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

@article {pmid41729099,
year = {2026},
author = {Zhang, B and Si, Y and Liu, Y and Wei, J and Li, M and Si, D and Li, H and Wang, X and Han, P and Wang, W and Bao, J and Cheng, L and Lei, Y and Ma, H and Liu, Y},
title = {Simulated microgravity induces cerebral dysfunction by disturbing protective microbiota-metabolite-microglia signaling across the gut‒brain axis.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2635820},
doi = {10.1080/19490976.2026.2635820},
pmid = {41729099},
issn = {1949-0984},
mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Rats ; *Weightlessness Simulation/adverse effects ; Male ; Fecal Microbiota Transplantation ; *Microglia/metabolism ; Hippocampus/metabolism ; Rats, Sprague-Dawley ; Signal Transduction ; *Brain/metabolism ; },
abstract = {Long-duration spaceflight characterized by microgravity adversely affects operator proficiency postlanding, yet the mechanisms by which microgravity induces cerebral dysfunction refractory to short-term recovery among astronauts remain poorly defined. Here, we demonstrate that simulated microgravity (SMG) leads to chronic behavior disorders and cognitive deficits via a microbiota-metabolite-brain axis. Fecal microbiota transplantation (FMT) from long-term SMG-treated donor rats to recipients (n = 5 per group) under normal gravity (NG) induces anxiety-like behaviors and spatial working memory disturbances by impairing synaptic plasticity in the hippocampus, reproducing the phenotype of SMG-exposed rats. SMG destroys intestinal barriers and alters the gut microbiota to a proinflammatory state with an increased abundance of Proteobacteria but decreased production of linoleic acid (LA) and LA-derived metabolites, which is highly associated with neuroinflammation in the hippocampus. Mechanistically, LA can be taken up by the hippocampus under NG conditions, and then block inflammatory microglial activation by interacting with signal transducer and activator of transcription 1 (STAT1) and inhibiting its phosphorylation at Tyr 701 and Ser 727. However, the Proteobacteria, especially Pseudomonas aeruginosa, tend to be the dominant phylum in gut microbiota under SMG conditions and consume large amounts of LA, breaking LA-dependent immune homeostasis in the central nervous system (CNS). Dietary supplementation with LA significantly mitigated SMG-induced neuroinflammation and cognitive impairment. Taken together, our findings in SD rats models reveal a critical role for gut microbiota dysbiosis in simulated microgravity-associated encephalopathy, offering a novel strategy for LA replenishment to improve brain function during spaceflight.},
}

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

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid41723574,
year = {2026},
author = {Benedé-Ubieto, R and Estévez-Vázquez, O and Acar, R and Leal-Lassalle, H and Gutierrez, AH and Redondo-Urzainqui, A and Iborra, S and Odintsova, VE and Tyakht, A and Herranz, JM and Firat, Z and Basol, M and Korkmaz, B and Sanz-García, C and Juanola, O and Caparrós, E and Francés, R and Ciudin, A and Pericàs, JM and Gómez-Santos, B and Aspichueta, P and Treichel, N and Clavel, T and Reißing, J and Bruns, T and Bartneck, M and Mazariegos, MS and Wolters, JC and Jorquera, G and Liedtke, C and Vaquero, J and Bañares, R and Cakan-Akdogan, G and Ávila, MA and Konu, O and Cubero, FJ and Nevzorova, YA},
title = {Alcohol consumption in metabolic dysfunction-associated steatotic liver disease (MASLD): understanding the gut-liver crosstalk for clinical translation.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2631834},
doi = {10.1080/19490976.2026.2631834},
pmid = {41723574},
issn = {1949-0984},
mesh = {Animals ; Humans ; *Gastrointestinal Microbiome/drug effects ; Mice ; Male ; *Liver/metabolism/pathology/drug effects ; Disease Models, Animal ; *Alcohol Drinking/adverse effects ; Zebrafish ; Mice, Inbred C57BL ; Diet, High-Fat/adverse effects ; *Fatty Liver/microbiology/metabolism/etiology ; Hep G2 Cells ; Fecal Microbiota Transplantation ; Female ; Diet, Western/adverse effects ; Hepatocytes/metabolism ; Dysbiosis ; Middle Aged ; },
abstract = {OBJECTIVE: In the present study, we investigated the role of the gut-liver crosstalk in the pathogenesis of steatotic liver disease (SLD) induced by the compounding and deleterious effects of alcohol and metabolic risk factors, and explored the potential translational aspects of microbiome-based interventions.

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

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

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

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

@article {pmid41723572,
year = {2026},
author = {Liang, H and Ding, X and Liu, S and Tong, S and Wang, X and Zhang, Z and Wang, W and Zhang, X and Yuan, Y and Jiang, Y and Sun, T},
title = {Aging-caused the changes of the gut microbiota drive intestinal barrier dysfunction and increase sepsis susceptibility.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2630475},
doi = {10.1080/19490976.2026.2630475},
pmid = {41723572},
issn = {1949-0984},
mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; Mice ; *Sepsis/microbiology/metabolism ; Humans ; *Aging ; Male ; Feces/microbiology ; Mice, Inbred C57BL ; Histamine/metabolism ; *Intestinal Mucosa/metabolism/microbiology ; Female ; Bacteria/classification/genetics/isolation & purification/metabolism ; Fecal Microbiota Transplantation ; Aged ; Disease Susceptibility ; Disease Models, Animal ; Middle Aged ; },
abstract = {Physiological and pathological changes associated with aging contribute to deteriorating disease prognosis in sepsis. However, the mechanisms by which these disturbances exacerbate inflammation remain underexplored. In this study, fecal samples were collected from aged and young septic patients and mice and subsequently transplanted into young pseudo-germ-free mice via fecal microbiota transplantation. Fecal, colon tissue, and blood samples were collected to be used 16S rDNA sequencing to characterize the gut microbiota, histopathological examination, enzyme-linked immunosorbent assay and FITC-dextran intestinal permeability assay to assess gut injury and gut barrier function. Additionally, nontargeted and targeted metabolomics were used to identify differential metabolites in the feces of aged and young septic mice. To further validate the roles of specific bacterial strains and their metabolites in sepsis, genetically engineered bacteria were used in both in vivo and in vitro experiments. The results showed that an increased abundance of Klebsiella aerogenes (K. aero) in aged hosts, which led to elevated histamine (HA) production and exacerbated intestinal barrier dysfunction. Importantly, K. aero strains carrying a histidine decarboxylase gene variant were identified as major HA producers. Mechanistically, HA was shown to drive intestinal barrier dysfunction by inhibiting Nlrp6 expression and its subsequent binding to LC3, thereby impairing autophagy. Treatments that modulated HA levels or overexpressed Nlrp6 ameliorated inflammation in septic mice. These findings suggest that targeting the HA-Nlrp6-LC3 axis could offer a novel therapeutic approach for managing sepsis, particularly in aged populations.},
}

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid41588460,
year = {2026},
author = {Geng, F and Zhao, N and Zhou, L and Liu, XT and Chen, X and Wang, ZT and Zhang, ZJ and Ren, QG},
title = {Cry2 deficiency leads to cognitive impairment through the microbiota-gut-brain axis mediated S1P/NLRP3/IL-1β pathway in mice.},
journal = {Journal of neuroinflammation},
volume = {23},
number = {1},
pages = {71},
pmid = {41588460},
issn = {1742-2094},
support = {KYCX23_0322//the Postgraduate Research & Practice Innovation Program of Jiangsu Province/ ; 81870850//National Natural Science Foundation of China/ ; GSP-LCYJFH07//Zhongda Hospital Affiliated to Southeast University, Jiangsu Province High-Level Hospital Construction Funds/ ; },
abstract = {BACKGROUND: Alzheimer’s disease (AD) is characterized by extracellular Aβ deposition and tau hyperphosphorylation, leading to synaptic dysfunction and cognitive decline. Mounting evidence indicates that circadian rhythm disorders are associated with increased AD risks. Growing evidence implicates the microbiota-gut-brain axis and its metabolites as critical modulators of both circadian physiology and AD pathology. However, the molecular mechanism through which circadian disturbance modulates gut-brain communication to influence AD pathogenesis remains poorly understood.

METHODS: Core circadian clock gene expression was assessed across four AD human brain datasets, and found Cry2 to be the only gene consistently downregulated. To investigate its functional role in vivo, we established a mouse model with hippocampal-specific Cry2 knockdown. Cognitive performance, gut microbiota composition, and metabolic alterations were evaluated using the Morris water maze, 16 S rRNA sequencing, and untargeted metabolomics, respectively. Intestinal barrier integrity, blood-brain barrier function, and neuroinflammatory signaling were examined through immunohistochemistry, immunofluorescence, and Western blotting. The contribution of microbiota disturbance was tested using fecal microbiota transplantation (FMT). The involvement of sphingolipid signaling was further assessed through FMT, pharmacological modulation with the S1PR agonist FTY720, NLRP3 knockout mice, and microglial assays.

RESULTS: We found that the expression of Cry2 consistently decreased in the AD group in four AD-related datasets. Then, knockdown of Cry2 in the hippocampus (shCry2) caused dysbiosis of gut microbiota, intestinal barrier impairment, cognitive dysfunction and tau pathology in mice. Intriguingly, along with the disturbance in intestinal sphingolipid metabolism pathways, activation of the S1P/NLRP3/IL-1β pathway was found in the brain of shCry2 mice. Transplantation of “shCry2 microbiota” mimicked the pathological and behavioral changes induced by hippocampal Cry2 deficiency. Administration of S1PR agonist FTY720 significantly improved cognitive impairment and decreased the expression of NLRP3 in shCry2 mice, and knockdown of Cry2 in NLRP3[−/−] mice alleviated tau pathology and cognitive impairment. FTY720 and S1PR1 antagonist W146 dose-dependently modulated the expression of NLRP3 in BV2 cells. Overexpressing Cry2 in the hippocampus significantly alleviated the tau pathology and cognitive decline in APP/PS1 mice.

CONCLUSION: Hippocampal Cry2 deficiency leads to cognitive impairment through the gut-brain axis mediated S1P/NLRP3/IL-1β pathway and might provide a potential therapeutic target for AD.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-026-03706-5.},
}

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid41708595,
year = {2026},
author = {Moses, AB and Yeh, AC},
title = {The gut microbiome in graft-versus-host disease: mechanisms of immune modulation and therapeutic approaches.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2631224},
doi = {10.1080/19490976.2026.2631224},
pmid = {41708595},
issn = {1949-0984},
mesh = {*Graft vs Host Disease/immunology/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome/immunology ; Animals ; Hematopoietic Stem Cell Transplantation/adverse effects ; Immunity, Innate ; T-Lymphocytes/immunology ; Gastrointestinal Tract/microbiology/immunology ; Adaptive Immunity ; Probiotics/administration & dosage ; },
abstract = {Graft-versus-host disease (GvHD) remains a major complication of allogeneic hematopoietic stem cell transplantation and occurs when T cells from the donor graft target recipient-derived antigen on host tissue. The involvement of the gastrointestinal (GI) tract drives morbidity and mortality-not coincidentally, the GI tract also harbors the most complex and abundant human microbial reservoir. In this review, we first revisit how the microbiota initiates, propagates, and protects against GvHD in the context of both innate and adaptive immunity. Historically, the impact of the microbiota on GvHD has been ascribed primarily to the activation of innate immunity, setting the stage for donor alloreactivity. Although established models of GvHD focus on donor-host genetic disparity as the principal driver of donor T-cell activation, commensal microbes in the GI tract, whose collective gene content exceeds that of the human genome by more than two orders of magnitude, constitutes an immense and poorly understood source of potential T-cell antigens. We next discuss the evolution of therapeutic approaches aimed at modifying the microbiota to improve GvHD outcomes, incorporating over 40 clinical studies spanning the last 40 years, from broad decontamination strategies to pre/probiotic approaches and targeted ecosystem replacement, including fecal microbiota transplantation.},
}

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid41580828,
year = {2026},
author = {Yi, S and Zhuang, X and Luo, L and Fu, L and Dong, Z and Wang, K and Jiang, Y and Yang, X and Hei, F},
title = {Gut microbiota and metabolites in acute lung injury: mechanisms and therapeutic perspectives.},
journal = {Respiratory research},
volume = {27},
number = {1},
pages = {82},
pmid = {41580828},
issn = {1465-993X},
support = {Grant CX24PY21//Chinese Institutes for Medical Research/ ; },
abstract = {UNLABELLED: Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), represent a clinical syndrome with high mortality, characterized by excessive pulmonary inflammation and oxidative stress. Despite advancements in conventional supportive care, mortality rates for ALI/ARDS remain persistently high (30%-50%). In recent years, increasing attention has focused on the regulatory mechanisms of the gut microbiota and their metabolites in ALI through the bidirectional ‘gut-lung axis’ interaction. This paper systematically reviews the mechanisms by which gut dysbiosis exacerbates lung inflammation and barrier damage via immune cell migration, inflammatory pathway activation, and metabolite imbalance. It also explores the potential of microbiome-based interventions—including probiotics, fecal microbiota transplantation (FMT), and dietary modification—for ALI treatment. This review not only elucidates the complex link between the gut microbiota and lung disease but also provides a theoretical basis for developing novel diagnostic and therapeutic approaches targeting the gut-lung axis. These insights hold significant implications for improving ALI patient prognosis and advancing precision medicine.

GRAPHICAL ABSTRACT: [Image: see text]},
}

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid41702649,
year = {2026},
author = {Qi, X and Yang, M and Liu, X and Ma, L and Kaifi, JT and Ericsson, AC and Kimchi, ET and Staveley-O'Carroll, KF and Li, G},
title = {Modulating Bacteroides to boost anti-PD-1 immunotherapy in HCC.},
journal = {Journal for immunotherapy of cancer},
volume = {14},
number = {2},
pages = {},
doi = {10.1136/jitc-2025-013755},
pmid = {41702649},
issn = {2051-1426},
mesh = {*Carcinoma, Hepatocellular/drug therapy/immunology/therapy ; Animals ; Mice ; *Liver Neoplasms/drug therapy/immunology ; Humans ; *Immunotherapy/methods ; *Gastrointestinal Microbiome/immunology ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors ; *Bacteroides ; *Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Male ; },
abstract = {BACKGROUND: The gut microbiota is increasingly recognized as a critical external regulator along the gut-liver axis, influencing hepatocarcinogenesis and modulating responses to immunotherapy. However, the specific microbial determinants, underlying mechanisms, and potential clinical applications remain incompletely elucidated.

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

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

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

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

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

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

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

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

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

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

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

@article {pmid41698880,
year = {2026},
author = {Huang, T and Yang, H and Zhang, L and Wang, X and Chen, Y and Dai, H and Hashimoto, K and Luo, Y and Pu, Y and Liu, Y},
title = {HLA-B27-associated gut microbiota and amino acid perturbations promote ankylosing spondylitis through M1 macrophage activation.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2630561},
doi = {10.1080/19490976.2026.2630561},
pmid = {41698880},
issn = {1949-0984},
mesh = {*Gastrointestinal Microbiome ; Humans ; *HLA-B27 Antigen/genetics/immunology/metabolism ; *Spondylitis, Ankylosing/microbiology/immunology/metabolism/genetics ; Animals ; Mice ; Male ; Female ; *Amino Acids/metabolism ; *Macrophage Activation ; Fecal Microbiota Transplantation ; Adult ; Middle Aged ; *Macrophages/immunology ; Bacteria/classification/genetics/isolation & purification/metabolism ; Feces/microbiology ; Metabolomics ; Dysbiosis ; },
abstract = {Ankylosing spondylitis (AS) is strongly associated with the human leukocyte antigen B27 (HLA-B27), yet how this genetic risk factor interacts with the gut microbiome remains unclear. We integrated fecal gut microbiota analysis, untargeted metabolomics, and clinical phenotyping in 88 participants, including HLA-B27-positive patients with AS (n = 28), HLA-B27-positive healthy controls (n = 30), and HLA-B27-negative healthy controls (n = 30). HLA-B27 positivity, particularly in AS, was associated with marked alterations in gut microbial composition and metabolic profiles, with forty bacterial species showing progressive disease-related shifts across cohorts. Integrated pathway and metabolomic analyses identified three amino acid-related pathways consistently disrupted in AS: tryptophan metabolism, cysteine metabolism, and pyruvate-centered biosynthesis of branched-chain amino acids, ornithine, and lysine. Correlation network analyses linking differential taxa, metabolites, and clinical indices revealed previously unrecognized microbial and metabolic signatures that robustly distinguished AS from both control groups. To explore causality, fecal microbiota transplantation (FMT) from clinical donors into antibiotic-treated mice recapitulated key disease-relevant features, including impaired intestinal barrier function, systemic inflammation, trabecular bone loss, and polarization of macrophages toward a proinflammatory M1 phenotype. Mechanistic validation identified cinnabarinic acid as a critical microbial-derived metabolite that suppresses M1 macrophage polarization via activation of the aryl hydrocarbon receptor (AhR) pathway and confers protection in the FMT model. Together, these findings support a model in which HLA-B27-associated gut dysbiosis and metabolic reprogramming promote AS pathogenesis through macrophage-mediated inflammation and osteocatabolic signaling, highlighting microbial-metabolic pathways as potential therapeutic targets.},
}

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

@article {pmid41578351,
year = {2026},
author = {He, Z and Guo, N and Yu, C and Zou, T and Lu, H and Lv, Y and Wang, T and Dong, H},
title = {Gut microbiota remodeling by Astragalus membranaceus stems and leaves correlates dual modulation of arachidonic acid and tryptophan metabolism to counteract perinatal stress-induced hemometabolic dysregulation in sows.},
journal = {Animal microbiome},
volume = {8},
number = {1},
pages = {21},
pmid = {41578351},
issn = {2524-4671},
support = {32302916//National Natural Science Foundation of China/ ; 2022YFD1801103//National Key Research and Development Program of China/ ; },
abstract = {UNLABELLED: Perinatal stress (PS) commonly occurring in high-yielding sows has gradually become a factor threatening the reproductive and immunoreactive performances by impairing their fecundity. Despite the Astragalus membranaceus, a herb native to northern China, has been applied to relieve PS, it is still unclear whether its aerial parts, i.e., Astragalus membranaceus stems and leaves (AMSL), protects against reproductive damage induced by PS in sows and how it works. Here, we aims to evaluate the novel roles of AMSL in alleviating PS-induced reproductive disorders in sows (n = 45) and their offsprings (n = 45). Amplicon-based microbiota analysis revealed that maternal dietary supplementation of AMSL significantly induced affluent Prevotella, Limosilactobacillus, Rikenellaceae_RC9_gut_group, and Clostridium_sensu_sticto_1 in perinatal sows and was correlated with accelerated maturation of gut microbiota in preweaning piglets. Untargeted metabolomics were used to profile serum and fecal metabolites, and serum arachidonic acid (AA)-related metabolites were markedly diminished on the day of farrowing and from neonatal piglets at birth post AMSL administration in sows. Pearson correlation analyses indicated that enriched indole-related metabolites and fewer kynurenine-related metabolites were strongly positively correlated with these four bacteria. Then, fecal microbiota transplantation (FMT) in pregnant mice were conducted to illustrate whether the protective role of AMSL is mediated by remodeling gut microbiota. PS and immunosuppressive symptoms were both largely ameliorated in mice that had received fecal bacteria of sows pretreated with AMSL. These results support the notion that the beneficial effects of AMSL were primarily achieved via gut microbiota modulation, which related to improved tryptophan metabolism and inhibited the excessive synthesis of AA in blood circulation. Our findings provide new insights into the potential application of AMSL as a sustainable feed additive.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42523-026-00518-z.},
}

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

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

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

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

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

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

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

@article {pmid41694125,
year = {2025},
author = {Fu, J and Zhang, Y and Gao, J and Lan, M and Zhang, Z and Liang, R and Zhou, H and Liu, S and Zhou, Z and Zhao, J and Yu, X and Liu, Y and Han, P and Chen, X and Lin, C and Guo, Q},
title = {Efficacy effects of fecal microbiota transplantation on depressive symptoms: a meta-analysis based on randomized controlled trials.},
journal = {Frontiers in psychiatry},
volume = {16},
number = {},
pages = {1629290},
pmid = {41694125},
issn = {1664-0640},
abstract = {BACKGROUND: The gut microbiota plays a crucial role in the bidirectional communication between the gut and the brain. Although there has been much discussion in recent years on the link between depression and fecal microbiota transplantation (FMT), its effectiveness in treating depression remains debatable. The purpose of this study was to examine if FMT alleviates depression or its symptoms and to examine the possible impacts of various demographic subgroups and supplementation techniques.

METHODS: A systematic search of articles in the database (PubMed, EMBASE, Web of Science, and Cochrane libraries) before March 2025. The Revman 5.3 software was used to incorporate standardized mean difference (SMD) and assess quality of evidence using recommended grading assessment, development and evaluation tools to investigate whether FMT efficacy on depressive symptoms or depression.

RESULTS: This meta-analysis included seven studies involving 235 subjects, and the results did not support a significant treatment effect of FMT on depression [SMD: -0.10; 95%CI: (-0.60,0.41); p = 0.71]. Subgroup analysis showed the correlation between the intervention effect of FMT and confirmed depression at baseline, intervention dose, donor source, repeated route of drug administration, and dietary habits of subjects.

CONCLUSIONS: There is insufficient evidence to support a significant efficacy of FMT on depressive symptoms, but subgroup analyses suggest that FMT may have a better antidepressant effect in the population with confirmed depression, and therefore more randomized controlled trials are necessary to validate the association between FMT and depressive symptoms.},
}

@article {pmid41691676,
year = {2026},
author = {Chen, Z and Chen, A and Chen, Y and Chen, X and Lin, H and Tu, H},
title = {Pathogenic Mechanisms and Therapeutic Approaches of Intestinal Flora in the Immune Microenvironment of Hepatocellular Carcinoma.},
journal = {Current medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0109298673423753251229070800},
pmid = {41691676},
issn = {1875-533X},
abstract = {This paper initially presents an overview of the fundamental aspects of Hepatocellular carcinoma (HCC), intestinal microbiota, and the immune microenvironment. The paper discusses how metabolites from intestinal microbiota, such as lipopolysaccharides (LPS), bile acids, short-chain fatty acids (SCFA), branched-chain amino acids (BCAA), tryptophan, choline, and inosine, influence immune cell activation and the immune microenvironment, thereby contributing to HCC development. Current laboratory methods focus on using immune checkpoint inhibitors, acetic acid, fecal microbiota transplantation, probiotics, antibiotics, and other strategies to alter intestinal microbiota composition or suppress metabolitemediated immune responses to treat HCC. This study offers suggestions for potential avenues of future investigation. A systematic analysis of the interrelationship between intestinal microbiota, HCC, and the immune microenvironment facilitates the provision of refined and personalized therapeutic options in clinical settings, enhances patient survival rates.},
}

@article {pmid41691535,
year = {2026},
author = {Blaney, H and Asgharpour, A},
title = {The alcohol-associated hepatitis treatment landscape.},
journal = {Current opinion in gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1097/MOG.0000000000001158},
pmid = {41691535},
issn = {1531-7056},
abstract = {PURPOSE OF REVIEW: Alcohol-associated hepatitis is a severe form of alcohol-associated liver disease and is associated with a high mortality. Treatment of alcohol-associated hepatitis has historically been limited, with few therapies demonstrating survival benefit. However, multiple promising new therapies are on the horizon, with this review highlighting recent advances in alcohol-associated hepatitis treatment.

RECENT FINDINGS: Multiple new pharmacological agents targeting different mechanisms are under study for alcohol-associated hepatitis, including larsucosterol, F-652, and INT-787. Manipulation of the gut-brain axis has also been leveraged for alcohol-associated hepatitis, with use of fecal microbiota transplant and other modalities. Early liver transplantation, while not universally available, has offered improved survival with similar outcomes compared to other etiologies of liver disease. Living donor liver transplantation has also been investigated in alcohol-associated hepatitis, with promising results. While steroids still remain the mainstay of therapy, recent studies have offered nuances to their use, including use of a taper to reduce risk of infection without changing efficacy.

SUMMARY: Medical management of alcohol-associated hepatitis has remained largely unchanged since the 1970 s. However, promising therapies targeting multiple aspects of pathophysiology are on the horizon, including a planned phase 3 trial for larsucosterol, an active phase 2a study with INT-787 and a planned trial using F-652.},
}

@article {pmid41690650,
year = {2026},
author = {Ma, C and Zou, Z and Zhao, W and Rao, Y and Liu, B and Sun, M and Chen, D},
title = {The Gut Microbiota in Salmonella Typhi Infection and Translocation: Mechanisms of Colonization Resistance, Pathogen Subversion, and Prospects for Microecological Intervention.},
journal = {Microbial pathogenesis},
volume = {},
number = {},
pages = {108381},
doi = {10.1016/j.micpath.2026.108381},
pmid = {41690650},
issn = {1096-1208},
abstract = {The systemic establishment of the strictly human-adapted pathogen Salmonella Typhi critically depends on functional interplay between its virulence effectors and the host gut microbiome. Organized within a "colonization-toxicity-immunity- microecological intervention" framework, this review synthesizes recent molecular and multi-omics evidence to delineate key host-pathogen-microbiota dynamics. During colonization, a healthy gut microbiota exerts multi-layered colonization resistance through nutrient and niche competition, as well as via microbial metabolites such as short-chain fatty acids and secondary bile acids. Current evidence more consistently supports DDR-associated cellular senescence and type I IFN signaling as major outcomes of typhoid toxin activity; pyroptosis, if observed, appears context-dependent and should not be presented as a universal endpoint. Concurrently, the Vi capsule and type III secretion system (T3SS) effector proteins (e.g., SteD) act in concert to disrupt innate and adaptive immunity, reprogram the mucosal immunometabolic landscape, and exacerbate microbial dysbiosis. We also evaluate the strength of evidence and applicability of microbiota-targeted interventions, including probiotics, prebiotics, synthetic microbial consortia, and fecal microbiota transplantation (FMT), and address the limitations of extrapolating from Salmonella Typhimurium mouse models to human Salmonella Typhi,typhoid toxin infection. Furthermore, we emphasize the need for cross-validation using human intestinal organoids, humanized immune mice, and population-level data, integrated with metabolomic and immune profiling, to establish a definitive "metabolism-immunity-toxicity" causal chain. Confronting the persistent evolution of H58 and other drug-resistant lineages, we propose a paradigm shift through the convergence of genomic epidemiology, microbiota-informed risk stratification, and vaccine-microbiota synergism; these elements collectively chart an implementable roadmap for precision medicine in disease control.},
}

@article {pmid41689915,
year = {2025},
author = {Li, M and Yuan, F and Li, G and Fu, Y and Wei, X},
title = {Clinical analysis of fecal microbiota transplantation for refractory acute gastrointestinal graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a five-year retrospective study.},
journal = {Cytotherapy},
volume = {28},
number = {4},
pages = {102043},
doi = {10.1016/j.jcyt.2025.102043},
pmid = {41689915},
issn = {1477-2566},
abstract = {BACKGROUND AIMS: Refractory acute gastrointestinal graft-versus-host disease (GI-aGVHD) is a severe complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is associated with significantly increased mortality. Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic strategy for this condition, and its efficacy and safety have garnered substantial attention in clinical research.

OBJECTIVE: To explore the clinical efficacy and safety of FMT for refractory acute GI-aGVHD after allo-HSCT.

METHODS: Data from 22 patients with refractory GI-aGVHD who received FMT and 20 patients who did not undergo FMT, all diagnosed with refractory GI-aGVHD after allo-HSCT and treated at Henan Cancer Hospital between December 2017 and March 2023, were retrospectively analyzed to evaluate short-term efficacy, safety, and long-term survival outcomes.

RESULTS: FMT significantly reduced the median diarrhea volume (1300 versus 450 mL, P = 0.017) and frequency (10 versus 5.5 times/d, P = 0.049) in the FMT group, whereas the control group showed no significant improvement in either parameter (diarrhea volume: 1350 versus 900 mL, P > 0.05; frequency: 10 versus 9 times/d, P > 0.05). The FMT group exhibited significantly higher complete response (CR) (31.8% versus 5%, P = 0.047) and overall response rate (ORR) (59.1% versus 25%, P = 0.033) compared with the control group. Subgroup analyses showed that patients with isolated intestinal involvement (ORR = 100%) and those without bloody stool before FMT (ORR = 78.6%) had superior responses to FMT. The FMT group achieved a median progression-free survival (PFS) of 30 (10-2113) days and a median overall survival (OS) of 150 (51-2130) days, with the 100-day, 1-year and 3-year PFS rates of 40.9%, 28.1%, and 28.1%, respectively, and the 100-day, 1-year and 3-year OS rates of 59.1%, 50.0% and 34.3%. In contrast, the control group had notably poorer survival outcomes: median PFS was 23 (7-1820) days, median OS was 80 (20-1901) days, while the 100-day, 1-year, and 3-year PFS rates remained 5% across all time points, and the 100-day, 1-year, and 3-year OS rates were 20.0%, 10.0%, and 10%.

CONCLUSION: FMT is effective and safe as a clinical treatment for refractory GI-aGVHD after allo-HSCT, and the effectiveness of FMT can be used as a prognostic indicator for long-term survival in refractory GI-aGVHD.},
}

@article {pmid41688126,
year = {2026},
author = {Edvinsson, M and Thelander, A and Dimopoulos, N and Pauksens, K},
title = {Chronic norovirus infection in a patient with Good's syndrome resolved after fecal microbiota transplantion and improved nutrional status.},
journal = {Infectious diseases (London, England)},
volume = {},
number = {},
pages = {1-6},
doi = {10.1080/23744235.2026.2631113},
pmid = {41688126},
issn = {2374-4243},
abstract = {Norovirus may cause chronic infection in immunocompromised patients. Both B-cell and T-cell responses are important for viral clearance. Currently, there is no established treatment but various substances have been evaluated, yielding mixedresults. This report presents a patient diagnosed with Good's syndrome, which includes hypogammaglobulinemia, who suffered from a chronic norovirus infection for several years. Nitazoxanide treatment was administered for 4 weeks due to ongoing diarrhoea and declining nutritional status; however, symptoms did not improve. Subsequently, fecal microbiota transplantation (FMT) was assessed using a single dose of cultured human microbiota. This procedure improved symptoms but did not eliminate the infection. The patient's symptoms returned after 6 months, at which time two FMT doses were administered, resulting in symptom amelioration. Three months later, a more pronounced relapse led to severe nutritional decline, most notably manifesting as overt vitamin A deficiency accompanied by visual impairment. Again, the patient underwent two administrations of FMT; however, relapse occurred shortly thereafter. Parenteral nutrition was then initiated after consultation with the hospital's clinical nutrition team. Symptoms promptly improved, with a decrease in diarrhoea and an increase in weight. A stool sample collected 2.5 months following the final FMT combined with parental nutrition demonstrated no detectable norovirus, and the patient has remained in stable health for 3 years. We believe that the patient's chronic norovirus infection was resolved through the combination of enhanced nutritional status and FMT.},
}

@article {pmid41687676,
year = {2026},
author = {Thiele, M and Bhadoria, AS and Mellinger, J and Zelber-Sagi, S and Manousou, P and Shawcross, DL and Bhala, N},
title = {Global gains, metabolic pains: unmasking the hidden burden on liver health.},
journal = {The lancet. Gastroenterology & hepatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2468-1253(26)00006-3},
pmid = {41687676},
issn = {2468-1253},
}

@article {pmid41687433,
year = {2026},
author = {Libriani, S and Facchinetti, G and Marti, F and Tolentino Diaz, MY and Sandri, E},
title = {The association between gut microbiota and cognitive decline: A systematic review of the literature.},
journal = {Nutrition research (New York, N.Y.)},
volume = {147},
number = {},
pages = {16-31},
doi = {10.1016/j.nutres.2026.01.003},
pmid = {41687433},
issn = {1879-0739},
abstract = {The gut-brain axis has emerged as a key pathway in the pathogenesis of neurodegenerative disorders, with age-related shifts in gut microbiota potentially contributing to cognitive decline and dementia progression. This systematic review evaluated the effects of microbiota-targeted interventions on cognitive outcomes in adults aged >45 years with cognitive impairment or at risk of dementia. Randomized controlled trials and quasi-experimental studies published up to June 2025 were identified through PubMed, COCHRANE, CINAHL, Web of Science, and EMBASE. Methodological quality, assessed using the Joanna Briggs Institute Critical Appraisal Checklist, ranged from moderate to high.Fifteen studies involving 4,275 participants across Europe, Asia, North America, and the Middle East met inclusion criteria. Interventions included probiotic supplementation, fecal microbiota transplantation, and dietary strategies such as Mediterranean and ketogenic diets. Cognitive outcomes were measured using validated tools, including the Mini-Mental State Examination, Montreal Cognitive Assessment, and Repeatable Battery for the Assessment of Neuropsychological Status. Narrative synthesis indicated that microbiota modulation was associated with improvements in memory, executive function, and global cognition, particularly in individuals with prodromal or mild cognitive impairment. Reported benefits correlated with increased microbial diversity, enhanced short-chain fatty acid production, and reduced neuroinflammatory markers. In contrast, effects were limited in advanced Alzheimer's disease.Overall, gut microbiota modulation represents a promising nonpharmacological strategy to support cognitive health, with early intervention appearing crucial for optimal benefit. Nevertheless, heterogeneity in study design and intervention protocols highlights the need for large-scale, longitudinal randomized controlled trials to confirm efficacy and clarify underlying biological mechanisms.},
}

@article {pmid41687425,
year = {2026},
author = {Xie, QX and Zeng, XN and Wang, YH and Tan, LX and Yang, M and Du, YX and Chen, XP},
title = {Gut microbiota influence pharmacokinetics variability in aging mice: Effects vary from drug to drug.},
journal = {Drug metabolism and disposition: the biological fate of chemicals},
volume = {54},
number = {3},
pages = {100241},
doi = {10.1016/j.dmd.2026.100241},
pmid = {41687425},
issn = {1521-009X},
abstract = {Pharmacokinetics (PKs) changes in the aging state are relatively common in clinical practice, but their underlying mechanisms remain unclear. This study aims to explore the potential effects of gut microbiota on PK of P450 probe drugs in old and young mice. A cocktail of probe drugs including phenacetin (PHE), midazolam (MID), dextromethorphan tartrate (DEX), and chlorzoxazone was gavage administered to control and pseudo-sterile old and young mice, and the PK parameters were compared. Subsequently, fecal microbiota transplantation (FMT) from young to old mice was performed to assess the impact of FMT on PK of the probe drugs. We observed that gut microbiota significantly affected the systemic exposure of PHE and MID, whereas age-related increase in DEX exposure in the old mice could be reversed by clearance of microbiota. No changes in PK parameters of the probe drugs were observed in old mice with FMT from young mice, suggesting that the alterations in PHE, MID, and DEX metabolism in the old mice could not be explained by unique microbiota from young mice. Our findings provide valuable guidance on how to improve the individualized medication for the elderly population. SIGNIFICANCE STATEMENT: This article offers new insights into the role of gut microbiota in the pharmacokinetic changes with aging, which is conducive to individualized medication for elderly patients and provides new insight for the research and development of drugs for elderly population.},
}

@article {pmid41685140,
year = {2026},
author = {Ma, H and Wu, Y and Li, D and Sun, H and Xie, Y and Zhao, S and Guo, W and Wang, M and Cui, R and Huang, Y and Zhang, X and Wan, JY and Yao, H and Yuan, CS},
title = {Gut microbiota drives the metabolic dysregulation in obesity-prone individuals by impairing GDCA-mediated activation of brown adipose thermogenesis and ileal GLP-1 secretion.},
journal = {Acta pharmaceutica Sinica. B},
volume = {16},
number = {2},
pages = {836-853},
pmid = {41685140},
issn = {2211-3835},
abstract = {Obesity-prone (OP) individuals exhibit an intrinsic predisposition to obesity and associated metabolic disorders, and early intervention in this population holds significant clinical value; however, the underlying mechanisms driving this susceptibility remain largely obscure. This study enrolled 46 OP subjects without diagnosed metabolic diseases and 35 healthy controls. Our findings revealed that, despite not reaching obesity diagnoses, OP subjects exhibited significant metabolic disturbances strongly associated with gut microbiota dysbiosis. They also displayed disturbed bile acid (BA) profiles, with depleted glycodeoxycholic acid (GDCA) identified as the most potent discriminator between the OP and healthy controls. Fecal microbiota transplantation (FMT) recapitulated metabolic dysfunction and BA pool remodeling, mediated by dysregulated hepatic expression of BA synthesis genes of Cyp8a1, Cyp7a1, and Cyp7b1. Notably, FMT-OP mice also phenocopied the diminished GDCA levels observed in OP subjects. GDCA supplementation in obese mice markedly improved body weight, hepatic steatosis, and metabolic dysfunction. Mechanistically, GDCA exerted anti-obesity effects by activating the TGR5 signaling, which enhanced brown adipose tissue (BAT) thermogenesis and stimulated ileal glucagon-like peptide-1 (GLP-1) secretion, thereby ameliorating obesity and associated metabolic dysregulation. Thus, these findings indicate that gut microbiota-driven dysregulation of BA signaling, particularly impaired TGR5 activation due to diminished GDCA, underlies glycolipid metabolic dysfunction in OP individuals.},
}

@article {pmid41684914,
year = {2026},
author = {Yang, G and Zhu, J and Wang, M and She, S and Dai, K},
title = {Research advances on gut microbiota dysbiosis and chronic liver diseases: a review.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1765047},
pmid = {41684914},
issn = {2296-858X},
abstract = {The gut microbiota is fundamental to human health, maintaining intricate symbiotic interactions with the host. Accumulating evidence highlights a critical association between gut microbiota dysbiosis and the initiation and progression of chronic liver diseases (CLDs). Particularly hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, alcoholic liver disease (ALD), metabolic-associated steatotic liver disease (MASLD), and cirrhosis. This microbial imbalance may contribute to the progression of CLDs primarily via the "gut-liver axis," the mechanisms involve gut barrier dysfunction, abnormal immune regulation, and metabolic alterations. This review synthesizes cutting-edge research on the interplay between gut dysregulation and CLDs, elaborating molecular mechanistic pathways including the TLR4/NF-κB signaling pathway, AMPK pathway, and farnesoid X receptor (FXR)-mediated bile acid signaling. Additionally, it discusses clinically oriented therapeutic strategies targeting microbiota modulation, including probiotics, fecal microbiota transplantation (FMT), and personalized dietary interventions, offering innovative insights for the prevention and management of chronic liver diseases.},
}

@article {pmid41684902,
year = {2025},
author = {Li, X and Li, G and Cui, K and Yin, X and Yang, W and Li, W and Xu, S},
title = {Electroacupuncture improves depression with constipation by balancing gut microbiota in WKY rats.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1680596},
pmid = {41684902},
issn = {1664-302X},
abstract = {Accumulating evidence underscores the pivotal role of the gut microbiota in the pathogenesis of depression. In this study, we employed the Wistar-Kyoto (WKY) rat, a well-established animal model of depression comorbid with constipation. Using 16S rRNA gene sequencing, we characterized the gut microbial community structure and investigated the impact of microbiota modulation on depressive-like behaviors and gastrointestinal dysfunction. Comparative analyses revealed that WKY rats exhibited significantly increased relative abundances of Proteobacteria, Bacteroidetes, and Desulfobacterota, accompanied by a marked reduction in Firmicutes compared to control Wistar rats. Fecal microbiota transplantation (FMT) demonstrated that colonization of WKY rats with microbiota from Wistar rats restored microbial composition, improved depressive-like behaviors, and normalized gut motility. In contrast, Wistar rats receiving microbiota from WKY donors developed depression-like phenotypes and impaired intestinal function. Moreover, electroacupuncture (EA) treatment not only alleviated depressive-like behaviors in WKY rats but also promoted recovery of colonic epithelial ultrastructure and rebalanced gut microbial composition. Collectively, these findings demonstrate that both FMT and EA effectively ameliorate depressive behaviors and constipation in WKY rats, with EA likely exerting its therapeutic effects through modulation of the gut microbiota.},
}

@article {pmid41684898,
year = {2025},
author = {Huang, J and Yin, X and Zhang, Y and Zheng, W and Li, G},
title = {Fecal microbiota transplantation from gestational diabetes mellitus patients induces glucose intolerance and subclinical inflammation in mice.},
journal = {Frontiers in microbiology},
volume = {16},
number = {},
pages = {1723816},
pmid = {41684898},
issn = {1664-302X},
abstract = {BACKGROUND: The pathogenesis of gestational diabetes mellitus (GDM) is not fully understood, with gut microbiota dysbiosis emerging as a potential contributing factor. Existing animal models primarily mimic type 1 or type 2 diabetes, inadequately representing GDM. This study aimed to investigate whether fecal microbiota transplantation (FMT) from GDM patients is associated with the development of GDM-like phenotypes in mice, comparing this approach to traditional modeling methods.

METHODS: Fecal microbiota from GDM patients and healthy controls were transplanted into antibiotic-treated pregnant mice, creating trimester-specific FMT models. Control groups included mice on a high-fat diet (HFD) and HFD combined with streptozotocin (STZ). Metabolic phenotypes were assessed via glucose and insulin tolerance tests, fasting blood glucose, and insulin measurements. Serum inflammatory markers were analyzed, and gut inflammation was evaluated. 16S rRNA sequencing was performed on key model groups.

RESULTS: Mice receiving FMT from mid-late trimester GDM donors or traditional treatments developed significant glucose intolerance, insulin resistance, and gestational weight gain. Serum levels of inflammatory factors (e.g., IL-1β, MMP-9) were elevated. 16S rRNA sequencing revealed markedly reduced gut microbiota diversity and increased Firmicutes/Bacteroidota ratio in both GDM-FMT and traditional model groups, with similar microbial community structures and alterations in metabolic and inflammation-related pathways.

CONCLUSION: Gut microbiota from GDM patients may disrupt glucose homeostasis and contribute to a pro-inflammatory state during pregnancy. The GDM-FMT model effectively recapitulates key metabolic, inflammatory, and microbial dysbiosis features of GDM, providing a novel and reliable experimental tool for mechanistic studies.},
}

@article {pmid41683874,
year = {2026},
author = {Kim, KJ and Zhong, H and Tai, D and Shah, P and Park, D and Goes, V and Li, J and Jung, C and Kim, L and Guzman, S and Brar, G and Castillo, D},
title = {Microbiome Signatures in Advanced Gastric Cancer: Emerging Biomarkers for Risk Stratification, Therapy Guidance, and Prognostic Insight.},
journal = {International journal of molecular sciences},
volume = {27},
number = {3},
pages = {},
pmid = {41683874},
issn = {1422-0067},
mesh = {Humans ; *Stomach Neoplasms/microbiology/therapy/diagnosis/pathology ; *Gastrointestinal Microbiome ; Prognosis ; *Biomarkers, Tumor ; Immunotherapy/methods ; Dysbiosis/microbiology ; Risk Assessment ; },
abstract = {Gastric cancer (GC), often diagnosed at advanced or metastatic stages, remains a significant clinical challenge requiring novel biomarkers for early detection, risk stratification, and effective, personalized treatment optimization. Emerging evidence underscores a strong association between gut microbiome dysbiosis and GC initiation, progression, and therapeutic outcomes. This review explores the potential of the advanced/metastatic gastric microbiome as a source of diagnostic and targetable biomarkers and its role in modulating responses to immunotherapy. Although Helicobacter pylori (H. pylori) is the most significant risk factor for GC, several other gastrointestinal taxa-including Fusobacterium nucleatum (F. nucleatum)-have been implicated in advanced GC (AGC). At its inception, microbial dysbiosis contributes to chronic inflammation and immune evasion, thereby influencing tumor behavior and treatment efficacy. Integrating microbiome-based biomarkers into risk stratification, GC staging, and targetable treatment frameworks may enhance early detection, inform immunotherapy strategies, and improve patient-specific treatment responses. Bifidobacterium and Lactobacillus rhamnosus GG have the potential to change the immunotherapy framework with their direct influence on dendritic cell (DC) and cytotoxic T cell (CTL) activity. However, clinical translation is impeded by methodological heterogeneity, causality limitations, and a lack of clinical trials. Nonetheless, the integration of microbiome profiling and the development of therapeutic microbiome modulation strategies, such as personalized probiotics regimens and fecal microbiota transplantation, hold substantial potential for improving clinical outcomes and reducing treatment-related toxicity in GC management.},
}

Humans
*Stomach Neoplasms/microbiology/therapy/diagnosis/pathology
*Gastrointestinal Microbiome
Prognosis
*Biomarkers, Tumor
Immunotherapy/methods
Dysbiosis/microbiology
Risk Assessment

@article {pmid41683859,
year = {2026},
author = {Unrug-Bielawska, K and Sandowska-Markiewicz, Z and Kaniuga, E and Cybulska-Lubak, M and Borowa-Chmielak, M and Czarnowski, P and Piątkowska, M and Bałabas, A and Goryca, K and Zeber-Lubecka, N and Kulecka, M and Dąbrowska, M and Surynt, P and Statkiewicz, M and Rumieńczyk, I and Mikula, M and Ostrowski, J},
title = {Human Fecal Transplantation Modifies the Gut Microbiota but Not Metabolites in Colon Cancer Patient-Derived Xenografts.},
journal = {International journal of molecular sciences},
volume = {27},
number = {3},
pages = {},
doi = {10.3390/ijms27031438},
pmid = {41683859},
issn = {1422-0067},
support = {2017/27/B/NZ5/01504//National Science Centre/ ; },
mesh = {*Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Animals ; Humans ; Mice ; Leucovorin/therapeutic use ; *Colonic Neoplasms/therapy/microbiology/metabolism/pathology ; Fluorouracil/therapeutic use/pharmacology ; Xenograft Model Antitumor Assays ; Feces/microbiology ; Fatty Acids, Volatile/metabolism ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; RNA, Ribosomal, 16S/genetics ; Male ; Organoplatinum Compounds/therapeutic use ; Colorectal Neoplasms/therapy/microbiology ; Female ; },
abstract = {Gut microbiota influences colorectal cancer (CRC) development, tumor progression, and response to therapy. Fecal microbiota transplantation (FMT) has been proposed as a strategy to restore microbial balance and modulate treatment outcomes. We evaluated the effects of human fecal transplantation on gut microbiota composition, metabolites, tumor growth, and the efficacy of folinic acid, fluorouracil and oxaliplatin (FOLFOX) chemotherapy in four CRC patient-derived xenograft (CRC PDX) models in NSG mice. Gut microbiota was profiled by 16S rRNA sequencing; short-chain fatty acids (SCFAs) and amino acids (AAs) were analyzed by mass spectrometry. Prolonged FMT significantly altered gut microbiota structure, increasing α-diversity and modifying β-diversity, and induced distinct changes in bacterial genera. FMT alone did not affect tumor growth. FOLFOX inhibited tumor progression in all CRC PDXs, with FMT enhancing therapeutic efficacy in two models. Despite substantial microbiota shifts, FMT exerted minimal or no effect on fecal SCFAs and AAs. FMT induced robust microbiota remodeling but did not modify selected stool metabolites or intrinsic tumor growth. However, FMT enhanced FOLFOX responsiveness in selected CRC PDXs, supporting a microbiota-mediated modulation of chemotherapy outcomes.},
}

*Fecal Microbiota Transplantation/methods
*Gastrointestinal Microbiome
Animals
Humans
Mice
Leucovorin/therapeutic use
*Colonic Neoplasms/therapy/microbiology/metabolism/pathology
Fluorouracil/therapeutic use/pharmacology
Xenograft Model Antitumor Assays
Feces/microbiology
Fatty Acids, Volatile/metabolism
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
RNA, Ribosomal, 16S/genetics
Male
Organoplatinum Compounds/therapeutic use
Colorectal Neoplasms/therapy/microbiology
Female

@article {pmid41683353,
year = {2026},
author = {Gong, B and Shi, Z and Qi, J and Wang, F and Chen, G and Su, H},
title = {GLP-1RA Liraglutide Attenuates Sepsis by Modulating Gut Microbiota and Associated Metabolites.},
journal = {Nutrients},
volume = {18},
number = {3},
pages = {},
doi = {10.3390/nu18030531},
pmid = {41683353},
issn = {2072-6643},
support = {Yunnan Province Medical High-level Talents Program, L2024012//Guobing Chen/ ; },
mesh = {*Liraglutide/pharmacology/therapeutic use ; Animals ; *Gastrointestinal Microbiome/drug effects ; *Sepsis/drug therapy/microbiology/metabolism ; Mice ; Humans ; Male ; Mice, Inbred C57BL ; Metabolome/drug effects ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Glucagon-Like Peptide 1/blood ; Citrulline/metabolism/blood ; Dysbiosis/drug therapy ; Feces/microbiology ; Glucagon-Like Peptide-1 Receptor Agonists ; Female ; },
abstract = {BACKGROUND: Sepsis-induced organ dysfunction poses a significant clinical challenge with limited therapeutic options. This study investigated the therapeutic potential of the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide in sepsis and its underlying mechanisms, focusing on modulation of the gut microbiota-derived metabolome.

METHODS: Public transcriptomic data analysis identified overlapping targets between liraglutide and sepsis-related genes. In a murine cecal ligation and puncture (CLP) model, liraglutide treatment was evaluated for its effects on survival, systemic inflammation, and organ injury. The gut microbiota composition and fecal metabolome were assessed via 16S rRNA sequencing and UPLC-MS. We also measured plasma GLP-1 in sepsis patients and examined the microbiota-dependency of liraglutide's effects using antibiotic-depleted mice and fecal microbiota transplantation (FMT) from liraglutide-treated mice. Additionally, citrulline, a key identified metabolite, was functionally validated both in vitro and in a clinical cohort.

RESULTS: Liraglutide significantly improved survival, reduced pro-inflammatory cytokines, and alleviated lung, liver, and colon damage in septic mice. It partially restored sepsis-induced gut dysbiosis and modulating associated metabolites, including increasing citrulline. The survival benefit of liraglutide was abolished in microbiota-depleted mice, while FMT from liraglutide-treated mice conferred protection against sepsis, confirming the gut microbiota as a critical mediator. Furthermore, citrulline exhibited direct anti-inflammatory properties in cellular assays, and its plasma levels were negatively correlated with sepsis biomarkers (PCT and CRP) in patients.

CONCLUSIONS: Taken together, our findings indicate that liraglutide mitigates sepsis by modulating the gut microbiota and regulating associated metabolic pathways. Citrulline may represent a potential microbial mediator or exploratory biomarker within this axis, warranting further mechanistic investigation.},
}

*Liraglutide/pharmacology/therapeutic use
Animals
*Gastrointestinal Microbiome/drug effects
*Sepsis/drug therapy/microbiology/metabolism
Mice
Humans
Male
Mice, Inbred C57BL
Metabolome/drug effects
Fecal Microbiota Transplantation
Disease Models, Animal
Glucagon-Like Peptide 1/blood
Citrulline/metabolism/blood
Dysbiosis/drug therapy
Feces/microbiology
Glucagon-Like Peptide-1 Receptor Agonists
Female

@article {pmid41683324,
year = {2026},
author = {Zhao, Z and Zhao, S and Li, W and Lai, Z and Zhou, Y and Guan, F and Liang, X and Zhang, J and Wang, L},
title = {Gut Microbiota and Exercise-Induced Fatigue: A Narrative Review of Mechanisms, Nutritional Interventions, and Future Directions.},
journal = {Nutrients},
volume = {18},
number = {3},
pages = {},
doi = {10.3390/nu18030502},
pmid = {41683324},
issn = {2072-6643},
support = {2022AH040100//The Scientific Research Project of Higher Education Institutions in Anhui Province/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Exercise/physiology ; *Fatigue/microbiology/etiology/physiopathology ; Animals ; Probiotics/administration & dosage ; Prebiotics/administration & dosage ; },
abstract = {Background: Exercise-induced fatigue (EIF) impairs performance and recovery and may contribute to overreaching/overtraining and adverse health outcomes. Beyond classical explanations (substrate depletion, metabolite accumulation, oxidative stress), accumulating evidence indicates that the gut microbiota modulates fatigue-related physiology through metabolic, immune, barrier, and neurobehavioral pathways. Methods: We conducted a structured narrative review of PubMed and Web of Science covering 1 January 2015 to 30 November 2025 using predefined keywords related to EIF, gut microbiota, recovery, and nutritional interventions. Human studies, animal experiments, and mechanistic preclinical work (in vivo/in vitro) were included when they linked exercise load, microbial features (taxa/functions/metabolites), and fatigue-relevant outcomes. Results: Across models, high-intensity or prolonged exercise is consistently associated with disrupted gut homeostasis, including altered community structure, reduced abundance of beneficial taxa, increased intestinal permeability, and shifts in microbial metabolites (e.g., short-chain fatty acids). Evidence converges on four interconnected microbiota-mediated pathways relevant to EIF: (1) energy availability and metabolic by-product clearance; (2) redox balance and inflammation; (3) intestinal barrier integrity and endotoxemia risk; and (4) central fatigue and exercise motivation via microbiota-gut-brain signaling. Nutritional strategies-particularly targeted probiotics, prebiotics/plant polysaccharides, and selected bioactive compounds-show potential to improve fatigue biomarkers and endurance-related outcomes, although effects appear context-dependent (exercise modality, baseline fitness, diet, and baseline microbiota). Conclusions: Current evidence supports a mechanistic role of the gut microbiota in EIF and highlights microbiota-targeted nutrition as a promising adjunct for recovery optimization. Future work should prioritize causal validation (e.g., fecal microbiota transplantation and metabolite supplementation), athlete-focused randomized trials with standardized fatigue endpoints, and precision approaches that stratify individuals by baseline microbiome features and training load.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Exercise/physiology
*Fatigue/microbiology/etiology/physiopathology
Animals
Probiotics/administration & dosage
Prebiotics/administration & dosage

@article {pmid41680132,
year = {2026},
author = {Raschdorf, A and de Almeida, LN and Solbach, P and Kirstein, MM and Marquardt, JU and Schmelter, F and Günther, UL and Schlichting, H and Hicken, M and Christiansen, L and Wiestler, M and Tews, HC and Bettenworth, D and , and Peipp, M and Valerius, T and Ragab, M and Sauer, T and Gemoll, T and Ehlers, M and Rosenstiel, P and Manz, RA and Künstner, A and Busch, H and Sina, C and Derer, S},
title = {Colonic spatial single-cell proteomics and murine models link mitochondrial dysfunction to dimeric IgA-secreting plasma cell deficiency in Crohn's disease.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {1590},
pmid = {41680132},
issn = {2041-1723},
mesh = {Animals ; *Crohn Disease/immunology/metabolism/pathology ; *Plasma Cells/metabolism/immunology/pathology ; *Colon/immunology/pathology/metabolism ; Mice ; *Mitochondria/metabolism/pathology ; Disease Models, Animal ; Humans ; Proteomics/methods ; Single-Cell Analysis ; *Immunoglobulin A, Secretory/metabolism/immunology ; Male ; Female ; Intestinal Mucosa/immunology/metabolism/pathology ; Mice, Inbred C57BL ; Cell Differentiation ; B-Lymphocytes/immunology/metabolism ; Oxidative Phosphorylation ; },
abstract = {Secretory IgA (SIgA) is critical for maintaining the intestinal barrier. A dysregulated B-cell compartment and altered Ig secretion have been well documented in Crohn's disease (CD) patients, although their origin is unknown. To unravel the role of mucosal humoral immunity in CD pathogenesis, we in-depth phenotype colonic plasma cell (PC) differentiation in CD at the single-cell level, linked to ex vivo functional characterization and experimental mouse models with a congenital mitochondrial defect or under glucose-free high-protein dietary intervention. Here, we demonstrate that despite expanded colonic B cells, CD patients in remission present significantly diminished mucosal dimeric IgA and fecal SIgA. Colonic plasmablasts and immature CD19[+]CD45[+] PCs are increased at the expense of the mature CD19[-]CD45[-] phenotype. Accordingly, CD-derived ex vivo differentiated PCs display impaired maturation into dimeric IgA-secreting PCs. In this study, patient-derived data from colonic RNA-seq, spatial single-cell proteomics, and plasma metabolomics are combined with data from both mouse models and highlight the crucial role of mitochondrial oxidative phosphorylation in colonic IgA[+]-PC differentiation, suggesting promising directions for future therapeutic strategies.},
}

Animals
*Crohn Disease/immunology/metabolism/pathology
*Plasma Cells/metabolism/immunology/pathology
*Colon/immunology/pathology/metabolism
Mice
*Mitochondria/metabolism/pathology
Disease Models, Animal
Humans
Proteomics/methods
Single-Cell Analysis
*Immunoglobulin A, Secretory/metabolism/immunology
Male
Female
Intestinal Mucosa/immunology/metabolism/pathology
Mice, Inbred C57BL
Cell Differentiation
B-Lymphocytes/immunology/metabolism
Oxidative Phosphorylation

@article {pmid41677424,
year = {2026},
author = {Zhang, Z and Yang, J and Chen, X and Shi, J and Li, B and Wang, L and Geng, Z and Li, J and Zhang, X and Wang, Y and Song, X and Li, Y and Hu, J and Zuo, L},
title = {Aucubin Restores Intestinal Mucosal Immunity and Barrier Integrity in Experimental Colitis via the Microbiota-SCFAs-GPR41/GPR43 Axis.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {40},
number = {4},
pages = {e71569},
doi = {10.1096/fj.202502948R},
pmid = {41677424},
issn = {1530-6860},
support = {82370534//National Natural Science Foundation of China/ ; 2019byyfyjq01//Research Project of Bengbu Medical University/ ; BYYFY2022TD002//Research Project of Bengbu Medical University/ ; 2021byfy001//Research Project of Bengbu Medical University/ ; gxyqZD2022066//Anhui Provincial Research Project/ ; 2024Aa40007//Anhui Provincial Research Project/ ; 2024Aa10051//Anhui Provincial Research Project/ ; 202427b10020093//Anhui Provincial Research Project/ ; 202427b10020088//Anhui Provincial Research Project/ ; 202427b10020099//Anhui Provincial Research Project/ ; 2022AH020085//Anhui Provincial Research Project/ ; 2023AH010067//Anhui Provincial Research Project/ ; },
mesh = {Animals ; *Receptors, G-Protein-Coupled/metabolism ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Intestinal Mucosa/drug effects/immunology/metabolism ; *Fatty Acids, Volatile/metabolism ; *Colitis/drug therapy/immunology/chemically induced/metabolism/microbiology ; Mice, Inbred C57BL ; *Iridoid Glucosides/pharmacology ; Th17 Cells/immunology/drug effects ; T-Lymphocytes, Regulatory/immunology/drug effects ; *Immunity, Mucosal/drug effects ; Male ; Dextran Sulfate/toxicity ; },
abstract = {BackgroundInflammatory bowel disease (IBD) pathogenesis involves immune dysfunction and gut microbiota dysbiosis. Aucubin (AU), a naturally occurring iridoid glycoside known for its ability to alleviate inflammation and modulate intestinal flora, has not yet been investigated in the context of colitis MethodsThe effects of AU on DSS-induced colitis in mice were evaluated, including disease severity, the balance of regulatory T cells (Tregs) and Th17 cells, intestinal barrier, inflammatory markers, fecal short-chain fatty acids (SCFAs), and safety. The gut microbiota was assessed using 16S rRNA sequencing. GPR41/43 involvement was tested using receptor antagonists. The antibiotic-treated mice and fecal transplantation were used to validate the microbiota-dependent effects. ResultsAU treatment broadly ameliorated the DSS-induced colitis and restored immune homeostasis by rebalancing Treg/Th17 cell populations. Meanwhile, intestinal barrier function was reinforced through upregulation of MUC2 and enhanced tight junction protein levels. Importantly, AU modulated gut microbiota composition, particularly enriching taxa associated with SCFA production, which indeed led to elevated fecal SCFA levels. Interestingly, the therapeutic effects of AU were absent in microbiota-depleted mice but could be conferred to DSS-induced recipients via fecal microbiota transplantation from AU-treated donors. Furthermore, the protective benefits of AU were partially attenuated upon pharmacological inhibition of the SCFA receptors GPR41/GPR43. No treatment-related toxicity was observed. ConclusionsAU safely alleviates colitis in mice by rebalancing the gut microbiota, activating SCFAs-GPR41/GPR43 axis to support mucosal immune regulation and barrier repair.},
}

Animals
*Receptors, G-Protein-Coupled/metabolism
Mice
*Gastrointestinal Microbiome/drug effects
*Intestinal Mucosa/drug effects/immunology/metabolism
*Fatty Acids, Volatile/metabolism
*Colitis/drug therapy/immunology/chemically induced/metabolism/microbiology
Mice, Inbred C57BL
*Iridoid Glucosides/pharmacology
Th17 Cells/immunology/drug effects
T-Lymphocytes, Regulatory/immunology/drug effects
*Immunity, Mucosal/drug effects
Male
Dextran Sulfate/toxicity

@article {pmid41676450,
year = {2025},
author = {Zhang, L and Liu, Y and Wang, S and Ching, JY and Tam, WH and Leung, TF and Leung, TY and Chan, PKS and Mak, JWY and Cheung, CP and Tun, HM and Chang, EB and DeLeon, O and Huang, Q and Chen, X and Huo, H and Miao, Y and Cheong, PK and Ip, KL and Yeung, YL and Chang, MK and Lyu, C and Yang, H and Li, B and Fan, Y and Sun, Y and Jiang, S and Ng, SC and Chan, FKL},
title = {MOMMY study profile: An integrative early-life multi-omics cohort in China.},
journal = {iMetaOmics},
volume = {2},
number = {4},
pages = {e70068},
pmid = {41676450},
issn = {2996-9514},
abstract = {Large-scale, prospective birth cohorts capturing the complex interplay between the gut microbiome, host biology, and environmental exposures are crucial to understanding early-life health but remain scarce, particularly within Asian populations. To address this gap, we established the MOMMY cohort (The MOther-infant Microbiota transmission and its link to long terM health of babY), a large, prospective birth cohort uniquely designed to investigate maternal-paternal-infant microbiota transmission and its impact on child health within the understudied Chinese population. MOMMY aims to recruit 20,000 families from three geographically and economically diverse regions across China. This cohort prospectively follows pregnant mothers, fathers, and their infants, with children up to 7 years of age. Since September 2019, we have systematically collected a comprehensive repository of longitudinal biospecimens-including maternal and infant stool, breast milk, cord blood, and parental blood-stored in an accredited biobank. This is complemented by extensive data on environmental exposures, diet, and health outcomes gathered through validated questionnaires and physician assessments. The MOMMY cohort's unique value lies in its unprecedented scale, geographic diversity, and its integrative multi-omics design, which will combine metagenomic, metabolomic, immunologic, and epigenetic data. By creating this unique resource, MOMMY will elucidate how early-life microbial and molecular trajectories, shaped by genetic and environmental factors, influence child development and disease risk, thereby filling a critical gap in global microbiome research.},
}

@article {pmid41676136,
year = {2026},
author = {Ni, FX and Wang, HX and Hu, J and Chen, PS and Xu, P and Chen, HH and Jiang, ZB and Huang, DH},
title = {The gut-lung axis in COPD: immunomodulatory roles of gut microbiota and novel therapeutic strategies.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1733726},
pmid = {41676136},
issn = {1664-3224},
mesh = {Humans ; *Pulmonary Disease, Chronic Obstructive/therapy/immunology/microbiology/metabolism ; *Gastrointestinal Microbiome/immunology ; *Lung/immunology/microbiology/metabolism ; Animals ; Dysbiosis/immunology ; Probiotics/therapeutic use ; Immunomodulation ; Prebiotics ; Fecal Microbiota Transplantation ; },
abstract = {Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory disorder characterized by persistent airflow limitation and systemic inflammation, with accumulating evidence implicating gut microbiota dysbiosis as a key modulator of disease pathogenesis via the gut-lung axis. This review synthesizes current knowledge on the bidirectional communication between the gut and lungs, highlighting how microbial metabolites-particularly short-chain fatty acids (SCFAs), tryptophan derivatives, and bile acids-regulate pulmonary immunity through G-protein-coupled receptors, histone deacetylase inhibition, and aryl hydrocarbon receptor signaling. Dysbiosis-driven disruptions in these pathways exacerbate neutrophilic inflammation, impair regulatory T-cell function, and sustain TLR4/NF-κB activation, amplifying lung tissue damage and remodeling. Therapeutic strategies targeting the gut-lung axis show promise in restoring microbial homeostasis and mitigating COPD progression. Probiotics (e.g., Lactobacillus and Bifidobacterium), prebiotics (e.g., inulin), and dietary interventions (e.g., high-fiber diets) enhance SCFA production, strengthen epithelial barriers, and suppress pro-inflammatory cytokines. Advanced approaches, including fecal microbiota transplantation, nanotechnology-enabled metabolite delivery (e.g., dendrimer-complexed indole-3-acetic acid), and traditional Chinese medicine (TCM) formulations (e.g., the postbiotic formulation Qipian), demonstrate efficacy in preclinical and clinical studies by synchronizing gut-lung microbiota and inhibiting inflammatory pathways. Despite these advances, challenges remain in translating findings to clinical practice, including methodological heterogeneity, antibiotic and corticosteroid confounding, and inter-individual microbiota variability. Future research must integrate multi-omics technologies, validate biomarkers (e.g., Bacteroidales/Lactobacillus ratio, SCFA levels), and develop personalized interventions to bridge the bench-to-bedside gap. Harnessing the gut-lung axis offers transformative potential for COPD management, shifting the paradigm from symptomatic treatment to disease-modifying strategies rooted in microbiome immunology.},
}

Humans
*Pulmonary Disease, Chronic Obstructive/therapy/immunology/microbiology/metabolism
*Gastrointestinal Microbiome/immunology
*Lung/immunology/microbiology/metabolism
Animals
Dysbiosis/immunology
Probiotics/therapeutic use
Immunomodulation
Prebiotics
Fecal Microbiota Transplantation

@article {pmid41676058,
year = {2026},
author = {Sivamaruthi, BS and Kesika, P and Chaiyasut, C and Ragu Varman, D},
title = {Gut dysbiosis in neurodevelopmental disorders: linking microbiota signatures to cognitive rigidity in autism spectrum disorder.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1760635},
pmid = {41676058},
issn = {1664-302X},
abstract = {Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterised not only by social-communication difficulties but also by restricted interests, stereotyped behaviours, and marked cognitive rigidity. Over the past decade, converging lines of evidence have implicated gut dysbiosis, an imbalance in intestinal microbial composition and function, as a potentially important modulator of these behavioural phenotypes via the microbiota-gut-brain axis. In this narrative review, we integrate preclinical and clinical data to examine how specific microbial signatures, metabolic pathways, and immune and synaptic mechanisms may contribute to inflexible cognition in ASD. The manuscript outlines the organisation of the microbiota gut-brain axis in neurodevelopment and summarises reproducible microbial alterations reported in ASD cohorts. We then discuss how microbial metabolites, including short-chain fatty acids and tryptophan-derived neuroactive molecules, as well as immune mediators and neurotransmitter precursors, converge on pathways regulating excitatory-inhibitory balance, synaptic plasticity, and corticostriatal circuit function. Evidence from germ-free, genetic, and environmental rodent models provides causal support for microbiota-dependent modulation of repetitive and rigid behaviours, whilst clinical studies reveal associations between dysbiosis, metabolomic profiles, gastrointestinal symptoms, and ASD severity. Finally, we consider the translational landscape of microbiota-targeted interventions, probiotics, prebiotics, dietary strategies, and faecal microbiota transplantation and highlight key methodological and ethical challenges for moving toward precision microbiome-based therapies. Taken together, current data support gut dysbiosis as both a mechanistic contributor and a tractable therapeutic target for cognitive rigidity in ASD.},
}

@article {pmid41675715,
year = {2025},
author = {Ren, H and Cao, B and Xu, Q and Zhao, R and Li, H and Wei, B},
title = {Role of microbiota in pain: From bench to bedside.},
journal = {iMetaOmics},
volume = {2},
number = {1},
pages = {e58},
pmid = {41675715},
issn = {2996-9514},
abstract = {Interactions between the microbiota and host have been proven to be critical regulators of homeostasis, and pain perception is no exception. Emerging evidence has identified the mechanisms by which microbiota dysbiosis contributes to hyperalgesia and revealed the potential value of microbiota-associated therapies in pain management. Herein, the authors introduce the basic knowledge of pain and microbiota for readers who are not simultaneously majoring in these two fields. The clarified mechanisms underlying the regulation of pain by the microbiota are outlined in terms of three ways. This review summarizes the current advancements in pain management and microbiology research for clinicians who wish to focus on this area. Probiotics, fecal microbiota transplantation, and other methods of microbiota modulation for pain management have entered clinical translation. The authors further propose the present limitations and prospects for high-quality development of preclinical and clinical investigations. Importantly, despite the large amount of attention given to gut bacteria, this review also puts forward great expectations on the role of nongut and nonbacterial microbiota in pain sensation. Efforts to decipher the mechanisms of microbiota functions will help to promote achievements in pain management from bench to bedside.},
}

@article {pmid41675700,
year = {2025},
author = {Zhong, P and Li, Q and Zhang, Y and Guo, C and Abdelsattar, MM and Bi, Y},
title = {Precision microbial regulation: Strategies for modulating GIT microbiota for host health.},
journal = {iMetaOmics},
volume = {2},
number = {1},
pages = {e54},
pmid = {41675700},
issn = {2996-9514},
abstract = {Recent advancements in analytical techniques have unveiled the spatiotemporal diversity of the gastrointestinal tract (GIT) microbiota and their associations with host well-being. Despite these insights, the precise regulation of GIT microbiota remains a significant challenge. Currently, microbial regulatory strategies, including fecal microbiota transplantation (FMT), synthetic microbial communities (SynComs), genetically engineered microorganisms (GEMs), phages, and nanomaterials, are increasingly utilized for their precise influence on GIT microbiota. This review emphasizes the necessity for developing targeted regulatory strategies in GIT and provides a comprehensive summary and comparison of these approaches to explore their regulatory potential. We discuss recent advancements in these strategies, focusing on their mechanisms, efficacy, safety considerations, clinical trials, and optimization at the application level. Finally, we highlight support methods for optimizing modulation strategies, including the timing of microbial regulation, the selection of microbial targets, and the importance of monitoring the gastrointestinal environment to guide effective microbial interventions.},
}

@article {pmid41675494,
year = {2025},
author = {Wu, Z and Wang, X and Guan, Z and Han, M and Ma, W and Li, J and Man, S and Wang, Z and Wu, Q},
title = {Deciphering the immunocellular regulatory network in inflammatory bowel disease: from susceptibility genes to cellular effectors and toward precision therapies.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1719366},
pmid = {41675494},
issn = {1664-3224},
mesh = {Humans ; *Inflammatory Bowel Diseases/therapy/immunology/genetics/etiology ; Precision Medicine/methods ; *Genetic Predisposition to Disease ; Animals ; },
abstract = {Inflammatory bowel disease (IBD) is a chronic, immune-mediated intestinal disorder driven by dysregulated immune responses in genetically susceptible individuals. Despite recent advances in treatment, more than 30% of patients either fail to respond initially or lose response over time, underscoring the need for a deeper mechanistic understanding of immunogenetic pathways and the development of individualized therapeutic strategies. We first discuss how newly identified susceptibility genes (e.g., IL23R, NOD2, BDNF, SLC) and their polymorphisms influence immune cell function and epithelial barrier integrity. Single-cell technologies have further revealed novel cell subsets and interactions underlying disease heterogeneity. We then explore the clinical efficacy of classical and emerging targeted therapies, including cytokine-specific biologics, JAK inhibitors, and novel strategies aimed at restoring regulatory T-cell function or blocking integrin-mediated lymphocyte trafficking. Additionally, we highlight promising therapeutic approaches such as fecal microbiota transplantation, microbial metabolite-based interventions, and nanotherapeutics. We further discuss how genetic insights and immune biomarkers can facilitate treatment personalization and improve prognostic stratification. Ultimately, this review emphasizes the transition from broad immunosuppression to precision medicine and proposes integrated approaches-combining multiomics profiling, immune monitoring, and novel therapeutics-to achieve sustained remission and improve long-term outcomes in IBD patients.},
}

Humans
*Inflammatory Bowel Diseases/therapy/immunology/genetics/etiology
Precision Medicine/methods
*Genetic Predisposition to Disease
Animals

@article {pmid41675345,
year = {2026},
author = {Mylavarapu, M and Tiwari, A and Kaur, H and Vempati, R and Kumar, H and Kodali, LSM and Khan, KG and Dadana, S and Garcia, I and Cabrera, FEP and Singh, A and Kyasa, SL and Purewal, VS},
title = {The Gut-Heart Axis: A Comprehensive Review of Microbiota's Role in Cardiovascular Health and Disease and Emerging Therapeutic Strategies.},
journal = {Cardiology research and practice},
volume = {2026},
number = {},
pages = {9920016},
pmid = {41675345},
issn = {2090-8016},
abstract = {This review examines the bidirectional relationship between the gut microbiota and cardiovascular diseases (CVDs), aiming to understand how microbial dysbiosis contributes to CVDs, including atherosclerosis, hypertension, and heart failure. Recent research emphasizes the gut microbiota's role in modulating immunity via SCFAs and tryptophan metabolites, maintaining intestinal barrier integrity, and producing metabolites such as SCFAs (acetate, propionate, butyrate) and pro-atherogenic TMAO. Dietary patterns, particularly the Mediterranean versus Western diet, significantly influence gut microbiota composition and CVD risk. Polyphenols and exercise have shown positive effects on gut microbiota and cardiovascular outcomes. A significant interplay exists between gut microbiota and cardiovascular health. Dysbiosis and metabolites like TMAO and LPS are implicated in CVD, while SCFAs and a balanced microbiota offer protection. Future research should focus on precision medicine, next-gen probiotics, optimized FMT, and multiomics approaches to identify personalized CVD therapies.},
}

@article {pmid41675162,
year = {2025},
author = {Lyu, Y and Shen, J and Che, Y and Dai, L},
title = {Skin microbiome engineering: Challenges and opportunities in skin diseases treatment.},
journal = {iMetaOmics},
volume = {2},
number = {2},
pages = {e70012},
pmid = {41675162},
issn = {2996-9514},
abstract = {The skin microbiome, consisting of a vast array of microorganisms, is essential for human skin health, aiding in barrier protection, immune regulation, wound repair, and defense against pathogens. Disruptions in this microbial balance are closely linked to the onset and worsening of various skin disorders. This review evaluates the potential of skin microbiome engineering as a therapeutic strategy for treating skin diseases. We discuss nontargeted approaches like probiotics and fecal microbiota transplantation that aim to reshape the microbial community, as well as targeted methods such as phage therapy, phage lysins, and engineered bacteria, which specifically modulate microbial populations or influence the skin environment. These approaches open new avenues for personalized dermatological treatments. Despite significant progress, challenges remain in the clinical translation of microbiome-based therapies. Safety, standardization, regulatory approval, and long-term ecological stability must be addressed to ensure efficacy and reproducibility in clinical settings, underscoring the critical need for further research in their dermatological applications.},
}

@article {pmid41674575,
year = {2025},
author = {Zhang, Z and Xu, Y and Pang, K and Wu, C and Zhao, C and Lei, T and Zhang, J and Hai, T and Zhao, F and Zhao, Y},
title = {Microbiota humanization drives human-like metabolic and immune transcriptomic shifts in pigs.},
journal = {iMetaOmics},
volume = {2},
number = {3},
pages = {e70034},
pmid = {41674575},
issn = {2996-9514},
abstract = {Pigs are increasingly recognized as promising candidates for clinical xenotransplantation and as large-animal models for biomedical research; however, interspecies differences in gut microbiota, immune function, and metabolism remain major barriers. To address this, we established gut microbiota-humanized (GMH) pigs by transplanting human fecal microbiota into antibiotic-treated pigs. We systemically evaluated alterations in microbiota composition, serum metabolites, and immune cell profiles using integrated metagenomic, quasi-targeted metabolomic and single-cell transcriptomic (scRNA-seq) analyses. Metagenomic profiling revealed a shift in the intestinal microbiota of GMH pigs toward a human-like composition, characterized by enrichment of Bacteroidia and depletion of Bacilli. Metabolomic analysis showed that GMH pigs exhibited serum metabolite profiles more closely resembling those of humans. Among 423 detected serum metabolites, 136 that were lower in control pigs than in humans were upregulated in GMH pigs, whereas 79 that were elevated in control pigs decreased post-transplantation. Notably, pathways related to tryptophan metabolism, bile acid biosynthesis, and fatty acid metabolism were enhanced in GMT pigs, while carbon-related and glycolytic pathways were attenuated, indicating partial convergence toward human metabolic phenotype. Integration of microbial and metabolite data identified 20 and 33 metabolites associated with Bacteroidia and Bacilli, respectively. scRNA-seq profiling of peripheral blood mononuclear cells demonstrated transcriptional and compositional remodeling of T cells, monocytes, and B cell subsets in GMH pigs. These findings demonstrated that human fecal microbiota can reshape both systemic metabolic and immune artitecture in pigs, offering a robust large-animal platform for studying host-microbiota interactions and advancing translational application in xenotransplantation and microbiome-based therapeutics.},
}

@article {pmid41674471,
year = {2026},
author = {Figura, M and Milanowski, Ł and Nowak, JM and Antoniak, A and Kopczyński, M and Zając, W and Sadowski, K and Hołubiuk, Ł and Walęcik-Kot, W and Szlufik, S and Friedman, A and Kaczmarczyk, B and Biliński, J and Koziorowski, D},
title = {Safety and Efficacy of Fecal Microbiota Transplantation in Alleviating Symptoms of Parkinson's Disease: A Randomized, Placebo-Controlled, Double-Blinded Study.},
journal = {Annals of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ana.78153},
pmid = {41674471},
issn = {1531-8249},
support = {2021//Biocodex Microbiota Foundation National Grant/ ; NZP/1/Z/GW/N/21//Medical University of Warsaw/ ; 09/M/MBS/N/21//Medical University of Warsaw/ ; 1/Z/MG/24//Medical University of Warsaw/ ; NZP/1/Z/MG/N/23//Medical University of Warsaw/ ; M/MG/77/22//Medical University of Warsaw/ ; },
abstract = {OBJECTIVES: Changes in the gut microbiome may be involved in the pathogenesis and progression of Parkinson's disease (PD). This randomized, placebo-controlled, double-blinded study aimed to assess the effects of fecal microbiota transplantation (FMT) on the manifestation of the motor symptoms of PD (The Movement Disorders Society - Unified Parkinson's Disease Rating Scale Part III [MDS-UPDRS III]) over a 12 month long observation and non-motor symptoms as secondary objectives: the Movement Disorders Society-Non-Motor Rating Scale; EuroQol-5 Dimension; PD Quality-of-Life Questionnaire; Montreal Cognitive Assessment (MoCA); UPDRS I, II, and IV; Gastrointestinal Dysfunction Scale for PD; modified Constipation Assessment Scale; and levodopa equivalent dose.

METHODS: The patients were randomly assigned to receive either fecal microbiota (Mbiotix, Human Biome Institute) or placebo (auto-fecal microbiota, prepared from the patient's stool) in a 1:1 ratio. The fecal microbiota transplantation was performed via colonoscopy. Assessments were performed before and after 12 months for the MoCA and at 1, 3, 6, and 12 months for the other scales. Intention-to-treat analysis was performed using a multivariable mixed regression model.

RESULTS: Of the 59 patients included, 28 were randomly assigned to the Mbiotix group (median age = 65 years; 15 male patients) and 31 to the placebo group (median age = 63 years; 14 male patients). No significant differences were observed in the MDS-UPDRS III "OFF" state score at 12 months between groups (1.50 points, 95% confidence interval [CI] = -4.28 to 7.28, p = 1.00), however, some non-motor symptoms improved in different study timepoints.

INTERPRETATION: A single FMT does not influence motor symptoms manifestation in patients with PD but could improve non-motor functioning via gut-brain axis. Trial registration information: Clinical Trial ID NCT05204641 was submitted on November 29, 2021. The first patient was enrolled on January 4, 2022. ANN NEUROL 2026.},
}

@article {pmid41673679,
year = {2026},
author = {Liao, J and Mou, H and Luo, S and Shen, L and Jiao, B},
title = {Microbiota and Alzheimer's disease: mechanistic insights from a multi-organ perspective.},
journal = {Translational neurodegeneration},
volume = {15},
number = {1},
pages = {3},
pmid = {41673679},
issn = {2047-9158},
support = {82371434//National Natural Science Foundation of China/ ; 2024JJ2097//Outstanding Youth Fund of Hunan Provincial Natural Science Foundation/ ; },
mesh = {Humans ; *Alzheimer Disease/microbiology/therapy ; *Dysbiosis/microbiology ; *Microbiota/physiology ; Probiotics/therapeutic use ; *Gastrointestinal Microbiome/physiology ; Animals ; Fecal Microbiota Transplantation/methods ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder driven by multifactorial mechanisms. Increasing evidence suggests that dysbiosis, a term denoting an imbalance in the composition of the microbiota, may play a pivotal role in the pathogenesis of AD across multiple bodily sites, including the gut, oral cavity, nasal passages, lungs, and skin. Microbial imbalances may promote neuroinflammation, immune dysfunction, and metabolic disturbances through complex host-microbiota networks. This review synthesizes current advances in the understanding of microbiota-driven modulation of AD, introduces the "Multi-Axis Co-Regulation" concept, and evaluates microbial biomarkers for early diagnosis. Finally, the translational potential of microbiota-targeting interventions, including probiotics, dietary modulation, fecal microbiota transplantation, and oral microbiome-based therapies, are discussed, which represent novel strategies for precision prevention and treatment of AD.},
}

Humans
*Alzheimer Disease/microbiology/therapy
*Dysbiosis/microbiology
*Microbiota/physiology
Probiotics/therapeutic use
*Gastrointestinal Microbiome/physiology
Animals
Fecal Microbiota Transplantation/methods

@article {pmid41672982,
year = {2026},
author = {D'Onofrio, AM and Gomez-Nguyen, A and Camardese, G and Scaldaferri, F and Burberry, A and Cominelli, F},
title = {Fecal microbiota transplantation from psychiatric patients to mice - systematic review of methodologies and a call for standardization.},
journal = {Translational psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41398-026-03847-4},
pmid = {41672982},
issn = {2158-3188},
support = {NIDDK097948//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; NIDDK097948//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; R01AG085316//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; },
abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has emerged as a key tool to explore the role of the microbiome-gut-brain axis in psychiatric disorders. However, the field is hindered by significant methodological inconsistencies.

METHODS: A comprehensive literature search identified 31 studies performing FMT from human patients with psychiatric conditions into rodent models.

RESULTS: None of the 31 studies followed an identical FMT protocol. Significant heterogeneity was observed across studies in rodent model selection, including germ-free, antibiotic-pretreated, or specific pathogen-free approaches, in antibiotic regimens, timing and microbiota depletion verification, as well as in FMT donor strategy, dosage, frequency, engraftment assessment, and behavioral testing schedules.

CONCLUSIONS: This review highlights the necessity for standardized methodologies in microbiome research. Evidence-based recommendations are provided to promote reproducibility in future work. Investigators are encouraged to publish transparent and rigorous protocols, to enhance the translational potential of microbiome-gut-brain axis research.},
}

@article {pmid41672583,
year = {2026},
author = {Fornero, L and Wille-Bille, A and Fabio, MC and Peñalver, P and Marengo, L and Ezquer, F and Pautassi, RM},
title = {Modeling microbiota-mediated risk for alcohol use disorder: a preclinical study of fecal transplantation from ethanol-exposed mice.},
journal = {The American journal of drug and alcohol abuse},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/00952990.2025.2609229},
pmid = {41672583},
issn = {1097-9891},
abstract = {Background: Alcohol use during adolescence and early adulthood promotes the development of alcohol use disorder (AUD). Emerging evidence suggests that ethanol-induced gut microbiota alterations may contribute to AUD vulnerability; however, it remains unclear whether microbiota imbalances are a causal risk factor or a consequence of alcohol exposure.Objectives: This preclinical study assessed if fecal microbiota transplantation (FMT) from donors exposed to ethanol during adolescence/early adulthood would alter ethanol drinking and other behaviors, in unrelated naïve mice.Methods: Forty-two (31 males and 11 females) C57BL/6J mice were exposed to a repeated 2-days-on, 2-days-off ethanol access protocol from postnatal day 43 to 80. Fecal microbiota from ethanol-exposed (or control) donors was transplanted into antibiotic-pretreated naïve male (n = 26) and female (n = 16) recipients. These were assessed for ethanol intake, including compulsive-like drinking (i.e. after quinine adulteration). Anxiety and repetitive behavior were measured in the light-dark box, elevated plus maze and marble-burying tests.Results: Female, but not male, recipients of FMT from ethanol-exposed donors showed significantly increased ethanol consumption (n[2]p = .32) and preference (n[2]p = .36) compared to controls (p < .05). This included sustained intake despite quinine adulteration (p < .05), suggestive of compulsive-like drinking. Ethanol-exposed male mice showed a significant increase in marble-burying (p < .05), consistent with compulsive-like tendencies. Additionally, both male (n[2]p = .30) and female (n[2]p = .28) donor mice exhibited behavioral disinhibition (p < .05).Conclusions: These findings provide preclinical evidence that microbiota alterations after ethanol exposure at late adolescence can transmit vulnerability to alcohol intake, with sex-specific effects. The results highlight the potential of microbiota-targeted interventions in prevention and treatment strategies for AUD.},
}

@article {pmid41672393,
year = {2026},
author = {Lan, Y and You, T and Feng, X and Guo, J and Xu, H},
title = {Combined Enterohepatic Toxicity of Polystyrene Microplastics and Di(2-ethylhexyl) Phthalate in Mice: Gut Microbiota-Dependent Synergistic Effects.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {},
number = {},
pages = {127792},
doi = {10.1016/j.envpol.2026.127792},
pmid = {41672393},
issn = {1873-6424},
abstract = {With growing toxicological research on microplastics (MPs), scientific attention has shifted from their single toxicity to their combined toxicity with other pollutants. Di(2-ethylhexyl) phthalate (DEHP), a common synthetic plasticizer, may co-occur with MPs through intrinsic association during production or through exogenous environmental pathways, posing the significant risk of co-exposure to organism. Oral exposure represents the primary route for MPs and DEHP, which traverse the gastrointestinal tract and target the enterohepatic system through direct intestinal interaction and systemic circulation. However, their combined toxicity, especially enterohepatic, remains poorly studied in the mammals. In this study, adult C57/BL6J mice were employed and exposed to polystyrene MPs (PS-MPs), DEHP or both for eight weeks. It was revealed that co-exposure to PS-MPs and DEHP induced more significant enterohepatic toxicity than the single exposures, involving enhanced enterohepatic inflammatory response and oxidative stress, as well as intestinal microbial disturbance. Furthermore, after fecal microbiota transplantation, the recipient mice developed similar trends of enterohepatic toxicity to those observed in the corresponding donor mice, revealing the key function played by intestinal microbiota. This study highlighted the crucial link of the gut-liver axis in the combined effects of PS-MPs and DEHP-induced enterohepatic toxicity in mammals and provided a mechanism insight of co-exposure to MPs and other environmental pollutants.},
}

@article {pmid41670365,
year = {2026},
author = {Ling, MTM and Krishnan, I and Govindaraju, K and Lokanathan, Y and Hoe, TC and Yusof, MRM and Subramani, B and Ibrahim, B},
title = {Metabolomic Analysis of Metabolic Syndrome and Effects of Wharton's Jelly Mesenchymal Stem Cell Small Extracellular Vesicles Therapy in Rat Models Using Nuclear Magnetic Resonance Spectroscopy.},
journal = {Cell biochemistry and function},
volume = {44},
number = {2},
pages = {e70180},
doi = {10.1002/cbf.70180},
pmid = {41670365},
issn = {1099-0844},
support = {FF-2022-065/1//Universiti Kebangsaan Malaysia/ ; DPK-2023-004//Universiti Kebangsaan Malaysia/ ; FF-2022-065//Medixcell Sdn. Bhd/ ; },
mesh = {Animals ; Rats, Sprague-Dawley ; *Metabolic Syndrome/metabolism/therapy ; *Extracellular Vesicles/metabolism/transplantation ; Rats ; *Metabolomics ; *Mesenchymal Stem Cells/cytology/metabolism ; *Wharton Jelly/cytology/metabolism ; Male ; Magnetic Resonance Spectroscopy ; Disease Models, Animal ; *Mesenchymal Stem Cell Transplantation ; Metabolome ; },
abstract = {Long-term management of metabolic syndrome (MetS) often involves polypharmacy, which may lead to undesirable outcomes. Regenerative approaches such as mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have gained attention due to their paracrine effects, lower immunogenicity, and safer profile compared to whole-cell therapies. Previous studies suggest that MSC-sEVs improve insulin sensitivity, reduce inflammation, and support cardiovascular health, yet their precise mechanisms remain unclear. This study aimed to compare fecal and serum metabolic profiles of healthy, MetS, and MSC-sEVs-treated MetS rats using NMR-based metabolomics and to identify metabolic pathways underlying the therapeutic effects of Wharton's jelly MSC-sEVs (WJMSC-sEVs). 18 Sprague Dawley rats were divided into three groups: healthy controls, MetS + saline, and MetS + WJMSC-sEVs. After 16 weeks of MetS induction, rats received intravenous saline or WJMSC-sEVs every 3 weeks for 12 weeks. Multivariate analysis revealed clear separations between groups. MetS was associated with reduced serum isoleucine, acetate, and propionic acid, and elevated lactate, threonine, and glucose; fecal samples showed increased valine, alanine, leucine, glutamate, and fructose but reduced threonine and SCFAs. Pathway analysis highlighted disturbances in starch and sucrose metabolism, pyruvate metabolism, and alanine, aspartate and glutamate metabolism. WJMSC-sEVs partially restored these imbalances, suggesting their therapeutic potential by targeting key metabolic pathways in MetS.},
}

Animals
Rats, Sprague-Dawley
*Metabolic Syndrome/metabolism/therapy
*Extracellular Vesicles/metabolism/transplantation
Rats
*Metabolomics
*Mesenchymal Stem Cells/cytology/metabolism
*Wharton Jelly/cytology/metabolism
Male
Magnetic Resonance Spectroscopy
Disease Models, Animal
*Mesenchymal Stem Cell Transplantation
Metabolome

@article {pmid41669940,
year = {2026},
author = {Zhong, J and Tang, J and Han, L and Wang, W and Zhang, X and Zhang, S},
title = {Compound probiotics alleviate Escherichia coli-induced diarrhea in calves by modulating tryptophan and bile acid metabolism of the fecal microbiota.},
journal = {Virulence},
volume = {17},
number = {1},
pages = {2629106},
doi = {10.1080/21505594.2026.2629106},
pmid = {41669940},
issn = {2150-5608},
mesh = {Animals ; *Probiotics/administration & dosage ; *Diarrhea/veterinary/microbiology/therapy ; Cattle ; *Bile Acids and Salts/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Tryptophan/metabolism ; *Escherichia coli Infections/veterinary/microbiology/therapy ; Feces/microbiology ; *Escherichia coli ; Mice ; *Cattle Diseases/microbiology/therapy ; Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S/genetics ; Male ; },
abstract = {Calf diarrhea, particularly that caused by diarrheagenic Escherichia coli, has become a major issue affecting the sustainable development of the calf farming industry. Although the use of traditional antimicrobial agents can alleviate symptoms, challenges such as antibiotic resistance, drug residues, and intestinal microbiota dysbiosis urgently need to be addressed. Therefore, this study investigates the mechanism by which compound probiotics alleviate diarrheagenic Escherichia coli-induced diarrhea in calves. Compound probiotics were administered to calves with diarrheagenic Escherichia coli-induced diarrhea, and their effects on growth performance, intestinal microbiota structure, and metabolic profiles were evaluated. The results showed that compound probiotic intervention significantly improved calf growth performance and weight gain. Integrated 16S rRNA sequencing and metabolomics analyses revealed that compound probiotic intervention markedly modulated the intestinal microbiota, particularly by increasing the abundance of the genus Blautia, while also improving tryptophan and bile acid metabolic pathways. Furthermore, fecal microbiota transplantation experiments conducted in both calves and antibiotic-induced microbiota depletion mouse models confirmed the regulatory effects of compound probiotics on the intestinal microbiota, especially with respect to tryptophan and bile acid metabolism. Compound probiotic intervention regulated key metabolites, including kynurenic acid, taurodeoxycholic acid, and ursodeoxycholic acid, which were positively correlated with Blautia, and significantly reduced inflammation by downregulating pro-inflammatory factors and upregulating anti-inflammatory factors, thereby alleviating diarrheagenic Escherichia coli-induced diarrhea in calves. Overall, this study provides new insights into the application of probiotics in intestinal health management and highlights the significant potential of compound probiotics as an alternative to antibiotics for the treatment of calf diarrhea.},
}

Animals
*Probiotics/administration & dosage
*Diarrhea/veterinary/microbiology/therapy
Cattle
*Bile Acids and Salts/metabolism
*Gastrointestinal Microbiome/drug effects
*Tryptophan/metabolism
*Escherichia coli Infections/veterinary/microbiology/therapy
Feces/microbiology
*Escherichia coli
Mice
*Cattle Diseases/microbiology/therapy
Fecal Microbiota Transplantation
RNA, Ribosomal, 16S/genetics
Male

@article {pmid41669929,
year = {2025},
author = {Qiu, J and Wu, C and Li, S and Yang, X},
title = {Fecal Microbiota Transplantation Attenuated Inflammation Through TGF-β1/Smad Signaling Pathway in Caco-2 and RAW264.7 Cells.},
journal = {The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology},
volume = {37},
number = {2},
pages = {161-169},
doi = {10.5152/tjg.2025.25172},
pmid = {41669929},
issn = {2148-5607},
mesh = {Humans ; Animals ; Mice ; *Signal Transduction ; Caco-2 Cells ; RAW 264.7 Cells ; *Fecal Microbiota Transplantation/methods ; *Transforming Growth Factor beta1/metabolism ; *Smad3 Protein/metabolism/genetics ; *Colitis, Ulcerative/therapy ; Inflammation/therapy ; Smad2 Protein/metabolism ; Smad7 Protein/metabolism ; },
abstract = {BACKGROUND/AIMS: Ulcerative colitis (UC) represents a persistent inflammatory condition that influences millions of people worldwide, with rising prevalence and limited treatment options. Current therapies, such as corticosteroids and immunosuppressants, offer symp tom relief but are associated with significant adverse effects. Fecal microbiota transplantation (FMT) is being increasingly viewed as an effective alternative, but the molecular basis for its benefits in UC is still not fully understood. This study aimed to explore the function of the transforming growth factor-beta 1 (TGF-β1)/Smad signaling cascade in FMT-induced remission of UC.

MATERIALS AND METHODS: Stable Smad3-knockdown and Smad3-overexpression Caco2 cell lines were established via lentivirus-medi ated transduction. These modified Caco-2 cells were co-incubated with RAW264.7 macrophages to mimic intestinal inflammation in vitro. Following FMT treatment, the expression of major components of the TGF β1/Smadsignaling cascade was assessed.

RESULTS: The results demonstrated that FMT markedly downregulated TGF-β1, Smad2, and Smad3 expression, while enhancing Smad7 expression in both Smad3-knockdown and overexpression cell lines. In addition, FMT treatment attenuated the phosphorylation of Smad2 and Smad3, indicating a decrease in the activation of the TGF-β1/Smad signaling pathway.

CONCLUSION: These findings suggest that optimizing FMT protocols targeting this pathway could improve therapeutic outcomes for UC patients.   Cite this article as:Qiu J, Wu C, Li S, Yang X. Fecal microbiota transplantation attenuated inflammation through TGF-β1/Smad signaling pathway in Caco-2 and RAW264.7 cells. Turk J Gastroenterol. 2026;37(2):161-169.},
}

Humans
Animals
Mice
*Signal Transduction
Caco-2 Cells
RAW 264.7 Cells
*Fecal Microbiota Transplantation/methods
*Transforming Growth Factor beta1/metabolism
*Smad3 Protein/metabolism/genetics
*Colitis, Ulcerative/therapy
Inflammation/therapy
Smad2 Protein/metabolism
Smad7 Protein/metabolism

@article {pmid41667440,
year = {2026},
author = {Jia, J and Liu, Y and Wang, D and Pan, Z and Zheng, Q and Lu, J and Liang, C and Li, D},
title = {Ulcerative colitis: signaling pathways, therapeutic targets and interventional strategies.},
journal = {Signal transduction and targeted therapy},
volume = {11},
number = {1},
pages = {51},
pmid = {41667440},
issn = {2059-3635},
support = {82073313//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {Humans ; *Colitis, Ulcerative/genetics/therapy/pathology/drug therapy ; *Signal Transduction/genetics/drug effects ; Endoplasmic Reticulum Stress/genetics ; MicroRNAs/genetics ; RNA, Long Noncoding/genetics ; Animals ; },
abstract = {Ulcerative colitis (UC) is the most common chronic inflammatory disease of the intestinal tract in clinical practice, and long-term chronic inflammation leads to repeated damage to and repair of the colonic mucosa, which may progress to malignancy through atypical hyperplasia. However, there are currently no fully targeted drugs for the treatment of UC. In this review, we discuss several cellular processes, such as autophagy, endoplasmic reticulum stress, mitochondrial dysfunction, macrophage polarization, ferroptosis and the Th/Treg cell balance, which are associated with the occurrence and development of UC. Many molecular targets and signaling pathways, such as nuclear factor kappa-B (NF-κB), phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT), Wnt/β-catenin, adenosine 5'-monophosphate-activated protein kinase (AMPK), toll-like receptor (TLR), Janus kinase/signal transducer and activator of transcription (JAK/STAT), long noncoding RNAs (lncRNAs), and microRNAs (miRNAs), play crucial roles in the progression of UC. We also summarize the common treatment strategies for UC, including lifestyle interventions, aminosalicylic acid preparations, corticosteroid drugs, biologics, fecal microbiota transplantation, and other drugs for symptomatic treatment. This review provides a detailed theoretical basis for the pathology and treatment of UC. Future research could focus on optimizing the treatment plan and achieving more precise and personalized treatment with multiple targets in multiple aspects.},
}

Humans
*Colitis, Ulcerative/genetics/therapy/pathology/drug therapy
*Signal Transduction/genetics/drug effects
Endoplasmic Reticulum Stress/genetics
MicroRNAs/genetics
RNA, Long Noncoding/genetics
Animals

@article {pmid41667242,
year = {2026},
author = {Chen, X and Zuo, Z and Xiao, B and Zhao, F},
title = {Modulating the gut-reproductive tract axis: microbial influence on gynaecological cancer pathogenesis and treatment.},
journal = {Gut},
volume = {},
number = {},
pages = {},
doi = {10.1136/gutjnl-2025-337778},
pmid = {41667242},
issn = {1468-3288},
abstract = {The gut microbiota plays a crucial role in regulating host immunity, metabolism and inflammation, with accumulating evidence linking its composition and function to the development and progression of cancers in the reproductive tract. Patients with ovarian, endometrial and cervical cancers exhibit distinct alterations in their gut microbiota, characterised by reduced microbial diversity and shifts towards taxa associated with dysbiosis and chronic inflammation. Mechanistically, gut-derived metabolites and microbial translocation appear to influence systemic immune responses and oestrogen metabolism, thereby fostering a tumour microenvironment conducive to cancer growth. Beyond its role in tumourigenesis, the gut microbiota also affects treatment outcomes. Dysbiosis can reduce sensitivity to chemotherapy and alter immunotherapy responses, while antibiotic use during cancer treatment has been linked to poorer prognosis. Clinically, these insights highlight emerging applications of microbiome modulation as biomarkers for patient stratification and as adjuvant approaches to enhance therapeutic efficacy in gynaecological oncology, underscoring the therapeutic potential of targeting the microbiota-through dietary interventions, probiotics or faecal microbiota transplantation-to improve cancer treatment outcomes. However, most of these applications remain investigational, and current evidence is limited by heterogeneity across study designs, patient cohorts and cancer subtypes. This review summarises current understanding of gut microbiota profiles in reproductive tract cancers, examines potential mechanisms by which the microbiota influences malignancy, discusses its impact on therapy response and explores its emerging role in precision oncology.},
}

@article {pmid41664444,
year = {2026},
author = {Xie, X and Li, X},
title = {Synergistic Modulation of the Tumor Microenvironment by Ultrasound-Assisted Fecal Microbiota Transplantation to Reverse Anti-PD-1 Resistance in Colorectal Cancer.},
journal = {Cancer biotherapy & radiopharmaceuticals},
volume = {},
number = {},
pages = {10849785251414759},
doi = {10.1177/10849785251414759},
pmid = {41664444},
issn = {1557-8852},
abstract = {BACKGROUND: Colorectal cancer (CRC) development and therapy resistance are heavily controlled by the tumor microenvironment (TME). Although anti-PD-1 immunotherapy has significant therapeutic advantages, resistance remains a key challenge. Recent research has identified the gut microbiota as a key regulator of host immunity and checkpoint inhibitor effectiveness. Ultrasound (US) has emerged as a viable biophysical technique for improving medication and microbial delivery and controlling immune activation within tumors.

OBJECTIVES: The purpose of this work was to assess the synergistic effects of US-assisted fecal microbiota transplantation (US-FMT) on TME remodeling and anti-PD-1 resistance in a CRC cell line-derived xenograft mouse model.

MATERIALS AND METHODS: Tumor-bearing mice were randomized into four treatment groups: vehicle control, anti-PD-1 alone, fecal microbiota transplantation (FMT) alone, and US-FMT plus anti-PD-1 therapy. Low-intensity focused US was utilized to promote microbial engraftment and intestinal permeability. Flow cytometry, ELISA, and transcriptome profiling were used to investigate tumor growth kinetics, immune cell infiltration, cytokine profiles, and TME-related gene expression.

RESULTS: In comparison with the other groups, US-FMT reduced tumor development and restored sensitivity to anti-PD-1 treatment. US facilitated beneficial microbial colonization, boosted CD8 T cell infiltration, and decreased immunosuppressive cell populations. Furthermore, US-FMT modified cytokine release and reduced pro-tumorigenic inflammatory mediators, reprogramming the TME to be immune-active.

CONCLUSIONS: US-assisted microbiota manipulation is a unique and synergistic biotherapeutic method for reversing immunological resistance in CRC. The combination of US and FMT has translational promise for enhancing immunotherapy response and developing noninvasive cancer treatment techniques.},
}

@article {pmid41663002,
year = {2026},
author = {Fang, J and Wu, M and Yu, J and Zhao, J and Liu, Y and Cui, Y and Chen, Y and Han, S and Chen, W and Peng, D and Yao, L},
title = {Mechanistic study of Dendrobium huoshanense polysaccharides improving ulcerative colitis by promoting Lachnoclostridium edouardi metabolism of short-chain fatty acids.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {121321},
doi = {10.1016/j.jep.2026.121321},
pmid = {41663002},
issn = {1872-7573},
abstract = {Dendrobium huoshanense C. Z. Tang et S. J. Cheng (DH) is a traditional medicinal herb with a long history of medicinal use in the treatment of gastrointestinal disorders. It has therapeutic effects on chronic atrophic gastritis, superficial gastritis, and duodenal ulcer, while also promoting gastric juice secretion and gastrointestinal motility. Dendrobium huoshanense polysaccharides (DHP) is an active ingredient extracted from it and has a variety of pharmacological activities, but its mechanism of action on ulcerative colon is worthy of further study.

AIMS OF THIS STUDY: This study aimed to investigate whether DHP could alleviate ulcerative colitis (UC) by activating PPARγ and to elucidate the mechanism behind it in relation to the short-chain fatty acid (SCFAs) content metabolized by gut microbiota.

METHODS: This study initially validated the preventive effects of DHP on UC using an animal model. The key gut microbiota affected by DHP were identified by 16S rRNA. The potential mechanism of DHP treatment for UC was demonstrated by LC-MS/MS to detect the levels of SCFAs, and by immunofluorescence and Western blotting to detect the expression of PPARγ/NF-κB pathway proteins. This potential mechanism was further confirmed by a fecal microbiota transplantation (FMT) experiment. Finally, through the in-depth study of the different intestinal flora regulated by DHP, Lachnoclostridium edouardi was found to be related to the production of SCFAs, and the effect of metabolites produced by DHP fermented by this strain on the inflammation of colonic epithelial cells was investigated through in vitro fermentation experiments, to clarify the intestinal strains that are specifically regulated by DHP.

RESULTS: The results showed that DHP significantly alleviated UC symptoms and reduced colonic tissue damage in mice, while restoring the balance of the intestinal microbiota. In addition, DHP substantially increased the concentration of SCFAs in the colon. These shifts triggered PPARγ activation and inhibited NF-κB phosphorylation in the colon tissue, effectively reducing inflammation and improving UC outcomes. The FMT assay further validated that the preventive benefits of DHP were mediated through the intestinal flora. Meanwhile, the DHP-specifically regulated strain Lachnoclostridium edouardi showed markedly higher short-chain fatty acid content in metabolites produced by fermentation with DHP in vitro and effectively suppressed inflammation in colonic epithelial cells.

CONCLUSIONS: This study suggests that DHP can play a role in the treatment of UC by modulating short-chain fatty acid metabolism in the gut microbiota and activating the PPARγ/NF-κB pathway. Moreover, DHP was able to promote the content of SCFAs produced by the metabolism of the Lachnoclostridium edouardi strain in the gut microbiota, and its metabolites also showed therapeutic effects on UC. These findings provide a basis for the clinical application of DHP in UC.},
}

@article {pmid41660969,
year = {2026},
author = {Bautista, J and Bazantes-Rodríguez, E and Cedeño, H and Anrango-Flores, C and Carrera-Cruz, F and Cisneros-Nieto, Z and López-Cortés, A},
title = {Reprogramming human health through the microbiome and precision medicine.},
journal = {Critical reviews in microbiology},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/1040841X.2026.2629269},
pmid = {41660969},
issn = {1549-7828},
abstract = {The human microbiome, comprising trillions of microorganisms across multiple body sites, is increasingly recognized as a key contributor to host immunity, metabolism, and neurobiology, influencing development and disease susceptibility throughout life. Rather than acting in isolation, microbial communities operate within a complex host-environment system shaped by genetics, diet, lifestyle, and medical exposures. Conceptually, the microbiome can be understood as part of a host-microbe meta-organism and, from a translational perspective, as a dynamic and potentially modifiable organ system. While short-term perturbations such as antibiotics may transiently disrupt microbial ecosystems, persistent maladaptive configurations, commonly termed dysbiosis, are associated with metabolic disease, chronic inflammation, neurodevelopmental disorders, and cancer, although causality remains context dependent. This review synthesizes the functional roles of beneficial microbes and their metabolites, the mechanistic and clinical implications of dysbiosis, and immune pathways shaped by microbial signals. We further discuss emerging therapeutic strategies, including dietary modulation, probiotics, engineered microbial consortia, postbiotics, and fecal microbiota transplantation, enabled by multi-omics technologies, organoid models, and computational frameworks. Key challenges include defining context-specific microbial health, ensuring durable engraftment, and addressing regulatory and ethical considerations. Framing the microbiome as a dynamic component of host physiology provides a foundation for microbiome-guided precision and preventive medicine.},
}

@article {pmid41660243,
year = {2026},
author = {Ding, Y and Chen, X and Tao, Y and Dong, H and Zhang, Z and Xiao, X and Chen, G and Li, X and Xie, R},
title = {Gut-lung axis perturbation and Bifidobacterium potential after spinal cord injury in humans and mice.},
journal = {iScience},
volume = {29},
number = {2},
pages = {114655},
pmid = {41660243},
issn = {2589-0042},
abstract = {Spinal cord injury (SCI) predisposes patients to severe respiratory complications. Integrating clinical observations with a mouse model, we identified gut-lung axis perturbation as a key mechanism. SCI increased the similarity between gut and lung microbial communities, consistent with cross-compartment convergence driven by intestinal dysbiosis. Fecal microbiota transplantation from SCI donors reproduced this convergence in healthy recipients. Crucially, oral Bifidobacterium supplementation restored intestinal community structure, reduced gut-lung similarity, and attenuated pulmonary inflammation following an Escherichia coli challenge. These findings indicate that SCI disrupts gut-lung compartmentalization and that augmenting beneficial gut taxa mitigates downstream pulmonary consequences. Microbiota-targeted strategies therefore warrant evaluation as adjuncts to reduce post-SCI respiratory risk.},
}

@article {pmid41659429,
year = {2026},
author = {Vallecillo-Zuniga, ML and Akeefe, A and Brown, DG and Wahlig, TA and Marchetti, M and Heiner, T and Davis, KL and Nieznanski, C and Flynn, A and Leung, DT},
title = {Longitudinal Changes in Nasal and Oral Microbiome and Antimicrobial Resistance Gene Profiles in Response to Human Fecal Microbiota Transplantation.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.01.27.701854},
pmid = {41659429},
issn = {2692-8205},
abstract = {The gut-lung axis describes interactions between intestinal and respiratory mucosal systems through microbial, metabolic, and immune pathways, but the systemic impact of gut-targeted therapies on upper respiratory tract (URT) communities remains underexplored. We conducted a longitudinal study in adult patients undergoing fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) alongside healthy controls. Fecal, nasal, and oral samples were collected at baseline (Day 0) and on Days 14 and 56 following FMT. Shotgun metagenomic sequencing was performed to quantify microbial diversity, taxonomic composition, and the abundance of antimicrobial resistance genes (ARGs). FMT was associated with increased gut diversity and decreased levels of key intestinal taxa commonly considered pathobionts, including Klebsiella spp., Escherichia spp., Shigella spp., and Klebsiella pneumoniae . At the phylum level, fecal Bacteroidota increased, while Mucoromycota decreased following treatment. Post-FMT nasal microbiome changes included reduced richness and diversity, expansion of Moraxella , and decreases in taxa linked with respiratory colonization, including Staphylococcus aureus and Streptococcus pneumoniae . By Day 56, nasal communities partially recovered toward healthy profiles. Baseline nasal ARG abundance decreased following FMT, particularly among β-lactam, aminoglycoside, and fluoroquinolone resistance genes, and remained comparable to healthy controls by Day 56. In contrast, the oral microbiome and oral resistome remained largely stable, with only minor fluctuations, and no consistent increases in respiratory pathobiont-associated taxa. In summary, FMT was associated with broader effects beyond the gut, including changes in the URT microbial ecology and antimicrobial resistance profiles. Together, these findings are consistent evidence of gut-lung microbial interactions, linking intestinal dynamics with respiratory microbial composition and antimicrobial resistance patterns.},
}

@article {pmid41659330,
year = {2025},
author = {Wu, H and Wei, G and Huang, S and Wan, L and Xu, Q and Huang, C},
title = {The gut-brain axis mediates precocious puberty induced by environmentally relevant low-dose endocrine-disrupting chemical mixtures.},
journal = {Frontiers in endocrinology},
volume = {16},
number = {},
pages = {1728811},
pmid = {41659330},
issn = {1664-2392},
mesh = {*Endocrine Disruptors/toxicity/adverse effects ; *Puberty, Precocious/chemically induced ; Humans ; Animals ; *Gastrointestinal Microbiome/drug effects ; Female ; *Brain/drug effects ; Dysbiosis/chemically induced ; *Brain-Gut Axis/drug effects ; },
abstract = {BACKGROUND: The global rise in precocious puberty (PP) is increasingly linked to exposure to endocrine-disrupting chemicals (EDCs). However, the mechanisms by which environmentally relevant, low-dose mixtures of EDCs influence PP remain inadequately explained by direct endocrine disruption.

OBJECTIVE: This systematic review evaluates a novel hypothesis: that disruption of the gut-brain axis (GBA) serves as a pivotal mechanism in EDC mixture-induced PP.

METHODS: We synthesized evidence from 87 studies (45 human, 32 animal, 10 in vitro) following PRISMA 2020 guidelines. An exploratory Random Forest analysis was employed to identify key mediators and estimate the relative contribution of the GBA pathway.

RESULTS: Perinatal exposure to low-dose EDC mixtures consistently induced gut dysbiosis, characterized by reduced microbial diversity (Shannon Δ = -1.8), a 40% decrease in Lactobacillus, and a 1.5-fold increase in Bacteroides. This dysbiosis was linked to impaired production of butyrate (↓50%) and secondary bile acids, increased intestinal permeability (FITC-dextran ↑80%), and systemic inflammation (IL-6 ↑1.8-fold). Fecal microbiota transplantation from PP donors into germ-free mice recapitulated early pubertal onset, supporting a causal role for gut microbiota. Exploratory modeling suggested that mediators within the GBA pathway could be associated with a large share (approximately 68%) of the model-internal variance explanation for PP risk at low experimental doses (≤1 μg/kg/day), indicating its potential prominence over direct endocrine disruption in this analysis. Significant synergistic effects (Synergy Index > 2.3) were observed under mixture exposures.

CONCLUSION: This review identifies the GBA as a critical and previously underappreciated mechanism for low-dose EDC mixture-induced precocious puberty in a dose-dependent manner. Our findings underscore the need for regulatory paradigms and future research to integrate this pathway when assessing the risks of complex, real-world chemical mixtures.},
}

*Endocrine Disruptors/toxicity/adverse effects
*Puberty, Precocious/chemically induced
Humans
Animals
*Gastrointestinal Microbiome/drug effects
Female
*Brain/drug effects
Dysbiosis/chemically induced
*Brain-Gut Axis/drug effects