and gut microbiota regulation of osteoarthritis progression: mechanisms and therapeutic strategies.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1851267},
doi = {10.3389/fmicb.2026.1851267},
pmid = {42490980},
issn = {1664-302X},
abstract = {Psychological stress is increasingly recognized as an important contributor to osteoarthritis (OA) progression, yet the underlying mechanisms remain incompletely understood. This review examines the gut microbiota as a potential mediator linking psychological stress to OA progression. Emerging evidence suggests that the gut microbiota is an integral component of the brain-gut-joint axis. Psychological stress may induce microbial dysbiosis, which can in turn contribute to immune dysregulation, metabolic alterations, intestinal barrier dysfunction, and sensitization of pain pathways. Through interconnected local and systemic effects, these changes may aggravate structural joint damage and worsen symptom burden in OA. We synthesize epidemiological, preclinical, and emerging clinical evidence linking psychological stress to OA, and integrate key modulators-including diet, host genetics, medications, and lifestyle factors-to provide a more comprehensive mechanistic framework. We also discuss potential interventions targeting this axis, including probiotics, prebiotics, dietary strategies, fecal microbiota transplantation, and psychological interventions, which may help slow OA progression and complement conventional OA management. Collectively, these insights provide a rationale for therapeutic approaches targeting the stress-microbiome-osteoarthritis axis, with the potential to improve clinical outcomes in patients with OA.},
}

@article {pmid42491661,
year = {2026},
author = {Chang, K and He, D and Dong, J and Zhang, Y and Deng, S and Zhao, M and Jin, J and Ji, X and Yin, H and Zhao, L},
title = {Microbiota-Targeted Chitooligosaccharides Intervention Restores Glucose Homeostasis After Islet Cell Transplantation in Rapamycin-Treated Mice.},
journal = {Food science & nutrition},
volume = {14},
number = {7},
pages = {e72122},
doi = {10.1002/fsn3.72122},
pmid = {42491661},
issn = {2048-7177},
abstract = {Islet cell transplantation (ICT) is an effective treatment for diabetes mellitus, but postoperative islet function recovery and inflammation are closely linked to immunosuppressants. Using multi-omics and fecal microbiota transplantation (FMT) in human microbiota-associated (HMA) mice, this study explored rapamycin-induced gut dysbiosis and its impacts on islet function and inflammation post-ICT. ICT significantly altered the gut microbiota of type 2 diabetes mellitus (T2DM) patients, and FMT from these patients to antibiotic-treated mice recapitulated metabolic disorders in the mice. These disorders included hyperglycemia, hepatic and pancreatic injury, and impaired intestinal barrier. Rapamycin decreased beneficial bacteria (Akkermansia, Faecalibacterium) and enriched Desulfovibrio in HMA-T2DM mice. Targeted microbial modulation by chitooligosaccharides (COS) ameliorated rapamycin-induced deficits in insulin and C-peptide secretion, as well as elevated glycated hemoglobin levels. COS also significantly reduced serum inflammatory markers IP-10 and MCP-1, while upregulating colonic barrier proteins (Muc2, Occludin) in HMA-T2DM-ICT mice. COS additionally mitigated postoperative hyperglycemia via the PI3K/AKT/GSK3β/FOXO1 signaling pathway. This study identified COS as a microbiota-targeted adjunctive strategy to improve metabolic recovery and islet function under post-transplant immunosuppression.},
}

@article {pmid42479871,
year = {2026},
author = {Gong, EJ and Bang, CS and Lee, JJ and Baik, GH},
title = {Post-Marketing Safety Signals of Microbiota-Based Live Biotherapeutic Products for Recurrent Clostridioides difficile Infection: A FAERS Pharmacovigilance Study.},
journal = {The American journal of gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.14309/ajg.0000000000004133},
pmid = {42479871},
issn = {1572-0241},
abstract = {BACKGROUND: REBYOTA and VOWST are the first FDA-approved live biotherapeutic products (LBPs) for recurrent Clostridioides difficile infection (rCDI). Prior FDA safety alerts (2019-2020) regarding invasive infections from investigational fecal microbiota transplantation underscore the need for post-marketing surveillance of these novel products.

AIMS: To characterize the real-world safety profiles of REBYOTA and VOWST using the FDA Adverse Event Reporting System (FAERS) and compare them against established CDI therapeutics.

METHODS: We performed disproportionality analysis of FAERS data (Q1;2020-Q4;2025). REBYOTA and VOWST were identified as primary suspect drugs using BLA numbers and drug name matching. Comparators included fidaxomicin, bezlotoxumab, and vancomycin (CDI-filtered). Four methods were applied: reporting odds ratio (ROR), proportional reporting ratio, information component, and empirical Bayes geometric mean. Signals required ≥2 methods agreement.

RESULTS: We identified 231 REBYOTA and 813 VOWST primary suspect reports, yielding 18 and 54 disproportionality signals, respectively. Both products' signals were consistent with known gastrointestinal adverse events. No signals were detected for bacteremia, septic shock, or anaphylaxis. Death was reported at lower-than-expected frequency for VOWST (ROR 0.29; 95% CI 0.15-0.53). A VOWST-specific UTI cluster (Klebsiella UTI ROR 405.73; Pseudomonal UTI ROR 168.54) was identified; head-to-head comparison showed no significant UTI difference versus REBYOTA (ROR 1.39, NS), suggesting stimulated reporting bias rather than a biological signal. Route-dependent adverse event profiles differed between oral VOWST and rectal REBYOTA.

CONCLUSIONS: FDA-approved LBPs demonstrate reassuring post-marketing safety profiles without transmitted infection signals. The extreme VOWST UTI signal is likely attributable to FDA-mandated expedited reporting obligations rather than a causal drug effect.},
}

@article {pmid42480123,
year = {2026},
author = {Mu, Z and Ren, P and Wang, Y and Su, X and Liu, X and Chaoke, B and Bao, W and Qin, S and Gao, R and Gong, Z and Liu, B},
title = {Gut microbiota derived Bifidobacterium pseudolongum alleviates endometritis caused by dysbiosis and Escherichia coli infection.},
journal = {Microbiological research},
volume = {312},
number = {},
pages = {128642},
doi = {10.1016/j.micres.2026.128642},
pmid = {42480123},
issn = {1618-0623},
abstract = {Endometritis is a prevalent uterine inflammatory disease that significantly compromises fertility; however, the host-microbial mechanisms governing disease susceptibility remain poorly defined. Although the gut microbiota is increasingly recognized as a central regulator of systemic and extraintestinal immunity, its role in uterine inflammation has received little attention. Here, we investigated whether gut microbiota dysbiosis modulates susceptibility to endometritis and sought to identify the microbial mediators underlying this relationship. Antibiotic-induced dysbiosis markedly exacerbated uterine inflammation and tissue injury in mice, whereas fecal microbiota transplantation (FMT) re-established microbial homeostasis and substantially ameliorated uterine pathology. 16S rRNA sequencing identified Bifidobacterium pseudolongum as a commensal species depleted during dysbiosis and restored following FMT. Monocolonization with B. pseudolongum conferred protection against dysbiosis-associated uterine inflammation, evidenced by diminished IL-1β, TNF-αand IL-10 production, reduced HMGB1 and HABP2 levels, restored epithelial tight junction protein expression-including ZO-1, Claudin-3, and Occludin, and attenuated neutrophil and macrophage infiltration. Beyond the dysbiosis model, B. pseudolongum demonstrated both prophylactic and therapeutic efficacy in murine models of Escherichia coli- and LPS-induced endometritis, suppressing inflammatory responses, limiting tissue damage, preserving epithelial barrier integrity, and reducing immune cell infiltration. In vitro assays showed that culture supernatants of B. pseudolongum inhibited E. coli growth under cell-free conditions, indicating a potential antimicrobial activity in vitro. Taken together, these findings support a gut-uterus immunological axis in which B. pseudolongum attenuates infection-driven uterine inflammation through the coordinated modulation of immune responses, epithelial barrier maintenance, and antimicrobial defense. Our study positions B. pseudolongum as a compelling microbiota-based candidate for the prevention and treatment of endometritis.},
}

@article {pmid42480622,
year = {2026},
author = {Ren, X and Ma, J and Zhao, Y and Yang, M and Li, Y and Song, W and Wang, N},
title = {Microbiome Remodeling During Aging: Integrative Multi-Omics and Spatiotemporal Perspectives on Immune and Metabolic Regulation.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103269},
doi = {10.1016/j.arr.2026.103269},
pmid = {42480622},
issn = {1872-9649},
abstract = {Changes in the gut microbiota occur throughout the human lifespan, and maintaining microbial homeostasis plays a critical role in promoting healthy aging. In recent years, substantial progress has been made in elucidating the mechanistic links between aging and microbiota remodeling, highlighting the central role of microbiota-host interactions in regulating immune responses and maintaining metabolic homeostasis. These findings provide new potential targets for the precision prevention and treatment of age-related diseases. This review systematically summarizes the patterns of gut microbiota succession across different stages of the human life cycle, including infancy, adolescence, adulthood, and old age, as well as the mechanisms through which the microbiota regulates immune and metabolic functions. Furthermore, the role of the gut microbiota as a key mediator linking aging with an increased risk of chronic inflammation, cardiovascular disease, cognitive impairment, neurodegenerative disorders, and cancer was explored. In addition, this review evaluates the therapeutic potential of microbiota-targeted interventions, such as dietary modification, probiotic and prebiotic supplementation, fecal microbiota transplantation (FMT), and lifestyle interventions-in maintaining microbiome homeostasis and mitigating age-related diseases. The feasibility of personalized microbiota-based intervention strategies is also discussed. Finally, we highlight the current challenges and limitations in this field and outline future research directions. In particular, integrating multi-omics approaches with metagenomic sequencing, including emerging spatial and spatiotemporal multi-omics technologies, is crucial for advancing our understanding of the complex interactions within the gut microbiome. These insights provide a theoretical framework for optimizing anti-aging therapeutic strategies and promoting healthy lifespan extension.},
}

@article {pmid42480795,
year = {2026},
author = {Yu, C and Yu, J and Yao, X and Wang, K and Wang, S and He, W and Zhang, Y and Wang, P},
title = {Mertk-dependent immune regulation is required for the therapeutic effects of fecal microbiota transplantation in a mouse model of constipation-predominant irritable bowel syndrome.},
journal = {Life sciences},
volume = {},
number = {},
pages = {124595},
doi = {10.1016/j.lfs.2026.124595},
pmid = {42480795},
issn = {1879-0631},
abstract = {BACKGROUND: Constipation-predominant irritable bowel syndrome (IBS-C) is a disorder of brain-gut axis dysfunction closely associated with gut microbiota dysbiosis and disruption of mucosal immune homeostasis. Fecal microbiota transplantation (FMT) has been shown to alleviate IBS symptoms; however, its underlying molecular mechanisms remain incompletely understood. MER proto-oncogene tyrosine kinase (MERTK), a member of the receptor tyrosine kinase family, plays an important role in macrophage polarization-related regulation and inflammation resolution.

OBJECTIVE: To investigate the role of Mertk-mediated immune regulation in FMT-induced improvement of IBS-C and its underlying mechanisms.

METHODS: IBS-C was induced in wild-type(WT) and Mertk conditional knockout(cKO) mice (Mertk[flox/flox]Lyz2[Cre/+]) by ice-water gavage combined with tail-clamping stress, followed by FMT treatment. Defecation, fecal water content, intestinal transit, and visceral sensitivity were assessed. Colonic histopathology, macrophage polarization-related markers, inflammatory cytokines, tight junction proteins, AKT-GSK3β signaling, and gut microbiota composition were examined by HE staining, immunohistochemistry, qPCR, Western blotting, and 16S rRNA sequencing.

RESULTS: In WT IBS-C mice, FMT improved constipation-like symptoms, intestinal transit, and visceral hypersensitivity, reduced colonic inflammation, restored Occludin and Claudin-1 expression, decreased CD86 and IL-1β, increased CD206 and IL-10, and activated AKT-GSK3β signaling. These beneficial effects were markedly attenuated in Mertk-deficient mice. However, FMT similarly remodeled gut microbiota composition in both WT and Mertk-deficient mice.

CONCLUSION: FMT alleviates IBS-C partly through Mertk-dependent immune regulation and AKT-GSK3β activation. Gut microbiota remodeling alone is insufficient for full therapeutic efficacy in the absence of intact host Mertk signaling.},
}

@article {pmid42482070,
year = {2026},
author = {Zachariassen, LF and Mortensen, FUF and Mentzel, CMJ and Jiang, PP and Lopez, PA and Krych, L and Canibe, N and Kirk, RK and Vegge, A and Rasmussen, MA and Stokholm, J and Hansen, CHF},
title = {Cesarean section-induced changes in the gut microbiota facilitate metabolic disease in high-fat diet-induced obese mice.},
journal = {Microbiome},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40168-026-02468-9},
pmid = {42482070},
issn = {2049-2618},
abstract = {BACKGROUND: The global rate of cesarean section (CS) births is increasing. Growing evidence suggests that CS birth may alter the gut microbiota (i.e., dysbiosis) and increase the risk of immune and metabolic disorders, although confounding factors make causality difficult to establish. The studies presented here aimed to investigate the causal relationship between CS-induced gut dysbiosis and obesity in a diet-induced obese mouse model and explore potential microbiota-targeted therapies.

RESULTS: In the first study, male C57BL/6 mice were delivered via CS or vaginally (VD) and fed a high- or low-fat diet (HFD, LFD) for 12 weeks. In the second study, male germ-free BALB/c mice were transplanted with fecal microbiota from 1-month-old infants born by CS or VD and fed a HFD or HFD + human milk oligosaccharides (HMOs) for 16 weeks. CS in mice induced only minor differences in weight gain and had no effect on other metabolic endpoints, likely because there was no difference in the gut microbiota between the CS and VD mice. In contrast, mice colonized with the human CS microbiota weighed significantly more and developed greater insulin resistance than mice colonized with the VD microbiota. These phenotypic changes were accompanied by alterations in serum cytokines, adipokines and metabolic hormones as well as differential gene expression across multiple metabolic tissues. Notably, these manifestations were partially ameliorated by HMO supplementation and by administration of Bacteroides fragilis, a taxon depleted in the CS donor microbiota, which directly reduced circulating FGF-21 levels, implicating this bacterium in host metabolic regulation.

CONCLUSIONS: CS-induced gut dysbiosis can increase the risk of developing obesity and insulin resistance, but without dysbiosis, the metabolic effects of CS birth in isolation are minimal, suggesting that promising therapeutic targets may be identified in the gut microbiome. Video Abstract.},
}

@article {pmid42482568,
year = {2026},
author = {Gao, T and Liu, X and Mi, W and Shi, L and Wang, X and Zhu, D and Geng, F and Fu, Y and Yang, Y and Li, X and Zheng, M and Zhu, K and Wen, K and Yang, Y and Zheng, Y and Chen, S and Sun, J and Zhou, X and Wang, Y and Vitiello, MV and Wang, Z and Bao, Y and Lu, L},
title = {Fecal microbiota transplantation-based treatment protocol for chronic insomnia disorder: A randomized, double-blind, placebo-controlled trial.},
journal = {Journal of internal medicine},
volume = {},
number = {},
pages = {},
doi = {10.1111/joim.70137},
pmid = {42482568},
issn = {1365-2796},
support = {2021ZD0200800//Brain Science and Brain-like Intelligence TechnologyNational Science and Technology Major Project/ ; 82288101//National Natural Science Foundation of China/ ; },
abstract = {OBJECTIVE: Chronic insomnia disorder is common and burdensome, and current treatments remain limited. We conducted a multicenter, randomized, double-blind, placebo-controlled trial to determine whether a fecal microbiota transplantation (FMT)-based treatment protocol improves sleep outcomes in adults with chronic insomnia disorder.

METHODS: Participants were randomly assigned 1:1 to receive short-course antibiotic pretreatment followed by donor microbiota capsules (n = 40) or placebo capsules without antibiotic pretreatment (n = 40). Within each group, participants were further randomized to receive synbiotic supplementation or matched placebo for prespecified exploratory subgroup analyses. The primary outcome was polysomnography-measured sleep efficiency (SE) at 1 month after treatment. Secondary outcomes included other polysomnographic parameters, patient-reported sleep outcomes, and safety; microbiota analyses were exploratory.

RESULTS: Compared with placebo, the FMT-based treatment protocol improved SE (adjusted between-group difference, 13.9 percentage points; 95% CI 7.29-20.41; p = 0.003) and reduced wake after sleep onset. Synbiotic assignment did not suggest meaningful differences in SE. Insomnia Severity Index and Pittsburgh Sleep Quality Index scores showed sustained improvement from 2 to 6 months. Treatment was well tolerated, with mild, self-limited adverse events and no serious adverse events. The intervention increased microbial richness and diversity and altered community structure; responders and non-responders showed similar posttreatment β-diversity change but differed in baseline microbiota composition.

CONCLUSION: In adults with chronic insomnia disorder, an FMT-based treatment protocol incorporating antibiotic pretreatment improved objective sleep continuity and sustained subjective insomnia outcomes. Baseline microbial composition may contribute to treatment heterogeneity and merits further investigation.},
}

@article {pmid42482939,
year = {2026},
author = {Zhao, F and Xiao, R and Li, X and Xin, Q and Chen, X and Zhou, D and Liu, W and Zhang, J and Lu, W and Jiang, C and Zhang, G},
title = {Modulation of gut microbiota and intestinal barrier by lotus seed, jujube, and longan aril in senna leaf-induced diarrhea in mice.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1796355},
pmid = {42482939},
issn = {1664-302X},
abstract = {OBJECTIVE: This study aimed to investigate the regulatory effects of lotus seed, jujube, and longan aril on the gut microbiota structure and barrier function in a senna leaf-induced diarrhea mouse model.

METHODS: Diarrhea was induced in ICR mice using senna leaf extract. Mice received aqueous extracts of lotus seed, jujube, or longan aril for treatment. Intestinal motility was assessed through fecal consistency scoring and the charcoal propulsion test. Colon tissues were collected for histopathological examination using H&E staining, as well as immunohistochemical and Western blot analyses of aquaporin 3 (AQP3) and sodium-hydrogen exchanger 8 (NHE8). Gut microbiota composition was analyzed via 16S rRNA sequencing.

RESULTS: All three herbal interventions significantly reduced the loose stool rate and diarrhea index (p < 0.05), inhibiting small intestinal hypermotility. Histological analysis revealed an increase in goblet cell numbers and improved crypt architecture in the colon. Immunohistochemical evaluation indicated downregulation of AQP3 and upregulation of NHE8 expression, which was confirmed by Western blot analysis. 16S rRNA sequencing demonstrated that all treatments restored α-diversity (Shannon index, p < 0.05). β-diversity analysis revealed that longan aril induced a more extensive reshaping of gut microbial community structure compared to lotus seed and jujube, which exhibited a "phased" restoration. The relative abundance of potential pathogens (e.g., Akkermansia muciniphila, Citrobacter spp.) significantly decreased, while beneficial short-chain fatty acid-producing bacteria (e.g., Blautia coccoides, Faecalibaculum rodentium, Alloprevotella rava) were enriched. Unique protective taxa, such as nitrogen-fixing Azospirillum and antioxidant Deinococcus, emerged in specific treatment groups.

CONCLUSION: Lotus seed, jujube, and longan aril synergistically alleviated diarrhea via multiple pathways, including modulation of gut microbiota structure, repair of barrier function, balance of water-electrolyte metabolism, and inhibition of intestinal hypermotility. This study provides a scientific foundation for the clinical application of medicinal and edible homology substances, as well as the development of microecological agents.},
}

@article {pmid42483733,
year = {2026},
author = {Pyrsopoulos, NT and Gunn, N and Jalal, PK and Catinis, GE},
title = {Reducing the Risk of Overt Hepatic Encephalopathy Recurrence: A Narrative Review.},
journal = {Journal of clinical and translational hepatology},
volume = {14},
number = {6},
pages = {674-686},
pmid = {42483733},
issn = {2310-8819},
abstract = {Hepatic encephalopathy (HE) is a neurologic complication of advanced liver disease (e.g., cirrhosis) resulting in impaired functioning and reduced quality of life. This condition is associated with a substantial burden for patients and their caregivers and carries a poor prognosis and increased risk of hospitalization and mortality. This narrative review discusses the burden of HE, precipitating risk factors, and clinical considerations for reducing the risk of overt HE (OHE) recurrence in adults with cirrhosis. Key precipitating factors include certain medications, constipation, dehydration, uncontrolled diabetes mellitus, electrolyte imbalances, gastrointestinal bleeding, infection, and sarcopenia, among others. Identification and treatment of precipitating factors are critical steps in the management of HE. Components of ongoing care include patient and caregiver education, nutritional supplementation and sleep management, pharmacotherapy, and nonpharmacologic interventions (e.g., spontaneous portosystemic shunt embolization and liver transplantation in appropriate patients). Clinical guidelines recommend lactulose therapy as secondary prophylaxis after an initial episode of OHE. Rifaximin is recommended as add-on therapy to lactulose when an additional OHE episode occurs. Polyethylene glycol has been investigated as an alternative to lactulose in patients with acute HE and in those with chronic HE and a poor response to lactulose. Oral L-ornithine-L-aspartate may reduce the risk of OHE recurrence in patients with cirrhosis. Investigational agents include nitazoxanide, fecal microbiota transplantation, and the use of artificial intelligence, app-based technology, and wearable devices to facilitate acute and prophylactic management of HE.},
}

@article {pmid42484159,
year = {2026},
author = {Guaraná, JB and Freitas, SH and Salem, JB and Silva, JM and Silva, FVD and Lanchotte, CF and Meirelles, FV and Galvão, FHF},
title = {Qualitative assessment of anal function in swine model for research in colorectal surgery: development of the swine anal function assessment table.},
journal = {Acta cirurgica brasileira},
volume = {41},
number = {},
pages = {e413726},
doi = {10.1590/acb413726},
pmid = {42484159},
issn = {1678-2674},
mesh = {Animals ; Male ; *Anal Canal/physiology/surgery/transplantation ; Swine ; Reproducibility of Results ; Models, Animal ; Colorectal Surgical Procedures ; *Rectum/surgery ; Disease Models, Animal ; },
abstract = {PURPOSE: The porcine model is widely used in preclinical studies of anorectal function due to its anatomical and physiological similarity to humans. However, appropriate behavioral and functional evaluation methods of anorectal segment are still lacking.

METHODS: This study introduces the swine anal function assessment table (SAFAT), a standardized qualitative tool developed to evaluate anorectal function. Six male Landrace × Large White pigs underwent evaluation following anorectal transplantation over up to one year.

RESULTS: The functional parameters assessed included cleanliness, fecal distribution, stool consistency, anal tone, anal skin sensitivity, anal reflexes, and other ones. Each indicator was rated using semi-quantitative scales based on behavioral observations.

CONCLUSION: SAFAT was effective for behavioral and functional evaluation after anorectal transplantation and may improve the reproducibility and reliability of functional evaluations in swine models of major anorectal surgeries, supporting translational research in colorectal treatments.},
}

Animals
Male
*Anal Canal/physiology/surgery/transplantation
Swine
Reproducibility of Results
Models, Animal
Colorectal Surgical Procedures
*Rectum/surgery
Disease Models, Animal

@article {pmid42476997,
year = {2026},
author = {Guan, YX and Wang, L and Kong, LX and Sun, YY and Zhou, JA and Wang, XL and Ma, YJ and Guo, LP and Song, TR and Zhu, L and Wang, SJ and Huang, YH and Tao, RL and Shang, WJ and Guo, WZ and Wang, H and Yang, JY and Zhong, L and Chen, G and Zhao, J and Liu, NN},
title = {Longitudinal multi-omics analysis identify multi-kingdom microbiome-host interaction dynamics and diagnostic biomarkers of postoperative infection after kidney transplantation.},
journal = {NPJ biofilms and microbiomes},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41522-026-01099-0},
pmid = {42476997},
issn = {2055-5008},
support = {2022YFC2304701//MOST Key R&D Program of China/ ; 2022YFC2304703//MOST Key R&D Program of China/ ; 32270202//the Natural Science Foundation of China/ ; 23XD1422300//Program of Shanghai Academic Research Leader/ ; 24X010301328//Medicine and Engineering Interdisciplinary Research Fund of Shanghai Jiao Tong University/ ; },
abstract = {Despite recent progresses in microbiome and infection, the role of multi-kingdom gut microbiome in kidney transplantation (KT) infection remains unexplored. Here we performed a longitudinal and integrative multi-omics analysis of the gut microbiome, fecal metabolome and plasma metabolome in 169 KT recipients across 5 different transplantation centers, comprising discovery and validation cohorts. We observed KT-specific four kingdom microbiome dysbiosis, including bacteria, fungi, archaea and viruses, with the most pronounced shifts in bacterial and fungal communities. Furthermore, we identified 6 infection-associated co-abundance groups (CAGs) composed of 23 bacterial and 3 fungal species, highlighting extensive bacterial-fungal interactions. Interestingly, infection-associated fecal metabolomic pattern F1, enriched in N-acetylputrescine and hydroxyproline, was positively correlated with Enterococcus-, Citrobacter- and Lactococcus-dominated CAGs, as well as the plasma metabolite signature, represented by phenylacetyl-l-glutamine, indoxyl sulfate and leukotriene. In contrast, cholesterol sulfate and menadione in plasma were aligned with fecal indoleacetic acid and stachyose, a metabolic signature more characteristic of non-infected recipients. Finally, the combinatorial biomarkers of fungal and bacterial species achieved powerful diagnosis ability of KT infection in an independent validation cohort (area under the receiver operating characteristic curve (AUROC) = 0.80) with the fecal metabolites achieving high accuracy (AUROC = 0.83). Collectively, our findings not only uncovered the postoperative infection-specific multi-kingdom microbial network dynamics, but also revealed the microbial and its metabolic biomarkers with powerful diagnostic ability for postoperative infection in kidney transplantation.},
}

@article {pmid42477314,
year = {2026},
author = {Almarzooqi, S and Yassin, LK and Alnuaimi, F and Alketbi, S and Skrabulyte-Barbulescu, J and AlAhbabi, N and Alremeithi, D and Almarashda, R and Almazrouei, S and Shehab, S and Statsenko, Y and Hamad, MIK},
title = {From association to causality: mechanistic pathways linking the gut microbiome to psychiatric disorders.},
journal = {Translational psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41398-026-04305-x},
pmid = {42477314},
issn = {2158-3188},
support = {12M295//United Arab Emirates University (UAEU)/ ; 12M159//United Arab Emirates University (UAEU)/ ; },
abstract = {The microbiota-gut-brain axis (MGBA) has emerged as a key framework for understanding how peripheral biological systems influence brain function and behaviour. However, despite extensive associative evidence linking gut microbiome to psychiatric disorders, robust causal and mechanistic insights remain limited. This review critically evaluates current evidence to determine whether microbiome alterations contribute to psychiatric pathophysiology and inform therapeutic strategies. We outline methodological frameworks for causal inference, highlighting the limitations of cross-sectional designs and the need for convergent evidence from longitudinal studies, experimental models, and human genetic approaches. We then synthesize mechanistic pathways linking the microbiota to brain function, including immune signaling, neuroendocrine regulation via the hypothalamic-pituitary-adrenal (HPA) axis, neural communication through vagal and enteric pathways, and intestinal and blood-brain barrier (BBB) integrity. Across these systems, microbial metabolites and immune mediators emerge as key mediators, although direct causal mechanisms in humans remain incompletely established. Disorder-specific evaluation across major depressive disorder (MDD), anxiety disorders, bipolar disorder (BD), schizophrenia (SCZ), and post-traumatic stress disorder (PTSD) reveals heterogeneous but converging evidence for microbiome involvement. Although preclinical and interventional studies support biological plausibility, human evidence remains constrained by confounding, variability, and limited mechanistic validation. Translational strategies, including psychobiotics, dietary interventions, fecal microbiota transplantation (FMT), and microbiome-based biomarkers, show promise but remain methodologically limited. Overall, the gut microbiome represents a biologically plausible and modifiable contributor to psychiatric disorders. Advancing toward clinical application will require integrative, longitudinal, and mechanism-driven research to enable precision psychiatry grounded in causal evidence.},
}

@article {pmid42478338,
year = {2026},
author = {Wang, Y and Medina, AA and Liu, X and Liu, Y and Du, W and Wang, Y and Yang, J and Jiang, T and Chen, X and Huang, K and Liu, Y},
title = {β-Nicotinamide mononucleotide reduces aflatoxin B1 induced liver injury via the gut microbiota-bile acid-farnesoid X receptor (FXR/NR1H4) axis.},
journal = {British journal of pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bph.70566},
pmid = {42478338},
issn = {1476-5381},
support = {S202510307228//National College Students' Innovative Training Program Support Project/ ; 32102741//National Natural Science Foundation of China/ ; BK20210399//Natural Science Foundation of Jiangsu Province/ ; KJYQ2026005//Fundamental Research Funds for the Central Universities/ ; K2025018//Key Program of Medical Research Project of Jiangsu Commission of Health/ ; },
abstract = {BACKGROUND: Aflatoxin B1 (AFB1) is a potent hepatotoxin that poses significant health risks to both livestock and humans. β-Nicotinamide mononucleotide (NMN) has potential therapeutic benefits for liver diseases. However, its mechanism against AFB1-induced liver injury remains unclear.

OBJECTIVE: This study investigates whether NMN supplementation reduces AFB1-induced liver injury through the modulation of the gut-liver axis and elucidates the underlying molecular mechanism.

METHODS: Mice were exposed to AFB1 (0.75 mg·kg[-1], p.o.) for 2 weeks to induce liver injury, with or without NMN (300 mg·kg[-1], p.o.). Changes in gut microbiota were assessed via 16S rRNA sequencing, while bile acids (BAs) profiles were quantified using targeted metabolomics. The farnesoid X receptor (FXR/NR1H4) pathway was analysed using qPCR, western blot and immunofluorescence. To establish causality, antibiotic depletion, faecal microbiota transplantation (FMT) and intestine-specific FXR knockout (FXR[ΔIE]) mice were utilized.

RESULTS: NMN supplementation attenuated AFB1-induced liver injury, inflammation and oxidative stress, while restoring intestinal barrier integrity and reducing hepatic bile acids accumulation. Mechanistically, NMN reshaped the gut microbiota, increased bile salt hydrolase (BSH) activity and lowered intestinal conjugated bile acids, which correlated with activation of intestinal FXR/fibroblast growth factor 15 (FGF-15) signalling and suppression of hepatic Cyp7a1 expression. Importantly, antibiotic depletion of gut microbiota abolished NMN protection, whereas FMT from NMN-treated donors conferred resistance. Importantly, NMN failed to protect FXR[ΔIE] mice, demonstrating that intestinal FXR is essential.

CONCLUSION: NMN alleviates AFB1-induced liver injury via a gut microbiota-bile acid-FXR axis, highlighting a novel mechanism for its hepatoprotective effects.},
}

@article {pmid42479457,
year = {2026},
author = {You, J and Khan, RM and Reji, N},
title = {Gut microbiome profiles as predictors of response to chemoradiotherapy in locally advanced rectal cancer.},
journal = {Acta microbiologica et immunologica Hungarica},
volume = {},
number = {},
pages = {},
doi = {10.1556/030.2026.02874},
pmid = {42479457},
issn = {1588-2640},
abstract = {This prospective cohort study investigates the predictive role of gut microbiota composition in determining the therapeutic response to neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC) at Qiqihar Jianhua Hospital. A total of 178 patients underwent standardized CRT protocols and were stratified into responders and non-responders based on pathological tumor regression grades. Gut microbiome profiling was conducted via 16S rRNA amplicon sequencing and shotgun metagenomics at three treatment stages (pre-, mid-, and post-CRT). Responders exhibited significantly higher alpha diversity (Shannon, Chao1) at baseline and maintained greater microbial richness throughout treatment. Taxonomic analysis identified Faecalibacterium, Akkermansia, and Bifidobacterium as enriched in responders, while non-responders showed elevated Clostridium, Escherichia, and Streptococcus. Multivariate regression confirmed Faecalibacterium (OR = 1.16, P = 0.0002) and Akkermansia (OR = 1.27, P = 0.0146) as independent predictors of CRT response. Functional profiling revealed enrichment of anti-inflammatory pathways (butyrate synthesis, tryptophan metabolism) in responders and pro-inflammatory, stress-related functions (lipopolysaccharide biosynthesis, oxidative stress) in non-responders. Exploratory microbiome modulation using probiotics or fecal microbiota transplantation (FMT) targeting Faecalibacterium and Akkermansia demonstrated increased responder rates by 12.5 and 18.2%, respectively. These findings highlight the potential of gut microbiome signatures as non-invasive biomarkers for CRT response prediction and as targets for adjunctive therapeutic strategies. Personalized microbiome-informed treatment may enhance CRT efficacy and reduce unnecessary exposure in non-responders, paving the way for precision oncology in rectal cancer.},
}

@article {pmid42479553,
year = {2026},
author = {Martinelli, M and Salomone, S and Strisciuglio, C and Zellos, A and Romano, C and Dipasquale, V and Bramuzzo, M and Lega, S and Aloi, M and D'Arcangelo, G and Rodríguez-Belvís, MV and Colucci, A and Miele, E and Staiano, A and Eleftheria, R},
title = {Disorders of Gut-Brain Interaction like symptoms in Children with Inflammatory Bowel Disease: A Multicenter Prospective Study from the Pediatric IBD Porto Group of the ESPGHAN.},
journal = {The American journal of gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.14309/ajg.0000000000004140},
pmid = {42479553},
issn = {1572-0241},
abstract = {BACKGROUND AIMS: Disorders of gut-brain interaction (DGBI) are frequently reported in patients with inflammatory bowel disease (IBD), but pediatric data are scarce. We aimed to determine the prevalence of DGBI-like symptoms in children with quiescent IBD compared with healthy controls (HC), and to evaluate their impact on health-related quality of life (HR-QoL), anxiety and symptoms burden.

METHODS: This multicenter, prospective, observational study enrolled children aged 10-18 years with biochemically quiescent IBD, with or without endoscopic confirmation of remission from seven European ESPGHAN centers (January 2021-August 2023). Age and sex-matched HC were recruited through primary care pediatricians and screened for subclinical inflammation using fecal calprotectin. DGBI were assessed using Rome IV criteria. HR-QoL and psychological burden were evaluated using IMPACT III, PROMIS Anxiety, Visceral Sensitivity Index-Child, and Behavioral Response Questionnaire-Child.

RESULTS: A total of 253 children were enrolled (IBD: n=131; HC: n=122). The prevalence of DGBI-like symptoms did not differ between IBD and HC [34.4% vs 41.8%, p=0.30]. Functional abdominal pain disorders were present in 24.4% of children with IBD. Children with IBD and DGBI-like symptoms showed significantly lower IMPACT III scores compared with those without DGBI [median 74 (IQR 62.5-81) vs 84 (70-90); p=0.001], with the greatest impairment in IBD symptoms, energy, and social domains. PROMIS Anxiety scores were higher in the DGBI group [31 (20-44) vs 21.5 (16-28); p<0.001], with a greater proportion exceeding the clinical threshold (>50) (17.8% vs 3.5%; p=0.008). Female sex was the only independent predictor of DGBI (OR 5.2, 95% CI 1.6-16.1; p=0.005).

CONCLUSIONS: DGBI-like symptoms are common in children with quiescent IBD and are associated with a substantial psychological and quality-of-life burden.},
}

@article {pmid42471352,
year = {2026},
author = {Long, K and Liu, Z and Liu, P and Zhang, W and Gao, M and Gan, G and Cao, X and Cheng, Y and Wang, B and Yuan, X and Wang, B and Zhao, D and Xu, A and Sulaiman, JE and Cheng, KK},
title = {Lipodystrophy induces gut microbiota dysbiosis and its related glucose dysmetabolism in mice.},
journal = {NPJ biofilms and microbiomes},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41522-026-01102-8},
pmid = {42471352},
issn = {2055-5008},
support = {P0056052//Hong Kong Polytechnic University Start-up Fund for RAPs under the Strategic Hiring Scheme/ ; P0059102//RiFood's Interdisciplinary Project Fund/ ; P0059102//RiFood's Interdisciplinary Project Fund/ ; C5044-23G//Hong Kong Research Grant Council Collaborative Research Fund/ ; 92357305//National Natural Science Foundation of China/ ; P0036848//PolyU internal funding/ ; },
abstract = {Both excessive white adipose tissue (WAT) in obesity and insufficient WAT in lipodystrophy disrupt metabolic homeostasis. Although a vicious cycle between WAT dysfunction and gut dysbiosis is known to drive insulin resistance in obesity, whether lipodystrophy impairs gut function and contributes to glucose dysregulation remains unclear. Using adipocyte-specific MDM2 knockout (Adipo-MDM2-KO) mice as a model of lipodystrophy, we identified a direct role of WAT in maintaining intestinal and gut microbiota homeostasis. Progressive adipose tissue loss in Adipo-MDM2-KO mice caused multiple intestinal abnormalities, including gut microbiota dysbiosis, altered microbial metabolism, impaired intestinal barrier integrity, defective immunoglobulin A (IgA) responses, and endotoxemia. These defects were largely reversed by transplantation of healthy subcutaneous WAT (sWAT). Moreover, fecal microbiota transplantation from Adipo-MDM2-KO mice into C57BL/6J recipients reproduced intestinal defects and glucose intolerance, whereas microbiota depletion in Adipo-MDM2-KO mice largely rescued intestinal abnormalities and partially restored glucose homeostasis. Furthermore, sWAT-secreted adipokines, including extracellular vesicles, directly modulated the abundance and growth of specific gut bacterial communities. Multi-omics analyses further linked lipodystrophy-induced microbiota and metabolomic alterations to systemic endotoxemia and impaired glucose metabolism. Altogether, our findings reveal a critical WAT-gut-microbiota axis in the regulation of intestinal homeostasis and host glucose metabolism.},
}

@article {pmid42472818,
year = {2026},
author = {Mohammed Abdelhadi, LA and Liang, Y and Liao, Y and Zhu, G},
title = {Current and emerging therapeutic strategies targeting adherent-invasive Escherichia coli in Crohn's disease: a review.},
journal = {Gut pathogens},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13099-026-00852-2},
pmid = {42472818},
issn = {1757-4749},
support = {S20250254//The Priority Academic Program of Development Jiangsu High Education Institution, and the High-end Talent Program for International Collaboration/ ; },
abstract = {Considerable evidence has accumulated over the past two decades demonstrating that Escherichia coli, specifically adherent-invasive E. coli, contributes to the pathogenesis of Crohn's disease. Adherent-invasive E. coli can adhere to and invade intestinal epithelial cells, survive, and replicate within macrophages, thereby enabling a key mechanism that induces chronic inflammation. Despite extensive knowledge of the molecular interactions between adherent-invasive E. coli and the host from these studies, translating this knowledge into targeted therapy remains limited.In this review, we summarize current and proposed treatments to prevent or eliminate adherent-invasive E. coli colonization. We provide a theoretical framework that categorizes these strategies into four main pillars: direct pathogen targeting (e.g., antibiotics, phage therapy), blockade of bacterial virulence factors (e.g., anti-adhesive compounds, QseC inhibitors), host-mediated clearance (e.g., autophagy inducers), and ecological intervention/restoration (e.g., fecal microbiota transplantation, Probiotic, Prebiotic and Probiotics). Finally, we discuss new modalities, including predatory bacteria, siderophore immunization, and other approaches. This review identifies the latest weapons against adherent-invasive E. coli, synthesizes experimental and clinical evidence to provide a comprehensive view of this evolving therapeutic arsenal, and offers ideas for future treatment of Crohn's disease.},
}

@article {pmid42473148,
year = {2026},
author = {Wang, M and Chen, P and Pei, S and Wang, R and Liu, S and Hou, Z and Liu, Z},
title = {Panax ginseng Extract Alleviates Qi Deficiency Liver Cancer via the Gut-Liver Axis: Insights from Metabolomics and Microbiome.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.6c00814},
pmid = {42473148},
issn = {1520-5118},
abstract = {Panax ginseng (PG), a valuable functional food known as the "King of Herbs," demonstrates therapeutic potential in the treatment of Qi deficiency liver cancer (QDLC). Regulating the gut-liver axis (GLA) may be an important mechanism of action of PG in the treatment of QDLC; however, its detailed mechanism remains unclear. This study aimed to elucidate this mechanism in QDLC rats using metabolomics and microbiome analysis. Metabolomics and microbiome experiments demonstrate that PG alleviates QDLC by modulating the composition of the gut microbiota, restoring its diversity, improving metabolic disorders, and increasing short-chain fatty acid levels. Antibiotics cocktail treatment, fecal microbiota transplantation, and probiotic colonization experiments further confirmed that PG's role in alleviating QDLC is gut microbiota-dependent. Additionally, PG alleviated GLA damage in QDLC rats by inhibiting the TLR4/MyD88/NF-κB signaling pathway. Collectively, our study provides a novel interpretation of the natural intervention mechanisms for QDLC and confirms the potential value of PG as a functional food.},
}

@article {pmid42473187,
year = {2026},
author = {Li, Q and He, R and Wang, X and Long, C and He, Z and Zhang, S and Liu, Y and Zhang, Z and Wu, J and Sun, G and Cui, B and Zhao, F and Zhang, F},
title = {Akkermansia muciniphila enhances washed microbiota transplantation in the treatment of epilepsy.},
journal = {Chinese medical journal},
volume = {},
number = {},
pages = {},
pmid = {42473187},
issn = {2542-5641},
abstract = {BACKGROUND: Refractory epilepsy remains a global clinical challenge. This first-in-human cohort study aimed to evaluate the efficacy and safety of washed microbiota transplantation (WMT) in the treatment of epilepsy.

METHODS: A prospective, single-center, open-label study of WMT in patients with epilepsy was conducted at the Second Affiliated Hospital of Nanjing Medical University from November 2016 to November 2023. The primary outcome was the clinical response rate (≥50% reduction in seizure frequency) at one month post-WMT. Parallel experiments using a pentylenetetrazole-induced epileptic mouse model were performed to validate clinical findings and investigate the role of specific core bacterial species.

RESULTS: Among 21 patients (mean age, 18.9 years), including 18 with refractory epilepsy, the clinical response rates were 43% (9/21), 57% (12/21), and 38% (8/21) at one, three, and six months post-WMT, respectively. A second maintenance WMT course at three months was associated with a higher response rate at six months compared to no maintenance therapy (odds ratio [OR] >999, 95% confidence interval [CI]: [1.12, +infinity], P = 0.080). WMT significantly increased Akkermansia muciniphila (A. muciniphila) levels in responders (P = 0.038). A higher baseline A. muciniphila abundance was associated with improved clinical outcomes (Z = 3.28, P = 0.001). The preclinical study confirmed that A. muciniphila augmented the effects of WMT against seizures, significantly reducing seizure severity and duration, and prolonging seizure latency.

CONCLUSIONS: Integrating clinical and preclinical findings, this study demonstrates that A. muciniphila synergistically enhances the effects of WMT against epileptic seizures. This study provides evidence for a new concept of microbiome-based therapeutics in epilepsy treatment.

TRIAL REGISTRATION: Clinicaltrials.gov, NCT02889627.},
}

@article {pmid42474869,
year = {2026},
author = {Li, Y and Xiao, X and Jiang, X and Li, X and Wang, W and Lin, R},
title = {Gut microbiota in health and disease.},
journal = {Molecular biomedicine},
volume = {7},
number = {1},
pages = {},
pmid = {42474869},
issn = {2662-8651},
support = {2024ZD0520800//National Major Science and Technology Projects of China/ ; 5003530167//Central University Basic Research Fund of China/ ; 82170571//National Natural Science Foundation of China/ ; 81974068//National Natural Science Foundation of China/ ; 82270586//National Natural Science Foundation of China/ ; 81900580//National Natural Science Foundation of China/ ; 2022YFF1203300//Ministry of Science and Technology of the People's Republic of China/ ; 2023YFC2307000//Key Technologies Research and Development Program/ ; 2022CFA009//Natural Science Foundation of Hubei Province/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; Dysbiosis/microbiology ; Homeostasis ; Fecal Microbiota Transplantation ; Intestinal Barrier Function ; Colorectal Neoplasms/microbiology ; },
abstract = {The gut microbiota is integral to host physiology, contributing to metabolic homeostasis, epithelial barrier integrity, immune balance, and bidirectional communication along gut-organ axes. Disruption of this ecosystem, commonly referred to as dysbiosis, is increasingly implicated in a wide range of gastrointestinal and extra-intestinal diseases. Rather than reflecting isolated compositional changes, microbiota-related pathology often involves interconnected disturbances in barrier function, microbial metabolism, immune regulation, genotoxicity, inflammatory and oncogenic signaling, and long-range communication with distal organs. However, key challenges remain, particularly in resolving causality, accounting for interindividual heterogeneity, and translating complex microbiome data into robust clinical tools. In this review, we summarize the role of the gut microbiota in maintaining host homeostasis and outline the concept, drivers, and consequences of dysbiosis. We then discuss the major mechanisms through which the gut microbiota contributes to disease development and progression, using colorectal cancer as a representative gastrointestinal example and gut-organ axes as a framework for extra-intestinal disorders. We further highlight current translational advances in microbiota-based biomarkers, dietary modulation, biotic and postbiotic strategies, fecal microbiota transplantation, and emerging precision microbiota therapies. By integrating mechanistic insights with translational perspectives, this review offers an updated framework for interpreting the gut microbiota in health and disease and may help inform the future development of more precise, mechanism-informed diagnostic and therapeutic strategies.},
}

Humans
*Gastrointestinal Microbiome/physiology
Animals
Dysbiosis/microbiology
Homeostasis
Fecal Microbiota Transplantation
Intestinal Barrier Function
Colorectal Neoplasms/microbiology

@article {pmid42476197,
year = {2026},
author = {Zhong, Y and Xia, D and Cui, T and Wang, H and Zhai, J and Wu, Z and Zhou, J and Li, Z and Zeng, L and Wu, M and Liu, K and Yang, Z and Song, S and Zeng, G and Chen, Z and Yan, B},
title = {Gut microbiota homeostasis alleviates mycobacterial granuloma pathology in zebrafish.},
journal = {Microbial pathogenesis},
volume = {},
number = {},
pages = {108723},
doi = {10.1016/j.micpath.2026.108723},
pmid = {42476197},
issn = {1096-1208},
abstract = {Growing evidence links the gut microbiota to host immune regulation and tuberculosis (TB) progressiond; however, its specific impact on the formation and necrosis of TB granulomas remains poorly defined. In this study, we established an adult zebrafish model of antibiotic-induced gut microbiota dysbiosis followed by Mycobacterium marinum (M.m) infection to investigate how gut microbiota perturbation influences host resistance to mycobacterial infection. Our results demonstrated that antibiotic-induced gut microbiota dysbiosis significantly increased the mycobacterial burden in zebrafish, thereby compromising host resistance to mycobacterial infection. Dysbiosis also intensified infection-associated inflammatory responses, as reflected by the elevated expression of the pro-inflammatory cytokines tnf-α and il-1β, resulting in more severe systemic pathology characterized by enhanced granuloma formation and necrosis, together with remodeling of the immune cell composition within granulomatous lesions. Importantly, fecal microbiota transplantation (FMT) from healthy donors effectively reduced the bacterial burden and alleviated granuloma-associated pathological changes in infected zebrafish. These findings demonstrate that the gut microbiota critically modulates the granuloma immune microenvironment, providing a robust platform and mechanistic support for gut microecological interventions as a host-directed therapy for TB.},
}

@article {pmid42476206,
year = {2026},
author = {Yang, N and Ye, M and Wang, H and Liang, Y and Huang, K and Zhao, Y and Zhang, X},
title = {Callistephus A from Callistephus chinensis Alleviates DSS-Induced Ulcerative Colitis and Gut-liver Axis Disruption by Targeting the JAK2/STAT1 Pathway and Remodeling Gut Microbiota.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {122213},
doi = {10.1016/j.jep.2026.122213},
pmid = {42476206},
issn = {1872-7573},
abstract = {Callistephus chinensis, a plant belonging to the genus Callistephus in the family Asteraceae, is a traditional Mongolian medicinal herb. In ancient times, it was commonly used for clearing heat, detoxifying, reducing swelling and relieving pain. CA is a 6/7-thickened sesquiterpenoid component isolated from the flowers of Callistephus chinensis, however, its pharmacological mechanism underlying the treatment of intestinal inflammation remains unclear.

AIM OF THE STUDY: To evaluate the therapeutic effect and mechanism of CA on UC.

MATERIALS AND METHODS: CA was tested in LPS-stimulated RAW264.7 macrophages and DSS-induced colitis mice. Multi-omics profiling, gut microbiota analysis, fecal microbiota transplantation, inhibitor and knockdown assays were performed.

RESULTS: CA treatment markedly alleviated colitis and liver injury, reducing the histological score to approximately 0.6 times and key pro-inflammatory cytokines TNF-α and IL-6 to below 0.3 times the levels in the DSS group, while restoring gut barrier integrity. Multi-omics reveals that CA reshapes the gut microbiota by significantly increasing the relative abundance of Firmicutes (1.1-fold) and restoring the Firmicutes/Bacteroidetes ratio compared to the DSS group, while promoting host short-chain fatty acid and amino acid metabolism.Mechanistically, CA directly bound JAK2 and STAT1, suppressing JAK2/STAT1 pathway phosphorylation to under 0.3 times the DSS group level, confirmed by inhibitor and knockdown assays. FMT confirmed that CA's efficacy depends on microbiota modulation. Furthermore, CA reduced gut-derived LPS translocation and alleviated liver injury.

CONCLUSIONS: CA treats UC by targeting the gut-microbiota-metabolite axis and the JAK2/STAT1 pathway, representing a promising therapeutic lead.},
}

@article {pmid42476661,
year = {2026},
author = {Zhang, F and Hu, W and Zhao, X and Fu, B and Lin, Y and Xie, C and Yang, R and Fu, Y and Tan, W and Ye, L},
title = {Comorbid depression exacerbates Gelsemium elegans toxicity via disruption of the Clostridium-LCA-PXR-CYP3A11 metabolic axis.},
journal = {Chinese journal of natural medicines},
volume = {24},
number = {8},
pages = {987-998},
doi = {10.1016/S1875-5364(26)61197-1},
pmid = {42476661},
issn = {1875-5364},
mesh = {Animals ; *Gelsemium/toxicity/chemistry ; Mice ; *Clostridium/metabolism ; Gastrointestinal Microbiome/drug effects ; *Pregnane X Receptor/metabolism/genetics ; Male ; *Depression/metabolism/microbiology/complications ; *Cytochrome P-450 CYP3A/metabolism/genetics ; *Plant Extracts/toxicity ; Indole Alkaloids/toxicity ; Alkaloids ; },
abstract = {Gelsemium elegans (G. elegans) is a toxic medicinal plant traditionally used to treat chronic pain, with its toxicity linked to indole alkaloids such as gelsemine and humantenmine (HMT). Chronic pain often co-occurs with depression, a condition known to disrupt host-microbiota interactions, potentially affecting drug metabolism and toxicity. However, the impact of comorbid depression on the toxicity of G. elegans remains unclear. This study investigates how depression exacerbates the neurotoxicity of G. elegans and explores the role of the gut microbiota-host metabolic axis in this process. Depression-model mice were treated with G. elegans aqueous extract, gelsemine and HMT. Multi-omics approaches, including 16S rRNA sequencing and shotgun metagenomics, were used to analyze microbiota changes under depressive conditions. Functional validation was performed using pseudo-germ-free mice, fecal microbiota transplantation, and supplementation with Clostridium species and lithocholic acid (LCA), as well as pregnane X receptor (Pxr) knockout models. The results showed that depression significantly heightened the neurotoxicity of G. elegans, gelsemine and HMT. Mechanistically, depression reduced Clostridium abundance and LCA levels, impairing PXR activation and downregulating hepatic CYP3A11 expression. This disruption of the Clostridium-LCA-PXR-CYP3A11 axis hindered the detoxification of indole alkaloids, leading to increased systemic exposure and exacerbated neurotoxicity. Restoration of this pathway through Clostridium or LCA supplementation alleviated the toxicity. These findings highlight the role of the Clostridium-LCA-PXR-CYP3A11 axis in the altered toxicity of G. elegans in a depressive state, and suggest that Clostridium species and their metabolites may serve as a potential strategy for mitigating toxicity.},
}

Animals
*Gelsemium/toxicity/chemistry
Mice
*Clostridium/metabolism
Gastrointestinal Microbiome/drug effects
*Pregnane X Receptor/metabolism/genetics
Male
*Depression/metabolism/microbiology/complications
*Cytochrome P-450 CYP3A/metabolism/genetics
*Plant Extracts/toxicity
Indole Alkaloids/toxicity
Alkaloids

@article {pmid42476727,
year = {2026},
author = {Ullern, A and Garborg, KK and Chauhan, SK and Holm, K and Bang, C and Dunn, C and Johnsen, PH and Hov, JER and Kyte, JA},
title = {Safety and efficacy of fecal microbiota transplantation in solid cancers resistant to immune checkpoint inhibitors: results of the MITRIC trial.},
journal = {Journal for immunotherapy of cancer},
volume = {14},
number = {7},
pages = {},
doi = {10.1136/jitc-2026-015122},
pmid = {42476727},
issn = {2051-1426},
mesh = {Humans ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Female ; Male ; Middle Aged ; *Fecal Microbiota Transplantation/methods/adverse effects ; Aged ; *Neoplasms/therapy/drug therapy ; *Drug Resistance, Neoplasm ; Adult ; },
abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has shown promise in overcoming resistance to immune checkpoint inhibitors (ICIs) in early-phase cancer trials. We investigated the safety, feasibility and efficacy of FMT from ICI responders to patients with advanced cancers progressing on ICIs.

METHODS: This was a single-arm phase IIa basket trial (MITRIC; NCT05286294) including patients with ICI-refractory cancer. Long-term ICI responders were used as FMT donors. Patients received FMTs in combination with ICIs; two FMT administrations (by colonoscopy) were scheduled before the first radiological evaluation after 6 weeks, and up to three later FMTs were allowed (by enema). Co-primary endpoints were the evaluation of FMT-related adverse events and objective response rate. Feasibility, clinical benefit rate, progression-free survival (PFS), overall survival (OS), implant engraftment, immune response and biomarkers were among the secondary objectives.

RESULTS: The study enrolled 12 patients with melanoma (n=9), head and neck squamous cell carcinoma (HNSCC; n=1), renal cell carcinoma (n=1) or microsatellite instability-high pancreatic cancer (n=1). FMT was well tolerated, whereas immune-related toxicity occurred in 6/12 patients. All patients received the first FMT; 10/12 patients also underwent the second FMT. No objective responses were observed, while 5/12 patients recorded stable disease. Clinical benefit per-protocol (stable disease >6 months) was achieved in a patient with melanoma, who had regression of some lesions and remains alive after 33 months without further systemic treatment. Mixed responses with regression of some lesions were observed in another melanoma patient, and in a patient with HNSCC. The median PFS was 1.5 months, and median OS was 10.1 months. Sequencing of fecal samples indicated engraftment after the first FMT in most patients. Mass cytometry analysis of peripheral blood cells suggested that an activated and differentiated T-cell signature was associated with improved PFS and OS, while a naïve T-cell phenotype and a myeloid-dominant environment were unfavorable. CD14[+] monocytes and serum interleukin-8 increased at group level over time.

CONCLUSION: FMT in combination with ICIs was safe and feasible in patients with advanced cancers, but with limited clinical activity. Further studies are required to clarify the potential benefit of FMT, identify the appropriate patient population and define criteria for donor selection.

TRIAL REGISTRATION NUMBER: NCT05286294.},
}

Humans
*Immune Checkpoint Inhibitors/therapeutic use/pharmacology
Female
Male
Middle Aged
*Fecal Microbiota Transplantation/methods/adverse effects
Aged
*Neoplasms/therapy/drug therapy
*Drug Resistance, Neoplasm
Adult

@article {pmid42470953,
year = {2026},
author = {Chen, Z and Li, W and Wang, M and Li, Y and Gao, J and Xie, Z and Tsering, T and Jia, J and Wang, A},
title = {Lonicera trichosantha alleviates LPS-induced endometritis in mice by modulating the gut microbiota and host metabolism.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {159},
number = {},
pages = {158577},
doi = {10.1016/j.phymed.2026.158577},
pmid = {42470953},
issn = {1618-095X},
abstract = {BACKGROUND: Endometritis is an inflammatory disorder of the endometrial lining. Conventional antibiotic therapy often fails to control the accompanying disruptive inflammation. The 95 % ethanol-eluted fraction of Lonicera trichosantha (95 %-LT), exhibits potent anti-inflammatory activity in vitro. Nevertheless, its efficacy in vivo and the mechanisms underlying its potential therapeutic effect on endometritis are largely unknown.

PURPOSE: This study aimed to elucidate the protective effects of 95 %-LT against endometritis and to define its mechanism of action, specifically through the gut microbiota-metabolite axis.

METHODS: The chemical profile of the 95 %-LT fraction was characterized using high-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The therapeutic effects of 95 %-LT were systematically investigated using in vitro cellular inflammation models, a murine endometritis model, 16S ribosomal RNA (16S rRNA) gene sequencing, untargeted metabolomics, pseudo-germ-free (PGF) models, fecal microbiota transplantation (FMT), and in vivo supplementation with key bacterial strains and metabolites.

RESULTS: Three primary chemical constituents were identified in the 95 %-LT. Dose-dependent mitigation of endometrial pathological injury was achieved following intervention with 95 %-LT. Gut flora reconstruction induced by 95 %-LT was validated through 16S rRNA gene sequencing, among which the commensal beneficial bacterium Lactobacillus murinus exhibited the most remarkable enrichment. Concurrently, untargeted metabolomics showed that 95 %-LT enhanced the production of kynurenic acid (KYNA), a tryptophan-derived metabolite. FMT and PGF model experiments confirmed that the gut microbiota is indispensable for this therapeutic effect. Finally, in vivo supplementation verified that both L. murinus and KYNA function as key mediators underlying the efficacy of 95 %-LT.

CONCLUSION: Our results demonstrate that 95 %-LT alleviates endometritis by orchestrating a gut microbiota-dependent mechanism, specifically through the "L. murinus-KYNA axis". This study provides a mechanistic foundation for exploiting Tibetan medicine-derived compounds in endometritis therapy.},
}

@article {pmid42468804,
year = {2026},
author = {Gong, Z and Wang, Y and Mao, W and Gao, R and Bao, W and Dai, J and Dong, Y and Mu, Z and Fu, Y and Hu, X and Zhang, S and Liu, B},
title = {Gut microbiota alterations are associated with uterine immune homeostasis via microbiota-metabolite interactions.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2026.07.043},
pmid = {42468804},
issn = {2090-1224},
abstract = {INTRODUCTION: Uterine inflammation is a major cause of infertility and is commonly associated with local bacterial infection. However, the association between gut microbiota and uterine immune homeostasis remains incompletely understood.

OBJECTIVES: This study aimed to examine the association between gut microbiota dysbiosis and uterine inflammation, and to identify microbiota-associated factors linked to host immune responses.

METHODS: An antibiotic-induced dysbiosis mouse model was established, followed by fecal microbiota transplantation (FMT), microbial supplementation, metabolite intervention, and acute E. coli challenge to assess inflammation-related outcomes. Uterine inflammation, barrier integrity, and immune responses were evaluated. Gut microbiota and fecal metabolites were profiled by 16S rRNA sequencing and untargeted metabolomics, respectively.

RESULTS: Gut microbiota dysbiosis was associated with increased uterine inflammation, as indicated by elevated cytokine levels, immune cell infiltration, and impaired epithelial barrier integrity, whereas FMT partially reversed these changes. Taxonomic analysis showed a marked reduction in Prevotellaceae abundance during dysbiosis, which increased following microbial reconstitution. Supplementation with Prevotella copri was associated with reduced uterine inflammation and improved barrier integrity in dysbiotic mice. Integrated microbiome-metabolome analysis revealed that allopregnanolone was strongly associated with Prevotellaceae abundance. Dysbiosis was accompanied by reduced allopregnanolone levels, which increased after FMT. Exogenous administration of allopregnanolone was associated with reduced inflammatory markers and improved epithelial barrier integrity. Importantly, gut microbiota dysbiosis was associated with increased susceptibility to E. coli-induced uterine inflammation, whereas FMT, Prevotella copri, and allopregnanolone were associated with attenuation of infection-related inflammatory responses and tissue injury.

CONCLUSION: Together, these findings support a microbiota-metabolite-host interaction pattern in which Prevotella copri, together with the host-associated metabolite allopregnanolone, is associated with uterine immune homeostasis. While these results provide functional insights, further studies are required to elucidate the mechanisms linking gut microbiota to uterine inflammation.},
}

@article {pmid42469824,
year = {2026},
author = {Song, M and Ping, L and Wang, Y and Zhou, W and Fan, J and Tao, S and Shen, Y},
title = {Gut-derived extracellular vesicle enriched miR-125a-5p mediates cadmium-induced intestinal injury through NF-κB pathway activation.},
journal = {Journal of nanobiotechnology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12951-026-04809-0},
pmid = {42469824},
issn = {1477-3155},
support = {2662026DKPY001//Fundamental Research Funds for the Central Universities/ ; 2024YFD1300500//Funding for the National Key R&D Program of China/ ; },
abstract = {Cadmium (Cd), as a prevalent environmental heavy metal pollutant, has an incompletely elucidated mechanism of intestinal toxicity following oral ingestion. This study aims to elucidate novel mechanisms underlying cadmium-induced intestinal injury. By establishing a murine model of cadmium exposure, it was found that cadmium not only directly disrupts the intestinal barrier structure but also induces intestinal microbiota dysbiosis. Fecal microbiota transplantation (FMT) experiments confirmed that the dysbiotic microbiota alone is sufficient to provoke intestinal injury, indicating that microbial dysregulation serves as a critical amplifier of cadmium toxicity. Further investigation revealed that cadmium exposure reshapes the intestinal microenvironment and alters the miRNA profile of gut-derived extracellular vesicles (EVs), with miR-125a-5p being significantly enriched in EVs from the cadmium-exposed group. Mechanistically, miR-125a-5p directly targets and suppresses TNFAIP3, a negative regulator of the NF-κB pathway, thereby relieving the inhibition of this signaling axis and driving sustained inflammation and barrier dysfunction, while inhibition of miR-125a-5p effectively blocks this toxic effect. This study is the first to delineate the axis of "cadmium exposure - intestinal microbiota dysbiosis - gut EV - miR-125a-5p - TNFAIP3 - NF-κB pathway activation - intestinal injury", providing new insights for the development of biomarkers and targeted interventions for cadmium-related intestinal disorders.},
}

@article {pmid42470694,
year = {2026},
author = {Yi-Hui, Z and George, S},
title = {Hierarchical Multi-Omics Trajectory Prediction for fecal microbiota transplantation: a novel machine learning framework for small-sample longitudinal multi-omics integration.},
journal = {Briefings in bioinformatics},
volume = {27},
number = {4},
pages = {},
doi = {10.1093/bib/bbag389},
pmid = {42470694},
issn = {1477-4054},
mesh = {Humans ; Multiomics ; *Machine Learning ; *Fecal Microbiota Transplantation ; *Clostridium Infections/therapy/microbiology ; Clostridioides difficile ; Longitudinal Studies ; Predictive Learning Models ; Metagenomics ; },
abstract = {Fecal microbiota transplantation (FMT) has emerged as a highly effective treatment for recurrent Clostridioides difficile infection and is being actively investigated for numerous other conditions. While multi-omics studies have revealed dynamic changes in microbial communities and host metabolism following FMT, existing approaches are primarily descriptive and lack the ability to model individual patient trajectories or identify early biomarkers of treatment response. Small-sample, multi-omics, longitudinal prediction presents unique computational challenges: high dimensionality ($p \gg n$), multi-omics integration, temporal dynamics, and interpretability. Here, we present Hierarchical Multi-Omics Trajectory Prediction (HMOTP), a purpose-built machine learning framework that addresses these challenges through hierarchical feature construction, multilevel attention mechanisms, and patient-specific trajectory prediction. We evaluated HMOTP on 15 patients with recurrent Clostridioides difficile infection who underwent FMT, with lipidomics and metagenomics profiling at four timepoints spanning 6 months. Notably, naively concatenating multi-omics features degraded Random Forest performance ($93.33\%$ to $87.18\%$ accuracy), whereas HMOTP's hierarchical integration benefited from the additional omics layer, demonstrating that its advantage stems from structure, not from access to more data. Through hierarchical interpretability, HMOTP identified key biomarkers and revealed cross-omics associations between host lipid metabolism and microbial energy pathways, demonstrating utility for longitudinal modeling and biological discovery in FMT response. HMOTP provides a generalizable, principled framework for personalized medicine applications across small-sample multi-omics problems. Source code and a demo dataset are publicly available.},
}

Humans
Multiomics
*Machine Learning
*Fecal Microbiota Transplantation
*Clostridium Infections/therapy/microbiology
Clostridioides difficile
Longitudinal Studies
Predictive Learning Models
Metagenomics

@article {pmid42462533,
year = {2026},
author = {Ren, H and Zhao, C and Fan, Q and Wang, X and Yan, K and Zhang, H and Jiang, S and Yang, C and Wang, Y and Liu, Y and Wang, N and Fan, S and Xu, X and Li, X},
title = {Paridis rhizoma total saponins ameliorate abnormal uterine bleeding via regulating Proteus mirabilis 2024-mediated estrogen metabolism in the gut-reproductive axis.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {159},
number = {},
pages = {158561},
doi = {10.1016/j.phymed.2026.158561},
pmid = {42462533},
issn = {1618-095X},
abstract = {BACKGROUND AND PURPOSE: Abnormal uterine bleeding (AUB) is a highly prevalent gynecological disorder worldwide, for which first-line steroid hormone therapy is limited by well-documented adverse effects. Paridis rhizoma total saponins (PRS) are the core pharmacodynamic material basis of Gongxuening Capsules, a classic traditional Chinese medicine (TCM) formula with well-validated clinical hemostatic efficacy for AUB. However, its active ingredients and underlying therapeutic mechanisms remain largely unclear, especially the potential regulatory role of the gut-reproductive axis. This study aimed to systematically elucidate the anti-AUB mechanism of PRS.

METHODS: The therapeutic effect of PRS was evaluated in a rat model of AUB induced by incomplete abortion in early pregnancy. Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used to characterize the chemical profile and in vivo distribution of PRS. Integrative analysis of uterine transcriptomics, fecal multi-omics, fecal microbiota transplantation, bacterial isolation, gene functional validation, and administration of individual monomeric compound was performed to decipher the mechanism.

RESULTS: PRS dose-dependently alleviated uterine and ovarian pathological damage, mitigated uterine inflammation and ovarian apoptosis, and restored systemic estrogen homeostasis in AUB rats, characterized by significantly reduced serum estradiol (E2) and elevated estrone (E1). Polyphyllin I (PI) and Paris saponin VII (PVII) were identified as the core active monomers of PRS. We first isolated and identified Proteus mirabilis 2024 (PM_2024) as the key bacterial strain driving the conversion of E2 to E1, and confirmed that the PM_2024_3180 gene was the core functional element encoding short-chain dehydrogenase/reductase (SDR) for estrogen metabolism. Mechanistically, PRS and its active monomers PI/PVII significantly enriched intestinal PM_2024, enhanced its E2 metabolic capacity, upregulated ovarian HSD17B2/HSD17B8 expression, and modulated FKBP5/PGR within the uterine estrogen signaling pathway to exert anti-AUB effects.

CONCLUSION: This study elucidates a novel estrogen-mediated gut-reproductive axis mechanism of PRS against AUB for the first time, deciphers the scientific connotation of the classic hemostatic TCM Paridis rhizoma, and provides a novel gut microbiota-targeted microecological therapeutic strategy for AUB and other hormone-related gynecological disorders.},
}

@article {pmid42465573,
year = {2026},
author = {Dixit, S and Welker, A and Ortiz, D and Athanasouli, M and Stein-Thoeringer, CK},
title = {Microbiome dysbiosis and its modulation in cancer development, prevention and therapy.},
journal = {Frontiers in oncology},
volume = {16},
number = {},
pages = {1852716},
pmid = {42465573},
issn = {2234-943X},
abstract = {Gut microbiome dysbiosis, a state of microbial imbalance, altered microbial function, and disturbed homeostasis between the gut microbiome and its host, is increasingly recognized as a key contributor to cancer development, progression, and variability in therapeutic response. These microbiome states can facilitate cancer development through chronic inflammation, expansion of microbial genotoxin producers, or disturbances of immune defense mechanisms. In this review, we will discuss current findings on gut microbiome dysbiosis in cancer initiation and progression, emphasizing mechanisms that links dysbiosis to oncogenic transformation and tumor microenvironment remodeling. Furthermore, we will explore microbiome-targeting strategies for cancer prevention and therapeutic support, including dietary modulation, probiotics, prebiotics, and fecal microbiota transplantation. These various microbiome modulations have shown promise in restoring microbial homeostasis, enhancing immunotherapy efficacy, and reducing treatment-associated toxicity. Advances in microbial genomics and metabolomics further enable the identification of biomarkers for predicting cancer risk and therapeutic outcomes. Despite significant progress, translation into clinical settings faces challenges related to interindividual variability, standardization, and mechanistic complexity. Understanding the microbiome-cancer interface provides a platform for personalized, microbiome-informed oncology, paving the way for prevention-driven and precision-guided therapeutics.},
}

@article {pmid42465768,
year = {2026},
author = {Zhou, P and Jiang, X and Zhang, H and Jiang, S and Zhang, X and Ma, C and Bai, X},
title = {Gut-lung axis in radiation-induced lung injury: mechanisms and interventions.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1806833},
pmid = {42465768},
issn = {1664-3224},
mesh = {Humans ; Animals ; *Gastrointestinal Microbiome/radiation effects/immunology ; *Radiation Pneumonitis/therapy/microbiology/etiology/immunology/metabolism ; *Lung/immunology/microbiology/radiation effects/metabolism ; Dysbiosis ; Radiation Injuries ; },
abstract = {Radiation-induced lung injury (RILI) constrains thoracic radiotherapy dosing and includes acute radiation pneumonitis (RP) and chronic radiation-induced pulmonary fibrosis (RPF). This narrative review explores the gut-lung microbiota axis in RILI, synthesizing evidence from preclinical models, clinical cohorts (N = 52-89), and randomized controlled trials (RCTs). Radiotherapy induces gut dysbiosis, barrier breakdown, and metabolite changes [e.g., short-chain fatty acid (SCFA) and desaminotyrosine (DAT) depletion], promoting inflammation and fibrosis via pathways such as Toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB), TGF-β/Smad, sphingosine-1-phosphate (S1P)-S1PR, and cGAS-STING in animal studies. Inter-species microbial variations hinder translation, while lung microbiota shifts remain nascent. In non-small cell lung cancer cohorts, lower gut microbiota stability (a marker of dysbiosis) is associated with an increased risk of grade ≥2 RP (multivariable-adjusted models, p < 0.05), with higher baseline Faecalibacterium abundance conferring protection; however, causality remains unproven due to antibiotic confounding. Mechanisms involve lipopolysaccharide (LPS) translocation, interleukin 25 (IL-25)/S1P-driven type 2 innate lymphoid cell (ILC2) migration, regulatory T cell/T helper 17 cell (Treg/Th17) imbalance, and extracellular vesicle (EV) signaling, with biomarkers such as 16S rRNA sequencing and EV-miRNAs (e.g., miR-486-5p). Artificial intelligence models predict RP with 75% accuracy. Phase-specific interventions, such as pre-radiotherapy gut microbiota monitoring, intra-radiotherapy SCFA supplementation, subacute DAT modulation, and RPF-targeted EV therapies, have been explored in preliminary pilot studies [for example, one small study reported approximately 12% FEV1 improvement following fecal microbiota transplantation (FMT)]. Future large-scale, stratified RCTs that properly account for antibiotics, chemotherapy, and immunotherapy are required to establish causality beyond the current largely associative clinical evidence. The integration of immunotherapy and proton therapy in such trials may help clarify gut-lung interactions, including any microbiota-preserving effects of proton therapy; the role of the lung microbiota in fibrosis remains preliminary.},
}

Humans
Animals
*Gastrointestinal Microbiome/radiation effects/immunology
*Radiation Pneumonitis/therapy/microbiology/etiology/immunology/metabolism
*Lung/immunology/microbiology/radiation effects/metabolism
Dysbiosis
Radiation Injuries

@article {pmid42466149,
year = {2026},
author = {Jiao, B and Jiang, S},
title = {Gut microbiota as modulators of obesity and overweight: a registry-based systematic review of clinical trial evidence.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1865785},
pmid = {42466149},
issn = {2296-861X},
abstract = {BACKGROUND: Background: Obesity is a global epidemic that remains inadequately addressed by healthcare systems. The gut microbiota offers a promising metabolic target, yet systematic reviews of clinical trials on microbiome modulators for obesity are scarce.

METHODS: Using the Trialtrove database (September 16, 2025), we performed a registry-based systematic review with the strategy: "(Disease: Obesity) AND (Mechanism: Microbiome modulator)." We included interventional trials targeting overweight/obese populations with defined microbiome-modulating mechanisms; observational and withdrawn/suspended trials were excluded. Extracted data covered phase, status, intervention type, sponsor, location, and participant characteristics. Descriptive analyses used R software (v4.4.3).

RESULTS: Among 217 included trials, 131 (60%) were completed and 37 (17%) ongoing., Academic institutions led sponsorship (157 trials), followed by commercial (45) and government (14). Trials rose sharply after 2011, peaking at 34 in 2023 (over 80% of Phase IV trials that year). Probiotics dominated (141 trials), followed by synbiotics (21) and FMT (22). China (52) and the US (24) led research. Probiotics prevailed in Phases III/IV, whereas FMT concentrated in Phases II/IV with a higher termination rate.

CONCLUSIONS: This study reveals a rapidly growing yet uneven landscape. Probiotics remain the primary focus, academic institutions the main sponsors, and China/US the core hubs. The field has entered a post-marketing evaluation phase dominated by Phase IV studies. Limitations include reliance on a single database and lack of efficacy data, but the study highlights rapid expansion and heterogeneity in this field. Future research should integrate multiple data sources and quality assessments for more comprehensive evidence.},
}

@article {pmid42466885,
year = {2026},
author = {Mengoli, M and Boccia, F and Barone, M and Mele, F and Bertolino, L and Della Ratta, EE and De Feo, M and Durante-Mangoni, E and Turroni, S and Brigidi, P and Zampino, R},
title = {Oral, gut, and skin microbiota characterization in patients with heart valve disease with or without infective endocarditis: a pilot study.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0190825},
doi = {10.1128/spectrum.01908-25},
pmid = {42466885},
issn = {2165-0497},
abstract = {The relationship between host microbiota and infective endocarditis (IE) has been investigated by few studies. We compared the oral, gut, and skin microbiota profiles of patients awaiting heart valve replacement, both with and without IE, and correlated the profiles with the patients' clinical data, including the etiological agents and antibiotics received. Thirty-six patients were enrolled in a prospective, observational pilot study: 25 with IE (cases) and 11 with non-infective valve disease requiring surgery (controls). Clinical data and oral, fecal, and skin samples were collected before surgical treatment. Microbiota was profiled using 16S rRNA amplicon sequencing. Cases and controls were comparable, except for inflammatory parameters and prevalence of prosthetic valves, which were higher in cases. Causative IE pathogens were Staphylococcus spp., Streptococcus spp., and Enterococcus spp. Compared to controls, cases showed dysbiotic features in their oral, gut, and skin microbiota, including lower diversity in oral and skin communities and overall community depletion. Only a few bacteria were enriched, such as Oxalobacteraceae in the oral cavity and Bacteroides in the gut. There was low concordance between bacterial changes and blood isolates for most IE-causing pathogens, suggesting that dysbiosis may have effects beyond merely acting as a reservoir for specific pathogens. Dysbiosis may be a relevant yet underexplored factor associated with IE. Further studies are needed to clarify the underlying pathogenetic mechanisms.IMPORTANCEThe relationship between microbiota alterations and infective endocarditis has been explored in the literature, but the majority of available studies focus only on the oral microbiota. In this prospective observational pilot study, we analyzed three microbial ecosystems (oral, skin, and gut) in patients awaiting heart valve replacement with and without infective endocarditis. We observed dysbiotic features that are potentially associated with infective endocarditis. While these findings are preliminary, they suggest that future studies should investigate whether microbiota-targeted interventions, such as a probiotic regimen, could play a preventive role in patients with established IE risk factors, including valve defects, presence of prosthesis, or a history of prior IE.},
}

@article {pmid42304372,
year = {2026},
author = {Hiep, ND and Van Nut, L and Vy, TTT and Tin, LD},
title = {Catastrophic pelvic-perineal injuries with traumatic hemipelvectomy following a motorcycle collision: a multidisciplinary reconstruction case report.},
journal = {BMC surgery},
volume = {26},
number = {1},
pages = {},
pmid = {42304372},
issn = {1471-2482},
mesh = {Humans ; Male ; Middle Aged ; *Perineum/injuries/surgery ; *Hemipelvectomy ; *Accidents, Traffic ; *Plastic Surgery Procedures/methods ; Motorcycles ; *Multiple Trauma/surgery ; *Pelvis/injuries/surgery ; Pelvic Bones/injuries/surgery ; Skin Transplantation ; Crush Injuries/surgery ; },
abstract = {BACKGROUND: Catastrophic pelvic and perineal trauma with associated traumatic hemipelvectomy is extremely rare and carries a high mortality risk. These injuries often involve multisystem destruction, including genitourinary, anorectal, musculoskeletal, and vascular structures, presenting extraordinary challenges for surgical management and reconstruction. Reports of survivors, particularly from resource-limited settings, remain limited.

CASE PRESENTATION: A 52-year-old man presented in 2022 with devastating pelvic-perineal trauma following a high-energy motorcycle crash. He received initial first aid at a district hospital before being urgently transferred to our tertiary care center in Vietnam. Upon arrival, he was in profound hemorrhagic shock, with non-palpable pulses and unrecordable blood pressure. Operative findings revealed complete avulsion of the left hemipelvis, severe crush injury of the left lower limb, full-thickness rectal transection, bladder rupture, and complete loss of the external genitalia. He underwent prompt resuscitation, left hemipelvectomy, and fecal and urinary diversion, followed by staged reconstruction. Definitive wound coverage was achieved using a combination of local rotational flap, right profunda artery perforator (PAP) flap, and autologous skin grafting. The patient recovered well and was discharged after 112 days with stable vital signs and functioning urinary and fecal diversion.

CONCLUSIONS: This case demonstrates the survivability of catastrophic pelvic-perineal trauma with traumatic hemipelvectomy. It emphasizes the importance of multidisciplinary care, early hemorrhage control and surgical intervention, as well as adaptable reconstruction strategies in low-resource settings.

CLINICAL TRIAL NUMBER: Not applicable.},
}

Humans
Male
Middle Aged
*Perineum/injuries/surgery
*Hemipelvectomy
*Accidents, Traffic
*Plastic Surgery Procedures/methods
Motorcycles
*Multiple Trauma/surgery
*Pelvis/injuries/surgery
Pelvic Bones/injuries/surgery
Skin Transplantation
Crush Injuries/surgery

@article {pmid42458266,
year = {2026},
author = {Zhu, C and Wang, M and Meng, L and Zhao, Z and Han, H and Chang, Y and Zhang, S and Yang, Y},
title = {Gut microbiota dysbiosis in the pathogenesis of ulcerative colitis and the therapeutic efficacy of fecal microbiota transplantation: a meta-analysis.},
journal = {BMC gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12876-026-05091-y},
pmid = {42458266},
issn = {1471-230X},
support = {82560927//the National Natural Science Foundation of China/ ; 2024AAC05095//Natural Science Foundation for Ningxia Province/ ; 2024SF025//the Science and Technology Program of Yinchuan City/ ; 2022LCZX0013//Ningxia Hui Autonomous Region Clinical Medical Research Center for Anorectal Diseases/ ; 2025DPC05028//Science and Technology Basic Condition Construction Project of Ningxia Hui Autonomous Region/ ; 2024BEG02024//Key Research and Development Program of Ningxia Hui Autonomous Region/ ; },
abstract = {OBJECTIVE: To explore the correlation between gut microbiota dysbiosis and the pathogenesis of ulcerative colitis (UC), and to provide an evidence-based basis for clinical diagnosis and treatment.

METHODS: Randomized controlled trials (RCTs) were included through a systematic search of the PubMed, Medline, Web of Science, Cochrane Library, and EMBASE databases. The Cochrane Risk of Bias Tool (RoB 2) was used to evaluate the quality of the literature. RevMan 5.3 software was employed to conduct a Meta-analysis, and the pooled effect size (OR/RR) and 95% confidence interval (CI) were calculated. The primary outcome measures included the associations between gut microbial diversity, changes in the abundance of specific microbial groups and the onset of UC.

RESULTS: A total of 6 literatures were included, involving 171 study subjects (100 cases in the fecal microbiota transplantation (FMT) group and 71 cases in the control group), all of which were randomized controlled trials. There was no significant difference in the clinical response between the FMT group (ulcerative colitis patients receiving fecal microbiota transplantation intervention) and the control group (ulcerative colitis patients receiving conventional treatment or placebo) (RD = 0.17, 95% CI [-0.05-0.40], P = 0.14); the clinical remission in the FMT group was significantly better than that in the control group (OR = 2.20, 95% CI [1.05-4.59], P = 0.04); the changes in the microbiota composition in the FMT group were significantly higher than those in the control group (MD = 0.20, 95% CI [0.11-0.28], P < 0.001); there was no significant difference in the occurrence of adverse events between the FMT group and the control group (RD=-0.00, 95% CI [-0.15-0.14], P = 0.98); there was no significant difference in endoscopic remission between the FMT group and the control group (OR = 1.53, 95% CI [0.57-4.11], P = 0.40).

CONCLUSION: This exploratory meta-analysis suggested that gut microbiota dysbiosis may be associated with the onset of UC, manifested as reduced diversity, imbalanced microbiota structure, and changes in the abundance of specific microbial groups. However, given the limited number of included studies, these findings are hypothesis-generating and require validation in larger, well‑powered trials. Further exploration of the potential value of microbiota intervention in the treatment of UC is needed.},
}

@article {pmid42458949,
year = {2026},
author = {Khan, H and Wang, YM and Iftikhar, I and Arif, B and Khan, B and Kiyani, MM and Al-Hussain, F and Bashir, S and Li, HT},
title = {Gut-Brain Axis Mechanisms and Microbiome Abnormalities in Autism Spectrum Disorder and Therapeutic Implications.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X423517260330192710},
pmid = {42458949},
issn = {1875-6190},
abstract = {ASD has been associated with alterations of the microbiota-gut-brain axis, a bidirectional system that links gut microbiota to neural, endocrine, and immune pathways. Multi-omics studies indicate that most of the ASD affected individuals have lower levels of beneficial taxa, including Bifidobacterium, Lactobacillus gemelhinis, Faecalibacterium prausnitzii, and Roseburia species, and also enrichment with potentially pathogenic strains. Dysbiosis likely affects SCFA, especially butyrate, production. Butyrate acts via GPR41 and GPR43, which maintain the gut barrier and reduce inflammation. Lower butyrate and receptor activity can weaken the barrier, leading to systemic and neuroinflammation implicated in ASD. Effects of the microbiota on neurotransmission also seem pertinent, with alteration in tryptophan metabolism being able to affect central nervous system serotonin availability, and imbalance in GABA glutamate signaling potentially playing a role in excitatory inhibitory dysregulation. Immune crosstalk is paramount in these processes, as micro-bial products and SCFAs are able to influence microglial activity and brain-derived neurotrophic factor signaling with consequent impacts on synaptic plasticity and behavior. This narrative review synthesises societal momentum with current understanding and treatment approaches related to the microbiome of ASD. Probiotics, prebiotics, precision nutrition, and faecal microbiota transplanta-tion (FMT) have reported promising evidence of symptom reduction and, in some studies, behavior. Evidence is still mixed because of strain variation, dosing, delivery protocols, and follow-up. We delineate priorities for randomized, adequately powered experiments that incorporate longitudinal multi-omics, immune phenotyping, and standardized neurobehavioral assessments, while taking into account developmental timing and individual variation. Collectively, the current evidence suggests the gut-brain axis as a potential contributor to ASD biology and a potential target of therapy. Customized plans to rehabilitate SCFA production, enhance barrier function, and normalize neuro-immune and neurotransmitter pathways may augment current practice. Establishing causality and determining which patients benefit from which interventions when are the essential next steps.},
}

@article {pmid42459086,
year = {2026},
author = {Pérez-Reytor, D and Isla, E and Urrutia, ÍM and Plaza, N and García, K and Karahanian, E},
title = {The Role of Microbiota, Gut Integrity, and Neuroinflammation in Relapse Vulnerability in Alcohol Use Disorder.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X458517260624074839},
pmid = {42459086},
issn = {1875-6190},
abstract = {Alcohol use disorder is a chronic relapsing condition with significant neurobiological, psychological, and social implications. Relapse, defined as the resumption of clinically significant alcohol consumption following abstinence, represents a major barrier to sustained recovery. Emerging evidence indicates that the gut-brain axis may contribute to relapse vulnerability through persistent peripheral and central biological alterations. Chronic alcohol consumption can induce intestinal dysbiosis and disrupt epithelial integrity. This increases intestinal permeability and facilitates the translocation of bacterial endotoxins. These processes may promote systemic inflammation and sustained neuroimmune activation. Also, this can alter glutamatergic, dopaminergic, and GABAergic signaling pathways involved in cravings, negative emotions, and stress sensitivity. Alcohol-related dysbiosis also modifies microbial metabolites, including short-chain fatty acids and tryptophan catabolites, potentially reinforcing inflammatory and neurochemical imbalances. Comorbid depression may further amplify these interactions by enhancing pro-inflammatory signaling and emotional dysregulation. This could increase the risk of relapse. Preclinical studies suggest that microbiota-targeted interventions, such as strain-specific probiotics, fecal microbiota transplantation, and postbiotics including butyrate derivatives, can restore intestinal barrier function, attenuate neuroinflammation, and reduce relapse-like behaviors in experimental models. However, clinical translation remains limited, and longitudinal studies specifically evaluating relapse outcomes are insufficient. This narrative review integrates mechanistic and translational evidence linking gut dysbiosis, intestinal barrier dysfunction, systemic inflammation, and neuroimmune activation to relapse vulnerability in AUD. By situating relapse within an integrated gut-brain framework, we propose that microbiota-informed strategies may represent promising adjunctive approaches to complement existing relapse-prevention treatments.},
}

@article {pmid42459342,
year = {2026},
author = {Quan, Y and Chen, M and Cai, Y and Ling, L and Lao, Y and He, X and Wu, L},
title = {Analysis of washed microbiota transplant efficacy for autism and donor-recipient gut microbiota characteristics.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1823988},
pmid = {42459342},
issn = {2235-2988},
mesh = {Child ; Child, Preschool ; Female ; Humans ; Male ; *Autism Spectrum Disorder/therapy/microbiology ; *Autistic Disorder/therapy/microbiology ; Bacteria/classification/genetics/isolation & purification ; Bacteroides/genetics ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; *Gastrointestinal Microbiome ; Prevotella ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome ; },
abstract = {UNLABELLED: Emerging evidence suggests that washed microbiota transplantation (WMT) can be used to effectively treat autism spectrum disorder (ASD). This study aimed to evaluate the efficacy of WMT, investigate structural changes in the gut microbiota of children with ASD after WMT, and determine the relationship between donor and recipient gut microbiota characteristics in ASD with different treatment efficacies. This study included 38 ASD patients who underwent a full course of WMT from a single donor between July 2019 and December 2024. The clinical rating scale and stool samples were collected before and 4 weeks after WMT. Using 16S rRNA sequencing, patients were stratified by enterotype, Bacteroides (ET-B), or Prevotella (ET-P), to compare gut microbiota features with healthy donors and assess how microbial characteristics influence WMT efficacy. Finally, we found that WMT has statistically significant effects on the scale scores changes of core symptoms, sleep disturbances, and gastrointestinal symptoms in patients with ASD. In addition, the efficacy of WMT for ASD was correlated with donor and recipient gut microbiota characteristics before WMT. Among donors and recipients with Bacteroides as the dominant genus, the closer the recipient gut microbiota was to that of the donor, the better the efficacy of WMT in patients with ASD.

CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/index.html, identifier ChiCTR2400089296.},
}

Child
Child, Preschool
Female
Humans
Male
*Autism Spectrum Disorder/therapy/microbiology
*Autistic Disorder/therapy/microbiology
Bacteria/classification/genetics/isolation & purification
Bacteroides/genetics
*Fecal Microbiota Transplantation/methods
Feces/microbiology
*Gastrointestinal Microbiome
Prevotella
RNA, Ribosomal, 16S/genetics
Treatment Outcome

@article {pmid42459365,
year = {2026},
author = {Xu, H and Chen, W and Xiao, Q and Ren, J and Yang, D and Li, S and Cai, Y and Tuerheng, J and Tang, R and He, K and Wu, D},
title = {Microbiota-gut-brain axis imbalance: a promising therapeutic target for preserving brain health in high-altitude environment.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1820153},
pmid = {42459365},
issn = {1662-4548},
abstract = {High-altitude hypobaric hypoxia poses a significant threat to brain function, yet effective neuroprotective strategies remain limited. Emerging evidence highlights the microbiota-gut-brain axis (MGBA) as a key mediator in high-altitude-induced cognitive impairment, positioning it as a potential therapeutic target. This review synthesizes current knowledge on how high-altitude exposure dynamically reshapes gut microbial ecology, characterized by reduced diversity, phylum-level instability, and functional metabolic shifts. Furthermore, we delineate how such altitude-induced dysbiosis has been associated with neural dysfunction through interconnected pathogenic mechanisms that are proposed to link gut ecology to brain outcomes: intestinal barrier disruption with metabolic dysregulation, LPS/TLR4-mediated neuroinflammation, vagal and enteric nervous system alterations, oxidative stress imbalance, and neuroendocrine dysregulation. Most current evidence is correlational, and further research is needed to establish causality. A critical unresolved question is whether short-term, transient gut dysbiosis at high altitude can instigate long-lasting neurological deficits independent of ongoing microbial perturbation. We further evaluate microbiota-targeted neuroprotective strategies, including probiotics, prebiotics, and fecal microbiota transplantation, highlighting their distinct mechanisms and summarizing the current evidence supporting MGBA-targeted interventions for high-altitude brain health. Preclinical studies suggest these approaches hold promise by restoring barrier integrity, attenuating inflammatory signaling, and rebalancing microbial metabolite profiles, while human intervention evidence remains scarce. Finally, we discuss critical challenges and future directions for translating these mechanistic insights into personalized interventions, emphasizing deeper mechanistic exploration and the synergistic interactions among microbial taxa. These insights may inform more effective therapeutic strategies for the growing populations residing in or traveling to high-altitude regions.},
}

@article {pmid42461015,
year = {2026},
author = {Dong, W and Yan, C and Korwin-Mihavics, B and Stack, K and Hughes, G and Schmidt, A and Schwartz, KJ and Caballero-Flores, G and Alexander, M},
title = {β-Hydroxybutyrate precursor 1,3-butanediol modulates enteric pathogen susceptibility and Th17 responses via commensal bacteria.},
journal = {mSystems},
volume = {},
number = {},
pages = {e0032426},
doi = {10.1128/msystems.00324-26},
pmid = {42461015},
issn = {2379-5077},
abstract = {T helper 17 (Th17) cells are a critical T lymphocyte subset involved in mucosal immunity and host defense against enteric pathogens. Although ketogenic diets (KD) and the major ketone body β-hydroxybutyrate (BHB) reshape gut microbiota and suppress Th17 responses under defined diet conditions, it remains unclear whether elevation of BHB alone, independent of dietary macronutrient composition and systemic metabolic shifts, is sufficient to remodel Th17-inducing commensals and alter host susceptibility to enteric infection. Here, we used 1,3-butanediol (BD), a precursor metabolized to BHB independently of KD, to elevate systemic BHB levels in mice. BD treatment significantly reduced the frequency of ileal Th17 cells, as assessed by flow cytometry for Th17 markers IL-17A and RORγt. 16S rRNA gene sequencing revealed that BD altered gut microbial community structure, as indicated by beta-diversity analysis based on Bray-Curtis dissimilarity, and reduced Shannon diversity and evenness. Linear discriminant analysis effect size identified segmented filamentous bacteria (SFB) as significantly decreased in the ileum following BD treatment, and SFB abundance positively correlated with Th17 markers. Microbiota transplantation demonstrated that BD-shaped microbiota was sufficient to suppress Th17 responses in recipient mice, accompanied by reduced SFB abundance. In a Citrobacter rodentium infection model, BD treatment was associated with increased pathogen burden, and fecal C. rodentium levels were negatively correlated with SFB abundance. Together, these results support a model in which BD treatment, accompanied by elevated circulating BHB, reshapes the commensal microbiota, including reducing SFB levels, and is associated with dampened Th17 responses as well as increased susceptibility to enteric infection.IMPORTANCEDiet is a key determinant of gut microbial composition and mucosal immune function, yet the microbial mechanisms linking diet-mediated metabolic changes to immune regulation remain incompletely understood. T helper 17 (Th17) cells play central roles in both protective mucosal immunity and inflammatory pathology, making them a critical target of immunometabolic regulation. In this study, we show that 1,3-butanediol (BD) treatment, which leads to elevated circulating β-hydroxybutyrate (BHB) independently of diet, is associated with suppression of intestinal Th17 responses, remodeling of the gut microbiota, and reduced levels of segmented filamentous bacteria (SFB). We further demonstrate that BHB-associated microbiota changes are linked to increased susceptibility to enteric infection. This work provides a mechanistic framework illustrating how metabolic state can influence host immunity through selective effects on commensal microbes. These findings inform future studies of microbiota-mediated immune regulation.},
}

@article {pmid42449149,
year = {2026},
author = {Nøhr, AK and Overby, MG and Nielsen, MM and Torp, EA and Jensen, RH and Poulsen, LØ and Thorlacius-Ussing, O and Rasmussen, SL and Andersen, B and Gögenur, I and Sørensen, E and Pedersen, OBV and Erikstrup, C and Brøns, N and Schwinn, M and Mikkelsen, C and Bruun, MT and Jørgensen, MM and Bertelsen, CA and Hillingsø, JG and Høgdall, E and Ostrowski, SR and , and , and Bøgsted, M and Brøndum, RF},
title = {Combining genome-wide polygenic scores with registry data for colorectal cancer risk-based screening.},
journal = {British journal of cancer},
volume = {},
number = {},
pages = {},
pmid = {42449149},
issn = {1532-1827},
support = {R374-A2269//Kræftens Bekæmpelse (Danish Cancer Society)/ ; R374-A2269//Kræftens Bekæmpelse (Danish Cancer Society)/ ; },
abstract = {BACKGROUND: Polygenic risk scores (PRS) show potential for risk-based colorectal cancer (CRC) screening, but their utility must be assessed across diverse ancestries and tumour characteristics and compared with the current standard, the faecal immunochemical test (FIT).

DESIGN: The cohort included 112,204 individuals from the Copenhagen Hospital Biobank (8995 with adenoma and 9246 with CRC), all with linked genetic and health registry data. A subset (N = 20,658) also had FIT results. CRC PRSs were evaluated for their association with lifetime adenoma and CRC risk and their predictive value individually and combined with FIT.

RESULTS: PRS stratified population-calibrated lifetime adenoma and CRC risk independently of ancestry and sex. Individuals with a high PRS reached the incidence of low-PRS individuals up to 10 years earlier, between ages 45-60. PRS stratified risk across tumour location and histologies but showed no association among individuals with deficient mismatch repair tumours (N = 623). Combining PRS with FIT did not meaningfully improve prediction of adenoma or CRC at first screening, negative colonoscopy outcomes among FIT-positive participants, or outcomes within 2 years after a negative FIT.

CONCLUSION: PRS stratifies lifetime adenoma and CRC risk and may inform risk-based screening initiation and intensity but adds limited predictive value when combined with FIT.},
}

@article {pmid42449656,
year = {2026},
author = {Clavo, B and Córdoba-Lanús, E and Martínez-Sánchez, G and Cánovas-Molina, Á and Federico, M and Galván, S and Ramchandani-Vaswani, A and Piñero, JE and Antonilli, C and Benítez, G and Cobiella-Hernández, L and Pérez-Rodríguez, D and Pérez-Santana, C and Martín-Alfaro, R and Fernández-Tagarro, M and Díaz-Garrido, JA and González-Martín, JM and Martínez-Pérez, R and Lorenzo-Morales, J and Rodríguez-Esparragón, F},
title = {Gut Microbiota Dysbiosis and CIPN: State-of-the-Art Evidence and a Microbiota-Ozone Therapeutic Framework.},
journal = {Cancers},
volume = {18},
number = {13},
pages = {},
doi = {10.3390/cancers18132112},
pmid = {42449656},
issn = {2072-6694},
support = {PI23/01324//Institute of Health Carlos III/ ; CIGC/23-24//Cabildo de Gran Canaria/ ; CGC/2025/12551//Cabildo de Gran Canarias/ ; PIFIISC25/52//Fundación Canaria Instituto de Investigación Sanitaria de Canarias/ ; PIFIISC24/37//Fundación Canaria Instituto de Investigación Sanitaria de Canarias/ ; },
abstract = {BACKGROUND/OBJECTIVES: Chemotherapy-induced peripheral neuropathy (CIPN) affects up to 85% of patients receiving neurotoxic regimens, often leading to dose reduction and impaired quality of life, yet effective preventive or therapeutic options remain scarce. Emerging evidence implicates chemotherapy-induced gut microbiota dysbiosis in CIPN pathogenesis via a gut-nerve axis. Concurrently, rectal ozone insufflation (ROI) has been shown to modulate the gut microbiota and reduce inflammation in preclinical models. This article critically examines the evidence on the role of gut dysbiosis in CIPN, evaluates the microbiota-modulating capacity of rectal ozone therapy (OT), and assesses the biological plausibility of ozone as a microbiota-targeting intervention for CIPN, while explicitly distinguishing between established evidence and hypothetical mechanisms.

EVIDENCE SYNTHESIS: Neurotoxic agents induce dysbiosis marked by reduced microbial diversity, loss of short-chain fatty acid-producing bacteria, and expansion of pro-inflammatory taxa. Preclinical models demonstrate a causal role for specific microbial communities in CIPN, with microbiota depletion or fecal transplantation modulating neuropathic phenotypes. In human cohorts, dysbiosis severity correlates with CIPN symptoms. Preclinical studies show that ROI restores microbial balance, enhances short-chain fatty acid levels, and strengthens intestinal barrier function via Nrf2/HO-1 and SIRT1 pathways. Preliminary retrospective data from small case series (n = 7 and n = 15) report sustained symptom improvement in CIPN patients receiving OT. However, no human study has directly linked ozone-induced microbiota changes to clinical outcomes, and the clinical evidence for OT in CIPN remains limited to uncontrolled observations.

CONCLUSIONS: Convergent preclinical evidence supports a biological rationale for investigating ROI as a microbiota-targeting intervention in CIPN. However, this rationale remains largely hypothetical in the clinical setting. High-quality randomized controlled trials with longitudinal microbiome profiling are urgently needed to establish mechanistic causality and to determine whether the promising preclinical findings translate into clinically meaningful benefits. Until such evidence is available, the framework presented here should be regarded as hypothesis-generating rather than as a basis for clinical practice.},
}

@article {pmid42450578,
year = {2026},
author = {Li, J and Cheng, S and Zhang, W and Qiao, S and Zhang, L and Yao, M and Zhang, Y and Wang, B and Wu, C},
title = {Mulberroside A Alleviates Scopolamine-Induced Cognitive Deficits by Suppressing Neuroinflammation and Oxidative Stress via the Dubosiella-Associated Microbiota-Gut-Brain Axis.},
journal = {Biology},
volume = {15},
number = {13},
pages = {},
doi = {10.3390/biology15131030},
pmid = {42450578},
issn = {2079-7737},
support = {262102310255//Henan Provincial Science and Technology Key Project/ ; 26A180030//Key Scientific Research Foundation of Henan Colleges and Universities/ ; 252300423668//Natural Science Foundation of Henan/ ; ZKNUC2024030//Zhoukou Normal University High-level Talent Start-up Foundation/ ; },
abstract = {Mulberroside A (MsA) possesses neuroprotective effects, but whether it alleviates Alzheimer's disease (AD)-like cognitive impairment through the microbiota-gut-brain axis remains unclear. Using a scopolamine-induced mouse model of acute cognitive impairment (male ICR mice, n = 10/group), we demonstrated that daily administration of MsA (10, 20, and 30 mg/kg/day) for 5 weeks significantly ameliorated cognitive performance in novel object recognition and Morris water maze tests. At the optimal dose (30 mg/kg/day), MsA suppressed hippocampal microglial activation, reduced pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), and attenuated oxidative stress by decreasing malondialdehyde (MDA) while restoring superoxide dismutase (SOD) and glutathione (GSH) levels. MsA also strengthened intestinal barrier integrity (ZO-1, occludin) and significantly altered the gut microbiota, notably increasing the beneficial genus Dubosiella. Brain metabolomics indicated that MsA reversed scopolamine-induced metabolic disturbances, mainly restoring phospholipid balance. Correlation analysis demonstrated a strong gut-brain connection, with Dubosiella abundance positively associated with neuroprotective phospholipids and negatively with stress markers. Furthermore, fecal microbiota transplantation from MsA-treated donors successfully replicated these behavioral improvements in recipient mice, underscoring the functional involvement of the reshaped microbiome rather than a simple autonomous recovery. These results suggest that MsA alleviates AD-like cognitive impairment by reducing neuroinflammation and oxidative stress through microbiota remodeling, enhancing the intestinal barrier, and modulating the Dubosiella-associated gut-metabolite-brain axis, making MsA a promising multi-target nutraceutical for ameliorating AD-like cognitive deficits.},
}