@article {pmid42916549,
year = {2026},
author = {Zhao, Z and Dong, Y and Xin, Y and Wang, D and Liu, X and Zhao, B},
title = {Intestinal Epithelial Bmal1 Contributes to High-Fat Diet-Induced Hepatic Lipid Dysmetabolism through Microbiota-Associated Bile Acid Remodeling.},
journal = {Journal of agricultural and food chemistry},
volume = {74},
number = {37},
pages = {29252-29265},
doi = {10.1021/acs.jafc.6c06528},
pmid = {42916549},
issn = {1520-5118},
support = {2025YFF1107800//National Key Research and Development Program of China/ ; 2024SF-ZDCYL-03-23//Key Research and Development Program of Shaanxi Province/ ; 32472354//National Natural Science Foundation of China (NSFC)/ ; 32502228//National Natural Science Foundation of China (NSFC)/ ; },
mesh = {Animals ; *Bile Acids and Salts/metabolism ; Diet, High-Fat/adverse effects ; *Liver/metabolism ; Mice ; Male ; *Lipid Metabolism ; Mice, Inbred C57BL ; *ARNTL Transcription Factors/metabolism/genetics ; *Gastrointestinal Microbiome ; *Intestinal Mucosa/metabolism/microbiology ; Humans ; },
abstract = {High-fat diet (HFD)-induced hepatic lipid dysmetabolism is closely associated with gut microbiota and bile acid remodeling, but the contribution of intestinal epithelial Bmal1 remains unclear. Here, intestinal epithelial Bmal1 deletion in HFD-fed mice reduced weight gain, improved glucose and lipid homeostasis, and attenuated hepatic steatosis. These changes were accompanied by coordinated regulation of hepatic lipid metabolic pathways, altered bile acid-related signaling along the gut-liver axis, and selective remodeling of the HFD-associated gut microbiota. Targeted analysis further revealed distinct shifts in circulating and fecal bile acid profiles. Fecal microbiota transplantation from HFD-fed Bmal1-deficient donors was associated with similar hepatic metabolic and bile acid-related changes in HFD-fed recipients. Together, these findings support a model in which intestinal epithelial Bmal1 contributes to HFD-induced hepatic lipid dysmetabolism in association with microbiota-associated bile acid remodeling.},
}

Animals
*Bile Acids and Salts/metabolism
Diet, High-Fat/adverse effects
*Liver/metabolism
Mice
Male
*Lipid Metabolism
Mice, Inbred C57BL
*ARNTL Transcription Factors/metabolism/genetics
*Gastrointestinal Microbiome
*Intestinal Mucosa/metabolism/microbiology
Humans

@article {pmid42918698,
year = {2026},
author = {Wang, X and Bao, Y and Li, W and Li, H and Song, J and Lan, Z and Han, D and Lin, W and Huang, W and Kang, X and Cao, P and Zeng, F and Wu, Z and Ye, Y and Wang, H and Ma, D and Chen, W and Li, S and You, S and Wu, S and Sun, X and Wang, SY and Mao, K and Li, H},
title = {Spatiotemporal mapping reveals microbiota-dependent maintenance of functional competence during postnatal immune maturation.},
journal = {Science bulletin},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.scib.2026.10.017},
pmid = {42918698},
issn = {2095-9281},
abstract = {Postnatal immune maturation is commonly viewed as a developmental milestone associated with weaning. However, how postnatal microbiota exposure shapes immune cell heterogeneity across tissues, and whether this maturation is self-sustaining or requires continuous microbial input, remain unclear. Here, we conducted spatiotemporal single-cell transcriptomic profiling of 120,649 immune cells isolated from 10 tissues in both germ-free (GF) and specific pathogen-free (SPF) mice from weaning to adulthood. We demonstrate that microbial colonization drives the expansion and functional maturation of distinct monocyte, macrophage, and neutrophil populations, marked by enhanced antigen-processing capabilities across tissues. Simultaneously, commensal-derived signals reprogram lymphocyte metabolic and translational states, promoting oxidative phosphorylation and relieving PDCD4-mediated translational repression to sustain effector readiness. Notably, microbiota reconstitution through both co-housing and fecal microbiota transplantation demonstrated that immune competence is not a fixed developmental endpoint but instead requires continuous microbiota-derived input. Without sustained microbial signals, immune cells adopted a persistent hyporesponsive state rather than remaining developmentally immature. Together, these findings redefine immune maturation as a microbiota-dependent maintenance process, revealing potential strategies to restore immune competence through microbiota-targeted interventions.},
}

@article {pmid42920157,
year = {2026},
author = {Tort-Miró, C and Pirolo, M and Bravo, M and Cobos, A and Argilaguet, J and Giler-Baquerizo, N and Guitart-Matas, J and Montoro-Dasi, L and Casals-Pascual, C and Aira, A and Guardabassi, L and Migura-Garcia, L},
title = {Comparing the effect of faecal microbiota and faecal filtrate transplantations on intestinal health in weaned piglets.},
journal = {BMC veterinary research},
volume = {22},
number = {1},
pages = {},
pmid = {42920157},
issn = {1746-6148},
support = {101136346//European Union's Horizon Europe Project/ ; 101136346//European Union's Horizon Europe Project/ ; PID2021-125641OB-C22 and PID2021-125641OB-C21//Spain I+D+I National Program/ ; },
mesh = {Animals ; *Fecal Microbiota Transplantation/veterinary/methods ; Swine ; Feces/microbiology ; Weaning ; Female ; *Intestines/microbiology ; *Gastrointestinal Microbiome ; Swine Diseases/prevention & control ; Diarrhea/veterinary/prevention & control ; Dysbiosis/veterinary/prevention & control ; },
abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) and faecal filtrate transplantation (FFT) have emerged as promising methods to prevent intestinal dysbiosis and diarrhoea in piglets after weaning. The aim of this study was to compare the effects of FMT and FFT on intestinal health and faecal microbiota dynamics in weaned piglets. Thirty-six 28-day old piglets were allocated into three groups (Control, FMT, and FFT, n = 12 each) at an experimental farm. Intact and filtered faeces from healthy sows were lyophilised, encapsulated, and administered upon arrival (day 0) and after 4 days (day 4). Clinical status, faecal consistency, and body weight were monitored over three weeks. Faecal samples were collected on days 4, 7, 11, 16, and 21 for microbiota analysis. On day 21, piglets were euthanised, and intestinal tissues were collected for morphometric analysis and ileal IgA measurement.

RESULTS: Both FMT and FFT altered faecal microbial composition, with an increased abundance of short-chain fatty acid (SCFA) producing genera and species. FMT induced the most significant changes on days 4 and 7 post-transplantation, whereas FFT led to sustained changes over time. FMT significantly improved intestinal morphology, increasing villus-to-crypt ratios in the jejunum, ileum, and duodenum, while the effect of FFT was limited to the duodenum. In addition, FMT increased secretory IgA (sIgA) concentrations in ileal content indicating microbiota-induced immune modulation. No differences in clinical signs, faecal scores, weight gain or abundance of antimicrobial resistance genes were observed among groups.

CONCLUSIONS: These results demonstrate that freeze-drying encapsulated FMT and FFT are safe and effective approaches to modulate the faecal microbiota in weaned piglets, with FMT offering additional benefits for intestinal development and immunity.},
}

Animals
*Fecal Microbiota Transplantation/veterinary/methods
Swine
Feces/microbiology
Weaning
Female
*Intestines/microbiology
*Gastrointestinal Microbiome
Swine Diseases/prevention & control
Diarrhea/veterinary/prevention & control
Dysbiosis/veterinary/prevention & control

@article {pmid42920555,
year = {2026},
author = {Dubois, A and Leenders, A and De Hertogh, G and Rustichelli, A and Boelhouwer, C and Wylin, T and Heedfeld, V and Bonaccorsi-Riani, E and Pirenne, J and Vanuytsel, T and Farré, R and Ceulemans, LJ},
title = {Changes in rat intestinal motility and absorption following intestinal transplantation: an experimental study.},
journal = {Transplant international : official journal of the European Society for Organ Transplantation},
volume = {39},
number = {},
pages = {17141},
pmid = {42920555},
issn = {1432-2277},
mesh = {Animals ; *Gastrointestinal Motility/physiology ; Male ; *Intestinal Absorption/physiology ; Rats ; Permeability ; Rats, Inbred Lew ; *Intestines/transplantation ; Dextrans ; Intestinal Barrier Function ; Fluorescein-5-isothiocyanate/analogs & derivatives ; },
abstract = {Intestinal transplantation (ITx) is a life-saving procedure for patients with complicated intestinal failure. In the acute phase, allograft permeability increases primarily due to ischemia-reperfusion injury. However, long-term allograft physiology after transplantation remains poorly understood, particularly the impact of lost autonomous graft innervation. This study aims to evaluate post-ITx allograft motility and permeability using orally administered fluorescein-labeled dextrans (TRITC70,FITC4). Lewis-to-Lewis orthotopic ITx (n = 6, 260-300 g) were performed. Intestinal permability and motility were evaluated in recipient at baseline (2 days pre-transplant, control) and 4 weeks post-transplant (experimental), using orally administered dextrans (TRITC70 and FITC4). Total GI motility was assessed by TRITC70 fecal excretion, while intestinal and colonic permeability were evaluated using TRITC70 (transcellular route) and FITC4 (paracellular route) plasma concentrations, measured at 3 h, 6 h, 24 h. Paired data were reported as mean (±SEM) and compared using paired t-test (normal distribution)/Wilcoxon rank test (non-normal distribution). Fecal excretion of TRITC70 was 9.58 (±0.85) hours in the control group and 11.02 (±1.40) hours in the experimental group (p = 0.287). Plasma concentrations (µg/mL) of FITC4 at 3 h, 6h, and 24 h were (control vs. experimental): 0.23 (±0.08) vs. 0.72 (±0.23) (p = 0.041), 0.12 (±0.06) vs. 0.53 (±0.16) (p = 0.031), and 0.04 (±0.02) vs. 0.12 (±0.04) (p = 0.625). For TRITC70, plasma concentrations were 11.20 (±1.81) vs. 11.11 (±1.39) (p = 0.975), 20.49 (±8.87) vs. 12.60 (±1.87) (p = 0.562), and 20.82 (±7.25) vs. 5.02 (±0.82) (p = 0.094). Finally, the AUC (µgh/mL) of FITC4 and TRITC70 absorption were 2.39 (±1.1) vs. 8.84 (±2.69) (p = 0.029) and 436 (±159) vs. 197 (±25) (p = 0.195), respectively. Four weeks after ITx, we observed an increased paracellular permeability compared to pre-transplant evaluation, while overall GI motility remained unchanged. Further research is needed to better understand intestinal graft physiology.},
}

Animals
*Gastrointestinal Motility/physiology
Male
*Intestinal Absorption/physiology
Rats
Permeability
Rats, Inbred Lew
*Intestines/transplantation
Dextrans
Intestinal Barrier Function
Fluorescein-5-isothiocyanate/analogs & derivatives

@article {pmid42920945,
year = {2026},
author = {Li, N and Yuan, M and Jin, X and Jiao, X and Wang, S and Zhong, Z and Guan, H and Le, X and Ren, Q and Liu, Y and Dong, X and Li, Q and Wang, M and Wang, G},
title = {Intestinal microbiota-associated LysoPC(16:0) promotes endometriosis via PPARγ-mediated M2 macrophage polarization and IL-10 secretion.},
journal = {iScience},
volume = {29},
number = {11},
pages = {117917},
pmid = {42920945},
issn = {2589-0042},
abstract = {Both gut microbiota dysbiosis and altered pelvic immune microenvironment have been linked to endometriosis (EM), but the metabolites connecting the two remain undefined. Combining 16S rDNA sequencing with non-targeted metabolomics in a murine EM model, we found altered gut microbiota composition alongside a marked rise in peritoneal lysophosphatidylcholine (LysoPC(16:0)), linked to the microbiota shift by correlation analysis and fecal transplantation. LysoPC(16:0) promoted M2 macrophage polarization through peroxisome proliferator-activated receptor gamma (PPARγ), an effect observed in two mouse strains. Clodronate-mediated macrophage depletion blocked LysoPC(16:0)-driven lesion growth. LysoPC(16:0) further induced PPARγ-dependent IL-10 transcription, and IL-10 neutralization in vivo reduced lesion weight. Conditioned medium from LysoPC(16:0)-stimulated THP-1 macrophages promoted migration of primary endometrial stromal cells from patients with EM, an effect reversed by GW9662 or IL-10 neutralization. Together, these results outline a gut microbiota-LysoPC(16:0)-PPARγ-M2-IL-10 axis in EM pathogenesis, a mechanistic and therapeutic target for future clinical study.},
}

@article {pmid42921032,
year = {2026},
author = {Huang, M and Xie, B and Liu, H},
title = {Gut microbiota-immune-bone axis in osteoporosis: mechanisms and intervention strategies.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1879472},
doi = {10.3389/fphar.2026.1879472},
pmid = {42921032},
issn = {1663-9812},
abstract = {Osteoporosis (OP) remains a major global health burden, yet current pharmacological interventions are constrained by adverse effects, limited efficacy, and a bone-centric therapeutic paradigm that overlooks upstream pathogenic drivers. Emerging evidence positions the gut microbiota (GM) as a critical rheostat of bone homeostasis, operating through a gut-immune-bone axis that integrates microbial metabolism, intestinal barrier integrity, and systemic immune regulation. This review systematically examines the immunopathological mechanisms of OP, with particular emphasis on the GM-derived metabolites-short-chain fatty acids, secondary bile acids, tryptophan derivatives, lipopolysaccharide, and trimethylamine N-oxide-that orchestrate osteoclastogenic versus osteoprotective outcomes via key immune checkpoints including the Th17/Treg, macrophage phenotypic polarization, and regulatory B cell axes. We further delineate the subtype-specific heterogeneity of this axis across postmenopausal, senile, glucocorticoid-induced, and diabetic osteoporosis, highlighting distinct microbial and immune signatures that mandate stratified therapeutic approaches. Importantly, we evaluate the translational potential of GM-targeted interventions-probiotics, prebiotics, fecal microbiota transplantation, and dietary modulation-as adjunctive or standalone strategies, and discuss their synergistic interplay with conventional anti-osteoporotic agents. By reframing OP as a systems-level disorder of the gut-immune-bone circuitry, this review establishes a mechanistic groundwork for precision medicine, identifies novel druggable targets, and charts a course toward safer, more durable, and disease-modifying anti-osteoporotic therapies.},
}

@article {pmid42921249,
year = {2026},
author = {Zhang, M and Zhang, S and Ren, X},
title = {Gut microbiota-host immunity crosstalk in psoriasis: from dysbiosis to cutaneous inflammation.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1957850},
doi = {10.3389/fimmu.2026.1957850},
pmid = {42921249},
issn = {1664-3224},
mesh = {Humans ; *Psoriasis/immunology/microbiology/therapy/metabolism ; *Dysbiosis/immunology ; *Gastrointestinal Microbiome/immunology ; Animals ; *Skin/immunology/metabolism/microbiology ; Intestinal Barrier Function ; Immunity, Innate ; Th17 Cells/immunology ; Inflammation/immunology ; },
abstract = {Psoriasis is a chronic inflammatory skin disease driven by the IL-23/IL-17 axis. Evidence accumulated over the past decade indicates that its pathogenesis extends beyond the skin and involves bidirectional communication between the intestinal microbiota and host immunity. This narrative review organizes current evidence along a proposed sequence running from gut dysbiosis and intestinal barrier damage, through altered microbial metabolites, to reprogrammed host immune responses and cutaneous inflammation. We summarize the gut microbiota changes reported in patients with psoriasis and the clinical evidence for impaired intestinal permeability. We describe how microbiota-derived metabolites-short-chain fatty acids (SCFAs), tryptophan/kynurenine metabolites, and bile acids-modulate Th17/Treg balance and innate immunity through the aryl hydrocarbon receptor (AhR) and G protein-coupled receptors. We then review clinical data on microbiome-directed interventions, chiefly probiotics and fecal microbiota transplantation (FMT), and close with the outstanding issues in causal inference, methodological heterogeneity, and standardization of interventions. The current evidence is consistent with the gut-skin axis hypothesis. The direction of causality between the microbiota and psoriasis, the dose-response relationship, and the clinical benefit of microbiome-directed therapy nonetheless remain to be confirmed in prospective cohorts and well-designed randomized controlled trials.},
}

Humans
*Psoriasis/immunology/microbiology/therapy/metabolism
*Dysbiosis/immunology
*Gastrointestinal Microbiome/immunology
Animals
*Skin/immunology/metabolism/microbiology
Intestinal Barrier Function
Immunity, Innate
Th17 Cells/immunology
Inflammation/immunology

@article {pmid42921324,
year = {2026},
author = {Balsamo, JM and Bess, EN},
title = {Leveraging the Gut Microbiota for Mechanistically Informed Therapeutics against Body-First Parkinson's Disease.},
journal = {ACS bio & med chem Au},
volume = {6},
number = {5},
pages = {508-521},
doi = {10.1021/acsbiomedchemau.6c00110},
pmid = {42921324},
issn = {2694-2437},
abstract = {Although some symptoms of Parkinson's disease can be pharmacologically alleviated, stopping disease progression is not currently possible. Motor impairment in Parkinson's disease is associated with accumulation of aggregates of the protein α-synuclein (α-syn) in dopaminergic neurons in the brain. In some Parkinson's disease cases, these pathogenic aggregates accumulate in the intestinal lining years before motor symptoms manifest. This long prodromal period provides a window of opportunity to detect Parkinson's disease and halt its progression. Specifically, elucidating the factors involved in disease onset in the gut would enable prevention of α-syn aggregation before it spreads to the brain. In this perspective, we highlight discoveries of gut bacteria that induce aggregation of intestinal α-syn as well as efforts to decipher the molecular-level mechanisms by which this process occurs. We also showcase the rationale and potential breadth of applications focused on manipulating the gut microbiome, including biotics, fecal microbiome transplants, and microbial editing. By understanding molecular mechanisms of intestinal α-syn aggregation, the microbiome may be harnessed to control the factors responsible for their pathogenic formation and spread. Such insights will ultimately enable the development of more effective therapeutics for prevention and treatment of Parkinson's disease.},
}

@article {pmid42921440,
year = {2026},
author = {Cotella, D},
title = {Gene, microbiome, and anti-aging doping in sport: molecular mechanisms, detection strategies, and implications for sports rehabilitation medicine.},
journal = {Frontiers in sports and active living},
volume = {8},
number = {},
pages = {1984895},
doi = {10.3389/fspor.2026.1984895},
pmid = {42921440},
issn = {2624-9367},
abstract = {Advances in gene transfer have created legitimate opportunities for tissue repair, but the same tools raise the prospect of illicit use to enhance athletic performance ("gene doping"). Evidence that elite athletes harbour a distinctive gut microbiota has raised a parallel concern that microbiome manipulation, including faecal microbiota transplantation (FMT) from high-performing donors, could be used as a form of biological enhancement ("microbiome doping"). A third, related frontier is anti-aging gene therapy (telomerase and Klotho gene delivery and partial cellular reprogramming) which targets the same muscle- and stem-cell-regenerative pathways relevant to injury recovery and has already reached unregulated human self-experimentation. This narrative review summarises the principal gene-doping targets relevant to performance and recovery (erythropoietin, myostatin/activin inhibitors, insulin-like growth factor 1, PPAR-δ/AMPK reprogramming), their delivery vectors, and current detection strategies. It then reviews athlete-associated gut microbiota signatures, notably the lactate-metabolising bacterium Veillonella atypica, and the feasibility and detection challenges of microbiota transplantation, before examining the rationale, targets, and governance challenges of anti-aging gene therapy. Attention is given to the overlap between all three frontiers and legitimate regenerative, microbiota-directed, or aging-biology therapies under investigation for musculoskeletal, metabolic, and gastrointestinal conditions, an overlap that places rehabilitation clinicians in a sensitive position, particularly with older or master athletes; across all three frontiers, the same biological pathways and delivery technologies are simultaneously being developed for legitimate therapeutic use, creating a recurring dual-use dilemma for clinicians and regulators alike. I review safety risks, the regulatory framework administered by the World Anti-Doping Agency (WADA) and its gaps regarding microbiome and longevity interventions, and the practical responsibilities of rehabilitation professionals. I conclude that interdisciplinary collaboration between molecular biologists, microbiome and aging researchers, anti-doping scientists, and clinicians is essential to keep detection methods and clinical governance aligned with the pace of innovation in these three areas, and we outline specific priorities, including clarification of the regulatory status of microbiota transfer and anti-aging gene constructs, strain-level metagenomic monitoring, and biological-age biomarkers, for achieving this alignment.},
}

@article {pmid42921543,
year = {2026},
author = {Ren, Y and Hu, Y and Qin, H and Zhang, Y and Zhao, H},
title = {Dynamic Gut-Lung Microbiome Interactions Beyond Dysbiosis Across the Course of COPD.},
journal = {International journal of chronic obstructive pulmonary disease},
volume = {21},
number = {},
pages = {649518},
doi = {10.2147/COPD.S649518},
pmid = {42921543},
issn = {1178-2005},
mesh = {Humans ; *Pulmonary Disease, Chronic Obstructive/microbiology/physiopathology/immunology/therapy/metabolism/diagnosis ; *Gastrointestinal Microbiome ; *Dysbiosis ; *Lung/microbiology/physiopathology/metabolism/immunology ; Animals ; *Bacteria/metabolism/immunology/growth & development/drug effects ; Disease Progression ; Host-Pathogen Interactions ; Fecal Microbiota Transplantation ; },
abstract = {Chronic obstructive pulmonary disease (COPD) is a heterogeneous respiratory disorder characterized by persistent airflow limitation, progressive functional decline, and recurrent exacerbations. Increasing evidence indicates that microbiome alterations in COPD extend beyond the airways and involve coordinated changes across respiratory and intestinal compartments. Importantly, these alterations are dynamic rather than static, varying across stable disease, disease progression, acute exacerbations, and distinct inflammatory phenotypes. Changes in the gut microbiome are accompanied by alterations in microbial metabolites, particularly short-chain fatty acids and tryptophan-derived metabolites, as well as impaired intestinal barrier integrity and systemic inflammatory responses. Emerging evidence from respiratory samples further suggests that airway microbial functional features and local metabolic alterations may contribute to pulmonary host responses, although respiratory microbial metabolites remain less extensively characterized. Experimental studies further suggest that microbiome-derived signals can modulate neutrophils, macrophages, T-cell balance, and innate lymphoid cells, thereby influencing pulmonary inflammation and tissue injury. Fecal microbiota transplantation studies provide additional evidence that disease-associated microbial communities can modify susceptibility to smoke-induced lung injury, supporting a potential causal contribution of the gut microbiome. Meanwhile, probiotics, dietary fiber, short-chain fatty acid supplementation, macrolides, and traditional Chinese medicine or natural products have shown preliminary microbiome-associated benefits, although clinical evidence remains limited and heterogeneous. This review summarizes dynamic airway and gut microbiome alterations across the course of COPD, integrates current evidence on microbial metabolism, intestinal barrier dysfunction, and immune responses, and evaluates emerging microbiome-related therapeutic strategies. Future studies should prioritize longitudinal multi-compartment sampling, standardized microbiome methodology, mechanistic validation, and adequately powered clinical trials to determine whether microbiome modulation can provide reproducible clinical benefit in defined COPD populations.},
}

Humans
*Pulmonary Disease, Chronic Obstructive/microbiology/physiopathology/immunology/therapy/metabolism/diagnosis
*Gastrointestinal Microbiome
*Dysbiosis
*Lung/microbiology/physiopathology/metabolism/immunology
Animals
*Bacteria/metabolism/immunology/growth & development/drug effects
Disease Progression
Host-Pathogen Interactions
Fecal Microbiota Transplantation

@article {pmid42921678,
year = {2026},
author = {Bonnet, M and Labussière-Wallet, H and Dumez, P and Jauffret, L and Aubert, L and Avondo-Ray, A and Seurret, C and Devic, P and Souci, S and Laperche, S and Saint Martin, L and Frobert, E and Gaymard, A and Giorgi, J and Semanas, Q and Chalvignac, R and Oblette, A and Lapendry, A and Pozzetto, B and Perpoint, T and Kelleci, M and Sécula, A and Foret-Lucas, C and Javaux, C and Morfin, F and Bal, A and Brottet, E and Krug, C and Jourdain, F and Meyronet, D and Ader, F and Guérin, JL and Josset, L and Destras, G},
title = {Fatal encephalitis caused by Shamonda virus Europe 1 (SHAV-EU1) in a patient with a severely weakened immune system, France, 2026.},
journal = {Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin},
volume = {31},
number = {42},
pages = {},
doi = {10.2807/1560-7917.ES.2026.31.42.2600883},
pmid = {42921678},
issn = {1560-7917},
mesh = {Humans ; Fatal Outcome ; France ; Viral Load ; *Bunyaviridae Infections/diagnosis/virology ; Reverse Transcriptase Polymerase Chain Reaction ; *Encephalitis, Viral/diagnosis/virology ; Male ; *Immunocompromised Host ; RNA, Viral ; Phylogeny ; Feces/virology ; Animals ; },
abstract = {New Shamonda virus clades (SHAV-EU1 and SHAV-EU2) emerged in Europe in summer 2026, primarily affecting cattle. We report the first human infection with SHAV-EU1: a French patient with a severely weakened immune system developed fatal encephalitis in September 2026, 1 month after their allogeneic stem cell transplantation. Metatranscriptomics detected SHAV-EU1 in cerebrospinal fluid, confirmed by RT-PCR. Biopsies from central nervous system showed high viral loads. Investigations revealed SHAV-EU1 in serum, respiratory and stool samples at least for 2 months before encephalitis onset.},
}

Humans
Fatal Outcome
France
Viral Load
*Bunyaviridae Infections/diagnosis/virology
Reverse Transcriptase Polymerase Chain Reaction
*Encephalitis, Viral/diagnosis/virology
Male
*Immunocompromised Host
RNA, Viral
Phylogeny
Feces/virology
Animals

@article {pmid42924218,
year = {2026},
author = {Matsuda, Y},
title = {The gut microenvironment in antibody-mediated rejection: from conventional immunosuppression to precision immunomodulation in organ transplantation.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1968780},
pmid = {42924218},
issn = {1664-3224},
mesh = {Humans ; *Graft Rejection/immunology/prevention & control/microbiology ; *Organ Transplantation/adverse effects ; Animals ; *Immunomodulation ; *Gastrointestinal Microbiome/immunology ; Immunosuppression Therapy/methods ; Graft Survival/immunology ; Immunosuppressive Agents/therapeutic use ; },
abstract = {The gut microbiota and broader gut microenvironment, comprising microbiota-derived metabolites and host-microbial interactions, have emerged as potentially modifiable factors associated with host immune regulation and have been implicated in altered drug responsiveness, immune-mediated diseases, and metabolic disorders. Accumulating evidence suggests that the gut microenvironment may modulate post-transplant immune responses and may provide candidate biomarkers and therapeutic targets in organ transplantation. Gut dysbiosis has been associated with immune dysregulation and adverse allograft outcomes, although direct causal evidence in human AMR remains limited. Profiling the gut microenvironment may therefore complement conventional immune monitoring for post-transplant risk stratification. In this review, current evidence on the interactions among the gut microbiota, microbiota-derived metabolites, and host immune regulation is synthesized, with particular emphasis on the role of the gut microenvironment in maintaining immune homeostasis and influencing transplant outcomes. The impact of alterations in the gut microenvironment on the development of antibody-mediated rejection-a major barrier to long-term graft survival-is examined by focusing on their effects on regulatory immune pathways and inflammatory responses. The potential role of microbiota-derived metabolites in promoting immune tolerance and graft accommodation, two complementary mechanisms that contribute to long-term allograft protection, is also discussed. Finally, gut microenvironment-based strategies for early diagnosis, risk stratification, and rejection prediction are evaluated, alongside therapeutic interventions including prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation. These strategies may facilitate pre-emptive intervention before irreversible graft injury develops and support a shift from conventional immunosuppression towards precision immunomodulation in transplantation medicine.},
}

Humans
*Graft Rejection/immunology/prevention & control/microbiology
*Organ Transplantation/adverse effects
Animals
*Immunomodulation
*Gastrointestinal Microbiome/immunology
Immunosuppression Therapy/methods
Graft Survival/immunology
Immunosuppressive Agents/therapeutic use

@article {pmid42924581,
year = {2026},
author = {Wang, Y and Zeng, H and Liu, N and Yang, D},
title = {Gut‑kidney axis in chronic kidney disease: Dysbiosis, uremic metabolites and therapeutic opportunities (Review).},
journal = {Molecular medicine reports},
volume = {34},
number = {6},
pages = {},
doi = {10.3892/mmr.2026.14047},
pmid = {42924581},
issn = {1791-3004},
mesh = {Humans ; *Dysbiosis/metabolism/microbiology/therapy ; *Renal Insufficiency, Chronic/metabolism/therapy/microbiology/pathology ; *Gastrointestinal Microbiome ; *Uremic Toxins/metabolism ; *Kidney/metabolism/pathology ; Animals ; Prebiotics ; Probiotics/therapeutic use ; Indican/metabolism ; Fecal Microbiota Transplantation ; },
abstract = {Chronic kidney disease (CKD) poses a notable global health burden. Beyond traditional pathways, the gut‑kidney axis has emerged as a potential contributor to disease progression. In the present narrative review, current evidence on the role of intestinal dysbiosis, characterized by reduced microbial diversity, depletion of beneficial short‑chain fatty acid producers and expansion of uremic toxin‑generating bacteria, in the accumulation of nephrotoxic metabolites (such as indoxyl sulfate, p‑cresyl sulfate and trimethylamine N‑oxide) is summarized. These toxins promote oxidative stress, inflammation and fibrosis, accelerating renal decline. By contrast, microbially derived short‑chain fatty acids exert protective effects. Although therapeutic strategies targeting the gut microbiome (including probiotics, prebiotics and adsorbents) and fecal microbiota transplantation (targeting the gut microbiome) exhibit potential in modulating toxin levels, evidence for clinical endpoint benefit remains insufficient. In the present review, mechanistic insights were critically evaluated, clinical intervention studies are systematically summarized in tabulated form and a roadmap for personalized, microbiota‑informed therapeutic strategies is proposed.},
}

Humans
*Dysbiosis/metabolism/microbiology/therapy
*Renal Insufficiency, Chronic/metabolism/therapy/microbiology/pathology
*Gastrointestinal Microbiome
*Uremic Toxins/metabolism
*Kidney/metabolism/pathology
Animals
Prebiotics
Probiotics/therapeutic use
Indican/metabolism
Fecal Microbiota Transplantation

@article {pmid42906827,
year = {2026},
author = {Odakura, R and Seki, N and Nomura, K and Inoue, Y and Yakabe, K and Akiyama, M and Yao, T and Okano, S and Suda, W and Masuoka, H and Zhang, X and Orikasa, M and Omori, M and Koma, M and Maruyama, T and Yanagisawa, N and Murakami, T and Mori, H and Toyoda, A and Suzuki, J and Izuta, H and Srirat, T and Haneda, T and Miki, T and Ito, M and Ito, T and Shibuya, T and Katsumata, R and Nakato, G and Mizutani, S and Yamada, T and Sasaki, N and Hase, K and Fukuda, S and Nagahara, A and Ishikawa, D and Kim, YG},
title = {Microbiota-Taurine Pathway Links Dietary Fiber to Mucosal Healing.},
journal = {Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1053/j.gastro.2026.09.028},
pmid = {42906827},
issn = {1528-0012},
abstract = {BACKGROUND AND AIMS: Dietary fibers modulate host-microbiota interactions. Whether fiber promotes epithelial repair through microbiota-dependent mechanisms remains unclear. We determined how alginate influences colitis recovery and whether the pathway is relevant to ulcerative colitis (UC).

METHODS: We screened fibers in dextran sodium sulfate (DSS)-induced murine colitis and assessed survival, inflammation, barrier function, and epithelial regeneration. Microbiota dependence was evaluated using antibiotics and bacterial supplementation. Metabolites were profiled using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS), and epithelial programs were analyzed using RNA-seq and colonic organoid injury assays. Slc6a6-/- and Cyp2c55-/- mice were used to determine mechanistic requirements. Translational relevance was examined in a randomized, placebo-controlled trial of UC patients receiving antibiotic-primed fecal microbiota transplantation (A-FMT) followed by alginate or placebo. Clinical outcomes, histology, fecal taurine, and colonic CYP2C18 expression were assessed.

RESULTS: Alginate improved DSS colitis recovery, reducing inflammation, restoring barrier integrity, and enhancing crypt proliferation. Alginate enriched taurine-releasing bacteria, including Bacteroides acidifaciens and Ligilactobacillus murinus, and increased intestinal taurine; antibiotic disruption abrogated these effects. Taurine was required for benefit, as alginate failed in Slc6a6-/- mice. Alginate and taurine induced epithelial Cyp2c55, and protection was lost in Cyp2c55-/- mice and organoids. In the clinical trial, the primary endpoint was not met. However, alginate supplementation was associated with biological changes, including fecal taurine levels and colonic CYP2C18 expression, consistent with preclinical mechanisms.

CONCLUSION: Alginate engages a fiber-microbiota-taurine-epithelial signaling pathway that promotes recovery in preclinical models. The clinical trial did not meet its primary endpoint; however, the biological changes warrant further investigation of alginate as a microbiota-targeted intervention.

CLINICAL TRIAL REGISTRY: jRCTs031200103 (https://jrct.mhlw.go.jp/), registered September 1, 2020: UMIN000041968 (https://www.umin.ac.jp/ctr/index.htm), October 1, 2020.},
}

@article {pmid42907031,
year = {2026},
author = {Zhou, Z and Zhang, Q and Zhong, L and Deng, X and Ma, Y and Ng, WH and Rahman, MSLR and Zhu, J and Li, C},
title = {A V-type starch-lycopene complex with enhanced cis-lycopene content alleviates hyperglycemia and glycogen fragility in type 2 diabetic db/db mice via gut microbiota.},
journal = {Carbohydrate polymers},
volume = {392},
number = {},
pages = {125905},
doi = {10.1016/j.carbpol.2026.125905},
pmid = {42907031},
issn = {1879-1344},
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Diabetes Mellitus, Type 2/drug therapy/metabolism/microbiology ; *Lycopene/chemistry/pharmacology/therapeutic use ; Mice ; *Hyperglycemia/drug therapy/metabolism ; *Glycogen/metabolism ; Male ; *Starch/chemistry/pharmacology ; Liver/metabolism/drug effects ; Mice, Inbred C57BL ; Blood Glucose ; *Hypoglycemic Agents/chemistry/pharmacology ; Proto-Oncogene Proteins c-akt/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; },
abstract = {Type 2 diabetes mellitus (T2DM) is a major global health challenge. Resistant starch type 5 (RS5), formed by complexing starch with guest components into V-type crystalline structures, represents a promising approach for glycemia control. Native lycopene has anti-diabetic potential but limited bioactivity. Here we developed a V-type corn starch-lycopene RS5 complex (CS-LYC) and evaluated its effects in T2DM db/db mice, focusing on glycemic control and gut microbiota-liver glycogen connection. CS-LYC contained 26.07% resistant starch and 11.8 mg/g lycopene, with complexation promoting isomerization to the more bioactive (13Z)-isomer and increasing lycopene accumulation in both plasma and liver in vivo. In db/db mice, CS-LYC improved insulin sensitivity and glucose homeostasis by remodeling gut microbiota (enriching Akkermansia and Alistipes) and increasing metabolites (short-chain fatty acids and indole derivatives), subsequently maintaining intestinal barrier function and stimulating GLP-1 secretion. Through the gut-liver axis, this GLP-1 activated the hepatic PI3K/AKT pathway and increased the proportion of stable glycogen α particles, thereby reducing glycogen fragility, with fecal microbiota transplantation further confirming that these effects were mediated by gut microbiota. Collectively, CS-LYC alleviates T2DM via the gut-liver GLP-1/PI3K-AKT axis, offering a new dietary strategy for diabetes management.},
}

Animals
*Gastrointestinal Microbiome/drug effects
*Diabetes Mellitus, Type 2/drug therapy/metabolism/microbiology
*Lycopene/chemistry/pharmacology/therapeutic use
Mice
*Hyperglycemia/drug therapy/metabolism
*Glycogen/metabolism
Male
*Starch/chemistry/pharmacology
Liver/metabolism/drug effects
Mice, Inbred C57BL
Blood Glucose
*Hypoglycemic Agents/chemistry/pharmacology
Proto-Oncogene Proteins c-akt/metabolism
Phosphatidylinositol 3-Kinases/metabolism

@article {pmid42908874,
year = {2026},
author = {Jie, Y and Yang, X and Lou, P and Chen, W},
title = {Pulsatilla decoction attenuates colorectal cancer progression in association with gut microbiota remodeling, T-cell immune restoration, and NF-κB/JAK2/STAT3 signaling suppression.},
journal = {American journal of cancer research},
volume = {16},
number = {9},
pages = {4170-4188},
pmid = {42908874},
issn = {2156-6976},
abstract = {Pulsatilla Decoction (PD) exhibits anti-inflammatory properties, but its impact on colorectal cancer (CRC) and the role of gut microbiota remain incompletely understood. This study investigated the antitumor effects of PD in a xenograft mouse model of HCT116 cells reconstituted with human peripheral blood mononuclear cells. We also analyzed corresponding changes in gut microbiota, T-cell immunity, inflammatory responses, and NF-κB/JAK2/STAT3 signaling. Tumor-bearing mice were treated for three weeks with low-, medium-, or high-dose PD, or with 5-fluorouracil. Gut microbiota composition and function were analyzed using 16S rRNA and metagenomic sequencing. Immune cell populations, cytokines, and pathway-related proteins were assessed via flow cytometry, immunofluorescence, ELISA, RT-qPCR, and western blotting. To further evaluate the involvement of microbiota, we performed antibiotic pretreatment followed by fecal microbiota transplantation (FMT). PD effectively reduced tumor volume and weight without causing significant body weight loss. High-dose PD partially restored microbial diversity and community structure, increased Akkermansia muciniphila, and modulated inflammation- and metabolism-related microbial pathways. Furthermore, PD enhanced peripheral and intratumoral CD4[+] and CD8[+] T-cell responses, improved the splenic Treg/Th17 balance, decreased TNF-α, IL-6, and IL-17A, increased IL-10, and suppressed NF-κB, JAK2, and STAT3 activation in tumor tissues. FMT from high-dose PD-treated donors partially transferred tumor inhibition, increased tumor CD8A and granzyme B, reduced Foxp3, and lowered NF-κB, JAK2, and STAT3 levels in recipient mice not directly treated with PD. These findings suggest that PD inhibits CRC progression by coordinately modulating gut microbiota, T-cell immunity, inflammation, and NF-κB/JAK2/STAT3 signaling, with the gut microbiota partially contributing to its antitumor effects.},
}

@article {pmid42909301,
year = {2026},
author = {Zeng, C and Liang, L and Lv, T},
title = {The role of gut microbiota in paediatric short bowel syndrome.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1970119},
pmid = {42909301},
issn = {2235-2988},
mesh = {Humans ; *Short Bowel Syndrome/microbiology/therapy/complications ; Dysbiosis/microbiology ; *Gastrointestinal Microbiome/physiology ; Intestinal Barrier Function ; Child ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; },
abstract = {Short bowel syndrome (SBS) is one of the leading causes of intestinal failure in children. Its development is influenced not only by the length and function of the residual intestine but is also closely related to the homeostasis of the gut microbiota. In recent years, the role of the gut microbiota in intestinal adaptation, metabolic regulation, and the development of complications in pediatric SBS has gradually garnered attention. This review summarizes the characteristics of the gut microbiota, mechanisms underlying dysbiosis, associations with complications, and microbiota-targeted therapeutic strategies in pediatric SBS. Existing studies indicate that children with SBS exhibit reduced microbiota diversity, compositional abnormalities, and metabolic dysfunction. Gut microbiota dysbiosis may be associated with intestinal barrier disruption, immune dysregulation, alterations in residual intestinal structure, and parenteral nutrition, and may contribute to the development and progression of complications such as small intestinal bacterial overgrowth (SIBO), D-lactic acidosis (D-LA), and liver injury. Strategies such as probiotics, nutritional modulation, and fecal microbiota transplantation (FMT) have shown potential clinical value, although their efficacy and safety require further validation. Future studies integrating multi-omics approaches and long-term longitudinal investigations are needed to elucidate the mechanisms underlying interactions between the microbiota and host, thereby providing a theoretical basis for microbiota-targeted interventions and improving long-term outcomes in children with SBS.},
}

Humans
*Short Bowel Syndrome/microbiology/therapy/complications
Dysbiosis/microbiology
*Gastrointestinal Microbiome/physiology
Intestinal Barrier Function
Child
Probiotics/therapeutic use
Fecal Microbiota Transplantation

@article {pmid42909651,
year = {2026},
author = {Venkatesh, V and Yodoshi, T and Seetharaman, K and Anushree, N},
title = {Targeting the gut-liver axis and gut microbiome in pediatric metabolic dysfunction-associated steatotic liver disease: current evidence and future directions.},
journal = {European journal of pediatrics},
volume = {185},
number = {11},
pages = {},
pmid = {42909651},
issn = {1432-1076},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Child ; Probiotics/therapeutic use ; Prebiotics ; *Fatty Liver/therapy/microbiology ; Fecal Microbiota Transplantation ; *Liver/metabolism ; Synbiotics ; Metabolic Syndrome/complications ; },
abstract = {UNLABELLED: Pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease in children, closely linked to the rising prevalence of childhood obesity and metabolic syndrome. Increasing evidence highlights the central role of the gut-liver axis and the gut microbiome in disease pathogenesis, offering potential targets for therapeutic modulation. This review aims to summarize current evidence on interventions targeting the gut-liver axis and the gut microbiome in pediatric MASLD and explore emerging strategies in this field. This narrative review was undertaken after searching PubMed and Embase databases for available up-to-date literature on pediatric MASLD and therapeutic interventions targeting the gut microbiome and gut-liver axis, including dietary therapy, prebiotics, probiotics, synbiotics, fecal microbiota transplantation (FMT), and pharmacological therapies. Dietary interventions, including low-free-sugar and Mediterranean-style diets, improve hepatic and metabolic outcomes, although microbiome-mediated benefits remain unproven in children. Probiotics and synbiotics show modest and variable effects, with heterogeneity in strains, dosing, and outcomes limiting definitive conclusions. Evidence for FMT in pediatric MASLD is absent, with only indirect evidence from adolescent obesity and other pediatric diseases. Pharmacological therapies, including glucagon-like peptide-1 receptor agonists and farnesoid X receptor agonists, have demonstrated metabolic and hepatic benefits primarily in adult populations, while effects on microbial metabolism, intestinal barrier integrity, and bile acid signalling provide potential mechanisms linking these therapies to the gut-liver axis. Although microbiome-mediated mechanisms have been proposed, direct evidence linking these therapies to microbiome changes in pediatric MASLD is currently lacking. Emerging approaches such as precision nutrition, engineered probiotics, and bacteriophage therapy offer potential avenues for targeted modulation of disease-relevant pathways.

CONCLUSION:   Therapeutic modulation of the gut-liver axis and the gut microbiome represents a biologically plausible and evolving strategy in pediatric MASLD. Current pediatric evidence remains limited, and robust, well-designed clinical trials incorporating microbiome profiling and clinically meaningful endpoints are needed to establish efficacy and enable personalized, therapeutic strategies.

WHAT IS KNOWN: • Pediatric MASLD is increasing in prevalence, and alterations in the gut-liver axis and the gut microbiome are known to contribute to the pathogenesis of the disease by influencing various disease-relevant pathways such as intestinal permeability, bile acid signaling, hepatic lipid metabolism, inflammation, and fibrogenesis.

WHAT IS NEW: • This review provides current evidence for interventions targeting the gut microbiome and gut-liver axis in pediatric MASLD including dietary modulation, probiotics, and pharmacological interventions and highlights new approaches such as precision nutrition, engineered probiotics, bacteriophage therapy, and personalized treatment strategies.},
}

Humans
*Gastrointestinal Microbiome/physiology
Child
Probiotics/therapeutic use
Prebiotics
*Fatty Liver/therapy/microbiology
Fecal Microbiota Transplantation
*Liver/metabolism
Synbiotics
Metabolic Syndrome/complications

@article {pmid42911041,
year = {2026},
author = {Shatila, M and Wali, S and Cruz, CC and Abdul-Baki, K and Natha, C and Takigawa, K and Gupta, T and Rivera, AU and Vemulapalli, V and Lu, L and Baerman, E and Salim, H and Sullivan, A and Lee, IJ and Menon, R and Khan, A and Coleman, G and Török, HP and Schneider, B and Thomas, M and Thomas, AS and Li, Z and Qiao, W and Wang, Y},
title = {Fecal calprotectin trends in immune-mediated colitis and their role in predicting treatment needs and clinical outcomes.},
journal = {European journal of gastroenterology & hepatology},
volume = {},
number = {},
pages = {},
doi = {10.1097/MEG.0000000000003300},
pmid = {42911041},
issn = {1473-5687},
abstract = {OBJECTIVES: Immune-mediated colitis (IMC) is a common toxicity of immune checkpoint inhibition. Fecal calprotectin is useful in the initial evaluation and surveillance of IMC. No studies have examined trends in calprotectin and its prognostic value. We explored these trends to identify clinically meaningful thresholds for changes in calprotectin.

METHODS: This was a single-center retrospective study including all patients who received immune checkpoint inhibitors from January 2010 to February 2024, developed IMC, and whose calprotectin levels at diagnosis and afterward were available for analysis.

RESULTS: Of the 767 patients meeting study criteria, 80.6% had elevated baseline calprotectin levels. Increased baseline calprotectin values were associated with the need for aggressive treatment (P < 0.001), with a cutoff of 849 µg/g maximizing specificity for future biologic therapy (88.3%). Most calprotectin-level improvements occurred within a median of 2-3 months, with normalization by about 4 months. Cutoffs of a 66.2% calprotectin-level improvement and a 234-µg/g fecal calprotectin-level decrease at 60-75 days from diagnosis achieved 100% specificity for clinical remission.

DISCUSSION: This is the first study to date to identify calprotectin cutoff values for predicting IMC outcomes. We found that baseline calprotectin values achieved high specificity in predicting future biologic therapy. Changes in calprotectin level by 2-3 months had a high specificity of 100% for clinical and endoscopic remission. Taken together, these findings suggest that fecal calprotectin can be a reliable biomarker to determine the need for biologic therapy for IMC and can be used to predict clinical and endoscopic remission.},
}

@article {pmid42912803,
year = {2026},
author = {Jiang, H and Peng, Y and Lam, B and Yang, K and Lin, Y and Mak, JWY and Tse, YK and Chan, FKL and Xu, Z and Ng, SC},
title = {Gut virome remodeling after fecal microbiota transplantation is associated with virus-bacteria co-variation and metabolic response in obesity and type 2 diabetes.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2746820},
doi = {10.1080/19490976.2026.2746820},
pmid = {42912803},
issn = {1949-0984},
mesh = {Humans ; *Diabetes Mellitus, Type 2/therapy/metabolism/microbiology/virology ; *Fecal Microbiota Transplantation ; *Obesity/therapy/metabolism/microbiology/virology ; *Virome ; Feces/microbiology/virology ; *Bacteria/genetics/classification/isolation & purification ; *Gastrointestinal Microbiome ; *Viruses/classification/genetics/isolation & purification ; },
abstract = {Fecal microbiota transplantation (FMT) modifies gut bacterial composition and improves metabolic outcomes in subjects with obesity and type 2 diabetes (ObT2), but bacterial changes alone do not fully explain the heterogeneity in clinical response. We performed virus-like particle (VLP)-enriched metagenomic sequencing coupled with bulk-DNA metagenomic sequencing on longitudinal fecal samples from a randomized controlled FMT trial in ObT2. Using random forest classification, post-FMT virome changes showed accuracy comparable to bacteriome changes (84.8% vs 81.4%) in distinguishing LDL responders from non-responders. Donor-derived viral contig engraftment was detected in 64.7% (11/17) of recipients receiving FMT alone and 58.8% (10/17) receiving FMT with lifestyle intervention (LSI), versus 5.6% (1/18) in the sham with LSI group. FMT was associated with increased virome diversity, compositional shifts toward the donor virome, and coordinated virus-bacteria associations, with most responsive viral contigs classified as Caudoviricetes. FMT-responsive viral contigs that were shared between the two FMT groups were predicted to infect Roseburia and Bifidobacterium, while contigs associated with clinical responses were predicted to infect Escherichia, Roseburia, Blautia, and Enterococcus. These findings suggest that the gut virome is a complementary ecological component associated with FMT responses and metabolic outcomes in ObT2.},
}

Humans
*Diabetes Mellitus, Type 2/therapy/metabolism/microbiology/virology
*Fecal Microbiota Transplantation
*Obesity/therapy/metabolism/microbiology/virology
*Virome
Feces/microbiology/virology
*Bacteria/genetics/classification/isolation & purification
*Gastrointestinal Microbiome
*Viruses/classification/genetics/isolation & purification

@article {pmid42914432,
year = {2026},
author = {Shi, J and Wang, G and Zhang, X and Zhang, N and Zhang, K and Wang, Q and Wang, Y and Li, T and Xue, M and Sha, Z},
title = {Astaxanthin alleviates Parkinson's disease via dual regulation of tryptophan metabolism: central STAT3/IDO1 inhibition and gut microbiota remodeling.},
journal = {Food research international (Ottawa, Ont.)},
volume = {245},
number = {Pt 2},
pages = {120737},
doi = {10.1016/j.foodres.2026.120737},
pmid = {42914432},
issn = {1873-7145},
mesh = {Animals ; Xanthophylls/pharmacology ; *STAT3 Transcription Factor/metabolism ; *Tryptophan/metabolism ; *Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism/antagonists & inhibitors ; *Gastrointestinal Microbiome/drug effects ; Mice ; Male ; Mice, Inbred C57BL ; Neuroprotective Agents/pharmacology ; Disease Models, Animal ; *Parkinson Disease/drug therapy/metabolism ; Dopaminergic Neurons/drug effects ; Signal Transduction/drug effects ; },
abstract = {Parkinson's disease (PD) is a progressive neurodegenerative disorder with limited disease-modifying treatments. Dysregulation of tryptophan metabolism via the gut-brain axis has emerged as a key pathogenic mechanism. Astaxanthin (AX), a dietary ketocarotenoid abundant in Haematococcus pluvialis and marine organisms, possesses potent antioxidant and anti-inflammatory properties; however, it remains unclear whether AX exerts neuroprotection in PD through specific modulation of tryptophan metabolism via the signal transducer and activator of transcription 3 (STAT3)/ indoleamine 2,3-dioxygenase 1 (IDO1) pathway and gut microbiota remodeling. In this study, an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced mouse model of PD was used to evaluate the neuroprotective effects of AX. AX ameliorated motor deficits, attenuated dopaminergic neuron loss in the substantia nigra (SN), suppressed neuroinflammation, and enhanced mitophagy. Mechanistically, AX directly inhibited STAT3 activation and downregulated IDO1 expression in the brain, reducing the conversion of tryptophan to neurotoxic quinolinic acid (QUIN). Concurrently, AX reshaped the gut microbiota by enriching Lactobacillus, which redirected tryptophan metabolism toward the production of neuroprotective indole derivatives, including indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA). Fecal microbiota transplantation (FMT) from AX-treated donors recapitulated key aspects of these effects, including suppression of signal transducer and activator of transcription 3(STAT3)/ indoleamine 2,3-dioxygenase 1(IDO1), elevation of IPA/IAA, and improvement of motor function, confirming that the gut microbiota mediates AX's neuroprotective action. These findings demonstrate that AX alleviates PD pathology through a dual mechanism: central inhibition of the STAT3/IDO1 pathway to block neurotoxic quinolinic acid production, and peripheral gut microbiota remodeling to enhance neuroprotective indole derivatives. This study positions AX as a promising functional food ingredient targeting tryptophan metabolism for PD intervention.},
}

Animals
Xanthophylls/pharmacology
*STAT3 Transcription Factor/metabolism
*Tryptophan/metabolism
*Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism/antagonists & inhibitors
*Gastrointestinal Microbiome/drug effects
Mice
Male
Mice, Inbred C57BL
Neuroprotective Agents/pharmacology
Disease Models, Animal
*Parkinson Disease/drug therapy/metabolism
Dopaminergic Neurons/drug effects
Signal Transduction/drug effects

@article {pmid42915120,
year = {2026},
author = {Zhang, Q and Zhou, Z and Cheung, YM and Yeung, HW and Li, M and He, C and Huang, S and Li, C and Chen, ZY and Wong, WT},
title = {Potato Turned Rice Mitigates Colitis through Gut Microbiota-Driven Regulation of SCFAs Production and Bile Acid Homeostasis.},
journal = {Journal of agricultural and food chemistry},
volume = {74},
number = {36},
pages = {28510-28525},
doi = {10.1021/acs.jafc.6c06560},
pmid = {42915120},
issn = {1520-5118},
support = {24B2/029A//Health Bureau/ ; 14104923//Research Grants Council, University Grants Committee/ ; 8300041//State Key Laboratory for Agrobiotechnology/ ; 8300068//State Key Laboratory for Agrobiotechnology/ ; },
mesh = {Animals ; *Solanum tuberosum/metabolism/chemistry ; *Bile Acids and Salts/metabolism ; *Colitis/microbiology/metabolism/diet therapy/chemically induced ; *Oryza/metabolism/chemistry ; *Gastrointestinal Microbiome ; Mice ; *Fatty Acids, Volatile/metabolism ; Homeostasis ; Humans ; Bacteria/classification/isolation & purification/genetics/metabolism ; Mice, Inbred C57BL ; Male ; Dextran Sulfate/adverse effects ; },
abstract = {Exploring alternative staple foods supports food security, yet fresh potatoes have storage and palatability limitations. Potato turned rice (PTR), a processed potato product to overcome these drawbacks, may benefit gut health, but its anticolitis effects and underlying mechanisms remain unclear. This study investigated PTR's physicochemical properties, gut microbiota modulation, and protection against dextran sulfate sodium (DSS)-induced colitis. PTR retained a stable postcooking V-type crystalline structure of type 5 resistant starch (RS5), distinct from normal rice (NRC). Long-term PTR intake elevated gut microbial α diversity and enriched beneficial genera. In colitis mice, PTR alleviated symptoms, preserved intestinal barrier, promoted short-chain fatty acids (SCFAs), and restored bile acid metabolism via farnesoid X receptor (FXR) upregulation. Antibiotic-induced microbiota depletion abolished PTR's benefits, while fecal microbiota transplantation (FMT) from PTR-fed donors transferred colitis protection. Collectively, PTR alleviates colitis through the gut microbiota-SCFAs-bile acid axis, showing potential as a gut-beneficial functional staple.},
}

Animals
*Solanum tuberosum/metabolism/chemistry
*Bile Acids and Salts/metabolism
*Colitis/microbiology/metabolism/diet therapy/chemically induced
*Oryza/metabolism/chemistry
*Gastrointestinal Microbiome
Mice
*Fatty Acids, Volatile/metabolism
Homeostasis
Humans
Bacteria/classification/isolation & purification/genetics/metabolism
Mice, Inbred C57BL
Male
Dextran Sulfate/adverse effects

@article {pmid42915644,
year = {2026},
author = {Li, J and Li, J and Chen, Y and Wang, M and Chen, Z and Yap, PS and Lu, K and He, B},
title = {Gut Microbiota-Derived Indole-3-propionic Acid Attenuates Titanium Dioxide Nanoparticle-Induced Liver Injury by Targeting Kupffer Cells via the Gut-Liver Axis.},
journal = {ACS nano},
volume = {20},
number = {39},
pages = {26766-26784},
doi = {10.1021/acsnano.6c12176},
pmid = {42915644},
issn = {1936-086X},
support = {22376097//National Natural Science Foundation of China (NSFC)/ ; 42207478//National Natural Science Foundation of China (NSFC)/ ; LMS26B070002//Zhejiang Provincial Natural Science Foundation of China/ ; YKK22215//General Medical Science and Technology Development Project of Nanjing/ ; },
mesh = {*Titanium/chemistry/toxicity ; Animals ; *Indoles/pharmacology/metabolism/chemistry ; *Kupffer Cells/drug effects/metabolism ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Liver/drug effects/metabolism/pathology ; Mice, Inbred C57BL ; Male ; *Chemical and Drug Induced Liver Injury/drug therapy/metabolism/pathology ; *Nanoparticles/chemistry/toxicity ; },
abstract = {Nanotitanium dioxide (nTiO2) is widely used as a food additive, leading to chronic dietary exposure and rising health concerns. Although adverse effects on the liver and gut microbiota have been individually investigated, whether gut microbiota mediates nTiO2-induced liver injury remains unclear, especially given the well-established role of the gut-liver axis in hepatic physiology and pathology. Herein, we explored the long-term hepatotoxic effects of oral nTiO2 in mice and the underlying mechanisms through the lens of gut-liver axis crosstalk. Our results showed that chronic exposure to nTiO2 induced dose-dependent liver injury and the disorder of the gut microbiota. Spearman correlation analysis suggested the reduced abundance of beneficial taxa, notably g_Lactobacillus and g_Bacteroides, was strongly associated with elevated intestinal inflammation markers, impaired liver function indicators, and altered hepatic metabolite profiles. Fecal microbiota transplantation demonstrated that nTiO2-perturbed microbiota directly caused liver injury, while colonization with Lactobacillus intestinalis reversed this toxic phenotype, confirming the important role of gut microbiota in the liver injury mediated by nTiO2. More importantly, we found the administration of indole-3-propionic acid (IPA), one of the Lactobacillus-derived indole compounds, restored microbiota homeostasis and alleviated liver toxicity. Mechanistically, IPA increased the expression of MERTK receptor in Kupffer cells, enhancing their phagocytic capacity to redirect nTiO2 accumulation from hepatocytes to Kupffer cells, thereby reducing hepatic oxidative stress and inflammation. Collectively, these findings establish gut microbiota as a critical mediator of nTiO2-induced liver injury, highlight the hepatoprotective role of microbiota-derived IPA, and provide effective strategies for risk intervention against foodborne nanomaterials.},
}

*Titanium/chemistry/toxicity
Animals
*Indoles/pharmacology/metabolism/chemistry
*Kupffer Cells/drug effects/metabolism
Mice
*Gastrointestinal Microbiome/drug effects
*Liver/drug effects/metabolism/pathology
Mice, Inbred C57BL
Male
*Chemical and Drug Induced Liver Injury/drug therapy/metabolism/pathology
*Nanoparticles/chemistry/toxicity

@article {pmid42915786,
year = {2026},
author = {Chang, S and Zha, Y and Chen, S and Xiao, Y and Zhou, Y and Tian, Y and Liu, Z and Zhang, X and Zhang, H and Li, W and Yang, Q and Ren, J},
title = {Lactarius hatsudake Tanaka Polysaccharides Inhibit Hepatocellular Carcinoma by Modulating the Gut Microbiota and Its Metabolites.},
journal = {Journal of agricultural and food chemistry},
volume = {74},
number = {39},
pages = {30768-30783},
doi = {10.1021/acs.jafc.6c06885},
pmid = {42915786},
issn = {1520-5118},
support = {CX20251260//Hunan Provincial Innovation Foundation for Postgraduate/ ; GJFP20230204//Ministry of Agriculture and Rural Affairs of the People's Republic of China/ ; 2019TP1029//Science and Technology Program of Hunan Province/ ; 2024JK2158//Key Research and Development Program of Hunan Province of China/ ; SKL-CSUFT202503//State Key Laboratory of Utilization of Woody Oil Resource/ ; U24A20466//National Natural Science Foundation of China (NSFC)/ ; U25A20730//National Natural Science Foundation of China (NSFC)/ ; XLK2024//Forestry Science and Technology Innovation Project in Hunan Province/ ; },
mesh = {Animals ; *Liver Neoplasms/microbiology/drug therapy/metabolism/immunology ; *Carcinoma, Hepatocellular/microbiology/drug therapy/metabolism/immunology ; *Gastrointestinal Microbiome/drug effects ; *Polysaccharides/administration & dosage ; Humans ; Mice ; Bacteria/isolation & purification/genetics/classification/metabolism/drug effects ; Male ; Interferon-gamma/immunology/genetics ; Fecal Microbiota Transplantation ; },
abstract = {We previously reported that Lactarius hatsudake Tanaka polysaccharide (LHP) can inhibit hepatocellular carcinoma, but the mechanism remains unclear especially gut microbe-mediated antitumor immunity. This research found that LHP and fecal microbiota transplantation were associated with reduced tumor growth. The ratio of CD8+/CD4+ T cells and levels of interferon-γ were increased following LHP intervention in the tumor, spleen, and blood. Additionally, in vivo and in vitro microbiome analyses indicated that LHP treatment significantly increased beneficial bacteria such as Bifidobacterium animalis while reducing Lactobacillus murinus. Furthermore, metabolomic analyses suggested that LHP may be metabolized into propionate via the succinate pathway, accompanied by changes in the microbial composition, which significantly inhibit the arginine and tryptophan metabolic pathways. These microbial and metabolite changes paralleled improvements in the tumor immune microenvironment and coincided with attenuated hepatocellular carcinoma progression. These findings suggest that LHP-induced gut microbiota remodeling is associated with antitumor immune modulation.},
}

Animals
*Liver Neoplasms/microbiology/drug therapy/metabolism/immunology
*Carcinoma, Hepatocellular/microbiology/drug therapy/metabolism/immunology
*Gastrointestinal Microbiome/drug effects
*Polysaccharides/administration & dosage
Humans
Mice
Bacteria/isolation & purification/genetics/classification/metabolism/drug effects
Male
Interferon-gamma/immunology/genetics
Fecal Microbiota Transplantation

@article {pmid42915815,
year = {2026},
author = {Wang, Y and Feng, L and Yuan, J and Yuan, C and Khan, EA and Qin, K and Chen, W and Wang, C and Gerunova, L and Li, N and Liao, M and Hua, J},
title = {Oral Exposure to Polystyrene Nanoplastics Disrupts Gut-Testis Metabolic Homeostasis and EGR1-Associated Steroidogenic Regulation in Male Mice.},
journal = {Journal of agricultural and food chemistry},
volume = {74},
number = {39},
pages = {31151-31166},
doi = {10.1021/acs.jafc.6c10448},
pmid = {42915815},
issn = {1520-5118},
support = {2024BBF01014//Science and Technology Department of Ningxia Province/ ; 2025BBF02007//Science and Technology Department of Ningxia Province/ ; 2022YFD130220//National Basic Research Program of China (973 Program)/ ; 2023YFF1000904//National Basic Research Program of China (973 Program)/ ; 32372970//National Natural Science Foundation of China (NSFC)/ ; NA//National Natural Science Foundation of China (NSFC)/ ; U24A20438//National Natural Science Foundation of China (NSFC)/ ; },
mesh = {Animals ; Male ; Mice ; *Polystyrenes/toxicity/adverse effects ; *Testis/metabolism/drug effects ; Mice, Inbred ICR ; *Early Growth Response Protein 1/metabolism/genetics ; Homeostasis/drug effects ; Humans ; Administration, Oral ; *Nanoparticles/toxicity ; Gastrointestinal Microbiome/drug effects ; *Steroids/biosynthesis ; *Microplastics/toxicity ; },
abstract = {Polystyrene nanoplastics (PS-NPs) may impair male reproduction through gut-testis metabolic disruption. ICR mice received 100 nm PS-NPs (1 mg/mouse/day) orally for 28 days; fecal microbiota transplantation, metabolomics, sodium butyrate (NaB) supplementation, and TM3-cell assays were used. PS-NPs impaired intestinal barrier integrity and testicular steroidogenesis. Following antibiotic pretreatment, these abnormalities were partially reproduced in exposed-donor recipients relative to control-donor recipients. Untargeted metabolomics showed an FDR-significant decrease in relative testicular butanoic acid levels, while serum butyrate decreased in PS-NP-exposed mice and exposed-donor recipients. In vivo NaB supplementation partially improved reproductive and steroidogenesis-related outcomes in PS-NP-exposed mice. Exploratory analyses and validation experiments implicated a NaB-responsive EGR1-Cyp11a1 regulatory relationship in Leydig cells. These findings suggest that gut-associated butyrate disturbance contributes to PS-NP-induced steroidogenic dysfunction.},
}

Animals
Male
Mice
*Polystyrenes/toxicity/adverse effects
*Testis/metabolism/drug effects
Mice, Inbred ICR
*Early Growth Response Protein 1/metabolism/genetics
Homeostasis/drug effects
Humans
Administration, Oral
*Nanoparticles/toxicity
Gastrointestinal Microbiome/drug effects
*Steroids/biosynthesis
*Microplastics/toxicity

@article {pmid42916022,
year = {2026},
author = {Du, Y and Li, Q and Yang, F and Zhang, B and Lei, M and Zhao, D and Xu, X and He, Y and Wen, L},
title = {Gut Microbiota Remodeling Drives Cognitive Improvement: A Microbiota-Dependent Study of Malvidin-3-O-glucoside against Alcohol-Related Cognitive Impairment.},
journal = {Journal of agricultural and food chemistry},
volume = {74},
number = {40},
pages = {31679-31703},
doi = {10.1021/acs.jafc.6c08126},
pmid = {42916022},
issn = {1520-5118},
support = {20260102167JC//Jilin Provincial Scientific and Technological Development Program/ ; },
mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Anthocyanins/administration & dosage ; *Glucosides/administration & dosage ; Mice ; Male ; Humans ; *Cognitive Dysfunction/drug therapy/microbiology/psychology/etiology ; Bacteria/isolation & purification/classification/genetics/drug effects ; Mice, Inbred C57BL ; *Ethanol/adverse effects ; Cognition/drug effects ; Fecal Microbiota Transplantation ; Zonula Occludens-1 Protein/metabolism/genetics ; Occludin/genetics/metabolism ; },
abstract = {Gut microbiota dysbiosis triggers alcohol-related cognitive impairment (ARCI). Malvidin-3-O-glucoside (Mv3G), a highly bioactive monomeric anthocyanin abundant in pigmented fruits and cereals, can relieve neurodegenerative diseases by regulating gut microbiota (GM). Nevertheless, the gut microbiota-mediated protective effect of Mv3G against ARCI remains unknown. In this study, an alcohol-induced ARCI mouse model combined with fecal microbiota transplantation (FMT) was built to explore Mv3G's protective effects. Results show that Mv3G acts in an intact gut flora-dependent manner. It repairs intestinal injury and restores intestinal barrier by upregulating tight junction proteins ZO-1 and occludin, enriches beneficial bacteria such as Lachnospiraceae_NK4A136_group and Akkermansia, adjusts the Bacteroidetes/Firmicutes ratio, and decreases pathogenic Pseudomonadales to remodel gut microbiota. Via the gut-brain axis, Mv3G suppresses central inflammation, maintains hippocampal synapses and improves cognitive performance. In vitro experiments further confirm that Mv3G alleviates ARCI relying on gut microbiota. This research provides a novel intervention strategy for alcohol-induced cognitive injury.},
}

Animals
*Gastrointestinal Microbiome/drug effects
*Anthocyanins/administration & dosage
*Glucosides/administration & dosage
Mice
Male
Humans
*Cognitive Dysfunction/drug therapy/microbiology/psychology/etiology
Bacteria/isolation & purification/classification/genetics/drug effects
Mice, Inbred C57BL
*Ethanol/adverse effects
Cognition/drug effects
Fecal Microbiota Transplantation
Zonula Occludens-1 Protein/metabolism/genetics
Occludin/genetics/metabolism

@article {pmid42902422,
year = {2026},
author = {Gao, H and Gu, J and Wang, Y and Zou, Y and Wang, Z and Fang, R and Jiang, S},
title = {Heat stress triggers bone performance degeneration via impairing intestinal barrier function and altering gut microbiota in chickens.},
journal = {Animal microbiome},
volume = {8},
number = {1},
pages = {},
pmid = {42902422},
issn = {2524-4671},
support = {32402955//National Natural Science Foundation of China/ ; SWU-KQ24004//Fundamental Research Funds for the Central Universities/ ; 202405AF140106//the Yunnan Province Science and Technology Talents and Platform Program/ ; },
abstract = {Heat stress (HS) is a pervasive environmental hazard in intensive poultry production that severely impairs skeletal health and causes substantial economic losses. While emerging evidence links gut microbiota dysbiosis to bone metabolism, its causal role in mediating HS-induced bone loss remains poorly defined. Here, we established a chicken model of HS and employed fecal microbiota transplantation (FMT) to investigate the mechanistic link between gut microbiota and skeletal deterioration. Our results demonstrated that HS reduced growth performance, disrupted gut microbial community structure, and impaired bone microarchitecture and biomechanical strength. Critically, FMT from HS-exposed donors recapitulated the key features of HS-induced bone loss in recipient chickens, characterized by impaired trabecular bone microarchitecture, reduced biomechanical strength, and enhanced bone resorption-related gene expression. Mechanistically, the HS-microbiota induces functional dysbiosis, characterized by a relative increase in the abundance of the genus Turicibacter, while compromising intestinal barrier integrity, triggering an inflammatory response, and inhibiting intestinal mineral absorption. Collectively, these factors contribute to reduced bone performance. These findings establish the gut microbiota as a key mediator of HS-induced bone loss, providing a novel mechanistic framework for understanding host-microbiota-environment interactions in the context of environmental hazards, which has broader implications for animal health and environmental toxicology.},
}

@article {pmid42903521,
year = {2026},
author = {Chen, K and Li, Q and Xing, Y and Liu, C and Yang, F},
title = {Gut microbiota dysbiosis in pediatric acute lymphoblastic leukemia: clinical consequences, mechanistic insights, and microbiota-targeted interventions.},
journal = {Frontiers in pediatrics},
volume = {14},
number = {},
pages = {1928304},
pmid = {42903521},
issn = {2296-2360},
abstract = {Gut microbiota dysbiosis has emerged as a key feature in pediatric acute lymphoblastic leukemia (ALL), driven by chemotherapy, antibiotic exposure, and treatment-related nutritional impairment. Increasing evidence indicates that disruption of microbial diversity and depletion of short-chain fatty acid-producing bacteria are closely associated with infectious complications, gastrointestinal toxicity, and potentially reduced treatment efficacy. This review synthesizes current evidence on the interplay between gut microbiota and pediatric ALL across four dimensions: clinical outcomes, treatment-related toxicity, pharmacological interactions, and prognosis. We further summarize how leukemia therapy reshapes microbial ecosystems through cytotoxic agents, antimicrobial exposure, and dietary alterations. In addition, we discuss microbiota-centered therapeutic strategies, including probiotics, prebiotics, synbiotics, postbiotics, dietary interventions, and fecal microbiota transplantation. While promising, these approaches require careful validation in pediatric oncology due to safety considerations and limited clinical trial data. Finally, we highlight methodological advances such as multi-omics integration and machine learning approaches, which may enable microbiome-based risk stratification and precision supportive care in the future. Overall, gut microbiota represents a potential modifiable factor influencing clinical outcomes in pediatric ALL.},
}

@article {pmid42903564,
year = {2023},
author = {Yan, H and Ren, J and Liu, GH},
title = {Fecal microbiota transplantation: A new strategy to delay aging.},
journal = {hLife},
volume = {1},
number = {1},
pages = {8-11},
pmid = {42903564},
issn = {2949-9283},
abstract = {The gut microbiota, the community of gut microorganisms that inhabit the gastrointestinal tract, plays a crucial role in modulating host immunity, metabolism, and neurological health, thereby influencing the entire organism. Aging is associated with changes in gut microbiota composition and functionality, often resulting in dysbiosis, an imbalance of gut microbiota and an aging hallmark. Recent studies have suggested that fecal microbiota transplantation (FMT), the transfer of fecal material containing beneficial microbes from a healthy donor to a recipient with a disturbed microbiota, may restore the balance of host gut microbiota and ameliorate some aging-associated impairments in diverse organs. In particular, FMT from young donors has shown more beneficial effects than FMT from aged donors. In this paper, we review recent advances in FMT for its effects on aging and discuss the potential mechanisms and challenges of this novel intervention, highlighting its potential to improve health outcomes in the aging population.},
}

@article {pmid42903936,
year = {2026},
author = {Wang, S and Huai, S and Yuan, Z and Ji, T and Xu, Y and Ren, Y and Qian, N and Sun, S and Li, J},
title = {Berberine alleviates radiation-induced lung injury by promoting microbiota-derived inosine via the gut-lung axis.},
journal = {hLife},
volume = {4},
number = {3},
pages = {165-185},
pmid = {42903936},
issn = {2949-9283},
abstract = {Radiation-induced lung injury (RILI) is a common complication of radiotherapy. Although berberine (BBR) has been suggested to be associated with reduced RILI incidence, the underlying mechanisms remain unknown. Here, we investigated whether the gut microbiota mediates the radioprotective effects of BBR using a C57BL/6 RILI mouse model with 20 Gy thoracic irradiation (n = 6 per group). BBR (100 mg/kg) and inosine (INO, 300 mg/kg) were administered orally in vivo. Antibiotic depletion and fecal microbiota transplantation were performed to assess microbiota dependence. Lung injury was assessed by histology, pulmonary function, and cytokine levels. Gut microbiota was analyzed by 16S rRNA sequencing, and metabolites were profiled using LC-MS/MS. Transcriptomic and epigenomic alterations were assessed by RNA sequencing, ATAC sequencing, and CUT&Tag analysis. Molecular docking and surface plasmon resonance were used to assess metabolite-protein interactions. We demonstrated that BBR alleviated RILI in a microbiota-dependent manner. BBR increased Akkermansia muciniphila abundance and metabolite INO levels. Mechanistically, INO was associated with reduced neuron navigator 3 (NAV3) expression, accompanied by decreased chromatin accessibility and increased histone H3 lysine 27 trimethylation (H3K27me3) at the NAV3 locus. Together, these findings reveal a gut microbiota-mediated mechanism underlying BBR-mediated protection against RILI, and suggest microbiota-informed biomarkers for risk stratification.},
}

@article {pmid42903958,
year = {2024},
author = {Tian, H and Wang, X and Fang, Z and Li, L and Wu, C and Bi, D and Li, N and Chen, Q and Qin, H},
title = {Fecal microbiota transplantation in clinical practice: Present controversies and future prospects.},
journal = {hLife},
volume = {2},
number = {6},
pages = {269-283},
pmid = {42903958},
issn = {2949-9283},
abstract = {The gut microbiota, serving as the only "organ" that humans can share, has been extensively applied in the treatment of various intestinal and extraintestinal diseases through fecal microbiota transplantation (FMT) technology. By optimizing the donor selection strategy, FMT exhibited the highest effectiveness (more than 90%) in treating acute intestinal inflammations, such as recurrent Clostridium difficile infection. However, the efficacy diminishes when addressing intestinal functional diseases (more than 60%), chronic intestinal inflammations or organic diseases (less than 60%), and extraintestinal diseases, particularly those lacking any gastrointestinal symptoms (less than 50%). Ongoing efforts to enhance the therapeutic response of FMT across diverse diseases represent a central focus of current clinical research. This review concentrates on donor selection, recipient management, precise donor-recipient matching, antagonistic mechanism of native bacteria to transplanted bacteria, and targeted treatment strategies for different diseases, with the aim of providing practical strategies to improve the clinical efficacy of FMT.},
}

@article {pmid42903976,
year = {2025},
author = {Wang, Y and Yan, H and Zheng, Q and Sun, X},
title = {Crucial functions of gut microbiota on gut-liver repair.},
journal = {hLife},
volume = {3},
number = {8},
pages = {364-385},
pmid = {42903976},
issn = {2949-9283},
abstract = {The gut microbiota exert a critical influence on the gut-liver axis by facilitating intestinal and hepatic repair via intricate bidirectional mechanisms. Inflammatory bowel disease (IBD), metabolic-associated steatohepatitis (MASH), and the gut-liver axis exemplify the complex interplay between the gut microbiota and hepatic function. This review explores the interplay between microbial metabolites and their roles in maintaining intestinal integrity and promoting liver regeneration. Emerging evidence shows that gut microbiota support intestinal and liver health by modulating immune responses via microbial metabolites and interactions with host immune cells. Moreover, advances in personalized therapies, including probiotics, prebiotics, and fecal microbiota transplantation (FMT), could potentially restore microbial balance and enhance tissue repair. Understanding these relationships presents opportunities for innovative interventions to improve gut and liver health, particularly in individuals with metabolic disorders.},
}

@article {pmid42905002,
year = {2026},
author = {Chu, Z and Zhang, X and Zhu, B and Liu, Q and Zeng, Y and Zhou, Y and Hu, Z and Luo, F},
title = {Protective Effects of Narirutin Against Exercise-Induced Fatigue in Mice: Insights from Integrated Microbiome, Metabolome, and Transcriptome Analysis.},
journal = {Journal of agricultural and food chemistry},
volume = {74},
number = {41},
pages = {32426-32447},
doi = {10.1021/acs.jafc.6c11203},
pmid = {42905002},
issn = {1520-5118},
support = {25B0319//Education Department of Hunan Province/ ; 32603353//National Natural Science Foundation of China/ ; 2022YFF1100200//National Key Research and Development Program of China/ ; 2024YJ006//Central South University of Forestry and Technology/ ; 2025QT-40//Hunan Province 2025 Furong Plan Youth Talent Project/ ; },
mesh = {Animals ; Mice ; *Fatigue/microbiology/metabolism/drug therapy/genetics/etiology/prevention & control ; Male ; *Gastrointestinal Microbiome/drug effects ; Metabolome/drug effects ; Physical Conditioning, Animal/adverse effects ; Humans ; Multiomics ; Bacteria/genetics/isolation & purification/classification/drug effects/metabolism ; Mice, Inbred C57BL ; Transcriptome/drug effects ; *Protective Agents/administration & dosage ; Gene Expression Profiling ; },
abstract = {Exercise-induced fatigue is linked to oxidative stress, inflammation and intestinal dysbiosis. Narirutin (NAR), a natural flavonoid, lacks systematic evidence and mechanistic clarification against exercise fatigue. Herein, a forced exercise fatigue mouse model was constructed, and behavioral, biochemical, histological and multiomics analyses including 16S rRNA sequencing, untargeted metabolomics, transcriptomics and RT-qPCR were performed. Fecal microbiota transplantation (FMT) and antibiotic-mediated microbiota depletion further verified the causal role of gut microbiota. NAR dose-dependently improved exercise endurance, muscle strength, glycogen storage, oxidative status and inflammatory profiles. It restored gut microbial diversity, remodelled microbial composition and altered metabolic signatures. Multiomics integration indicated NAR regulated immune genes via the gut microbiota-metabolite-gene axis. FMT reproduced antifatigue effects, whereas antibiotic treatment eliminated NAR protection. This study demonstrates that NAR alleviates exercise-induced fatigue largely relying on intact gut microbiota, although microbiota-independent peripheral effects cannot be fully excluded. These findings support its exploitation as a natural antifatigue functional component.},
}

Animals
Mice
*Fatigue/microbiology/metabolism/drug therapy/genetics/etiology/prevention & control
Male
*Gastrointestinal Microbiome/drug effects
Metabolome/drug effects
Physical Conditioning, Animal/adverse effects
Humans
Multiomics
Bacteria/genetics/isolation & purification/classification/drug effects/metabolism
Mice, Inbred C57BL
Transcriptome/drug effects
*Protective Agents/administration & dosage
Gene Expression Profiling

@article {pmid42905003,
year = {2026},
author = {Wang, Z and Lu, Y and Zhao, Y and Li, H and Liao, X and Li, J and Huang, J and Wang, K and Liu, Z and Zhu, M},
title = {Dihydromyricetin Alleviates Reserpine-Induced Depression by Modulating the Microbiota-Gut-Brain Axis.},
journal = {Journal of agricultural and food chemistry},
volume = {74},
number = {41},
pages = {32288-32308},
doi = {10.1021/acs.jafc.6c05330},
pmid = {42905003},
issn = {1520-5118},
support = {20B282//Education Department of Hunan Province/ ; 32172217//National Natural Science Foundation of China/ ; 32472797//National Natural Science Foundation of China/ ; 2022RC1142//Department of Science and Technology of Hunan Province/ ; 2023JJ50004//Natural Science Foundation of Hunan Province/ ; 2025JJ20022//Natural Science Foundation of Hunan Province/ ; 25KJ025//Hunan Agricultural University/ ; 2022YFD2101103//National Key Research and Development Program of China/ ; 2024JK2150//Key Research and Development Program of Hunan Province of China/ ; },
mesh = {Animals ; *Depression/drug therapy/microbiology/metabolism/chemically induced/psychology ; *Flavonols/administration & dosage ; Rats ; *Gastrointestinal Microbiome/drug effects ; *Brain/drug effects/metabolism ; Male ; Reserpine/adverse effects ; Humans ; Rats, Sprague-Dawley ; *Antidepressive Agents/administration & dosage ; Brain-Derived Neurotrophic Factor/genetics/metabolism ; Bacteria/isolation & purification/classification/genetics/drug effects/metabolism ; },
abstract = {Dihydromyricetin (DMY) is a natural flavonoid with neuroprotective and antidepressant potential, but its role in the microbiota-gut-brain axis remains unclear. Using a reserpine-induced depression rat model, we integrated behavioral, inflammatory, histological, microbiota, metabolomic, and fecal microbiota transplantation (FMT) analyses. DMY alleviated anhedonia, behavioral despair, and cognitive dysfunction, reduced circulating pro-inflammatory cytokines and hippocampal neuronal damage, and increased brain-derived neurotrophic factor expression. DMY also restored gut microbial diversity and composition and partially normalized bile acid and short-chain fatty acid profiles. Notably, FMT from DMY-treated donors reproduced antidepressant-like behavioral effects and restored key microbial metabolites. These findings suggest that DMY may alleviate depression-like phenotypes through coordinated regulation of gut microbiota, microbial metabolites, and neuroinflammatory responses, supporting its potential as a dietary strategy for depression management.},
}

Animals
*Depression/drug therapy/microbiology/metabolism/chemically induced/psychology
*Flavonols/administration & dosage
Rats
*Gastrointestinal Microbiome/drug effects
*Brain/drug effects/metabolism
Male
Reserpine/adverse effects
Humans
Rats, Sprague-Dawley
*Antidepressive Agents/administration & dosage
Brain-Derived Neurotrophic Factor/genetics/metabolism
Bacteria/isolation & purification/classification/genetics/drug effects/metabolism

@article {pmid42906799,
year = {2026},
author = {Huo, W and Hou, X and Huang, Y and Li, Z and Chen, X and Feng, J and Kong, Y and Pan, S and Wang, Q and Xu, J and Chen, J and Li, J and Yang, R and Lu, Y and Liu, Y},
title = {Tao-He-Cheng-Qi decoction protects against sepsis-associated acute lung injury by modulating gut microbiota and succinate-associated pulmonary macrophage polarization.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {122520},
doi = {10.1016/j.jep.2026.122520},
pmid = {42906799},
issn = {1872-7573},
abstract = {Sepsis-associated acute lung injury (SA-ALI) has high mortality and limited therapies.Tao-He-Cheng-Qi decoction protects against sepsis-associated acute lung injury by modulating gut microbiota and succinate-associated pulmonary macrophage polarization.

AIM OF THE STUDY: To evaluate the protective effects of THCQ pretreatment against LPS-induced SA-ALI and examine associated changes in gut microbiota, succinate levels, SUCNR1-PKA-CREB signaling and macrophage polarization.

MATERIALS AND METHODS: A murine SA-ALI model was induced by intraperitoneal LPS. Lung injury, inflammatory cytokines (IL-1β, TNF-α), and M1/M2 polarization were assessed. Gut microbiota was analyzed by 16S rRNA sequencing. Succinate levels, SUCNR1, and PKA-CREB signaling were measured. Microbiota dependence was tested using antibiotic depletion, fecal microbiota transplantation (FMT) from THCQ-treated donors, exogenous succinate, and macrophage depletion with clodronate liposomes.

RESULTS: THCQ pretreatment attenuated lung injury, reduced IL-1β and TNF-α levels, and shifted pulmonary macrophage polarization toward an M2-like phenotype. These effects were accompanied by altered gut microbiota composition, a lower abundance ratio of bacterial families grouped in the exploratory succinate-metabolism analysis, reduced serum and pulmonary succinate levels, lower SUCNR1 expression, and increased PKA/CREB phosphorylation. Antibiotic treatment attenuated the protective responses to THCQ, while FMT from THCQ-treated donors reproduced improvements in lung injury. Exogenous succinate attenuated THCQ-mediated protection. Clo-Lipo treatment reduced the proportions of alveolar and interstitial macrophages and markedly attenuated the protective effects of THCQ.

CONCLUSION: THCQ treatment protects against SA-ALI and suppresses M1-like macrophage polarization. These effects are accompanied by changes in gut microbiota composition, reduced succinate levels, and altered SUCNR1-PKA-CREB signaling. Together, the findings support a role for gut microbiota-metabolism-immune interactions in the protective effects of THCQ.},
}

@article {pmid42901457,
year = {2026},
author = {Zuo, Y and Li, Y and Huang, Z and Zeng, H and Liu, Q and Zhou, Y and Chen, X and Chen, W and Wang, K and Chen, Q},
title = {Yupingfeng alleviates allergic rhinitis by modulating gut microbiota and succinate to inhibit mTOR/S6K signaling.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {122558},
doi = {10.1016/j.jep.2026.122558},
pmid = {42901457},
issn = {1872-7573},
abstract = {Yupingfeng granules (YPF), derived from the classic traditional Chinese medicine prescription Yupingfeng powder, have been recommended in clinical practice guidelines for the management of allergic rhinitis (AR), and their clinical efficacy is widely recognized. However, the underlying pharmacological mechanisms have not been thoroughly investigated.

AIM OF THE STUDY: This study aimed to investigate whether YPF protects the nasal epithelial barrier and alleviates AR by modulating the gut microbiota and pathways related to its metabolites.

MATERIALS AND METHODS: An OVA-induced AR mouse model was established and phenotypically evaluated. The dependence of YPF efficacy on gut microbiota was assessed by 16S rRNA sequencing, antibiotic depletion, and fecal microbiota transplantation. [1]H-NMR metabolomics was used to identify key metabolites, followed by exogenous supplementation for validation. Nasal mucosal transcriptome sequencing was performed to explore downstream pathways, and functional validation was conducted in OVA-induced HNEpCs through metabolite intervention, YPF co-treatment, mTOR knockdown, and MHY1485 treatment.

RESULTS: YPF dose-dependently reduced nasal rubbing and sneezing, attenuated IgE-mediated type 2 inflammation, and ameliorated nasal epithelial barrier injury in OVA-induced AR mice. YPF remodeled the gut microbiota and increased microbial diversity. Gut microbiota depletion attenuated the protective effects of YPF, whereas FMT from YPF donors reproduced them. Metabolomic analysis identified succinate as a key YPF-responsive metabolite, and exogenous succinate aggravated nasal epithelial barrier injury. Transcriptomic analysis suggested that succinate-induced nasal mucosal injury may involve mTOR signaling activation. In vitro, succinate aggravated OVA-induced barrier injury in HNEpCs, with disrupted Occludin distribution and enhanced mTOR/S6K phosphorylation, whereas YPF co-treatment reversed these changes. mTOR knockdown mimicked the protective effects of YPF, whereas MHY1485 attenuated them.

CONCLUSION: YPF alleviates OVA-induced AR by remodeling the gut microbiota, reducing succinate accumulation, and suppressing mTOR/S6K signaling to preserve nasal epithelial barrier integrity.},
}

@article {pmid42902271,
year = {2026},
author = {Asna Ashari, K and MacRae, R and Hoytema van Konijnenburg, DP and Platt, CD and Ashoor, M and See, AP and Kielian, A and Danehy, A and Kumar, R and James, E and Houghton, K and Harder, S and Gorman, MP and Kahn, SA and Daga, A and Hussain, SH and Johnston, AM and Casey, A and Ouahed, JD and Wong, W and Jenkins, K and Prockop, S and Eloseily, E and Risma, K and Ombrello, MJ and Dedeoglu, F and Andzelm, MM},
title = {Neurological manifestations and vasculopathy in PLCG2-associated antibody deficiency and immune dysregulation (APLAID): a case series.},
journal = {Pediatric rheumatology online journal},
volume = {24},
number = {1},
pages = {},
pmid = {42902271},
issn = {1546-0096},
mesh = {Humans ; Female ; *Phospholipase C gamma/genetics ; Infant ; Male ; Magnetic Resonance Imaging ; *Immunologic Deficiency Syndromes/genetics/complications ; Magnetic Resonance Angiography ; },
abstract = {BACKGROUND: Autosomal dominant pathogenic variants in PLCG2 are associated with autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID), characterized by immunological abnormalities and multi-system inflammation. Descriptions of associated neurological manifestations and vascular anomalies are limited. We describe three patients with APLAID, vasculopathies, neuroinflammation, and cerebral vascular tortuosity. These cases highlight underrecognized and clinically important manifestations of APLAID.

CASE PRESENTATIONS: All three patients had de novo variants in PLCG2 and early systemic inflammatory and immunodeficiency findings within the spectrum of APLAID (e.g. immune laboratory abnormalities, skin and gastrointestinal inflammation, and frequent infections). Additionally, they had notable neurological and vascular findings. Patient #1 (PLCG2 c.3420T > A; p.Asp1140Glu) is a female who had focal seizures at 16 months old. Magnetic resonance imaging (MRI) revealed right parietal leptomeningeal enhancement with white matter changes. MR angiography (MRA) showed cerebrovascular tortuosity and stenoses without evidence of vasculitis. She had extensive veno-lymphatic malformation in the thorax, abnormal renal vasculature, inferior vena cava (IVC) atresia, and bilateral pulmonary vein stenosis (PVS). Patient #2 (PLCG2 c.2122G > C; p.Ala708Pro) is a male who at four years old had an episode of status epilepticus. MRI revealed a right parietal infarct with surrounding leptomeningeal enhancement and MRA demonstrated abnormal caliber of the right middle cerebral artery (MCA), arterial tortuosity, and carotid aneurysms. His course was complicated by aortic root dilation and bilateral PVS. Patient #3 (PLCG2 c.2122G > C; p.Ala708Pro) is a male who at 16 months had a right sided focal motor seizure. MRI demonstrated infarct with associated sulcal enhancement predominantly in the left cerebral hemisphere. MRA found excessive vascular tortuosity and fenestrations. He has a dilated aortic root and ventricular septal defect (VSD).

CONCLUSION: We present three cases of APLAID complicated by significant cerebrovascular tortuosity and seizure and two with cerebral ischemia. The etiology of stroke and/or seizures in these patients is unclear, but vasculopathy leading to perfusion deficits, neuroinflammation, or thrombosis due to underlying thrombotic diathesis or abnormal vascular anatomy may have contributed. We recommend all patients with APLAID undergo monitoring for neurologic manifestations. Additionally, we highlight important vasculopathic findings such as PVS, where early recognition for directed treatment is critical.},
}

Humans
Female
*Phospholipase C gamma/genetics
Infant
Male
Magnetic Resonance Imaging
*Immunologic Deficiency Syndromes/genetics/complications
Magnetic Resonance Angiography

@article {pmid42895822,
year = {2026},
author = {Jiang, H and Zhao, T and Zhang, X and Moriyama, H},
title = {Abdominal ultrasound mitigates neurodegenerative pathology and alters specific gut microbial taxa in senescence-accelerated mice.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1093/gerona/glag250},
pmid = {42895822},
issn = {1758-535X},
abstract = {Age-related changes in gut microbiota composition have been implicated in brain aging and cognitive decline, acting through the gut-brain axis on amyloid accumulation, tau pathology, synapse damage, and glial activation. Live microbial approaches such as probiotics, prebiotics, and fecal microbiota transplantation address this mechanism, but they still suffer from low efficacy and unknown safety issues. We tested whether abdominal ultrasound, an approach that does not involve microbes, can alleviate age-related neurodegeneration in the senescence-accelerated mouse strain SAMP8. We treated 6-month-old male SAMP8 mice for 1 month. We then assessed behavior, neuropathology, and synaptic proteins, and quantified four pre-specified fecal bacterial taxa. Ultrasound preserved neuronal survival in the hippocampal CA3, decreased amyloid-β load in the cortex and CA3, decreased tau hyperphosphorylation in all three regions, reduced Iba-1 and GFAP immunoreactive areas, and increased synaptophysin and cortical PSD-95. Neuronal survival in the cortex and CA1 did not differ significantly from sham-treated SAMP8 mice. In the gut microbiota, ultrasound significantly reduced the enriched taxon Tyzzerella, whereas the changes in Lactobacillus, Akkermansia and Atopobiaceae were large in magnitude but not statistically significant. In an exploratory analysis, four of 64 microbiota-neuropathology associations survived correction for multiple testing. Neither object recognition memory nor spatial memory differed significantly between treated and sham-treated SAMP8 mice. Abdominal ultrasound applied to the periphery therefore reduced age-associated neuropathology in the brain, accompanied by changes in specific gut microbial taxa whose causal contribution remains untested.},
}

@article {pmid42898166,
year = {2026},
author = {Zhu, J and Zeng, B and Zhu, W and Liu, Y and Li, X and Zhang, Y and Xu, Z and Xu, Q and Wu, W and Li, J and Shang, X and Lin, Y and Zhou, T and Lu, F and Qian, Y},
title = {Gut microbiota-driven imbalance of the gut-brain-immune homeostatic network in constipation: Pathogenic mechanisms and evolving therapeutic prospects.},
journal = {iScience},
volume = {29},
number = {11},
pages = {117850},
pmid = {42898166},
issn = {2589-0042},
abstract = {Chronic constipation (CC) is increasingly recognized as a systems-level disorder that cannot be explained by impaired intestinal motility alone. Here, we integrate evidence from clinical cohorts, animal models, and mechanistic studies to examine how gut microbial dysbiosis and altered microbial metabolites perturb epithelial barrier integrity, immune homeostasis, enteric neural activity, and gut-brain signaling. We propose a "gut-brain-immune homeostatic network" in which short-chain fatty acids (SCFAs), tryptophan metabolites, bile acids, and other microbial signals may sustain self-reinforcing interactions linking dysmotility, inflammation, and neurobehavioral disturbances. We further evaluate microbiota-directed interventions, including prebiotics, probiotics, postbiotics, fecal microbiota transplantation, engineered bacteria, and multi-omics-guided personalized strategies. This framework reframes CC as a multisystem homeostatic disorder and provides a mechanistic basis for patient stratification, therapeutic target discovery, and precision interventions for constipation and related gut-brain-immune disorders.},
}

@article {pmid42898827,
year = {2026},
author = {Li, Y and Zhou, L and Huang, R and Wang, Y and Zhao, H and Sun, M and Zhang, Y and Wu, Z and Li, J},
title = {Gut microbiota in esophageal cancer: mechanisms, clinical implications, and therapeutic potential.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1955627},
pmid = {42898827},
issn = {1664-302X},
abstract = {Esophageal cancer (EC) is a highly prevalent and aggressive gastrointestinal malignancy. Late diagnosis and heterogeneous responses to chemoradiotherapy and immune checkpoint inhibitor (ICI) therapies severely challenge clinical management. Accumulating evidence suggests that gut microbiota dysbiosis influences esophageal mucosal malignant transformation, tumor progression, and therapeutic outcomes through the gut-esophageal axis. However, most existing research remains correlational. To bridge this gap, this review critically synthesizes the dysbiosis signatures of EC and establishes a five-tier evidence grading framework to rigorously distinguish causal mechanisms from preclinical inferences. This microbial regulation is predominantly driven by metabolite-mediated signaling, remodeling of the tumor immune microenvironment (TME), intestinal barrier disruption, and oncogenic pathway activation. We functionally classify EC-associated dysbiosis into pro-tumorigenic, anti-tumorigenic, and context-dependent taxa, emphasizing a multidimensional ecosystem perspective. Furthermore, we evaluate the utility of gut microbial signatures as predictive biomarkers for neoadjuvant therapy and prognosis. Microbiota-targeted intervention strategies, including fecal microbiota transplantation (FMT), microecological preparations, and Traditional Chinese Medicine (TCM), have entered clinical exploration as adjunctive approaches to optimize treatment efficacy. Finally, we address current translational barriers and propose future directions, emphasizing multi-omics integration, spatial transcriptomics, and artificial intelligence (AI). This provides an objective, mechanistically grounded framework for advancing microbiota-guided personalized oncology in EC.},
}

@article {pmid42898941,
year = {2026},
author = {Bai, X and Zhu, L and Sun, Y and Shi, Y and Zhou, P and Wang, C and Cui, L and Shi, L},
title = {Gut microbiota and innate immune barrier dysfunction in hepatic portal venous gas: a hypothesis-generating review.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1974872},
pmid = {42898941},
issn = {1664-3224},
mesh = {Humans ; *Immunity, Innate ; *Gastrointestinal Microbiome/immunology ; Intestinal Barrier Function ; *Portal Vein/immunology ; Animals ; Dysbiosis/immunology ; *Embolism, Air/immunology/microbiology ; },
abstract = {Hepatic portal venous gas (HPVG) is an uncommon radiographic sign whose prognosis is driven by bowel necrosis and shock rather than by intraportal gas. Immunological events along the gut-liver axis have not been synthesized for adult HPVG, and dedicated microbiome, metabolomic, gut-vascular barrier (GVB), and immune-profiling data are lacking. This hypothesis-generating review proposes gut dysbiosis as a putative contributor to mucosal and hepatic innate immune failure, inferred from cirrhosis, porto-sinusoidal vascular disease (PSVD), and intestinal ischemia/reperfusion. In those proxy states, loss of acetyl-CoA butyrate-production capacity, context-dependent bile-acid shifts, lipopolysaccharide-Toll-like receptor 4 priming, facultative-anaerobe expansion, and fermentative H2/CO2 pathways documented in cultured HPVG isolates-Clostridium perfringens (pyruvate-ferredoxin oxidoreductase-hydrogenase) and Escherichia coli (pyruvate-formate lyase-formate hydrogen lyase)-compromise epithelial and GVB integrity. These links are not assembled as a demonstrated sequence in adult HPVG. We propose a physical-core model in which a route of entry and a local driving pressure gradient are necessary, whereas pathway-defined fermentative isolates, dysbiosis, mucosal inflammation, ischemia, and impaired portal clearance are optional amplifiers. Iatrogenic or purely pressure-related HPVG can occur without dysbiosis or a substantial pathogen-associated molecular pattern load; in necrosis-driven HPVG, dysbiosis is proposed only as a concurrent immune amplifier; when HPVG occurs in cirrhosis or PSVD, portal hypertension is treated as a host modifier of barrier geometry and washout, not as an independent generator of intraportal gas. Portal vein thrombosis, portal hypertension, pneumatosis intestinalis, pyogenic liver abscess, and HPVG may share the portal vein as a conduit but are not interchangeable. No microbiota-directed intervention has been tested against an HPVG endpoint and none should delay source control; probiotics, rifaximin, fecal microbiota transplantation, diet, and phage remain research questions.},
}

Humans
*Immunity, Innate
*Gastrointestinal Microbiome/immunology
Intestinal Barrier Function
*Portal Vein/immunology
Animals
Dysbiosis/immunology
*Embolism, Air/immunology/microbiology

@article {pmid42899031,
year = {2026},
author = {O'Flaherty, EAA and van Sinderen, D},
title = {Faecal microbiota transplant revisited - potential metabolic outcomes of regional microbiome mismatches.},
journal = {Microbiome research reports},
volume = {5},
number = {3},
pages = {24},
pmid = {42899031},
issn = {2771-5965},
}

@article {pmid42899795,
year = {2026},
author = {Dai, Y and Song, P and Cheng, C and Cheng, L and Dai, C and Lu, W},
title = {Schaftoside, a functional flavonoid from fenugreek (Trigonella foenum-graecum L.), alleviates depression and cognitive deficits via the microbiome-gut-brain axis in stressed mice.},
journal = {Food & function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6fo04156f},
pmid = {42899795},
issn = {2042-650X},
abstract = {Depression involves dysregulation of central and peripheral networks, with gut microbiota alterations increasingly implicated in pathogenesis. Trigonella foenum-graecum L. (fenugreek), a functional food and medicinal herb, has been used traditionally for neurological disorders, yet its specific neuroprotective constituents remain poorly characterized. This study evaluated the antidepressant potential of schaftoside, the predominant flavonoid of fenugreek seed flavonoids, and explored its mechanisms involving the microbiome-gut-brain axis in a chronic restraint stress (CRS) mouse model. Male Kunming mice were subjected to CRS and orally administered schaftoside (20, 50, and 125 mg kg[-1]) or fluoxetine (10 mg kg[-1]) for 28 days. Behavioral assessments (tail suspension, forced swim, novel object recognition, and Y-maze) demonstrated that schaftoside dose-dependently ameliorated depressive-like behaviors and cognitive impairments. It attenuated hippocampal neuronal damage and neuroinflammation, restoring hippocampal 5-HT, NE, and ACh levels. Intestinal barrier integrity was improved, evidenced by enhanced tight junction proteins (ZO-1, occludin) and mucin (MUC2) expression, alongside reduced colonic pro-inflammatory cytokines and elevated IL-10. 16S rRNA profiling revealed that schaftoside reshaped gut microbiota composition, notably suppressing stress-enriched Bacteroides and promoting butyrate-producing Butyricicoccus. Untargeted metabolomics identified restoration of tryptophan and α-linolenic acid metabolism pathways. Spearman correlation analysis revealed significant associations between specific gut genera, fecal metabolites, and host inflammatory/neurochemical markers. Hippocampal transcriptomics indicated enrichment of cAMP signaling, dopaminergic, and serotonergic synapse pathways. Fecal microbiota transplantation (FMT) from schaftoside-treated donors partially recapitulated the behavioral, anti-inflammatory, and intestinal barrier-protective effects in antibiotic-pretreated recipient mice, accompanied by restoration of the gut microbiota and metabolite profiles. These findings demonstrate that schaftoside, the major flavonoid of fenugreek seeds, exhibits promising antidepressant-like potential through modulation of the microbiome-gut-brain axis, supporting the functional food application of fenugreek-derived flavonoids for stress-related mood disorders.},
}

@article {pmid42892458,
year = {2026},
author = {Ren, X and Yan, X and Tang, P and Jin, J and Qin, Z and Zhang, Y and Zhang, T and Yao, G and Yin, X and Zhao, Z and Wang, Z and Zhang, Q},
title = {Nifedipine-modulated gut microbiota attenuates hypertensive vascular injury through Bifidobacterium-associated inosine-Adora2b signaling.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {109684},
doi = {10.1016/j.phrs.2026.109684},
pmid = {42892458},
issn = {1096-1186},
abstract = {Although antihypertensive drugs mitigate hypertensive vascular injury, their vascular benefits are not fully explained by blood pressure reduction alone. Many cardiovascular drugs reshape the gut microbiota, which in turn influences their vascular pharmacology. We therefore investigated whether gut microbiota remodeling contributes to nifedipine-mediated vascular protection in high-salt hypertensive rats and a pilot patient cohort. Combining 16S rRNA sequencing, untargeted metabolomics, fecal microbiota transplantation, microbiota depletion, supplementation, and selective receptor antagonism, we found that nifedipine ameliorated gut dysbiosis. Transplantation of nifedipine-modulated microbiota improved intestinal barrier integrity and reduced vascular inflammation, oxidative stress, collagen deposition, and vascular smooth muscle cell (VSMC) phenotypic switching, while only marginally lowering blood pressure. Conversely, microbiota depletion markedly attenuated these vascular benefits despite preserving nifedipine-induced blood pressure lowering. These vascular benefits were associated with nifedipine-restored Bifidobacterium animalis subsp. lactis 420 (B420) and increased inosine availability. Supplementation with either recapitulated major vascular protective effects of nifedipine without statistically significant changes in blood pressure. In hypertensive patients, nifedipine treatment was associated with higher intestinal B420 abundance and inosine levels. In vitro, inosine modulated macrophages in an Adora2b- and Rap1-dependent manner, with accompanying changes in cAMP and KLF4, ameliorating VSMC dysfunction via paracrine signaling. In vivo, systemic Adora2b antagonism attenuated the vascular protective effects of both inosine and B420. Together, our findings support a gut microbiota-dependent component of nifedipine-mediated vascular protection that extends beyond blood pressure lowering, involving B420, increased inosine availability, and Adora2b signaling. We also nominate B420 and inosine as candidate adjuncts to calcium channel blocker therapy.},
}

@article {pmid42894314,
year = {2026},
author = {Zhao, M and Li, S and Fu, G and Deng, T and Jin, Y and Ye, Y and Li, Z},
title = {Evaluation of Clinical Practice Guidelines on Fecal Microbiota Transplantation in Adults: A Cross-Sectional Study.},
journal = {Journal of evidence-based medicine},
volume = {},
number = {},
pages = {e70202},
doi = {10.1111/jebm.70202},
pmid = {42894314},
issn = {1756-5391},
support = {2025‑AISJK‑02015//Ministry of Industry and Information Technology/ ; 2412055210//University-Industry Collaborative Education Program/ ; },
abstract = {OBJECTIVE: Fecal microbiota transplantation (FMT) is an emerging multi-disease therapy, yet the quality and consistency of its available clinical practice guidelines (CPGs) remain unknown. This study aimed to systematically evaluate the quality, content coverage and recommendation consistency of FMT-related guidelines and develop an optimization framework for evidence-informed future guideline revision and standardized FMT clinical practice.

METHODS: We searched PubMed, Embase, Web of Science Core Collection, The Cochrane Library, CNKI, WanFang Data, and official websites of guideline development organizations and professional societies from inception to March 11, 2026. Two reviewers independently screened and selected CPGs with actionable recommendations and conducted quality evaluation via the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. Intraclass correlation coefficient (ICC) with 95% confidence intervals (CIs) was computed for each AGREE II domain and interpreted according to Fleiss' criteria. Inter-guideline agreement was reported as the percentage of CPGs endorsing each recommendation.

RESULTS: Eighteen CPGs (3 general, 15 FMT-specific) with 191 recommendations were included. Applicability obtained the lowest AGREE II score (37.8%), followed by rigor of development (47.4%) and stakeholder involvement (49.7%). General guidelines scored higher than FMT-specific guidelines in applicability (62.5% vs. 32.9%) and stakeholder involvement (59.3% vs. 47.8%), but lower in rigor of development (38.9% vs. 49.1%). The coverage of recommendations showed marked inter‑guideline heterogeneity. Recurrent Clostridioides difficile infection (rCDI) was the most consistently recommended indication with the highest level of evidence (10/16). Over 75% of guidelines ignored transplant-center management, and non-CDI indications and key operational steps lacked sufficient high-certainty evidence. ICCs (0.86-0.97) showed excellent evaluator consistency.

CONCLUSIONS: Current FMT guidelines exhibit significant methodological deficiencies, heterogeneous recommendation coverage, and limited consensus beyond rCDI. FMT-specific guidelines show better developmental rigor but poorer applicability than general guidelines. Future FMT guideline development should establish core topic sets, adopt multidisciplinary collaborative mechanisms, and develop implementation toolkits with regular update protocols.},
}

@article {pmid42894858,
year = {2026},
author = {Geng, Z and Li, Q and Wang, D and Yang, H and Wang, H and Bao, J and Wang, Y and Wei, L},
title = {L-Histidine alleviates tacrolimus-induced islet dysfunction via the gut-pancreas axis.},
journal = {iScience},
volume = {29},
number = {11},
pages = {117802},
pmid = {42894858},
issn = {2589-0042},
abstract = {Tacrolimus is widely used after organ transplantation but can impair pancreatic β-cell function and glucose homeostasis. Using rodent models, antibiotic-mediated microbiota depletion, fecal microbiota transplantation, 16S rRNA sequencing, metabolomic profiling, and MIN-6 cells, we examined whether microbiota-associated L-histidine contributes to β-cell protection. Tacrolimus altered gut microbial composition and increased histidine-associated microbial and metabolic signals. L-histidine supplementation improved glucose tolerance and insulin secretion, reduced β-cell apoptosis, and increased PI3K/Akt/mTOR/p70S6K signaling and PDX-1, NeuroD1, and MafA expression. Microbiota depletion attenuated several protective effects of L-histidine, supporting a contribution of the gut microbiota to this response. These findings connect a microbiota-associated amino acid with tacrolimus-related β-cell dysfunction and provide a framework for investigating microbiota-metabolite contributions to metabolic complications of immunosuppression.},
}

@article {pmid42895099,
year = {2026},
author = {Liu, Y and Qiu, Y and Li, D and Zhai, S and Xia, T and Wang, M},
title = {Vinegar polyphenol extract alleviates alcohol-induced liver injury through suppressing the hepatic MAPK signaling pathway and restoring gut microbiota homeostasis and short-chain fatty acid generation in male mice.},
journal = {Food & function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6fo02941h},
pmid = {42895099},
issn = {2042-650X},
abstract = {Traditional brewed vinegar is rich in polyphenolic compounds that exhibit antioxidant, anti-inflammatory, and hepatoprotective activities. However, the protective mechanisms of vinegar polyphenol extract (VE) against alcohol-associated liver disease (ALD) involving gut homeostasis remain unclear. The phenolic composition of VE was characterized using UPLC-QTrap-MS/MS. Its hepatoprotective mechanisms in alcohol-treated mice were investigated through hepatic transcriptomic profiling and identification of key signaling pathways. Additionally, whether the hepatoprotective effects of VE were dependent on the gut microbiota were explored via antibiotic-mediated microbiota depletion and fecal microbiota transplantation. Twenty phenolic compounds were identified in VE, and 4-hydroxybenzoic acid was the predominant component accounting for 46.67%. VE administration at 750 mg kg[-1] significantly reduced serum ALT and AST levels, attenuated hepatic oxidative stress and inflammation, and suppressed alcohol-induced phosphorylation of p38, JNK, and ERK1/2. Meanwhile, VE restored the integrity of the intestinal barrier and reduced the LPS burden. Moreover, VE remodeled the gut microbiota by upregulating Akkermansia and Bacteroides and reducing Escherichia, which was accompanied by restoration of SCFA generation, notably acetic acid and propionic acid. Microbiota depletion weakened the protective effects of VE, whereas fecal microbiota transplantation restored its hepatoprotective activity. These findings suggest that VE alleviates alcohol-associated liver disease by suppressing the hepatic MAPK signaling pathway and restoring intestinal homeostasis. VE is a promising food-derived functional ingredient for the prevention of ALD.},
}

@article {pmid42895196,
year = {2026},
author = {Halder, U and Hamida, H and Kakar, K and Yang, X and Zhong, Y and Nagarkatti, M and Nagarkatti, P},
title = {Acute liver injury is triggered by dysbiosis and microbial translocation involving gut-liver axis.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2749977},
doi = {10.1080/19490976.2026.2749977},
pmid = {42895196},
issn = {1949-0984},
mesh = {Animals ; *Dysbiosis/microbiology/complications ; *Liver/microbiology/immunology/pathology ; *Bacterial Translocation ; Mice ; *Gastrointestinal Microbiome ; Intestinal Barrier Function ; Disease Models, Animal ; Humans ; Mice, Inbred C57BL ; Bacteria/classification/isolation & purification/genetics ; Male ; *Chemical and Drug Induced Liver Injury/microbiology ; },
abstract = {Acute liver injury (ALI) is a severe clinical condition that can progress to chronic liver failure, cirrhosis, or hepatocellular carcinoma, yet therapeutic options remain limited. Here, we investigated how hepatotoxin-induced gut-liver dysbiosis drives hepatic inflammation through microbial crosstalk. Using three murine ALI models, we assessed liver injury, intestinal barrier integrity, microbial composition along the gut-liver axis, and immune activation. Each hepatotoxin recapitulated distinct features of human ALI and induced unique patterns of hepatic and intestinal injury, enabling the progressive translocation of live bacteria from the gut to the liver and bloodstream. ALI was consistently associated with depletion of commensal taxa (Lactobacillaceae, Ruminococcaceae, and Bifidobacteriaceae) and enrichment of opportunistic pathogens (Enterococcaceae, Clostridiaceae, Enterobacteriaceae, and Burkholderiaceae). Dysbiosis also involved reduced gut bacteriophages and the expansion of viral families, including Retroviridae and Herpesviridae, in the liver and blood. Transplantation of the fecal or liver microbiota from ALI mice into microbiota-depleted recipients reproduced liver injury, immune activation, and intestinal barrier disruption, demonstrating that dysbiotic microbial communities alone are sufficient to trigger hepatic inflammation. These communities activated Th1/Th17 associated pathways (NF-κB, IL-17, TGF-β, and antigen presentation networks) and expanded pro-inflammatory immune populations. A key advance of this study is the direct comparison of fecal- versus liver-derived microbiota, revealing distinct mechanistic roles for each in driving liver pathology. Across all models, hepatotoxin-induced intestinal barrier breakdown drives gut-liver dysbiosis, microbial translocation, and immune-mediated liver injury. These findings uncover a unifying mechanism by which microbial imbalance reprograms hepatic immunity and accelerates ALI progression.},
}

Animals
*Dysbiosis/microbiology/complications
*Liver/microbiology/immunology/pathology
*Bacterial Translocation
Mice
*Gastrointestinal Microbiome
Intestinal Barrier Function
Disease Models, Animal
Humans
Mice, Inbred C57BL
Bacteria/classification/isolation & purification/genetics
Male
*Chemical and Drug Induced Liver Injury/microbiology

@article {pmid42891334,
year = {2026},
author = {Yu, Y and Wen, Q and Wang, X and Song, M and Yuan, T and Deng, F and Chai, J and Li, Y and Zhang, YP},
title = {Pioneering the canine model in microbiota-gut-brain research for social and affective disorders.},
journal = {iMetaOmics},
volume = {3},
number = {3},
pages = {e70113},
pmid = {42891334},
issn = {2996-9514},
abstract = {This commentary highlights the translational potential of canine models in investigating the microbiota-gut-brain (MGB) axis, focusing on their relevance to human social cognition and affective disorders, including major depressive disorder and autism spectrum disorder. While traditional rodent models provide foundational knowledge, the unique socio-behavioral complexity of dogs offers a potential bridge to study the shared neuroendocrine and microbial substrates underlying human psychopathology. This commentary outlines the promising avenues for canine-based research while critically addressing the practical limitations inherent in generalizing these findings to human populations, including genetic heterogeneity, standardization challenges, and ethical considerations. We propose a phased research pathway incorporating fecal microbiota transplantation and neurobehavioral phenotyping to define a clear trajectory for future translational research. Leveraging this canine platform creates a One Health paradigm, delivering mutual diagnostic and therapeutic advancements for both human and veterinary medicine, with applications for conditions such as anxiety and gastrointestinal disorders.},
}

@article {pmid42887877,
year = {2026},
author = {Carson, M and Meadows, V and Nejak-Bowen, K},
title = {Microbiome Targeted Therapies for Primary Sclerosing Cholangitis.},
journal = {Seminars in liver disease},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2983-7443},
pmid = {42887877},
issn = {1098-8971},
abstract = {Primary sclerosing cholangitis is a rare, progressive cholestatic liver disease of the intrahepatic and extrahepatic bile ducts with poor prognosis. The only life-extending treatment for PSC is liver transplantation, with up to 25% of post-transplant patients developing recurrent disease, highlighting an extrahepatic influence on disease. The gut-liver axis has been widely studied in the development and pathogenesis of PSC, with preclinical and clinical work demonstrating that targeting gut microbiota and its metabolites can elicit therapeutic effects against PSC. This review describes various microbiome-based therapeutics and their effectiveness in treating PSC, including antibiotics, probiotics, fecal microbiota transplantation, and bacteriophages. In conclusion, the use of microbiota-derived metabolites as potential therapeutics is also addressed.},
}

@article {pmid42888516,
year = {2026},
author = {Kelly, CR and Kelly, BJ and Wu, Q and Laine, L and Wu, GD and Kim, A and Fredell, L and Serra, S and Lewis, JD},
title = {Incidence and Risk Factors for C. difficile Reinfection After Faecal Microbiota Transplantation or Antibiotic Therapy.},
journal = {Alimentary pharmacology & therapeutics},
volume = {},
number = {},
pages = {},
doi = {10.1111/apt.71035},
pmid = {42888516},
issn = {1365-2036},
abstract = {BACKGROUND: Faecal microbiota transplant (FMT) is an effective treatment for multiply recurrent C. difficile infection (mrCDI). Less is known about rates of reinfection after successful FMT. We aimed to estimate the incidence of CDI reinfection, 6 or more months after FMT, to determine whether rates differ between mrCDI treated with and without FMT and whether proton pump inhibitor (PPI) therapy increases the risk of reinfection.

METHODS: Among patients with mrCDI (defined as ≥ 2 recurrences after the initial CDI episode) we compared reinfection with CDI (defined as a first recurrence > 183 days after treatment completion) in patients who underwent antibiotics followed by FMT with those treated with antibiotics alone in Optum's de-identified Clinformatics Data Mart Database (OPTUM CDM). We also compared reinfection between those with and without PPI use in OPTUM CDM and the American Gastroenterological Association FMT Registry.

RESULTS: In OPTUM CDM, 6384 patients treated with antibiotics alone and 1786 with antibiotics + FMT met inclusion criteria (median follow-up 704 days). One-year and 3-year CDI reinfection incidences were 5% and 10% in the FMT group and 6% and 12% in the antibiotics group: Cox regression HR 0.89, 95% CI 0.73-1.08. PPI use was associated with an increased risk of reinfection following FMT (HR 1.57, 1.03-2.41) in OPTUM CDM and in the FMT Registry (HR 1.62, 95% CI 0.84-3.12).

CONCLUSIONS: CDI reinfection rates are low after successful FMT and similar to rates in patients treated with antibiotics alone. PPI use was associated with reinfection, supporting reassessment of the ongoing indication for PPI therapy in patients with mrCDI.},
}

@article {pmid42889310,
year = {2026},
author = {Wang, H and Ou, G and Xu, H and Liu, T and Jiang, Y and Wang, S and Wu, J and Wu, S and Deng, L and Xu, L},
title = {Gegen Qinlian decoction alleviates ulcerative colitis by remodeling the gut microbiota-bile acid axis and inhibiting NLRP3-mediated pyroptosis.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1895206},
doi = {10.3389/fimmu.2026.1895206},
pmid = {42889310},
issn = {1664-3224},
mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Drugs, Chinese Herbal/pharmacology ; *Gastrointestinal Microbiome/drug effects ; *Colitis, Ulcerative/drug therapy/metabolism/microbiology ; Humans ; *Pyroptosis/drug effects ; *Bile Acids and Salts/metabolism ; Mice ; Caco-2 Cells ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Inflammasomes/metabolism ; },
abstract = {BACKGROUND: Gegen Qinlian Decoction (GQD) is used to treat intestinal disorders, but its mechanism in ulcerative colitis (UC) induced by combined high-fat diet (HFD) and dextran sulfate sodium (DSS) exposure remains unclear.

METHODS: A UC mouse model was induced by HFD plus DSS. GQD constituents were identified by UPLC-MS/MS. Colonic pathology and barrier integrity were assessed by H&E and immunofluorescence. Gut microbiota and bile acids were analyzed by 16S rRNA gene sequencing and targeted metabolomics. Transcriptomics, ELISA, Western blotting, fecal microbiota transplantation (FMT), and molecular docking were used to investigate mechanisms. LPS-stimulated Caco-2 cells were treated with 20 or 50 μM DCA; cell viability, NLRP3 inflammasome-related gene expression, and ZO-1/Occludin immunofluorescence were evaluated.

RESULTS: GQD ameliorated gut dysbiosis, decreasing the Firmicutes/Bacteroidetes ratio, increasing Akkermansia muciniphila, and reducing Clostridium perfringens. It remodeled bile acid metabolism, decreasing primary bile acids (CA, TCA, and CDCA, etc.) and increasing secondary bile acids (DCA, 6,7-DKLCA and 3β-DCA, etc.). Transcriptomics indicated inhibition of NOD-like receptor signaling. GQD suppressed NLRP3 inflammasome activation and reduced ASC, pro-caspase-1, cleaved caspase-1, GSDMD-N, and IL-18. Docking prioritized DCA as a candidate NLRP3-interacting metabolite. In Caco-2 cells, DCA dose-dependently reduced LPS-induced NLRP3, ASC, GSDMD, IL1B, and IL18 mRNA expression and partially restored ZO-1 and Occludin signals without appreciable cytotoxicity. FMT supported the involvement of gut microbiota in GQD-mediated anti-inflammatory effects.

CONCLUSION: GQD alleviates UC induced by combined HFD and DSS exposure by reshaping the gut microbiota and correcting bile acid dysregulation, thereby inhibiting NLRP3 inflammasome activation. This study highlights the gut microbiota-bile acid axis in GQD's therapeutic effects.},
}

Animals
*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
*Drugs, Chinese Herbal/pharmacology
*Gastrointestinal Microbiome/drug effects
*Colitis, Ulcerative/drug therapy/metabolism/microbiology
Humans
*Pyroptosis/drug effects
*Bile Acids and Salts/metabolism
Mice
Caco-2 Cells
Male
Disease Models, Animal
Mice, Inbred C57BL
Inflammasomes/metabolism

@article {pmid42890138,
year = {2026},
author = {Chen, Z and Gao, Z and Zhu, Z},
title = {Targeting the gut microbiota to promote motor rehabilitation after spinal cord injury: mechanisms, evidence, and translational challenges.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1946470},
doi = {10.3389/fneur.2026.1946470},
pmid = {42890138},
issn = {1664-2295},
mesh = {*Spinal Cord Injuries/rehabilitation/physiopathology/microbiology ; Humans ; Animals ; *Gastrointestinal Microbiome/physiology ; Translational Research, Biomedical ; Recovery of Function/physiology ; Fecal Microbiota Transplantation ; *Dysbiosis ; },
abstract = {Spinal cord injury (SCI) is a devastating central nervous system trauma that frequently results in permanent motor dysfunction. Over the past decade the gut microbiota has emerged as a potentially modifiable contributor to secondary injury and neural repair, giving rise to the concept of the gut-spinal cord axis. In this narrative review we synthesize current understanding of how SCI-associated gut dysbiosis may relate to the recovery of motor function, focusing on immune modulation, microbial metabolites such as short-chain fatty acids and bile acids, and gut-central nervous system signaling. Throughout, we deliberately separate evidence obtained in SCI models or in people with SCI from mechanistic evidence generated in other diseases or experimental systems, because conflating these sources is a recurring source of over-interpretation in this field. We then summarize microbiota-targeted interventions studied in animal models-probiotics and prebiotics, fecal microbiota transplantation (FMT), antibiotics and bacteriophages, and direct supplementation with microbial metabolites-and appraise the small, predominantly observational human literature. Several of these interventions improve locomotor outcomes in rodent SCI models, but, with rare exceptions, the causal chain from a microbial change to a functional improvement has not been demonstrated within a single SCI study, and no randomized controlled trial in people with SCI has used motor function as its primary endpoint. We conclude by dissecting the principal translational barriers-inter-individual variability in microbiota composition, uncertain intervention timing and duration, unresolved safety questions, and the absence of standardized pre-clinical-to-clinical pipelines-and by outlining the study designs and reporting standards required to move this field from association toward causation.},
}

*Spinal Cord Injuries/rehabilitation/physiopathology/microbiology
Humans
Animals
*Gastrointestinal Microbiome/physiology
Translational Research, Biomedical
Recovery of Function/physiology
Fecal Microbiota Transplantation
*Dysbiosis

@article {pmid42890816,
year = {2026},
author = {Peng, O and Liu, Y and Wang, X and Huang, Y and Yang, Y and Kang, Q and Geng, R and Hu, G and Lv, A and Hu, F and Xia, Y and Luo, X and Liao, J and He, Y and Kuang, Z and Du, Y and Zhang, Y and Xue, C and Han, Z and Li, WJ and Dong, L and Zhang, H and Cao, Y},
title = {Akkermansia muciniphila enhances chicken resistance to infectious bronchitis virus by boosting GABA synthesis and suppressing the NF-κB inflammatory pathway.},
journal = {iMetaOmics},
volume = {3},
number = {1},
pages = {e70086},
doi = {10.1002/imo2.70086},
pmid = {42890816},
issn = {2996-9514},
abstract = {Infectious bronchitis virus (IBV) is a major viral pathogen causing substantial economic losses in the global poultry industry. However, the limited efficacy of commercial vaccines and the absence of approved antiviral drugs underscore the urgent need for novel strategies to combat IBV, particularly in the context of antibiotic-free poultry production. Emerging evidence suggests that gut microbiota plays a crucial role in shaping host immunity and antiviral resilience. In this study, we demonstrated that gut microbiota composition is a key determinant of IBV resistance in chickens, as revealed through a fecal microbiota transplantation (FMT) model. Utilizing multi-omics approaches, we conducted a comprehensive characterization of microbiomic, viromic, and metabolic differences among adult chickens, young chickens, and FMT-treated young chickens for the first time, establishing a mechanistic link between gut microbiota and IBV resistance. Building on these insights, longitudinal microbiome profiling in a newly developed persistent IBV infection model identified Akkermansia muciniphila as the key bacterium conferring IBV resistance, with its administration improving survival rates from 30-35% to 90-95%. Additionally, two novel candidate probiotics, Cloacibacillus porcorum and Neglecta timonensis, exhibited moderate yet measurable protective effects. Mechanistic investigations revealed that Akkermansia muciniphila enhances γ-aminobutyric acid (GABA) production, which suppresses NF-κB-driven inflammatory responses, reduces pro-inflammatory cytokine levels, alleviates nephritis, and upregulates antiviral interferon expression, thereby fortifying host defenses against IBV infection. These findings provide a scientific foundation for deploying live biotherapeutic products as an intervention strategy against IBV and highlight the broader potential of gut microbiota modulation in mitigating infectious diseases and optimizing poultry health management.},
}

@article {pmid42891232,
year = {2026},
author = {Xu, T and Tao, X and Fang, D and Zhang, H and Wang, Z and Liu, Y},
title = {Lactobacillus derived small RNAs protect against Klebsiella pneumoniae infection.},
journal = {iMeta},
volume = {},
number = {},
pages = {e70184},
doi = {10.1002/imt2.70184},
pmid = {42891232},
issn = {2770-596X},
abstract = {Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major multidrug-resistant pathogen with limited treatment options. Plant-derived natural products have broad biological activities, but their protective effects against extraintestinal multidrug-resistant bacterial infections remain poorly understood. Herein, we show that selected plant-derived natural products protect mice against CRKP pulmonary infection by remodeling the gut microbiota. Fecal microbiota transplantation and microbiota-depletion experiments demonstrated that this protection was microbiota dependent, with Lactobacillus emerging as a key genus associated with reduced pulmonary bacterial burden. Among four isolated Lactobacillus species, Lactobacillus murinus (L. murinus) conferred the strongest protection against CRKP infection. Mechanistically, L. murinus-derived membrane vesicles (MVs) delivered the small RNA mim-miR-21a-5p to pulmonary macrophages, where it targeted PDCD4 and activated the Nrf2/SOD2 antioxidant pathway. This signaling cascade preserved mitochondrial oxidative phosphorylation, promoted an M2-like macrophage phenotype, and ultimately restricted CRKP infection. Consistent with these findings, intestinal Lactobacillus, particularly L. murinus, was reduced in patients with CRKP infection compared with healthy controls. Collectively, our findings reveal a mechanism by which plant-derived natural products enhance host resistance to CRKP through microbiota remodeling and identify L. murinus-derived small RNAs and membrane vesicles as key mediator of this gut-lung protective axis.},
}

@article {pmid42880811,
year = {2026},
author = {Juanola, A and Moreta, MJ and Solé, C and Sánchez, J and Albillos, A and Martínez González, J and Poca Sans, M and Alvarado, E and Campos-Varela, I and Cespedes, C and Alonso, S and Bañares, R and Fortea, JI and Puente, Á and Llop, E and Fernández-Carrillo, C and Moya, A and Ruiz-Ruiz, S and Fernandez-Real, JM and Mayneris-Perxachs, J and Bonfill, E and Rivera, C and Pich, J and Piano, S and Solà, E and Torres, F and Iavarone, S and Pérez-Guasch, M and Casanova, NC and González-Suárez, B and Fabrellas, N and Graupera, I and Pose, E and Ginès, P},
title = {Randomised, double-blind, placebo-controlled trial of faecal microbiota transplantation in patients with decompensated cirrhosis: the Livergut protocol.},
journal = {BMJ open},
volume = {16},
number = {10},
pages = {e118486},
doi = {10.1136/bmjopen-2026-118486},
pmid = {42880811},
issn = {2044-6055},
}

@article {pmid42881491,
year = {2026},
author = {Zehra, H and Kuchma, N and Lin, AW and Morris, G and Solano, O and Lopez, S and Kabage, AJ and Vaughn, BP and Weingarden, A and Fischer, M and Khoruts, A and Teigen, L},
title = {The Trajectory of Gastrointestinal Symptom Experience Following Fecal Microbiota Transplant for Recurrent Clostridioides Difficile Infection.},
journal = {Journal of clinical gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1097/MCG.0000000000002424},
pmid = {42881491},
issn = {1539-2031},
abstract = {INTRODUCTION: Recurrent Clostridioides difficile infection (rCDI) increases the risk of persistent gastrointestinal symptoms after treatment. Although fecal microbiota transplantation (FMT) effectively prevents CDI recurrence after antibiotics, the trajectory of gastrointestinal symptom severity remains poorly characterized.

METHODS: We tracked gastrointestinal symptom severity in a prospective, multicenter cohort study of adults with rCDI after treatment with standardized FMT products. Patients who experienced a CDI recurrence during the follow-up period were excluded. The IBS Symptom Severity Scale (IBS-SSS) was used as a measure of symptom severity, not as a diagnostic tool. Patients completed the IBS-SSS at the time of FMT, 1-week, 1-month, and 3-months post-FMT. The primary outcome was the change in IBS-SSS score after treatment. Subgroup analyses were conducted among patients with baseline IBS-SSS ≥175 (moderate/severe symptom severity) and <175 (none/mild symptom severity). Linear mixed-effects models were used to evaluate longitudinal changes and identify clinical predictors of IBS-SSS scores.

RESULTS: Among 107 patients included, median IBS-SSS scores decreased from 170 (range: 0 to 440) at baseline to 76 (range: 0 to 390) at week 1 and 54 (0 to 445) at month 3 (P<0.001). In those with baseline IBS-SSS ≥175 (n=51), 64% had none or mild symptom severity at month 3. In those with baseline IBS-SSS <175 (n=53), symptom severity was observed to remain as none or mild at month 3 in all but one patient.

CONCLUSION: FMT administered for prevention of rCDI was followed by a rapid (1 wk) and sustained (3 mo) reduction in gastrointestinal symptom scores in patients who did not develop CDI recurrence. These data help characterize the expected early post-FMT symptom trajectory, providing foundational evidence to better inform patient expectations and future interventions for persistent symptoms.},
}

@article {pmid42881530,
year = {2026},
author = {Springer, R and Claus, P and Hörner, M and Otto, C and Burkard, N and Lauerer, J and Deinlein, H and Fekete, A and Schmitz, W and Seyfried, F and Schlegel, N},
title = {High-fat diet-derived metabolite uridine diphosphate (UDP) impairs epithelial regeneration by P2Y 6 -receptor signaling.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2748160},
doi = {10.1080/19490976.2026.2748160},
pmid = {42881530},
issn = {1949-0984},
mesh = {Animals ; Male ; *Diet, High-Fat/adverse effects ; Rats, Wistar ; *Obesity/metabolism/microbiology ; Rats ; Signal Transduction ; *Uridine Diphosphate/metabolism ; Gastrointestinal Microbiome ; *Intestinal Mucosa/metabolism ; *Receptors, Purinergic P2/metabolism/genetics ; *Regeneration ; Intestinal Barrier Function ; Feces/microbiology ; },
abstract = {Obesity is associated with a chronic low-grade inflammation affecting metabolic changes and organ dysfunction. Impairment of the intestinal epithelial barrier (IEB) and alterations in gut microbiota are considered to contribute to this phenotype by largely undefined mechanisms. Here, we used a diet-induced obesity model in rats to investigate the early interplay between a high-fat diet (HFD), gut microbiota composition, metabolic stool contents and IEB regeneration. Male Wistar rats received either a high-fat diet or a low-fat diet (LFD) ad libitum. HFD feeding resulted in weight gain and impaired oral glucose tolerance. Impairment of IEB function was evident by augmented lipopolysaccharide levels in the blood and reduced expression of junctional proteins Claudin-3, 4, and Desmoglein-2 in colonic samples of HFD rats. 16S-rRNA marker-gene sequencing of colonic microbiota revealed decreased phylogenetic diversity in HFD rats and significant alterations in microbial community composition. Detailed analysis revealed that content from HFD rats impaired intestinal epithelial regeneration in organoid assays. Metabolomic profiling identified uridine monophosphate/uridine diphosphate (UMP/UDP) metabolites as strongly enriched in HFD samples. UDP emerged as a key metabolite mediating impaired epithelial regeneration through P2Y6 receptor signaling, as pharmacological inhibition of P2Y6 with antagonist MRS2578 attenuated both UDP- and HFD-induced loss of epithelial regeneration. In summary, these data demonstrate that the diet-dependent stool metabolite UDP compromises intestinal epithelial repair via P2Y6 receptor signaling in early obesity. These findings link impaired epithelial regeneration to the onset of obesity-associated low-grade inflammation.},
}

Animals
Male
*Diet, High-Fat/adverse effects
Rats, Wistar
*Obesity/metabolism/microbiology
Rats
Signal Transduction
*Uridine Diphosphate/metabolism
Gastrointestinal Microbiome
*Intestinal Mucosa/metabolism
*Receptors, Purinergic P2/metabolism/genetics
*Regeneration
Intestinal Barrier Function
Feces/microbiology

@article {pmid42882498,
year = {2026},
author = {Siemińska, I},
title = {The Gut Microbiota-Immunity Axis in Colorectal Cancer: Implications for Immunotherapy and Clinical Translation.},
journal = {Cells},
volume = {15},
number = {19},
pages = {},
doi = {10.3390/cells15191800},
pmid = {42882498},
issn = {2073-4409},
mesh = {Humans ; *Colorectal Neoplasms/immunology/therapy/microbiology ; *Immunotherapy/methods ; *Gastrointestinal Microbiome/immunology ; *Translational Research, Biomedical ; Animals ; *Immunity ; },
abstract = {Colorectal cancer (CRC) arises within a complex microbial ecosystem that may influence carcinogenesis, tumor immunity, and therapeutic response. This is particularly relevant in metastatic disease, where most tumors are microsatellite-stable/mismatch repair-proficient (MSS/pMMR) and derive little meaningful benefit from immune checkpoint inhibitor (ICI) monotherapy. Specific pathobionts, including Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli, have been implicated in genotoxic, inflammatory, and checkpoint-related mechanisms that may contribute to tumor progression and immune evasion, whereas selected commensals and microbiota-derived metabolites may support antitumor immunity in a context-dependent manner. This review integrates translational evidence linking microbial taxa and functions, metabolites, neutrophil biology, bacterial extracellular vesicles, and T-cell dysfunction with CRC progression and immunotherapy response. This review critically examines emerging microbiome-directed strategies, including fecal microbiota transplantation, next-generation probiotics, defined bacterial consortia, dietary and perioperative interventions, postbiotics, and bacteriophage-based approaches, as potential means of modifying immune resistance in MSS/pMMR CRC. Although early clinical signals from microbiota-modulating combinations are encouraging, the available evidence remains limited by small cohorts, heterogeneous interventions, and the absence of randomized CRC-specific studies. Microbiome-based biomarkers and therapeutics therefore remain investigational, and standardized sampling, prospective validation, and carefully designed trials will be required before microbiome modulation enters routine CRC care.},
}

Humans
*Colorectal Neoplasms/immunology/therapy/microbiology
*Immunotherapy/methods
*Gastrointestinal Microbiome/immunology
*Translational Research, Biomedical
Animals
*Immunity

@article {pmid42883057,
year = {2026},
author = {Zhang, J and Sun, Y and Li, X and You, D and Zhang, Z and Xu, M and Wu, D},
title = {Effects of Colostrum-Period Fecal Microbiota Transplantation on Growth Performance, Immune Function and Gut Microbiota in Pre-Weaned Calves.},
journal = {Animals : an open access journal from MDPI},
volume = {16},
number = {19},
pages = {},
doi = {10.3390/ani16193088},
pmid = {42883057},
issn = {2076-2615},
support = {2023LHMS03048//the Natural Science Foundation of Inner Mongolia Autonomous Region/ ; },
abstract = {Neonatal calf diarrhea caused by intestinal microbial dysbiosis severely restricts rearing efficiency, and fecal microbiota transplantation (FMT) emerges as a promising antibiotic-free strategy for regulating gut homeostasis. Nevertheless, to the best of our knowledge, the effects of colostrum-period FMT and the functional differences between colonic and colostrum delivery routes remain poorly characterized in pre-weaned dairy calves. We hypothesized that colostrum-period FMT would accelerate gut microbiota maturation, improve immune status and reduce diarrhea incidence in pre-weaned calves, with delivery-route-dependent effects. This study aimed to investigate how two colostrum-phase FMT delivery routes shape growth performance, serum immune profiles and gut microbiota in neonatal Holstein calves. Sixty newborn calves were randomly assigned to three groups (n = 20 per group): control (no FMT), colon-FMT (colonic perfusion), and colostrum-FMT (FMT mixed with colostrum). Donor feces were homogenized with sterile saline at a 1:9 ratio for FMT suspension preparation, and the trial lasted 56 days. For growth performance, the colon-FMT calves exhibited significantly higher average daily gain from D29 to D56 (p < 0.05). In terms of intestinal health, the colostrum-FMT group exhibited lower diarrhea incidence during D15-28 (p < 0.05) but markedly higher diarrhea rates during D29-56 (p < 0.01). For serum immunity, colon-FMT calves had elevated serum IgG at D14 (p < 0.05). At D56, the concentrations of IL-2 (p < 0.01) and IL-4 (p = 0.05) were significantly lower in the colostrum-FMT group than the colon-FMT group; no intergroup differences were detected for other serum cytokines and immunoglobulins. 16S rRNA gene sequencing of D28 fecal samples revealed that the colon-FMT group possessed a significantly higher relative abundance of Lactobacillus compared with the other two treatments (p < 0.05). Collectively, colonic FMT is associated with remodeling intestinal microbiota by enriching beneficial Lactobacillus, improved late-stage growth and sustained long-term intestinal health in pre-weaned calves, whereas colostrum-mediated FMT only provides transient protection against early diarrhea.},
}

@article {pmid42884619,
year = {2026},
author = {Ibrahim, I and Lawrence, K and Forte, OA and Huitt, L and Naidu, NC and Ajibola, N and Xu, J and Boakai, RK and Akabanda, F and Owusu-Kwarteng, J and Ajayi, OS and Ayariga, JA},
title = {Diffuse Idiopathic Skeletal Hyperostosis (DISH): Potential Links Between Gut Microbiota and Spinal Degenerative Diseases.},
journal = {Nutrients},
volume = {18},
number = {19},
pages = {},
doi = {10.3390/nu18193168},
pmid = {42884619},
issn = {2072-6643},
support = {Title III- HBGI-RES//United States Department of Education/ ; },
mesh = {Humans ; *Hyperostosis, Diffuse Idiopathic Skeletal/microbiology ; *Gastrointestinal Microbiome/physiology ; *Intervertebral Disc Degeneration/microbiology ; Dysbiosis ; Animals ; },
abstract = {Diffuse Idiopathic Skeletal Hyperostosis (DISH) is a systemic, non-inflammatory skeletal disorder characterized by progressive calcification and ossification of spinal ligaments and entheses. Its strong associations with aging, obesity, type 2 diabetes, and metabolic syndrome raise the possibility that metabolic and inflammatory pathways may contribute to disease development. The gut microbiota participates in nutrient metabolism, short-chain fatty acid production, bile-acid transformation, intestinal-barrier maintenance, and immune regulation; these functions provide a plausible framework for examining whether intestinal dysbiosis may influence spinal and musculoskeletal tissues. This narrative review therefore evaluates the potential relationship between gut microbiota, DISH, and related spinal degenerative diseases. It considers the nutritional, metabolic, immunological, and host-interaction functions of the gut microbiota before examining proposed gut-spine, gut-bone, gut-joint, gut-disc, gut-ligament, and gut-muscle pathways. Particular attention is given to the apparent paradox that most microbiome-bone evidence concerns osteoporosis and bone loss, whereas DISH is characterized by excessive ectopic bone formation. Differences in short-chain fatty acid concentration, receptor expression, local versus systemic signaling, and osteoblast-osteoclast microenvironments may produce divergent skeletal effects, but these mechanisms have not been tested directly in DISH. Recent studies support associations between selected microbial taxa and intervertebral disc degeneration or spinal stenosis; however, direct clinical evidence linking gut microbiota to DISH remains limited. Consequently, dietary modification, probiotics, prebiotics, and fecal microbiota transplantation should be regarded as research considerations rather than established treatments for DISH. Well-characterized case-control and longitudinal studies integrating microbiome profiling, metabolomics, inflammatory markers, and serial imaging are required to determine whether reproducible microbial or metabolite signatures precede DISH onset or progression. The pathways discussed in this review are therefore presented as biologically plausible, testable hypotheses and not as established causal relationships.},
}

Humans
*Hyperostosis, Diffuse Idiopathic Skeletal/microbiology
*Gastrointestinal Microbiome/physiology
*Intervertebral Disc Degeneration/microbiology
Dysbiosis
Animals

@article {pmid42884675,
year = {2026},
author = {Yang, F and Xie, S and Yang, W and Zhu, C and Chen, Y and Yang, H and Yuan, H and Li, Q},
title = {Multi-Omics Analysis Reveals the Potential Role of Inonotus obliquus in Mit-Igating Hemolytic Jaundice.},
journal = {Nutrients},
volume = {18},
number = {19},
pages = {},
doi = {10.3390/nu18193225},
pmid = {42884675},
issn = {2072-6643},
support = {No. CKD/SXMU-2025-07//Shanxi Medical University/ ; No. 202303021221129//Shanxi Science and Technology Department/ ; },
mesh = {Animals ; Mice ; *Gastrointestinal Microbiome/drug effects ; Phenylhydrazines ; Male ; Liver/metabolism/drug effects ; Multiomics ; Bilirubin/blood ; Disease Models, Animal ; Limosilactobacillus reuteri ; *Jaundice/drug therapy/chemically induced ; *Plant Extracts/pharmacology ; },
abstract = {Background: Hemolytic jaundice, characterized by excessive bilirubin production and hepatic dysfunction, currently lacks effective therapeutic strategies targeting its underlying mechanisms. Methods: This study evaluated the therapeutic potential of the aqueous extract of Inonotus obliquus (IO) in ameliorating hemolytic jaundice through modulation of the gut-liver axis. A murine model of hemolytic jaundice was induced by phenylhydrazine (PHZ) administration, and IO was orally administered as the intervention. Antibiotic depletion and FMT verified gut microbiota dependence. Liver injury, serum bilirubin, gut microbiome, and metabolites were assessed. Results: IO treatment significantly alleviated PHZ-induced hemolytic jaundice in mice. Notably, antibiotic-mediated depletion of the gut microbiota abolished the hepatoprotective effects of IO, whereas fecal microbiota transplantation (FMT) from IO-treated donors conferred marked amelioration of hyperbilirubinemia in recipient mice. Integrative multi-omics analysis identified Limosilactobacillus reuteri and Lactobacillus johnsonii as the predominant microbial species altered by IO. Furthermore, IO upregulated the expression of farnesoid X receptor (FXR) and pregnane X receptor (PXR) in both hepatic and intestinal tissues and also increased the expression of bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2). These alterations were correlated with an increased excretion of bile acids and bilirubin into the intestinal lumen, thereby mitigating hepatic injury. This process may be associated with the modulation of gut microbiota. Conclusions: These findings collectively provide evidence of a significant correlation between IO treatment and the mitigation of hemolytic jaundice, achieved by modulating the enterohepatic circulation of bile acids and bilirubin through the regulation of gut microbiota. Our results highlight the potential of IO as a microbiota-directed nutritional strategy for the management of jaundice.},
}

Animals
Mice
*Gastrointestinal Microbiome/drug effects
Phenylhydrazines
Male
Liver/metabolism/drug effects
Multiomics
Bilirubin/blood
Disease Models, Animal
Limosilactobacillus reuteri
*Jaundice/drug therapy/chemically induced
*Plant Extracts/pharmacology

@article {pmid42884732,
year = {2026},
author = {Samardžić, S and Božić, DD and Drobac, M and Marčetić, M and Arsenijević, J and Medarević, D and Maksimović, Z},
title = {The Gut Microbiota as a Mediator of the Metabolic Benefits of Fungi and Their Polysaccharides: A Review of Evidence Addressing Causality.},
journal = {Nutrients},
volume = {18},
number = {19},
pages = {},
doi = {10.3390/nu18193281},
pmid = {42884732},
issn = {2072-6643},
support = {451-03-33/2026-03/200161; 451-03-34/2026-03/200161//Ministry of Science, Technological Development, and Innovation/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; *Prebiotics/administration & dosage ; *Fungi/metabolism ; *Polysaccharides ; *Fungal Polysaccharides ; *Metabolic Diseases/microbiology ; },
abstract = {Prebiotic supplementation has emerged as a promising strategy to ameliorate metabolic disorders through beneficial reshaping of the gut microbiota. Accumulating evidence suggests that fungi and their polysaccharides (e.g., those from Auricularia auricula-judae, Boletus edulis, Hirsutella sinensis, Isaria cicadae, Ramaria botrytoides, and Wolfiporia cocos) possess considerable potential in this context. The present review summarizes studies providing data relevant to the potential involvement of the gut microbiota in mediating the metabolic benefits of fungal interventions. Observed outcomes, potentially linked to the gut microbiota, included reductions in body, visceral fat, and liver weights, improved lipid and glycemic profiles, enhanced insulin sensitivity, and decreased circulating lipopolysaccharide, leptin, and proinflammatory cytokines (TNF-α, IL-1β, IL-6). Upregulation of tight junction proteins in the colon implied strengthened gut barrier function. Histological analyses revealed smaller adipocytes and attenuation of hepatic steatosis. Additional effects included stimulation of white adipose tissue browning and enhanced hepatic thermogenesis. Alterations in gut microbiota composition were diverse; however, a reduction in the Firmicutes/Bacteroidetes ratio was commonly reported. Furthermore, oral administration of bacterial species enriched by fungal interventions, such as Papillibacter cinnamivorans, Parabacteroides goldsteinii, Bacteroides intestinalis, Lactobacillus johnsonii, and Enterococcus casseliflavus, reproduced the metabolic improvements, supporting their possible mediating role. Collectively, current evidence indicates that fungi and their polysaccharides may exert metabolic benefits, at least in part, through gut microbiota modulation; however, further investigation is needed to determine the extent to which the gut microbiota contributes causally to these benefits.},
}

Humans
*Gastrointestinal Microbiome/physiology
Animals
*Prebiotics/administration & dosage
*Fungi/metabolism
*Polysaccharides
*Fungal Polysaccharides
*Metabolic Diseases/microbiology

@article {pmid42885915,
year = {2026},
author = {Gries, M and Schäfer, KH and Endres, K},
title = {Targeting the microbiota-gut-brain axis in Alzheimer's and Parkinson´s disease: recent therapeutic approaches.},
journal = {Expert opinion on therapeutic targets},
volume = {},
number = {},
pages = {},
doi = {10.1080/14728222.2026.2748747},
pmid = {42885915},
issn = {1744-7631},
abstract = {INTRODUCTION: Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative disorders with limited disease-modifying treatment options. Evidence suggests that the microbiota-gut-brain axis (MGBA) plays a role in these diseases by facilitating communication between the gut and the central nervous system. Associations have been found between altered gut microbiota composition and function, impaired barrier integrity, dysregulated metabolite production, and immune activation to neuroinflammation and progressive neurodegeneration.

AREAS COVERED: This review summarizes and critically assesses recent studies from the past year to provide an updated overview of therapeutic strategies targeting the MGBA in both diseases. We discuss dietary interventions, probiotics, postbiotics, microbial metabolites, and approaches targeting gut barrier function. We also highlight strategies such as fecal transplantation, photobiomodulation, and PD-targeted metabolism therapies using butyrate and resistant starch.

EXPERT OPINION: While these interventions have shown promising results in preclinical and early clinical trials, their clinical application is limited by methodological heterogeneity, interindividual variability and a lack of standardized protocols. Successful implementation requires carefully designed clinical trials, particularly longitudinal studies of presymptomatic cohorts, standardized microbiome analyses, and integrated multi-omics approaches to elucidate causal relations and facilitate personalized treatment strategies.},
}

@article {pmid42886170,
year = {2026},
author = {Park, K and Joo, MK and Lee, IH and Woo, JH and Park, HS and Kong, CH and Jung, SY and Woo, SY and Kim, JY and Park, HJ and Kim, JW and Kim, DH and Ryu, JH and Choi, JH},
title = {Schizophrenia-associated gut microbiota are linked to reduced colonic PRODH expression and behavioral changes in mice.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2748081},
doi = {10.1080/19490976.2026.2748081},
pmid = {42886170},
issn = {1949-0984},
mesh = {Animals ; Male ; *Proline Oxidase/genetics/metabolism ; Mice ; Mice, Inbred C57BL ; *Schizophrenia/microbiology/physiopathology ; *Gastrointestinal Microbiome ; *Colon/microbiology/enzymology ; Humans ; Fecal Microbiota Transplantation ; Bacteria/classification/genetics/isolation & purification/enzymology ; Behavior, Animal ; Proline/blood ; },
abstract = {Schizophrenia (SCZ) is a chronic neuropsychiatric disorder whose biological basis remains incompletely understood. Growing evidence implicates the gut-brain axis in SCZ, but the host pathways through which disease-associated microbiota may influence behavior remain unclear. Here, we examined whether the gut microbiota from patients with SCZ is associated with behavioral and metabolic alterations in male C57BL/6N mice. Fecal microbiota transplantation (FMT) from patients with SCZ was associated with impaired short-term recognition memory, reduced social novelty preference, and decreased prepulse inhibition in recipient mice. Transcriptomic profiling of colonic tissue identified reduced expression of Prodh, which encodes proline dehydrogenase (PRODH), together with elevated plasma proline levels. Comparative microbiome analyses identified a five-species candidate consortium associated with the SCZ donor microbiome - Escherichia fergusonii, Shigella sonnei, Morganella morganii, Citrobacter freundii, and Enterococcus faecalis. Oral administration of this five-species mixture (5-SM) was associated with similar behavioral changes, reduced colonic PRODH expression, and hyperprolinemia in mice. Together, these findings support a possible association between schizophrenia-associated changes in the gut microbiota, altered intestinal proline metabolism, and behavioral changes in mice.},
}

Animals
Male
*Proline Oxidase/genetics/metabolism
Mice
Mice, Inbred C57BL
*Schizophrenia/microbiology/physiopathology
*Gastrointestinal Microbiome
*Colon/microbiology/enzymology
Humans
Fecal Microbiota Transplantation
Bacteria/classification/genetics/isolation & purification/enzymology
Behavior, Animal
Proline/blood

@article {pmid42886304,
year = {2026},
author = {Zhu, Y and Ma, J and Wang, D and Cui, M and Peng, J and Lu, X and Pei, X and Wang, Y and Lv, J and Yan, Y and Ma, W and Zhao, M and You, S and Ma, J and Tang, Y and Zhu, Y},
title = {Curcumin alleviates metabolic dysfunction-associated steatotic liver disease via gut microbiota-dependent epigenetic alterations.},
journal = {Molecular biomedicine},
volume = {7},
number = {1},
pages = {},
pmid = {42886304},
issn = {2662-8651},
support = {82300661//National Natural Science Foundation of China/ ; 82203866//National Natural Science Foundation of China/ ; 2024AH030020//Outstanding Youth Science Foundation of the Department of Education of Anhui Province/ ; 2308085QH246//Natural Science Foundation of Anhui province/ ; KJ2021A0205//Natural Science Foundation of the Anhui Higher Education Institutions/ ; 2022xkjT013//Basic and Clinical cooperative research program of Anhui Medical University/ ; 2023xkj002//Scientific Research Foundation of Anhui Medical University/ ; },
mesh = {Animals ; *Epigenesis, Genetic/drug effects ; *Curcumin/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; *Fatty Liver/drug therapy/metabolism/genetics ; Rats ; Male ; Liver/metabolism/drug effects/pathology ; Diet, High-Fat/adverse effects ; Humans ; *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism ; },
abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent, yet effective therapies remain limited. Curcumin (Cur), a polyphenol with well-documented metabolic benefits, shows therapeutic promise in MASLD, but its efficacy and underlying mechanisms remain incompletely understood. A meta-analysis of seven clinical studies indicated that Cur supplementation reduced serum aminotransferase levels, supporting its potential clinical benefit. In high-fat diet (HFD)-fed rats, Cur reduced hepatic lipid accumulation and metabolic dysfunction, whereas these effects were markedly weakened in antibiotic-induced pseudo-germ-free rats, indicating microbiota dependence. Fecal microbiota transplantation from Cur-treated donors transferred these metabolic and histological benefits to antibiotic-conditioned recipients. Fecal 16S rRNA sequencing identified Clostridium_sensu_stricto_1 (C. sensu) as a Cur-suppressed, pro-steatotic taxon, and targeted reconstitution of this taxon abolished Cur-mediated protection. Untargeted hepatic metabolomics and liquid chromatography-mass spectrometry identified kynurenine (KYN) as a C. sensu-derived metabolite and showed that Cur reduced hepatic KYN accumulation. Integrated H3K27ac ChIP-seq, bulk RNA-seq, and single-cell analyses pinpointed hepatocyte-enriched CEBPB as a key epigenetically regulated effector. Luciferase reporter assays, ChIP-qPCR, and gain- and loss-of-function experiments showed that KYN activated the aryl hydrocarbon receptor (AHR), increased H3K27ac enrichment at the Cebpb locus, and induced Cebpb transcription. CEBPB knockdown blocked KYN-induced PI3K-AKT activation and lipid accumulation, whereas in vivo KYN supplementation largely reversed Cur-mediated protection. Collectively, this study reveals a novel gut-liver axis in MASLD pathogenesis, demonstrating that Cur alleviates hepatic steatosis by targeting the microbiota-KYN-AHR-H3K27ac-Cebpb epigenetic axis, positioning Cur supplementation and KYN modulation as promising therapeutic strategies for MASLD intervention.},
}

Animals
*Epigenesis, Genetic/drug effects
*Curcumin/pharmacology/therapeutic use
*Gastrointestinal Microbiome/drug effects
*Fatty Liver/drug therapy/metabolism/genetics
Rats
Male
Liver/metabolism/drug effects/pathology
Diet, High-Fat/adverse effects
Humans
*Non-alcoholic Fatty Liver Disease/drug therapy/metabolism

@article {pmid42887564,
year = {2026},
author = {Stallmach, A and Guse, J and Katzer, K and Reuken, PA and Knafla, F and Schauer, A and Thon, S and Kiehntopf, M and Haziri, D and Steube, A},
title = {Fecal Microbiota Transfer for Recurrent Clostridioides difficile Infection: A Retrospective Single-Center Analysis.},
journal = {Zeitschrift fur Gastroenterologie},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2954-8029},
pmid = {42887564},
issn = {1439-7803},
abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is the leading cause of healthcare-associated infectious diarrhea. Despite high initial response rates to antibiotic therapy, recurrence occurs in approximately 20% of patients. Fecal microbiota transplantation (FMT) has emerged as an effective treatment option for multiple recurrences, demonstrating high efficacy and a favorable safety profile. This study aimed to evaluate the effectiveness and safety of FMT in patients with recurrent CDI (rCDI).

METHODS: In this single-center retrospective study, 75 patients who underwent FMT for rCDI between November 2016 and January 2026 after experiencing at least two recurrences despite standard antibiotic therapy were included. Donor screening was performed according to the requirements of the German Federal Institute for Drugs and Medical Devices (BfArM). Following CDI-directed antibiotic pretreatment, FMT was administered either by colonoscopy, oral capsules, or a combination of both. Patients were followed for three months. The primary endpoint was the absence of diarrhea as a surrogate marker for rCDI, including a predefined subgroup analysis of patients with inflammatory bowel disease (IBD).

RESULTS: Follow-up data were available for 65 patients, of whom 56 (86.1%) achieved sustained clinical remission. Patients with concomitant IBD (n=15) showed a comparable response rate (86.7%). The route of FMT administration had no significant impact on treatment outcome. Overall, FMT was well tolerated, with only four patients (5.3%) reporting predominantly self-limiting adverse events.

CONCLUSION: FMT is a highly effective and safe treatment for recurrent CDI, including in multimorbid patients and those with concomitant IBD.},
}

@article {pmid42875381,
year = {2026},
author = {Zhu, X and Cheng, L and Li, S and Guo, D and Guo, W and Du, X and Yan, R and Wang, X and Yuan, S and Chen, M and Zhang, W and Li, S and Li, F and Zhang, L},
title = {Fecal microbiota transplantation for the treatment of neurogenic rosacea: protocol of a randomized, blinded, placebo-controlled explorer study.},
journal = {Annals of medicine},
volume = {58},
number = {1},
pages = {2735091},
doi = {10.1080/07853890.2026.2735091},
pmid = {42875381},
issn = {1365-2060},
mesh = {Humans ; *Rosacea/therapy/microbiology ; Double-Blind Method ; *Fecal Microbiota Transplantation/methods ; Female ; Treatment Outcome ; Adult ; Quality of Life ; Male ; *Gastrointestinal Microbiome/physiology ; Middle Aged ; *Dysbiosis/therapy ; Feces/microbiology ; },
abstract = {INTRODUCTION: Neurogenic rosacea is a distinct phenotype of rosacea characterized by persistent facial erythema, flushing, burning, and stinging, and it often responds poorly to conventional therapies. Increasing evidence suggests that gut microbiota dysbiosis may be involved in the pathogenesis of NR. Fecal microbiota transplantation may provide a novel therapeutic strategy by restoring microbial homeostasis.

OBJECTIVE: This study aims to evaluate the efficacy and safety of FMT in patients with NR and to explore its potential mechanisms through modulation of the gut microbiota.

PATIENTS AND METHODS: This is a single-center, randomized, double-blind, placebo-controlled exploratory trial. Sixty patients with NR will be randomly assigned (1:1) to receive either FMT capsules or placebo capsules for 3 consecutive weeks and followed for 12 weeks. The primary outcome is the proportion of participants achieving CEA success at week 12, defined as a CEA score of 0 or 1 or a reduction of ≥2 grades from baseline. Secondary outcomes include flushing severity, symptom scores, quality of life, psychological status, objective erythema index, and safety. Exploratory analyses will assess gut microbiota composition, fecal and serum metabolomics, and neurovascular-related cytokines.

DISCUSSION: This study is the first clinical trial to explore the effects of fecal microbiota transplantation in the treatment of neurogenic rosacea. The trial may provide clinical evidence for the application of fecal microbiota transplantation as a novel therapeutic strategy for refractory neurogenic rosacea.

TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2500109957) on September 28, 2025.},
}

Humans
*Rosacea/therapy/microbiology
Double-Blind Method
*Fecal Microbiota Transplantation/methods
Female
Treatment Outcome
Adult
Quality of Life
Male
*Gastrointestinal Microbiome/physiology
Middle Aged
*Dysbiosis/therapy
Feces/microbiology

@article {pmid42875799,
year = {2026},
author = {He, D and Zhang, HC and Shen, BB and Zhao, D and Tang, XY and Xie, J and Zhou, RR and Zeng, HL and Zhang, SH},
title = {Extract from Eucommia ulmoides Oliv. Leaves alleviates APAP-induced acute liver injury via reshaping gut microbiota and attenuating microbial bile acids metabolism disorder.},
journal = {Chinese medicine},
volume = {21},
number = {1},
pages = {},
pmid = {42875799},
issn = {1749-8546},
support = {2025M773945//China Postdoctoral Science Foundation/ ; 2024JJ7292//Natural Science Foundation of Hunan Province/ ; No. 2024JK2120//This work was supported by Hunan Provincial Science and Technology Department Project/ ; 2060302-2304-02//the Key project at central government level: The ability establishment of sustainable use for valuable Chinese medicine resources/ ; },
abstract = {BACKGROUND: Increasing studies suggest that supplementing flavonoids from Eucommia ulmoides Oliv. Leaves (EUL) exerts liver protective effects via reshaping gut microbiota and regulating bile acids (BAs) metabolism. However, the relationship between EUL, gut microbiota and BAs metabolism remains unclear and the potential mechanisms of action has not been expounded clearly.

PURPOSE: To demonstrate the important role of gut microbiota and microbial BAs metabolism in alleviation acetaminophen-induced liver injury (AILI) by EUL.

METHODS: AILI mice model was employed to evaluate the therapeutic efficacy of EUL. The hepatic function was assessed, and biological samples were collected for histopathological examination, bacterial 16S rRNA sequencing analysis, BAs-targeted metabolomics, and the evaluation of the intestinal barrier function. Additionally, antibiotic cocktail-triggered gut microbiota deficiency and fecal microbiome transplantation were investigated to the relationship of molecular mechanistic between the protective efficiency of EUL in AILI, gut microbiota, and the metabolism of microbial BAs.

RESULTS: EUL alleviate liver damage, involving reduction of liver function index, down-regulation of inflammatory cytokines and oxidative stress index, and restoration of pathological changes of liver tissue. EUL also improved intestinal barrier dysfunction and reshaped gut microflora dysbiosis in AILI mice. Moreover, antibiotic cocktail-triggered intestinal microbiota deficiency and fecal microbiome transplantation (FMT) evidenced that the liver protection of EUL was tightly related with gut microbiota. BAs-targeted metabolomics assay demonstrated that EUL mitigated the altered metabolism of microbial BAs during the development of AILI. EUL promoted the abundance of Firmicutes phylum, and elevating the beneficial microbes in Ruminococcaceae and Lachnospiraceae family, which were associated with up-regulated proportion of secondary bile acids (including DCA, NorDCA and 7-ketoLCA), leading to the reduction intestinal inflammation and preservation intestinal integrity. In particular, EUL enriched the beneficial microbes in Lachnoclostridium, Lachnospiraceae_UCG-006, [Eubacterium]_xylanophilum_group, Oscillibacter, Ruminiclostridium, and Desulfovibrio genera. Furthermore, EUL administration increased levels of CDCA, which could activate FXR-FGF15, enabling to decreased synthesis of BAs in the liver and promoting excretion.

CONCLUSIONS: EUL supplementation alleviate AILI by reshaping the dysfunctional gut microbiota and attenuating disordered BAs metabolism, resulting to improvements in BAs enterohepatic circulation and gut barrier function. The mechanism may be closely related to the gut microbiome-BAs-FXR signaling in gut-liver axis.},
}

@article {pmid42875867,
year = {2026},
author = {Zhang, J and Han, K},
title = {Metabolic-Epigenetic Reprogramming of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis: Perspectives for Traditional Chinese Medicine.},
journal = {Immunological investigations},
volume = {},
number = {},
pages = {1-47},
doi = {10.1080/08820139.2026.2747770},
pmid = {42875867},
issn = {1532-4311},
abstract = {BACKGROUND: In rheumatoid arthritis (RA), persistent synovial inflammation and clinical relapse cannot be fully explained by immune activation alone, as fibroblast-like synoviocytes (FLS) can acquire stable pathogenic states that sustain synovitis and joint destruction. Metabolic reprogramming and epigenetic remodeling are functionally integrated in RA-FLS, thereby promoting hyperproliferation, invasiveness, apoptosis resistance, and inflammatory memory.

METHODS AND RESULTS: In this review, we summarize the interplay between altered cellular metabolism and epigeneticmechanisms, including DNA methylation, histone modifications, non-coding RNAs, RNA modifications, and chromatin remodeling, and discuss how this interplay contributes tostabilizing pathogenic FLS phenotypes.We further discuss gut microbiota-associated metabolites, including short-chain fatty acids, bile acids, tryptophan derivatives, and one-carbon metabolites, as potential mediators linking systemic metabolic imbalance to FLS epigenetic states. These metabolites may act through histone deacetylase (HDAC) inhibition, modulation of methyl donor availability, and receptor-mediated inflammatory signaling. From the perspective of Traditional Chinese Medicine (TCM), we propose that TCM formulations and bioactive compounds may modulate this network through microbiota-dependent metabolic remodeling and direct suppression of FLS activation. Finally, we identify current evidence gaps and highlight emerging therapeutic strategies, including metabolomics-guided fecal microbiota transplantation and FLS-targeted epigenetic interventions.

CONCLUSION: This review highlights metabolic-epigenetic reprogramming as a key mechanism underlying persistent RA-FLS phenotypes. Interactions among thegut microbiota, microbial metabolites, and epigenetic regulation provide a promising framework for linking systemic metabolic disturbances to local joint damage. Future studies integrating multi-omics profiling, microbiome modulation, and FLS-targeted epigenetic interventions are needed to clarify causality and facilitate more precise therapeutic strategies.},
}

@article {pmid42876317,
year = {2026},
author = {Wang, X and Wang, L and Liu, Y},
title = {The Role of Gut Microbiota in Chronic Constipation and the Therapeutic Potential of Fecal Microbiota Transplantation.},
journal = {Journal of gastroenterology and hepatology},
volume = {},
number = {},
pages = {},
doi = {10.1111/jgh.70807},
pmid = {42876317},
issn = {1440-1746},
abstract = {OBJECTIVE: This study investigates the relationship between gut microbiota dysbiosis and chronic constipation (CC) and evaluates the therapeutic efficacy of fecal microbiota transplantation (FMT) in restoring microbial homeostasis and metabolic function.

METHODS: We retrospectively analyzed existing before-after clinical data from 206 patients with CC who received FMT. No placebo or case-control group was included. Gut microbiota profiles were analyzed before and after FMT using 16S rRNA sequencing. Alpha and beta diversity indices were calculated to assess microbial community evolution. Gas chromatography-mass spectrometry (GC-MS) was employed to quantify short-chain fatty acids (SCFAs). Patients were stratified into butyrate-high and butyrate-low metabolic subtypes using a partitioning around medoids (PAM) algorithm based on pre-transplant butyrate levels. Clinical severity was independently defined using Rome IV criteria, CSBM, BSFS, and PAC-SYM.

RESULTS: FMT significantly increased microbial α-diversity and shifted the community structure toward that of healthy donors. Post-transplant, the Bacteroidetes/Firmicutes ratio decreased from 46.8% to 38.9%, with a marked enrichment of beneficial taxa such as Faecalibacterium, Akkermansia, and Bifidobacterium. These shifts correlated with a significant rise in SCFA concentrations, particularly acetic and butyric acids. Butyrate deficiency was characterized by broader SCFA deficiencies and fragmented microbial networks. Multivariable binary logistic regression identified Faecalibacterium, ACE index, and acetic acid as independent predictors of clinically defined constipation severity.

CONCLUSION: FMT was associated with increased microbial diversity, restoration of SCFA-producing taxa, and increased SCFA concentrations in patients with CC. These changes accompanied improvements in CSBM, BSFS, PAC-SYM, and PAC-QOL.},
}

@article {pmid42876954,
year = {2026},
author = {Negi, P and Upreti, A and Budhlakoti, P and Sen, AK and Danu, M and Tewari, S and Joshi, N and Chandra Joshi, D},
title = {Gut microbiota-cancer crosstalk: emerging molecular targets for personalized cancer treatment- a comprehensive review.},
journal = {Frontiers in molecular biosciences},
volume = {13},
number = {},
pages = {1924197},
pmid = {42876954},
issn = {2296-889X},
abstract = {Cancer remains a major global health challenge, and growing evidence indicates that the gut microbiota plays an important role in cancer initiation, progression, metastasis, and response to treatment through complex interactions with host signaling, metabolism, and immunity. This comprehensive narrative review discusses the molecular mechanisms underlying gut microbiota-cancer crosstalk, with particular emphasis on dysbiosis, microbial metabolites, immune modulation, and microbiota-regulated oncogenic pathways, including TLR/NF-κB, Wnt/β-catenin, JAK/STAT, PI3K/Akt/mTOR, and Hippo-YAP signaling. The review also examines emerging molecular targets, including microbial extracellular vesicles, bacterial small RNAs, ferroptosis-related mechanisms, and microbiota-mitochondria interactions. In addition, current microbiota-targeted therapeutic strategies, such as fecal microbiota transplantation, engineered bacterial therapeutics, CRISPR-based microbiome engineering, and microbiome-informed approaches to precision oncology are discussed. Relevant peer-reviewed literature published primarily within the recent 5-year period was considered from major scientific databases and publisher platforms, including PubMed, Scopus, Web of Science, Springer, Elsevier, and MDPI. Overall, the available evidence suggests that gut microbiota represents an important component of the tumor ecosystem and may provide promising biomarkers and therapeutic targets. Integration of microbiome research with multi-omics and artificial intelligence may further support the development of personalized cancer treatment.},
}

@article {pmid42877054,
year = {2026},
author = {Niu, C and Hua, Y and Kang, J and Li, F and Chen, B and Guo, R and Wei, Y},
title = {Gut Microbiota-Dependent Tryptophan Metabolism Drives the Therapeutic Effects of Baitouweng Tang in Colitis via the AhR Pathway.},
journal = {Food science & nutrition},
volume = {14},
number = {10},
pages = {e72434},
pmid = {42877054},
issn = {2048-7177},
abstract = {With dysregulation of the gut microbiota and its metabolic byproducts playing a pivotal role in inflammatory bowel disease (IBD) pathogenesis. Baitouweng Tang (BTWT), a traditional herbal formulation, has long been employed to treat gastrointestinal disorders and shows promising potential in the management of IBD. However, its precise pharmacological mechanisms remain elusive. In this study, we employed targeted metabolomics, high-throughput sequencing, and molecular biology techniques to elucidate the therapeutic mechanisms of BTWT in the treatment of ulcerative colitis (UC). BTWT significantly enhanced the relative abundance of Bifidobacterium, improved the indole metabolic pathway of tryptophan, and restored the levels of indole metabolites, such as indole-3-lactic acid (ILA). These changes activated the aryl hydrocarbon receptor (AhR) and led to marked improvements in the clinical symptoms of UC in mice. Conversely, the therapeutic effects of BTWT were substantially diminished in an antibiotic-induced gut microbiota depletion model. Notably, fecal microbiota transplantation (FMT) partially restored BTWT efficacy, underscoring the critical role of the gut microbiota in mediating its therapeutic effects. Furthermore, in an in vitro lipoteichoic acid (LTA)-induced HT-29 inflammation model, ILA treatment attenuated inflammation and concurrently increased the expression of AhR, CYP1A1, and CYP1B1. These findings suggest a potential link between BTWT-induced changes in tryptophan metabolites, AhR pathway activation, and the amelioration of colitis, though the causal relationship remains to be established. Our study provides a basis for further mechanistic investigation into the AhR pathway as a possible therapeutic target in UC.},
}

@article {pmid42877110,
year = {2026},
author = {Chen, G and Li, J and Huang, T and Zeng, D and Mo, L and Li, J and Zhu, C},
title = {Gut microbiota in genetic diseases: from Mendelian disorders to complex traits.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1908644},
pmid = {42877110},
issn = {1664-3224},
mesh = {Humans ; *Genetic Diseases, Inborn/microbiology/genetics/etiology/immunology ; *Gastrointestinal Microbiome/immunology ; *Dysbiosis/microbiology/immunology ; Animals ; Phenotype ; },
abstract = {As a core component of the human microecosystem, the dynamic balance of the composition and function of gut microbiota is essential to host health. In recent years, numerous studies have demonstrated that gut dysbiosis is not only associated with metabolic diseases and immune disorders but also plays a pivotal role in the pathogenesis of hereditary diseases. Ranging from chromosomal diseases (e.g., Down syndrome), monogenic diseases (e.g., cystic fibrosis, phenylketonuria, familial adenomatous polyposis, hereditary hemolytic anemia), mitochondrial diseases (e.g., Leber's hereditary optic neuropathy, mitochondrial encephalomyopathy) to polygenic hereditary diseases (e.g., inflammatory bowel disease, autism spectrum disorder, obesity and diabetes), gut microbiota can markedly alter the manifestation and severity of disease phenotypes by regulating host immune responses, metabolic pathways and gene expression. Nevertheless, the bidirectional interaction network between host genes and gut microbiota has not been fully elucidated. Most existing studies merely focus on correlation analysis, and in-depth exploration of causal mechanisms remains insufficient. This review elaborates on the mechanisms of gut microbiota in monogenic diseases and hereditary diseases with complex phenotypes. By integrating the latest advances in genomics, metabolomics and microbiomics, it discusses how gut dysbiosis affects disease progression via immune modulation, metabolite reprogramming and epigenetic modification. Meanwhile, this paper summarizes the current status and challenges of clinical translation of microbiota-targeted therapies, such as probiotics and fecal microbiota transplantation(FMT), in the treatment of hereditary diseases. This review aims to provide a microecological perspective for understanding the pathogenesis of hereditary diseases and offer theoretical support for personalized and precise intervention.},
}

Humans
*Genetic Diseases, Inborn/microbiology/genetics/etiology/immunology
*Gastrointestinal Microbiome/immunology
*Dysbiosis/microbiology/immunology
Animals
Phenotype

@article {pmid42879046,
year = {2026},
author = {Ahmed, LA and Al-Massri, KF},
title = {Gut Microbiota Modulation in CNS Disorders: Therapeutic Strategies and Implications for Drug Efficacy.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42879046},
issn = {1559-1182},
mesh = {Humans ; Animals ; *Central Nervous System Diseases/microbiology/drug therapy/therapy ; *Gastrointestinal Microbiome/drug effects/physiology ; Probiotics/therapeutic use ; Treatment Outcome ; },
abstract = {Various central nervous system (CNS) disorders, including neurodegenerative diseases, depression, schizophrenia, epilepsy, and anxiety, present significant obstacles to public health because of their intricate causes and the scarcity of effective treatments. Recent studies have shown that gut microbiota (GM) and CNS communicate bidirectionally. Modulation of immune system, neurotransmitters, and neuroactive metabolites are only a few examples of how GM can significantly influence CNS. Dysbiosis or changes in composition and function of gut microbes play a contributing role in various CNS disorders. In these disorders, probiotics, prebiotics, fecal microbiota transplantation, antibiotics use, and interventions based on microbial metabolites have demonstrated beneficial effects in animal models and some clinical studies. By restoring microbial equilibrium, increasing microbial diversity, and promoting the generation of beneficial metabolites, these approaches can improve the efficacy of traditional medications while minimizing their side effects and the disease itself, based on preclinical evidence and emerging clinical studies. Nevertheless, several obstacles should be overcome before the clinical translation of these approaches, such as using of standardized methods for modulating GM, identifying specific microbial signatures linked to various CNS illnesses, and understanding the exact mechanisms of gut-brain communication. This review provides a novel integrated perspective by comprehensively clarifying the bidirectional interactions between CNS pharmacological agents and microbiota-based therapeutic strategies in different neurological and psychiatric disorders, offering a unified framework to improve traditional pharmacological therapies. Importantly, future studies should concentrate on exploring the mechanisms and the exact interconnections between GM and CNS problems to elaborate targeted therapies for these disorders.},
}

Humans
Animals
*Central Nervous System Diseases/microbiology/drug therapy/therapy
*Gastrointestinal Microbiome/drug effects/physiology
Probiotics/therapeutic use
Treatment Outcome

@article {pmid42879156,
year = {2026},
author = {Diefenhardt, M and Fokas, E and Kosmala, R and Polat, B and Germer, CT and Schlenska-Lange, A and Kuhnt, T and Ghadimi, M and Rieken, S and Wiegering, A and Schwarzbach, M and Fleischmann, M and Grützmann, R and Ott, OJ and Martus, P and Königsrainer, A and Zips, D and Hofheinz, RD and Gani, C and Rödel, C},
title = {Organ Preservation and Quality of Life After Total Neoadjuvant Treatment in Rectal Cancer.},
journal = {JAMA network open},
volume = {9},
number = {10},
pages = {e2639063},
doi = {10.1001/jamanetworkopen.2026.39063},
pmid = {42879156},
issn = {2574-3805},
mesh = {Humans ; *Quality of Life ; *Rectal Neoplasms/therapy/psychology/surgery ; Male ; *Neoadjuvant Therapy/methods ; Female ; Middle Aged ; Aged ; *Adenocarcinoma/therapy ; Watchful Waiting ; Germany ; Cohort Studies ; *Organ Preservation ; },
abstract = {IMPORTANCE: Data on quality of life (QOL) after total neoadjuvant therapy (TNT) are important for counseling patients on the benefits of watch-and-wait (WW) vs total mesorectal excision (TME) for rectal cancer. A thorough understanding of both options and their long-term impact on bowel, urinary, sexual function, and other QOL domains remains limited.

OBJECTIVE: To examine the association of organ preservation with QOL and functional outcomes among patients with rectal cancer treated in 2 phase 2 clinical trials.

This unplanned, post hoc, cohort study used data from the CAO/ARO/AIO-12 and CAO/ARO/AIO-16 trials, recruiting participants from June 15, 2015, through October 7, 2020, from 19 centers in Germany. Included patients had cT3 to cT4 or node-positive rectal adenocarcinoma. Total neoadjuvant treatment included chemoradiation therapy combined with induction or consolidation chemotherapy. The statistical analysis was performed from March 6 to December 23, 2025.

MAIN OUTCOMES AND MEASURES: The association of WW with functional outcomes and QOL was assessed using prospectively recorded EORTC QLQ-C30, EORTC QLQ-CR29, and Wexner score questionnaires. Differences in QOL scores were estimated using adjusted longitudinal and cross-sectional analyses with a predefined clinically meaningful difference of at least 5 points.

RESULTS: Baseline questionnaires were available from 346 of 385 eligible patients (89.9%; median [range] age, 60 [19-80] years; 257 male [67%]), while available QOL questionnaires decreased over time to 185 (48.1%) at 5 years. Using the longitudinal analytic approach, statistically significant and clinically meaningful differences in favor of WW were noted for fecal incontinence (-21.2 [95% CI, -30.0 to -12.3]; P < .001); stool frequency (-19.8 [95% CI, -27.6 to -11.9]; P < .001); embarrassment (-17.0 [95% CI, -27.4 to -6.6]; P = .002); flatulence (-15.2 [95% CI, -24.4 to -6.0]; P < .001), buttock pain (-11.9 [95% CI, -20.8 to -3.0]; P = .01); social (9.7 [95% CI, 1.1-18.3]; P = .03), physical (10.2 [95% CI, 4.1-16.3]; P = .002), and role (13.9 [95% CI, 4.9-22.9]; P = .003) functioning; and global health status (9.2 [95% CI, 3.2-15.2]; P = .004). These clinically meaningful differences were detectable in both the intended organ preservation and disease-free groups. Patients with sustained clinical complete response at 3 years (n = 29) vs those with pathologic complete response or matched baseline characteristics favored WW for fecal incontinence (-24.0 and -11.6, respectively), stool frequency (-34.6 and -19.1), sore skin (-18.0 and -18.1), buttock pain (-14.7 and -17.6), embarrassment (-41.1 and -20.5), role functioning (19.1 and 10.9), and social functioning (20.0 and 8.4).

CONCLUSIONS AND RELEVANCE: In the absence of prospective randomized trials, this study provides evidence suggesting long-term clinically meaningful benefits for organ preservation regarding QOL, especially for most gastrointestinal subscales, social functioning, and global health status, over a 5-year period among patients with rectal cancer. As treatment options for patients with rectal cancer now routinely include WW in cases of clinical complete response after TNT, patient-reported QOL measures have become paramount for informed shared decision-making.

TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT02363374 and NCT03561142.},
}

Humans
*Quality of Life
*Rectal Neoplasms/therapy/psychology/surgery
Male
*Neoadjuvant Therapy/methods
Female
Middle Aged
Aged
*Adenocarcinoma/therapy
Watchful Waiting
Germany
Cohort Studies
*Organ Preservation

@article {pmid42879923,
year = {2026},
author = {Chen, X and Zhao, X and Zheng, J and Jiang, J and Wu, F},
title = {Low-dose triclosan induces neurotoxicity in zebrafish via gut microbiota disruption.},
journal = {Journal of hazardous materials},
volume = {518},
number = {},
pages = {143683},
doi = {10.1016/j.jhazmat.2026.143683},
pmid = {42879923},
issn = {1873-3336},
abstract = {Triclosan (TCS), a broad-spectrum antibacterial agent, is widely detected in environmental and human samples, yet its neurotoxic risks and mechanisms following long-term environmental exposure remain unclear-particularly the role of gut microbiota. Using germ-free zebrafish and fecal microbiota transplantation, we established a causal link between TCS-induced gut dysbiosis and neurotoxicity. Integrating transcriptomics, 16S rRNA sequencing, and gut-derived metabolite transplantation, we elucidated the underlying molecular mechanisms. Three-month exposure to environmentally relevant TCS concentrations significantly enriched gut Proteobacteria, increasing lipopolysaccharide (LPS) levels. LPS subsequently crossed the damaged blood-brain barrier via the gut-brain axis, triggering neuroinflammation and behavioral abnormalities in female zebrafish. Notably, TCS exhibited dose-dependent neurotoxicity: low doses (0.4 and 4.0 μg/L) acted primarily through gut microbiota disruption, while high-dose (40 μg/L) effects involved both microbiota-dependent and independent pathways. This study provides new insights into the neurotoxic mechanisms of TCS and highlights the critical role of gut microbiota in mediating its effects. However, this study was conducted exclusively in female zebrafish, and further investigations in males are warranted to assess potential sex differences.},
}

@article {pmid42868115,
year = {2026},
author = {Qian, X and Shen, Y and Luo, X and Zhang, S and Wang, L and He, H and Wang, B},
title = {Adult-sourced fecal microbiota transplantation ameliorates early-life antibiotic-induced intestinal immune stress in juvenile mice associated with the modulation of the TLR4/MyD88 signaling pathway.},
journal = {PloS one},
volume = {21},
number = {10},
pages = {e0359634},
pmid = {42868115},
issn = {1932-6203},
mesh = {Animals ; *Fecal Microbiota Transplantation ; *Toll-Like Receptor 4/metabolism ; *Myeloid Differentiation Factor 88/metabolism ; *Signal Transduction/drug effects ; *Anti-Bacterial Agents/adverse effects/pharmacology ; Mice ; *Gastrointestinal Microbiome/drug effects/immunology ; *Intestines/immunology/microbiology/drug effects ; Male ; RNA, Ribosomal, 16S/genetics ; Mice, Inbred C57BL ; Bacteroides ; Dysbiosis/therapy/chemically induced/immunology ; Intestinal Mucosa/immunology/microbiology ; Interleukin-22 ; },
abstract = {Early-life antibiotic (ABX) exposure profoundly disrupts gut microbiota assembly, triggering long-lasting intestinal immune stress. While fecal microbiota transplantation (FMT) is a promising intervention, its immunological and ecological mechanisms in the juvenile gut remain underexplored. In this study, juvenile mice were subjected to a broad-spectrum ABX cocktail for 8 days followed by 4 days of adult-sourced FMT. 16S rRNA sequencing (n = 6/group) revealed that ABX drastically altered the microbial landscape, causing a severe relative reduction of core commensals and an opportunistic expansion of Bacteroides. Subsequent molecular analyses on day 13 (n = 3/group) demonstrated that this dysbiosis significantly upregulated the mucosal TLR4/MyD88 signaling axis and effector cytokines IL-17 and IL-22. Strikingly, adult FMT administration effectively attenuated the TLR4 cascade and reduced pro-inflammatory cytokine transcript levels while immunoregulatory IL-10 transcripts remained partially elevated. Ecologically, FMT did not merely revert the gut to its naive juvenile baseline. Instead, it suppressed Bacteroides overgrowth and established a distinctly new, highly complex community enriched with putative mature, adult-signature taxa such as Parabacteroides, Tannerellaceae, and Desulfobacterota. Interestingly, the downregulation of TLR4 occurred concurrently with the engraftment of these Gram-negative, LPS-bearing taxa. Collectively, adult-sourced FMT ameliorates ABX-induced immune stress not by restoring the original microbiota, but by driving the juvenile gut towards a putatively mature, structurally distinct, and potentially immunologically tolerant ecological state.},
}

Animals
*Fecal Microbiota Transplantation
*Toll-Like Receptor 4/metabolism
*Myeloid Differentiation Factor 88/metabolism
*Signal Transduction/drug effects
*Anti-Bacterial Agents/adverse effects/pharmacology
Mice
*Gastrointestinal Microbiome/drug effects/immunology
*Intestines/immunology/microbiology/drug effects
Male
RNA, Ribosomal, 16S/genetics
Mice, Inbred C57BL
Bacteroides
Dysbiosis/therapy/chemically induced/immunology
Intestinal Mucosa/immunology/microbiology
Interleukin-22

@article {pmid42871658,
year = {2026},
author = {Liu, W and Lan, Y and Chen, X and Wei, H and Zhang, T and Wang, Y},
title = {Deciphering the gut-liver axis in MASLD: from dysbiosis-driven pathogenesis to precision microbiome therapeutics.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1971785},
pmid = {42871658},
issn = {1664-302X},
abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic liver disorder worldwide, characterized by a multifactorial pathogenesis involving genetic predisposition, metabolic disturbances, environmental influences, and gut microbiota interactions. In recent years, the gut microbiota has garnered significant attention for its pivotal role in MASLD development and progression through the gut-liver axis. This review comprehensively summarizes current understanding of the molecular mechanisms by which gut microbiota and their metabolites contribute to MASLD pathogenesis, including intestinal barrier dysfunction, bile acid metabolism dysregulation, abnormalities in short-chain fatty acid and tryptophan metabolism, oxidative stress, and mitochondrial impairment. Furthermore, we comprehensively discuss advances in therapeutic strategies targeting gut microbiota modulation, such as probiotics/prebiotics, fecal microbiota transplantation, dietary interventions, bioactive compounds from traditional Chinese medicine, and surgical approaches. By integrating these insights, this review aims to provide novel perspectives for precise prevention and treatment of MASLD, highlighting the gut microbiota as a promising target for future clinical management.},
}

@article {pmid42871751,
year = {2026},
author = {Villafuerte-Gálvez, JA and Noriega, MA and Cakir Colak, S and Crawford, CV},
title = {The Patients' Voice in Clostridioides difficile Infection: Large Language Model-Assisted Thematic Analysis of Patient Testimonials.},
journal = {Open forum infectious diseases},
volume = {13},
number = {10},
pages = {ofag650},
pmid = {42871751},
issn = {2328-8957},
abstract = {BACKGROUND: Clostridioides difficile infection (CDI) imposes a burden that extends well beyond the gastrointestinal tract, yet existing outcome measures only partially capture the patient experience. We used frontier large language models (LLMs) on patient and caregiver narratives at scale to describe how burden shifts with disease course.

METHODS: We analyzed 189 testimonials from the Peggy Lillis Foundation corpus, sorted into 4 cohorts with recurrence (r) and fulminant (f) severity as axes (rfCDI, fCDI, rCDI, non-rfCDI). Two independent LLMs coded 8 thematic domains, 4 fulminant flags, 13 emerging semantic fields, the dominant dimension, and narrative arcs. Two physicians independently coded a subset for inter-rater reliability (PABAK, Gwet's AC1).

RESULTS: Treatment trajectory was the dominant theme in recurrent disease, whereas death and near-death dominated nonrecurrent fulminant narratives. Psychological burden was near-universal in fulminant disease (98.0% in rfCDI, 97.2% in fCDI). Caregiver and bereavement content concentrated in fCDI (66.7%). Diagnostic failure was frequent across recurrent cohorts (47.6-56.1%). Mentions of bacteriotherapy (fecal microbiota transplantation) concentrated in recurrent cohorts (60.2% rfCDI versus 5.6% fCDI). Financial, mental-health, and caregiver burdens were prominent and remain largely unaddressed by guidelines. Human-human reliability was substantial (PABAK 0.79 for semantic fields, 0.76 for domains); arc coding was least reliable.

CONCLUSIONS: Patient narratives reveal a course-dependent, multidimensional burden in CDI. Concrete gaps exist between what patients prioritize, what guidelines recommend, and what therapy access provides. Frontier-LLM coding, validated against clinicians, offers a reproducible route to translate these priorities into research, care, and policy.},
}

@article {pmid42871959,
year = {2026},
author = {Wu, Q and Li, C and Song, S and Wang, H and Zhao, R and Sun, L and Shang, B and Geng, Y},
title = {Maternal Diglyceride Diet Attenuates Selected Metabolic Effects of Maternal High-Fat Feeding in Offspring via Energy Metabolism and Microbiota Modulation.},
journal = {Food science & nutrition},
volume = {14},
number = {10},
pages = {e72427},
pmid = {42871959},
issn = {2048-7177},
abstract = {Diglyceride (DAG) has been shown to improve obesity in animals, but its effects on mothers and offspring were unclear. This study investigated whether maternal DAG intake affects male offspring by mating female C57BL/6J mice on a DAG diet with normal males. Male offspring were weaned at 3 weeks, with some euthanized and others fed normal, high-fat (HFD), or DAG diets for 9 weeks. Results showed that offspring from DAG-fed mothers had lower blood lipids than those from HFD-fed mothers, and maternal DAG intake was associated with restoration of purine/pyrimidine metabolism while altering gut microbiota (lower Firmicutes/Bacteroidetes ratio, higher butyrate). Fecal transplants confirmed DAG partially reversed HFD-induced gut dysbiosis. Although DAG mitigated maternal obesity effects, post-weaning diet had a stronger influence, suggesting DAG oil may help prevent intergenerational obesity transmission.},
}

@article {pmid42873094,
year = {2026},
author = {Pizzi, A and Creta, E and Pallozzi, M and Stella, L and Gasbarrini, A and Ponziani, FR and Cerrito, L},
title = {Gut microbiota-considered pharmacotherapeutic management of hepatocellular carcinoma.},
journal = {Expert opinion on pharmacotherapy},
volume = {},
number = {},
pages = {},
doi = {10.1080/14656566.2026.2749646},
pmid = {42873094},
issn = {1744-7666},
abstract = {INTRODUCTION: Treatment efficacy for hepatocellular carcinoma (HCC) remains limited. Increasing evidence indicates that gut microbiota may influence treatment response, toxicity and clinical outcomes.

AREAS COVERED: Our review synthesizes recent literature from PubMed and Wiley Online Library regarding gut microbiota, microbial metabolites, HCC and immunotherapy by critically analyzing the main research frameworks and identifying current research gaps. Clinical studies suggest that microbial diversity and specific taxa, including Akkermansia, Bifidobacterium, Faecalibacterium, and Ruminococcus may be associated with improved responses to immune checkpoint inhibitors (ICIs). Microbiota-targeted approaches, including fecal microbiota transplantation (FMT), probiotics, engineered bacteria, dietary interventions, selective antimicrobial strategies, and postbiotics, are biologically promising but remain experimental in HCC.

EXPERT OPINION: Despite the encouraging results about the modulation of ICIs response by FMT in other solid tumors (melanoma, colorectal cancer, renal cell carcinoma and mixed solid-tumor), whether this strategy is effective and safe in HCC remains to be established in prospective HCC-specific trials. The availability of a preliminary detailed characterization of gut microbial before undertaking HCC treatment would be tempting, especially if it could lead to a more precision-tailored approach with the possibility to foresee, within certain limits, the therapeutic outcome. Moreover, the eventual discovery of specific bacterial patterns in responders and non-responders to ICIs could open the possibility to administer FMT as a standard of care at least in selected patients with the target of re-stablishing HCC response to ICIs.},
}

@article {pmid42874318,
year = {2026},
author = {Zimmermann, DM and Diamantino, D and Andrade, SO and Julio, PR and Appenzeller, S},
title = {The gastrointestinal pathway leading to autoimmune diseases.},
journal = {Current opinion in immunology},
volume = {103},
number = {},
pages = {102856},
doi = {10.1016/j.coi.2026.102856},
pmid = {42874318},
issn = {1879-0372},
abstract = {The gut microbiota are important in maintaining immune homeostasis through complex interactions with both innate and adaptive immune systems. Disruptions in microbial composition, referred to as dysbiosis, have been increasingly associated with the development and progression of autoimmune diseases. This review explores the key gastrointestinal pathways linking microbiota alterations to immune dysregulation, emphasizing mechanisms that operate from extracellular barrier function to intracellular signaling cascades. Critical processes include impairment of intestinal barrier integrity, modulation of neuroimmune communication via the enteric nervous system and vagus nerve, and the activation of immune responses through molecular mimicry. In addition, pattern recognition receptors, particularly Toll-like receptors, act as essential mediators of host-microbe interactions, integrating microbial signals into pro- or anti-inflammatory immune pathways. These interconnected mechanisms contribute to chronic inflammation, loss of immune tolerance, and systemic autoimmune responses. Emerging evidence highlights the therapeutic potential of targeting the gut microbiota through dietary interventions, probiotics, and fecal microbiota transplantation, as well as through modulation of microbial metabolites and immune signaling pathways. A deeper understanding of these host-microbiota interactions may enable the development of novel, microbiota-directed strategies for the prevention and treatment of autoimmune diseases.},
}

@article {pmid42874908,
year = {2026},
author = {Tan, Z and Zeng, J and Huang, F and Gao, F and Hu, Y and Guo, L and Guo, P and Chen, L},
title = {Gut Microbiota-Derived Short-Chain Fatty Acids Mediate the Bone-Protective Effects of Metformin Against Postmenopausal Osteoporosis.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {179442},
doi = {10.1016/j.ejphar.2026.179442},
pmid = {42874908},
issn = {1879-0712},
abstract = {BACKGROUND: Dysbiosis-induced inflammation has been implicated in postmenopausal osteoporosis (PMOP). Although metformin has shown benefits for bone health, the exact role of the gut microbiota in the mechanism underlying this relationship remains unclear.

HYPOTHESIS/PURPOSE: We hypothesised that metformin could alleviate systemic inflammation in PMOP by augmenting the synthesis of short-chain fatty acids (SCFAs) by gut microbes.

METHODS: Micro-computed tomography (μCT) was used to analyse the femurs. Faecal samples were collected for 16S rRNA sequencing and SCFAs detection. Quantitative real-time PCR (qRT-PCR) and western blotting were used to detect mRNA and protein expression, respectively. Primary bone marrow mesenchymal stem cells (BMSCs) and bone marrow macrophages (BMMs) were isolated to explore the effects of SCFAs on bone cell activity following inflammatory stimulation.

RESULTS: Metformin improved trabecular bone microarchitecture in OVX mice, as shown by higher BV/TV, Tb.Th, and Tb.N, and reduced serum and tibial IL-1β and TNF-α. Metformin also increased the abundance of SCFA-producing genera, including Butyricimonas, Prevotella, Ruminococcus, Coprococcus, Oscillospira, and Sutterella, and elevated faecal propionate, butyrate, and valerate. Transplantation of metformin-adapted microbiota reproduced the bone-protective and anti-inflammatory effects, whereas GPR41/GPR43 deficiency abolished the benefits of metformin, propionate, and butyrate. In vitro, propionate and butyrate, but not valerate, promoted BMSC osteogenic differentiation and inhibited BMM-derived osteoclast differentiation under IL-1β/TNF-α-induced inflammation.

CONCLUSIONS: Metformin modulates the gut microbiota by increasing propionate and butyrate synthesis, thereby reducing dysbiosis-induced inflammation and regulating BMSC and BMM differentiation to protect against PMOP.},
}

@article {pmid42874932,
year = {2026},
author = {Chen, L and Tayier, N and Wu, H and Liu, G and Wang, S and Zhu, Y and Sun, J and Niu, Y and Feng, C and You, L and Hu, G and Cao, X and Liu, H and Zhu, M},
title = {Scalable cultured gut microbiota-derived nanovesicles for oral augmentation of checkpoint blockade therapy.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {},
number = {},
pages = {115456},
doi = {10.1016/j.jconrel.2026.115456},
pmid = {42874932},
issn = {1873-4995},
abstract = {Microbiota-targeted strategies, such as fecal microbiota transplantation (FMT), hold promise for enhancing immunotherapy but face clinical challenges including safety risks, batch-to-batch variability, and dependence on substantial quantities of donor fecal material. To overcome these limitations, we established a standardized in vitro expansion platform for responder patient-derived gut microbiota. Through optimization of culture conditions, we achieved stable viability and retention of key immunotherapy-enhancing strains over serial passages, enabling a scalable 6.4 × 10[7]-fold expansion. Leveraging this platform, we engineered hybrid nanovesicles derived from bacterial protoplasts, followed by silica surface coating (HNVs@Silica) for oral delivery. The silica shell significantly improved nanovesicle stability under gastrointestinal conditions and conferred superior antitumor efficacy compared with uncoated counterparts. Notably, HNVs@Silica produced from the 2nd, 4th, and 6th passages retained comparable potency in augmenting anti-PD-1 (αPD-1) therapy. Mechanistically, HNVs@Silica remodeled intestinal immunity, particularly within Peyer's patches, by activating and expanding effector CD8[+] T cells. This local response enhanced the priming and systemic dissemination of tumor-specific T cells, thereby improving the efficacy of αPD-1. Collectively, our findings establish a safe, scalable, and orally bioavailable alternative to FMT for enhancing cancer immunotherapy.},
}

@article {pmid42861983,
year = {2026},
author = {Kutyłowski, K and Alster, P and Madetko-Alster, N},
title = {The link between inflammation and autonomic dysfunction in alpha-synucleinopathies - narrative review.},
journal = {Neurologia i neurochirurgia polska},
volume = {},
number = {},
pages = {},
doi = {10.5603/pjnns.112453},
pmid = {42861983},
issn = {0028-3843},
abstract = {INTRODUCTION: Alpha-synucleinopathies are a group of disorders characterized by the accumulation of the pathological form of alpha-synuclein. This group comprises Parkinson's disease, Parkinson's disease dementia, multiple system atrophy, dementia with Lewy bodies, pure autonomic failure, and idiopathic REM sleep behavior disorder. Despite sharing a similar molecular basis, these disorders differ in their clinical presentation. Characteristic manifestations include signs of autonomic failure such as orthostatic hypotension, postural orthostatic tachycardia syndrome, constipation, gastroparesis, urinary incontinence, and erectile dysfunction, among others. These symptoms significantly impair patients' daily functioning and are also negative prognostic factors.

STATE OF THE ART: Currently, research is investigating the link between inflammation and dysautonomic symptoms. Elevated levels of pro-inflammatory cytokines, such as IFN-γ, TNF-α, IL-6, IL-1β, and IFN-α, have been found to accompany these symptoms. Notably, in other diseases characterized by chronic inflammation, autonomic dysfunction is also common.

CLINICAL IMPLICATIONS: In two human studies of dysautonomic symptoms in other conditions, intravenous immunoglobulin therapy was shown to improve these symptoms. Animal studies have shown that other immunomodulatory agents reduce symptom severity.

FUTURE DIRECTIONS: Modulation of inflammation, dietary modification, the use of probiotics and prebiotics, and fecal microbiota transplantation are potential therapeutic approaches for these diseases. These approaches offer hope for improving the quality of life of patients with alpha-synucleinopathies. Further research in this area is needed.},
}

@article {pmid42864919,
year = {2026},
author = {Hu, Y and Wei, T and Wang, S and Yang, Y and Yang, L and Chu, H},
title = {The Role and Mechanisms of Gut Microbiota in the Progression of Hepatic Encephalopathy.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X513988260915065036},
pmid = {42864919},
issn = {1875-6190},
abstract = {Hepatic encephalopathy (HE) is a severe complication of end-stage liver disease that is associated with high mortality; however, its therapeutic options remain limited. The traditional mechanistic understanding focuses on ammonia neurotoxicity, although intestinal bacteria also play a significant role through the gut-liver-brain axis. This review primarily discusses the characteristics of gut dysbiosis in HE, which is marked by a progressive loss of beneficial commensals (e.g., Lachnospiraceae, Ruminococcaceae, and Faecalibacterium) and an overgrowth of potentially pathogenic bacteria (e.g., Enterobacteriaceae, Streptococcaceae, and Veillonellaceae). Unlike previous reviews which have largely focused on phylum- or genus-level changes, this review provides a species-level synthesis of gut microbial alterations in HE. We further summarise the multifaceted mechanisms by which the gut microbiota contributes to HE pathogenesis, including the impairment of intestinal barrier integrity, activation of systemic and neuroinflammation, alterations in microbial metabolites (such as ammonia, short-chain fatty acids, bile acids, and aromatic amino acids), and disruption of neuroendocrine signalling pathways. Furthermore, herein we summarise the microbiota-targeted intervention measures for HE, including aetiological treatments, drug therapies (lactulose and rifaximin), live microbial therapies (probiotics, prebiotics, synbiotics, faecal microbiota transplantation, etc.), and dietary adjustments. Emerging approaches, such as engineered bacteria and phage therapy, are also discussed, along with the barriers to their clinical translation and safety considerations. In summary, targeting the gut microbiota offers a new approach for the precise treatment of HE, although challenges remain in translating these findings into routine clinical practice.},
}

@article {pmid42864924,
year = {2026},
author = {Suresh, N and Singh, V and Rathore, A and Dwivedi, S and Bansal, A},
title = {The Gut Microbiota-inflammation-immune Axis in Cancer: Anti-inflammatory Mechanisms and Therapeutic Implications.},
journal = {Anti-inflammatory & anti-allergy agents in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715230502786261001104534},
pmid = {42864924},
issn = {1875-614X},
abstract = {Through its mediation between inflammatory and immune pathways, the gut microbiota has proved to be a key regulator of cancer development, progression, and treatment response. Changes in microbial composition known as dysbiosis might facilitate chronic inflammation, immune dysregulation, and genomic instability, thereby facilitating carcinogenesis. Conversely, positive commensal microbes can generate short-chain fatty acids, bile acids, and tryptophan derivatives, which help maintain the epithelial barrier, cytokine signaling, and innate and adaptive immune responses. These microbial metabolites regulate immune cell differentiation, including regulatory T cells, dendritic cells, macrophages, and cytotoxic CD8+ T cells, thereby impacting the tumor microenvironment and tumor progression. Recent research highlights the microbiota as an outcome of response to cancer therapies, particularly immune checkpoint inhibitors, chemotherapy, and targeted therapies. Certain microbial genera, e.g., Akkermansia muciniphila, Bifidobacterium species, and Faecalibacterium prausnitzii, have been linked to augmented antitumor immunity and treatment efficacy. To enhance treatment outcomes and minimize toxicity during therapy, therapeutic interventions that target the regulation of the gut microbiome, such as dietary interventions, probiotics, prebiotics, fecal microbiota transplantation, and engineered microbial platforms, are under investigation. Moreover, improvements in metagenomics, metabolomics, and immunomics are now enabling the discovery of microbiome-based biomarkers to inform precision oncology. Knowledge of the gut microbiota-inflammation-immune axis thus presents promising possibilities in creating new treatment modalities and in designing individualized treatments in cancer management.},
}

@article {pmid42865601,
year = {2026},
author = {Ma, G and Deng, S},
title = {Research progress on intestinal probiotics-mediated protection of the intestinal mucosal barrier in ulcerative colitis.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1943748},
pmid = {42865601},
issn = {1664-3224},
mesh = {Humans ; *Probiotics/therapeutic use ; *Colitis, Ulcerative/microbiology/therapy/immunology/metabolism ; Intestinal Barrier Function ; *Intestinal Mucosa/immunology/microbiology/metabolism ; Animals ; *Gastrointestinal Microbiome ; Immunity, Mucosal ; },
abstract = {Ulcerative colitis (UC) is a major subtype of inflammatory bowel disease characterized by a chronic, relapsing course. Its pathogenesis involves complex interactions among gut microbial dysbiosis, epithelial barrier disruption, dysregulated immune responses, and oxidative stress. Impairment of the intestinal mucosal barrier facilitates the translocation of luminal antigens, bacteria, and microbial metabolites into the mucosa, thereby aggravating local inflammation. Probiotics may help maintain barrier homeostasis by reshaping the gut microbial community, reinforcing epithelial and mucus barriers, modulating mucosal immunity, and reducing oxidative injury. This review summarizes recent evidence on the protective effects of probiotics, including Lactobacillus spp., Bifidobacterium spp., and Akkermansia muciniphila, on the intestinal mucosal barrier in UC. Current findings suggest that probiotics can inhibit pathogen adhesion and colonization, enhance the production of beneficial metabolites such as short-chain fatty acids and tryptophan-derived compounds, and promote the expression of tight-junction proteins, including ZO-1, occludin, claudin-1, and claudin-4, as well as mucins such as MUC1 and MUC2. These effects may be mediated through the regulation of NF-κB, NLRP3, aryl hydrocarbon receptor (AhR), mitogen-activated protein kinase (MAPK), and related signaling pathways, thereby attenuating inflammation and oxidative stress and promoting epithelial repair. Combination strategies involving probiotics and prebiotics, traditional Chinese medicine-derived components, postbiotics, fecal microbiota transplantation, or novel delivery systems may improve microbial engraftment, enhance colon-targeted delivery, and strengthen microbiota remodeling and barrier repair. Nevertheless, the available evidence remains limited by substantial strain specificity, insufficient clinical validation, and the absence of standardized intervention protocols. Further multi-omics studies and well-designed clinical trials are warranted to clarify the efficacy, mechanisms, optimal dosing, and safety of these interventions in UC.},
}

Humans
*Probiotics/therapeutic use
*Colitis, Ulcerative/microbiology/therapy/immunology/metabolism
Intestinal Barrier Function
*Intestinal Mucosa/immunology/microbiology/metabolism
Animals
*Gastrointestinal Microbiome
Immunity, Mucosal

@article {pmid42866850,
year = {2026},
author = {Gu, L and Chen, Y and Jin, L and Liu, Y},
title = {A narrative review of the gut microbiota-testis axis: mechanisms and implications for male reproductive health.},
journal = {Translational andrology and urology},
volume = {15},
number = {9},
pages = {350},
pmid = {42866850},
issn = {2223-4691},
abstract = {BACKGROUND AND OBJECTIVE: Infertility affects approximately 8-12% of couples worldwide, with male factors accounting for nearly half of all cases. The gut microbiota is widely recognized as a key regulator of host physiology, yet its specific role in male reproductive health remains to be elucidated. This narrative review synthesizes current evidence on the "gut microbiota-testis axis" and provides a critical evaluation of the strength of evidence derived from different study designs.

METHODS: We conducted a comprehensive literature search in PubMed/MEDLINE up to May 2026 using Boolean search strategies combining terms related to the gut microbiota (e.g., "Gastrointestinal Microbiome", "gut microbiota", "gut microbiome") with terms related to male reproduction (e.g., "Semen Analysis", "Spermatozoa", "Infertility, Male", "semen quality", "sperm quality"). Separate search strategies were developed for human and animal studies. Literature screening and data extraction were performed independently by two reviewers according to predefined inclusion and exclusion criteria.

KEY CONTENT AND FINDINGS: Although human studies remain preliminary, several genera, including Anaerotruncus, Bacteroides, and Faecalibacterium prausnitzii, have been reproducibly associated with semen quality, with microbial metabolites such as butyrate, trimethylamine-N-oxide (TMAO), and succinate potentially serving as important mediators. At the mechanistic level, microbiota-derived metabolic and inflammatory signals act on Leydig cells, Sertoli cells, and germ cells, thereby influencing testosterone synthesis and spermatogenesis. Fecal microbiota transplantation (FMT) experiments in animal models have provided direct evidence for these causal links.

CONCLUSIONS: The gut microbiota-testis axis has emerged as a critical physiological pathway linking the microbiome to male reproductive function. This review provides an evidence-based framework for understanding this axis and highlights key knowledge gaps that must be addressed. Future research should integrate large-scale longitudinal cohorts, mechanistic exploration, and randomized controlled trials with fertility outcomes as primary endpoints to advance the field from descriptive correlations toward mechanism-driven clinical translation.},
}

@article {pmid42867288,
year = {2026},
author = {Kong, W and Zhang, H and Gui, J and Long, X and Chen, X and Ge, Y and Shao, W and Zhao, G and Cubero, FJ and Jiang, Z and Gu, A},
title = {Prophylactic oral diosgenin attenuates acute sleep deprivation-induced liver injury in mice via modulation of the gut microbiota and vascular barrier.},
journal = {Food & function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6fo01836j},
pmid = {42867288},
issn = {2042-650X},
abstract = {Acute sleep deprivation (SD) is an increasingly prevalent health risk, yet the early inflammatory processes associated with acute hepatic injury following SD remain largely elusive. Following a two-step screening of 265 natural products and bioactive small molecules, diosgenin (DG), a sapogenin found in Dioscorea species, was prioritized for subsequent in vivo evaluation. Under the rotating-platform paradigm in mice, 24-hour SD (SD24h) was associated with acute hepatic inflammation, increased overall intestinal permeability, gut vascular barrier (GVB)-associated alterations, gut microbiota dysbiosis, and elevated intestinal and hepatic lipopolysaccharide (LPS) levels. Prophylactic oral DG pretreatment attenuated hepatic and intestinal inflammatory responses, intestinal permeability changes, and GVB-associated alterations, while partially ameliorating SD-associated changes in the gut microbiota and intestinal and hepatic LPS levels. Fecal microbiota transplantation further showed that microbiota from SD24h donors transferred part of the hepato-intestinal inflammatory and barrier-associated phenotypes to antibiotic-pretreated recipients, whereas microbiota from DG-pretreated SD24h donors transferred an attenuated phenotype. Collectively, these findings support the involvement of the gut microbiota and intestinal barrier in acute SD-associated liver injury and indicate that prophylactic oral DG pretreatment attenuates these hepato-intestinal responses.},
}

@article {pmid42859560,
year = {2026},
author = {Dewan, A and Goulart, DB and Mascellino, MT},
title = {Gut microbiota dysbiosis: Pathogenic drivers and emerging phage-based therapeutics.},
journal = {AIMS microbiology},
volume = {12},
number = {3},
pages = {632-665},
pmid = {42859560},
issn = {2471-1888},
abstract = {Gut microbiota dysbiosis driven by pathogenic and opportunistic bacteria, including Clostridioides difficile, adherent-invasive Escherichia coli (AIEC), Salmonella enterica serovar Typhimurium, Fusobacterium nucleatum, Klebsiella pneumoniae, Enterococcus faecalis, and Campylobacter spp., disrupts colonization resistance, epithelial barrier integrity, and immune homeostasis, thereby contributing to the development of inflammatory and metabolic diseases. In this review, we summarize the mechanisms through which these microorganisms promote gut dysbiosis and critically evaluate current microbiome-targeted therapeutic strategies, including fecal microbiota transplantation (FMT), live biotherapeutic products (LBPs), probiotics, and bacteriophage (phage) therapy. We review the preclinical and emerging clinical evidence supporting phage-based targeting of major dysbiosis-associated pathogens and examine the principal challenges limiting clinical translation, including phage resistance, immune-mediated clearance, safety considerations related to temperate phages, manufacturing and delivery constraints, and regulatory barriers. Although evidence remains predominantly preclinical, advances in phage engineering, artificial intelligence-guided phage selection, and systems-level microbiome modeling are expanding the potential of personalized phage therapeutics. Collectively, these developments position bacteriophage therapy as a promising addition to future microbiome-directed strategies for restoring gut microbial homeostasis and managing dysbiosis-associated disease.},
}

@article {pmid42860401,
year = {2026},
author = {Xu, Z and Jiang, H and Huang, W and Chan, A and Lin, Y and Chan, T and Lui, RN and Wong, MTL and Mak, JWY and Chan, FKL and Chevarin, C and Colombel, JF and Buisson, A and Ng, SC},
title = {Fecal microbiota transplantation for the decolonization of mucosal adherent-invasive Escherichia coli in Crohn's disease: an open-label pilot study.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {42860401},
issn = {2041-1723},
mesh = {Humans ; *Crohn Disease/therapy/microbiology ; Pilot Projects ; *Fecal Microbiota Transplantation/methods/adverse effects ; Female ; *Escherichia coli/genetics/physiology ; Male ; Feces/microbiology ; Adult ; *Intestinal Mucosa/microbiology ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; *Escherichia coli Infections/therapy/microbiology ; Young Adult ; Gastrointestinal Microbiome ; Treatment Outcome ; },
abstract = {Adherent-invasive Escherichia coli (AIEC) is implicated in Crohn's disease (CD) pathogenesis, but whether fecal microbiota transplantation (FMT) clears mucosal AIEC and alters fecal and mucosal microbiomes has not been studied. In this open-label pilot study, thirty adults with CD and seropositivity for serum anti-E.coli antibody (AEcAb) received a single colonoscopic FMT from one of two donors (ClinicalTrials.gov identifier NCT05611866). The primary outcome was adverse events (AEs) within 12 weeks after FMT; secondary outcomes included changes in mucosal AIEC, clinical measures, and fecal and mucosal microbiome profiles. Shotgun metagenomic sequencing for fecal samples and 16S rRNA sequencing for ileal mucosal samples were performed at baseline and after FMT. Baseline AEcAb levels were higher in patients with mucosal AIEC colonization (p = 0.019) and remained elevated after FMT. No FMT-related serious adverse events were reported. FMT was associated with mucosal AIEC decolonization in all 8 evaluable baseline-positive patients. Mucosal alpha diversity increased after FMT (p = 0.023), which correlated with reduced fecal calprotectin (p = 0.034). Microbial pathway profiles in CD patients resembled those of their respective donors with reduced donor-recipient dissimilarity post-FMT (p = 0.030), particularly among recipients with mucosal AIEC decolonization (p = 0.039). In conclusion, this open-label pilot study demonstrates the feasibility of FMT for modulating mucosal AIEC colonization in CD and highlights the importance of capturing microbial changes at the disease site that may be undetectable in fecal samples.},
}

Humans
*Crohn Disease/therapy/microbiology
Pilot Projects
*Fecal Microbiota Transplantation/methods/adverse effects
Female
*Escherichia coli/genetics/physiology
Male
Feces/microbiology
Adult
*Intestinal Mucosa/microbiology
Middle Aged
RNA, Ribosomal, 16S/genetics
*Escherichia coli Infections/therapy/microbiology
Young Adult
Gastrointestinal Microbiome
Treatment Outcome

@article {pmid42860646,
year = {2026},
author = {Tai, YC and Lin, CH},
title = {Targeting the Gut to Modify Parkinson's Disease: From Mechanisms to Potential Therapeutics.},
journal = {Journal of movement disorders},
volume = {},
number = {},
pages = {},
doi = {10.14802/jmd.26285},
pmid = {42860646},
issn = {2005-940X},
abstract = {Parkinson's disease (PD) is the second most common neurodegenerative disorder and its prevalence continues to rise with population aging. Its cardinal motor features arise from the loss of dopaminergic neurons in the substantia nigra, accompanied by intraneuronal α-synuclein aggregates known as Lewy bodies. Neuropathological evidence suggests that, in a subset of patients, α-synuclein pathology first appears in the enteric nervous system and ascends to the brain via the gut-brain axis. Consistent with this "body-first" trajectory, a growing body of work has documented distinct alterations in gut microbial composition and microbiota-derived metabolites in people with PD relative to healthy individuals, with some changes detectable in the prodromal phase. Current management, whether dopaminergic pharmacotherapy or deep brain stimulation, alleviates motor symptoms but does not slow neurodegeneration, and long-term treatment is complicated by motor fluctuations and other adverse effects. Therapies directed at the underlying disease process are therefore urgently needed. Because early perturbations of the gut microenvironment appear to contribute to PD pathogenesis, interventions that restore gut homeostasis represent a rational disease-modifying strategy, particularly for patients whose pathology originates in the gut. This review synthesizes current understanding of how the gut microbiota shapes the gut-brain axis in PD, spanning immune, metabolic, neuroendocrine, and neural pathways, and critically appraises the emerging evidence for microbiota-directed interventions, including fecal microbiota transplantation, probiotics, and prebiotics, as candidate disease-modifying therapies.},
}

@article {pmid42861589,
year = {2026},
author = {Xie, YZ and Sun, CX and Fu, TT and Jin, Z and Nalinratana, N and Rojsitthisak, P and Zhao, K and Hua, JS and Pei, FY and Wang, XH},
title = {Nanoformulated Curcumin Ameliorates Ulcerative Colitis via Gut Microbiota Modulation and Barrier Function Restoration.},
journal = {The American journal of Chinese medicine},
volume = {},
number = {},
pages = {1-26},
doi = {10.1142/S0192415X26500837},
pmid = {42861589},
issn = {1793-6853},
abstract = {The gut microbiota is increasingly recognized as a key mediator of the anticolitis effects of curcumin (CUR). However, the clinical translation of this promising activity is severely hampered by CUR's low solubility and poor bioavailability. Although nanoencapsulation represents a promising strategy to address these limitations, the preventive effect of nanocurcumin (nano-CUR) against colitis remains largely unexplored. The present study aimed to elucidate the preventive effects of nano-CUR on intestinal barrier function, gut microbiota composition, and metabolic profiles in a murine model of dextran sulfate sodium (DSS)-induced colitis. The results demonstrated that pre-supplementation of nano-CUR significantly ameliorated disease severity, attenuated intestinal barrier disruption, and suppressed colonic inflammation in mice with DSS-induced colitis. Mechanistically, integrated 16S rRNA sequencing and untargeted metabolomics demonstrated that nano-CUR-restored microbial homeostasis and enhanced the production of short-chain fatty acids, linking microbial shifts to anti-inflammatory outcomes. Fecal microbiota transplantation (FMT) further validated the causal role of the nano-CUR-remodeled microbiota in conferring protection. Collectively, these findings decipher the mechanism by which nano-CUR interacts with the gut microbiota, confirming that dietary nano-CUR consumption protects against ulcerative colitis by modulating the gut microbiome and its metabolic output.},
}

@article {pmid42861819,
year = {2026},
author = {Zhao, W and Yan, D},
title = {Supplementation with Akkermansia muciniphila Enhances the αPD-1 Efficacy in Mice Transplanted with Gut Microbiota from Patients with Colorectal Cancer.},
journal = {Current cancer drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115680096507014261001062033},
pmid = {42861819},
issn = {1873-5576},
abstract = {INTRODUCTION: The resistance of colorectal cancer (CRC) to PD-1 blockade has positioned it as a critical focus of global research efforts. The gut microbiota is a key regulator of anti-tumor immunity, but research on bacteria that are clearly associated with primary resistance to PD-1 blockade in colorectal cancer remains incomplete.

METHODS: In this study, C57BL/6 mice were subjected to antibiotic pretreatment to deplete endogenous gut microbiota. The mice were then gavaged with fecal suspensions from treatment-naïve CRC patients or healthy donors, subsequently implanted with MC38 tumor cells to establish the tumor model, and then treated with the drug. Gut microbial composition was analyzed by 16S rRNA sequencing, while tumor-infiltrating immune cells and cytokine profiles were characterized using flow cytometry and immunohistochemistry, respectively.

RESULTS: CRC patient microbiota conferred resistance to anti-PD-1 therapy in mice, an effect completely reversed by oral Akkermansia muciniphila (Akk). Mechanistically, Akk reconfigured the tumor immune microenvironment, leading to a substantial increase in CD8+ T cell infiltration and function. Crucially, this potent local anti-tumor immunity was achieved without systemic immune activation.

DISCUSSION: In summary, this study establishes that Akk amplifies the local CD8⁺ T cell response, sensitizing tumors to anti-PD-1 therapy, without inducing a systemic inflammatory response.

CONCLUSION: These findings position Akk supplementation as a promising, targeted strategy to overcome PD-1 immunotherapy resistance of MSS-CRC with a favorable safety profile.},
}

@article {pmid42852084,
year = {2026},
author = {Fan, Y and Du, L and Luo, Q and Mei, T and Zhou, A and Liu, H and Khan, MQ and Gao, F and Dong, J},
title = {The lung-gut-brain axis in non-small-cell lung cancer: a narrative review with a systematic search of three signaling pathways.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1932225},
pmid = {42852084},
issn = {1664-3224},
mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung/metabolism/immunology/microbiology/therapy ; *Lung Neoplasms/metabolism/immunology/microbiology/therapy ; *Signal Transduction ; Animals ; *Gastrointestinal Microbiome ; *Brain/metabolism ; *Lung/metabolism/immunology ; },
abstract = {BACKGROUND: The gut-lung axis, the long-range communication between the intestinal microbiota and the lungs, has been shown to influence immunotherapy responses in non-small-cell lung cancer (NSCLC). Existing reviews, however, focus almost exclusively on the chemical signaling dimension of microbial metabolites. The relay function of enteroendocrine hormones and the integrative role of the nervous system have yet to be incorporated into a unified framework.

METHODS: We searched seven databases (PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, Wanfang, and VIP) from inception to June 2026 for original studies and reviews addressing gut microbiota and lung-gut-brain axis mechanisms in the context of NSCLC or small-cell lung cancer. Two authors independently performed study selection, data extraction, and thematic classification. A narrative synthesis was conducted, with evidence organized along three signaling axes: soluble metabolites, the metabolic-endocrine axis, and neuroimmune integration. As a narrative review with a systematic search, this study was registered on PROSPERO (CRD420261425826), while formal risk-of-bias assessment and GRADE evaluation were not performed.

RESULTS: A total of 168 studies was included (only a subset of these included studies cited in the main text). The volume of evidence across the three axes formed a pronounced gradient. Soluble metabolites (short-chain fatty acids, tryptophan metabolites, and bile acids) have been cross-validated in clinical cohorts, animal models, and in vitro experiments; fecal microbiota transplantation and prebiotic strategies have entered clinical trials. The metabolic-endocrine axis rests on a solid foundation in normal physiology, but the key bridging nodes in the NSCLC disease context remain untested. Evidence for the neuroimmune integration axis is the sparsest: the only support for a direct transport function of the vagus nerve comes from a non-peer-reviewed preprint in a non-cancer model, and the full neuroendocrine signal transduction chain remains hypothetical. To address this gap, we outline a pathway model annotated with evidence levels at each node.

CONCLUSIONS: Research on the lung-gut-brain axis is heavily concentrated in the chemical dimension. The mechanistic gaps in the endocrine and neural dimensions represent the principal barrier for the field's transition from correlational description to causal mechanism studies.},
}

Humans
*Carcinoma, Non-Small-Cell Lung/metabolism/immunology/microbiology/therapy
*Lung Neoplasms/metabolism/immunology/microbiology/therapy
*Signal Transduction
Animals
*Gastrointestinal Microbiome
*Brain/metabolism
*Lung/metabolism/immunology

@article {pmid42856694,
year = {2026},
author = {Soveral, LF and Holanda, LRL and Assunção, IBF and Gomes, LG and de Souza, IB and Rodrigues, GS and Vanny, PA and Bruna-Romero, O and Palmeiro, JK and Scheffer, MC and Sincero, TCM and Zárate-Bladés, CR},
title = {Identification of antibiotic resistance genes in fecal microbiota selected donors during the establishment of a biobank in the south of Brazil.},
journal = {Frontiers in antibiotics},
volume = {5},
number = {},
pages = {1905540},
pmid = {42856694},
issn = {2813-2467},
abstract = {Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI) and is increasingly explored for other dysbiosis-related disorders. However, its implementation as a regulated therapeutic strategy requires robust donor screening, biosafety frameworks, and standardized processing workflows. Here, we describe the establishment of the first fecal microbiota biobank in southern Brazil and evaluate the incorporation of metagenomic sequencing as a complementary layer of donor characterization and safety assessment. A structured donor selection pipeline based on international guidelines was implemented, integrating clinical screening, biochemical and serological testing, and microbiological analyses. Of 100 screened candidates, only four donors met all eligibility criteria and were included in the biobank, highlighting the stringency of the selection process. Shotgun metagenomic sequencing revealed a diverse resistome across all donors, including a shared core set of resistance genes alongside marked interindividual variability. Dominant resistance determinants included tetracycline-associated genes, ermF, CfxA-type β-lactamases, and aminoglycoside-modifying enzymes, which were associated with specific gut taxa. Genomic context analysis further identified four ARG-containing contigs with features compatible with potential mobility, although active horizontal gene transfer was beyond the scope of this study. Notably, tet(Q) and ermF were predominantly associated with Bacteroides fragilis, supporting its role as a reservoir of resistance determinants in the gut microbiota. These findings support the use of metagenomic profiling as a complementary approach to donor characterization and risk assessment rather than as a standalone criterion for donor exclusion. Overall, this study provides a framework for microbiota biobank implementation and highlights the potential of metagenomic analysis to complement conventional biosafety screening in FMT.},
}

@article {pmid42856976,
year = {2026},
author = {Sharma, S and Pachauri, A and Nagar, H and Thakkar, V and Patel, K},
title = {Targeting gut dysbiosis: a new frontier in MASLD management.},
journal = {Frontiers in systems biology},
volume = {6},
number = {},
pages = {1937809},
pmid = {42856976},
issn = {2674-0702},
abstract = {Globally, Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prominent leading cause of CLD, which is intricately linked with obesity, T2D, and metabolic syndrome. Recent insights in pathophysiologically of MASLD have shifted from the traditional "two-hit" model to a "multiple-hit" paradigm, demonstrating the importance of understanding the gut-liver axis and gut dysbiosis as central drivers of disease progression. Hence, this narrative review explores the mechanistic pathways through which an altered gut microbiome contributes to MASLD, by specifically emphasizing intestinal barrier disruption, endotoxemia, altered bile acid metabolism, and SCFA imbalance. These dysregulations trigger oxidative stress, leading to systemic inflammation and insulin resistance, propelling simple steatosis toward steatohepatitis and fibrosis at last. Furthermore, we also highlighted the diagnostic utility of microbial signatures and multi-omics approaches in identifying disease-specific microbial shifts, such as the depletion of beneficial SCFA-producing bacteria like Faecalibacterium and Akkermansia. Eventually, to address the growing hepatic-associated health burden, microbiome-targeted therapeutics can emerge as one of the promising contributors. In this review, we synthesise and demonstrate the current and prospective interventions, including dietary modifications, biotics (probiotics, prebiotics, synbiotics), and FMT. Additionally, we also show the transition of care toward precision microbiome therapies utilizing engineered bacteria, bacteriophages, and AI-guided patient stratification. While current microbiome-centric treatments demonstrate promise in modulating hepatic inflammation and restoring mucosal integrity, their clinical translation remains hindered by patient heterogeneity and a lack of standardized protocols. Ultimately, managing MASLD effectively will require moving beyond broad ecosystem resets toward highly tailored, multi-omics-driven precision medicine to accurately target individualized microbial deficits.},
}

@article {pmid42857238,
year = {2026},
author = {Ma, J and Hou, Z},
title = {Gut Microbiota-Immune-Inflammation Axis as a Putative Pathogenic Axis in Chronic Insomnia: Mechanistic Dissection of NLRP3 Inflammasome and NF-κB Signaling.},
journal = {International journal of general medicine},
volume = {19},
number = {},
pages = {645057},
pmid = {42857238},
issn = {1178-7074},
abstract = {Chronic insomnia represents one of the most prevalent sleep disorders worldwide, yet current symptomatic treatments largely fail to target its root pathophysiology. Moving beyond conventional neurocentric frameworks, converging evidence positions gut microbiota dysbiosis as a potential upstream contributor to insomnia via the microbiota-gut-brain axis, with immune-inflammatory cascades serving as proposed mediating pathway. Mechanistically, disrupted gut microbial communities compromise intestinal mucosal barrier integrity, enabling lipopolysaccharide translocation that activates TLR4-mediated NF-κB signaling. This triggers systemic low-grade inflammation, marked by elevated pro-inflammatory cytokines IL-1β, IL-6, IL-17 and TNF-α, reduced anti-inflammatory IL-4 and IL-10, and Th17/Treg immune imbalance. Centrally, circulating inflammatory signals activate the NLRP3 inflammasome, driving caspase‑1‑dependent pyroptosis and a pro‑inflammatory microglial activation state (conventionally described as "M1‑like" polarization), which disrupts sleep-wake neural circuitry and hypothalamic-pituitary-adrenal axis homeostasis. Dysregulated PI3K/Akt signaling and aberrant microbial metabolites-including depleted short-chain fatty acids and a pathological shift in tryptophan metabolism toward the neurotoxic kynurenine pathway-further amplify the vicious cycle between sleep disturbance and neuroinflammation. This review systematically maps the full pathological cascade from intestinal dysbiosis to central insomnia phenotypes, and compares translational strategies including psychobiotic strains, fecal microbiota transplantation, dietary intervention and traditional Chinese medicine formulas targeting this axis. Collectively, this work proposes an integrated microbiota-immune-sleep regulatory framework, offering novel mechanistic insights and microbiome-based therapeutic avenues for precision insomnia management.},
}