@article {pmid42304911,
year = {2026},
author = {Ding, W and Li, R and Gong, L and Yi, J and Wang, Y and Xiao, D and Wu, H and Hu, W and Li, J and Li, H and Lu, X and Liu, Z and Qin, Z and Lu, X and Li, Z},
title = {Efficacy and Safety of Fecal Microbiota Transplantation for Patients with Treatment-resistant Schizophrenia: A Double-blind, Randomized Clinical Trial Protocol.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X431672260406044032},
pmid = {42304911},
issn = {1875-6190},
abstract = {OBJECTIVES: This randomized, double-blind, placebo-controlled trial was designed to evaluate the efficacy and safety of Fecal Microbiota Transplantation (FMT) in patients with Treatment-Resistant Schizophrenia (TRS), comparing two delivery methods: intraduodenal administration via gastroscopy and oral capsule ingestion.

METHODS: This study employed a randomized, double-blind, placebo-controlled design. Eligible subjects will be randomized into three groups: (1) intraduodenal FMT administration via gastroscopy, (2) oral FMT capsule administration, and (3) placebo control. Before and after the intervention, fecal, urine, and venous blood samples will be collected for microbiomics and metabolomic analyses. Clinical symptom severity will be assessed using standardized psychiatric scales to evaluate the efficacy and safety of FMT.

DISCUSSION: Should Fecal Microbiota Transplantation be found to be as clinically and cost-effective for patients with treatment-resistant schizophrenia, this approach has the potential to be considered as an adjunctive treatment for those with a broader range of psychiatric conditions.

ChiCTR2400092799.},
}

@article {pmid42305042,
year = {2026},
author = {Xie, X and Yan, W and Zhang, X and Gan, C and Lei, X and Huang, Y and Xiong, W and Tang, H and Zhu, H},
title = {FMT from IBS-D Rats Impairs Intestinal Barrier Function and is Associated with Increased Intestinal Benzoic Acid and Ruminococcus Abundance.},
journal = {Journal of microbiology and biotechnology},
volume = {36},
number = {},
pages = {e2602004},
doi = {10.4014/jmb.2602.02004},
pmid = {42305042},
issn = {1738-8872},
mesh = {Animals ; *Fecal Microbiota Transplantation/adverse effects ; *Irritable Bowel Syndrome/therapy/microbiology/physiopathology ; Rats ; Gastrointestinal Microbiome ; Intestinal Barrier Function ; Disease Models, Animal ; Male ; *Ruminococcus/isolation & purification ; Tumor Necrosis Factor-alpha/blood/genetics ; Rats, Sprague-Dawley ; Dysbiosis ; Intestinal Mucosa/metabolism ; Amine Oxidase (Copper-Containing)/blood ; Intestines/microbiology ; Feces/microbiology ; },
abstract = {While the etiology of diarrhea-predominant irritable bowel syndrome (IBS-D) is multifactorial, current studies have converged to identify gut microbiota dysbiosis as a principal contributor. This study aimed to elucidate the role of the gut microbiota in IBS-D progression and to uncover the underlying mechanisms. In this study, a rat model of IBS-D was successfully established, characterized by prominent visceral hypersensitivity and diarrhea. To assess the impact of the gut microbiota, recipient rats pretreated with broad-spectrum antibiotics underwent fecal microbiota transplantation (FMT) from IBS-D model rats. The model-microbiota recipient rats (the MR group) developed IBS-D-like symptoms, such as abdominal pain, diarrhea, and depression-like behaviors. Both the IBS-D and MR groups exhibited elevated serum diamine oxidase (DAO) concentrations, reduced intestinal tight junction protein levels, increased serum TNF-α concentrations, upregulated TNF-α mRNA expression, and downregulated IL-10 mRNA expression in the intestine. These findings indicated that the transplanted microbiota disrupted intestinal barrier integrity and triggered low-grade inflammation. Moreover, an elevated abundance of Ruminococcaceae in the gut microbiota was a common feature of both the IBS-D and MR groups. Metabolomic analysis revealed an enrichment in the phenylalanine, tyrosine, and tryptophan biosynthesis pathway in both IBS-D and recipient groups, with benzoic acid being particularly prominent. Pearson correlation analysis demonstrated a strong positive correlation between the Ruminococcus abundance and benzoic acid levels. Together, these findings indicated that FMT robustly recapitulated core IBS-D pathophysiology in recipient rats, and the identified bacteria and metabolites provided novel insights into the pathogenesis of IBS-D.},
}

Animals
*Fecal Microbiota Transplantation/adverse effects
*Irritable Bowel Syndrome/therapy/microbiology/physiopathology
Rats
Gastrointestinal Microbiome
Intestinal Barrier Function
Disease Models, Animal
Male
*Ruminococcus/isolation & purification
Tumor Necrosis Factor-alpha/blood/genetics
Rats, Sprague-Dawley
Dysbiosis
Intestinal Mucosa/metabolism
Amine Oxidase (Copper-Containing)/blood
Intestines/microbiology
Feces/microbiology

@article {pmid42305614,
year = {2026},
author = {Jiang, C and Nageeb, WM and Batool, S and Hashish, A and Alkhawagah, SM and Abdelsattar Ibrahim, HA and Zhu, W and Che, C and Li, X and Jin, M and Zhang, X and Ghonaim, AH and Ren, M and Li, S},
title = {Unraveling the gut microbiota-brain axis: Mechanisms, pathophysiology, and therapeutic opportunities.},
journal = {iScience},
volume = {29},
number = {6},
pages = {116224},
pmid = {42305614},
issn = {2589-0042},
abstract = {The gut microbiota-brain axis constitutes a dynamic, bidirectional communication network that integrates neural, endocrine, immune, and metabolic pathways to regulate host physiology and behavior. Accumulating evidence indicates that disturbances within this axis have been consistently associated with metabolic, autoimmune, and neuropsychiatric disorders; however, much of the current evidence, particularly from human studies, remains largely correlative, and causal relationships are still under active investigation, highlighting its systemic relevance to health and disease. This review synthesizes current understanding of the structural and functional components of the gut microbiota-brain axis, including microbial community dynamics, neural signaling pathways, and key endocrine and immune mediators. We examine mechanistic insights into how microbial-derived metabolites influence brain function, cognition, mood regulation, stress responses, and disease pathogenesis. In addition, we discuss emerging therapeutic strategies targeting the gut microbiota-brain axis, including psychobiotics and fecal microbiota transplantation, while acknowledging dietary approaches, such as prebiotic supplementation, fiber-rich diets, and fermented food consumption, as complementary strategies that modulate microbiota composition that may indirectly support gut-brain axis function. By integrating mechanistic, clinical, and translational perspectives, this review aims to clarify current knowledge gaps and highlight future directions for leveraging the gut microbiota-brain axis in personalized approaches to neuropsychiatric disease management.},
}

@article {pmid42307051,
year = {2026},
author = {Lang, T and Farowski, F and Al-Gousous, J and Langguth, P and Vehreschild, MJGT},
title = {Validation of an Automated Fluorescence- and Image-Based Viable Cell Counting Method for Fecal Microbiota Transplantation Drug Products.},
journal = {Biotechnology journal},
volume = {21},
number = {6},
pages = {e70269},
pmid = {42307051},
issn = {1860-7314},
support = {//German Centre for Infection Research/ ; },
mesh = {*Fecal Microbiota Transplantation/methods ; *Feces/microbiology ; Escherichia coli/cytology ; Humans ; Bacillus subtilis ; Reproducibility of Results ; Cell Count/methods ; Fluorescence ; },
abstract = {Fecal microbiota transplantation (FMT) is an established treatment for recurrent Clostridioides difficile infection. As a drug product, FMT is subject to pharmaceutical quality standards, including accurate quantification of viable bacteria to ensure product consistency. We developed and validated an automated fluorescence- and image-based viable-cell counting method for FMT products; total-cell enumeration was examined secondarily. The QUANTOM Tx system (Logos Biosystems) was validated according to ICH Q2(R2) using Escherichia coli and Bacillus subtilis as reference strains. The Viable Cell Staining Kit was validated with Escherichia coli, whereas the Total Cell Staining Kit was examined in selected experiments using both strains. Applicability to complex FMT matrices was confirmed using authentic fecal samples. Viable-cell counting showed strong linearity across a range of 9.4 × 10[6]-1.2 × 10[8] cells/mL, with adequate accuracy and precision. Specificity was ensured by particle-size gating, unaffected by nonviable cells or diluent. Robustness was confirmed across operators and time points. Fecal samples showed linear quantifiability and acceptable precision; total-cell enumeration fulfilled linearity and precision requirements. The validated method enables rapid, reproducible viable-cell quantification suitable for Quality Control of FMT drug products, supporting formulation development, and dosing verification. Viable-cell quantification remains the analytical focus, despite limitations in spore detection. Total-cell enumeration provides complementary process information.},
}

*Fecal Microbiota Transplantation/methods
*Feces/microbiology
Escherichia coli/cytology
Humans
Bacillus subtilis
Reproducibility of Results
Cell Count/methods
Fluorescence

@article {pmid42309058,
year = {2026},
author = {Li, J and Wang, Y and Li, R and Huang, H and Zhu, X and Li, X and Sun, Z and Zhang, L and Zheng, P and He, Y and Liu, J and Zhang, X and Ren, S and Liu, M and Wang, H and Luo, Y and Wang, F and Zhou, J and Yang, J and Wang, G},
title = {Adjunctive fecal microbiota transplantation for major depressive disorder: A randomized, double-blind, placebo-controlled trial.},
journal = {Cell host & microbe},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.chom.2026.05.017},
pmid = {42309058},
issn = {1934-6069},
abstract = {Gut microbiota may influence antidepressant treatment outcomes, yet whether targeted modulation can enhance efficacy remains unclear. We conducted a randomized, double-blind, placebo-controlled trial in patients with major depressive disorder, administering a 2-week course of fecal microbiota transplantation (FMT) capsules or placebo as an adjunct to escitalopram (ChiCTR2300071421). Remission rates at week 8 did not differ significantly between groups, but FMT produced greater reductions in Hamilton Depression Rating Scale, 17-item version (HAMD-17) scores at weeks 2 and 8. FMT was well-tolerated with a safety profile comparable to placebo. Multi-omics analyses show durable donor microbial engraftment and enrichment of beneficial Lachnospiraceae and Oscillospiraceae taxa. Microbial remodeling is accompanied by an increase in serum bile acids that correlate with the alleviation of depressive symptoms. Mediation analysis supports a bile-acid-mediated suppression of inflammatory pathways linking microbial changes to antidepressant effects. Overall, FMT may provide a safe avenue to enhance escitalopram efficacy through microbiota-directed regulation of bile-acid metabolism and inflammation.},
}

@article {pmid42311013,
year = {2026},
author = {Pouliou, C and Poulios, P and Piperi, C},
title = {Unravelling the Critical Interplay of Oral and Gut Microbiota in Disease Development.},
journal = {Current medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0109298673440488260516210738},
pmid = {42311013},
issn = {1875-533X},
abstract = {The oral microbiota, comprising bacteria, fungi, and viruses, plays a critical role in initiating food digestion, serving as the first defense against pathogenic invasion and maintaining oral homeostasis. In contrast, the gut microbiota, consisting of trillions of microorganisms, functions as a barrier protection, modulating the immune system and facilitating the absorption of nutrients. Although they have distinct anatomical locations, these ecosystems are highly interconnected and play a pivotal role in human health and disease. The most common routes of interaction between the oral and gut microbiota are the enteral, the hematogenous, and the immune cell migration routes. Many oral pathogens interact with intestinal microbes, activating the host's mechanisms that establish dysbiosis and pave the way for the development of various diseases, ranging from inflammatory bowel disease and colorectal cancer to metabolic and neurodegenerative disorders. In this review, we delineate the mechanisms underlying these ecosystems to offer novel insights into disease pathogenesis while also unveiling new avenues for preventive and therapeutic interventions. Although current therapeutic approaches include the administration of antibiotics, prebiotics, and probiotics, novel personalized therapeutic approaches have also emerged. Fecal microbiota transplantation (FMT), gut bacteria engineering, nanomedicine-based techniques, and the use of miRNA to foster microbiota balance in both compartments hold great promise and may prove critical for the prevention and management of systemic diseases.},
}

@article {pmid42298631,
year = {2026},
author = {Yan, Q and Li, M and Wang, G and Zhang, A and Li, Y and Guo, R and Zhang, Y and Yang, W and Zhang, Y and Liu, X and Li, X and Zheng, N and Wang, L and Fan, S and Ma, R and Lu, T and Zhou, S and Guan, T and Xing, G and Li, S and Wang, L and Li, Y},
title = {Cross-kingdom microbial associations characterize responsiveness to fecal microbiota transplantation in patients with irritable bowel syndrome.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08269-w},
pmid = {42298631},
issn = {1479-5876},
abstract = {BACKGROUND: Precise outcome prediction for fecal microbiota transplantation (FMT) in irritable bowel syndrome (IBS) remains a clinical challenge. The roles of the gut virome and its interplay with bacteria in FMT efficacy are particularly underexplored. This secondary analysis aimed to conduct an exploratory, hypothesis-generating investigation into these cross-kingdom dynamics.

METHODS: We conducted a secondary, integrative analysis of a published cohort, performing longitudinal, cross-kingdom metagenomic profiling on 83 samples from 22 IBS patients and healthy donors. We integrative approach combined microbial diversity, species-specific biomarker identification, bacterial-viral associated networks, and exploratory random forest modeling to identify microbial features associated with FMT outcomes.

RESULTS: IBS patients showed higher bacterial and viral alpha diversity than donors. Cross-kingdom profiling identified 223 bacterial and 724 viral biomarkers. Donor-enriched biomarkers were predominantly health-associated Bacteroidetes (e.g., B. ovatus, B. faecis), whereas pre-FMT-enriched biomarkers were largely Firmicutes (e.g., B. obeum) with potential pathobiont roles. The Effect and No effect groups displayed different microbial trajectories. Although both groups shifted toward a donor-like composition initially, only responders maintained a stable donor-like ecology throughout the 12-month follow-up, supported by more resilient bacterial-viral association networks. Exploratory random forest modeling highlighted microbial features, such as R. pickettii, with high relative importance for outcome discrimination. However, permutation testing (p = 0.548-0.616) confirmed that model performance on this small cohort did not exceed chance level, underscoring the risk of overfitting and the exploratory nature of these computational findings.

CONCLUSIONS: This integrative re-analysis provides preliminary evidence that cross-kingdom gut microbiome profiles are strongly associated with FMT outcomes in IBS. Successful outcomes appear linked to sustained donor-like remodeling and stable bacterial-viral networks. Our findings are primarily hypothesis-generating and offer a framework of candidate biomarkers for future validation in larger cohorts. This work underscores the necessity of external validation to develop robust, microbiome-based tools for personalized FMT therapy.},
}

@article {pmid42301720,
year = {2026},
author = {Zuo, G and Yao, Y and Shen, Y and Liu, F and Chang, F and Tang, B and Huang, H and Huang, JA and Liu, Z and Lin, Y},
title = {Optimized Extraction Process of Fu Brick Tea Polysaccharides Using Ultrasound-Assisted Enzymatic Strategy and Their Enhanced Antioxidant and Immunoprotective Activities.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.6c01025},
pmid = {42301720},
issn = {1520-5118},
abstract = {The immunomodulatory mechanisms of Fu brick tea polysaccharides (FBTPs) remain poorly defined, particularly regarding their structure-bioactivity relationship and the causal involvement of the gut microbiota. To address this, we investigated structurally distinct FBTPs prepared via an optimized ultrasound-assisted enzymatic extraction protocol (designated UAEPS). Characterization revealed that UAEPS possesses unique structural features, such as a lower molecular weight and higher carbohydrate content, distinguishing it from polysaccharides obtained via traditional method (HWEPS). Functionally, UAEPS exhibited potent in vitro bioactivities, including significant antioxidant, anti-inflammatory, and cytoprotective effects. In immunosuppressed mouse model, UAEPS restored immune homeostasis, attenuated multiorgan damage, and reshaped the gut microbiota, with marked enrichment of Lactobacillus. The causal role of the gut microbiota was further confirmed by a fecal microbiota transplantation experiment, where recipients mirrored the protective immunomodulatory effects. Collectively, UAEPS represents structurally distinct FBTPs whose immunomodulatory activity is mediated through gut microbiota remodeling.},
}

@article {pmid42301903,
year = {2026},
author = {Yuan, S and Liu, Y and Gao, P and Sun, J and Wang, Y and Du, Z and Lei, J and Hong, J and Fang, X and Tu, P and Lu, Y and Jiang, Y},
title = {Lactobacillus reuteri targets FXR-dependent bile acid homeostasis to ameliorate alcoholic liver disease.},
journal = {The ISME journal},
volume = {},
number = {},
pages = {},
doi = {10.1093/ismejo/wrag153},
pmid = {42301903},
issn = {1751-7370},
abstract = {Alcoholic liver disease (ALD) is characterized by gut dysbiosis, yet the functional contribution of specific commensals remains largely unexplored. Here, we identify a significant reduction of Lactobacillus reuteri in both ALD patients and mouse models compared with their respective healthy controls. Using fecal microbiota transplantation (FMT), we first establish a causative role of the dysbiotic gut microbiota in driving ALD pathophysiology. In line with this finding, oral supplementation with L. reuteri ameliorates ALD phenotypes. Mechanistically, L. reuteri activates the farnesoid X receptor (FXR) signaling pathway, thereby restoring bile acid homeostasis, as evidenced by reduced levels of cholic acid (CA) and deoxycholic acid (DCA). The functional importance of FXR is further validated in Fxr-/- mice, where the protective effects of L. reuteri on both ALD and bile acid metabolism are largely abrogated. Moreover, both in vitro and in vivo experiments confirm that CA and DCA directly compromise hepatocyte viability and exacerbate liver injury, reinforcing their roles as pathogenic effectors downstream of FXR dysregulation. Expanding upon these mechanistic insights, we identify the natural compound echinacoside as a gut microbiota-targeting intervention that not only enriches L. reuteri but also potentiates FXR signaling, leading to significant improvement of ALD. Collectively, our findings define a microbiota-host metabolic axis centered on L. reuteri and FXR-dependent bile acid homeostasis, offering a conceptual framework for targeting host-microbe interactions in alcoholic liver disease.},
}

@article {pmid42302008,
year = {2026},
author = {Fei, Y and Gao, MY and Qiao, N and Hu, J and He, L and Zhou, JL and Zheng, NN and Liu, TT},
title = {Bioinformatic identification of CD8+ T cell activation mediated by key genes in fecal microbiota transplantation for irritable bowel syndrome.},
journal = {PloS one},
volume = {21},
number = {6},
pages = {e0351574},
doi = {10.1371/journal.pone.0351574},
pmid = {42302008},
issn = {1932-6203},
mesh = {Humans ; *Irritable Bowel Syndrome/therapy/genetics/immunology/microbiology ; *CD8-Positive T-Lymphocytes/immunology/metabolism ; *Fecal Microbiota Transplantation/methods ; *Lymphocyte Activation/genetics ; *Computational Biology/methods ; Gene Expression Profiling ; Transcriptome ; },
abstract = {BACKGROUND: The effect of fecal microbiota transplantation (FMT) in treating irritable bowel syndrome (IBS) may be attributed to the modulation of CD8 + T cells. This study aims to identify FMT-mediated key genes to explore the underlying mechanism.

METHODS: Transcriptomic datasets GSE138297 (colonic biopsies from 8 IBS patients pre- and post-FMT) and GSE134649 (single-cell data from 3 healthy colon tissues) were obtained from GEO during December 2023-December 2024. Key genes were identified by intersecting differentially expressed genes (DEGs) and the most relevant co-expression module derived from weighted correlation network analysis. Functional enrichment, gene set enrichment analysis, immune infiltration profiling via TIMER 2.0, single-cell annotation using PanglaoDB and Seurat, and drug-gene interaction screening from DrugBank were conducted to decipher the regulatory mechanisms.

RESULTS: Ten key genes were identified through integration of DEGs and the MEgreen module. Functional analyses revealed significant involvement in the positive regulation of CD8 + T cells activation. Immune infiltration assessment demonstrated a marked increase in CD8 + T cells abundance post-FMT. Single-cell data indicated predominant expression of LILRB1, P2RY13, CLEC10A, and CLEC12A in dendritic cells, and LILRB1, PIPOX, and CLEC11A were annotated within CD8 + T cells clusters in healthy colonic tissue. Nine (database-derived and speculative) drugs targeting seven key genes were identified, most implicated in the management of IBS symptoms or immunomodulation.

CONCLUSION: An association between key gene regulation and CD8 + T cell-related immunoregulation is correlated with the therapeutic effect of FMT in IBS.},
}

Humans
*Irritable Bowel Syndrome/therapy/genetics/immunology/microbiology
*CD8-Positive T-Lymphocytes/immunology/metabolism
*Fecal Microbiota Transplantation/methods
*Lymphocyte Activation/genetics
*Computational Biology/methods
Gene Expression Profiling
Transcriptome

@article {pmid42302222,
year = {2026},
author = {Pereira, MAOM and Tudella, GCN and Klostermann, AU and Ohannesian, VA and Gonçalves, OR and da Silva, RO and Andrade Fernandes, JV and Ahmed, A and Alencar, ABB and de Morais, STA and Almeida, KJ},
title = {Fecal Microbiota Transplantation in Parkinson Disease: A Systematic Review, Meta-Analysis, and Meta-Regression.},
journal = {Neurology},
volume = {107},
number = {1},
pages = {e218175},
doi = {10.1212/WNL.0000000000218175},
pmid = {42302222},
issn = {1526-632X},
mesh = {Humans ; *Parkinson Disease/therapy ; *Fecal Microbiota Transplantation/methods ; Treatment Outcome ; },
abstract = {BACKGROUND AND OBJECTIVES: Parkinson disease (PD) is a progressive neurodegenerative disorder increasingly linked to gut microbiota dysbiosis, which may influence disease mechanisms and symptom expression. Fecal microbiota transplantation (FMT) targets the gut-brain axis, but clinical evidence remains inconsistent. This study aimed to evaluate the efficacy and safety of FMT in PD.

METHODS: We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with protocol registration in International Prospective Register of Systematic Reviews (CRD420251142846). MEDLINE, Embase, and the Cochrane Library were searched from inception through September 2025. Randomized controlled trials (RCTs) and observational studies enrolling adults with mild-to-moderate PD who received FMT through any administration route were eligible. The primary outcome was motor function assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) part III. Secondary outcomes included UPDRS part II, quality of life (Parkinson's Disease Questionnaire-39 [PDQ-39]), constipation severity (Wexner score), and adverse events. Random-effects models pooled effect estimates with 95% CIs, and exploratory meta-regression assessed follow-up duration, publication year, and sample size.

RESULTS: Eight studies (5 RCTs and 3 observational studies) including 220 participants were analyzed. The mean age ranged from approximately 60 to 70 years, and women comprised about 40% of participants. FMT was associated with significant improvement in motor function (UPDRS part III: mean difference [MD] -9.67, 95% CI -16.81 to -2.53) and constipation severity (Wexner score: MD -3.91, 95% CI -7.68 to -0.13). Improvements in UPDRS part II and PDQ-39 were observed at 12 weeks but not sustained at 24 weeks. In RCT-only analyses, UPDRS part III improvement remained significant (MD -6.82, 95% CI -11.23 to -2.40), whereas other outcomes were not consistently significant. Meta-regression indicated that longer follow-up was associated with greater improvement in UPDRS part II (p = 0.043). FMT was generally well tolerated; however, gastrointestinal adverse events were more frequent in the FMT group (risk ratio 3.12, 95% CI 1.14-8.53), predominantly mild to moderate.

DISCUSSION: FMT may provide short-term improvements in motor and gastrointestinal symptoms in PD, but effects appear transient. Small sample sizes, heterogeneity, and limited follow-up restrict conclusions, underscoring the need for larger randomized trials. Pooled estimates reflected evidence from observational studies and should be interpreted cautiously.},
}

Humans
*Parkinson Disease/therapy
*Fecal Microbiota Transplantation/methods
Treatment Outcome

@article {pmid42304226,
year = {2026},
author = {Yan, Y and Liang, S and Li, S and Xie, S and Wang, X and Zhang, H},
title = {Gut dysbiosis modulates hyperoxia-induced bronchopulmonary dysplasia by promoting EMT through activating TLR4/NF-κB pathway.},
journal = {Molecular medicine (Cambridge, Mass.)},
volume = {},
number = {},
pages = {},
doi = {10.1186/s10020-026-01529-x},
pmid = {42304226},
issn = {1528-3658},
support = {2024BS022//Research foundation of Guangzhou Women and Children's Medical Center for Clinical Doctor/ ; 011302064//Guangzhou Postdoctoral Science Foundation/ ; 20261A031030//Guangzhou Health and Wellness Science and Technology Youth Talent Cultivation Project/ ; },
abstract = {BACKGROUND: Bronchopulmonary dysplasia (BPD) is a major cause of morbidity and mortality in premature infants. Although gut microbial dysbiosis is implicated in BPD pathogenesis, the underlying mechanisms are poorly defined. This study aims to elucidate the specific pathway through which gut dysbiosis drives BPD pathology and to identify potential therapeutic targets.

METHODS: The experimental BPD model was established by hyperoxia (FiO2 85%) in neonatal mice from postnatal days 1 to 14. Pulmonary alveolarization and inflammation were analyzed at postnatal day 15. The modulatory role of gut microbiota was assessed using antibiotic-induced dysbiosis and fecal microbiota transplantation (FMT) from normoxic mice. Gut microbiome analysis was performed using 16S rRNA gene sequencing. The specific signaling pathway was investigated using a pharmacological inhibitor of TLR4. Furthermore, the molecular mechanisms were investigated through western blotting, real-time quantitative PCR, ELISA, and immunofluorescence.

RESULTS: Hyperoxia exposure induced impaired alveolarization, disrupted gut barrier integrity, and gut dysbiosis. These pathological changes were accompanied by elevated pulmonary inflammation, potent activation of the TLR4/NF-κB pathway, and upregulation of epithelial-mesenchymal transition (EMT) associated markers. These changes were exacerbated by early postnatal antibiotic administration, whereas FMT from normoxic mice rescued these phenotypes, restored gut barrier function, suppressed TLR4/NF-κB signaling, and reversed EMT progression. Notably, pharmacological inhibition of TLR4 mirrored the protective effects of FMT, effectively attenuating hyperoxia-induced lung injury and EMT.

CONCLUSIONS: Our findings establish a mechanistic link for the gut-lung axis in BPD, demonstrating that gut dysbiosis is a critical modulator of lung development impairment and pathological EMT via activation of the TLR4/NF-κB pathway.},
}

@article {pmid42304699,
year = {2026},
author = {Feng, YC and Liu, XX and Yu, H and Liu, R and Pang, TS and Wang, HN and Peng, ZW},
title = {Fecal Microbiota Transplantation From Patients With Social Anxiety Disorder Is Associated With General Anxiety-Like Behavior and Gut Microbiota Alterations in Mice.},
journal = {Brain and behavior},
volume = {16},
number = {6},
pages = {e71561},
doi = {10.1002/brb3.71561},
pmid = {42304699},
issn = {2162-3279},
support = {82171512//National Natural Science Foundation of China/ ; XJZT25QN50//Xijing Hospital/ ; LHJJ24YF06//Xijing Hospital/ ; //Boost plan of Xijing Hospital/ ; },
mesh = {Animals ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome/physiology ; Mice ; Male ; Humans ; *Anxiety/microbiology ; *Phobia, Social/microbiology/therapy ; *Behavior, Animal/physiology ; Female ; Mice, Inbred C57BL ; Adult ; *Dysbiosis/microbiology ; Tryptophan/blood ; },
abstract = {PURPOSE: Growing evidence implicates gut microbiota dysbiosis in social anxiety disorder (SAD), yet direct causal evidence remains limited. This study investigated whether fecal microbiota transplantation (FMT) from individuals with SAD was associated with general anxiety-like behaviors and accompanying gut microbial and predicted metabolic alterations in mice.

METHODS: Fecal samples were collected from five patients diagnosed with SAD and five matched healthy controls and transplanted into antibiotic-treated mice. Anxiety-like behaviors were evaluated using the open-field test (OFT) and elevated-plus maze test (EPMT). Gut microbiota composition was assessed by 16S rRNA gene sequencing, microbial functional potential was inferred using PICRUSt2, and plasma tryptophan-pathway metabolites were quantified.

RESULTS: Mice receiving SAD microbiota (SAD group) showed general anxiety-like behaviors, characterized by more time spent in the periphery of the OFT and fewer entries and less time in the open arms of the EPMT compared to mice receiving healthy control microbiota (control group). Although α-diversity did not differ significantly, β-diversity was distinct between groups. The SAD group showed enrichment of Bacteroidota/Bacteroidales-related bacteria (e.g., Muribaculum), whereas the control group had higher abundance of butyrate producers (e.g., Butyricimonas). Functional prediction indicated lower predicted abundance of selected DNA-repair and biosynthetic pathways in the SAD group. Plasma tryptophan levels were nominally lower in the SAD group.

CONCLUSIONS: These findings suggest that specific gut microbiota alterations and predicted functional pathway changes in individuals with SAD may be associated with anxiety-related behavioral phenotypes, supporting the gut microbiome as a potential contributing factor to the pathophysiology of SAD.},
}

Animals
*Fecal Microbiota Transplantation/adverse effects
*Gastrointestinal Microbiome/physiology
Mice
Male
Humans
*Anxiety/microbiology
*Phobia, Social/microbiology/therapy
*Behavior, Animal/physiology
Female
Mice, Inbred C57BL
Adult
*Dysbiosis/microbiology
Tryptophan/blood

@article {pmid42304879,
year = {2026},
author = {Mirjalili, S and Hosseini Hooshiar, M and Abbasabadarabi, S and Aliramezani, A},
title = {Host immunity and recurrent Clostridioides difficile infection: a comprehensive review.},
journal = {Pathogens and global health},
volume = {},
number = {},
pages = {1-20},
doi = {10.1080/20477724.2026.2686115},
pmid = {42304879},
issn = {2047-7732},
abstract = {Clostridioides difficile is a leading cause of healthcare-associated gastrointestinal infection, with outcomes that range widely in severity. The pathogenesis of C. difficile is driven by virulence factors that induce colonic inflammation and epithelial damage. This illness is categorized as an urgent threat, and in recent years, its prevalence has increased, with recurrent episodes occurring in approximately 15-35% of cases. The life cycle of C. difficile infection (CDI) is multifactorial and strongly influenced by antibiotic exposure, host immune responses, the gut microbiota, and microbial metabolites. Disruption of intestinal homeostasis gradually alters the ecological niches of C. difficile and the immunological landscape of the disease. In addition to these risk factors, recurrent C. difficile infection (rCDI) can be exacerbated by certain 'hypervirulent' strains that are more difficult to eradicate. As in many infectious diseases, host immunological responses, particularly in rCDI, appear to play a crucial role in determining recovery versus recurrence. Recent strategies to address this problem include fecal microbiota transplantation (FMT) and novel therapeutic approaches such as polyclonal and monoclonal antibodies. Nevertheless, the immunological mechanisms underlying rCDI remain incompletely understood. A deeper insight into how the immune response develops and functions during rCDI may facilitate the identification of new therapeutic targets. In this review, we summarize current knowledge on C. difficile recurrence and highlight the host immune response in the context of rCDI.},
}

@article {pmid42304908,
year = {2026},
author = {Patel, AK and Singh, N and Chandra, P and Sachan, N and Goswami, PK and Shivam, },
title = {Microbiome Drug Interactions in Cancer Pharmacology: Mechanisms and Therapeutic Opportunities.},
journal = {Current reviews in clinical and experimental pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/0127724328479943260605055353},
pmid = {42304908},
issn = {2772-4336},
abstract = {INTRODUCTION: Interindividual variability in cancer therapy response cannot be fully explained by host genetics or tumor characteristics alone. Emerging evidence indicates that the gut microbiome is a critical modulator of anticancer drug metabolism, immune responses, and therapeutic outcomes, positioning it as an important determinant in cancer pharmacology.

METHODS: This narrative review employed a structured literature search of PubMed, Scopus, and Web of Science (2005-2025) to synthesise preclinical and clinical evidence on microbiome-drug interactions, focusing on pharmacokinetics, immune modulation, toxicity, and resistance across chemotherapy, immunotherapy, and targeted therapies.

RESULTS AND DISCUSSION: The gut microbiome influences anticancer therapy through enzymatic biotransformation, immune regulation, metabolite signalling, and maintenance of intestinal barrier integrity. Clinically, favourable microbiome profiles have been associated with improved immunotherapy outcomes, with reported hazard ratios for survival ranging from ~0.5 to 0.7, while prior antibiotic exposure is linked to a 20-40% reduction in response rates. Microbial enzymes such as β- glucuronidase contribute to irinotecan-induced toxicity, affecting up to 20-40% of patients. Specific taxa, including Akkermansia muciniphila and Bifidobacterium spp., are associated with enhanced therapeutic response. Microbiome-targeted interventions, including faecal microbiota transplantation, have demonstrated response restoration in approximately 30-40% of refractory cases in early clinical studies. However, heterogeneity in microbial composition, lack of standardisation, and safety concerns limit clinical translation.

CONCLUSION: The gut microbiome represents an adaptable determinant of cancer pharmacology. Integrating microbiome-informed strategies offers a promising pathway toward precision oncology, although robust clinical validation remains essential for routine implementation.},
}

@article {pmid42294809,
year = {2026},
author = {Wu, Z and Yang, J and Zhang, M and Li, Y and Tu, Z and Wang, J and Yu, JT and Guo, K and Luo, R},
title = {Microplastics-Induced Gut Microbiota Dysbiosis Accelerates Alzheimer's-Like Pathology and Cognitive Decline via the Gut-Brain Axis.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e76072},
doi = {10.1002/advs.76072},
pmid = {42294809},
issn = {2198-3844},
support = {82471445//National Natural Science Foundation of China/ ; 32170988//National Natural Science Foundation of China/ ; 561120215//Talent Scientific Fund of Lanzhou University/ ; 842024017//Gansu Longyuan Youth Talents Program/ ; 26JRRA026//Basic Research Program of Gansu Province/ ; 2026QNTD004//Gansu Province Youth Talent Project (Team)/ ; },
abstract = {Alzheimer's disease (AD) is incurable and increasingly attributed to gene-environment interactions. Microplastics (MPs) are omnipresent in the human food chain, yet their impact on neurodegeneration is largely unknown. Here we show that chronic oral exposure to 2-µm amine-modified polystyrene microparticles accelerates cognitive decline, amplifies Aβ deposition, gliosis, and synaptic loss, and cripples autophagic flux in 5XFAD mice through the gut-brain axis. MPs accumulate in the gut, breach the epithelial barrier, and selectively expand the taurine-depleting pathobiont Bilophila, while suppressing taurine-synthesizing commensals. Untargeted metabolomics reveal a systemic taurine deficit that precedes and predicts exacerbated Aβ deposition, gliosis, synaptic loss, and autophagic blockade in 5XFAD mice. Antibiotic-mediated microbiota ablation and fecal microbiota transplantation (FMT) demonstrate that the neurotoxic phenotype is fully microbiota-dependent. Restoring taurine level rebalances microglial homeostasis, reinstates autophagic flux, and rescues memory deficits in MPs-treated 5XFAD mice. Translational validation using Alzheimer's Disease Neuroimaging Initiative (ADNI) plasma shows taurine is significantly lower in AD patients versus cognitively normal controls and inversely correlates with cognitive decline. Our findings identify MPs-induced gut-microbiota dysbiosis as a modifiable environmental driver of AD pathogenesis and establish taurine supplementation as a readily translatable intervention that simultaneously fortifies the intestinal barrier and neutralizes microbiota-mediated neurodegeneration.},
}

@article {pmid42294884,
year = {2026},
author = {Tao, E and Wang, L and Yuan, T},
title = {The gut microbiome in preterm infants: development, dysbiosis, and disease implications.},
journal = {Clinical microbiology reviews},
volume = {},
number = {},
pages = {e0008826},
doi = {10.1128/cmr.00088-26},
pmid = {42294884},
issn = {1098-6618},
abstract = {SUMMARYPreterm infants face a unique trajectory of gut microbiome assembly, shaped by the convergence of physiological immaturity, necessary clinical interventions, and the neonatal intensive care unit environment. This dysbiotic ecosystem-characterized by low diversity, depletion of beneficial commensals such as Bifidobacterium, and expansion of pathobionts, including Enterobacteriaceae-is increasingly recognized as a central mediator of neonatal morbidity. This review synthesizes current evidence on preterm microbiome development, its role in necrotizing enterocolitis through mechanisms involving Toll-like receptor 4 signaling, bile acid dysmetabolism, and immune dysregulation, and its systemic impact via gut-organ axes linking the intestine to the brain, lung, eye, and systemic circulation. We critically evaluate microbiome-targeted interventions across the translational spectrum, from foundational practices such as human milk feeding and antibiotic stewardship to active modulation with probiotics and prebiotics, and emerging precision strategies, including postbiotics, phage therapy, and fecal microbiota transplantation. Methodological advances in multi-omics, machine learning, and digital twin modeling are paving the way for personalized, predictive microbiome-mediated care. We also address the hidden burden of antimicrobial resistance in the preterm gut and the challenges of translating mechanistic insights into clinical practice. Looking forward, embracing the complexity of the preterm microbiome as a dynamic, multi-kingdom ecosystem is essential for developing holistic interventions that improve both short-term survival and long-term neurodevelopmental, respiratory, and metabolic outcomes.},
}

@article {pmid42294946,
year = {2026},
author = {Thonghem, A and Chattipakorn, N and Chattipakorn, SC},
title = {Potential Roles of Gut Microbiome and Metabolomes in Interstitial Lung Disease: Evidence across Preclinical and Clinical Research.},
journal = {Journal of applied microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jambio/lxag138},
pmid = {42294946},
issn = {1365-2672},
abstract = {Interstitial lung disease (ILD) is a heterogeneous condition that affects the lung parenchyma with varying degrees of inflammation and/or fibrosis. Several studies have suggested a potential link between the gut microbiome and the pathophysiology of lung diseases, including ILD. Accumulating evidence supports bidirectional gut-lung axis interactions potentially mediated by the microbiota. Alterations in the gut microbiome have been associated with the onset and severity of interstitial lung disease. This review aims to summarize findings from in vivo and clinical studies that have investigated the associations between the gut microbiome and ILD. Changes in the gut microbiome have been consistently found in various ILD subtypes, including idiopathic pulmonary fibrosis, radiation pneumonitis, silicosis, coal worker's pneumoconiosis, and connective tissue disease-related ILD. Preclinical studies demonstrate that gut dysbiosis is associated with altered immune responses, increased pro-inflammatory cytokines, and enhanced fibrotic pathways, with mechanistic evidence suggesting the involvement of specific microbial metabolites (short-chain fatty acids, bile acids, and immune mediators. Interventional studies in animal models suggest that fecal microbiota transplantation may attenuate pulmonary inflammation and fibrosis; however, clinical evidence remains limited. This review synthesizes findings across study types, highlights proposed mechanistic pathways, discusses contradictory results, and identifies critical knowledge gaps requiring future investigation to establish causality and inform potential therapeutic development.},
}

@article {pmid42295788,
year = {2026},
author = {Pan, G and Pang, K and Duan, S and Liu, L and Ma, X and Qi, H and Zhao, T},
title = {Study on the Effects and Mechanisms of an Ulvan Derivative in NAFLD through Gut Microbiota Fermentation.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.6c01387},
pmid = {42295788},
issn = {1520-5118},
abstract = {Nonalcoholic fatty liver disease (NAFLD) is closely associated with gut microbiota dysbiosis and lacks effective therapies. This study evaluated the effects of HU, a high-sulfated derivative of Ulva pertusa polysaccharide, using an HFD-induced NAFLD mouse model. Structural characterization showed that HU possessed a porous and aggregated surface morphology with heterogeneous nanoscale features. In HFD-fed mice, HU significantly reduced body weight gain, hepatic lipid accumulation, and inflammation, while improving serum biochemical parameters, including 44.0% lower triglycerides and 30.7% lower aspartate aminotransferase levels.16S rRNA sequencing revealed that HU markedly modulated gut microbial composition. In vitro fermentation showed enrichment of beneficial genera, while in vivo experiments demonstrated increased Faecalibaculum and reduced Acinetobacter. Fecal microbiota transplantation further supported the involvement of HU-modulated gut microbiota in the protective effects against HFD-induced NAFLD. These findings suggest that HU ameliorates NAFLD by reshaping gut microbiota, suppressing inflammation, and alleviating hepatic lipid accumulation.},
}

@article {pmid42296911,
year = {2026},
author = {Kim, OY and Song, J},
title = {Tryptophan metabolism as a key integrator within the gut-lung-brain axis: Mechanistic insights and nutritional therapeutic strategies for inflammatory and neuropsychiatric disorders.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {201},
number = {},
pages = {119527},
doi = {10.1016/j.biopha.2026.119527},
pmid = {42296911},
issn = {1950-6007},
abstract = {The gut-lung-brain (GLB) axis is a multidirectional communication network linking the gastrointestinal tract, respiratory system, and central nervous system (CNS) through neural, endocrine, and immune pathways. Emerging evidence suggests that tryptophan (Trp) metabolism serves as a key integrating node within this axis, modulating host-microbe interactions involved in systemic homeostasis. Trp catabolism follows three divergent pathways: the kynurenine (Kyn) pathway, which is involved in immune tolerance but can generate neuroactive and potentially neurotoxic metabolites; the serotonin pathway, essential for mood and gastrointestinal motility; and the microbial indole pathway, which supports epithelial barrier function through aryl hydrocarbon receptor activation. Gut dysbiosis and chronic inflammation may disrupt these pathways and contribute to the "metabolic hijacking" of Trp, shifting its metabolism away from serotonin and indole synthesis toward increased production of Kyn pathway metabolites. This shift has been implicated in the pathogenesis of respiratory diseases, such as chronic obstructive pulmonary disease, asthma, and pulmonary fibrosis, as well as neuropsychiatric conditions, including depression and Alzheimer's disease. These alterations contribute to systemic low-grade inflammation and immune dysregulation, which further propagate cross-organ pathology within the GLB axis. This review synthesizes current evidence on how Trp metabolites may function as cross-organ mediators, contributing to the "leaky gut" and "leaky brain" phenotypes. Furthermore, we evaluate the potential of precision nutrition and therapeutic interventions, including psychobiotics, dietary phytochemicals, cofactor supplementation, and fecal microbiota transplantation, to restore metabolic equilibrium. Targeting the Trp-GLB metabolic axis may therefore offer an integrative therapeutic framework for managing interconnected inflammatory and neuropsychiatric comorbidities.},
}

@article {pmid41222715,
year = {2025},
author = {Almutawif, YA and Khan, NU},
title = {Gut microbiome dysbiosis and antimicrobial resistance in the Middle East: a converging public health crisis in conflict and fragile settings.},
journal = {Archives of microbiology},
volume = {208},
number = {1},
pages = {15},
pmid = {41222715},
issn = {1432-072X},
abstract = {The Middle East is confronting a converging public health crisis as gut microbiome dysbiosis and antimicrobial resistance (AMR) amplify in conflict and fragile settings, driven by war, displacement, and systemic healthcare collapse. This review examines the bidirectional relationship between disrupted gut microbiota and escalating AMR, particularly among vulnerable refugee populations and war-affected communities. Key findings reveal alarming resistance rates in ESKAPE pathogens (e.g., Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp), exacerbated by unregulated antibiotic use, malnutrition, and poor sanitation. Dysbiosis fosters AMR through loss of colonization resistance and horizontal gene transfer, while conflict-related healthcare breakdowns—such as empiric antibiotic overuse and absent diagnostics—accelerate resistance spread. Refugee camps, with overcrowding and contaminated water, emerge as critical AMR hotspots. Urgent interventions are needed, including microbiome restoration therapies (e.g., probiotics and faecal microbiota transplantation (FMT), rapid diagnostic tools, and integrated One Health surveillance. Moreover, the increasing trend of AMR is further amplified by the COVID-19 pandemic, which led to widespread antibiotic use and disrupted healthcare services. Review emphasises the importance of regional policy coordination, targeted humanitarian aid focused on microbiome health, and global advocacy to mitigate this crisis, which poses a threat to both local and international health security. Without action, the intersection of dysbiosis and AMR will deepen health inequities in conflict zones, with far-reaching consequences.},
}

@article {pmid41718784,
year = {2026},
author = {Peltz, Z and Wiblin, R and Kattunga, VM and Pai, CG and Andersen, JK and Chinta, SJ},
title = {The role of gut dysbiosis in Parkinson's disease: pathophysiology, epidemiology, and emerging therapeutic strategies.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {},
pmid = {41718784},
issn = {1573-7365},
abstract = {Parkinson’s disease (PD) is a prevalent neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra, leading to motor and non-motor symptoms. While the underlying pathobiology remains incompletely understood, emerging evidence suggests a pivotal role for neuroinflammation, microglial activation, and misfolded α-synuclein aggregates. Recent research has highlighted gut dysbiosis as a contributing factor in PD pathology, with potential implications for disease onset and progression. Recent studies suggest that gut dysbiosis may influence PD onset and progression, highlighting the gut-brain axis as a critical mechanistic link. This review explores epidemiology, molecular etiology, genetic predispositions, and risk factors associated with PD, with particular emphasis on the role of gut microbiota. Furthermore, we discuss emerging gut-targeted therapeutic strategies, including probiotics, dietary interventions, and fecal microbiota transplantation (FMT), and their potential in mitigating PD pathology. Addressing gut dysbiosis may offer novel therapeutic avenues for early intervention and disease modification in PD.},
}

@article {pmid41746368,
year = {2026},
author = {Tsuzaka, S and Deie, K and Ebihara, M and Matsuda, R and Tsutsuno, T and Taki, S and Ogawa, S and Kondo, Y and Takezoe, T and Naya, I and Mizuta, K and Hosokawa, T and Kawashima, H},
title = {Association of preoperative ultrasonography with the bowel function at 5 years of age in low-type anorectal malformation: a retrospective cohort study.},
journal = {Surgery today},
volume = {},
number = {},
pages = {},
pmid = {41746368},
issn = {1436-2813},
abstract = {PURPOSE: Low-type anorectal malformation (LARM) is commonly associated with favorable fecal continence; however, some patients experience a suboptimal bowel function during early childhood. We evaluated whether the rectal pouch–perineum (P–P) distance, measured using preoperative ultrasonography, is associated with the postoperative bowel function. METHODS: Forty-seven children with LARMs who underwent surgery between 2006 and 2020 were analyzed over a 5-year follow-up. We measured the P–P distance on day 0/1 of life using transperineal ultrasonography. The bowel function at five years of age was assessed using the Japan Society of ARM Study Group evacuation score (ES). We conducted simple and multiple regression analyses to examine the association between the P and P distance and postoperative outcomes. RESULTS: A shorter P–P distance correlated with higher ES (B = − 0.833, P = 0.014), less soiling (B = − 0.282, P = 0.038), and less incontinence (B = − 0.357, P = 0.049). Lumbosacral malformations were independently associated with a lower ES, worse soiling, and urgency. CONCLUSION: Ultrasonographic measurement of the P–P distance is useful for surgical planning and it is associated with the bowel function at 5 years of age in patients with LARMs. Although a shorter P–P distance was associated with a better bowel function in early childhood, a longer follow-up is required to determine whether P–P distance is associated with the ultimate long-term functional outcomes.},
}

@article {pmid42284364,
year = {2026},
author = {Li, M and Sun, P and Zhou, X and Yang, X and Li, W},
title = {Microbial modulation of CNS remyelination in multiple sclerosis: the missing link in gut-brain axis research.},
journal = {Nutritional neuroscience},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/1028415X.2026.2686736},
pmid = {42284364},
issn = {1476-8305},
abstract = {Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system (CNS) marked by demyelination and neurodegeneration. While much attention has focused on immune dysregulation and neuroinflammation, the failure of effective remyelination is a key driver of disease progression, especially in progressive MS. Recently, the gut microbiome has emerged as a potent modulator of systemic immunity and CNS function, influencing processes such as neuroinflammation and neurogenesis. This review examines current evidence on microbiota-derived metabolites, including short-chain fatty acids (SCFAs), indole derivatives, and bile acids, and their potential roles in pathways associated with oligodendrocyte precursor cell (OPC) biology and remyelination. Evidence from preclinical models, including germ-free systems, fecal microbiota transplantation (FMT), and probiotic interventions, suggests that microbial signals can modulate immune responses and CNS environments that may indirectly affect demyelination and repair processes. However, direct causal effects on OPC differentiation and functional remyelination remain incompletely established. We critically evaluate the strengths and limitations of existing studies, highlighting inconsistencies across experimental models and the context-dependent nature of microbiota-host interactions. Clinical evidence remains limited, with current studies primarily assessing inflammatory or metabolic outcomes rather than direct measures of remyelination. Key translational challenges include uncertainties regarding metabolite bioavailability in the CNS, cell-specific mechanisms of action, and reproducibility of microbiome-targeted interventions.},
}

@article {pmid42286318,
year = {2026},
author = {La Rosa, F and Guzzardi, MA and Conti, G and Petroni, D and Pardo Tendero, M and Bernardi, S and Barone, M and Panetta, D and Tedeschi, L and Fabbri, C and Casavecchia, F and Riabitch, D and Granziera, F and Ragusa, R and Caselli, C and Giorgetti, A and Campani, D and Baglini, E and Menichetti, L and Elsinga, P and Luurtsema, G and Brigidi, P and Iozzo, P},
title = {Functional PET imaging of gut microbiota with [[18]F]fluorodeoxyglucose, [[18]F]fluorodeoxysorbitol and [[11]C]choline reflects Clostridia and Lactobacillales abundance in caecum and small intestine and host metabolic interactions.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {42286318},
issn = {1619-7089},
abstract = {PURPOSE: Interaction of gut microbiota (GM) with dietary sugars (glucose, sorbitol) and choline has been transversely implicated in the pathogenesis of multiple chronic diseases. Our aim was to develop functional PET imaging of GM, using a multi-tracer approach to capture bacteria classes involved in sugar fermentation and choline catabolism at their gastrointestinal (GI) location.

METHODS: Adult and young sex-balanced groups of mice underwent oral administration of [[18]F]FDG, [[18]F]FDS or [[11]C]choline ([[11]C]cho) and repeated PET imaging over 4-5 h. Antibiotics, probiotic or faecal microbiota transplantation (FMT) served to quantify the specific role and site of bacteria action. GM was sequenced ex-vivo; gut histology and metabolic profiles were assessed in subsets.

RESULTS: [[18]F]FDG and [[18]F]FDS reflected caecum abundance of Clostridia and Bacteroidia fermenters, with [[18]F]FDG exhibiting strongest and broadest relations. Clearance of [[11]C]cho from small gut reflected Bacilli and Lactobacilli abundance. In vitro cultures supported these relationships. Urinary [11]C-excretion was nearly abolished by antibiotics. PET imaging was able to differentiate and predict gut bacteria classes in mice receiving FMT from two age-extreme human donors. Urinary [[18]F]FDS excretion reflected small-gut goblet cell activation; high caecum [[18]F]FDG retention and small gut [[11]C]cho clearance predicted body glucose use and low systemic inflammation.

CONCLUSION: Imaging of ingested probes is simple and effective to map GM characteristics in situ and the functional crosstalk with host processes in mice in real-time. Our data confirm that the GI ecosystem is highly diversified, pointing to small intestine and caecum GM as dominant players in gut-body handling of our target nutrients.},
}

@article {pmid42286837,
year = {2026},
author = {Gavanji, S and Suhail, M and Bencurova, E and Dandekar, T and Othman, EM},
title = {Recent advances and clinical relevance of microbiome dynamics in health and disease.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2679197},
doi = {10.1080/19490976.2026.2679197},
pmid = {42286837},
issn = {1949-0984},
mesh = {Humans ; Probiotics/administration & dosage ; Dysbiosis/microbiology/therapy ; Prebiotics ; *Microbiota ; *Gastrointestinal Microbiome ; Animals ; Bacteria/classification/genetics/metabolism/isolation & purification ; Gastrointestinal Tract/microbiology ; Fecal Microbiota Transplantation ; },
abstract = {The human microbiome, comprising trillions of bacteria, viruses, fungi, and archaea, represents an essential partner in human biology rather than a passive collection of microbes. These microbial communities inhabit diverse niches, including the gut, skin, oral cavity, respiratory tract, and urogenital system, where they contribute to digestion, vitamin biosynthesis, immune development, and regulation of host metabolism. Their dynamic interactions form a complex ecosystem that profoundly shapes health across the lifespan. However, with ever increasing reports on the microbiome including perceived health benefits, diagnostic use, detrimental species and immune modulation, we synthesize findings from multiple biomedical fields for this review. It first describes beneficial functions of commensal microbes in maintaining immune tolerance and metabolic balance, then analyzes the effect of diet, geography and medication exposure, the consequences of dysbiosis in gastrointestinal, metabolic, neurological, cardiovascular, autoimmune, and oncological disorders. The article examines the functional potency of the gut microbiome, keystone taxa as well as disease-stage-specific and general dynamics, how microbiomes modulate drug absorption, metabolism, and efficacy, thereby influencing individualized responses to therapy. Furthermore, it evaluates therapeutic approaches, including probiotics, prebiotics, fecal microbiota transplantation, and engineered microbial strategies that seek to restore microbial equilibrium. The significance of this review lies in its integrative perspective, as it links microbiome research to precision medicine, emphasizing that safeguarding microbial diversity is crucial for prevention, early diagnosis, and the personalization of future medical interventions.},
}

Humans
Probiotics/administration & dosage
Dysbiosis/microbiology/therapy
Prebiotics
*Microbiota
*Gastrointestinal Microbiome
Animals
Bacteria/classification/genetics/metabolism/isolation & purification
Gastrointestinal Tract/microbiology
Fecal Microbiota Transplantation

@article {pmid42286862,
year = {2026},
author = {Othman, EM and Bencurova, E and Ferretti, P and Bork, P and Rodriguez Del Rio, A and Huerta-Cepas, J and Caruana, I and Abdel-Latif, R and Akash, A and Albacete, A and Lafi, F and Dandekar, T and Naseem, M},
title = {Diet and microbiome shape small-molecule cytokinin pools in mammals.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2679497},
doi = {10.1080/19490976.2026.2679497},
pmid = {42286862},
issn = {1949-0984},
mesh = {Animals ; *Cytokinins/blood/metabolism ; Humans ; Mice ; *Diet ; *Gastrointestinal Microbiome ; *Mammals/metabolism ; Metabolomics ; Metagenomics ; Feces/chemistry ; Swine ; Bacteria/classification/genetics/metabolism/isolation & purification ; *Microbiota ; },
abstract = {Cytokinins (CKs) are adenine-derived metabolites traditionally characterized as plant hormones, yet their origin, distribution, and functions in mammalian systems remain largely undefined. Using integrated metabolomics, microbiome, and metagenomics approaches, we provide a systematic characterization of CK occurrence and potential sources in mammals. Serum profiling across five animal species revealed consistent detection of multiple CK derivatives, with concentrations markedly lower than in plant tissue. The CK storage form, zeatin-O-glucoside, predominated in mammalian sera, followed by trans-zeatin and kinetin, indicating a CK composition distinct from that in plants. Species-specific differences, such as reduced trans-zeatin in mice and lower kinetin in humans, further suggest divergent regulatory patterns. In mice, CKs were present in vascular tissues of the kidney, heart, and liver, demonstrating systemic distribution. Dietary manipulation showed that starvation significantly reduced CK abundance in serum, colon, feces, and urine, confirming that diet is a major contributor to the mammalian CK pool. Meta-omics analysis of gut microbiomes identified CK-related genes across multiple microbial taxa, with the highest representation in human microbiomes, followed by those of mouse and pig. Germ-free mouse experiments showed substantially lower CK levels than conventionally raised counterparts, establishing a microbiome-dependent contribution. Collectively, our findings identify CKs as diet and microbiome modulated metabolites in mammals, warranting future investigation to elucidate their physiological significance in mammalian biology.},
}

Animals
*Cytokinins/blood/metabolism
Humans
Mice
*Diet
*Gastrointestinal Microbiome
*Mammals/metabolism
Metabolomics
Metagenomics
Feces/chemistry
Swine
Bacteria/classification/genetics/metabolism/isolation & purification
*Microbiota

@article {pmid42286999,
year = {2026},
author = {Felten, V and West, EA and Martini, F and Favrot, C and Unterer, S and Suchodolski, J and Scharl, M and Renz, H and Fischer, NM and Rostaher, A},
title = {Faecal Microbiota Transplantation Reduces Lesion Severity and Medication Use in Canine Atopic Dermatitis: A Randomised, Placebo-Controlled, Double-Blinded Clinical Trial.},
journal = {Veterinary dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1111/vde.70092},
pmid = {42286999},
issn = {1365-3164},
support = {215128/WT_/Wellcome Trust/United Kingdom ; 03162//American Kennel Club Canine Health Foundation/ ; //Westie Foundation of America/ ; },
abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an established therapy for gastrointestinal disease, yet its role in canine atopic dermatitis (cAD) remains unclear.

HYPOTHESIS/OBJECTIVES: We hypothesised that adjunctive FMT improves clinical severity and reduces symptomatic medication use in dogs with cAD. The objective was to evaluate efficacy and safety versus placebo.

ANIMALS: Forty-six client-owned dogs with naturally occurring cAD were enrolled from a referral hospital population; 40 completed the study (FMT n = 20, placebo n = 20).

MATERIALS AND METHODS: Prospective, randomised, placebo-controlled, double-blinded clinical trial. Dogs received daily oral lyophilised FMT capsules for 90 days plus three monthly rectal FMT administrations (Day [D]0, D30, D60) or placebo capsules with sham handling. Concomitant symptomatic therapies were permitted. Outcomes included Canine Atopic Dermatitis Extent and Severity Index, fourth iteration (CADESI-04), pruritus Visual Analog Scale (PVAS), Medication Score (D0-90) and Owner Global Assessment of Treatment Efficacy (OGATE, D90).

RESULTS: CADESI-04 scores were lower with FMT at month (M) 2 (7 ± 6 vs. 16 ± 12; p = 0.006) and month 3 (8 ± 6 vs. 15 ± 12; p = 0.020). Sustained responders (≥ 50% CADESI-04 improvement at M2 and M3) were more frequent with FMT (35% vs. 5%; p = 0.044). In the FMT group, the medication scores were lower at M2 (16 ± 10 vs. 23 ± 11; p = 0.033) and M3 (13 ± 10 vs. 24 ± 15; p = 0.007) compared to placebo. PVAS decreased in both groups without between-group differences. OGATE favoured FMT (p = 0.028). FMT was well tolerated.

Adjunctive FMT reduced lesion severity and medication requirements, supporting its use as a safe microbiome-based add-on therapy in cAD.},
}

@article {pmid42287485,
year = {2026},
author = {Yang, X and Zhang, J and Jiang, N and Yang, L and Li, H and Dong, Y and Chen, Y and Chang, R and Li, R and Ma, Y and Yang, Y and Liu, P and Song, P},
title = {Intestinal microecology regulates neutrophil recruitment through TLR4/MAPK/CXCR2 signaling pathway to promote liver ischemia/reperfusion injury.},
journal = {Journal of bioenergetics and biomembranes},
volume = {58},
number = {1},
pages = {},
pmid = {42287485},
issn = {1573-6881},
mesh = {Animals ; *Reperfusion Injury/metabolism/pathology ; Mice ; *Toll-Like Receptor 4/metabolism ; *Gastrointestinal Microbiome ; *Neutrophil Infiltration ; Male ; *Receptors, Interleukin-8B/metabolism ; *Liver/pathology/metabolism ; Mice, Inbred C57BL ; *MAP Kinase Signaling System ; Signal Transduction ; Disease Models, Animal ; },
abstract = {Liver ischemia/reperfusion injury (IRI) is a major complication of hemorrhagic shock, hepatectomy and liver transplantation. Intestinal microecology has momentous functions in various human diseases. The present study aimed to elucidate the role and underlying mechanism of intestinal microecology in liver IRI. A liver IRI mouse model was constructed and validated using hematoxylin and eosin staining, enzyme-linked immunosorbent assay and Naphthol AS-D chloroacetate esterase staining. The function of intestinal microecology in liver IRI was evaluated using flow cytometry and western blot analysis. Moreover, the mechanisms of intestinal microecology in liver IRI were assessed using a series of molecular experiments. The results revealed that liver IRI associated with intestinal microecology dysbiosis exhibited increased hepatic neutrophil infiltration, MAPK pathway activation and inflammatory cytokine production. The 16 S rRNA gene sequencing of fecal samples from Sham, IRI, IRI+antibiotic pre-treatment and fecal transplantation (FT) groups revealed microbial community alterations, with shifts in Bacteroidota and Firmicutes abundance associated with liver injury and neutrophil recruitment. PCA, PCoA and taxonomic profiling further confirmed group-dependent remodeling of the gut microbial community. FT using fecal microbiota from IRI donor mice exacerbated liver neutrophil infiltration, MAPK/CXCR2 activation and inflammatory responses, whereas TAK-242-mediated TLR4 blockade attenuated these effects. Overall, the present study suggests that gut microbiota dysbiosis may enhance liver IRI by promoting neutrophil recruitment, at least in part through the TLR4/MAPK/CXCR2 axis, revealing a novel microbe-immune-liver interaction that may be targeted therapeutically.},
}

Animals
*Reperfusion Injury/metabolism/pathology
Mice
*Toll-Like Receptor 4/metabolism
*Gastrointestinal Microbiome
*Neutrophil Infiltration
Male
*Receptors, Interleukin-8B/metabolism
*Liver/pathology/metabolism
Mice, Inbred C57BL
*MAP Kinase Signaling System
Signal Transduction
Disease Models, Animal

@article {pmid42287567,
year = {2026},
author = {Hao, YY and Zhao, ZA and Zhang, LM and Zhao, ZG},
title = {Targeting the gut-brain axis: microbial interventions for neurological disorders.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {},
pmid = {42287567},
issn = {1573-7365},
support = {82570586//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Nervous System Diseases/microbiology/therapy/metabolism ; Animals ; *Gastrointestinal Microbiome/physiology ; *Brain/metabolism ; Probiotics/therapeutic use ; *Fecal Microbiota Transplantation/methods ; *Brain-Gut Axis/physiology ; Diet, Ketogenic/methods ; Blood-Brain Barrier/metabolism ; },
abstract = {The pathogenesis of neurological disorders involves complex interactions among genetic, environmental, immunological, and metabolic factors. Characterized by high disability rates and prolonged disease courses, these conditions impose a significant burden on patients and society. As a dynamic and modifiable component of the internal environment, gut microbiota plays a central role in the onset and progression of neurological disorders through the "gut-brain axis." Bidirectional communication occurs between gut microbiota and the central nervous system via neural, immune, and endocrine pathways. This interplay regulates blood-brain barrier integrity, modulates neuroinflammatory responses, and maintains neurotransmitter balance, thereby influencing disease progression. This review systematically summarizes current evidence on the role of gut microbiota in representative neurological disorders, such as traumatic brain injury, stroke, and epilepsy, and critically evaluates the therapeutic potential of microbiota-targeted interventions, including fecal microbiota transplantation, ketogenic diets, and probiotics. Collectively, this review provides novel insights into disease pathogenesis and highlights innovative microbiome-based therapeutic strategies for the prevention and management of neurological diseases.},
}

Humans
*Nervous System Diseases/microbiology/therapy/metabolism
Animals
*Gastrointestinal Microbiome/physiology
*Brain/metabolism
Probiotics/therapeutic use
*Fecal Microbiota Transplantation/methods
*Brain-Gut Axis/physiology
Diet, Ketogenic/methods
Blood-Brain Barrier/metabolism

@article {pmid42287814,
year = {2026},
author = {Li, Y and Zhang, B and He, G and Shen, C and Chang, F and Yang, J and Wang, S and Wang, Y and Zong, J and Luo, Y and Wang, N and Sun, Y and Sui, Y and Wu, M and Lu, D and Li, C and Zhou, X},
title = {Saikosaponin A restores the IDO1-driven gut-testis kynurenine axis to alleviate oligozoospermia.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {158},
number = {},
pages = {158414},
doi = {10.1016/j.phymed.2026.158414},
pmid = {42287814},
issn = {1618-095X},
abstract = {BACKGROUND: Busulfan (Bus)-induced oligozoospermia still lacks a disease-modifying therapy, and its pathogenesis has been largely attributed to germ-cell DNA damage. Emerging evidence indicates that microbiota-derived metabolites are key determinants of spermatogenic failure. Saikosaponin A (SSA), a major triterpenoid from Bupleurum, has never been evaluated in male infertility. Consequently, its regulatory role in the gut microbiota-metabolite axis and causal efficacy remain completely undefined.

PURPOSE: To determine whether SSA rescues Bus-induced oligozoospermia via the gut microbiota-metabolite axis, and to uncover a novel pathogenic mechanism of Bus, beyond the known germ-cell DNA damage pathway, revealing a gut microbiota-metabolite-mediated regulatory axis.

METHODS: Bus-induced oligozoospermia was established in male C57BL/6 J mice and followed by SSA treatment. Sperm count, testis index, and histology were assessed; spermatogenic proteins were quantified by Western blot. Microbiota and metabolites were profiled via 16S rDNA sequencing; serum metabolomics; and fecal microbiota transplantation (FMT) from SSA donors. Testicular transcriptome sequencing identified differentially expressed pathways. Indole-3-carboxaldehyde (ICA) administration and Kynurenine (Kyn) supplementation were performed in parallel. Indoleamine 2,3-dioxygenase 1 (IDO1) protein level and activity were measured by Western blot and ELISA. ICA-IDO1 interaction was verified by molecular docking and surface plasmon resonance (SPR). The l-tryptophan/L-kynurenine ratio was determined by targeted liquid chromatography-mass spectrometry (LC-MS/MS).

RESULTS: SSA restored sperm count, testis index, and tubular architecture while increasing DDX4, DAZL, and SYCP1/3. It reversed Bus-induced Lactobacillus expansion, decreased colonic ICA, relieved ICA-mediated IDO1 inhibition, thereby restoring colonic IDO1 activity, and elevated Kyn. FMT from SSA donors reproduced these protective effects. Transcriptomics showed up-regulation of AKT-mediated targets: pro-growth (CCND1), antioxidant (NRF2), and anti-apoptotic (Bcl-2), with down-regulation of pro-apoptotic genes. Mechanistically, SSA reshaped the gut microbiota, lowered colonic ICA, relieved ICA-mediated IDO1 inhibition, and restored Kyn-dependent testicular antioxidant and anti-apoptotic signaling.

CONCLUSION: By reshaping the gut microbiota, reducing colonic ICA and relieving ICA-mediated IDO1 inhibition, SSA restored Kyn-driven testicular antioxidant and anti-apoptotic signaling. This suggests a microbiota-directed, non-hormonal candidate preclinical approach for Bus-induced oligozoospermia; the gut microbiota-ICA-IDO1-Kyn axis offers a framework awaiting human validation.},
}

@article {pmid42288145,
year = {2026},
author = {Zhang, X and Wang, XR and Gai, SL and Han, YQ and Quan, XY and Yin, S and Li, J and Wang, N},
title = {Gut microbiota reshaped by exercise improved glycolipid metabolism in obese mice via increasing the production of medium and long chain fatty acids: a multi-omics study.},
journal = {The Journal of nutritional biochemistry},
volume = {},
number = {},
pages = {110447},
doi = {10.1016/j.jnutbio.2026.110447},
pmid = {42288145},
issn = {1873-4847},
abstract = {Exercise is effective in combating obesity and regulating the composition of the gut microbiota. However, the molecular mechanism by which exercise alters gut microbiota and its metabolites to exert weight loss has not been fully elucidated. In this study, the mechanism of gut microbiota and microbial metabolites reshaped by exercise in weight loss were investigated by macrogenomic sequencing, metabolomics analysis and fecal microbiota transplantation (FMT). The results showed that exercise significantly increased the abundance of beneficial bacteria such as Oscillibacter, Lachnoclostridium, and unclassified_f__Lachnospiraceae, and decreased the abundance of Lactobacillus and Desulfovibrio. Meanwhile, exercise significantly increased medium- and long-chain fatty acid (MCFA and LCFA) content, as well as butyric acid, and decreased fructose levels. These metabolites were associated with fatty acid degradation, and unsaturated fatty acid synthesis pathways. In addition, FMT from exercised mice significantly reduced high-fat diet (HFD)-induced obesity and lipid accumulation, increased insulin sensitivity, and improved glucose homeostasis, with decreased the levels of serum lipids and lipopolysaccharide (LPS). FMT also attenuated hepatic and pancreatic dysfunction, as well as hepatic steatosis. Notably, FMT from exercised mice significantly increased the content of MCFAs and LCFAs in the intestines of HFD-treated mice and upregulated the expression of genes related to glycolipid metabolism and the secretion of Glucagon-like Peptide-1 (GLP-1). Finally, caprylic, lauric, cardamic and stearic acids can significantly increase GLP-1 levels in Caco-2 cells. Taken together, the mechanism by which exercise suppresses obesity may inhibit appetite by optimizing the intestinal microbiota, promoting the synthesis of MCFAs and LCFAs, and up-regulating GLP-1 secretion.},
}

@article {pmid42288685,
year = {2026},
author = {Lin, ML and Gao, HN},
title = {Transplantation of encapsulated fecal microbiota: research progress and future trends.},
journal = {World journal of pediatrics : WJP},
volume = {},
number = {},
pages = {},
pmid = {42288685},
issn = {1867-0687},
support = {2022YFC2304500//National Key Research and Development Program/ ; 2021YFA1301104//National Key Research and Development Program/ ; },
abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) demonstrates significant efficacy in treating intestinal disorders, such as recurrent Clostridioides difficile infection (rCDI). However, traditional FMT relies on invasive delivery methods (e.g., colonoscopy or use of a nasoenteric tube) and lacks standardized donor screening, limiting its widespread clinical adoption and scalability. As a key formulation of live biotherapeutic products (LBPs), encapsulated FMT represents a transition from empirical microbial transfer to engineered biotherapeutics, offering a safer and more convenient approach for clinical application.

DATA SOURCES: This review synthesizes, compares, and integrates data in a narrative fashion from PubMed and the China National Knowledge Infrastructure.

RESULTS: Research on encapsulated FMT in adults has progressed toward standardization and the exploration of new indications. In contrast, pediatric studies remain primarily focused on rCDI treatment and lack large-scale randomized controlled trials. Evolution toward encapsulated, standardized products is driving a shift from whole-community microbial formulations toward more defined consortia and, ultimately, synthetic biology-based innovations. Concurrent significant regulatory challenges persist, as definitions of LBPs remain inconsistent and clear, harmonized international guidelines are yet to be established.

CONCLUSIONS: This review summarizes progress and emerging research priorities in encapsulated FMT while also examining current regulatory challenges and innovative directions within the LBP framework. Future developments are poised to advance encapsulated FMT from whole-community transplantation toward the precise modulation of functional microbial consortia. This progression will help drive microbial therapeutics toward greater standardization and personalization, offering improved treatment strategies for intestinal and other microbiome-associated diseases.},
}

@article {pmid42289709,
year = {2026},
author = {Lei, L and Wang, A and Dong, L and Wu, T and He, W and Yang, Y and Li, J and Bi, X and Cai, Y and Guan, X and Zhu, X},
title = {Food-grade TiO2 impairs intestinal mucus barrier via disrupting the gut microbiota-ILA-mucin sulfation axis: novel insights and dietary intervention strategies.},
journal = {Journal of nanobiotechnology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12951-026-04679-6},
pmid = {42289709},
issn = {1477-3155},
support = {82304152//National Natural Science Foundation of China/ ; 2024040801020373//Natural Science Foundation (Exploration Project) of Wuhan City/ ; WX23Q28//the Funding for Scientific Research Projects from Wuhan Municipal Health Commission/ ; 2023AFB392//Natural Science Foundation of Hubei Province/ ; },
abstract = {The use of titanium dioxide (TiO2) as a food additive has persistently elicited concerns about its potential toxicity, primarily attributed to the significant presence of nanoparticles. Studies have recently demonstrated that nano- or micro-sized food-grade TiO2 (fg-TiO2) particles can disrupt gut microbial balance and weaken the intestinal barrier; however, the underlying mechanisms remain poorly understood. Furthermore, research on dietary interventions for repairing fg-TiO2-induced intestinal injury is limited. This study delved into the role of the interactions among gut microbes, indole-3-lactic acid (ILA) and mucin sulfation in fg-TiO2-induced intestinal mucosal barrier damage through multi-omics analysis, and revealed the protective effects of quercetin. Prolonged oral administration of fg-TiO2 at doses pertinent to human exposure resulted in notable intestinal inflammation and mucosal barrier damage through diminishing mucin sulfation. Further analysis demonstrated that fg-TiO2 caused significant gut microbiota dysbiosis and metabolite changes. It was found that Lactobacillus and its metabolite ILA, an aryl hydrocarbon receptor (AHR) agonist, was significantly downregulated following oral ingestion of fg-TiO2, which decreased the activation of AHR and ultimately led to a loss in mucin sulfation in colon tissues. Notably, experiments involving fecal microbiota transplantation (FMT) and ILA supplementation indicated gut microbial shifts and the consequent decrease in colonic ILA levels were accountable for the detrimental effects of fg-TiO2 on mucin sulfation and intestinal barrier integrity. Moreover, this study found that dietary intervention with quercetin could effectively reverse the damage to the intestinal mucosal barrier induced by fg-TiO2 through targeting gut microbiota-ILA-mucin sulfation axis. This research uncovered the adverse impacts of fg-TiO2 on gut homeostasis and indicates the potential of quercetin to combat the intestinal toxicity of fg-TiO2. These findings enhanced our comprehension of the safety profile of fg-TiO2 and proposed a nutritional approach to mitigate the health risks associated with fg-TiO2 exposure.},
}

@article {pmid42290978,
year = {2026},
author = {Jin, Z and Zhang, Y and Zhong, Z and Shen, Z and Huang, L and Hu, H and Chen, X and Liu, W and Li, L and Gao, C},
title = {Dynamic feedback BacGuard anchors microbial metabolism to host symbiosis in real-time ulcerative colitis therapy.},
journal = {Bioactive materials},
volume = {65},
number = {},
pages = {365-379},
pmid = {42290978},
issn = {2452-199X},
abstract = {The escalating global burden of ulcerative colitis (UC) underscores the limitations of conventional anti-inflammatory therapies. Although multi-omics insights have propelled gut microbiota modulation to the forefront of therapeutic innovation, current strategies relying on probiotics or fecal transplants remain constrained by empirical designs due to the lack of spatiotemporal precision and real-time monitoring of microbial metabolic vitality in situ. In this study, BacGuard, a metabolically orthogonal microgel platform, was developed to unify the probiotic surveillance and guided dynamic dose regulation with spatially targeted microbiota-associated metabolic modulation. Our core design featured a β-xylosidase-activated chemiluminescent probe (XOS-CL) that was conjugated with xylooligosaccharide-based hyperbranched polymers (HBXOK) and orally delivered via microgels. Thereby, this system enabled real-time monitoring of probiotic abundance and metabolic activity in the colon through enzyme-responsive signaling, while simultaneously promoting short-chain fatty acid (SCFA) production via redirected bacterial metabolic flux. This dual-action system created a self-reinforcing therapeutic loop and optically quantifying the microbial activity in a dynamic manner. By resolving the causal disconnects between enzymatic activity, microbiota proliferation, and host interactions, the BacGuard bridged the diagnostic metrics to functional therapeutic outcomes. Anchoring both sensing and treatment to microbial metabolic flux, our platform reimagined the precision gut ecosystem engineering, establishing an image-guided dynamic dose regulation framework that actively preserved the microbiota-host symbiosis through in-time and function-adaptive modulation.},
}

@article {pmid42292220,
year = {2026},
author = {Ge, J},
title = {Functional redundancy as a stabilizing principle in bacterial communities under antibiotic perturbation: mechanisms, trade-offs, and emerging frameworks.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1834295},
pmid = {42292220},
issn = {2296-858X},
abstract = {The widespread use of antibiotics has severely disrupted the structure of microbial communities, but the responses of these communities vary in different environments. Interestingly, even when the species composition changes, some microbial communities can still maintain crucial functions, a phenomenon known as "decoupling of structure and function." Among them, functional redundancy (FR) - the characteristic that multiple microorganisms perform the same ecological function - is the key mechanism for maintaining this stability. This review focuses on how functional redundancy may enhance microbial community resilience under antibiotic perturbation. We first start from the insurance hypothesis and the YAS (yield - acquisition - stress) framework to explain the ecological principles behind functional redundancy, and explain how microorganisms allocate resources and make trade-offs in different environments. We systematically analyze the multi-level defense strategies of microorganisms at five levels, including: ecological niche differentiation at the species level, horizontal transfer of resistance genes at the genetic level, cross-feeding reconstruction of metabolic networks, dormancy strategies at the temporal dimension (seed bank), and population regulation mediated by bacteriophages. Methodologically, we review metatranscriptomic approaches for distinguishing active signals from residual DNA, structural entropy algorithms for inferring FR, and AI-based tools for identifying latent resistance genes. Evidence from ecosystems such as the gut, respiratory tract, soil, and wastewater suggests the broad relevance of functional redundancy, although its stabilizing effect depends on antibiotic type, exposure duration, initial community composition, and ecological context. Finally, we explore the application prospects of this principle in the construction of synthetic communities and the optimization of fecal microbiota transplantation, and point out the evolutionary costs that may accompany maintaining functional redundancy, which is an important challenge that future research needs to address.},
}

@article {pmid42292438,
year = {2026},
author = {Wang, K and Zhu, X and Ju, X and Zhou, M and Shen, G},
title = {From nutritional intervention to immune modulation: a multi-database bibliometric and topic modeling study of vitamin D in inflammatory bowel disease.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1845767},
pmid = {42292438},
issn = {1664-3224},
mesh = {Humans ; *Inflammatory Bowel Diseases/immunology/diet therapy ; *Vitamin D/therapeutic use ; Bibliometrics ; Animals ; *Immunomodulation ; },
abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a chronic condition characterized by recurrent inflammatory episodes in the gastrointestinal tract. Conventional therapies, including biologics, corticosteroids, and immunosuppressive drugs, can effectively alleviate disease activity. However, their utility is often limited by adverse effects. Vitamin D plays a role in modulating immune function, intestinal barrier integrity, and the gut microbiota. It has emerged as a promising adjunctive therapy for IBD.

OBJECTIVE: To map the research landscape of vitamin D in IBD using bibliometric analysis, focusing on knowledge evolution, core themes, and emerging trends.

METHODS: Publications from 2006 to 2025 were collected by searching the Web of Science Core Collection (WoSCC) and Scopus databases. After removing duplicates, 2,659 articles and reviews were obtained for analysis. Networks were constructed using CiteSpace, VOSviewer, R, and Python. PubMed clinical trials were included for complementary analysis, and BERTopic was applied to identify latent topics and their temporal dynamics.

RESULTS: A total of 2,659 publications spanning 970 journals were identified, with a steady increase in output. The USA was the leading contributor and also demonstrated strong international collaboration. Ananthakrishnan Ashwin N. was the most influential author, and Inflammatory Bowel Diseases was the journal with the leading journal. Core themes included vitamin D deficiency, gut microbiota, inflammatory response, diet and nutrition. The focus has shifted toward gut microbiota, immune regulation, micronutrients, and evidence-based approaches. Furthermore, BERTopic modeling identified 12 latent topics, with increasing emphasis on gut microbiota, fecal microbiota transplant, and nutritional deficiencies.

CONCLUSION: This bibliometric analysis provides a concise, data-driven overview of research on vitamin D in IBD. The results highlighting its structure, evolution, and emerging trends, and informing future mechanistic and translational research.},
}

Humans
*Inflammatory Bowel Diseases/immunology/diet therapy
*Vitamin D/therapeutic use
Bibliometrics
Animals
*Immunomodulation

@article {pmid42292442,
year = {2026},
author = {Leng, F and Xia, R and Pei, J and Shi, Y and Gao, C and Wang, F and Li, Y},
title = {The role of the intratumoral microbiota in breast cancer metastasis and immune regulation: mechanisms and therapeutic implications.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1840903},
pmid = {42292442},
issn = {1664-3224},
mesh = {Humans ; *Breast Neoplasms/immunology/pathology/therapy/microbiology ; Female ; *Tumor Microenvironment/immunology ; *Microbiota/immunology ; Animals ; Neoplasm Metastasis ; Epithelial-Mesenchymal Transition/immunology ; Immunomodulation ; Neoplastic Cells, Circulating/immunology ; },
abstract = {Breast cancer metastasis remains the leading cause of cancer-related mortality and is closely linked to immune evasion and tumor microenvironment (TME) remodeling. Emerging evidence suggests that intratumoral microbiota (ITM), typically low in biomass and predominantly intracellular, may be associated with tumor progression. This review summarizes the compositional features of ITM and their potential roles in metastasis, including epithelial-mesenchymal transition (EMT), circulating tumor cell (CTC) survival, pre-metastatic niche formation, and distant colonization. Mechanistically, ITM may influence these processes through immune-related signaling pathways (e.g., PRR-mediated cascades) and modulation of immune cell function. However, current evidence is largely derived from preclinical or correlative studies, and causal roles in human breast cancer remain unproven. Methodological challenges associated with low biomass further complicate interpretation. We also discuss microbiota-targeted strategies, including probiotics, antibiotics, and fecal microbiota transplantation, which remain experimental. Future studies using rigorous methodologies and longitudinal human data are required to clarify the role of ITM and its clinical potential.},
}

Humans
*Breast Neoplasms/immunology/pathology/therapy/microbiology
Female
*Tumor Microenvironment/immunology
*Microbiota/immunology
Animals
Neoplasm Metastasis
Epithelial-Mesenchymal Transition/immunology
Immunomodulation
Neoplastic Cells, Circulating/immunology

@article {pmid42292452,
year = {2026},
author = {Li, Y and Zhang, J and Wu, S and Liu, Z and Qin, S},
title = {The impact of gut microbiota on cervical cancer and precancerous lesions: neglected status, mechanisms, challenges, and a call to action.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1826283},
pmid = {42292452},
issn = {1664-3224},
mesh = {Female ; Humans ; *Uterine Cervical Neoplasms/immunology/microbiology/therapy ; *Gastrointestinal Microbiome/immunology ; *Papillomavirus Infections/immunology/microbiology/virology ; Human Papillomavirus Viruses/immunology ; *Precancerous Conditions/immunology/microbiology ; Animals ; Vagina/microbiology/immunology ; *Uterine Cervical Dysplasia/immunology/microbiology ; Dendritic Cells/immunology ; },
abstract = {Cervical cancer (CC) remains a major global health threat closely associated with persistent high-risk human papillomavirus (HPV) infection. Although immune checkpoint inhibitors (ICIs) have emerged as a therapeutic option, their objective response rates remain unsatisfactory. Variations in the local vaginal microbiota alone cannot fully explain inter-individual differences in HPV clearance, suggesting that additional systemic immune determinants are involved. The gut microbiota, a central regulator of host systemic immunity, can profoundly influence HPV clearance and antitumor immune responses by shaping dendritic cell (DC) function, modulating the Th1/Th2 balance, regulating regulatory T cell (Treg) expansion, and affecting natural killer (NK) cell activity. Emerging evidence indicates that specific gut microbial taxa are causally associated with HPV infection, cervical intraepithelial neoplasia (CIN), and cervical cancer, and may reshape the vaginal microecological environment and enhance immunotherapy responses. However, this dimension has long received insufficient attention. This Perspective systematically addresses four core issues: the neglected status of gut microbiota research and the functional boundaries of vaginal microecology; key mechanisms through which gut microbiota regulate HPV clearance and cervical lesion progression; major challenges restricting progress; and potential strategies for promoting clinical translation. This work aims to establish a theoretical framework for gut microbiota-based interventions in cervical cancer prevention and treatment, providing directional guidance for this emerging interdisciplinary field.},
}

Female
Humans
*Uterine Cervical Neoplasms/immunology/microbiology/therapy
*Gastrointestinal Microbiome/immunology
*Papillomavirus Infections/immunology/microbiology/virology
Human Papillomavirus Viruses/immunology
*Precancerous Conditions/immunology/microbiology
Animals
Vagina/microbiology/immunology
*Uterine Cervical Dysplasia/immunology/microbiology
Dendritic Cells/immunology

@article {pmid42293159,
year = {2026},
author = {Ike, I and Teymouri, F and Crook, C and Guzman, S and Hazeltine, M and Castillo, D and Li, D and Brar, G},
title = {The interplay between bile acid metabolism and gut microbiome in biliary tract cancers.},
journal = {Frontiers in microbiomes},
volume = {5},
number = {},
pages = {1774429},
pmid = {42293159},
issn = {2813-4338},
abstract = {The gut microbiota and bile acids (BAs) exist in a tightly regulated, bidirectional relationship that influences host metabolism, immune function, and disease. Primary BAs synthesized in the liver are chemically transformed by intestinal microbes into a diverse pool of secondary BAs, which exert antimicrobial effects and activate host signaling pathways including Farnesoid X Receptor (FXR), Takeda G protein-coupled receptor 5 (TGR5), and sphingosine-1-phosphate receptor 2 (S1PR2). These pathways regulate BA homeostasis, epithelial barrier integrity, inflammation, and carcinogenesis. Disruption of this BA-microbiome axis has been implicated in biliary tract cancers (BTCs), a group of aggressive malignancies with rising global incidence and limited therapeutic options. Secondary BAs and BA receptor signaling contribute to tumor initiation and progression through NF-κB activation, oxidative stress, and altered cell survival, whereas reduced FXR signaling and obstructed enterohepatic circulation further promote inflammatory dysregulation. Emerging evidence demonstrates that microbial dysbiosis and altered BA metabolism are associated with distinct BTC microbial profiles, enriched in taxa such as Fusobacterium, Salmonella, Prevotella, and Actinomyces, alongside depletion of commensals including Lactobacillus. These taxa influence inflammatory signaling, BA transformation, and epithelial injury, contributing to carcinogenesis. Microbiome-BA interactions also shape anti-tumor immunity and responses to immune checkpoint inhibitors (ICIs). Specific microbial signatures-particularly enrichment of Lachnospiraceae, Erysipelotrichaceae, Bacteroidetes, and Alistipes-correlate with enhanced immune activation and improved clinical outcomes in hepatobiliary cancers. Modulation of gut microbiota through antibiotics, probiotics, or fecal microbiota transplantation can influence BA composition, immune surveillance, and therapeutic efficacy. Collectively, these data highlight the central role of the BA-microbiome axis in BTC pathogenesis and treatment response. Microbial and BA metabolite profiling represent promising avenues for biomarker development, while targeted manipulation of BA signaling and microbial ecology offers potential therapeutic strategies to improve BTC outcomes.},
}

@article {pmid42293221,
year = {2026},
author = {Gong, L and Kong, J and Shao, X and Meng, W and Zhang, R and Zhang, Y and Feng, Y},
title = {Dietary L-arginine supplementation exerts preventive effects on colitis through modulation of the gut microbiota.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1848380},
pmid = {42293221},
issn = {2296-861X},
abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic, relapsing gastrointestinal disease that imposes an increasing global health burden. Our previous study showed that L-arginine (Arg) could markedly alleviate experimental colitis; however, the relative efficacy of its prophylactic versus therapeutic intervention remains unclear, and the underlying mechanisms require further elucidation.

METHODS: Mice received Arg supplementation either prior to DSS exposure (BeArg) or during DSS treatment (DuArg). Intestinal barrier function, inflammatory cytokines and gut microbiota alterations were evaluated, followed by fecal microbiota transplantation (FMT) validation.

RESULTS: BeArg markedly alleviated DSS-induced mice body weight loss, disease activity index (DAI) elevation, and colon shortening, exhibiting a protective efficacy comparable to full-course Arg administration. BeArg also lowered serum lipopolysaccharide, consistent with improved intestinal barrier integrity. In addition, BeArg reduced the expression of tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) while augmenting interleukin-10 (IL-10) at both the transcriptional and protein levels. By comparison, DuArg produced only modest clinical improvement and showed limited efficacy in modulating barrier dysfunction and inflammatory responses. 16S rRNA sequencing revealed that BeArg and Arg interventions induced similar alterations in the gut microbial community structure, while FMT further confirmed that Arg-mediated remodeling of the gut microbiota effectively protected against DSS-induced colitis.

CONCLUSION: These data indicate that Arg exerts a prophylactic effect against colitis by modulating the gut microbiota, underscoring the pivotal role of intervention timing in optimizing its protective effects.},
}

@article {pmid42293516,
year = {2026},
author = {Zou, Y and Liu, L and Chen, H and Luo, Z and Zhu, Z and Li, Z and Lin, B and Zhuang, Z and Li, W and Yang, Q and Yang, X and Zhou, H and Luo, M and Dai, D},
title = {Study protocol for a randomized controlled trial of fecal microbiota transplantation via different routes in children with moderate-to-severe autism spectrum disorder.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1829532},
pmid = {42293516},
issn = {1664-302X},
abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) shows promise for autism spectrum disorder (ASD) by modulating the gut-brain axis, but the optimal delivery route remains unknown. Our previous single-arm study suggested efficacy of nasojejunal FMT in children with moderate-to-severe ASD, yet could not exclude placebo effects or compare routes. This randomized controlled trial aims to determine the most effective and tolerable FMT administration route.

METHODS: This single-center, randomized, triple-blind, double-dummy, placebo-controlled, three-arm parallel-group trial will enroll 75 children (aged 3-16 years) with moderate-to-severe ASD [Childhood Autism Rating Scale, Second Edition (CARS-2) ≥36]. Participants are randomized 1:1:1 to: (1) FMT via nasojejunal tube + sham colonoscopy (FMT-NJT); (2) active FMT via colonoscopy with transendoscopic enteral tube placement (first session) + two subsequent infusions via the indwelling tube + sham nasojejunal intubation (FMT-C); (3) placebo via both routes (sham procedures). Three FMT/placebo sessions (5 mL/kg, max 100 mL) are administered over 5 days. Primary outcome is change in CARS-2 score from baseline to Week 24. Secondary outcomes include changes in Social Responsiveness Scale, Autism Behavior Checklist, Gastrointestinal Symptom Rating Scale, Short Sensory Profile, Children's Sleep Habits Questionnaire, gut metagenomic profiles (baseline, Weeks 2,6,12,24,48), and adverse events.

RESULTS: This is a study protocol; no results are available.

CONCLUSIONS: This first head-to-head comparison of FMT routes in pediatric ASD will provide high-level evidence to guide treatment standardization, directly addressing the translational gap identified in our preliminary work.},
}

@article {pmid42281763,
year = {2024},
author = {Winston, JA and Suchodolski, JS and Gaschen, F and Busch, K and Marsilio, S and Costa, MC and Chaitman, J and Coffey, EL and Dandrieux, JRS and Gal, A and Hill, T and Pilla, R and Procoli, F and Schmitz, SS and Tolbert, MK and Toresson, L and Unterer, S and Valverde-Altamirano, É and Verocai, GG and Werner, M and Ziese, AL},
title = {Clinical Guidelines for Fecal Microbiota Transplantation in Companion Animals.},
journal = {Advances in small animal care},
volume = {5},
number = {1},
pages = {79-107},
pmid = {42281763},
issn = {2666-450X},
}

@article {pmid42283215,
year = {2026},
author = {Chernova, VO and van Prehn, J and Groenewegen, B and van Lingen, E and Kuijper, EJ and Lambregts, MMC and van Nood, E and Choi, G and Hazenberg, MD and Keller, JJ and Terveer, EM},
title = {Biovigilance in Faecal Microbiota Transplantation: 7-Year Cohort Study and Framework for Microbiological Assessments of Infectious Adverse Events.},
journal = {United European gastroenterology journal},
volume = {14},
number = {5},
pages = {e70239},
doi = {10.1002/ueg2.70239},
pmid = {42283215},
issn = {2050-6414},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Clostridioides difficile/isolation & purification ; *Clostridium Infections/therapy/microbiology ; *Fecal Microbiota Transplantation/adverse effects/methods/standards ; Netherlands/epidemiology ; Prospective Studies ; Recurrence ; Treatment Outcome ; Aged, 80 and over ; },
abstract = {BACKGROUND AND AIMS: Faecal microbiota transplantation (FMT) is increasingly used. However, no systematic approach exists to assess infectious risks after FMT, leading to underreporting. We evaluated infectious complications at the Netherlands Donor Feces Bank (NDFB) and proposed a structured biovigilance approach aligned with the EU Regulation on Substances of Human Origin (SoHO).

METHODS: We conducted a prospective observational cohort study of all patients receiving frozen donor faecal suspensions from the NDFB (May 2016-December 2023) for recurrent Clostridioides difficile infection (rCDI) or via an extended access programme (EAP) for non-CDI indications. (Serious) adverse events ((S)AEs) were reported by physicians and recorded at 3 weeks, 3 months, and 6 months. Serious adverse reactions (SARs) were defined as SAEs probably or definitely related to FMT.

RESULTS: We included 290 rCDI patients (322 FMTs) and 35 EAP patients (75 FMTs). FMT efficacy was favourable overall: 92% of rCDI patients remained free of rCDI within 8 weeks, and 49% of EAP patients achieved at least a partial response. Sixty-one per cent of rCDI patients and 34% of EAP patients had mild gastrointestinal AEs. AE incidences were comparable across groups (rCDI: 5.1 vs. EAP: 4.4 per 100 patient-weeks). SAEs were more frequent in EAP patients (0.66 vs. 0.28 per patient), reflecting higher immunosuppression and comorbidity. FMT-attributable SARs occurred after 6 of 322 FMTs (1.9%) in the rCDI group and after 3 of 75 FMTs (4.0%) in the EAP group. Two donor-derived Escherichia coli infections in EAP patients with predisposing conditions were confirmed, consistent with early donor-strain colonisation rather than a direct FMT effect. Most SAEs were unrelated.

CONCLUSIONS: In this 7-year cohort, donor-derived infections were rare but present, particularly in non-CDI patients with substantial comorbidity, whereas overall safety remained favourable. A SoHO-compliant biovigilance protocol incorporating microbiological investigation and donor/sample traceability is essential for the safe clinical use of FMT and faecal microbiota products.},
}

Adult
Aged
Female
Humans
Male
Middle Aged
Clostridioides difficile/isolation & purification
*Clostridium Infections/therapy/microbiology
*Fecal Microbiota Transplantation/adverse effects/methods/standards
Netherlands/epidemiology
Prospective Studies
Recurrence
Treatment Outcome
Aged, 80 and over

@article {pmid42283380,
year = {2026},
author = {Van Hoef, S and Welvaert, C and Allaeys, M and Berrevoet, F},
title = {Incidence of tissue-based inguinal hernia repair in Belgium: a web-based national survey.},
journal = {Acta chirurgica Belgica},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/00015458.2026.2689120},
pmid = {42283380},
issn = {0001-5458},
abstract = {BACKGROUND: Inguinal hernia repair is one of the most commonly performed procedures worldwide. Several different methods for repair exist, where the preferred surgical procedure for a non-complicated unilateral inguinal hernia is still up for debate. Originally described as a tissue repair, the introduction of prostheses have led many surgeons to move away from this type of repairs. However, recently updated guidelines still recommend non-mesh treatment, in a subgroup of patients, with a preference for the Shouldice technique. Therefore, we set out to map the incidence and knowledge about tissue-based repair of a primary inguinal hernia in Belgium.

METHODS: We designed a voluntary, open web-based survey for both surgeons and trainees asking about their knowledge, experience and indication for tissue-based suture repair, using a Google-forms document. The survey included level of experience and surgical preference, practice of tissue-based inguinal repair, indications for tissue-based repair, and technique and knowledge about tissue-based repair. Data was collected between 1[st] of December 2023 and 31[st] of January 2024 and analyzed using Microsoft Excel (version 16.77.01).

RESULTS: A total of 122 respondents filled out the questionnaire, 47 trainees and 75 surgeons, of which 4 were discarded due to inaccurate data. Only 15 out of 71 surgical respondents still performed a non-mesh based repair in an elective setting., where the Shouldice repair was the preferred technique (n = 12, 80%).Knowledge about tissue-based mesh was rated mainly moderate (43.7%) and a non-mesh based repair was still considered an option when faced with fecal contamination (54.9%). Upon patient's request, 67.7% respondents would convince patients of mesh superiority.Among surgical trainees eighteen respondents (38.3%) had never seen a tissue based repair before and 36.1% respondents said tissue-based repair was not taught in their current or previous hospital(s).Most surgical trainees (48.9%) had basic knowledge and know a single technique. Considering indications for primary tissue repair, 57.4% mentioned a contaminated field as a valid indication. Comparable to the surgeon's response, 66% of surgical trainees would convince the patient of mesh superiority when asked for a pure tissue-based repair.

CONCLUSION: Our survey confirms the declining rate of tissue based repairs, with only 7% of surgical respondents performing sufficient procedures to allow for equivocal result compared to mesh-based repairs. Centralizing these procedures into specific hernia centers might allow for an increased case-load and dedicated training pathways giving trainees and future surgeons proper training.},
}

@article {pmid41121479,
year = {2026},
author = {Sahoo, A and Singh, J and Alam, K and Alruwaili, NK and Aodah, A and Almalki, WH and Almujri, SS and Alrobaian, M and Barkat, MA and Singh, T and Lal, JA and Rahman, M},
title = {Addressing Unmet Needs in Clostridium difficile Infection: Advances in Diagnosis, Treatment, and Prevention.},
journal = {Current medicinal chemistry},
volume = {33},
number = {10},
pages = {1900-1917},
pmid = {41121479},
issn = {1875-533X},
mesh = {Humans ; *Clostridium Infections/diagnosis/prevention & control/drug therapy/therapy ; *Clostridioides difficile/drug effects ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Fecal Microbiota Transplantation ; Antibodies, Monoclonal/therapeutic use ; },
abstract = {INTRODUCTION: Clostridium difficile infection (CDI) is a serious global health concern characterized by toxin-induced colonic damage, ranging from diarrhea to life-threatening conditions. Despite improved diagnostics and treatments, recurrence rates of up to 30% underscore persistent gaps in effective disease management.

METHODS: CDI pathogenesis is driven by the disruption of the gut microbiota, often due to broad- -spectrum antibiotic use. Risk factors such as advanced age, hospitalization, IBD, and immunosuppression increase the severity and recurrence of the infection. The hypervirulent ribotype 027 strain has been associated with increased mortality and treatment resistance, necessitating targeted therapies.

RESULTS: Emerging treatments such as FMT and monoclonal antibodies show promise for CDI management, with FDA approvals marking progress in microbiome restoration. However, hurdles remain in safety, regulation, and donor screening. Advances in diagnostic and scoring tools have aided in the detection and treatment, but differentiating between colonization and infection remains a challenge. Preventive measures and novel agents such as bacteriocins and bacteriophages offer targeted, microbiome-sparing strategies.

DISCUSSION: Despite recent advances, CDI management remains challenging because of diagnostic uncertainty and frequent recurrences. Innovative treatments such as FMT and monoclonal antibodies are promising but face limitations in safety, access, and cost. Preventive strategies and decision tools help, yet distinguishing colonization from infection remains difficult, underscoring the need for ongoing and multidisciplinary innovation.

CONCLUSION: This review highlights current approaches to CDI diagnosis, treatment, and prevention, stressing the urgent need for innovative strategies to reduce recurrence. Targeted research and policy efforts are vital to improving outcomes and quality of life for those affected.},
}

Humans
*Clostridium Infections/diagnosis/prevention & control/drug therapy/therapy
*Clostridioides difficile/drug effects
Anti-Bacterial Agents/therapeutic use/pharmacology
Fecal Microbiota Transplantation
Antibodies, Monoclonal/therapeutic use

@article {pmid42274997,
year = {2026},
author = {Hirsch, W and Enns, EA and Khoruts, A and Rajasingham, R and Vaughn, BP},
title = {Cost-effectiveness of Commercial or Traditional Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciag263},
pmid = {42274997},
issn = {1537-6591},
abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is the cost-effective strategy for managing recurrent Clostridioides difficile infection (rCDI). Prior costing models assumed FMT administration via colonoscopy. With the commercialization of microbiota therapeutics for rCDI, this study sought to determine the impact of commercial, Food and Drug Administration (FDA) approved microbiota-based therapeutics relative to traditional FMT on the cost-effectiveness for rCDI.

METHODS: We used a Markov model to simulate a cohort of patients with rCDI to evaluate the cost-effectiveness of varied methods of FMT administration for rCDI. The model includes estimates of cure, recurrence, and mortality. Data sources were taken from national guidelines and published literature on treatment outcomes. Outcome measures were quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs).

RESULTS: FMT by colonoscopy is the cost-effective strategy for preventing second or subsequent rCDI with an incremental cost-effectiveness ratio (ICER) of $44 158. Assuming a willingness-to-pay threshold of $100 000 per quality adjusted life years (QALY) gained, FMT by colonoscopy was optimal in the majority (70%) of simulations. At a willingness-to-pay threshold of $100 000 per quality adjusted life year (QALY), commercial, FDA approved microbiota therapeutics were not cost effective under any circumstance when donor-derived FMT products are available.

CONCLUSIONS: Traditional FMT administered by colonoscopy is the optimal cost-effective strategy for preventing second or subsequent episodes of rCDI. If FMT is not available, then microbiota therapeutics are not a cost-effective option for rCDI at current pricing.},
}

@article {pmid42275128,
year = {2026},
author = {Takahashi, K and Yoshikawa, Y and Chaki, T and Yamakage, M},
title = {Gut Microbiota Modulation Attenuates Myocardial Ischemia-Reperfusion Injury in Diabetic Mice.},
journal = {Shock (Augusta, Ga.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/SHK.0000000000002882},
pmid = {42275128},
issn = {1540-0514},
abstract = {BACKGROUND: The gut microbiome is increasingly being recognized as a regulator of cardiometabolic health; however, whether microbiome interventions can attenuate myocardial ischemia-reperfusion injury (IRI) in diabetic hearts remains unclear. Therefore, we tested whether fecal microbiota transplantation (FMT) from lean non-diabetic donors could mitigate myocardial IRI in type 2 diabetes mellitus (T2DM) db/db mice and explored candidate taxa associated with protection.

METHODS: Male db/db mice (T2DM model) received a 14-day course of FMT from lean db/m donors or a vehicle after antibiotic pretreatment. Myocardial IRI was induced, and infarct size was quantified. The gut microbiota was evaluated by 16S rRNA gene sequencing.

RESULTS: FMT significantly reduced the infarct size as a percentage of the area at risk compared to the IRI group (38.7 ± 13.4% vs. 58.7 ± 4.3%, P = 0.003). Microbiome analysis revealed that among alpha-diversity metrics only the Simpson index differed between the donor and diabetic groups. In beta-diversity analyses, diabetic mice clustered separately from donor mice, and the microbiome intervention induced a modest but significant shift detected by the presence or absence of Unweighted UniFrac. Differential abundance analysis and exploratory LEfSe further suggested Akkermansia, particularly Akkermansia muciniphila, as a candidate taxon reduced in diabetic mice and partially restored after the FMT intervention.

CONCLUSION: A donor-derived microbiome intervention attenuated myocardial IRI in db/db mice and was accompanied by partial remodeling of the gut microbiota. Akkermansia muciniphila emerged as a candidate taxon associated with a reduced susceptibility to IRI in diabetic hearts.},
}

@article {pmid42276984,
year = {2026},
author = {Lange-Andrzejewska, O and Budny, A and Janczy, A and Wilczynski, M and Szymanski, M and Proczko-Stepaniak, M and Sledzinski, T and Mika, A},
title = {Longitudinal analysis of short-chain fatty acid profiles in stool of sleeve gastrectomy patients.},
journal = {Nutrition & diabetes},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41387-026-00441-x},
pmid = {42276984},
issn = {2044-4052},
support = {2021/43/B/NZ5/00039//Narodowe Centrum Nauki (National Science Centre)/ ; },
abstract = {Obesity presents significant health risks, including metabolic disorders and depressive symptoms, necessitating effective interventions such as sleeve gastrectomy (SG), which enables substantial weight loss and metabolic improvements. The primary question of this study was whether SG also affects faecal short-chain fatty acid (SCFA) profiles over 12 months, and whether these changes are related to anthropometric, biochemical, and psychological parameters. A total of 37 female patients with obesity were included in this prospective, observational study. Patients underwent SG and were followed for 12 months postoperatively. SCFA profiles were analysed by gas chromatography-mass spectrometry (GC-MS). Faecal samples for SCFA analysis, anthropometric measurements, blood biochemical markers, food intake and psychological assessments were collected at baseline and at regular intervals after surgery. Our results indicate that SG leads to significant reductions in body mass index, lipid profiles, and systemic inflammation markers, with concurrent alterations in SCFA concentrations, particularly a decrease in major SCFAs (acetic, propionic, and butyric acids) over time. An increase in branched SCFAs was observed post-surgery, which may reflect shifts in the gut microbiota composition and fermentation processes. Patients also reported improvements in emotional well-being and dietary habits. These findings support the hypothesis that SG induces changes in gut microbiota metabolism and underscore the complex interplay between bariatric surgery, gut microbiota, SCFA metabolism, and psychological health. They highlight the need for further research to clarify the long-term implications of these changes and the mechanisms involved.},
}

@article {pmid42277050,
year = {2026},
author = {Xu, J and Han, Z and Xue, Q and Wang, H and Li, Y and Song, J and Li, L and Hu, M and Wang, D},
title = {Gut commensal Odoribacter splanchnicus attenuates hyperlipidemic periodontitis via gut-oral metabolic transmission of β-GPA.},
journal = {NPJ biofilms and microbiomes},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41522-026-01033-4},
pmid = {42277050},
issn = {2055-5008},
support = {82470987//National Natural Science Foundation of China/ ; jcsz2025678-2//Science and Technology Project of Jilin Province Department of Finance/ ; 2024JBGS07//"Medicine+X" Interdisciplinary Innovation Project/ ; },
abstract = {Hyperlipidemic periodontitis (HPD) represents a prevalent comorbidity linking systemic metabolic dysregulation with local inflammation, yet the microbial mechanisms driving this gut-oral crosstalk remain elusive. Here, the comorbid state of HPD is linked to hyperlipidemia-associated gut microbiota changes, which are prominently accompanied by the depletion of Odoribacter splanchnicus in both patients and mice. Fecal microbiota transplantation demonstrates that this gut dysbiosis exacerbates periodontal destruction when local inflammation is present. Mechanistically, intragastric administration of live O. splanchnicus ameliorates HPD by remodeling the gut ecosystem and upregulating the metabolite β-guanidinopropionic acid (β-GPA). Notably, direct supplementation with β-GPA reproduces these protective effects. Furthermore, β-GPA is proposed as a systemic effector linking the gut and periodontal tissues, where its protective effect is associated with the suppression of the pro-inflammatory Toll-like receptor 4 (TLR4) signaling cascade. These findings highlight a link involving O. splanchnicus, β-GPA, and the modulation of TLR4 signaling, offering a potential microbiome-based therapeutic strategy for managing complex metabolic-inflammatory comorbidities.},
}

@article {pmid42278360,
year = {2026},
author = {Mardnaybin, H and Demirci, M and Kirkoyun Uysal, H},
title = {The Gut Microbiome in HIV Pathogenesis: Interconnections Between Dysbiosis, Immune Dysfunction, and Viral Persistence.},
journal = {International journal of molecular sciences},
volume = {27},
number = {11},
pages = {},
doi = {10.3390/ijms27114830},
pmid = {42278360},
issn = {1422-0067},
abstract = {The human gut microbiome is essential for immune regulation and mucosal homeostasis, functions that are profoundly disrupted during HIV infection. Early viral replication in the gut-associated lymphoid tissue (GALT) triggers a self-reinforcing cycle of CD4[+] T-cell depletion, epithelial barrier breakdown, and increased microbial translocation. This persistent immune activation continues even under effective antiretroviral therapy (ART). A growing body of evidence indicates that HIV infection is consistently associated with alterations in gut microbial communities. This dysbiosis is typically characterized by fewer beneficial butyrate-producing commensal bacteria and an enrichment of pro-inflammatory microbial taxa. It also involves disturbances in key microbial metabolites, including short-chain fatty acids (SCFAs) and tryptophan catabolites. Such changes not only exacerbate systemic inflammation but may also contribute to incomplete immune reconstitution and the persistence of latent viral reservoirs despite long-term ART. In this review, we summarize current knowledge of microbiome-HIV interactions, with particular emphasis on the mechanisms through which gut dysbiosis contributes to immune dysfunction and viral persistence. We discuss recent advances in multi-omics technologies, as well as experimental systems such as gnotobiotic and humanized mouse models and intestinal organoid platforms that are helping to elucidate these complex interactions. Furthermore, we evaluate emerging microbiome-targeted interventions-including probiotics, prebiotics, fecal microbiota transplantation, and engineered bacterial therapeutics-and consider their potential role as adjunctive strategies in HIV treatment and cure research. By integrating microbiological, immunological, and clinical perspectives, this review highlights key knowledge gaps and outlines future research directions aimed at harnessing the gut microbiome as a novel therapeutic avenue in HIV management and eradication.},
}

@article {pmid42278620,
year = {2026},
author = {Lu, Z and Chen, G and Chang, M and Wang, N and Xia, T and Zhang, Y and Xu, G and Zhao, Q and Shen, P and Zhou, W and Ni, Z and Gao, Y},
title = {Effects of High-Altitude Environments on Gut Microbiota and Their Mechanisms in Immune Regulation and High-Altitude Adaptation.},
journal = {International journal of molecular sciences},
volume = {27},
number = {11},
pages = {},
doi = {10.3390/ijms27115096},
pmid = {42278620},
issn = {1422-0067},
support = {2025YFC3507500//National Natural Science Foundation of China/ ; 2025YFC3507502//National Natural Science Foundation of China/ ; zyyzdxk-2023311//State Administration of Traditional Chinese Medicine of the People's Republic of China/ ; },
abstract = {High-altitude environments, characterized by hypoxia, low temperature, and intense ultraviolet radiation, profoundly disrupt host intestinal homeostasis and reshape the gut microbiota, thereby influencing immune regulation and acclimatization. This review systematically summarizes the dynamic compositional and functional changes in the gut microbiota in high-altitude natives, immigrant populations, short-term visitors, and relevant animal models. Current evidence indicates that long-term high-altitude adaptation is associated with directional microbial remodeling, including the enrichment of anaerobic and short-chain fatty acid (SCFA)-associated taxa, which may support energy metabolism and immune homeostasis. In contrast, acute high-altitude exposure more readily induces dysbiosis, impairs intestinal barrier integrity, and promotes the translocation of endotoxins and bioactive metabolites. Mechanistically, the gut microbiota and its metabolites participate in high-altitude adaptation and high-altitude-related disease pathogenesis by modulating barrier function, inflammatory responses, oxidative stress, and immune signaling, and by mediating interorgan communication-characterized by metabolite-driven systemic inflammation or tolerance-through the gut-lung, gut-heart, gut-brain, gut-kidney, and gut-testis axes. SCFAs, bile acids, amino acid-derived metabolites, and succinic acid may control immune homeostasis and inflammatory responses through pathways including TLR4/NF-κB and NLRP3. Although the causal relationships, core microbial effectors, and population-specific heterogeneity remain incompletely defined, microbiota-targeted interventions, including probiotics, prebiotics, and fecal microbiota transplantation, have shown promise for promoting acclimatization and preventing high-altitude-related disorders. Overall, this review provides an integrated framework linking environmental stress, gut microbial ecology, and host immune-metabolic adaptation at high altitude, and highlights future directions for mechanistic and translational research in high-altitude medicine.},
}

@article {pmid42279278,
year = {2026},
author = {Liu, Z and Ang, MY and Kue, CS},
title = {Gut Microbiota in Colorectal Cancer: Mechanistic Insights, Clinical Strategies, and a Regional Perspective with a Focus on Sichuan, China.},
journal = {Cancers},
volume = {18},
number = {11},
pages = {},
doi = {10.3390/cancers18111693},
pmid = {42279278},
issn = {2072-6694},
abstract = {CRC remains a major cause of cancer-related morbidity and mortality worldwide. In recent years, the gut microbiota has gained increasing attention in CRC research. Intestinal microbes are not passive bystanders in tumor development. They may promote persistent inflammation, disrupt epithelial barrier integrity, alter microbial metabolites, and affect host immune and signaling pathways. Emerging evidence also suggests that microbiota-related metabolites and microbial functional alterations may influence host epigenetic regulation, including DNA methylation and chromatin-associated signaling, thereby further shaping colorectal carcinogenesis. Together, these changes can create a microenvironment that favors tumor initiation and progression. Several bacterial species, including Fusobacterium nucleatum, Parvimonas micra, and Peptostreptococcus anaerobius, have been repeatedly associated with CRC. In contrast, beneficial commensal microbes and their metabolites, especially short-chain fatty acids, may help maintain intestinal homeostasis and limit tumor-promoting processes. Because the gut microbiota is strongly shaped by diet, lifestyle, and environmental exposure, regional differences are also relevant. This is particularly important in Sichuan, China, where distinctive dietary habits and environmental features may influence microbial patterns associated with CRC risk and disease behavior. This review summarizes the main mechanisms linking the gut microbiota to CRC, examines the regional context of Sichuan, China, and discusses current and emerging clinical strategies. These include dietary intervention, probiotics, fecal microbiota transplantation, and microbiome-informed approaches to prevention, diagnosis, and treatment.},
}

@article {pmid42279294,
year = {2026},
author = {Newell, LF and Twohey, E and Sweetnam, J and Skendzel, S and Stingle, J and Vartanian, KA and Davis, BA and Layman, CE and Carbone, L and Ray, K and Fei, SS and Karstens, L and He, FC and El Jurdi, N and Blaes, AH and Meyers, G and Cook, RJ and Baraki, A and Dengel, DR and Holtan, SG},
title = {Attenuation of Immune Senescence Markers After Intensive Cancer Therapy Through Resistance Training: A Pilot Study.},
journal = {Cancers},
volume = {18},
number = {11},
pages = {},
doi = {10.3390/cancers18111710},
pmid = {42279294},
issn = {2072-6694},
abstract = {Background: Chemotherapy and radiation accelerate aging of multiple systems, including the immune and musculoskeletal systems. Resistance training may mitigate some of the late physiologic effects of cancer therapy. Methods: We developed a community-based pilot study of resistance training for long-term cancer survivors meeting criteria for pre-frailty or frailty (N = 8; 6 allogeneic hematopoietic cell transplant, 1 autologous hematopoietic transplant, 1 breast cancer survivor) and their caregivers (N = 8 healthy controls) consisting of a baseline assessment, 10 weeks of personalized resistance training at least once weekly as a group and as many additional times on an individual basis as their schedule allowed, and an end-of-study assessment to measure change in strength and body composition. Blood samples were collected at the start of the study and after the 10-week training program to assess changes in peripheral blood mononuclear cell DNA methylation patterns, gene expression measured by RNA sequencing, and stool microbiome analysis using metagenomics. The median number of resistance training sessions was 25 sessions. Results: Cancer survivors and controls both more than doubled their squat and press volume after 10 weeks. At baseline, cancer survivors exhibited a pro-inflammatory transcriptomic and epigenetic profile with elevated interferon signaling and reduced naïve T cell signatures compared to healthy controls, consistent with immune senescence. After 10 weeks of resistance training, these differences normalized, suggesting that exercise exerted anti-inflammatory and immune-restorative effects in cancer survivors at both gene expression and methylation levels. Ten fecal microbial pathways that were lower in relative abundance in patients compared with controls at baseline were no longer significantly different post-exercise. Conclusions: Our data suggest that in addition to beneficial changes in body composition, resistance training may exert an immune restorative effect in cancer survivors.},
}

@article {pmid42280407,
year = {2026},
author = {Acierno, C and Caturano, A and Barletta, F and Rinaldi, L and Sasso, FC and Adinolfi, LE and Nevola, R},
title = {Nutritional Interventions Targeting the Gut Microbiome in MASLD: From Prebiotics and Probiotics to Postbiotics and Fecal Microbiota Transplantation.},
journal = {Nutrients},
volume = {18},
number = {11},
pages = {},
doi = {10.3390/nu18111765},
pmid = {42280407},
issn = {2072-6643},
mesh = {Humans ; *Prebiotics/administration & dosage ; *Fecal Microbiota Transplantation ; *Probiotics/administration & dosage ; *Gastrointestinal Microbiome ; *Fatty Liver/therapy/microbiology ; Synbiotics/administration & dosage ; Dysbiosis ; },
abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent liver-centred manifestation of systemic metabolic dysfunction. The gut-liver axis provides a biologically credible therapeutic rationale because intestinal dysbiosis, impaired barrier integrity, microbial metabolites, bile acid signalling, short-chain fatty acids, and trimethylamine N-oxide may influence hepatic steatosis, inflammation, and fibrogenesis. This narrative review critically evaluates dietary patterns, prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT) as microbiome-directed strategies in MASLD. The comparative framework prioritises disease-specific human evidence, clinically meaningful endpoints, trial duration and sample size, reproducibility, safety, and feasibility. Dietary optimisation remains the most clinically grounded intervention, whereas probiotics and synbiotics show modest and heterogeneous signals on biochemical or metabolic surrogate endpoints. Prebiotics are mechanistically coherent but supported by limited liver-centred trials. Postbiotics and microbiome-mediated bioactives remain early-stage and require stricter definitional boundaries. FMT is investigational and should not be extrapolated from its established role in recurrent Clostridioides difficile infection. Most available evidence across all intervention categories relies principally on surrogate endpoints-including aminotransferases, insulin resistance indices, lipid parameters, and microbiome compositional shifts-rather than on validated liver-centred outcomes such as histological improvement or quantitative liver fat assessment; this constrains the strength of conclusions that can currently be drawn. Across all categories, microbiome modulation does not by itself establish liver disease modification, and no microbiome-targeted nutritional intervention has yet demonstrated histological benefit in MASLD. Future trials in this field should prioritise validated hepatic endpoints, phenotype-stratified patient enrolment, adequate follow-up duration, and direct comparisons between intervention categories to determine which microbiome-directed strategies, if any, deliver measurable and reproducible hepatic benefit beyond surrogate markers.},
}

Humans
*Prebiotics/administration & dosage
*Fecal Microbiota Transplantation
*Probiotics/administration & dosage
*Gastrointestinal Microbiome
*Fatty Liver/therapy/microbiology
Synbiotics/administration & dosage
Dysbiosis

@article {pmid42281500,
year = {2026},
author = {Rashidi, SK and Dezfouli, MA and Khalili, H and Kiani, AKD},
title = {The role of gut microbiota in the neurobiology and treatment of Alzheimer's disease.},
journal = {General physiology and biophysics},
volume = {45},
number = {2},
pages = {129-151},
doi = {10.4149/gpb_2025042},
pmid = {42281500},
issn = {0231-5882},
mesh = {Humans ; *Alzheimer Disease/therapy/microbiology/physiopathology ; *Gastrointestinal Microbiome ; Animals ; *Brain/physiopathology ; Amyloid beta-Peptides/metabolism ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; },
abstract = {Alzheimer's disease (AD) is the most common cause of dementia in the elderly population and characterized by progressive cognitive decline. The major pathological features of AD are the accumulation of extracellular amyloid-beta protein as neuritic plaques and intracellular hyperphosphorylated tau protein as neurofibrillary tangles. Studies have shown that gut microbiota are involved in several central nervous system disorders through regulation of neurotransmitter production, blood-brain barrier permeability and immune responses. The gut microbiota establishes a two-way communication between the gut and the brain through neural, endocrine, and immune pathways, which play a role in various neurological diseases, including AD. Alterations in the composition and function of the gut microbiota may influence neuroinflammation, amyloid-beta accumulation, and tau pathology. Targeting the balance of the gut microbiota through probiotics, prebiotics, and fecal microbial transplantation could be promising therapeutic approach against neurodegeneration. Understanding the complex relationship between the gut microbiota and AD pathobiology could pave the way for novel preventive and therapeutic strategies. Here, we summarized advances in the role of gut microbiota in AD pathobiology and updated rising concerns from recent reports. Moreover, the possibility of applying the capability of the gut microbiota as a promising treatment against AD has been discussed in this review.},
}

Humans
*Alzheimer Disease/therapy/microbiology/physiopathology
*Gastrointestinal Microbiome
Animals
*Brain/physiopathology
Amyloid beta-Peptides/metabolism
Probiotics/therapeutic use
Fecal Microbiota Transplantation

@article {pmid41593844,
year = {2026},
author = {Tamburini, G and Daprai, L and Gazzola, A and Rossetti, D and Tomassini, E and Dilio, G and Ria, T and Dato, L and Mancuso, MC and Luini, M and Tel, F and Possenti, I and Magistrali, CF and Callegaro, AP and Ardissino, G and , },
title = {Epidemiology of Bloody Diarrhea, Shiga Toxin-producing Escherichia coli and Hemolytic Uremic Syndrome in Children.},
journal = {The Pediatric infectious disease journal},
volume = {45},
number = {7},
pages = {642-648},
pmid = {41593844},
issn = {1532-0987},
mesh = {Humans ; *Hemolytic-Uremic Syndrome/epidemiology/microbiology/diagnosis ; *Shiga-Toxigenic Escherichia coli/genetics/isolation & purification ; Child, Preschool ; *Escherichia coli Infections/epidemiology/microbiology/diagnosis ; Child ; Adolescent ; Male ; *Diarrhea/epidemiology/microbiology ; Infant ; Female ; Italy/epidemiology ; Feces/microbiology ; Young Adult ; },
abstract = {BACKGROUND: Shiga Toxin-producing Escherichia coli -associated hemolytic uremic syndrome (STEC-HUS) remains a leading cause of acute kidney failure, worldwide. The disease often presents with acute bloody diarrhea and supportive care is the only therapeutic option; thus, early diagnosis and early management are of paramount importance.

AIM: Herein, we share the results of a proactive diagnostic approach to acute bloody diarrhea in children as shown by a surveillance activity devoted to the early diagnosis of STEC infection.

METHODS: Since 2010, in a well-defined area of Northern Italy (referral pediatric population of 2 million), children and teenagers (age <20) with acute bloody diarrhea had their stool screened for Shiga toxin (Stx) genes. Positive patients were hydrated and followed until recovery or the development of HUS.

RESULTS: Stool specimens from 7518 children with acute bloody diarrhea were tested, and 464 (6.2%) turned out to be positive for Stx genes. During the same period and in the same area, 178 STEC-HUS cases were diagnosed. The most common Stx encountered was the Stx2 (n: 217; 52.3%), followed by the combination of Stx1 and 2 (n: 111; 26.7%) while Stx1 was less commonly detected (n: 87; 21.0%). Acute bloody diarrhea, STEC infection and STEC-HUS were all more common in younger children <5 years except in the age group <1 year-old. The percentage of Stx+ acute bloody diarrheas doubles during the summer months, peaking as high as 10% in August and September.

CONCLUSIONS: The specific diagnostics for Stx genes can guide patients' management and help in identifying the source of the infection by revealing a significant proportion of children with STEC infection among patients with acute bloody diarrhea.},
}

Humans
*Hemolytic-Uremic Syndrome/epidemiology/microbiology/diagnosis
*Shiga-Toxigenic Escherichia coli/genetics/isolation & purification
Child, Preschool
*Escherichia coli Infections/epidemiology/microbiology/diagnosis
Child
Adolescent
Male
*Diarrhea/epidemiology/microbiology
Infant
Female
Italy/epidemiology
Feces/microbiology
Young Adult

@article {pmid41707880,
year = {2026},
author = {Sun, H and Yu, Z and Piao, C and Gu, J and Geng, F and Ai, H and Jiang, S and Ren, Y and Gao, J and Wang, Z and Liu, J and Zhang, N and Xu, H},
title = {A multi-omics investigation of Zuojin Wan in alleviating ulcerative colitis: Involvement of gut microbiota, SCFAs, and serum metabolites.},
journal = {Fitoterapia},
volume = {190},
number = {},
pages = {107135},
doi = {10.1016/j.fitote.2026.107135},
pmid = {41707880},
issn = {1873-6971},
mesh = {Animals ; *Colitis, Ulcerative/drug therapy/microbiology ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Fatty Acids, Volatile/metabolism ; Male ; Multiomics ; *Drugs, Chinese Herbal/pharmacology ; Cytokines/blood ; Disease Models, Animal ; Dysbiosis/drug therapy ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Metabolomics ; Dextran Sulfate ; Colon/pathology/drug effects ; },
abstract = {OBJECTIVE: Ulcerative colitis (UC) involves barrier disruption, dysbiosis, and altered host-microbe metabolism. Zuojin Wan (ZJW) benefits gastrointestinal disorders, but its systems-level mechanisms in UC are unclear.

METHODS: In DSS-induced UC mice, ZJW chemistry was profiled by HPLC-MS, and efficacy was assessed by DAI, colon length, histology, and serum cytokines. Mechanistic assays included 16S sequencing, GC-MS SCFA quantification, serum metabolomics, tight-junction immunohistochemistry, and FMT from ZJW-treated donors.

RESULTS: ZJW reduced DAI, protected colon structure, improved mucosal injury, and decreased IL-6, TNF-α, IL-1β, and IL-18. It corrected dysbiosis with increased beneficial taxa (e.g., Akkermansia), elevated SCFAs-especially propionic and n-pentanoic acids-and remodeled metabolites in glycerophospholipid and aromatic amino-acid pathways. SCFAs correlated with key serum metabolites. ZJW restored Claudin-5 and Occludin localization, and FMT transferred protection to depleted recipients.

CONCLUSIONS: ZJW ameliorates colitis via a microbiota-SCFA-metabolic axis that suppresses inflammation and strengthens tight junctions, supporting its multi-target utility in UC.},
}

Animals
*Colitis, Ulcerative/drug therapy/microbiology
*Gastrointestinal Microbiome/drug effects
Mice
*Fatty Acids, Volatile/metabolism
Male
Multiomics
*Drugs, Chinese Herbal/pharmacology
Cytokines/blood
Disease Models, Animal
Dysbiosis/drug therapy
Mice, Inbred C57BL
Fecal Microbiota Transplantation
Metabolomics
Dextran Sulfate
Colon/pathology/drug effects

@article {pmid42266271,
year = {2026},
author = {Dulay, MS and Chrysostomou, D and Campos, M and Storch, M and Roberts, LA and Dev, DS and Raza, N and Assaf, R and Tan, T and Marber, M and Sharma, R and Lüscher, T and Marchesi, JR and Dar, O},
title = {Investigating the gut microbiota in advanced heart failure and cardiac cachexia.},
journal = {Gut microbes reports},
volume = {3},
number = {1},
pages = {2670244},
pmid = {42266271},
issn = {2993-3935},
abstract = {Cardiac cachexia (CC) is associated with advanced heart failure (AHF), characterized by unintentional weight loss (UWL) of fat/muscle. It is exacerbated by right ventricular systolic dysfunction (RVSD). The potential pathogenic role of gut microbiota (GM) changes has not been investigated in CC. We aimed to explore this. Patients with AHF with or without CC/UWL, stable chronic heart failure (HF), and healthy controls (HCs) were recruited following national ethical approval. Fecal bacterial DNA was extracted, quantified, and 16S rRNA gene sequencing was performed. GM composition, alpha, and beta diversity were compared between CC/UWL-AHF and the rest of the cohort (ROC). The secondary analyses compared AHF, HF, and HCs, and patients with and without RVSD. Sixty-seven patients returned samples, including 14 with CC/UWL-AHF. No taxonomic differences were observed between CC/UWL-AHF and ROC. A weak trend toward compositional differences was observed (beta diversity R[2] = 0.016, p = 0.071). No differences were observed in RVSD. Numerous significant GM alterations were observed across the HF spectrum, including changes to Streptococcus spp., Alistipes, and Bacteroides. CC/UWL-AHF may be associated with subtle GM compositional changes. Larger studies are required to investigate this further.},
}

@article {pmid42266678,
year = {2026},
author = {Rao, X and Zou, L and Cai, X and Yao, Y and Zhong, L},
title = {Microbiome-orchestrated cross-organ immunity in autoimmunity: from metabolites to therapeutic targets.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1761834},
pmid = {42266678},
issn = {1664-3224},
abstract = {Autoimmune diseases are systemic disorders in which barrier-site immune activation, especially in the gut, can reshape inflammatory programs in distant organs. This review advances a metabolite-centered, cross-organ framework for understanding how gut microbial ecology influences autoimmunity beyond individual gut-organ axes. We synthesize evidence that short-chain fatty acids, bile acid derivatives, tryptophan catabolites, polyamines and related microbial products act as mobile biochemical checkpoints linking intestinal barrier integrity, pattern-recognition signaling, immune-cell metabolism and tissue-specific inflammation in joints, kidneys, skin, lungs and the central nervous system. Across these axes, shared mechanisms include barrier failure, altered microbial metabolite pools, dysregulated MAMP sensing, trafficking or systemic conditioning of lymphoid and myeloid cells, and local stromal imprinting in target organs. We also discuss sex-dependent microbiome-immune interactions, including the microgenderome concept, as a framework for explaining why microbiome composition, hormone metabolism and immune responses may shape autoimmune risk and treatment response differently in females and males. Finally, we evaluate multi-omics, single-cell and spatial profiling, organ-on-chip platforms and causal computational tools, and we outline translational strategies ranging from diet, probiotics, fecal microbiota transplantation and engineered consortia to pharmacologic targeting of metabolite receptors. By treating microbial metabolites as actionable cross-organ immune checkpoints, this review highlights opportunities and limitations for biomarker-guided, metabolite-focused precision therapy in autoimmunity.},
}

@article {pmid42266888,
year = {2026},
author = {Mesonero-Cavia, S and Freixas-Bermejo, M and Álvarez-Beltran, M and Redecillas-Ferreiro, S and Cabello-Ruiz, V and Raya-Muñoz, J and Mercadal-Hally, M and Martin-Nalda, A and Segarra-Cantón, O},
title = {De novo Crohn's Disease Treated with Ustekinumab in a Pediatric Liver Transplant Recipient with Tyrosinemia: A Case Report.},
journal = {Case reports in gastroenterology},
volume = {20},
number = {1},
pages = {138-148},
pmid = {42266888},
issn = {1662-0631},
abstract = {INTRODUCTION: De novo inflammatory bowel disease (IBD) is more frequent in transplant recipients than in the general population and should be considered in the differential diagnosis of chronic diarrhea. In pediatric liver transplant recipients, an incidence of 206 vs. 20 cases per 100,000 patient-years has been reported, suggesting an underrecognized complication of immunosuppression.

CASE PRESENTATION: We report an 11-year-old girl with tyrosinemia type 1 who underwent liver transplantation and later developed de novo Crohn's disease. Despite maintenance therapy with tacrolimus, methylprednisolone, and everolimus, she presented with chronic diarrhea, weight loss, and elevated inflammatory markers after several episodes of Clostridioides difficile infection treated with oral vancomycin and only transient improvement. Initial inflammatory markers were only mildly elevated but showed a progressive rise over 18 months despite antibiotic therapy, alongside positive ASCA IgG and ASCA IgA with negative pANCA at the time of formal evaluation. Colonoscopy showed patchy aphthous and serpiginous ulcers with a cobblestone appearance, and histology revealed cryptitis and a mixed lymphoplasmacytic infiltrate without granulomas. Magnetic resonance enterography demonstrated ileocolic inflammation with wall thickening and mesenteric vessel engorgement. Infectious and drug-induced colitis and Epstein-Barr virus-related disease were excluded, and de novo ileocolic Crohn's disease (Paris A1b L3 B1 G1) was diagnosed. Ustekinumab (260 mg intravenously, then 90 mg subcutaneously every 4 weeks) was added to baseline immunosuppression, inducing clinical remission with normalization of C-reactive protein and a decrease in fecal calprotectin to 10 µg/g by week 20, sustained at 18 months with preserved graft function.

CONCLUSION: This case illustrates the diagnostic challenges of de novo Crohn's disease in pediatric liver transplant recipients with metabolic liver disease and supports ustekinumab as a safe and effective option when other biologics are limited by prior infectious or lymphoproliferative.},
}

@article {pmid42267483,
year = {2026},
author = {Sun, Y and Ma, T and Chen, R and Shen, L and Tang, X and Shen, Z and Zhao, H},
title = {Anti-inflammatory and osteogenic effects of transcutaneous electrical nerve stimulation in knee osteoarthritis rats via the regulation of the intestinal microbiota.},
journal = {Animal models and experimental medicine},
volume = {},
number = {},
pages = {},
doi = {10.1002/ame2.70209},
pmid = {42267483},
issn = {2576-2095},
support = {202201AY070001-008/202401AY070001-091/202501AY0001//Joint Foundation of Department of Science and Technology of Yunnan Province/ ; 202302AA310021//Joint Foundation of Department of Science and Technology of Yunnan Province/ ; CYJS-2019-036//Joint Foundation of Department of Science and Technology of Yunnan Province/ ; JG2023001//Joint Foundation of Department of Science and Technology of Yunnan Province/ ; 202501AT070594//Applied Basic Research Foundation of Yunnan Province/ ; },
abstract = {BACKGROUND: This study revealed the function and mechanism of the intestinal microbiota in knee osteoarthritis (KOA) rats treated using transcutaneous electrical nerve stimulation (TENS).

METHODS: KOA model rats were randomly divided into low-/medium-/high-intensity TENS groups, sodium hyaluronate (SH)-positive control group (SH), and model control group (KOA rat). After 1, 2, and 3 weeks of treatment, the improvement in KOA severity was assessed, and the expression of interleukin-1β (IL-1β)/IL-6/IL-8/bone morphogenetic protein 2 (BMP-2)/transforming growth factor β (TGF-β) was analyzed. The diversity of the intestinal microbiota in KOA rats was analyzed via 16S ribosomal DNA (rDNA) sequencing. After fecal microbiota transplantation (FMT), which was induced by TENS, the improvement in the intestinal microbiota in KOA rats was analyzed.

RESULTS: After 3 weeks of treatment using TENS, compared to those in the model control group, the biomechanical parameters increased in the SH and TENS groups (p < 0.05); the gait parameters improved in the SH and TENS groups; the bone mineral density (BMD) increased in the TENS group (p < 0.05); the Mankin scores of the distal femur and proximal tibiofibular muscles decreased in the SH and TENS groups (p < 0.05). IL-1β/6/8 expression levels decreased in the SH and TENS groups (p < 0.05). BMP-2/TGF-β expression in the distal femur increased in the TENS group (p < 0.05). 16S rDNA sequencing revealed that the intestinal microbiota of KOA rats was changed after TENS treatment, including increases in Escherichia-Shigella, Lachnospira, Eubacterium, Gastranaerophilales, and Rikenellaceae RC9 and decreases in Fusicatenibacter and Mycoplasma. After FMT, which is induced by TENS, similar improvements in KOA rats were obtained.

CONCLUSIONS: TENS promoted anti-inflammatory and osteogenic effects by downregulating the Il-1β/6/8 expression levels and upregulating the BMP-2/TGF-β signaling pathway. 16S rDNA sequencing revealed that the intestinal microbiota of KOA rats was changed after TENS treatment via the gut-knee joint axis, and that these dominant genera of FMT elicited improvements in KOA rats. TENS caused improvements in KOA rats by regulating the intestinal microbiota; thus, TENS and induced FMT altered intestinal microbiota suggest a potential novel therapeutic avenue for KOA in clinical settings.},
}

@article {pmid42269582,
year = {2026},
author = {Bian, L and Cai, Y and Zhang, Y and Shen, L and Wang, H and Gao, F and Cai, N and Chen, W and You, C and Yang, Y and Wang, F and Yuan, Y and Han, B and Yao, H},
title = {Microbiota-driven gut-brain signaling underlies antidepressant effects of a GLP-1 analog.},
journal = {Cell host & microbe},
volume = {34},
number = {6},
pages = {1000-1017.e5},
doi = {10.1016/j.chom.2026.05.003},
pmid = {42269582},
issn = {1934-6069},
abstract = {Despite widespread clinical use of glucagon-like peptide-1 receptor (GLP-1R) agonists for metabolic disease, their neuropsychiatric effects remain poorly understood and controversial. Here, we demonstrate that liraglutide alleviates depression through a gut-brain pathway that operates independently of GLP-1R. Using both pharmacological and genetic approaches, we demonstrated that liraglutide retained antidepressant efficacy in GLP-1R antagonist-Exn9-treated mice or in Glp1r[-/-] mice, whereas gut microbiota depletion abolished its effects. Multi-omics analyses revealed that liraglutide increased the abundance of Lactobacillus delbrueckii, which in turn restored the levels of the endocannabinoid 2-arachidonoylglycerol (2-AG). The elevation of 2-AG mediated the antidepressant effects by normalizing excessive neuronal activity in emotional processing brain regions. Importantly, fecal microbiota transplantation from liraglutide-treated mice or Lactobacillus delbrueckii colonization replicated the antidepressant effects. These findings uncover a non-canonical mechanism of action for GLP-1 analogs, highlighting a specific microbiota-endocannabinoid metabolic pathway as a potential therapeutic target for depression.},
}

@article {pmid42269666,
year = {2026},
author = {Dewey, CW and Rojas, CA and Pomeroy, C and Gerardi, J and Ganz, HH},
title = {Fecal microbiota transplantation shows promise in slowing or reducing cognitive impairment in aging dogs.},
journal = {Journal of the American Veterinary Medical Association},
volume = {},
number = {},
pages = {1-6},
doi = {10.2460/javma.26.03.0231},
pmid = {42269666},
issn = {1943-569X},
abstract = {OBJECTIVE: To investigate potential effects of fecal microbiota transplantation (FMT) on cognitive scores and bacterial microbiota composition in dogs with suspected canine cognitive dysfunction (CCD).

METHODS: The study was conducted from September 19, 2024, to September 11, 2025. Dogs with presumptive CCD were given oral FMT capsules daily for 90 days. Each dog received 1 FMT capsule every 12 hours. Fecal samples and cognitive (disorientation, impaired social interactions, sleep disturbance, house soiling, learning and memory loss, activity changes, and anxiety and fear [DISHAA]) assessments were completed at baseline and on days 30, 60, and 90. Fecal samples were submitted for 16S rRNA gene sequencing.

RESULTS: 11 dogs were enrolled; 10 dogs had no adverse events from FMT treatment, and 1 dog developed gastrointestinal signs and was removed from the study. All 10 remaining dogs had complete microbiome data; however, owners of 4 dogs did not report final (90-day) DISHAA scores. Of the 6 dogs with complete data, cognition improved in 4 (mean, -8.25 points) but worsened in 2 (mean, +7 points) according to owner-reported DISHAA scores. Microbiome richness and diversity increased in 4 of the 6 dogs. Several dogs also showed positive modulation of microbiome composition including reductions in Streptococcus spp and increases in Peptacetobacter hiranonis, Prevotella copri, and Bacteroides spp.

CONCLUSIONS: These findings provided preliminary evidence that FMT may help improve cognitive function in dogs with CCD. However, the study sample size was small and ideal FMT dosing level and treatment duration remain undefined. A larger study with longer follow-up is warranted, based on our results.

CLINICAL RELEVANCE: FMT showed promise in slowing or reducing cognitive impairment in aging dogs and may be considered as adjunct therapy in these cases.},
}

@article {pmid42270269,
year = {2026},
author = {Wang, X and Zhang, J and Wang, Y and Zhou, Y and Xu, H},
title = {Lactobacillus reduction drives oxidative gut-liver adverse effects of heterogeneous aggregates polylactic acid nanoplastics and silica nanoparticles.},
journal = {Food research international (Ottawa, Ont.)},
volume = {239},
number = {},
pages = {119558},
doi = {10.1016/j.foodres.2026.119558},
pmid = {42270269},
issn = {1873-7145},
abstract = {Polylactic acid (PLA) plastics are increasingly used in food packaging as biodegradable substitute to petroleum-based plastics. However, the high temperatures used to reconstitute powdered foods, which often contain silica nanoparticles (SiNPs), readily induce PLA degradation, generating large amounts of PLA nanoplastics (PLA NPs). Due to the high affinity of PLA NPs to contaminants, this study investigated the interactions between PLA NPs and SiNPs, and their gut-liver adverse effects. Following the oral administration of PLA NPs and SiNPs to C57BL/6J male mice for 90 days, liver, colon, blood, and fecal samples were collected to assess liver damage, gut function and microbiota composition. The results showed that PLA NPs and SiNPs formed heterogeneous aggregates complexes (HAC), resulting in different hydrodynamic size and zeta potential. Compared with PLA NPs or SiNPs, HAC induced more severe hepatic and intestinal injuries and further disrupted gut microbial homeostasis. In the fecal microbiota transplantation and key bacteria supplementation experiments, liver oxidative stress induced by HAC was partly attributed to gut dysbiosis and the reduced abundance of Lactobacillus. In conclusion, HAC exhibited different physicochemical and toxicological properties than single contaminant, and oxidative stress is the key factor in gut-liver adverse effects. These findings uncover the potential interactions among contaminants and their combined adverse effects, and provided a new perspective for risk assessment process related to food contaminant exposure.},
}

@article {pmid42270545,
year = {2026},
author = {Louvet, A and Ntandja Wandji, LC and Mathurin, P},
title = {Updates in clinical science: Alcohol-related hepatitis.},
journal = {Journal of hepatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jhep.2026.04.016},
pmid = {42270545},
issn = {1600-0641},
abstract = {Alcohol-related hepatitis (AH) is a complex disease associated with numerous unmet needs, particularly in diagnosis and treatment. The epidemiology of AH has evolved in recent years, reflecting changes in alcohol consumption during the COVID-19 pandemic and the increasing incidence of AH following bariatric surgery. Advances have also been made in the non-invasive diagnosis of AH, helping to reduce the need for liver biopsy, as well as in the management of infection. Several novel therapeutic strategies have been evaluated, including faecal microbiota transplantation, IL-1 receptor antagonists, oxysterols, and reduced exposure to corticosteroids or antibiotics. Although the results of these trials have been relatively disappointing, they have helped identify promising directions for future research. In patients with the most severe form of AH, particularly those who do not respond to corticosteroids, several studies have suggested that the indications for early liver transplantation could be expanded. Overall, developments over recent years have generated increased optimism regarding the management of patients with severe AH.},
}

@article {pmid42271360,
year = {2026},
author = {Chen, Y and Kang, H and Yang, B and Feng, L and Tong, R and Zhao, Z and Liang, L and Li, X and Liu, X and Tong, Z},
title = {Gut mycobiota alteration contributes to the pathogenesis of Pneumocystis pneumonia.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08153-7},
pmid = {42271360},
issn = {1479-5876},
abstract = {BACKGROUND: Pneumocystis is an opportunistic fungal pathogen that causes life-threatening pneumonia in immunocompromised hosts, with increasing incidence in HIV-negative individuals. Although the gut mycobiota has emerged as a critical regulator of distal immunity, its role in HIV-negative Pneumocystis pneumonia (PCP) remains entirely unexplored.

METHODS: We established a murine model of Pneumocystis murina infection and performed full-length internal transcribed spacer (ITS) sequencing to characterize longitudinal changes in gut fungal communities over five weeks. Untargeted metabolomics was conducted on plasma samples to identify systemic metabolic alterations. To investigate causality, gut fungal communities were depleted using fluconazole, and fecal microbiota transplantation (FMT) was performed in germ-free mice to assess the functional role of gut fungi in modulating pulmonary immune responses.

RESULTS: While α diversity of the gut mycobiota remained unchanged, β diversity analysis revealed significant structural alterations beginning week 3 (w3) post-infection, coinciding with peak pulmonary fungal burden. Linear discriminant analysis effect size identified Purpureocillium lilacinum and Talaromyces verruculosus as enriched opportunistic taxa. Untargeted metabolomics demonstrated marked metabolic reprogramming at w3, with significant perturbations in glycine, serine, and threonine metabolism, as well as the tricarboxylic acid cycle. Fluconazole-mediated depletion of gut fungi significantly increased pulmonary Pneumocystis burden and exacerbated lung inflammation, accompanied by reduced pulmonary Th1 cell responses. Critically, FMT from fluconazole-treated donors into germ-free mice recapitulated the exacerbated phenotype, confirming that gut fungal dysbiosis is sufficient to impair Th1-mediated antifungal immunity and worsen disease severity.

CONCLUSIONS: This study establishes, for the first time, that gut fungal dysbiosis actively contributes to the pathogenesis of HIV-negative PCP via the gut-lung axis. Our findings reveal that commensal gut fungi support pulmonary Th1 immune responses essential for controlling PCP, and their disruption exacerbates disease. These results provide new insights into the gut mycobiota as a potential therapeutic target in PCP and caution against indiscriminate antifungal use in susceptible populations.},
}

@article {pmid42260668,
year = {2026},
author = {Wang, Y and Ren, C and Dong, W and Li, Q and Deng, F and Zhao, F and Cheng, Y and Sun, P and Li, H and Wang, Y},
title = {Polygala oligosaccharide esters improve memory disorder by restoring gut microbiota homeostasis through the regulation of the "gut-brain" axis.},
journal = {Chinese medicine},
volume = {21},
number = {1},
pages = {},
pmid = {42260668},
issn = {1749-8546},
support = {[2024SJ327]//the Graduate Practice and Innovation Project of Shanxi Provincial Education Department, China/ ; [X2024SJ017]//the Graduate Innovation and Practice Project of Shanxi University of Chinese Medicine, China/ ; [2023ZYYB2017]//The Shanxi Administration of Traditional Chinese Medicine,China/ ; [2023PY-TH-03]//the Taihang Materia Medica Research and Development Guidance Special Project, China/ ; [2025XK36]//The Traditional Chinese Medicine Pharmacology and Toxicology Discipline Construction Project of Shanxi University of Chinese Medicine,China/ ; [2021-143]//Shanxi Scholarship Council of China/ ; },
abstract = {BACKGROUND: Yuanzhi (Polygala tenuifolia Willd.) possesses the effects of calming the spirit, enhancing intelligence, regulating the heart-kidney connection, eliminating phlegm, and reducing swelling. It is commonly used in the treatment of insomnia and forgetfulness. Previous studies have indicated that the oligosaccharide esters (OE) derived from Yuanzhi exhibit neuroprotective and memory-enhancing activities. However, its underlying mechanisms, particularly those involving the gut-brain axis, remain unclear.

PURPOSE OF THE RESEARCH: This study aimed to investigate the therapeutic efficacy and underlying mechanisms of Oligosaccharide Esters (OE) from Polygala tenuifolia Willd. against memory dysfunction in mice, with a specific focus on the gut-brain axis.

METHODS: A mouse model of memory dysfunction was induced using D-galactose combined with AlCl₃. Behavioral tests, molecular biology techniques (histopathology, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and Western blot), and multi-omics approaches (16S rRNA sequencing and lipidomic analysis) were employed to investigate the therapeutic efficacy of OE against memory dysfunction. Meanwhile, with the aid of fecal microbiota transplantation (FMT) assay, we observed the repair of brain and colonic tissues, inflammatory responses and intestinal permeability, further clarified the regulatory effect of OE on gut microbiota, and ultimately revealed the underlying mechanisms of OE mediated by the gut-brain axis.

RESULTS: OE administration significantly enhanced learning and memory in MD mice, repaired neuronal damage in the hippocampal regions (CA1, CA3, DG) of the MD mouse brain, and increased the number of Nissl bodies. OE elevated the serum levels of BDNF and CREB and reduced the TMAO level; simultaneously, it enhanced the activities of SOD and GSH-Px and decreased the MDA content in the brain tissue. OE treatment modulated the relative abundance of the gut microbiota in MD mice, restored the microbial imbalance induced by memory deficits, and particularly affected the abundances of Firmicutes, Bacteroidetes, their ratio (F/B), and genera such as Ligilactobacillus. Lipidomics analysis indicated that OE exerts its therapeutic effects primarily by regulating the glycerophospholipid metabolism pathway, and a total of 17 key differential lipid metabolites were identified. Correlation analysis further revealed that the levels of key differential lipid metabolites, LysoPC(22:2) and PC(38:4), were significantly positively correlated with the levels of neuroprotective factors (CREB, BDNF) and the activities of antioxidant enzymes (SOD, GSH-Px), but were significantly negatively correlated with the harmful metabolite TMAO and the oxidative damage product MDA. In contrast, the lipid metabolite GPEA exhibited a trend opposite to that of LysoPC(22:2) and PC(38:4). Further investigation results demonstrated that OE could repair pathological damage in colon tissue, regulate the levels of the microbial metabolite TMAO and the neurotransmitter 5-HT, reduce the levels of pro-inflammatory factors (LPS, TNF-α, IL-6) in both the brain and colon, and inhibit the abnormal activation of astrocytes and the abnormal hyperphosphorylation of Tau protein. The results of correlation analysis indicated that beneficial bacteria [e.g., Ligilactobacillus) and beneficial lipids (e.g., LysoPC(22:2) and PC(38:4)] were collectively significantly negatively correlated with key pathological indicators (e.g., TMAO and TNF-α) and were positively correlated with the neurotransmitter (e.g., 5-HT). OE also significantly up-regulated the expression of tight junction proteins (Occludin, Claudin-5) in both brain and colon tissues, thereby structurally repairing the damaged gut-brain barrier. FMT experiments showed that FMT improved the learning and memory abilities of mice, repaired neuronal damage in the hippocampus (CA1, CA3, DG), and increased the number of Nissl bodies. In addition, FMT alleviated colonic tissue injury, attenuated inflammatory responses in the brain and colon, and reduced intestinal permeability in MD mice, exerting a therapeutic effect similar to that of OE.

CONCLUSION: OE exerted anti-amnestic effects via the gut-brain axis, primarily by alleviating neuroinflammation and oxidative stress, restoring gut microbiota homeostasis, and regulating glycerophospholipid metabolism, ultimately improving learning and memory abilities in MD mice.},
}

@article {pmid42261357,
year = {2026},
author = {Zhu, Q and Liu, Y and Hu, W and Liu, Y and Fu, S and Xie, W and Liu, J and Xiong, Y and Sun, T and Gong, B},
title = {Lactobacillus johnsonii-Derived Extracellular Vesicles Ameliorate Alcohol-Exacerbated Experimental Autoimmune Prostatitis by Inhibiting M1 Macrophage Polarization.},
journal = {International journal of nanomedicine},
volume = {21},
number = {},
pages = {596237},
pmid = {42261357},
issn = {1178-2013},
abstract = {PURPOSE: This study investigated how alcohol exacerbated chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and assessed gut microbiota-targeted therapeutic strategies.

METHODS: An alcohol‑treated experimental autoimmune prostatitis (EAP) mouse model was established to evaluate the exacerbating effect of alcohol on CP/CPPS. The involvement of gut microbiota was assessed by antibiotic depletion and fecal microbiota transplantation (FMT). 16S rRNA sequencing was applied to profile microbial alterations, particularly the abundance of Lactobacillus johnsonii (L. john). Oral administration of live L. john or intravenous injection of Lactobacillus johnsonii-derived extracellular vesicles (LjEVs) was tested as therapeutic interventions. Mechanistic studies were conducted in lipopolysaccharide (LPS)‑stimulated RAW 264.7 macrophages using transcriptomics, qRT-PCR, Western blot, and flow cytometry.

RESULTS: Alcohol consumption aggravated pelvic tactile hypersensitivity and prostatic inflammation, increased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and promoted M1 macrophage polarization in EAP mice. Fecal microbiota transplantation from alcohol-fed EAP mice reproduced the aggravated phenotype, confirming that gut microbiota mediates this effect. Alcohol specifically reduced the relative abundance of L. john. Oral L. john or intravenous LjEVs alleviated tactile hypersensitivity and inflammation, and inhibited M1 macrophage polarization in alcohol-fed EAP mice. In vitro, LjEVs were internalized by macrophages, suppressed LPS-induced M1 macrophage polarization and pro-inflammatory gene expression, and inhibited TNF-α/NF-κB signaling. Exogenous TNF-α reversed the inhibitory effects of LjEVs on M1 macrophage polarization.

CONCLUSION: Alcohol exacerbated EAP by reducing L. john, which in turn promoted prostatic M1 macrophage polarization via the TNF-α/NF-κB pathway. Supplementation with L. john or LjEVs ameliorated the disease by suppressing this pathway, offering a microbiota-targeted therapy for alcohol-aggravated CP/CPPS.},
}

@article {pmid42262096,
year = {2026},
author = {Li, G and Li, L and Shen, P and Wang, J and Feng, Y and Yu, Y and Xu, H and Wang, H and Li, J and Zheng, X and Mao, Y},
title = {Harmane induces apoptosis through RRM2B and suppresses colorectal cancer progression.},
journal = {mSystems},
volume = {},
number = {},
pages = {e0170425},
doi = {10.1128/msystems.01704-25},
pmid = {42262096},
issn = {2379-5077},
abstract = {Colorectal cancer (CRC) is a common malignant tumor of the digestive system, and chemotherapy resistance often leads to poor patient prognosis. Harmane, a natural indole alkaloid, is found in Leguminosae plants (particularly those of the Crotalaria genus), as well as in mammalian tissues and certain food products. It exhibits potential anticancer activities through multiple mechanisms in various cancers, including liver, breast, and thyroid cancers. However, the role of harmane in the treatment of CRC remains unclear. In this study, we demonstrate that harmane induces cell cycle arrest and apoptosis in CRC cells via the p53-RRM2B axis. Furthermore, at the level of the gut microbiota, harmane reshapes microbial composition, thereby contributing to its anti-tumor effects.IMPORTANCEThis study is the first to demonstrate a progressive decline of harmane levels in the gut from healthy individuals to advanced adenoma and CRC patients, suggesting its potential protective role in CRC development. We further found that harmane promotes CRC cell apoptosis via RRM2B-mediated regulation, revealing the underlying molecular mechanism. Moreover, in vivo experiments showed that harmane can modulate gut microbial composition and its derived metabolites, and fecal microbiota transplantation experiments indicated that harmane exerts anticancer effects by regulating both the gut microbiota and microbial metabolites. This study proposes a novel therapeutic strategy for CRC, highlighting the importance of incorporating gut microbiota modulation into cancer treatment.},
}

@article {pmid42262109,
year = {2026},
author = {Mehta, N and Hvas, CL},
title = {Revisiting Cost-Effectiveness of Commercial or Traditional Fecal Microbiota Transplantation to Prevent C. difficile Recurrence.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciag264},
pmid = {42262109},
issn = {1537-6591},
support = {NNF22OC0074080//Novo Nordisk Foundation/ ; },
}

@article {pmid42264080,
year = {2026},
author = {Abdullah, M and Jayadevan, K and Therayil, A and Kumaraguruparan, N and Kavyasree, PKV and Dilna, P and Faiza, A},
title = {Pharmaco-microdynamics (PMD): Redefining Dose, Exposure, and Control for Living Drug Carriers.},
journal = {Annales pharmaceutiques francaises},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.pharma.2026.06.002},
pmid = {42264080},
issn = {2772-803X},
abstract = {Living drug delivery systems including probiotics, engineered microbial therapeutics, and live biotherapeutic products represent a rapidly emerging therapeutic modality whose behavior fundamentally diverges from the assumptions underlying classical pharmacokinetics and pharmacodynamics (PK/PD). Unlike chemically defined, non-replicating drugs, living therapeutics persist, replicate, adapt, and generate bioactive molecules in situ, such that therapeutic exposure is not externally imposed but biologically generated over time. As a result, administered dose functions only as an initiating condition, while realized exposure emerges from population dynamics, ecological establishment, spatial localization, and regulated functional output. These properties render concentration-based PK/PD frameworks insufficient for predicting efficacy, safety, and controllability of living drug carriers. We introduce pharmaco-microdynamics (PMD) as a quantitative delivery-science framework designed to define, measure, and control exposure for living therapeutics. PMD is operationalized through a set of formal metrics including the functional exposure integral (F-AUC), colonization efficiency (CE), residence-time-weighted activity (RTWA), effective functional concentration (EFC50), and the genetic stability index (GSI)that serve as living-system analogues of AUC, bioavailability, mean residence time, EC50, and product-identity specifications. PMD reconceptualizes exposure as a time-integrated biological process governed by four interdependent axes: population kinetics, functional output kinetics, spatial pharmacology, and evolutionary dynamics. By integrating principles from pharmacology, microbial ecology, synthetic biology, biomaterials science, and systems modeling, PMD provides an operational vocabulary for translating adaptive biological agents into predictable and engineerable delivery systems. We further delineate PMD from adjacent frameworks such as quantitative systems pharmacology (QSP) and ecological microbiome modeling, and critically discuss boundary conditions under which classical PK/PD remains applicable to non-replicating or transient microbial interventions. This review critically examines the limitations of classical PK/PD in modeling living drug carriers, formalizes the core principles of PMD, and illustrates them through three quantitative case studies: SYNB1618 for phenylketonuria, synchronized-lysis bacterial tumor therapies, and fecal microbiota transplantation for recurrent Clostridioides difficile infection. Regulatory and clinical implications are addressed, emphasizing the need to shift from dose- and concentration-centric evaluation toward functional biomarkers, persistence metrics, and model-informed assessment of biological activity. Collectively, pharmaco-microdynamics establishes a unifying conceptual and quantitative foundation for the rational development of living medicines.},
}

@article {pmid42264216,
year = {2026},
author = {Guo, L and Li, J and An, J and Miao, J and Yi, Y and Zhu, K and Cai, Q and Wang, S and Su, Z and Ye, X and Wang, Y and Pan, M and Lu, Q and Cui, B and Zhang, F and Mao, J and Liu, X and Lu, Y and Ding, D},
title = {Neuroprotective role of Faecalibacterium prausnitzii-derived butyrate in diabetic gastrointestinal autonomic neuropathy.},
journal = {Journal of genetics and genomics = Yi chuan xue bao},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jgg.2026.06.005},
pmid = {42264216},
issn = {1673-8527},
abstract = {Diabetic gastrointestinal autonomic neuropathy (DGAN) is a common yet poorly understood complication of diabetes that is characterized by gastrointestinal dysmotility and enteric neurodegeneration. Here, we investigate whether gut microbiota dysbiosis contributes to DGAN pathogenesis and explore the potential involvement of microbiota-derived metabolites in enteric nervous system (ENS) injury. Gut microbiota profiling reveals disease-associated compositional alterations in patients with DGAN, including depletion of Faecalibacterium-associated signals, with Faecalibacterium prausnitzii identified as a putative species-level annotation and negatively associated with gastrointestinal symptom severity. Fecal microbiota transplantation from patients with DGAN into db/db mice aggravates gut dysmotility and increases apoptosis of ChAT[+] and nNOS[+] myenteric neurons. Further experiments indicate that butyrate, the predominant metabolite produced by F. prausnitzii, attenuates neuronal apoptosis under high-glucose conditions. This biological process is accompanied by enhanced BCL2 expression, downregulation of cleaved caspase-3, and activation of the PI3K/Akt signaling cascade. Collectively, our findings support the presence of a gut microbiota-ENS axis in DGAN and identify butyrate as an important candidate neuroprotective metabolite associated with F. prausnitzii. These results provide a rationale for microbiota-targeted therapeutic strategies for diabetic enteric neuropathy.},
}

@article {pmid42266133,
year = {2026},
author = {Duggar, M and Leardini, D and Muratore, E and Margolis, EB and Masetti, R},
title = {Gut Microbiome-Immune Interactions During Pediatric Hematopoietic Cell Transplantation: From Conditioning to GvHD Prevention.},
journal = {Pediatric transplantation},
volume = {30},
number = {6},
pages = {e70371},
doi = {10.1111/petr.70371},
pmid = {42266133},
issn = {1399-3046},
abstract = {Hematopoietic stem cell transplantation (HCT) offers curative potential for children with high-risk hematologic malignancies. However, this treatment carries significant risks, particularly acute graft-versus-host disease (aGvHD), which affects 30%-60% of pediatric recipients and causes 15%-20% of post-transplant deaths. The gut microbiome has emerged as a critical factor in aGvHD development, yet pediatric microbiome dynamics differ substantially from adult patterns. This review seeks to evaluate the current state of knowledge of how the gut microbiome impacts aGvHD pathogenesis and the methods of microbiome modulation that may lead to aGvHD prevention and treatment. Children's microbiomes undergo more rapid compositional shifts and contain distinct bacterial compositions enriched in taxa like Bifidobacterium and Lactobacillus. During transplant, conditioning regimens and antibiotics cause dramatic microbiome disruption in children. This eliminates beneficial bacteria that normally maintain intestinal barrier integrity and produce immunomodulatory metabolites. Consequently, this disruption triggers inflammatory cascades through bacterial translocation, impaired immune education, and altered metabolite production. Unlike adults, where low diversity consistently predicts poor outcomes, pediatric studies show inconsistent diversity-outcome relationships, with only pre-transplant microbiome patterns reliably predicting aGvHD risk. Several promising interventions have emerged from this research. These include enteral nutrition to preserve beneficial bacteria, targeted antibiotic strategies, and fecal microbiota transplantation. Fecal microbiota transplantation has shown remarkable response rates in pediatric steroid-resistant aGvHD cases. Nevertheless, significant knowledge gaps remain regarding pediatric-specific mechanisms, optimal biomarkers, and age-appropriate therapeutic approaches for microbiome-directed aGvHD prevention.},
}

@article {pmid42258310,
year = {2026},
author = {Mehboob, AA and Fatima, R and Kanwal, S and Ali, M and Karim, M and Fatima, S},
title = {Exploring the gut-lung axis in post-liver transplant acute lung injury: A multi-omics approach.},
journal = {Acta microbiologica et immunologica Hungarica},
volume = {},
number = {},
pages = {},
doi = {10.1556/030.2026.02911},
pmid = {42258310},
issn = {1588-2640},
abstract = {Acute lung injury (ALI) is a significant post-operative complication of liver transplant (LT), with mounting evidence suggesting a role for the gut-lung axis. However, the mechanistic link between gut microbiota dysbiosis and ALI pathogenesis in LT recipients remains poorly understood. This hybrid translational investigation integrates transcriptomic profiling (bulk and single-cell RNA-seq), immune infiltration analysis, fecal microbiota composition (16S rRNA), and predictive functional profiling in ALI vs. non-ALI (NALI) LT patients. Machine learning algorithms (LASSO, SVM-RFE, Random Forest) were used to identify key gene biomarkers. Microbiota-host gene correlations and canonical correspondence analysis (CCA) were performed to evaluate multi-omic relationships. ALI patients exhibited reduced gut microbial diversity and increased abundance of Enterococcus and Escherichia-Shigella, alongside a depletion of beneficial taxa (Faecalibacterium, Bacteroides). CXCL3, CD48, and IRAK3 were identified as robust ALI biomarkers (Area Under the Curve >0.83), validated in both serum and Bronchoalveolar Lavage Fluid. These genes correlated positively with pro-inflammatory microbes and immune cell infiltration. Functional prediction revealed enrichment in lipopolysaccharide biosynthesis, Toll-like receptor signaling, and bacterial chemotaxis. CCA confirmed that microbiota variation significantly explained host transcriptomic variance. Our study uncovers a functional gut-lung immunological axis in post-LT ALI. Gut dysbiosis modulates immune gene expression and lung inflammation, suggesting that the microbiome serves as a potential source of diagnostic biomarkers and therapeutic targets in transplant-associated lung injury.},
}

@article {pmid42259000,
year = {2026},
author = {Wen, S and Shi, M and He, S and Zhu, Y},
title = {Gut microbiota in blood pressure control: Friend or foe?.},
journal = {Microbiological research},
volume = {311},
number = {},
pages = {128571},
doi = {10.1016/j.micres.2026.128571},
pmid = {42259000},
issn = {1618-0623},
abstract = {Hypertension is a major global public health issue characterized by complex pathogenesis and a high risk of multiple comorbidities. Gut microbes play a crucial role in blood pressure regulation. This review aims to clarify the roles of distinct gut microbiota compositions in regulating blood pressure and to analyze their potential mechanisms of action in hypertension. Gut microbes produce metabolites that regulate the host immune system, metabolic homeostasis, and other physiological processes, including blood pressure. Key microbial metabolites, such as short-chain fatty acids (SCFAs) and trimethylamine N-oxide (TMAO), have been shown to regulate blood pressure through complex mechanisms. Hypertension disrupts intestinal barrier integrity, allowing inflammatory factors and noxious substances to enter the circulation, creating a vicious cycle between hypertension and gut dysregulation and possibly even inducing other diseases. Current strategies targeting gut microbiota for blood pressure control include fecal microbiota transplantation (FMT) and probiotic supplementation, but further clinical validation of their efficacy and safety is required. In conclusion, the relationship between gut microorganisms and hypertension is intricate and context-dependent, rather than being simply classified as entirely beneficial or detrimental. Future studies should further elucidate the mechanisms of various gut microorganisms regulating blood pressure and explore safer and more effective therapeutic strategies.},
}

@article {pmid42259432,
year = {2026},
author = {Hao, L and Li, ZF and Qu, YN and Zhao, FY and Lu, SY and Li, BQ and Zhang, HY and Wang, HQ},
title = {IUPHAR review. Gut Microbial Metabolites as Remote Regulators of Behavior and Neuropsychiatric Disease.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {108284},
doi = {10.1016/j.phrs.2026.108284},
pmid = {42259432},
issn = {1096-1186},
abstract = {The gut-brain axis has emerged as a fundamental pathway through which gut-derived microbial metabolites exert remote control over brain development, neural circuit function and behavior. This Review synthesizes evidence that key microbial metabolites including short-chain fatty acids, tryptophan derivatives, bile acids and trimethylamine N-oxide modulate neuroimmune, neuroendocrine and synaptic signaling in a context-dependent manner, influencing whether the brain maintains homeostasis or progresses toward pathology. We critically evaluate how these metabolites contribute to the etiology and symptomatology of neurodevelopmental and psychiatric disorders such as autism spectrum disorder, major depressive disorder, anxiety and post-traumatic stress disorder. Causal insights are highlighted by studies demonstrating that fecal microbiota transplantation from affected individuals to rodents transfers core behavioral phenotypes. It is important to note, however, that while FMT and gnotobiotic studies establish causality in animal models, evidence from human studies remains predominantly correlative, and we have explicitly distinguished these evidence tiers throughout. We also explore the translational potential of microbiome-derived biomarkers for diagnosis and the challenges in developing targeted therapeutics, including probiotics, postbiotics and metabolite-sequestering agents. Moving forward, the field should prioritize decoding the contextual determinants of microbial influence and adopt personalized, function-based strategies to effectively modulate the gut-brain metabolic axis for brain health.},
}

@article {pmid42259828,
year = {2026},
author = {Yang, X and Li, X and Xu, D and Feng, Y and Guo, Y and Hu, Y},
title = {Faecalibacterium-derived spermidine mediates the amelioration of fatty liver hemorrhagic syndrome by inulin in laying hens.},
journal = {NPJ biofilms and microbiomes},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41522-026-01037-0},
pmid = {42259828},
issn = {2055-5008},
support = {32402778//National Natural Science Foundation of China/ ; 32372824//National Natural Science Foundation of China/ ; 2022YFA1304201//National Key Research and Development Program of China/ ; 2023TZXD037//Shandong Provincial Key Research and Development Program of China/ ; },
abstract = {Fatty liver hemorrhagic syndrome (FLHS) is a critical disease threatening the laying hen industry. Inulin, a widely used prebiotic, has shown promise in alleviating metabolic disorders, but its role in mitigating FLHS in laying hens is not fully understood. Here, we investigated the effects and underlying mechanisms of inulin-mediated alleviation of FLHS in a high-carbohydrate low-protein diet (HCD)-induced laying hen model. We found that inulin supplementation significantly ameliorated HCD-induced hyperlipidemia, hyperglycemia, hepatic steatosis, liver injury, and oxidative stress. These phenotypic improvements were accompanied by enhanced fatty acid oxidation and suppressed lipid synthesis and inflammation. Microbiota analysis revealed that inulin reshaped the HCD-perturbed cecal microbiota, with Faecalibacterium identified as the only dominant genus substantially depleted by HCD and restored by inulin. Targeted metabolomics showed that inulin elevated cecal spermidine levels, which strongly correlated with Faecalibacterium abundance and improved metabolic traits. Fecal microbiota transplantation (FMT) from inulin-treated donors replicated the protective effects, confirming the causal role of gut microbiota in mediating inulin's anti-FLHS activity. Further mechanistic investigation using the representative species Faecalibacterium prausnitzii demonstrated that inulin enhanced spermidine production through transcriptional activation of the spermidine biosynthetic pathway. Spermidine, in turn, upregulated hepatic ALDH1A2 expression, enhancing retinoic acid synthesis and activating the AMPK-SIRT1 axis, thereby reducing lipid accumulation in hepatocytes. Collectively, these findings establish a novel Faecalibacterium-spermidine-ALDH1A2-retinoic acid-AMPK-SIRT1 axis through which inulin alleviates FLHS, highlighting inulin as a dietary intervention targeting the gut-liver axis and offering novel therapeutic avenues for preventing this disorder in laying hens.},
}

@article {pmid42260597,
year = {2026},
author = {Rynikova, M and Gancarcikova, S and Lauko, S and Mudronova, D and Adamkova, P and Janicko, M and Demeckova, V},
title = {Exploring new animal models of ulcerative colitis: evaluating chemical and patient-derived microbial triggers to advance translational relevance.},
journal = {Laboratory animal research},
volume = {42},
number = {1},
pages = {},
pmid = {42260597},
issn = {1738-6055},
abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with multifactorial aetiology involving genetic, immune, environmental, and microbial factors. Alterations in the gut microbiome are a consistent feature of UC, yet their causal contribution to disease onset and progression remains unresolved. Current animal models rely largely on chemical or genetic induction and fail to capture the complexity of host-microbiome interactions characteristic of human disease. To address this limitation and enhance the translational relevance of preclinical research, this study employed patient-derived microbiota to model UC-associated dysbiosis and investigated its effects alone and in combination with chemical induction.

RESULTS: We compared three mouse models using different UC-induction triggers: dextran sulphate sodium (DSS), faecal microbiota transplantation (FMT) from a UC patient, and their combination (COMB). DSS and COMB treatments induced marked clinical symptoms, whereas FMT alone caused only mild changes, likely due to the short exposure period. Immunophenotyping revealed distinct immune profiles across all models, with leukocyte and neutrophil infiltration in the colonic mucosa of all groups, demonstrating that the microbiota alone can elicit localized immune activation. Transcriptomic analysis showed that FMT significantly modulated tight junction and mucin gene expression and induced microbiome shifts resembling those observed in human UC. In contrast, DSS triggered a strong pro-inflammatory transcriptional response and reduced microbial diversity, but with compositional changes mostly opposing those seen in UC patients. The COMB model combined features of both approaches - producing clinical symptoms and inflammatory activation similar to DSS and tight junction dysregulation resembling FMT.

CONCLUSIONS: This study investigated novel experimental models of ulcerative colitis by incorporating patient-derived microbiota as an inducing factor. DSS induced strong clinical and inflammatory responses, FMT primarily altered barrier gene expression and microbiome composition, and their combination merged both inflammatory and epithelial characteristics. These microbiota-based models show promise for more accurately reproducing UC pathophysiology and thereby improving translational relevance. Further optimization is needed, including adjustment of exposure duration and sequence of induction, as well as validation for reproducibility.},
}

@article {pmid42249511,
year = {2026},
author = {Stahl, S and Widmaier, H and Sakk, V and Nalapareddy, K and Kissmann, AK and Rosenau, F and Mulaw, MA and Haslam, DB and Geiger, H},
title = {Aging of the adaptive immune system affects the gut microbiome and systemic levels of vitamin B6.},
journal = {Microbiome},
volume = {14},
number = {1},
pages = {},
pmid = {42249511},
issn = {2049-2618},
support = {GRK 2254 HEIST//Deutsche Forschungsgemeinschaft/ ; },
abstract = {BACKGROUND: Age-associated dysregulation of the gut microbiota is a hallmark of aging and has been linked to multiple age-related diseases, yet upstream host factors driving these changes remain incompletely defined. Extensive bidirectional crosstalk between gut microbiota and mucosal immunity has been described. Aging is accompanied by a progressive decline in immune function, collectively termed aging-associated immune remodeling (AAIR). AAIR encompasses widespread compositional and functional changes that impair an effective response to pathogens, vaccines, and tissue damage. We examined whether AAIR is an upstream host factor influencing the composition of the microbiome upon aging.

RESULTS: Hallmarks of AAIR were also present in the ileal lamina propria, including reduced naïve CD4[+] and CD8[+] T cell populations and expansion of memory and regulatory T cell subsets. To test whether mucosal AAIR reflects intrinsic aging of the hematopoietic system, we used an HSC transplantation model where young RAG1[-/-] recipients develop an adaptive immune system derived exclusively from either young or aged donor HSC in an otherwise young host environment. Recipients of aged HSCs recapitulated key features of mucosal AAIR, particularly loss of naïve T cells, demonstrating that AAIR in the ileal LP is driven at least in part by aged HSCs. Shotgun metagenomic sequencing of fecal samples revealed that ileal AAIR is associated with alterations in gut microbiota. In detail, there was a reduced abundance of taxa associated with the vitamin B6 (VB6) biosynthesis and salvage pathways. Accordingly, VB6 levels in serum were reduced in mice with aged immune systems.

CONCLUSION: Our findings link AAIR to reduced microbial VB6 pathway abundance and lower systemic VB6 availability, suggesting that immune aging shapes the functional output of the microbiome in ways that diminish its VB6 biosynthetic capacity. This postulates an immune-microbiome-VB6 association that warrants further investigations for therapeutic strategies to increase VB6 levels upon aging. Video Abstract.},
}

@article {pmid42250785,
year = {2026},
author = {Wang, M and Yao, Y and Li, Z and Wang, S and Yan, K and Romer, A and Li, S and Zhong, J and Su, P and Li, B and Zhu, H and Li, J},
title = {Hypertension-associated gut dysbiosis drives target organ damage through impaired polyunsaturated fatty acids metabolism and immune activation.},
journal = {Pharmacological research},
volume = {230},
number = {},
pages = {108281},
doi = {10.1016/j.phrs.2026.108281},
pmid = {42250785},
issn = {1096-1186},
abstract = {Hypertension (HTN) is a major risk factor for cardiovascular diseases, with chronic low-grade inflammation emerging as a critical contributor to its development and target organ damage. Emerging evidence implies gut microbiota in blood pressure regulation. However, the long-term impact of patient-derived gut dysbiosis on the chronic progression of HTN remains insufficiently characterized. This study aimed to determine how HTN-associated gut microbiota contributes to sustained blood pressure elevation and target organ damage during long-term colonization, and to elucidate underlying immune-metabolic mechanisms using multi-omics analyses. Fecal microbiota from hypertensive patients or normotensive controls were transplanted into germ-free mice, followed by continuous monitoring for 10 weeks to mimic the long-term adaptive remodeling of humanized microbiota within the host. Temporal dynamics of gut microbiota were assessed by 16S rRNA sequencing. Integrated metabolomic and transcriptomic analyses were performed on intestinal, cardiac, fecal, and serum samples. FMT from hypertensive patients induced sustained systolic blood pressure elevation and structural damage in target organs. HTN-FMT mice exhibited reduced microbial diversity and a dysbiotic signature characterized by enrichment of pro-inflammatory taxa and depletion of beneficial commensals. Metabolomic profiling revealed marked disturbances in polyunsaturated fatty acids metabolism. These metabolic alterations were accompanied by enhanced CD4[+] T cell activation, elevated systemic inflammatory cytokines, and concordant enrichment of interleukin-17 signaling pathways in both intestinal and myocardial transcriptomes. These findings reveal interactions among gut dysbiosis, metabolic imbalance, and immune activation during long-term colonization with HTN-associated microbiota, underscoring the central role of the gut-immune axis in the chronic progression of hypertensive target organ injury.},
}

@article {pmid42250826,
year = {2026},
author = {Kinoshita, Y and Sato, W and Ueno, T},
title = {Evaluation of autologous fecal microbiota transplantation for restoring equine gut microbiota after antibiotic-induced dysbiosis.},
journal = {Journal of equine veterinary science},
volume = {},
number = {},
pages = {106049},
doi = {10.1016/j.jevs.2026.106049},
pmid = {42250826},
issn = {0737-0806},
abstract = {Microbial resilience is important to maintain a healthy gut environment in horses, especially after antibiotic administration, but the efficacies of post-antibiotic recovery strategies remain poorly characterized. We used microbial amplicon sequencing to compare spontaneous recovery, autologous fecal microbiota transplantation (FMT), and probiotic administration in 18 horses following antibiotic-induced dysbiosis. Clinically healthy horses received a combination of cephalothin and minocycline for 5 consecutive days before intervention. Fecal microbial recovery was longitudinally evaluated by using community-level dissimilarity metrics. Antibiotic treatment induced marked dysbiosis in all horses. Autologous FMT resulted in significantly faster recovery toward individual pre-treatment baselines compared with spontaneous recovery (significantly lower dissimilarity at day 3 post-treatment, P < 0.05), whereas the effects of probiotics were only evident in cumulative recovery metrics and not at specific time points. These findings indicate that autologous FMT has the potential to accelerate the recovery of the equine gut microbiota following antibiotic-induced dysbiosis.},
}

@article {pmid42251131,
year = {2026},
author = {Cai, J and Wang, M and You, Y and Sun, F and Wang, M and Wang, N and Wang, R and Zhang, K and Ge, R and Wang, H},
title = {AS-IV attenuates nigral NLRP3 inflammasome in a Parkinson's disease mouse model via gut microbiota.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-026-10415-5},
pmid = {42251131},
issn = {2399-3642},
support = {81601108//National Natural Science Foundation of China (National Science Foundation of China)/ ; ZR2021MH135 and ZR2016HQ14//Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)/ ; },
abstract = {Astragaloside IV (AS-IV) neuroprotection against rotenone (ROT)-induced Parkinson's pathology was examined via microbiota-gut-brain axis mechanisms. Methods included intraperitoneal AS-IV, fecal microbiota transplantation (FMT) from AS-IV-treated mice, and AS-IV-modulated microbiota transplantation. Substantia nigra dopaminergic neurons/microglia were evaluated by confocal imaging, while NLRP3, caspase-1, IL-1β, and α-synuclein (α-syn) levels were quantified via Western blot. Gut microbiota (16S rRNA sequencing) and striatal metabolites (LC-MS/MS) were analyzed. AS-IV attenuated ROT-induced motor deficits, dopaminergic neuron loss, α-syn overexpression, and NLRP3/caspase-1 activation, while elevating fecal SCFAs and increasing Bacteroidetes/Porphyromonadaceae with reduced Firmicutes. FMT from AS-IV-treated to ROT mice improved motor function, suppressed TH[+] neuron loss, and inhibited microglial/NLRP3 activation. AS-IV-modulated microbiota transplantation upregulated Bacteroidetes, Porphyromonadaceae, Barnesiella, and downregulated Firmicutes, Lactobacillaceae, Lactobacillus, and Desulfovibrio. Crucially, FMT from AS-IV-treated to naïve mice alleviated ROT-induced damage, whereas ROT microbiota transplantation induced rotations and decreased Bacteroidetes, Actinobacteria, Porphyromonadaceae, Sutterellaceae, and Parasutterella. AS-IV reversed these microbial changes. Genus-level microbiota alterations correlated with motor severity. ROT microbiota reduced 5-HIAA, indole-3-carboxaldehyde, thyroxine, and glutathione; AS-IV restored indole-3-carboxaldehyde and thyroxine. AS-IV exerts neuroprotection by suppressing NLRP3 inflammasome activation via gut microbiota remodeling and metabolic regulation through the microbiota-gut-brain axis.},
}

@article {pmid42253950,
year = {2026},
author = {Han, X and Guo, XL and Qiu, J},
title = {From gut-reproductive microbiota to ferroptosis: a comprehensive insight into the molecular-pathogenicity of endometriosis.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1762013},
pmid = {42253950},
issn = {1664-3224},
abstract = {Endometriosis (EMS) is a highly heterogeneous chronic gynecological disease characterized by pain, infertility, and relapse, with its etiology and pathogenesis not yet fully elucidated. Traditional theories, including "retrograde menstruation," "implantation theory," and "abnormalities in immune tolerance," struggle to adequately explain the complex lesion behavior, diverse phenotypic characteristics, and accompanying immune-metabolic disorders. In recent years, the key roles of imbalances in the gut and reproductive microbiomes, abnormal iron metabolism, and the newly proposed ferroptosis in the occurrence and development of EMS have gradually gained attention, suggesting that this disease may be a systemic condition involving the interplay of microbial ecology, iron metabolism, and cell death. Existing studies indicate that the gut-reproductive microbiome profoundly influences the body's iron homeostasis and iron load by regulating mucosal immunity, systemic inflammatory responses, and metabolic environments. This, in turn, activates the ferroptosis pathway through iron-dependent lipid peroxidation and cell membrane damage, participating in the formation, maintenance, and inflammatory microenvironment shaping of ectopic lesions. Based on these findings, this article systematically reviews the interactions between gut-reproductive microbiome imbalance and iron metabolism disorders, integrating multi-omics evidence such as microbiome analysis, metabolomics, and iron metabolism/ferroptosis-related molecular markers. It proposes a new pathological mechanism framework of "dysbiosis-iron overload-ferroptosis" incorporating microecological imbalance and ferroptosis into a unified picture of the pathogenesis of EMS. Furthermore, this article discusses potential therapeutic strategies and application prospects surrounding microbiome remodeling (such as probiotics, fecal microbiota transplantation, dietary and lifestyle interventions) and pharmacological targeting of key ferroptosis-related molecules. Through a comprehensive and critical analysis of existing evidence, this review aims to provide a more systematic theoretical framework for the mechanistic research of EMS and offer ideas and directions for future clinical translation of precise classification, individualized intervention, and novel treatment plans.},
}

@article {pmid42253976,
year = {2026},
author = {Liu, M and Wang, W and Qian, L},
title = {Microbiota-targeted therapeutic strategies for elderly-onset rheumatoid arthritis: based on the gut-joint axis.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1850656},
pmid = {42253976},
issn = {1664-3224},
mesh = {Humans ; *Arthritis, Rheumatoid/therapy/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; *Dysbiosis/immunology ; Animals ; Fecal Microbiota Transplantation ; *Joints/immunology/microbiology ; Immunosenescence ; Age of Onset ; },
abstract = {Elderly-onset rheumatoid arthritis (EORA) presents distinct clinical challenges, including more refractory disease activity, higher comorbidity burden, and increased disability and mortality compared to younger-onset RA. Emerging evidence implicates the gut-joint axis-specifically the synergistic interplay between immunosenescence, inflammaging, and gut microbiota dysbiosis-in the pathogenesis of EORA. This review aims to synthesize current evidence on the role of the gut microbiota in EORA, elucidate the mechanistic links between age-related immune changes and microbial dysbiosis, and evaluate the therapeutic potential of microbiota-targeted interventions, including dietary modifications, nutraceuticals, and fecal microbiota transplantation.},
}

Humans
*Arthritis, Rheumatoid/therapy/immunology/microbiology
*Gastrointestinal Microbiome/immunology
*Dysbiosis/immunology
Animals
Fecal Microbiota Transplantation
*Joints/immunology/microbiology
Immunosenescence
Age of Onset

@article {pmid42254003,
year = {2026},
author = {Sun, S and Lang, H and Cheng, S and Ren, R and Yao, W and Ma, Y and Nashun, D and Wang, Y and Si, Q},
title = {Gut microbiota in Henoch-Schönlein purpura: from pathogenesis to therapeutic strategies.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1838103},
pmid = {42254003},
issn = {1664-3224},
abstract = {Henoch-Schönlein purpura (HSP), also known as immunoglobulin A vasculitis, is a common systemic vasculitis in children. Although its pathogenesis remains unclear, recent studies suggest that the gut microbiota may play a significant role in its initiation and progression. In patients with HSP, gut microbiota dysbiosis and associated metabolic alterations are linked to impaired intestinal barrier integrity, activation of the innate immune system, and dysregulation of adaptive immune cell subsets; this includes imbalances in the T helper 17 (Th17)/regulatory T (Treg) and follicular helper T (Tfh)/follicular regulatory T (Tfr) axes. These changes may ultimately trigger immunoglobulin A immune complex deposition and dysregulation of the complement system, potentially establishing a positive feedback loop that drives immune-mediated inflammatory injury. Modulation of the gut microbiota has been shown to restore intestinal barrier function and immune homeostasis; this indicates its potential as a therapeutic target. This review summarizes recent research on gut microbiota alterations in patients with HSP, and evaluates its role in the pathogenesis of the condition. It also discusses promising therapeutic strategies, including probiotics and prebiotics, traditional Chinese medicine and its active components, fecal microbiota transplantation, and targeted-release formulations. This review aims to identify potential microbial biomarkers and therapeutic targets for improving the clinical management of HSP.},
}

@article {pmid42254009,
year = {2026},
author = {Chen, S and Zhang, C and Liu, X and Zhu, Y and Niu, C and Lv, W},
title = {Pasteurized Akkermansia muciniphila alleviates high-fat diet-induced bone loss via Nr4a1-dependent Treg differentiation.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1833607},
pmid = {42254009},
issn = {1664-3224},
abstract = {BACKGROUND: Obesity, a global epidemic, disrupts bone metabolism via gut microbiota dysbiosis, and probiotic/postbiotic supplementation emerges as a promising intervention. Akkermansia muciniphila (Akk), a next-generation probiotic, exerts metabolic benefits in obesity, yet its effects on bone homeostasis-especially in pasteurized form (pAkk)-and underlying mechanisms remain unclear.

METHODS: High-fat diet (HFD)-induced obese mice were used to establish bone loss models, with fecal microbiota transplantation to verify gut microbiota's role. Mice were gavaged with live Akk, pAkk, or control for 4 weeks. Bone microarchitecture was assessed via micro-computed tomography (μCT), and bone formation/resorption were detected by histomorphometry, ELISA, and TRAP staining. Flow cytometry, immunofluorescence, and qRT-PCR analyzed regulatory T (Treg) cell differentiation. RNA sequencing identified key genes, and Nr4a1 knockout mice validated the mechanism. Cell coculture confirmed pAkk-induced Tregs' inhibitory effect on osteoclastogenesis.

RESULTS: Obesity-related gut microbiota induced trabecular bone loss, with reduced intestinal Akk abundance. pAkk (but not live Akk) rescued HFD-induced bone loss, increased bone formation marker (P1NP), decreased resorption marker (β-CTX), and inhibited osteoclast differentiation. pAkk promoted CD4[+]CD25[+]Foxp3[+] Treg differentiation in the intestine and spleen via CD103[+] dendritic cells, and these Tregs suppressed osteoclastogenesis. Transcriptomic and functional validation showed Nr4a1 was upregulated by pAkk and essential for Treg differentiation; Nr4a1 knockout abrogated pAkk's bone-protective effects.

CONCLUSION: Pasteurized Akkermansia muciniphila alleviates HFD-induced bone loss in obese mice by promoting intestinal and systemic Treg differentiation to inhibit osteoclastogenesis, dependent on the nuclear hormone receptor Nr4a1. Our findings identify pAkk as a promising postbiotic for obesity-related bone loss and uncover a novel Nr4a1/Treg axis linking gut microbiota to bone homeostasis.},
}

@article {pmid42254101,
year = {2026},
author = {Khan, SA and Qamar, MA and Ali, T and Omer, MH and Tahir, A},
title = {Reconsidering immunotherapy resistance: the emerging role of the tumor microbiome in head and neck and lung cancers.},
journal = {Annals of medicine and surgery (2012)},
volume = {88},
number = {6},
pages = {3812-3814},
pmid = {42254101},
issn = {2049-0801},
abstract = {Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized treatment for non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC), yet resistance limits durable responses in many patients. Emerging evidence implicates the intratumoral microbiome - comprising bacteria, fungi, and viruses within tumor tissues - as a key modulator of tumor biology, immune infiltration, and ICI sensitivity, beyond traditional tumor-intrinsic and immune factors. In HNSCC, human papillomavirus (HPV)-negative tumors exhibit higher oncobacteria abundance than HPV-positive ones, with elevated levels linked to worse survival in HPV-positive oropharyngeal cases, suggesting an immunosuppressive tumor microenvironment that may influence ICI outcomes. In NSCLC, intratumoral taxa such as Fusobacterium nucleatum and Bacteroides fragilis promote progression and evasion via immune checkpoint modulation (PD-1/PD-L1), pro-inflammatory pathways (toll-like receptors and cytokines like interleukin-6/tumour necrosis factor-alpha), metabolic reprogramming (PI3K/AKT), and recruitment of suppressive cells (neutrophils and myeloid-derived suppressor cells). Pan-cancer studies show microbial enrichments and compositional shifts in responders versus non-responders to ICI, with metabolites (e.g., lactate and succinic acid) driving M2 macrophage polarization, T-cell suppression, and resistance. The gut-tumor axis further exacerbates refractoriness through systemic dysbiosis and immune alterations. Preclinical models indicate that targeted microbiome interventions - such as fecal microbiota transplantation, specific probiotics (e.g., Bifidobacterium spp. and Akkermansia muciniphila), or selective antibiotics - can restore antitumor immunity, enhance ICI efficacy, and minimize broad dysbiosis risks. Integrating intratumoral microbial profiling into HNSCC and NSCLC clinical trials could refine patient stratification, uncover predictive biomarkers, and accelerate microbiome-directed adjunct therapies, advancing precision oncology and expanding immunotherapy benefits.},
}

@article {pmid42254157,
year = {2026},
author = {Arif, L and Abbasi, MM and Raza, AA and Samadi, A},
title = {From microbiome profiling to precision medicine: diagnostic and therapeutic potential in gastrointestinal disorders: current evidence, challenges, and future directions.},
journal = {Annals of medicine and surgery (2012)},
volume = {88},
number = {6},
pages = {3348-3359},
pmid = {42254157},
issn = {2049-0801},
abstract = {Gastrointestinal (GI) disorders, affecting millions globally (approximately 1.5 billion people with IBS alone), impose a significant healthcare burden and remain challenging to diagnose and manage. Current approaches are often invasive or symptom based, highlighting an urgent need for more precise and personalized strategies. The gut microbiome may offer novel diagnostic biomarkers and therapeutic targets, potentially transforming patient care. It supports GI and systemic health via metabolism, immune modulation, and neurochemical signaling. The dysbiosis of the gut microbiota contributes significantly to the pathogenesis of various GI disorders, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), colorectal cancer (CRC), and small intestinal bacterial overgrowth. This narrative review critically evaluates the diagnostic potential of microbiome profiling and its clinical applications in developing personalized therapeutic strategies. We examine cutting-edge techniques such as 16S rRNA sequencing, metagenomics, and metabolomics, and discuss how dietary modulation, precision probiotics, and fecal microbiota transplantation are being increasingly used to reshape gut microbial composition. However, it is critical to note that while microbiome alterations show consistent associations with GI diseases, current evidence remains largely observational and associative. To date, no microbiome-based test has achieved regulatory approval or clinical validation as a standalone diagnostic tool for IBD, IBS, or CRC, and therapeutic applications remain investigational with modest clinical benefits in select conditions. Additionally, we highlight the translational challenges of integrating microbiome-based diagnostics into mainstream clinical practice and propose future research imperatives. This review provides a balanced perspective on the promise and challenges of integrating microbiome-based approaches into clinical gastroenterology, while proposing actionable research priorities to guide future investigations toward clinically validated, patient-centered diagnostic, and therapeutic solutions.},
}

@article {pmid42254520,
year = {2026},
author = {Zhang, L and Lin, S and Zu, B and Chen, Z and Li, S and Lin, W and Dong, T and Chen, Z},
title = {Safety and efficacy of fecal microbial transplantation for the prevention and treatment of acute graft-versus-host disease: a meta-analysis.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1802260},
pmid = {42254520},
issn = {1664-302X},
abstract = {OBJECTIVE: In recent years, fecal microbiota transplantation (FMT) has been increasingly investigated for the prevention and treatment of acute graft-versus-host disease (aGVHD). Nevertheless, its clinical efficacy remains uncertain. Therefore, this study aims to systematically evaluate the clinical efficacy of FMT in preventing and treating aGVHD.

METHODS: We systematically searched Cochrane Library, PubMed, Embase, and Web of Science from inception to October 2025 for studies comparing FMT with conventional regimens (corticosteroids and/or immunosuppressants) for aGVHD prevention and treatment. All statistical analyses were performed using RevMan 5.4.1 and Stata 16.

RESULTS: Six studies involving 262 patients were included. Among them, 85 patients received FMT for aGVHD prevention, 65 received conventional prophylaxis, 68 received FMT for Gastrointestinal aGVHD (GI-aGVHD) treatment, and 44 received conventional treatment for GI-aGVHD. Meta-analysis showed no significant difference in the incidence of aGVHD between the FMT and conventional groups [odds ratio (OR) = 1.30, 95% confidence interval (CI) = 0.10-16.72, p = 0.84]. However, the FMT group demonstrated significantly higher 14-day and 30-day complete response (CR) rates, as well as 14-day clinical response rates, in patients with GI-aGVHD compared to the conventional group (OR = 8.54, 95% CI = 2.49-29.29, p = 0.0007; OR = 8.44, 95% CI = 2.98-23.96, p < 0.0001; OR = 4.66, 95% CI = 1.73-12.55, p = 0.002). No significant differences were observed in the incidence of bacteremia or sepsis between the two groups (OR = 0.37, 95% CI = 0.13-1.01, p = 0.05; OR = 0.38, 95% CI = 0.11-1.33, p = 0.13). Additionally, the abundances of Bacteroides and Bifidobacterium were significantly higher in the FMT group than in the conventional group [standardized mean difference (SMD) = 1.59, 95% CI = 0.15-3.03, p = 0.03; SMD = 1.01, 95% CI = 0.41-1.60, p = 0.0009].

CONCLUSION: FMT showed favorable effects in improving clinical symptoms of GI-aGVHD and increasing the abundance of beneficial gut bacteria, and no increased risk of bloodstream infection was observed. These findings suggest that, for patients with established GI-aGVHD who may respond poorly to conventional regimens, FMT can serve as an effective adjunctive or salvage treatment. However, no significant advantage was observed for FMT in preventing aGVHD.},
}

@article {pmid42256217,
year = {2026},
author = {Yao, G and Pan, X and Chen, F and Yang, L and Zhou, L and Peng, M and Yang, X},
title = {Gut Bacteroidales and AMH/INH-B ratio predict sperm retrieval: mechanistic insights via SCFA-mediated regulation of blood-testis barrier and steroidogenesis.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1777930},
pmid = {42256217},
issn = {2235-2988},
abstract = {OBJECTIVE: To establish a non-invasive predictive model for microdissection testicular sperm extraction (micro-TESE) outcomes in FSH-normal non-obstructive azoospermia (NOA) patients by integrating gut microbiota profiling with serum biomarkers.

METHODS: We conducted a retrospective clinical analysis of 58 men and established a busulfan-induced FSH-normal NOA mouse model. Serum hormone levels (FSH, INH-B, AMH, testosterone) were measured by ELISA, and gut microbiota was analyzed via 16S rRNA sequencing. Testicular histology and ultrastructure were assessed by H&E staining and TEM, while protein expression was evaluated by IHC, IF, and Western blot. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive efficacy of the serum AMH/INH-B ratio for sperm retrieval outcomes.

RESULTS: In both patients and model mice, serum INH-B, AMH, and the AMH/INH-B ratio were significantly decreased (P < 0.01), correlating with severe spermatogenic impairment. Mice exhibited a marked reduction in the abundance of Bacteroidales and Muribaculaceae. Fecal microbiota transplantation (FMT) restored these microbial populations, improved testicular function, and upregulated key proteins involved in proliferation (PCNA, PGK2), blood-testis barrier integrity (ZO-1, Claudin11), and steroidogenesis (StAR, CYP17A1) (P < 0.05). Mechanistically, FMT increased serum short-chain fatty acid (SCFA) levels, which served as the chemical messengers correlating directly with the recovery of BTB proteins and steroidogenic enzymes. Clinically, the serum AMH/INH-B ratio showed strong predictive efficacy for micro-TESE outcomes, with an area under the ROC curve (AUC) of 0.92 (95% CI: 0.86-0.98), optimal cut-off value of 0.65, sensitivity of 88.2%, and specificity of 85.7%. The gut Bacteroidales abundance (from mouse data) was mechanistically linked to spermatogenic function, suggesting its potential as a future clinical biomarker pending validation.

CONCLUSIONS: Our findings elucidate an SCFA-mediated gut-testis axis, highlighting the therapeutic potential of microbiota modulation and providing a novel tool to guide clinical decision-making, potentially reducing unnecessary surgeries in FSH-normal NOA.Additionally, the serum AMH/INH-B ratio serves as a robust non-invasive biomarker for predicting micro-TESE outcomes in FSH-normal NOA, while gut Bacteroidales abundance may represent a complementary mechanistic target for future clinical investigation.},
}

@article {pmid42256221,
year = {2026},
author = {Giju, JK and John, S and Sivadas, A and Prabhakar, M and K, K and Sunilkumar, D and Nair, BG and Pal, S and Prakash, V},
title = {From dysbiosis to precision medicine: targeting the microbial-metabolic axis in IBD management.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1826972},
pmid = {42256221},
issn = {2235-2988},
abstract = {Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory condition that has a rapidly changing global epidemiology. IBD has been traditionally viewed as a primary immune system dysfunction, but emerging evidence more accurately describes IBD as a perturbance of the intricate balance between host immunity, the intestinal microbiome, and intestinal metabolism. Although genetic and environmental components have long been recognized as contributors, accumulating evidence increasingly highlights the pivotal role of microbial dysbiosis in the pathogenesis of IBD. In patients with IBD, intestinal dysbiosis, which is often characterized by reduced Firmicutes and increased pro-inflammatory bacteria, triggers a cascade of pathogenic events. These pathogenic events include impaired epithelial barrier function, dysregulated immune activation against luminal antigens, and immune reprogramming. Central to these processes are functional changes in microbial metabolism, particularly in pathways involving short-chain fatty acids (SCFAs), bile acids, and redox homeostasis, which critically contribute to the development of chronic mucosal inflammation. The current therapeutic backbone of IBD-including aminosalicylates, biologics, and immunomodulators-largely targets the inflammatory response. However, the challenges such as primary non-response, secondary loss of response, and systemic side effects are often problematic. Consequently, there is an urgent need to develop novel therapeutic and preventive strategies that target the underlying microbial and metabolic causes of the disease rather than modulating immune responses. This review integrates the pathomechanistic implications of the microbiome-metabolic axis in the maintenance of gut homeostasis and its disruption in IBD, with particular emphasis on the global epidemiology of the disease. We further evaluate emerging therapeutic and preventive strategies aimed at restoring the microbiome-metabolic axis, including fecal microbiota transplantation (FMT), probiotic therapy, bacteriophage therapy, and helminth-based therapies. In addition, we explore the potential of advanced approaches such as microbiome engineering and precision genome editing to enable highly personalized therapeutic paradigms. By bridging microbial ecology with clinical pathology, this review highlights the transformative potential of targeting the host-microbiota interface to achieve improved long-term outcomes in IBD.},
}

@article {pmid42257798,
year = {2026},
author = {Zhou, AN and Liu, L and Huang, MM and Yang, S and Fei, H},
title = {The microbiota-gut-immunity axis in teleost fish: dual regulatory mechanisms of viral infections and prospects for microbiome-based antiviral strategies.},
journal = {Fish physiology and biochemistry},
volume = {52},
number = {3},
pages = {},
pmid = {42257798},
issn = {1573-5168},
abstract = {Bacteria and viruses engage in complex synergistic and antagonistic interactions with profound implications for host health, particularly through functional modulation by intestinal and other mucosal (e.g., skin, gill) microbiota. In teleost models, intestinal microbiota demonstrates dual regulatory capacities-either potentiating or suppressing viral infections. However, the mechanistic underpinnings of these interactions remain inadequately explored in aquatic species. This review systematically delineates the dual regulatory pathways (facilitative vs. inhibitory) through which the gut microbiota modulates viral infections in fish. Based on these mechanisms, we propose a novel microbiota-gut-immunity axis framework-defined as the bidirectional communication network linking gut microbial communities, intestinal barrier function, and host systemic immunity-for the development of integrated antiviral interventions. Furthermore, we critically evaluate emerging strategies-including probiotics, prebiotics, postbiotics, synbiotics, fecal microbiota transplantation (FMT), microalgae, seaweed, and phytoactive compounds-to develop preventive and therapeutic countermeasures. Based on mechanistic insights, probiotics and prebiotics emerge as the most promising candidates for large-scale application, as they directly reshape gut microbial composition and enhance host immunity along the microbiota-gut-immunity axis. In contrast, FMT and herbal medicines, while acting on multiple nodes of the axis, currently face safety and standardization challenges, positioning them as adjunctive therapies. Importantly, these mechanistic insights reveal evolutionarily conserved immune pathways with significant translational potential for human virology.},
}

@article {pmid42248125,
year = {2026},
author = {Niu, M and Li, J and Huang, J and Qiao, T and Zhang, L and Yin, L and Zhang, K and Yin, L and Zhang, Y and Li, Q and Song, X and Zuo, L and Geng, Z and Song, C and Hu, J},
title = {Dipsacoside B alleviates experimental colitis by reshaping gut microbiota and metabolically regulating the balance of macrophage polarization.},
journal = {International immunopharmacology},
volume = {185},
number = {},
pages = {116947},
doi = {10.1016/j.intimp.2026.116947},
pmid = {42248125},
issn = {1878-1705},
abstract = {Gut dysbiosis-driven macrophage polarization plays a critical role in the pathogenesis of ulcerative colitis (UC). Dipsacoside B (DB), a natural saponin, possesses potential anti-inflammatory properties; however, its influence on mucosal immunity and the gut microbiota remains to be elucidated. To evaluate the therapeutic effects of DB, this study employed a DSS-induced colitis model in C57BL/6 mice, testing three different doses. The role of the gut microbiota was investigated through antibiotic-induced depletion and fecal microbiota transplantation (FMT). Both in vivo and in vitro experiments were carried out to assess intestinal barrier function and immune responses, with the latter involving colonic organoid and Caco-2 cells exposed to macrophage-conditioned media. Further mechanistic insights were gained via integrated 16S rRNA sequencing and untargeted metabolomics. In terms of colitis outcomes, DB exerted dose-dependent relief of symptoms and restored intestinal barrier integrity. At the immune level, DB encouraged macrophages within the lamina propria to transition from an M1 to an M2 phenotype. Importantly, the gut microbiota was essential for these effects, when antibiotics were used to deplete the microbiota, the protective effects of DB were abolished, but its protective effects on the mucosa could be transferred via FMT. Omics analyses pointed to increased Akkermansia and activation of the alpha-linolenic acid (ALA) pathway, accompanied by elevated methyl jasmonate (MeJA). In vitro, MeJA was found to regulate macrophage polarization tipping the balance away from M1 and toward M2 and to preserve tight junctions in epithelial cells exposed to inflammatory stress. Collectively, this work reveals that DB ameliorates UC via microbiota-dependent enrichment of MeJA, a microbiota-associated ALA-derived metabolite. Furthermore, this study demonstrates that MeJA exerts immunomodulatory effects by balancing macrophage polarization, thereby providing a novel strategy for targeted therapeutic interventions in UC.},
}

@article {pmid42248955,
year = {2026},
author = {Yan, S and Wang, L and Xu, Y and Zhu, W and Li, N and Chen, Q and Li, L},
title = {An Integrated Dataset of Clinical and Microbial Profiles for Fecal Microbiota Transplantation.},
journal = {Scientific data},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41597-026-07502-x},
pmid = {42248955},
issn = {2052-4463},
support = {YJXYS-C-003//the Program for Research-oriented Physician of Shanghai Tenth People's Hospital/ ; 20234Y0079//the Shanghai Municipal Health Commission Research Project/ ; 21Y11908300//the Shanghai Science and Technology Innovation Action Plan/ ; 2022YFC2010201//the China National Key R& Program during the 13th Five-Year Plan Period/ ; 2022YFA1304101//the National Key R& Program of China/ ; },
abstract = {Functional gastrointestinal disorders (FGIDs) are prevalent and burdensome, yet progress in microbiota-targeted therapies such as fecal microbiota transplantation (FMT) has been hampered by the lack of large-scale, integrated datasets. Current studies are mostly limited in sample size and scope, constraining mechanistic insight and precision application. To address this gap, we established FMTdb, a curated dataset focused on FGID patients treated with FMT. This resource integrates demographic, clinical, and multi-omic microbiota data from 15 rigorously screened long-term donors, 370 FGID recipients, and 2,008 healthy community controls. Longitudinal metadata include donor follow-up and pre- and post-treatment observations of recipients across multiple time points. By providing a multi-layered dataset that connects microbial composition with host response, FMTdb offers a robust platform for biomarker discovery, mechanistic exploration, and the development of personalized microbiota-based interventions for FGIDs.},
}

@article {pmid42249360,
year = {2026},
author = {Shao, X and Li, R and Lan, Y and Gao, X and Liu, DZ and Li, R and Niu, J},
title = {Early prediction of sepsis in the ICU: a comparative analysis of multiple machine-learning algorithms using the MIMIC-III database.},
journal = {BMC medical informatics and decision making},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12911-026-03610-1},
pmid = {42249360},
issn = {1472-6947},
support = {LHGJ20240911//Exploration of Beneficial Populations and Mechanism Analysis of Fecal Microbiota Transplantation in the Treatment of Hepatic Encephalopathy/ ; },
abstract = {Sepsis is a high-burden, highly heterogeneous clinical challenge that affects up to 30% of ICU patients. Reliable early prediction is essential for timely intervention and improved outcomes. We aimed to develop and validate a machine-learning model for predicting sepsis onset beyond the first 24 h of ICU admission. Data from septic patients were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Feature selection was performed with the Boruta algorithm. Nine algorithms-XGBoost-DART, Gaussian Naïve Bayes, LightGBM-DART, Random Forest, AdaBoost, Multi-Layer Perceptron (MLP), Support Vector Machine (SVM-RBF), k-Nearest Neighbors (KNN), and Ridge Regression-were trained and comprehensively evaluated with respect to discrimination, calibration, and clinical utility. Class imbalance was addressed using SMOTE on the training set and cost-sensitive learning for applicable algorithms. Among 1,634 ICU patients included (after excluding those meeting Sepsis-3 criteria within the first 24 h), 349 (21.4%) developed sepsis after the 24-hour observation window. AUROCs ranged from 0.794 to 0.881 across the nine models. AUROCs ranged from 0.810 to 0.895 across the nine models. XGBoost-DART achieved the highest AUROC (0.881, 95% CI: 0.854-0.908) along with the best accuracy (0.847), F1-score (0.762), and specificity (0.897). Decision-curve analysis demonstrated that XGBoost-DART delivered the greatest net benefit over the widest range of threshold probabilities, underscoring its strong clinical utility. In summary, machine-learning models provide a reliable tool for early sepsis prediction in the ICU. The XGBoost-DART model, with its outstanding performance, empowers clinicians to identify high-risk patients and initiate timely interventions to reduce mortality.},
}

@article {pmid42243405,
year = {2026},
author = {Su, H and Xu, T and Hu, W and Wang, H and Pei, Z and Lu, W},
title = {A multi-strain biofilm consortium enhances gut microbiota resilience and restores post-antibiotic homeostasis.},
journal = {World journal of microbiology & biotechnology},
volume = {42},
number = {6},
pages = {},
pmid = {42243405},
issn = {1573-0972},
support = {32172216//National Natural Science Foundation of China/ ; JUSRP202504013//Fundamental Research Funds for the Central Universities/ ; },
abstract = {Antibiotics can significantly disrupt gut microbiota homeostasis, reducing microbial diversity and causing dysbiosis associated with health issues. Gut biofilms play a critical role in resilience and stress tolerance of the intestinal ecosystem. Mucosal microbial communities also help restore the gut microbiota after interventions like probiotics, antibiotics, or fecal transplants. Previously, we developed a core bacterial consortium with strong in vitro biofilm-forming and stress-resilient properties, but its colonization ability and in vivo function remained unclear. In this study, we first validated the in vivo biofilm formation of the microbial consortium using a germ-free (GF) mouse model, then introduced single-, dual-, and multi-strain combinations with varying biofilm-forming abilities into specific-pathogen-free mice to assess their potential for recovering antibiotic-disrupted gut microbiota. Our findings indicate that the robust, in vitro-selected consortium continued to form substantial biofilms in GF mouse intestines. 16 S rRNA sequencing showed that, compared to single- or dual-strain treatments, administering the core consortium significantly increased microbial richness and diversity. The gut microbiota of consortium-treated mice more closely resembled healthy controls, suggesting the core consortium has superior potential to restore healthy gut microbiota. Overall, our research demonstrates the core consortium markedly improves gut microbiota resilience to antibiotic-induced disruptions in mice, accelerates restoration of health-associated taxa, and reestablishes gut homeostasis. This approach could transform probiotic interventions from passive supplementation to active ecological engineering, providing a theoretical and experimental basis for next generation of engineered probiotics and microbiome restoration therapies.},
}

@article {pmid42243519,
year = {2026},
author = {Lima, AP and Novais, JB and Antunes, AEC and Calgaro, M and Merege-Filho, C and Rezende, DN and Romero, MA and Santo André, HC and Baptista, I and de Sá Pinto, AL and de Cleva, R and Santo, MA and Dantas, WS and Gil, S and Rodrigues, MRC and Artioli, GG and Vitulo, N and Roschel, H and Gualano, B and Nicoletti, CF and Benatti, FB},
title = {Exercise reprograms the gut microbiota to enhance metabolic outcomes after bariatric surgery: a translational, cross-species study.},
journal = {International journal of obesity (2005)},
volume = {},
number = {},
pages = {},
pmid = {42243519},
issn = {1476-5497},
abstract = {BACKGROUND/OBJECTIVES: Exercise training has been associated with metabolic improvements in bariatric patients beyond weight and fat loss, potentially involving modulation of the gut microbiota. We investigated whether exercise-related microbial changes are associated with metabolic adaptations in women undergoing Roux-en-Y gastric bypass (RYGB) by combining a randomized controlled exercise intervention trial in women post-surgery with a human-to-mouse fecal microbiota transplantation (FMT) experiment.

SUBJECTS/METHODS: Thirty-two women were randomized to RYGB (n = 16) or RYGB plus a 6-month exercise training program initiated three months post-surgery (RYGB + ET; n = 16), while a lean control group (LEAN; n = 16) was evaluated at baseline. Blood and fecal samples were collected before surgery, and at 3 (POST3) and 9 (POST9) months following surgery for biochemical, inflammatory, and microbiota analyses.

RESULTS: Both surgical groups showed comparable improvements in body composition and inflammation; however, RYGB + ET was associated with greater improvements in HDL, triglycerides, fasting glucose, and fasting insulin. Exercise was also associated with increased gut microbiota α-diversity and shifts in microbial composition, including enrichment of genera previously linked to short-chain fatty acid (SCFA) metabolism and host metabolic health. To explore the potential contribution of these microbial communities, fecal microbiota collected at POST9 were transplanted into 36 high-fat diet-fed female mice, generating recipient groups rRYGB, rRYGB+ET, and rLEAN. Mice receiving RYGB + ET microbiota displayed similar inflammatory status and glucose tolerance, but lower fasting insulin and HOMA-IR, along with partial preservation of intestinal morphology, compared with mice receiving RYGB microbiota.

CONCLUSIONS: These findings suggest that exercise following bariatric surgery is associated with distinct gut microbial configurations and metabolic improvements, and that exercise-conditioned microbiota may contribute to aspects of host metabolic regulation after surgery.},
}

@article {pmid42243653,
year = {2026},
author = {Zhang, YL and Gou, HZ and Li, ZJ and Xi, JH and Wang, XJ and Shang, J and Zhu, D and Ren, LF and Shu, XJ and Zhang, L},
title = {Role of the gut microbiota-bile acid axis in liver fibrosis based on microbiomics and targeted metabolomics.},
journal = {BMC microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12866-026-05224-z},
pmid = {42243653},
issn = {1471-2180},
support = {ldyyyn2023-87//Fund of the First Hospital of Lanzhou University/ ; 2025B-010//Gansu Provincial University Teachers' Innovation Fund Project/ ; 31960236//National Natural Science Foundation of China/ ; EEMRE202403//Open Fund of Gansu Key Laboratory of Microorganisms for Extreme Environments/ ; 23JRRA1498//Joint Scientific Research Foundation of Gansu Province/ ; 2019-RC-34//Lanzhou Talent Innovation and Entrepreneurship Project/ ; },
abstract = {BACKGROUND: Effective diagnoses and treatments for liver fibrosis (LF) are lacking. The gut microbiota (GM)-bile acid (BA) axis is critically associated with LF development and may represent a potential target for delaying or reversing LF.

METHODS: We combined fecal microbiomics and BA-targeted metabolomics to characterize the GM-BA axis in rats with carbon tetrachloride (CCl₄)-induced LF and used fecal microbiota transplantation (FMT) and probiotics (Bifidobacterium quadruple viable tablet solution) to regulate the GM-BA axis to investigate the role of the GM-BA axis in LF and its related mechanisms.

RESULTS: The GM composition and GM β-diversity differed significantly between the control and model rats. Clostridia and others were significantly increased, whereas Bifidobacteriales and others were significantly decreased in model rats. Serum BA metabolism differed significantly between the groups. The concentrations of 19 BAs were significantly increased in model rats. FMT improved the disordered GM by increasing Bifidobacteriales and others and decreasing Clostridia and others. Probiotics improved the disordered GM by decreasing Clostridia, Lachnospiracea_incertae_sedis and others. FMT and probiotics improved BA metabolism by decreasing BAs such as tauroursodeoxycholic acid (TUDCA). FMT and probiotics were associated with a reduced degree of LF in model rats.

CONCLUSIONS: The GM-BA axis is strongly associated with LF, and the use of FMT and probiotics may contribute to regulating the GM-BA axis and to alleviating LF.},
}

@article {pmid42243780,
year = {2026},
author = {Kim, NH and Lee, JH and Oh, J and Lee, S and Jung, ES and Suh, DH and Kang, HJ and Kim, B and Kim, HS and Kim, H and Yun, INR and Kim, EH and Kim, E and Jeong, JY and Ji, Y and Cho, SY and Lee, SW},
title = {Emphysema severity-associated gut microbiota modulates smoke-induced emphysema: evidence from fecal microbiota transplantation.},
journal = {Respiratory research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12931-026-03743-x},
pmid = {42243780},
issn = {1465-993X},
support = {2021R1A2C3008021//National Research Foundation of Korea/ ; RS-2023-NR077159//National Research Foundation of Korea/ ; RS-2022-NR067421//Bio&Medical Technology Development Program of the NRF/ ; 2024ER080601//National Institute of Health research project/ ; },
abstract = {BACKGROUND: Cigarette smoking is the key risk factor for chronic obstructive pulmonary disease, but even similar levels of smoking can result in different disease severity. We hypothesize that differences in gut microbiota and metabolites contribute to differences in emphysema severity through the gut-lung axis. In this study, we compared the microbiome and metabolome among non-emphysema, non-severe emphysema and severe emphysema groups. Additionally, the impact of fecal microbiota transplantation from non-emphysema, non-severe emphysema and severe emphysema groups on emphysema were investigated.

METHODS: A total of 78 participants with a smoking history were included in this study and categorized into three groups: non-emphysema, non-severe emphysema, and severe emphysema. Gut microbiota and metabolites were analyzed, and germ-free mice underwent fecal microbiota transplantation with feces from donors representative of each group prior to smoking exposure.

RESULTS: Significant differences in gut microbiota and metabolites were observed among the groups, with lower acetic acid levels in patients with severe emphysema, and a greater abundance of Prevotellaceae and Megasphaera in patients without emphysema. Fecal microbiota transplantation from donors with severe emphysema worsened lung pathology in mice subjected to smoking exposure, whereas fecal microbiota transplantation from donors without emphysema attenuated emphysema development.

CONCLUSIONS: Gut microbiota and metabolites in participants with a smoking history differ according to the presence of emphysema and its severity, and can affect emphysema development. This suggests a role for gut microbiota in lung disease and provides a foundation for exploring gut microbiota as a potential therapeutic target for chronic obstructive pulmonary disease.},
}