@article {pmid42127421,
year = {2026},
author = {Li, Y and Yuan, Q and Yang, Y and Wang, L and Han, Q and Yang, Y and Zhang, J and Wei, H and Yin, Y and Tao, S and Yin, J},
title = {Gut microbiota control host lipid deposition through HDAC9-driven PPARγ acetylation.},
journal = {The ISME journal},
volume = {},
number = {},
pages = {},
doi = {10.1093/ismejo/wrag109},
pmid = {42127421},
issn = {1751-7370},
abstract = {The healthy gut microbiota communities play a complex and significant role in lipid absorption and deposition, leading to multiple health benefits. Here, we confirmed an impaired absorption and deposition function in germ-free pigs and mice, which was partially reversed after human fecal microbiota transplantation. By integrating single-cell data from adipose tissue, we identified HDAC9 as a key regulator, marked by the presence of a population of small mature adipocytes exhibiting high HDAC9 and low PPARγ expression in germ-free pigs. HDAC9 deficiency of preadipocytes drove FABP4/5-mediated lipid deposition by directly targeting PPARγ expression and acetylation modification. Finally, we verified the interaction between gut microbiota and host HDAC9/PPARγ/FABP4/5 signaling cascade might be microbial receptors (ie, Dectin1 or TLRs)-dependent rather than microbial metabolites. Altogether, our study uncovers the gut microbiota-HDAC9-PPARγ axis as a key regulator of adipocyte function and lipid deposition, offering a potential therapeutic target for lipid-related metabolic diseases.},
}

@article {pmid42128051,
year = {2026},
author = {Rondeau, LE and Da Luz, BB and Haas, D and Muppidi, P and Wang, X and Dang, R and Rueda, G and Nardelli, A and De Palma, G and Sokol, H and Bercik, P and Caminero, A},
title = {Dietary tryptophan enhances aryl hydrocarbon receptor activation and reduces colitis through microbial metabolism.},
journal = {Cellular and molecular gastroenterology and hepatology},
volume = {},
number = {},
pages = {101811},
doi = {10.1016/j.jcmgh.2026.101811},
pmid = {42128051},
issn = {2352-345X},
abstract = {BACKGROUND & AIM: Disrupted microbial tryptophan metabolism and impaired aryl hydrocarbon receptor (AhR) activation are implicated in inflammatory bowel disease (IBD) pathogenesis. However, strategies to restore this pathway through diet or microbial modulation remain poorly defined. This study investigates how dietary tryptophan and human and mouse microbiota modulate metabolism, AhR activation, and intestinal inflammation in preclinical models.

METHODS: Gnotobiotic mice colonized with microbiota of varying complexity or human fecal microbiota from ulcerative colitis (UC) patients and healthy controls were used to assess the impact of microbiota and dietary tryptophan supplementation on AhR activation and colitis severity. Chemically induced and spontaneous colitis models were investigated.

RESULTS: IBD fecal samples showed reduced AhR activation compared to healthy controls, and fecal microbiota transplantation into germ-free mice demonstrated that impaired AhR is microbiota-dependent. Mice colonized with minimal microbiota had impaired microbial tryptophan metabolism, lower AhR activation, and worsened colitis severity compared to those colonized with complex microbiota. Dietary tryptophan supplementation in conventional and UC-humanized mice enhanced microbial production of AhR agonists, restored AhR activation, and reduced colitis severity in an AhR-dependent manner. Co-colonization with a tryptophan-metabolizing bacterium, Clostridium sporogenes, further improved tryptophan metabolism and colitis severity in mice with impaired microbial tryptophan metabolism.

CONCLUSIONS: Microbial tryptophan metabolism is critical for determining intestinal inflammation. Dietary tryptophan supplementation restores microbial metabolic pathways, mitigates colitis severity in preclinical models, and may address key metabolic deficiencies in IBD patients with impaired tryptophan metabolism. This study demonstrates the therapeutic potential of targeting microbial metabolism with diet in IBD management.},
}

@article {pmid42128395,
year = {2026},
author = {Cho, E and Lee, JH and Hong, JT and Kwon, KS and Shin, YW},
title = {Fecal microbiota transplantation for marked colonic dilatation.},
journal = {The Korean journal of internal medicine},
volume = {41},
number = {3},
pages = {560-562},
pmid = {42128395},
issn = {2005-6648},
}

@article {pmid42129837,
year = {2026},
author = {Wang, MZ and Du, ZB and Xu, WQ and Xie, YH and Wang, LL and He, XX and Wang, YH and Zheng, HY and Yao, YL and Song, YB and Lin, ZN and Lin, YC},
title = {Butyrate-producing gut bacteria restrain PBAT microplastic-triggered brain microglial lipotoxicity via a microbiota-butyrate-mTORC1-ISR relay along the gut-brain axis.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-026-03869-1},
pmid = {42129837},
issn = {1742-2094},
support = {82273667//the National Natural Science Foundation of China/ ; 82574139//the National Natural Science Foundation of China/ ; 3502Z202573032//the Natural Science Foundation of Xiamen, China/ ; 2023XAKJ0101024//the Scientific Research Foundation of State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory/ ; 2022Y4009//the Industry-University-Research Cooperation Project of Fujian Science and Technology Plan/ ; FJHYF-L-2025-04-008//the Fujian Province Special Fund Project for Promoting High-Quality Development of Marine and Fishery Industries/ ; 20720250004//the Fundamental Research Funds for the Central Universities/ ; S202210384407//the XMU Undergraduate Innovation and Entrepreneurship Training Programs/ ; },
abstract = {Eco-friendly poly(butylene adipate-co-terephthalate) (PBAT) is widely marketed as biodegradable, yet the neurotoxicity of derived PBAT microplastics (PBAT-MPs) and their underlying mechanisms remain poorly characterized. Here we identify a previously unrecognized "gut microbiota-butyrate-neuro-lipid" axis linking intestinal PBAT-MPs exposure to hippocampal microglial lipotoxicity and cognitive impairment. By integrating fecal microbiota transplantation (FMT) with multi-omics analyses, we demonstrate that orally administered PBAT-MPs preferentially accumulate in the colon, impair epithelial barrier integrity, deplete butyrate-associated taxa, including Muribaculaceae and Alloprevotella, and enrich Escherichia-Shigella. Butyrate depletion elevates systemic lipopolysaccharide (LPS) levels and, via the gut-brain inflammatory route, activates mTORC1-integrated stress response (ISR) signaling in microglia. Consequently, microglia acquire a lipotoxic phenotype characterized by transcriptional up-regulation of DGAT- and ACSL-dependent lipid droplet (LD) biogenesis genes, accumulation of toxic lipids and inflammatory mediators, synaptic stripping, and memory loss. In vivo butyrate supplementation in PBAT-MP-exposed mice alleviates hippocampal pathology, normalizes microglial lipid accumulation, suppresses neuroinflammation, reduces ceramide levels, and improves cognitive performance. Mechanistically, butyrate inhibits mTORC1, attenuates eIF2α-ATF4-dependent ISR signaling, and represses DGAT/ACSL-dependent LD biogenesis, whereas microglial Rptor overexpression abolishes these protective effects, identifying mTORC1 as an upstream metabolic checkpoint. Collectively, our findings establish the microbiota-butyrate-mTORC1-ISR relay as a core driver of PBAT-MPs-induced neurotoxicity and highlight restoration of butyrate signaling as a promising microbiota-based strategy for preventing microplastic-induced brain lipotoxic injury.},
}

@article {pmid42130360,
year = {2026},
author = {Li, Y and Niu, HS and Lu, XL and Li, XC and Xiao, M and Wang, Y and Yang, SJ and Guo, YY and Sun, Y},
title = {[Fecal microbiota transplantation attenuates gastrointestinal inflammation in murine acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation by inhibiting RIPK1/RIPK3-mediated necroptosis].},
journal = {Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics},
volume = {28},
number = {5},
pages = {598-606},
pmid = {42130360},
issn = {1008-8830},
mesh = {Animals ; *Receptor-Interacting Protein Serine-Threonine Kinases/physiology ; *Graft vs Host Disease/therapy/etiology ; *Necroptosis ; Mice ; Mice, Inbred BALB C ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Fecal Microbiota Transplantation ; Male ; Acute Disease ; Transplantation, Homologous ; Female ; Gastrointestinal Microbiome ; Protein Kinases ; },
abstract = {OBJECTIVES: To investigate the molecular mechanism by which fecal microbiota transplantation (FMT) alleviates gastrointestinal inflammation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in murine acute graft-versus-host disease (aGVHD).

METHODS: A murine aGVHD model after allo-HSCT was established, and BALB/c mice were randomly assigned to blank control, bone marrow transplantation, aGVHD model, and FMT treatment groups (n=6 per group). Disease severity was assessed by histopathology. Expression of receptor-interacting protein kinase (RIPK)1, RIPK3, and mixed lineage kinase domain-like protein (MLKL) was evaluated by immunohistochemistry. Protein levels of RIPK1, RIPK3, MLKL, phosphorylated RIPK1 (p-RIPK1), and phosphorylated MLKL (p-MLKL) were determined by Western blotting. Plasma regenerating islet-derived protein 3 alpha (Reg3α) was measured by enzyme-linked immunosorbent assay. The intestinal microbiota was profiled by 16S rRNA gene sequencing.

RESULTS: Compared with the aGVHD model group, the FMT group showed higher relative abundances of Firmicutes and Bacteroidetes and a lower relative abundance of Proteobacteria; body weight loss was markedly attenuated, and survival time was prolonged. Alpha-diversity indices (Simpson, Pielou, Shannon) increased in the FMT group (P<0.05). Intestinal pathology scores, expression of RIPK1, RIPK3, and MLKL, protein levels of RIPK1, RIPK3, MLKL, p-RIPK1, and p-MLKL, and plasma Reg3α levels were significantly reduced in the FMT group versus the aGVHD model group (all P<0.05).

CONCLUSIONS: FMT may attenuate gastrointestinal inflammation in aGVHD by restoring intestinal microbial balance and inhibiting the RIPK1/RIPK3-mediated necroptosis pathway.},
}

Animals
*Receptor-Interacting Protein Serine-Threonine Kinases/physiology
*Graft vs Host Disease/therapy/etiology
*Necroptosis
Mice
Mice, Inbred BALB C
*Hematopoietic Stem Cell Transplantation/adverse effects
*Fecal Microbiota Transplantation
Male
Acute Disease
Transplantation, Homologous
Female
Gastrointestinal Microbiome
Protein Kinases

@article {pmid42130461,
year = {2026},
author = {Tian, M and Wang, D and Zhang, C and Fan, J and Li, W and Liu, X and Shi, J},
title = {Gut Microbiota Dysbiosis Drives Early Alzheimer's Pathogenesis via Microglial TREM2/SYK/NF-κB Signaling Axis.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.6c00173},
pmid = {42130461},
issn = {1948-7193},
abstract = {Gut microbiota dysbiosis is implicated in Alzheimer's disease (AD), but causal evidence and mechanisms linking it to microglial dysfunction remain unclear. This study aimed to determine whether gut microbiota drives neuroinflammation and cognitive impairment via the microglial TREM2/SYK signaling axis in early AD. Using six-month-old APP/PS1 mice, fecal microbiota transplantation (FMT) was performed between AD and wild-type mice. Cognitive function, gut microbiota composition (16S rRNA sequencing), serum metabolites, hippocampal neuroinflammation, microglial polarization, and TREM2/SYK/NF-κB pathway activity were assessed. BV2 microglial cells were treated with Aβ oligomers, a TREM2 agonist, or a SYK inhibitor for mechanistic validation. AD mice exhibited cognitive decline, reduced microbial diversity (e.g., decreased Bacteroidetes and Lactobacillus), and altered circulating metabolites, including decreased butyrate and elevated LPS. Their hippocampi exhibited heightened glial activation, elevated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and a shift toward pro-inflammatory activation markers (M1-associated). At the molecular level, TREM2 expression was downregulated, whereas SYK phosphorylation and NF-κB activation were enhanced, concomitant with synaptic protein loss. Critically, FMT from healthy donors reversed these abnormalities and improved cognition, whereas AD microbiota induced mild pathology in wild-type mice. In vitro, TREM2 activation or SYK inhibition attenuated Aβ-induced M1 polarization and cytokine release in microglia. Gut microbiota dysbiosis promotes early AD pathogenesis by dysregulating the microglial TREM2/SYK/NF-κB pathway, thereby driving neuroinflammation and synaptic dysfunction. Targeting this microbiota-signaling axis may offer novel therapeutic strategies.},
}

@article {pmid42130741,
year = {2026},
author = {Long, J and Zhao, J and Gu, X and Huang, C},
title = {Post-transplant diabetes mellitus after kidney transplantation: pathogenesis, risk factors, and management strategies.},
journal = {Frontiers in endocrinology},
volume = {17},
number = {},
pages = {1829579},
pmid = {42130741},
issn = {1664-2392},
mesh = {Humans ; *Kidney Transplantation/adverse effects ; Risk Factors ; *Postoperative Complications/etiology/therapy ; *Diabetes Mellitus/etiology/therapy ; Gastrointestinal Microbiome ; Immunosuppressive Agents/adverse effects ; },
abstract = {Post-transplant diabetes mellitus (PTDM) affects 7-39% of kidney transplant recipients and substantially worsens cardiovascular, infectious, and allograft outcomes. Although PTDM shares core pathophysiological features with type 2 diabetes-peripheral insulin resistance and impaired β-cell secretion-its etiology is fundamentally shaped by immunosuppressive therapy. Calcineurin inhibitors suppress insulin gene transcription via NFAT inhibition and exacerbate lipotoxicity; corticosteroids drive hepatic gluconeogenesis and impair GLUT4-mediated glucose uptake; and mTOR inhibitors reduce β-cell mass through mTORC1-dependent mechanisms. Chronic NF-κB/JNK-driven inflammation further amplifies insulin resistance and promotes β-cell apoptosis. Beyond these established mechanisms, we propose a unifying "gut-immune-metabolic axis" in which immunosuppression-induced gut microbiota dysbiosis-characterized by depletion of short-chain fatty acid-producing taxa (Roseburia, Faecalibacterium prausnitzii) and Akkermansia muciniphila-drives intestinal barrier dysfunction, endotoxemia, impaired FXR/TGR5-mediated GLP-1 secretion, and TMAO-associated metabolic inflammation, collectively perpetuating glucose dysregulation. Risk stratification integrates non-modifiable factors (advanced age, African American/Hispanic/South Asian ethnicity, TCF7L2 polymorphisms, autosomal dominant polycystic kidney disease) with modifiable determinants (pre-transplant dysglycemia, obesity, hypomagnesemia, hepatitis C and cytomegalovirus infections, acute rejection, and diuretic use). Diagnosis requires OGTT-centered assessment per the 2024 International Consensus guidelines, with cautious interpretation of HbA1c during the early post-transplant period. Management encompasses personalized immunosuppression (corticosteroid minimization, tacrolimus trough levels <10 ng/mL, and belatacept-based regimens in high-risk patients), structured lifestyle interventions, and emerging pharmacotherapies-particularly SGLT2 inhibitors and GLP-1 receptor agonists-which offer cardiometabolic benefits beyond glycemic control. Microbiome-targeted strategies, including prebiotics, probiotics, and fecal microbiota transplantation, represent a conceptually compelling frontier warranting prospective investigation. This framework reframes PTDM as a multi-hit, immunometabolic syndrome and provides a translational roadmap toward precision prevention and improved long-term transplant outcomes.},
}

Humans
*Kidney Transplantation/adverse effects
Risk Factors
*Postoperative Complications/etiology/therapy
*Diabetes Mellitus/etiology/therapy
Gastrointestinal Microbiome
Immunosuppressive Agents/adverse effects

@article {pmid42131202,
year = {2026},
author = {Sivamaruthi, BS and Kesika, P and Chaiyasut, C and Ragu Varman, D},
title = {Microbiome driven modulation of neurotransmitters: implications for neurotransmission and mood disorders.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1750377},
pmid = {42131202},
issn = {1664-302X},
abstract = {The human gut microbiome has emerged as a crucial regulator of neurophysiological processes by engaging with the central nervous system (CNS) via the microbiota-gut-brain (MGB) axis. One of the most significant ways gut microorganisms influence brain functions is by altering the levels of neurotransmitters. A significant relationship exists between microbial activity and mood, behavior, and cognition. Gut microorganisms can make or break down bioactive substances like serotonin, dopamine, γ-aminobutyric acid (GABA), glutamate, acetylcholine, and histamine. These microbial modulations influence precursor availability, receptor sensitivity, synaptic signaling dynamics, and neuroimmune modulation, thereby indirectly shaping neurotransmission within central circuits. These neurochemical effects, particularly involving serotonergic, dopaminergic, GABAergic, and glutamatergic pathways, are mediated through microbial metabolites such as short-chain fatty acids (SCFAs), alterations in tryptophan metabolism, immune system activation, vagal nerve transmission, and the control of the hypothalamic-pituitary-adrenal (HPA) axis. Changes in the composition of the microbiome have been frequently linked to mood disorders, such as depression, anxiety, bipolar disorder, and schizophrenia. The current review integrates findings from preclinical and clinical studies on microbiome-related neurotransmitter modulation, emphasizing novel therapeutics such as probiotics, prebiotics, fecal microbiota transplantation, and dietary alterations. Unlike previous reviews that primarily focus on microbiome composition or therapeutic interventions such as probiotics and fecal microbiota transplantation, this review adopts a neurotransmitter-centered framework, integrating microbial regulation of serotonergic, dopaminergic, GABAergic, glutamatergic, cholinergic, and histaminergic systems with the pathophysiology of mood disorders. Connecting microbiota-driven modulation of neurochemistry to mental outcomes offers a promising adjunctive avenue for mood disorder management, pending rigorous mechanistic and clinical validation.},
}

@article {pmid42131305,
year = {2026},
author = {Toto, F and Cardile, S and Scanu, M and Marzano, V and Petito, V and Masi, L and Puca, P and Giorgio, V and Alterio, T and Diamanti, A and De Angelis, P and Lopetuso, LR and Scaldaferri, F and Putignani, L and Del Chierico, F},
title = {Ecological patterns of the gut mycobiome and microbiome in ulcerative colitis across life stages.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1769892},
pmid = {42131305},
issn = {2235-2988},
mesh = {Humans ; *Colitis, Ulcerative/microbiology/immunology ; *Mycobiome ; *Gastrointestinal Microbiome ; Adult ; Child ; Male ; Female ; *Fungi/classification/genetics/isolation & purification ; Bacteria/classification/genetics/isolation & purification ; Middle Aged ; Young Adult ; Adolescent ; Dysbiosis/microbiology ; Metagenome ; Child, Preschool ; Age Factors ; Aged ; Feces/microbiology ; },
abstract = {INTRODUCTION: Age-related variations in the gut microbial communities may influence immune regulation and inflammatory processes in inflammatory bowel diseases (IBD). However, distinguishing age effects from differences in clinical characteristics remains challenging.

METHODS: We investigated life-stage-associated patterns of the gut microbiome and mycobiome while accounting for clinical heterogeneity between paediatric and adult ulcerative colitis (UC) populations. We analysed 73 targeted metagenomes of bacteria and 69 targeted metagenomes of fungi from 26 paediatric and 47 adult patients with UC. Microbial diversity metrics and multivariate analyses were applied to evaluate community variation, and mucosal immune markers were assessed by ELISA. Clinical variables, including disease activity, duration, and treatment exposure, were considered when interpreting age-related microbial differences.

RESULTS: Fungal communities exhibited higher richness in adults and formed distinct age-related clusters in beta-diversity analyses, whereas bacterial composition remained largely comparable across age groups. Children were enriched in inflammation-associated fungi (Saccharomycetes, Aureobasidium, Cladosporium) and depleted in taxa commonly linked to gut health (Clavispora, Vishniacozyma, Betamyces). Stratification by life stage identified young adults as displaying the most pronounced dysbiosis, characterised by Basidiomycota/Ascomycota and Firmicutes/Bacteroidota ratios, and reduced Faecalibacterium prausnitzii abundance. Age-associated immune patterns were observed, with lysozyme levels increasing across life stages, correlating with sIgA, and positively associating with F. prausnitzii, although declining with increasing disease severity.

DISCUSSION: Age-related variation was more evident in fungal than bacterial communities, suggesting that host developmental and immunological factors contribute to mycobiome configuration beyond clinical imbalance alone. Together, these findings indicate that life stage is linked to ecological variation of the gut mycobiome and mucosal immune responses in UC, while bacterial communities appear primarily shaped by disease-related factors. The transition from childhood to adulthood may represent a critical window of host-fungal interaction relevant for age-tailored microbiome-based strategies.},
}

Humans
*Colitis, Ulcerative/microbiology/immunology
*Mycobiome
*Gastrointestinal Microbiome
Adult
Child
Male
Female
*Fungi/classification/genetics/isolation & purification
Bacteria/classification/genetics/isolation & purification
Middle Aged
Young Adult
Adolescent
Dysbiosis/microbiology
Metagenome
Child, Preschool
Age Factors
Aged
Feces/microbiology

@article {pmid42131376,
year = {2026},
author = {Prosty, C and Desormeau, B and Lee, TC and McDonald, EG},
title = {Diagnosis, treatment, and prophylaxis of Clostridioides difficile infections: A cross-sectional survey of Canadian clinicians.},
journal = {Journal of the Association of Medical Microbiology and Infectious Disease Canada = Journal officiel de l'Association pour la microbiologie medicale et l'infectiologie Canada},
volume = {11},
number = {1},
pages = {37-50},
pmid = {42131376},
issn = {2371-0888},
abstract = {BACKGROUND: A recent international survey of clinician practices in the management of Clostridioides difficile infections (CDIs) identified numerous areas of practice heterogeneity. The degree of practice variability within Canada is unknown.

METHODS: Data from Canadian participants of an international survey of clinician CDI practices were extracted. Practice alignment with the Association of Medical Microbiology and Infectious Disease (AMMI) Canada CDI treatment guidelines was assessed. CDI practices were compared across provinces using the Fisher exact test with a simulated P value.

RESULTS: A total of 112 responses were obtained from eight provinces. Vancomycin (85.3% for first episode), vancomycin pulse and taper (P-T) (61.8% and 32.4% for first and second recurrences, respectively), and fecal microbiota transplant (32.4% for third recurrence) were preferred treatment strategies. Practice alignment with the AMMI Canada CDI guidelines for the treatment of recurrences was low (range 23.5%-32.4%, depending on the recurrence number). With respect to secondary CDI prophylaxis during antibiotic reexposure, there were interprovincial differences in the perceived indication (P = .03), whether to prescribe at all (P < .001), and duration of prophylaxis (P = .004). There was significant clinician support (>50%) for randomized clinical trials testing treatment strategies for recurrent episodes and for secondary prophylaxis.

CONCLUSION: Despite the availability of national guidelines, we found significant heterogeneity in practice across Canada, often not aligned with guideline recommendations. These findings underscore the need for a platform trial comparing treatment strategies and a trial to establish the efficacy of secondary prophylaxis.},
}

@article {pmid42132238,
year = {2026},
author = {Roostaei, G and Riahi, T and Nikfar, S and Abdollahi, M},
title = {Harnessing the immune system in lung cancer: emerging role of the microbiome.},
journal = {Expert review of clinical immunology},
volume = {},
number = {},
pages = {},
doi = {10.1080/1744666X.2026.2661805},
pmid = {42132238},
issn = {1744-8409},
abstract = {INTRODUCTION: The microbiome has emerged as a critical regulator of tumor biology and immune response in lung cancer. Once considered sterile, the lung is now recognized to harbor a diverse microbiome that interacts with the gut - lung axis to shape inflammation, immune evasion, and therapeutic outcomes.

AREAS COVERED: This study reviews current evidence linking microbiome composition and function to lung cancer development and response to immune checkpoint inhibitors (ICIs). We explore mechanisms of microbial influence on host immunity, identify key taxa associated with treatment outcomes, and summarize therapeutic strategies such as fecal microbiota transplantation, probiotics, postbiotics, dietary changes, antibiotics, and engineered live biotherapeutics. The literature search was performed across multiple databases and sources, including PubMed, Scopus, Embase, and clinical trial registries, up to August 2025, focusing on both preclinical and clinical studies related to lung cancer, immunotherapy, and microbiome-targeted interventions.

EXPERT OPINION: Microbiome research is redefining precision oncology by presenting new biomarkers and therapeutic targets. Although early-phase trials show potential to improve ICI efficacy, implementation is limited by donor variability, methodological differences, and biosafety issues. Standardized protocols, mechanistic studies, and biomarker-driven patient selection will be crucial to incorporating microbiome modulation into routine lung cancer treatment.},
}

@article {pmid42116139,
year = {2026},
author = {Liaqat, A},
title = {A spotlight on the inflammatory role of uremic toxins in the dysbiosis-CKD axis: a review.},
journal = {Journal of inflammation (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12950-026-00505-w},
pmid = {42116139},
issn = {1476-9255},
abstract = {There is growing evidence that gut-derived metabolites activate specific signaling pathways that lead to renal inflammation and injury, suggesting that the gut-kidney axis plays a significant role in the inflammatory processes that underlie chronic kidney disease (CKD). Alterations in the gut microbiota in CKD patients known as dysbiosis increases the production of uremic toxins such as p-cresyl sulfate, indoxyl sulfate and Trimethylamine N-oxide. These toxins trigger pro-inflammatory signaling pathways in renal tubular cells by initiating a series of inflammatory events, such as immune dysregulation, oxidative stress, and endotoxemia. As a result, cytokines like TNF-α, IL-6, and IL-1β are expressed more frequently, creating a chronic inflammatory environment that increase kidney damage and the progression of CKD. Emerging therapeutic strategies that alter gut microbiota composition, such as prebiotics, probiotics, dietary fiber, and fecal microbiota transplantation, have demonstrated promise in decreasing the burden of inflammation-inducing toxins. As research reveals new linkages between microbial metabolites and inflammatory signaling in CKD, addressing uremic toxin-mediated inflammation could revolutionize disease management. Understanding these interrelated signaling systems provides a more detailed understanding of how gut microbes influence renal inflammation at the molecular level. The aim of this review is to investigate the underlying signaling pathways by which gut-renal dysbiosis induces inflammation in CKD. The review attempts to guide the development of targeted treatment approaches that can reduce the inflammatory load and slow the progression of CKD by examining the mechanisms in which gut-derived uremic toxins alter oxidative stress, immunological responses, and inflammatory cascades.},
}

@article {pmid42117718,
year = {2026},
author = {Hao, W and Stocker, N and Gaugler, B and Mohty, M and Malard, F},
title = {The Role of the Gut Microbiota in Allogeneic Hematopoietic Cell Transplantation.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.70360},
pmid = {42117718},
issn = {1096-8652},
abstract = {Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective treatment for patients with high-risk hematologic malignancies. Over the last decade, gut microbiota composition during allo-HCT has been associated with patients' outcomes. Treatment-related factors, in particular the use of broad-spectrum antibiotics and the conditioning regimen, frequently induce gut dysbiosis, which is associated with immune dysregulation, toxicity, and adverse outcomes, particularly after allo-HCT. Microbial metabolites further modulate immune responses and therapeutic efficacy. Emerging microbiota-targeted strategies-including antibiotic stewardship, nutritional interventions, probiotics, fecal microbiota transplantation, and postbiotics-show promise in reducing graft-versus-host disease, controlling inflammation, and improving treatment responses.},
}

@article {pmid42118793,
year = {2026},
author = {Kawashima, M and Aoki, T and Hamada, H and Watanabe, C and Oyanagi, E and Kono, T and Yamagata, T and West, NP and Yano, H},
title = {Continuous high-fat high-sugar diet overrides the therapeutic potential of fecal microbiota transplantation from exercised and/or inulin-conditioned donors in obese mice.},
journal = {PloS one},
volume = {21},
number = {5},
pages = {e0349286},
doi = {10.1371/journal.pone.0349286},
pmid = {42118793},
issn = {1932-6203},
mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Inulin/pharmacology/administration & dosage ; Male ; *Diet, High-Fat/adverse effects ; *Obesity/therapy/etiology/microbiology/metabolism ; Mice ; Gastrointestinal Microbiome/drug effects ; Mice, Inbred C57BL ; *Physical Conditioning, Animal ; Fatty Acids, Volatile/metabolism ; Mice, Obese ; Feces/microbiology ; },
abstract = {Fecal microbiota transplantation (FMT) is a promising therapeutic strategy for obesity and related metabolic disorders. Exercise and dietary fiber intake, such as inulin supplementation, have been shown to differentially modulate the gut microbiota and synergistically improve metabolic health. The present study aimed to investigate whether FMT from lean donor mice subjected to voluntary exercise and/or inulin supplementation could ameliorate metabolic dysfunction in high-fat high-sugar diet (HFHSD)-induced obese mice. Four-week-old male C57BL/6J mice were fed HFHSD throughout the experimental period and assigned to one of five groups: sham FMT, FMT from sedentary donors, from exercised donors, from inulin-supplemented donors, or from donors receiving both interventions. Following 12 weeks of obesity induction, mice were treated with antibiotics and then underwent a 4-week FMT protocol. Physical and metabolic parameters, gut microbial composition, and cecal short-chain fatty acid (SCFA) levels were examined in both donors and recipients. The results demonstrated that FMT from exercised and/or inulin-supplemented donors failed to improve obesity-related phenotypes or glucose intolerance in recipients. These outcomes were accompanied by only partial alterations in gut microbiota and SCFA profiles. Collectively, our findings suggest that persistent HFHSD exposure compromises the colonization and function of beneficial microbes, limiting the metabolic benefits of FMT. Successful application of FMT in severe obesity may require prior optimization of the host intestinal environment through dietary interventions or microbiome-targeted strategies.},
}

Animals
*Fecal Microbiota Transplantation/methods
*Inulin/pharmacology/administration & dosage
Male
*Diet, High-Fat/adverse effects
*Obesity/therapy/etiology/microbiology/metabolism
Mice
Gastrointestinal Microbiome/drug effects
Mice, Inbred C57BL
*Physical Conditioning, Animal
Fatty Acids, Volatile/metabolism
Mice, Obese
Feces/microbiology

@article {pmid42121529,
year = {2026},
author = {Lei, M and Xu, H and Jin, X and Chen, X and Chen, K and Yang, Z and Xie, Y and Li, D and Ao, M and Zhu, Y and Yu, L},
title = {Theabrownin from Dark Tea Attenuates Age-Related Cognitive Decline in Naturally Aged Mice by Modulating Gut Microbiota and Metabolites.},
journal = {Foods (Basel, Switzerland)},
volume = {15},
number = {9},
pages = {},
doi = {10.3390/foods15091587},
pmid = {42121529},
issn = {2304-8158},
support = {202505AF350038//Yunnan Academician (Expert) Workstation/ ; No. 32502186//Young Scientists Fund (Category C) of the National Natural Science Foundation of China/ ; 2023XCZX001//Fundamental Research Funds for the Central Universities/ ; },
abstract = {Dietary factors play an important role in cognitive health during aging. Dark tea has shown potential cognitive benefits, but its key bioactive component and underlying mechanisms remain unclear. In a naturally aged C57BL/6J mouse model, instant dark tea (IDT) samples with different fermentation degrees were evaluated together with behavioral outcomes using composition-effect relationship analysis. This analysis identified theabrownin (TB) as the component most strongly associated with improved cognitive performance. Compared with aged controls, TB increased Y-maze spontaneous alternation from 51.91% to 71.59% and reduced escape latency on day 5 of the Morris water maze from 44.84 s to 26.59 s. In contrast, the corresponding TB-depleted fraction produced no comparable cognitive improvement. TB also alleviated hippocampal injury and neuroinflammation. Antibiotic treatment abolished the cognitive benefits of TB, whereas fecal microbiota transplantation partially restored them. Multi-omics analyses suggested that TB treatment was associated with gut microbiota remodeling and increased serum acetate and 3-hydroxybutyrate; both metabolites partially recapitulated these benefits. Together, these findings show that TB attenuates age-related cognitive decline in naturally aged mice and suggest that modulation of gut microbiota and metabolites may contribute to this effect, supporting its potential as a functional food ingredient for healthy brain aging.},
}

@article {pmid42122957,
year = {2026},
author = {Terry, C and Hall, LA and Halle-Smith, J and Edwards, LA and Sivakumar, S and Chapple, I and Beggs, A and Iqbal, T and Roberts, KJ},
title = {Pancreatic Cancer in the Holobiont and Therapeutic Targets: A Review.},
journal = {Journal of clinical medicine},
volume = {15},
number = {9},
pages = {},
doi = {10.3390/jcm15093225},
pmid = {42122957},
issn = {2077-0383},
abstract = {Increasing evidence suggests pancreatic cancer develops within a host-microbe ecosystem in which microbial communities across anatomical niches interact with tumour biology, immune regulation, metabolism, and therapeutic response. This review examines pancreatic cancer through the lens of humans as holobionts, integrating evidence from the oral, gut, biliary, and intratumoural microbiomes. Epidemiological and sequencing studies demonstrate consistent microbial alterations across these niches in pancreatic cancer, including oral dysbiosis associated with periodontal pathogens, gut microbial shifts toward pro-inflammatory taxa, disease-specific biliary microbial signatures, and the presence of distinct intratumoural microbial communities. Mechanistic studies indicate that intestinal barrier disruption, microbial translocation, immune and metabolite signalling can influence tumour immune architecture, macrophage polarisation, T-cell infiltration, oncogenic signalling pathways, and chemotherapeutic metabolism, particularly inactivation by tumour-associated bacteria. Microbiome-driven shifts in immunometabolism can reprogramme immune-cell metabolic pathways, impairing effective T-cell activation, promoting tumour-supportive macrophage phenotypes. Emerging therapeutic strategies aim to modulate the microbiome-tumour axis, including dietary interventions, probiotics and immunonutrition, faecal microbiota transplantation, engineered microbial therapies, and microbiome-informed antibiotic strategies. While pre-clinical findings are compelling and early-phase clinical studies suggest feasibility, most evidence remains associative and heterogeneous across cohorts and methodologies. Understanding pancreatic cancer as a multi-site ecological system may help explain inter-patient variability in disease progression and treatment response. This could usher in a new era for therapeutic manipulation where future progress will depend on longitudinal, multi-omic, and interventional studies to determine whether microbiome-targeted strategies can produce clinically meaningful improvements in pancreatic cancer outcomes.},
}

@article {pmid42123931,
year = {2026},
author = {Maragno, P and Amoroso, C and Conforti, S and Michelon, M and Honcharyuk, I and Ciafardini, C and Noviello, D and Strati, F and Caprioli, F and Facciotti, F and Vecchi, M},
title = {The Assessment of Multidimensional Clinical, Biological and Patient-Reported Outcomes to Evaluate the Efficacy of Add-On Lactobacillus rhamnosus GG Supplementation in Mild Ulcerative Colitis: A Randomized Pilot Trial.},
journal = {Nutrients},
volume = {18},
number = {9},
pages = {},
doi = {10.3390/nu18091329},
pmid = {42123931},
issn = {2072-6643},
mesh = {Humans ; *Colitis, Ulcerative/therapy/drug therapy/microbiology ; Pilot Projects ; Female ; Male ; *Lacticaseibacillus rhamnosus ; Adult ; Double-Blind Method ; Middle Aged ; Mesalamine/therapeutic use/administration & dosage ; *Probiotics/administration & dosage/therapeutic use ; *Dietary Supplements ; Patient Reported Outcome Measures ; Quality of Life ; Gastrointestinal Microbiome/drug effects ; Treatment Outcome ; *Cholecalciferol/administration & dosage/therapeutic use ; Leukocyte L1 Antigen Complex/analysis ; Feces/chemistry/microbiology ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; },
abstract = {Background: Ulcerative colitis (UC) is a multifactorial disease characterized by aberrant mucosal immune activation in response to intestinal dysbiosis. Contemporary management strategies aim to target inflammation and microbiome alterations while reducing relapse risk. A multidimensional assessment integrating clinical, inflammatory, immune, and microbial endpoints may better capture therapeutic effects beyond symptom control. Aims: To evaluate whether supplementation with Lactobacillus rhamnosus GG co-formulated with vitamin D3 (Dicoflor IBD Immuno) as an adjunct to optimized mesalamine (5-ASA) is associated with coordinated changes across clinical and biological domains in mild-to-moderate UC, using a multidimensional assessment framework. Methods: This single-center, randomized, double-blind, placebo-controlled pilot trial was conducted at Fondazione Ca' Granda IRCCS Policlinico di Milano between May 2022 and May 2024. Thirty-six patients with mild-to-moderate UC receiving optimized 5-ASA were randomized to LGG+VitD3 (ALD3) or placebo (AP) for 4 weeks. Clinical activity, health-related quality of life (HRQoL), fecal calprotectin, peripheral immune cell subsets, and gut microbiota composition were assessed at baseline and week 4. Results: Both 5-ASA-LGG+VitD3 (ALD3)- and 5-ASA-placebo (AP)-treated patients showed significant improvement in clinical activity and HRQoL, without between-group differences. A higher proportion of clinical responders was observed in the ALD3 group, although this was not statistically significant. LGG+VitD3-supplemented patients showed reduced fecal calprotectin levels and increased frequencies of IL-22-producing CD4[+] T cells. Microbiome analysis revealed enrichment of short-chain fatty acid-producing taxa, including Coprococcus and Fusicatenibacter, in ALD3-treated patients. Conclusions: In patients with mild UC receiving optimized 5-ASA, LGG+VitD3 supplementation does not improve short-term clinical outcomes beyond placebo but is associated with favorable modulation of inflammatory, immune, and microbial parameters, supporting the relevance of multidimensional biological endpoints in adjunctive UC management.},
}

Humans
*Colitis, Ulcerative/therapy/drug therapy/microbiology
Pilot Projects
Female
Male
*Lacticaseibacillus rhamnosus
Adult
Double-Blind Method
Middle Aged
Mesalamine/therapeutic use/administration & dosage
*Probiotics/administration & dosage/therapeutic use
*Dietary Supplements
Patient Reported Outcome Measures
Quality of Life
Gastrointestinal Microbiome/drug effects
Treatment Outcome
*Cholecalciferol/administration & dosage/therapeutic use
Leukocyte L1 Antigen Complex/analysis
Feces/chemistry/microbiology
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use

@article {pmid42123938,
year = {2026},
author = {Chiang, CK and Lai, CL and Chiu, MH and Huang, CJ},
title = {The Gut-Lung Axis in Allergic Asthma: A Narrative Review of Microbial Dysbiosis, Immune Regulation, and Nutritional Modulation.},
journal = {Nutrients},
volume = {18},
number = {9},
pages = {},
doi = {10.3390/nu18091336},
pmid = {42123938},
issn = {2072-6643},
support = {CGH-MR-B-11316//Cathay General Hospital/ ; },
mesh = {Humans ; *Dysbiosis/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; *Asthma/immunology/microbiology ; *Lung/immunology/microbiology ; Animals ; Diet ; },
abstract = {Allergic asthma is a prevalent chronic inflammatory disease of the airways whose pathogenesis has traditionally been attributed to localized immune dysfunction within the lung. However, accumulating evidence from microbiome research supports a broader system-level perspective in which cross-organ interactions contribute to disease susceptibility and progression. In particular, the gut-lung axis has emerged as a key regulatory pathway linking intestinal microbial ecology, immune development, and respiratory health. This review synthesizes current epidemiological, mechanistic, and experimental evidence supporting the role of gut microbiota dysbiosis in allergic asthma. We examine how early-life environmental and nutritional exposures and gut microbiota establishment during critical developmental windows shape long-term immune tolerance and asthma susceptibility. We then summarize characteristic features of asthma-associated gut dysbiosis and discuss how microbial-derived metabolites, including short-chain fatty acids, tryptophan metabolites, pro-allergic lipid mediators such as 12,13-dihydroxy-9Z-octadecenoic acid, and bacterial-derived histamine, modulate distal airway immune responses through epigenetic, receptor-mediated, and immune trafficking mechanisms. Particular emphasis is placed on the role of diet as a key upstream regulator of gut microbiota composition and metabolic function. Finally, we evaluate experimental and translational studies targeting the gut-lung axis, including dietary modulation, microbiome-targeted interventions such as fecal microbiota transplantation, and emerging postbiotic approaches. Collectively, current evidence indicates that gut microbial composition and metabolic function are critical determinants of respiratory immune homeostasis. Targeting the gut-lung axis through nutrition- and microbiome-based strategies offers a promising avenue for the prevention and precision treatment of allergic asthma.},
}

Humans
*Dysbiosis/immunology/microbiology
*Gastrointestinal Microbiome/immunology
*Asthma/immunology/microbiology
*Lung/immunology/microbiology
Animals
Diet

@article {pmid42124058,
year = {2026},
author = {Quattrini, S and Galeazzi, T and Monachesi, C and Palpacelli, A and Catassi, G and Quatraccioni, C and Annulli, G and Di Sario, A and Cianfruglia, L and Orciani, M and Armeni, T and Faragalli, A and Gesuita, R and Lionetti, ME and Catassi, C and Gatti, S},
title = {The Oxidative Stress Imbalance in Children and Adults with IBD and Associated Factors.},
journal = {Nutrients},
volume = {18},
number = {9},
pages = {},
doi = {10.3390/nu18091458},
pmid = {42124058},
issn = {2072-6643},
support = {RF 2018-12366976//Italian Ministry of Health/ ; D-ECCO grant 2023//European Crohn's and Colitis Organisation/ ; },
mesh = {Humans ; *Oxidative Stress ; Male ; Female ; Adult ; Child ; *Inflammatory Bowel Diseases/blood/metabolism ; Adolescent ; Antioxidants/metabolism ; Biomarkers/blood ; Thiobarbituric Acid Reactive Substances/metabolism ; Middle Aged ; Young Adult ; Glutathione/blood ; Advanced Oxidation Protein Products/blood ; Reactive Oxygen Species/blood ; Case-Control Studies ; Age Factors ; },
abstract = {Background/Objectives: An imbalance in oxidative stress (OS) has been implicated in the pathogenesis of Inflammatory Bowel Disease (IBD). We compared OS status in IBD children and adults versus healthy controls by exploring variables impacting the OS disruption in IBD. Methods: Total antioxidant capacity (ferric-reducing ability of plasma (FRAP)), reactive species (ROS), oxidative products (advanced oxidation protein products (AOPPs) and thiobarbituric acid reactive substances (TBARSs)), and antioxidant defenses (glutathione, GSH and intracellular activity of the main antioxidant enzymes) were evaluated. Correlations between OS markers, clinical features, disease characteristics, and inflammatory indices were explored. Results: Eighty-two IBD patients (67.5% in clinical remission) and 73 healthy subjects were enrolled. IBD children showed significant FRAP reduction compared to controls and IBD adults (p < 0.0001), increased AOPPs and reduced GSH compared to controls (p < 0.0001 and p = 0.0011, respectively), higher total GSH (p = 0.020), and lower TBARSs (p = 0.023) compared to IBD adults. In the pediatric group, FRAP was significantly reduced in those with IBD and increased in older subjects and males, while AOPP levels were positively affected by increasing age. In the total IBD cohort, higher FRAP was associated with male gender, increasing age, overweight, and mesalazine therapy. The diagnosis of Ulcerative Colitis was associated with lower FRAP and AOPP levels compared to Crohn's disease. Increased fecal calprotectin significantly decreased the total antioxidant capacity. Conclusions: The antioxidant system shows significant differences in IBD compared to controls, particularly in the pediatric group. The observed pediatric-adult pattern may suggest age-related differences in oxidative balance, but these findings should be interpreted with caution, given the modest sample size. Clinical Trial Registration Number: NCT04513015.},
}

Humans
*Oxidative Stress
Male
Female
Adult
Child
*Inflammatory Bowel Diseases/blood/metabolism
Adolescent
Antioxidants/metabolism
Biomarkers/blood
Thiobarbituric Acid Reactive Substances/metabolism
Middle Aged
Young Adult
Glutathione/blood
Advanced Oxidation Protein Products/blood
Reactive Oxygen Species/blood
Case-Control Studies
Age Factors

@article {pmid42124415,
year = {2026},
author = {Wang, X and Sun, Y and Liu, M and He, Z and Cao, W and Liu, W},
title = {[Role of Gut Mycobiome in Lung Cancer Immunotherapy: Mechanisms, Challenges and Translational Prospects].},
journal = {Zhongguo fei ai za zhi = Chinese journal of lung cancer},
volume = {29},
number = {3},
pages = {200-207},
doi = {10.3779/j.issn.1009-3419.2026.101.07},
pmid = {42124415},
issn = {1999-6187},
mesh = {Humans ; *Lung Neoplasms/immunology/therapy/microbiology ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy ; *Mycobiome ; Animals ; Translational Research, Biomedical ; },
abstract = {Lung cancer is one of the most common malignancies with the highest morbidity and mortality worldwide. Immune checkpoint inhibitors (ICIs) have significantly improved the prognosis of patients with advanced lung cancer, but more than half of patients derive limited benefit. The gut microbiota can regulate tumor immunity and ICIs efficacy via the gut-lung axis. Although accounting for a small proportion, the gut mycobiome exerts key immunomodulatory effects, yet relevant research lags far behind that of bacteria. This review systematically summarizes the clinical association between the gut mycobiome and lung cancer, clarifies the potential mechanisms by which the mycobiome and its metabolites influence ICIs efficacy through immune regulation, metabolic modulation, and cross-kingdom interactions, and summarizes potential strategies including dietary intervention, fecal microbiota transplantation, and fungal targeting. It provides theoretical support for establishing mycobiome-based predictive models, developing precise interventions, and improving the efficacy of ICIs. .},
}

Humans
*Lung Neoplasms/immunology/therapy/microbiology
*Gastrointestinal Microbiome/immunology
*Immunotherapy
*Mycobiome
Animals
Translational Research, Biomedical

@article {pmid42125246,
year = {2026},
author = {Hjørne, AP and Moretti, CH and Greiner, TU and Procházková, N and Roager, HM and Mortensen, MS and Bäckhed, F and Licht, TR and Laursen, MF},
title = {Intestinal transit time phenotype is not transferred through gut microbiota transplantation.},
journal = {PeerJ},
volume = {14},
number = {},
pages = {e21064},
pmid = {42125246},
issn = {2167-8359},
mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; Female ; Mice ; Humans ; *Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; *Gastrointestinal Transit/physiology ; Phenotype ; Feces/microbiology ; Germ-Free Life ; },
abstract = {Intestinal transit time (TT) varies considerably between healthy individuals and affects gut microbiota composition and activity. Whether differences in the gut microbiota composition also affect the TT is not well elucidated. In this study, we conducted two animal experiments to explore causality between the gut microbiota and TT. In the first experiment, we transplanted two groups of female germ-free (GF) Swiss-Webster mice with fecal material from two healthy human donors with fast and slow TT phenotypes. Following transplantation with human feces, we observed a decrease in TT for both groups of GF recipient mice (from 300 min to 167 min, 95% CI: ±45; and from 369 vs 205 min, 95% CI: ±52) corresponding to reductions of approximately 45% in each group, supporting previous findings that the mere presence of a gut microbiota reduces TT. However, we found no differences in TT between the two recipient groups. In the second experiment, we transplanted two groups of female GF C57Bl/6J mice with cecal material from two different conventional C57Bl/6J mouse donor groups treated with the TT-increasing drug loperamide or a saline vehicle. Again, no differences in TT were observed between the two recipient groups. These findings indicate that either the transferred microbiota did not engraft effectively, or that gut microbiota composition itself is not the principal driver of inter-individual TT variation.},
}

*Gastrointestinal Microbiome/physiology
Animals
Female
Mice
Humans
*Fecal Microbiota Transplantation
Mice, Inbred C57BL
*Gastrointestinal Transit/physiology
Phenotype
Feces/microbiology
Germ-Free Life

@article {pmid42125443,
year = {2026},
author = {Guaraná, JB and de Freitas, SH and Lanchotte, C and Araki, J and Cruz, RJ and Galvão, FHF},
title = {Anorectal Transplantation: Current Overview and Translational Perspectives.},
journal = {Journal of the anus, rectum and colon},
volume = {10},
number = {2},
pages = {189-198},
pmid = {42125443},
issn = {2432-3853},
abstract = {Anorectal transplantation (ART) belongs to the emerging field of vascularized composite allotransplantation. Researchers have studied this procedure experimentally for over two decades as a strategy to restore anal function in patients with severe fecal incontinence and permanent colostomy. These conditions significantly impact the quality of life and pose a global public health issue. This narrative review provides a comprehensive analysis of anorectal transplantation research, covering experimental studies in animal models, and ex vivo investigations. It examines and compares different surgical techniques, considering both procedural effectiveness and functional recovery. These experiments indicate that ART can be successfully performed from a technical standpoint. Ex vivo studies demonstrate acceptable surgical times, and studies in animal models confirm graft viability and functional restoration. Future research should refine surgical techniques, investigate neural regeneration mechanisms, and develop immunosuppressive protocols to advance the field toward clinical application. ART holds the potential to completely change the treatment of severe anorectal dysfunction and permanent colostomy, offering a definitive solution to these irreversible conditions.},
}

@article {pmid42126928,
year = {2026},
author = {Song, J and He, J and Liang, Z},
title = {Sucralose Exposure During Pregnancy Elevates Gestational Diabetes Risk via Gut Microbiota-Metabolic Axis in Mice.},
journal = {Journal of diabetes research},
volume = {2026},
number = {1},
pages = {e8638903},
pmid = {42126928},
issn = {2314-6753},
support = {GZY-KJS-ZJ-2025-037//Joint TCM Science & Technology Projects of National Demonstration Zones/ ; ZDFY2022-4XB101//4 + X Clinical Research Project of Women's Hospital, School of Medicine, Zhejiang University/ ; 82571935//National Natural Science Foundation of China/ ; },
mesh = {Animals ; Pregnancy ; Female ; *Gastrointestinal Microbiome/drug effects ; *Diabetes, Gestational/metabolism/chemically induced/microbiology ; *Sucrose/analogs & derivatives/adverse effects ; Mice ; Dysbiosis/chemically induced ; *Prenatal Exposure Delayed Effects ; Feces/microbiology ; Mice, Inbred C57BL ; Blood Glucose/metabolism/drug effects ; *Sweetening Agents ; Insulin Resistance ; },
abstract = {Sucralose, a widely used nonnutritive artificial sweetener, has gained increasing popularity during pregnancy due to its low-calorie properties. The influence of sucralose on gestational diabetes mellitus (GDM) risk via alterations in gut microbiota composition is not yet well understood. This study sought to explore how gestational sucralose exposure influences GDM development in mice through gut microbiota dysbiosis, impaired intestinal barrier, and metabolic disorders. As an exploratory extension, we also preliminarily assessed early growth in offspring. In our experimental design, pregnant mice were administered sucralose solution to evaluate GDM incidence. Fecal samples were collected for 16S rRNA sequencing and untargeted metabolomic analysis. To establish causality, gut microbiota from sucralose-exposed pregnant mice was transplanted into control pregnant mice to assess subsequent GDM development and alterations in fecal 16S rRNA profiles. Additionally, we monitored postpartum glucose metabolism in sucralose-treated pregnant mice and tracked offspring body weight changes. Our results demonstrated that sucralose exposure significantly increased GDM incidence, accompanied by higher glucose levels and diminished insulin sensitivity. Furthermore, sucralose administration caused significant gut microbiota imbalance. It reduced beneficial taxa like Prevotellaceae UCG-001 and Lachnospiraceae UCG-001 while increasing the proinflammatory taxon Parasutterella. These changes strongly correlated with key fecal metabolites, including 5-aminopentanoic acid. Notably, maternal sucralose consumption during pregnancy also affected offspring body weight. These findings collectively indicate that gestational sucralose exposure elevates GDM risk in mice through the gut microbiota-metabolism axis, providing critical scientific evidence regarding the safety of low-calorie sweeteners in clinical applications during pregnancy.},
}

Animals
Pregnancy
Female
*Gastrointestinal Microbiome/drug effects
*Diabetes, Gestational/metabolism/chemically induced/microbiology
*Sucrose/analogs & derivatives/adverse effects
Mice
Dysbiosis/chemically induced
*Prenatal Exposure Delayed Effects
Feces/microbiology
Mice, Inbred C57BL
Blood Glucose/metabolism/drug effects
*Sweetening Agents
Insulin Resistance

@article {pmid42113681,
year = {2026},
author = {Wang, S and Yuan, X and Wang, T and Yang, M and Dong, P and Han, H},
title = {Mechanisms and Therapeutic Targeting of the GutMicrobiota-Immune-Brain Axis in Alzheimer's Disease.},
journal = {Immunological investigations},
volume = {},
number = {},
pages = {1-31},
doi = {10.1080/08820139.2026.2669375},
pmid = {42113681},
issn = {1532-4311},
abstract = {BACKGROUND: Alzheimer's disease (AD) is a highly prevalent neurodegenerative disease globally. The main pathological features of AD are amyloid-β (Aβ) deposition and tau hyperphosphorylation. Recent studies suggest that the gut microbiota-immunity-brain axis plays an important role in the onset and progression of AD. Gut microbiota dysbiosis may impair intestinal barrier integrity and promote the entry of pro-inflammatory mediators into the circulation. Pro-inflammatory signals in the bloodstream may further activate the central immune system, drive microglial polarization, and increase the release of inflammatory factors in the brain. The resulting neuroinflammatory cascade may aggravate Aβ accumulation, tau phosphorylation, and cognitive impairment, although this mechanism has not been conclusively established in humans.

METHODS AND RESULTS: Based on relevant literature on AD, gut microbiota, immunity, neuroinflammation, and the gut-brain axis, this article systematically reviews the mechanism of action of the microbiota-immunity-brain axis in AD. Current intervention strategies targeting this axis, including probiotics, fecal microbiota transplantation, dietary interventions, and traditional Chinese medicine, were also discussed. Such intervention measures have the potential to regulate the balance of the gut microbiota, reduce neuroinflammation, and slow the progression of AD pathology.

CONCLUSION: It is essential to integrate multi-omics approaches in future research to deepen the understanding of AD pathogenesis and support the development of more precise and personalized treatment strategies.},
}

@article {pmid42114686,
year = {2026},
author = {Liu, J and Bai, Y and Feng, Y and Shao, X and Ma, H and Yan, X and Ye, Y and Wei, S and Lai, J and Yan, P},
title = {Gut microbiota and SCFA dysregulation drive MDPV-induced behavioral and neuroimmune adaptations in male mice.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106800},
doi = {10.1016/j.bbi.2026.106800},
pmid = {42114686},
issn = {1090-2139},
abstract = {BACKGROUND: 3,4-methylenedioxypyrovalerone (MDPV), a synthetic cathinone-derived novel psychoactive substance, exhibits potent stimulant effects and high abuse potential. However, the neurobiological mechanisms underlying MDPV dependence, particularly those involving the gut microbiota, remain unclear.

METHODS: Male C57BL/6 mice were used to establish an MDPV-induced behavioral sensitization model. Gut microbiota composition and short-chain fatty acids (SCFAs) were analyzed by 16S rRNA sequencing and metabolomics. Antibiotics and fecal microbiota transplantation (FMT) were employed to manipulate microbiota, while valeric acid supplementation was used to assess functional effects. Microglial activation and inflammatory cytokines in the VTA were evaluated.

RESULTS: Repeated MDPV administration (1 mg/kg) induced robust behavioral sensitization, accompanied by alterations in gut microbiota and SCFA profiles. Antibiotic-induced microbiota depletion abolished sensitization. FMT from control donors attenuated sensitization, whereas FMT from MDPV-treated donors restored it in antibiotic-treated mice. Valeric acid was significantly associated with behavioral outcomes, and its supplementation mitigated sensitization, reduced microglial activation in the VTA, and decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α).

CONCLUSIONS: Gut microbiota and their metabolites, particularly valeric acid, regulate MDPV-induced behavioral sensitization by modulating neuroinflammation and microglial activation. Targeting microbiota-SCFA signaling may offer a potential therapeutic strategy for MDPV -induced neurobehavioral effects.},
}

@article {pmid42115187,
year = {2026},
author = {Zhang, J and Chen, F and Xu, X and Zhang, L and Zhang, L and Qin, B and Li, K and Liu, Q and Hou, H and Li, Y and Liu, C and Li, Y and Shi, J and Teng, T and Wang, C and Zhou, X},
title = {Gut microbiota dysbiosis drives depression-like behavior in adolescent rats via lysine-regulated mTOR autophagy pathway.},
journal = {Translational psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41398-026-04095-2},
pmid = {42115187},
issn = {2158-3188},
abstract = {The prevalence of major depressive disorder (MDD) is increasing globally, particularly among adolescents. Although gut-brain axis dysfunction has been implicated in adolescent depression, the mechanisms by which gut microbiota dysbiosis drives depressive behaviors and potential antidepressant targets remain unclear. In this study, fecal microbiota transplantation (FMT) was performed from either healthy controls (HCs) or adolescents with MDD into antibiotic-treated adolescent rats. FMT from MDD adolescents induced depressive-like behaviors in recipient rats. Metagenomic sequencing revealed that FMT from MDD adolescents led to alterations in gut microbiota in recipient rats. While qPCR, Western blotting, immunofluorescence, and transmission electron microscopy (TEM) confirmed that these rats exhibited prefrontal cortex (PFC) autophagy hyperactivation, evidenced by a reduction in SQSTM1/p62 levels, an elevation in the LC3-II/LC3-I ratio, upregulated Beclin1, and increased numbers of autolysosomes. Similar autophagy-related transcriptional changes were observed in peripheral blood from MDD adolescents. Furthermore, ELISA showed reduced plasma lysine levels in MDD adolescents and decreased lysine concentrations in the PFC of FMT-MDD rats. The antidepressant effect of lysine and its interaction with autophagy were explored in a chronic unpredictable mild stress (CUMS) rat model with or without rapamycin (the autophagy activator, RAPA). Lysine supplementation alleviated depressive-like behaviors and suppressed PFC autophagy hyperactivation, while these effects were abolished by RAPA co-treatment. These findings reveal lysine deficiency as a metabolic bridge between gut microbiota imbalance and neuronal autophagy dysregulation, suggesting a gut microbiota-lysine-autophagy axis as an innovative mechanism and therapeutic focus for adolescent depression.},
}

@article {pmid42105281,
year = {2026},
author = {Zhao, Z and Shi, R and Ye, J and Wang, D and Zhao, B and Ren, B and Wang, L and Liu, X and Liu, X},
title = {Gut microbiota-regulated glutathione metabolic rhythms restore obesity-induced colonic inflammatory oscillations.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2670048},
doi = {10.1080/19490976.2026.2670048},
pmid = {42105281},
issn = {1949-0984},
mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; *Glutathione/metabolism ; *Obesity/microbiology/metabolism/complications ; Diet, High-Fat/adverse effects ; Circadian Rhythm ; Colon/microbiology/metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Male ; Fecal Microbiota Transplantation ; Inflammation ; *Colitis/microbiology/metabolism ; Oligosaccharides ; },
abstract = {Obesity disrupts circadian inflammatory rhythms, a defining feature of metabolic syndrome. However, the mechanisms connecting microbial and host circadian communication remain unclear. By using the fermentable fiber fructo-oligosaccharide (FOS) to restore microbial rhythmicity, we found that a high-fat diet (HFD) disrupts microbiota-regulated oscillations in glutathione metabolism, thereby dampening colonic inflammatory rhythms independently of the core clock machinery. Fecal microbiota transplantation (FMT) further supported a causal role for rhythmic fecal microbial signals in restoring inflammatory oscillations. Integrated multi-omics analysis highlighted circadian glutathione metabolism as a prominent candidate pathway linking microbial rhythmicity to host inflammatory oscillations. Importantly, colon-specific knockdown of Gclc, the rate-limiting enzyme in glutathione synthesis, abolished the restorative effects of microbial rhythms, functionally positioning host glutathione metabolism as a critical downstream mediator. Collectively, our study supports the existence of a microbiota-glutathione axis that contributes to the regulation of colonic inflammatory rhythms, uncovering a new chronobiological layer of microbial control over host inflammation.},
}

*Gastrointestinal Microbiome/physiology
Animals
*Glutathione/metabolism
*Obesity/microbiology/metabolism/complications
Diet, High-Fat/adverse effects
Circadian Rhythm
Colon/microbiology/metabolism/pathology
Mice
Mice, Inbred C57BL
Male
Fecal Microbiota Transplantation
Inflammation
*Colitis/microbiology/metabolism
Oligosaccharides

@article {pmid42106371,
year = {2026},
author = {Shi, X and Hu, Y and Wang, C and Hua, G and Liu, S},
title = {Gut microbiota and their role in male reproductive health.},
journal = {NPJ science of food},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41538-026-00845-0},
pmid = {42106371},
issn = {2396-8370},
support = {No. 2023YFD1300604)//the National Key R&D Program of China/ ; },
abstract = {The gut microbiota, as the "second genome" of the human body, plays a central regulatory role in maintaining host physiological homeostasis; conversely, its dysbiosis can impair male reproductive function via the "gut-testis axis", leading to a series of pathological manifestations such as abnormal semen quality, sexual dysfunction, and reproductive organ damage. Gut microbiota exerts multidirectional effects on host metabolism, immunity, endocrinology, and the neural system, collectively forming a complex regulatory network for male reproduction. Among these, microbiota-derived metabolites such as short-chain fatty acids (SCFAs), serotonin (5-HT), and secondary bile acids, function as systemic signaling molecules that exert direct and indirect effects on the testis through blood circulation and modulation of gut barrier integrity, regulation of systemic inflammation, epigenetic reprogramming, respectively. The potential and limitations of microbiota-targeted intervention strategies, including probiotics, prebiotics, synbiotics, traditional natural herbal extracts, and fecal microbiota transplantation (FMT), are also discussed. Finally, we propose that future interventions should be tailored to individual gut microbiota profiles to achieve precise regulation of male reproductive function. This review aims to provide a new systems biology perspective for understanding the complex etiology of male infertility and to lay a theoretical foundation for the development of innovative microbiome-based diagnostic tools and therapeutic strategies.},
}

@article {pmid42107896,
year = {2026},
author = {Zheng, W and Xu, Q and Ren, M and Wang, Z and Wang, M and Gao, Y and Zhang, J and Zhang, M and Chen, Y},
title = {Polysaccharide from Armillariella tabescens mycelia alleviates lipopolysaccharide-induced neuroinflammation via regulating the microbiota-gut-brain axis.},
journal = {International immunopharmacology},
volume = {182},
number = {},
pages = {116814},
doi = {10.1016/j.intimp.2026.116814},
pmid = {42107896},
issn = {1878-1705},
abstract = {Neuroinflammation is a prevalent pathological characteristic of numerous neurodegenerative disorders. Inhibition of neuroinflammation can slow the progression of these diseases. Armillariella tabescens is a valuable medicinal fungus that is often used in traditional Chinese medicine to treat acute and chronic hepatitis, appendicitis, otitis media and cholecystitis. Its mycelium polysaccharide (ATMP) has excellent biological activities, including anti-inflammatory, antioxidation and anti-aging. However, the mechanism of ATMP against neuroinflammation has not been elucidated. This study aimed to investigate the intervention effects of ATMP on lipopolysaccharide (LPS)-induced neuroinflammation and to elucidate the underlying mechanisms. The neuroprotective effects of ATMP were evaluated by behavioral tests, histological analysis of brain and colon tissues, and quantification of relevant inflammatory biomarkers. Gut microbiota composition and metabolic changes were assessed by 16S rRNA gene sequencing and serum non-targeted metabolomics. Fecal microbiota transplantation (FMT) was used to confirm gut microbiota-dependent effects of ATMP. Additionally, real-time quantitative PCR was performed to determine the expression of genes in related metabolic pathways. The results demonstrated that ATMP significantly alleviated LPS-induced cognitive impairment, inhibited brain inflammation and neuronal damage, attenuated intestinal inflammation and repaired the intestinal barrier function. Its neuroprotective effect was mediated via the microbiota-gut-brain axis (MGBA) by regulating gut microbiota composition and modulating amino acid and fatty acid metabolites, particularly balancing linoleic acid (LA) and arachidonic acid (AA) metabolic pathways. This work provides new mechanistic insights into the protective effect of ATMP against neuroinflammation and highlights its potential as an MGBA-mediated intervention strategy.},
}

@article {pmid42109273,
year = {2026},
author = {Lorentsen, RD and Borup, C and Poulsen, A and Jørgensen, EM and Rohde, U and Hansen, SH and Rainteau, D and Lamazière, A and Munck, LK},
title = {Prevalence of Bile Acid Diarrhea and Effect of Budesonide on the Bile Acid Homeostasis in Flare of Microscopic Colitis.},
journal = {Gastro hep advances},
volume = {5},
number = {6},
pages = {100954},
pmid = {42109273},
issn = {2772-5723},
abstract = {BACKGROUND AND AIMS: Microscopic colitis (MC) and bile acid diarrhea (BAD) are common causes of chronic watery diarrhea. Retrospective studies suggest that BAD coexists in a subset of patients with MC, but the interplay and therapeutic implications remain unclear. We aimed to determine the prevalence of BAD in patients with an MC flare using biochemical markers, to assess the effects of budesonide on BAD biomarkers, and to correlate with clinical outcomes.

METHODS: In this prospective multicenter study conducted at 3 Danish secondary care outpatient clinics, 49 patients with an MC flare were treated with budesonide for 6 weeks. 7α-hydroxy-4-cholesten-3-one (C4) levels ≥46 ng/mL defined BAD. C4 allows timely testing but has 47% sensitivity. Fecal bile acids (BAs) and fibroblast growth factor 19, stool habits, and quality of life were evaluated.

RESULTS: BAD was diagnosed in 6 (12%; 95% confidence interval, 5%-25%) of 49 patients (C4 range 47-92 ng/mL). Three patients had a gray zone C4 between 33 and 46 ng/mL. Patients with BAD had lower fibroblast growth factor 19 and high levels of primary and total BA in spot stool samples. Budesonide significantly reduced diarrhea and improved health-related quality of life in all patients. In patients with BAD, budesonide normalized stool BA, but C4 levels remained elevated.

CONCLUSION: These data demonstrate that some patients with MC flare have BAD. In patients with MC and BAD, budesonide reduced diarrhea symptoms and normalized stool BA levels but did not improve an underlying dysregulation of BA homeostasis. Clinicians may consider testing for BAD in patients with recurrent MC. Trials on therapies targeting BAD in MC patients are warranted.},
}

@article {pmid42110505,
year = {2026},
author = {Li, J and Zhang, H and Zhang, P and Hu, J},
title = {Potential Benefits of Gut Microbiota Modulation in Chronic Obstructive Pulmonary Disease.},
journal = {International journal of chronic obstructive pulmonary disease},
volume = {21},
number = {},
pages = {594405},
pmid = {42110505},
issn = {1178-2005},
mesh = {*Gastrointestinal Microbiome/drug effects ; *Pulmonary Disease, Chronic Obstructive/microbiology/therapy/physiopathology/metabolism ; Animals ; Humans ; *Dysbiosis/therapy ; Disease Models, Animal ; *Lung/physiopathology/microbiology/metabolism/pathology ; *Fecal Microbiota Transplantation ; Male ; Mice, Inbred C57BL ; Metabolomics/methods ; Anti-Bacterial Agents ; Female ; *Bacteria/genetics/metabolism/drug effects/growth & development/classification ; Middle Aged ; Ribotyping ; Aged ; Case-Control Studies ; Mice ; RNA, Ribosomal, 16S/genetics ; T-Lymphocytes, Regulatory/immunology/metabolism ; },
abstract = {BACKGROUND: The gut-lung axis is increasingly recognized. This study aimed to find out whether and how the gut microbiome involved in the pathogenesis of chronic obstructive pulmonary disease (COPD).

METHODS: Gut microbiota was characterized via 16S rRNA gene sequencing in COPD patients and a smoking-induced mouse model. Gut dysbiosis was induced by antibiotic cocktail (ABX) and restored by fecal microbiota transplantation (FMT). Plasma metabolomics was conducted using liquid chromatography-mass spectrometry (LC-MS), and pathway analysis was performed with MetaboAnalyst 5.0. Differentially expressed genes were identified by RNA sequencing and functionally interpreted through gene set enrichment analysis (GSEA).

RESULTS: Both COPD patients and mice showed altered gut microbiota, characterized by a unique microbial composition and reduced diversity. ABX induced gut dysbiosis exacerbated pathological lung changes, impaired lung function, and promoted Treg cell exhaustion in COPD mice. Restoration of gut homeostasis via FMT attenuated these alterations. Higher plasma levels of acetylcholine (ACh) were observed in COPD mice, while the highest ACh levels were found in ABX treated COPD mice compared to controls. Notably, ACh levels correlated positively with genus Parasutterella, which was more abundant in COPD mice, and inversely with genera Candidatus Saccharimonas and Lactobacillus, which were predominant in control mice. Metabolomic pathways analysis revealed enrichment in unsaturated fatty acids biosynthesis and purine metabolism in COPD mice relative to controls.

CONCLUSION: These findings highlight the involvement of the gut microbiome in COPD development and suggest that maintaining gut homeostasis may represent a novel therapeutic strategy for COPD.},
}

*Gastrointestinal Microbiome/drug effects
*Pulmonary Disease, Chronic Obstructive/microbiology/therapy/physiopathology/metabolism
Animals
Humans
*Dysbiosis/therapy
Disease Models, Animal
*Lung/physiopathology/microbiology/metabolism/pathology
*Fecal Microbiota Transplantation
Male
Mice, Inbred C57BL
Metabolomics/methods
Anti-Bacterial Agents
Female
*Bacteria/genetics/metabolism/drug effects/growth & development/classification
Middle Aged
Ribotyping
Aged
Case-Control Studies
Mice
RNA, Ribosomal, 16S/genetics
T-Lymphocytes, Regulatory/immunology/metabolism

@article {pmid42111070,
year = {2026},
author = {Zurdo-López, M and Sagredo Del Rio, M and Cháfer Rudilla, M and Ibarra, A and Doncel-Pérez, E},
title = {Microbiota and Guillain-Barré syndrome: role of microbial metabolites, biomarkers, and emerging therapeutic strategies.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1815899},
pmid = {42111070},
issn = {1664-2295},
abstract = {Guillain-Barré syndrome (GBS) is an acute autoimmune polyradiculoneuropathy that follows infection and is characterized by immune-mediated demyelination or axonal injury of the peripheral nervous system. While established triggers such as Campylobacter jejuni are well recognized, increasing evidence implicates the gut microbiota as a key modulator of immune responses relevant to GBS pathogenesis. The intestinal microbiota produces a diverse array of bioactive metabolites, including short-chain fatty acids (SCFAs), tryptophan-derived indoles, and neurotransmitter-like molecules, which influence immune tolerance, gut barrier integrity, and neuroinflammatory signaling. SCFAs, particularly butyrate, exert anti-inflammatory effects and support epithelial and blood-nerve barrier function. Microbial tryptophan metabolites regulate astrocyte and microglial activity via aryl hydrocarbon receptor (AHR) signaling, thereby restraining central and peripheral neuroinflammation. In contrast, dysbiosis-associated metabolites such as lipopolysaccharide (LPS) may enhance systemic inflammation, disrupt immune tolerance, and promote autoantibody production through mechanisms including molecular mimicry. Studies suggest that specific microbial taxa and metabolite signatures may serve as diagnostic or prognostic biomarkers in GBS, offering insights into disease susceptibility and progression. Microbiota-targeted therapeutic strategies are emerging as promising adjuncts to immunotherapy. Probiotics and prebiotics may restore beneficial microbial communities and rebalance immunoregulatory metabolite production, while host-directed metabolic interventions such as creatine supplementation may further support mitochondrial function, immunometabolic homeostasis, and neuroprotection. Fecal microbiota transplantation (FMT), though still experimental in GBS, has shown benefit in related neuroinflammatory disorders by reestablishing eubiosis and dampening immune activation. Future studies integrating metagenomic, metabolomic, and immunologic profiling in well-characterized GBS cohorts are essential to validate these findings and advance personalized microbiota-based interventions.},
}

@article {pmid42111748,
year = {2026},
author = {Chowdhary, R and Goyal, MK and Arora, K and Sehgal, T and Dawer, P and Anirudh, FNU and Berinstein, J and Bishu, S and Matt-Amaral, L},
title = {Gut Microbiota and Extraintestinal Cancers: Mechanistic Insights and Microbiome-Targeted Interventions.},
journal = {JGH open : an open access journal of gastroenterology and hepatology},
volume = {10},
number = {},
pages = {e70409},
pmid = {42111748},
issn = {2397-9070},
abstract = {The gut microbiota is a dynamic community of bacteria, viruses, fungi, and archaea that plays a pivotal role in regulating host immunity, metabolism, and systemic homeostasis. Dysbiosis, characterized by an imbalance in the microbial composition, is being increasingly recognized as a contributor not only to gastrointestinal cancers but also to extraintestinal malignancies. Mechanistic studies highlight the gut-microbiota-cancer axis, where microbial metabolites such as bile acids, short-chain fatty acids (SCFAs), and tryptophan derivatives influence genetic, epigenetic, and immune pathways, influencing carcinogenesis. Germ-free models demonstrate that commensal signals are essential for CD4[+] and CD8[+] T-cell differentiation, IgA production, and anti-tumor immunity. Dysbiosis-induced immune dysregulation is believed to impair immune checkpoint inhibitor (ICI) efficacy, while specific taxa such as Bifidobacterium and Akkermansia have been shown to enhance therapeutic responses. Emerging evidence links gut microbiota to breast cancer via estrogen metabolism "estrobolome" to lung cancer through the gut-lung axis and modulation of ICI responses, to melanoma by shaping systemic T-cell function and immunotherapy outcomes, and to prostate cancer through androgen receptor signaling and microbial metabolite interactions. These findings underscore the systemic oncogenic and tumor-suppressive potential of microbial communities. Microbiome-targeted interventions, including fecal microbiota transplantation (FMT), defined live biotherapeutics, probiotics, prebiotics, dietary modulation, and postbiotic delivery, are being actively investigated to optimize cancer treatment. While early trials have demonstrated feasibility, variability between individuals and methodological challenges remain significant hurdles. Hence, understanding how gut microbes influence extraintestinal cancers could revolutionize diagnostics, risk prediction, and treatment strategies.},
}

@article {pmid42112133,
year = {2026},
author = {Liu, H and Zhang, R and Mao, Z and Zhang, H and Lu, J},
title = {The cardioprotective mechanism of total saponins from mountain cultivated ginseng against doxorubicin-induced heart failure: Insights from gut-heart axis modulation based on gut microbiota and fecal metabolomics.},
journal = {Journal of ginseng research},
volume = {50},
number = {3},
pages = {100983},
pmid = {42112133},
issn = {1226-8453},
abstract = {BACKGROUND: Mountain cultivated ginseng (MCG) has been reported to exert superior therapeutic efficacy in heart failure (HF) models, but the mechanism of total saponins from MCG (TSMCG) remains unclear.

METHODS: This study aimed to elucidate the mechanism of TSMCG protects against doxorubicin-induced HF through the gut-heart axis. The phytochemical profile of TSMCG was identified using UPLC/Q-TOF-MS. TSMCG (50 or 200 mg/kg) was administered to mice daily for one week before and after doxorubicin exposure. Cardiac function was evaluated via echocardiography, followed by blood biochemical and cardiac histological analyses. Metabolic profiles and gut microbiota composition were analyzed. Fecal microbiota transplantation experiments were employed for mechanistic validation.

RESULTS: TSMCG treatment significantly improved cardiac function in HF mice, as evidenced by increased ejection fraction. TSMCG markedly attenuated doxorubicin-induced myocardial injury (CK-MB, NT-proBNP, AST, LDH), oxidative stress (SOD, MDA, CAT, GSH), and cardiac fibrosis. TSMCG effectively regulated key metabolic pathways, particularly tryptophan and bile acid metabolism, and alleviated gut microbiota dysbiosis, particularly Parasutterella and Akkermansia, in HF mice. Close associations between differential microbiota and metabolites were observed. The cardioprotective effects of TSMCG were associated with fecal microbiota transplantation.

CONCLUSION: These findings elucidated the gut-heart axis-based mechanism by which TSMCG alleviated doxorubicin-induced HF and highlighted its potential as a candidate for HF intervention.},
}

@article {pmid42112348,
year = {2026},
author = {Hua, M and Luo, J and Li, P and Zhang, Y and Zhang, X and Wu, Y and Dong, H},
title = {The microbiota-systemic lupus erythematosus axis: mechanisms, diagnostics, and therapeutic frontiers.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1782828},
pmid = {42112348},
issn = {1664-3224},
mesh = {Humans ; *Lupus Erythematosus, Systemic/therapy/diagnosis/immunology/microbiology ; Dysbiosis/immunology ; Animals ; *Microbiota/immunology ; *Gastrointestinal Microbiome/immunology ; Autoimmunity ; },
abstract = {Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease in which host-microbiota crosstalk plays a pivotal role in immune dysregulation. Recent metagenomic studies have revealed that disease-specific dysbiosis--characterized by the expansion of pathobionts and depletion of immunoregulatory commensals--occurs across the gut, oral cavity, skin, and genital tract. Integrative multi-omics analyses have identified three mechanistic pathways linking microbial imbalance to autoimmunity: (1) microbial peptides trigger molecular mimicry and epitope spreading, activating autoreactive lymphocytes: (2) microbial metabolites disrupt redox homeostasis, impair epithelial barriers, and skew the AhR-mediated Th17/Treg balance; and (3) dysbiosis alters epigenetic regulation by inhibiting DNA methyltransferases, leading to hypomethylation of SLE-risk genes. Translational studies have shown that microbiome-targeted interventions, including probiotics, prebiotics, fecal microbiota transplantation, and even B cell-depleting chimeric antigen receptor T-cell (CAR-T) therapy, can restore microbial balance, reduce autoantibody levels, and modulate the gut-immune axis. Furthermore, microbial signatures are emerging as potential biomarkers for disease activity and treatment response. Despite this promise, challenges remain, such as the impact of immunosuppressants on the microbiota, spatial heterogeneity in host-microbe interactions, and limitations in causal inference. Looking forward, integrating single-cell metagenomics, microbiota-directed diets, and engineered microbial consortia may pave the way for personalized microbiome-based therapies. Reframing SLE as a "meta-organismal imbalance" positions microbial ecology at the forefront of precision medicine.},
}

Humans
*Lupus Erythematosus, Systemic/therapy/diagnosis/immunology/microbiology
Dysbiosis/immunology
Animals
*Microbiota/immunology
*Gastrointestinal Microbiome/immunology
Autoimmunity

@article {pmid42112377,
year = {2026},
author = {Tschang, MA and Deo-Campo Vuong, R and Eilers, B and Chac, D and Waalkes, A and Penewit, K and Easton, A and Schuessler, B and Daniels, R and Weil, AA and Salipante, SJ and Gibbons, SM and Schindler, AG},
title = {If you give a mouse a poopsicle: a novel fecal microbiota transplant method for exploring the role of the gut microbiome in stress-related outcomes in mice.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1816919},
pmid = {42112377},
issn = {1664-3224},
mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Mice ; Corticosterone/blood ; *Stress, Psychological/therapy/microbiology ; Male ; Feces/microbiology ; Disease Models, Animal ; Mice, Inbred C57BL ; Anxiety ; Behavior, Animal ; Stress, Physiological ; },
abstract = {BACKGROUND: The microbiome-gut-brain axis is a mediator of stress-related disorders. The number of preclinical studies exploring the potential causal mechanism of this connection using fecal microbiota transplantation (FMT) is growing. However, the most common method for delivering fecal transplants in rodent models is still oral gavage, which creates an adverse experience that may confound stress-related outcomes. Here, we establish an alternative methodology for FMT that decreases stress induced by traditional experimental procedures.

METHODS: We first used preference and anxiety behavior assays to identify antibiotic therapies having maximal tolerability and minimal anxiolytic properties. We then collected feces from donor mice and homogenized them with a microbe-stabilizing buffer to create a slurry, which was frozen into aliquots ("poopsicles") for subsequent FMT. Recipient mice voluntarily consumed the frozen aliquots, and blood was collected to compare corticosterone relative to that after delivery via traditional gavage.

RESULTS: Plasma corticosterone levels were found to be significantly lower in mice receiving frozen aliquots compared to oral gavage. Furthermore, relative to controls, microbial signatures of mice receiving FMT via frozen aliquots were more similar to those of the donors at one week following final FMT and were sustained for up to six weeks, as assessed by comparing Bray-Curtis beta diversity distances.

CONCLUSION: Together, these results establish antibiotic and FMT methods that minimize treatment-induced stress, while effectively transplanting fecal microbes between murine conspecifics.},
}

Animals
*Fecal Microbiota Transplantation/methods
*Gastrointestinal Microbiome
Mice
Corticosterone/blood
*Stress, Psychological/therapy/microbiology
Male
Feces/microbiology
Disease Models, Animal
Mice, Inbred C57BL
Anxiety
Behavior, Animal
Stress, Physiological

@article {pmid42112384,
year = {2026},
author = {Oyedokun, PA and Oyeleke, BT and Akanji, OO and Oyelaran, AO and O, KP and Akanbi, GB and Oyedokun, PO and Oyedokun, MD and Naomi, CC and Imoleayo, OO and Akhigbe, RE},
title = {The role of the microbiome in gynecological cancers: implications for diagnosis and treatment.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1718883},
pmid = {42112384},
issn = {1664-3224},
mesh = {Humans ; Female ; *Genital Neoplasms, Female/therapy/diagnosis/microbiology/etiology ; *Microbiota ; Dysbiosis ; Animals ; Tumor Microenvironment ; Fecal Microbiota Transplantation ; },
abstract = {Gynecological malignancies such as cancer of the cervix, ovary, endometrium, vulva, and vagina pose a severe global health burden. Although conventionally attributed to genetic mutation, hormonal imbalance, and chronic viral infection, including high-risk human papillomavirus, recent evidence suggests that the human microbiome plays a central role in their pathogenesis and development. This review summarizes existing evidence that microbial dysbiosis, specifically the depletion of beneficial Lactobacillus species and overrepresentation of anaerobic organisms such as Fusobacterium, Atopobium, and Sneathia, is implicated in carcinogenesis pathways. These include chronic inflammation, immune modulation, loss of epithelial barrier integrity, microbial metabolite toxicity, and estrogen metabolism by the estrobolome. Dysbiosis in the gut and reproductive tract has been associated with HPV persistence, tumor microenvironment remodeling, and immune surveillance/therapy resistance. Consequently, microbial signatures are being investigated as a potentially successful non-invasive biomarker for early diagnosis, prognosis, and monitoring of therapy in gynecological oncology. In addition, emergent microbiome-based therapies are being considered as potential adjunct therapies, including probiotics, prebiotics, dietary manipulation, vaginal microbiota transplantation, and fecal microbiota transplantation. This review connects the basic research microbiome research to translational and clinical practice, identifies associated limitations, and highlights how it may transform gynecological cancer prevention, detection, and treatment.},
}

Humans
Female
*Genital Neoplasms, Female/therapy/diagnosis/microbiology/etiology
*Microbiota
Dysbiosis
Animals
Tumor Microenvironment
Fecal Microbiota Transplantation

@article {pmid41947174,
year = {2026},
author = {Wu, L and Zhang, Y and Zhang, G and Feng, X and Zhu, W and Yang, H and Ji, X and Yin, M and Li, S and Li, Y and Shi, W and Cong, B},
title = {Microbiota-associated metabolite pantothenic acid enhances skeletal muscle contusion repair via epigenetic regulation of macrophage M2 polarization.},
journal = {Journal of translational medicine},
volume = {24},
number = {1},
pages = {},
pmid = {41947174},
issn = {1479-5876},
support = {82293651//Major Projects of the National Natural Science Foundation of China/ ; 82130055//Key Projects of the National Natural Science Foundation of China/ ; 253A5601D//Hebei Province Innovation Capability Improvement Project/ ; },
abstract = {BACKGROUND: The quality of skeletal muscle contusion repair hinges on the timely resolution of inflammation and the initiation of regeneration, processes in which M2 macrophage polarization plays a critical role. Nevertheless, the upstream signals that regulate this polarization—particularly specific instructions mediated via the “gut-muscle axis”—remain poorly defined.

METHODS: The study was conducted as follows. First, intestinal barrier integrity following skeletal muscle contusion was assessed using histochemical staining and molecular assays. To elucidate the role of the gut microbiota in skeletal muscle repair, dysbiosis models and fecal microbiota transplantation (FMT) were established. Key gut microbiota and metabolites were subsequently identified through 16S rDNA sequencing and untargeted metabolomics analysis of fecal and serum samples. Based on these findings, targeted metabolite intervention experiments were conducted to evaluate their effects on the repair process of skeletal muscle contusion. To delineate the role of macrophages in this context, macrophage depletion was achieved via administration of clodronate liposomes. The impact of the key metabolites on macrophage polarization was then tested both in vivo and in vitro and the subsequent effect of polarized macrophages on C2C12 myoblast differentiation was examined in co-culture system. Finally, we explored the underlying epigenetic mechanisms through which the important metabolites regulates macrophage polarization.

RESULTS: Here, we identify a gut microbiota-dependent pathway that facilitates skeletal muscle injury repair. We observed that gut microbiota dysbiosis following skeletal muscle contusion was accompanied by a marked enrichment of the microbial metabolite pantothenic acid (vitamin B5). Functional assays demonstrated that depletion of the gut microbiota severely compromised muscle repair, whereas exogenous supplementation with pantothenic acid significantly enhanced regeneration and attenuated fibrosis. Mechanistically, pantothenic acid exerted its beneficial effects not by acting directly on myocytes, but through remodeling the immune microenvironment. In cultured macrophages, pantothenic acid elevated intracellular acetyl-CoA levels, promoted histone H3 lysine 27 acetylation (H3K27ac) at the promoter of the M2-associated gene Arg1, and acted synergistically with IL-4 to drive macrophage polarization toward the M2 phenotype. This epigenetic regulation was validated in vivo by ChIP-qPCR on macrophages sorted from contused muscles of pantothenic acid-treated mice, confirming that the modification occurs within the muscle microenvironment. This shift in macrophage polarization subsequently promoted myoblast differentiation and maturation.

CONCLUSION: Collectively, our findings delineate a comprehensive mechanism whereby a gut microbiota-associated metabolite, pantothenic acid, epigenetically programs macrophage M2 polarization via a “metabolism-epigenetics” axis to accelerate skeletal muscle repair. This work provides a novel conceptual framework for therapeutic interventions targeting the gut-muscle axis.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-026-08087-0.},
}

@article {pmid42103164,
year = {2026},
author = {Cheng, C and Zheng, L and Bao, X and Wei, L and Jiang, H and Jiang, T},
title = {An integrated study of gut microbiota and serum metabolites in T2DM-ED rats after fecal microbiota transplantation.},
journal = {Free radical biology & medicine},
volume = {252},
number = {},
pages = {227-248},
doi = {10.1016/j.freeradbiomed.2026.05.012},
pmid = {42103164},
issn = {1873-4596},
abstract = {Erectile dysfunction (ED) is a highly prevalent and refractory complication of type 2 diabetes mellitus (T2DM), with penile cavernosal dysfunction, inflammation, apoptosis, and fibrosis as core pathological features. Here we identify gut microbiota dysbiosis and its downstream metabolite arachidonic acid (AA) as critical mediators of T2DM-associated erectile dysfunction (T2DM-ED) through a systemic gut-penis axis. Gut dysbiosis is sufficient to induce an ED phenotype, as demonstrated by fecal microbiota transplantation (FMT) from T2DM-ED rats into pseudo-germ-free recipients, which successfully transferred the erectile impairment with significantly decreased ICP/MAP ratios. Recipient rats showed impaired colonic barrier integrity, mucosal damage, goblet cell depletion, and downregulated tight junction proteins (Occludin, Claudin-4). Multi-omics integration of 16S rRNA sequencing and serum metabolomics identified AA as a key elevated metabolite that drives inflammatory signaling via the HIF-1α and NF-κB pathways. In penile corpus cavernosum tissue, ED-FMT rats displayed smooth muscle loss, fibrosis, increased apoptosis, and hyperactivation of the TLR4-MyD88-NF-κB-HIF-1α axis. In primary corpus cavernosum smooth muscle cells (CCSMCs), AA stimulation recapitulated pathological activation, including a pro-apoptotic shift in the Bax/Bcl-2 ratio, elevated Cleaved Caspase-3, reduced α-SMA, increased COX-2, stabilized HIF-1α, and excessive PGE2 production; these effects were abolished by pharmacological inhibition of NF-κB. Mechanistically, gut dysbiosis-induced systemic AA accumulation triggers inflammatory damage, apoptosis, and functional impairment in penile smooth muscle via the TLR4-MyD88-NF-κB/HIF-1α cascade. These findings define a gut-AA-NF-κB-penis axis that drives T2DM-ED pathogenesis, highlighting AA and its downstream signaling as promising therapeutic targets for diabetic erectile dysfunction.},
}

@article {pmid42103932,
year = {2026},
author = {Wang, F and Zeng, W and Zhang, Z and Li, N and Cui, Z and Bai, J and Yan, J and Zhang, Y and Miao, Y and Gu, L and Xiong, B},
title = {Gut microbiota-modulated glutamic acid rejuvenates the quality of oocytes deteriorated by advanced reproductive age.},
journal = {EMBO molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {42103932},
issn = {1757-4684},
support = {2023YFD1300502//MOST | National Key Research and Development Program of China (NKPs)/ ; BYSYSZKF2023029//State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital/ ; KYCX25_1007//Postgraduate Research & Practice Innovation Program of Jiangsu Province/ ; },
abstract = {The gut microbiota plays a vital role in maintaining the physiological function of host health and the pathogenesis of various diseases. However, its relationship with maternal age-associated decline in oocyte quality remains elusive. Here, we report that establishment of gut microbiota from young donors in aged mice by fecal microbiota transplantation (FMT) is an effective method to rejuvenate the quality of maternally aged oocytes. Specifically, young gut microbiota promoted the ovulation and maturation of aged oocytes, and inhibited occurrence of cytoplasm fragmentation and spindle/chromosome abnormalities, hence enhancing the oocyte quality and female fertility. By integrating metagenome and untargeted metabolome of intestinal digesta, as well as targeted metabolome of ovaries and micro-transcriptome of oocytes, we identified that Bacteroides_caecimuris-modulated glutamic acid levels mediated the restorative effects of young gut microbiota on the aged oocytes through strengthening the mitochondria function. In addition, we demonstrated that in vivo supplementation of glutamic acid also enhanced the quality of aged oocytes, and the improvement of oocyte quality by glutamic acid was conserved across species. Altogether, our findings highlight the importance of gut microbiota in the oocyte aging and provide potential improvement strategies for age-related decline in oocyte quality and female fertility.},
}

@article {pmid42104017,
year = {2026},
author = {Sun, Q and Gao, Y and Zheng, J and Liao, R and Jiang, H and Zhu, Z and Xie, M and Yu, Y and Zhu, Y and Li, W and Shangguan, W and Li, L and Shi, X and Yang, Q and Zeng, J and Wang, Z and Zhao, J and Cheng, B and Wu, P},
title = {Akkermansia muciniphila drives viscero-visceral crosstalk via 5-HT3aR-mediated sensitization of dichotomizing gut-bladder neurons.},
journal = {Experimental & molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {42104017},
issn = {2092-6413},
support = {82503289//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82570912, 82370782, 82173304//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2025M782052//China Postdoctoral Science Foundation/ ; },
abstract = {The comorbidity of overactive bladder (OAB) and irritable bowel syndrome (IBS) presents a major clinical challenge, with the underlying neural and microbial mechanisms of the gut-bladder axis poorly understood. Here we aimed to delineate the complete causal pathway from a specific gut microorganism to bladder dysfunction and validate it as a therapeutic target. We combined analysis of human OAB-IBS cohorts with a postinflammatory mouse model, integrating retrograde neuronal tracing, multiomics (16S rDNA and metabolomics), fecal microbiota transplantation, urodynamics, dorsal root ganglion (DRG) electrophysiology and pharmacological and/or surgical interventions. We first confirmed a direct anatomical link, identifying dichotomized DRG neurons co-innervating the colon and bladder. Patients with OAB-IBS and mice exhibited a shared gut dysbiosis characterized by Akkermansia muciniphila enrichment. This comorbidity occurred in the absence of local bladder inflammation or urinary colonization with A. muciniphila, confirming a functional, noninfectious mechanism. Fecal microbiota transplantation of A. muciniphila or patient microbiota causally exacerbated visceral hypersensitivity, the OAB phenotype and DRG hyperexcitability. Mechanistically, A. muciniphila enrichment shunted host tryptophan metabolism toward the serotonin (5-HT) pathway. The resulting excess 5-HT acted on specifically upregulated colonic 5-HT3a receptors to drive neuronal sensitization. Crucially, pharmacological blockade of the colonic 5-HT3a receptor or surgical severing of the mesenteric nerves reversed the bladder dysfunction and visceral hypersensitivity. Our findings delineate a novel pathway wherein A. muciniphila drives functional gut-bladder comorbidity by promoting a gut-derived serotonergic signal that sensitizes shared afferent neurons, establishing the gut-specific 5-HT3a receptor as a key, druggable therapeutic target.},
}

@article {pmid42097977,
year = {2026},
author = {Krifors, A and Larsson, T and Wångdahl, A and Stensvold, CR},
title = {Time to rethink Blastocystis in faecal microbiota transplantation.},
journal = {Trends in parasitology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.pt.2026.04.005},
pmid = {42097977},
issn = {1471-5007},
abstract = {Blastocystis commonly colonises the human gut, but its presence has traditionally led to the exclusion of faecal microbiota transplantation donors. Emerging evidence links it to greater microbial diversity and favourable metabolic profiles, while no harm is seen in immunocompetent recipients. Routine screening may be unnecessary, except for subtype-specific testing in immunocompromised patients.},
}

@article {pmid42098025,
year = {2026},
author = {Fukushima, H and Ishikawa, D and Nagahara, A},
title = {[Gut Microbiota Transplantation for Esophageal and Gastric Cancer].},
journal = {Gan to kagaku ryoho. Cancer & chemotherapy},
volume = {53},
number = {3},
pages = {175-181},
pmid = {42098025},
issn = {0385-0684},
mesh = {Humans ; *Gastrointestinal Microbiome ; *Stomach Neoplasms/therapy/microbiology/immunology ; *Esophageal Neoplasms/therapy/microbiology/immunology ; *Fecal Microbiota Transplantation ; },
abstract = {Immune checkpoint inhibitors(ICIs)have remarkably improved survival with durable response for patients with multiple cancer type. But, the accurate predictors of response and toxicity to immunotherapy are still unclear. In recent years, the human microbiota, specially the gut microbiota, has been attracting attention in various fields, and it is one of the topics in the field of oncology. The gut microbiome, which refers to the microorganisms and their genes, affects the host immunity both locally and systemically. Modulation of the gut microbiota alters the immune systems and affects the efficacy of ICI. Many clinical trials targeting the gut microbiota, such as fecal microbiota transplantation(FMT)and biotics intervention, are currently being conducted. In this review, we consider the evidence on the role of the microbiome in cancer patients and research began the impact of FMT on the efficacy of ICIs in cancer. ln the future, research on carcinogenesis mechanisms and advance cancer treatment focusing on the human microbiota will become in creakingly active.},
}

Humans
*Gastrointestinal Microbiome
*Stomach Neoplasms/therapy/microbiology/immunology
*Esophageal Neoplasms/therapy/microbiology/immunology
*Fecal Microbiota Transplantation

@article {pmid42098851,
year = {2026},
author = {Dong, J and Cao, Y and Chen, X and Xie, T and Zhang, X and Zhao, Q and Shi, C and Miao, Q and Xu, Z and Yan, L and Dong, L},
title = {Buyang Huanwu Decoction promotes neurorepair after spinal cord injury through a Lactobacillus johnsonii-indole-3-lactic acid-AhR-PI3K/Akt axis.},
journal = {Chinese medicine},
volume = {21},
number = {1},
pages = {},
pmid = {42098851},
issn = {1749-8546},
support = {YSJ2025009//Postgraduate Research & Practice Innovation Program of Yan'an University/ ; 22XYJ0002//Xi'an Innovation Capability Strong Foundation Plan - Medical Research Project/ ; 2025PT-01//Platform Construction Project of Shaanxi Province's Health and Wellness Scientific Research and Innovation Capacity Enhancement Program/ ; },
abstract = {BACKGROUND: Spinal cord injury (SCI) induces gut microbiota dysbiosis, which significantly affects recovery. Buyang Huanwu Decoction (BHD), a traditional Chinese medicine formula, has shown therapeutic effects on SCI. Although BHD is known to modulate gut microbiota, whether its benefits are mediated through the gut-spinal cord axis remains unclear.

METHODS: A rat SCI model was established. BHD was administered orally, and fecal microbiota transplantation (FMT) from BHD-treated rats (BHD-FMT) was performed to assess neuroprotective and gut-protective effects. Behavioral testing, histology, and immunofluorescence evaluated motor recovery, inflammation, and neuroregeneration. Gut microbiota profiling was performed using 16S rDNA sequencing and metagenomics, while targeted metabolomics quantified tryptophan metabolites. Transcriptomics validated key pathways, and a microbiota-metabolite-signaling network was constructed.

RESULTS: BHD significantly improved motor function, reduced spinal inflammation, and promoted neuronal survival and axonal regeneration. It restored gut function, reduced colonic inflammation, and enhanced ZO-1 and Occludin expression, which were further confirmed by FMT. BHD-FMT reshaped the gut microbiota and enriched Lactobacillus johnsonii, which correlated positively with recovery. Metabolomics showed increased tryptophan metabolites, including indole-3-lactic acid (ILA) and indole-3-propionic acid (IPA), with ILA strongly associated with functional improvement. Transcriptomic analysis and Western blot validation demonstrated that BHD-FMT activated the AhR-PI3K/Akt pathway, which was suppressed by an AhR antagonist.

CONCLUSION: BHD promotes neuroregeneration after SCI by reshaping gut microbiota and enhancing tryptophan metabolism, potentially exerting its effects through the L. johnsonii-ILA-AhR-PI3K/Akt network. These findings reveal a gut-spinal cord axis-mediated mechanism of BHD and highlight microecological targets for SCI therapy.},
}

@article {pmid42099129,
year = {2026},
author = {Occhiali, E and Renard, D and Molkhou, C and Kerdelhué, G and Clavier, T and Baulier, C and Achamrah, N},
title = {Systematic Review with Qualitative Synthesis of Gut Microbiota Alterations after Acute Brain Injury.},
journal = {Journal of neurotrauma},
volume = {},
number = {},
pages = {8977151261449708},
doi = {10.1177/08977151261449708},
pmid = {42099129},
issn = {1557-9042},
abstract = {Acute brain injury (ABI), traumatic or nontraumatic, profoundly disrupts the gut microbiota (GM). To provide intensive care physicians with a clearer understanding of this phenomenon, we conducted a systematic review with qualitative synthesis. Due to significant heterogeneity in study designs, populations, and outcomes, a meta-analysis was not feasible. Instead, findings were synthesized thematically, focusing on study types, microbiota metrics, and clinical associations. Across studies, ABI is consistently associated with reduced microbial diversity, a decline in the relative abundance of several species, and increased interindividual variability in GM composition. Notably, phyla, such as Pseudomonadota, Bacteroidota, and Verrucomicrobiota, are frequently enriched, whereas Bacillota tends to be depleted. These patterns of dysbiosis appear largely consistent regardless of ABI etiologies. Furthermore, GM alterations can occur within a few hours postinjury and often return to baseline levels within months. The review highlights the metabolic, immune, and neuronal disruptions induced by ABI, which may contribute to gastrointestinal dysfunction and negatively influence patient prognosis. Moreover, standard intensive care unit (ICU) therapies may exacerbate GM disturbances. Importantly, dysbiosis has been linked to adverse clinical outcomes (delayed recovery, increased mortality). Emerging therapeutic strategies (metabolite supplementation, fecal microbiota transplantation) have shown potential to modulate the GM and support postinjury recovery. However, the underlying mechanisms of ABI-related dysbiosis and its consequences remain incompletely understood. Future research should aim to clarify the pathophysiological drivers of GM disruption, explore the potential prognostic value of GM dynamics, and assess how ICU therapies influence GM evolution. Developing GM-targeted interventions may offer novel opportunities to modulate ABI-related complications and improve patient outcomes.},
}

@article {pmid42099164,
year = {2026},
author = {Nayak, RK and Mohapatra, SR and Sahoo, SK and Sahu, SK and Chowdhury, B and Banu, Z and Das, NR},
title = {Gut Microbiota Dysbiosis in Alzheimer's Disease and Possible Therapeutic Options.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050448298260303052535},
pmid = {42099164},
issn = {1875-5828},
abstract = {Human microbiota consists of trillions of microbial cells dominated by bacteria, which live in the human body, while the term microbiome refers to the collective genetic material of microorganisms. Among them, the gut microbiota has emerged as pivotal, producing its own metabolites, neurotransmitter precursors, and immune mediators that affect brain development and function. These signals function via the complex, bidirectional Gut-Brain Axis (GBA). This is a communication network that connects the gastrointestinal tract to the central nervous system. This axis plays an important role in the regulation of gastrointestinal homeostasis, neurodevelopment, emotional regulation, and cognitive processes. Increasing evidence suggests that microbial dysbiosis within the gastrointestinal tract is involved in the pathogenesis and progression of several neurological and neurodegenerative disorders, including mood disorders, schizophrenia, autism spectrum disorder, Alzheimer's Disease (AD), Parkinson's Disease (PD), and Huntington's Disease. These insights have opened new therapeutic possibilities, and multiple microbiota-targeted interventions, such as dietary modification, prebiotics, probiotics, postbiotics, psychobiotics, antibiotics, and Fecal Microbiota Transplantation (FMT), are now being explored for their therapeutic value, especially in Alzheimer's disease.},
}

@article {pmid42099577,
year = {2026},
author = {Penton, CR and Vadakattu, G},
title = {The root rhizosphere as a functional analog to the gut microbiome: Cases for microbial symbiosis and dysbiosis in parallel contexts.},
journal = {PNAS nexus},
volume = {5},
number = {5},
pages = {pgag132},
pmid = {42099577},
issn = {2752-6542},
abstract = {Microbiomes associated with both the human gut and plant root rhizosphere are essential for the maintenance of host health and function as holobionts where both the host and microbiome operate as an integrated unit. Though substantial differences exist in both host biology and environment, these systems share functional parallels: both are enriched by host-derived nutrients, undergo successional shifts during development, and maintain core microbiomes that are taxonomically variable yet functionally redundant. Central to both systems is the balance that is maintained where beneficial microbes regulate nutrient cycling, modulate host immune response, and suppress pathogens in the presence of biotic and abiotic influences that may serve to disrupt this equilibrium. When dysbiosis occurs, there is a disruption in the composition and/or function of the associated microbiome and a loss of beneficial functional guilds, which results in a reduction in host fitness. These shared dynamics underscore dysbiosis as a cross-kingdom pathology that may be treated with similar interventions. Probiotics and prebiotics mirror microbial inoculants and organic amendments; synbiotics incorporate both biotic and abiotic factors, while fecal and soil microbiome transplants represent parallel strategies to restore a beneficial microbiome. By framing dysbiosis within a "One Health" perspective and illustrating the connectedness between human and plant health, this review advocates for microbial stewardship as a unifying strategy to mitigate disease, enhance resilience, and ensure sustainable health across both systems.},
}

@article {pmid42099620,
year = {2026},
author = {Mo, M and Chen, L and Wang, Y and Lin, X and Li, H and Chen, B and Yuan, J and Tao, E},
title = {The gut-lung axis in childhood asthma: from early-life programming to microbiome-informed precision medicine-a narrative review.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1814901},
pmid = {42099620},
issn = {1664-3224},
mesh = {Humans ; *Asthma/microbiology/immunology/etiology/therapy ; *Gastrointestinal Microbiome/immunology ; Precision Medicine ; *Lung/immunology/microbiology ; Child ; Dysbiosis ; },
abstract = {The gut-lung axis links early-life microbial programming to long-term respiratory health, offering a pivotal framework for understanding childhood asthma pathogenesis. This review synthesizes current evidence on how disruptions in microbial-immune crosstalk during critical developmental windows shape asthma susceptibility. Perinatal determinants-including maternal diet, delivery mode, antibiotic exposure, and breastfeeding-establish gut microbial communities that educate the developing immune system. Distinguishing itself from recent reviews, this review offers three novel contributions: (i) an integrated multi-omics framework linking early-life microbial maturation trajectories to specific asthma endotypes; (ii) a systematic synthesis of the molecular mechanisms by which microbial metabolites-including short-chain fatty acids, tryptophan derivatives, and bile acids-orchestrate gut-lung immune crosstalk; and (iii) a clinically actionable precision medicine algorithm that translates multi-omics profiling into personalized risk prediction, endotype-driven therapy selection, and targeted preventive strategies. Dysbiosis, characterized by delayed microbial maturation and depletion of short-chain fatty acid-producing taxa, compromises epithelial barrier integrity and skews immune homeostasis toward pro-allergic type-2 responses. Microbial metabolites, particularly short-chain fatty acids (acetate, propionate, butyrate) and tryptophan derivatives (indole-3-lactic acid, indole-3-propionic acid), serve as key molecular mediators that regulate regulatory T cells differentiation, reinforce mucosal barriers, and modulate distal airway inflammation. Microbial signatures correlate with specific asthma endotypes, offering opportunities for patient stratification. We critically evaluate emerging microbiome-targeted interventions-including strain-specific probiotics, prebiotics, postbiotics, and fecal microbiota transplantation-highlighting both therapeutic promise and the need for rigorous, well-powered clinical trials. Integrating multi-omics microbial profiling with host genetics and clinical phenotyping holds potential for microbiome-informed precision medicine, enabling personalized risk prediction, endotype-driven therapy selection, and novel preventive strategies targeting the gut-lung axis from the earliest stages of life.},
}

Humans
*Asthma/microbiology/immunology/etiology/therapy
*Gastrointestinal Microbiome/immunology
Precision Medicine
*Lung/immunology/microbiology
Child
Dysbiosis

@article {pmid42100690,
year = {2026},
author = {Gao, Q and Xiong, M and Zhou, S and Lu, J and Ren, B and Peng, Q and Zeng, M and Song, H},
title = {Gut microbiota and uveitis: exploring novel mechanisms of inflammatory ocular diseases via the gut-eye axis.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1749111},
pmid = {42100690},
issn = {1664-302X},
abstract = {Uveitis is an inflammatory ocular condition that primarily affects young adults and is often associated with systemic and autoimmune disorders. This disease primarily affects intraocular structures such as the iris, ciliary body, and choroid. Clinically, it manifests through a series of symptoms, including eye redness, pain, and blurred vision, which significantly impact the quality of life for patients worldwide. Recently, the role of gut microbiota (GM) in the immune regulation and pathogenesis of inflammatory diseases has garnered significant scientific interest. This study aimed to investigate the potential association between GM and uveitis, with the objective of demonstrating novel mechanisms underlying inflammatory ocular diseases through the emerging concept of the "gut-eye axis." Current research suggests that gut dysbiosis may influence the immune status of distal organs via various pathways, including molecular mimicry, modulation by microbial metabolites, disruption of intestinal immune homeostasis, and compromise of the intestinal mucosal barrier. Building on these mechanisms, we further explored innovative therapeutic strategies targeting GM and its metabolites, including probiotics, prebiotics, antibiotics, immunomodulators, phage therapy, fecal microbiota transplantation, and dietary interventions. This review systematically examined the association between GM dysbiosis and uveitis pathogenesis, offering new insights and directions for future research in this emerging field and establishing a theoretical foundation for developing targeted therapies based on the modulation of the microbiome.},
}

@article {pmid42100955,
year = {2026},
author = {Alsheikh, ZSA and Qingsong, T and Qinjie, L and Youkun, C},
title = {Re-arming checkpoint blockade in MSS colorectal cancer: A precision-microbiome playbook from mechanisms to clinic.},
journal = {Turkish journal of surgery},
volume = {},
number = {},
pages = {},
doi = {10.47717/turkjsurg.2026.2025-8-3},
pmid = {42100955},
issn = {2564-6850},
abstract = {Immune checkpoint blockade transforms outcomes for the 15% of colorectal cancers (CRCs) with mismatch-repair deficiency; yet most tumours remain refractory. Beneficial gut microbes can change this. Akkermansia muciniphila, Bacteroides fragilis, and short-chain fatty acid producers prime dendritic cells to produce interleukin (IL)-12, polarise Th1 cells, and reinvigorate CD8[+] T-cells. Antibiotics, Western-style diets, and Fusobacterium nucleatum foster myeloid suppression and β-catenin- or IL-17-mediated signalling, which blunt checkpoint activity. Multi-omics analyses link biosynthetic genes for inosine, riboflavin, and folate to durable clinical benefit. Faecal microbiota transplantation from responders has produced objective regressions in otherwise refractory microsatellite-stable disease. This narrative review maps CRC-microbiota-immune crosstalk, evaluates biomarkers and interventions, and proposes a CRC-specific, three-tiered clinical algorithm. We outline standards for trial design and manufacturing processes to facilitate the translation of microbiota-guided therapy into routine practice.},
}

@article {pmid42101655,
year = {2026},
author = {Miwa, T and Hsu, CL and Shimizu, M and Bloom, PP and Schnabl, B},
title = {Covert hepatic encephalopathy as a multi-organ syndrome: the gut-liver-muscle-brain axis, diagnosis, treatment, and multidisciplinary care.},
journal = {Journal of gastroenterology},
volume = {},
number = {},
pages = {},
pmid = {42101655},
issn = {1435-5922},
support = {JP24K18908//Japan Society for the Promotion of Science/ ; },
abstract = {Covert hepatic encephalopathy (CHE) is a highly prevalent complication of liver cirrhosis. Despite the absence of overt symptoms, CHE is strongly associated with impaired quality-of-life, overt hepatic encephalopathy, and mortality. Over the past two decades, evidence regarding the pathophysiology, diagnosis, and treatment of CHE has accumulated considerably, and clinical guidelines recommend screening in patients with cirrhosis. Nevertheless, diagnostic and therapeutic algorithms have not been fully implemented in real-world practice, and many patients remain undiagnosed and untreated. Understanding the natural history of CHE is essential to improve cirrhosis care, as it provides a framework for appropriate screening, treatment decision-making, and patient counseling. CHE is a multi-organ syndrome with complex interactions between the liver, gut, skeletal muscle, kidneys, and brain, with impaired ammonia handling and systemic inflammation acting as central drivers of this organ crosstalk. Hyperammonemia induces astrocytic dysfunction, brain edema, and neuroinflammation, while systemic inflammation, oxidative stress, sarcopenia, gut dysbiosis, and altered microbial metabolites, including bile acids and short-chain fatty acids, further modulate disease expression. In this review, we summarize current understanding of CHE pathophysiology, diagnostic testing, including psychometric batteries and point-of-care tools, such as the Stroop test and animal naming test, and therapeutic options, ranging from lactulose and rifaximin to microbiome-targeted approaches, including fecal microbiota transplantation. We also highlight major challenges in CHE management, including limited implementation of testing, inadequate biomarkers, diagnostic difficulties in geriatric cirrhosis, and unmet needs in fall and driving risk management, and emphasize the importance of multidisciplinary team-based approaches to improve patient outcomes.},
}

@article {pmid42101707,
year = {2026},
author = {He, LJ and Zhang, SC and Cai, YC},
title = {The role of gut microbiota in thyroid cancer: from pathogenesis to diagnosis and treatment.},
journal = {Journal of endocrinological investigation},
volume = {},
number = {},
pages = {},
pmid = {42101707},
issn = {1720-8386},
support = {2024ZD0525600//National Major Science and Technology Projects of China/ ; },
abstract = {In recent years, the key role of the gut microbiota (GM) in the diagnosis, prognosis, and treatment of thyroid cancer (TC) has become increasingly clear. This review examines the complex interactions between gut dysbiosis and the occurrence and development of TC; focuses on changes in specific microbiotas that are directly related to tumor stage, lymph node metastasis, and drug resistance; and evaluates the potential of these microbiotas as novel biomarkers for treating TC. To elucidate the underlying molecular mechanisms, this review systematically evaluates the pathways through which the GM regulates the host immune response through metabolites (such as short-chain fatty acids and lipopolysaccharides) and reveals the core role of chronic inflammation in the formation of the microenvironment and the immune escape of TC. Furthermore, by exploring the effects of the microbiota on the hypothalamic-pituitary-thyroid axis and the peripheral thyroid hormone conversion, this review elucidates the profound role of the GM in the regulation of thyroid homeostasis. Based on this evidence, this review highlights the clinical applications of intervention strategies targeting the microbiota, including probiotics, dietary adjustments, and fecal microbiota transplantation, as adjuvant approaches for TC management.},
}

@article {pmid42101756,
year = {2026},
author = {Cai, S and Sun, C and Wu, Q and Yao, X},
title = {Saikosaponin D Attenuates Postherpetic Neuralgia and Reduces Inflammation by Regulating Gut Microbiota in a Rodent Model.},
journal = {Biochemical genetics},
volume = {},
number = {},
pages = {},
pmid = {42101756},
issn = {1573-4927},
support = {WZ24A20//Explore the improvement effect and immune mechanism of stellate ganglion block combined with Xiaochaihu decoction on post-herpetic neuralgia of the head and face based on the "intestinal flora-intestine-brain axis"/ ; WZ24A20//Explore the improvement effect and immune mechanism of stellate ganglion block combined with Xiaochaihu decoction on post-herpetic neuralgia of the head and face based on the "intestinal flora-intestine-brain axis"/ ; },
abstract = {Saikosaponin D (SSD) is a triterpenoid saponin derived from Bupleuri Radix and has therapeutic potential for the treatment of neuropathic pain. This study investigates the roles and underlying mechanisms of SSD in cellular and mouse models of resiniferatoxin (RTX)-induced postherpetic neuralgia (PHN). C57BL/6 mice were randomly assigned into four groups: control, RTX, RTX + vehicle, and RTX + SSD. Mechanical and thermal sensitivity were assessed to evaluate pain behaviors. Gut microbiota was depleted using antibiotic treatment, and fecal microbiota transplantation was used to restore gut flora in RTX-treated mice that received either vehicle or SSD. In vitro, RTX-stimulated human neuroblastoma SH-SY5Y cells were used as a cellular model of PHN. TRPA1 expression levels in mouse dorsal root ganglion and SH-SY5Y cells were measured by RT-qPCR and immunofluorescence staining. The levels of proinflammatory cytokines were evaluated in serum samples and SH-SY5Y cells via RT-qPCR or ELISA. Western blot was performed to assess protein levels of genes involved in TLR4/NF-κB and JAK/STAT3 pathways. Results showed that SSD attenuated RTX-induced neuralgia in mice. In both in vitro and in vivo models, SSD significantly reduced TRPA1 expression and proinflammatory cytokine levels. The protective effects of SSD against neuralgia were abolished following antibiotic-mediated gut microbiota depletion in mice. Fecal microbiota transplantation from SSD-treated mice alleviated RTX-induced neuralgia and inflammation in PHN model mice. Moreover, SSD reduced TLR4 protein level and reduced phosphorylation ratios of NF-κB p65, STAT3, and JAK in the lumbar spinal cord of RTX-treated mice and in SH-SY5Y cells. In conclusion, SSD alleviates RTX-induced PHN and inflammation in mice by modulating gut microbiota via the TLR4/NF-κB and JAK/STAT3 pathways.},
}

@article {pmid42102609,
year = {2026},
author = {Zeng, M and Feng, A and Zhang, B and Li, S and Guo, P and Zhu, D and Zhang, Y and Zhang, Z and Tie, Q and Wu, Y and Feng, W and Zheng, X},
title = {A novel triterpenoid from Alisma orientale alleviates allergic asthma through the gut microbiota-acetate-FFAR2 immunoregulatory axis.},
journal = {International immunopharmacology},
volume = {182},
number = {},
pages = {116809},
doi = {10.1016/j.intimp.2026.116809},
pmid = {42102609},
issn = {1878-1705},
abstract = {BACKGROUND: Allergic asthma is characterized by immune dysregulation and airway inflammation, and increasing evidence implicates gut microbiota-derived metabolites in its pathogenesis. However, the microbial and metabolic mediators underlying the anti-asthmatic effects of natural products remain insufficiently defined. This study investigated the protective effects of a novel triterpenoid (Tri) isolated from Alisma orientale against ovalbumin-induced allergic asthma and explored the underlying mechanisms.

METHODS: The therapeutic effects of Tri were evaluated in ovalbumin-induced allergic asthma mice by assessing airway hyperresponsiveness, histopathological changes, and inflammatory mediators. Gut microbiota depletion, fecal microbiota transplantation, 16S rDNA sequencing, targeted short-chain fatty acid analysis, and lung transcriptomic profiling were performed to characterize microbiota-associated changes related to Tri treatment. In addition, Lactobacillus murinus and acetate intervention experiments were conducted in vivo. A co-culture system of 16HBE cells and bone marrow-derived dendritic cells (BMDCs), together with free fatty acid receptor 2 (FFAR2) silencing or overexpression, was used to further assess the involvement of FFAR2 in the immunoregulatory actions associated with Tri.

RESULTS: Tri markedly attenuated airway hyperresponsiveness, inflammatory cell infiltration, collagen deposition, and the production of asthma-related inflammatory mediators in asthmatic mice. These protective effects were attenuated after gut microbiota depletion and were partially transferred by fecal microbiota transplantation. Tri restored gut microbial homeostasis, increased the abundance of Lactobacillus murinus, and elevated short-chain fatty acids, particularly acetate. Supplementation with Lactobacillus murinus or acetate reproduced the anti-asthmatic effects of Tri and was associated with upregulation of FFAR2 and restoration of the Th17/Treg balance. In the co-culture system, FFAR2 silencing or overexpression further supported the involvement of FFAR2 in the immunoregulatory effects of Tri and acetate.

CONCLUSION: Tri alleviates OVA-induced allergic asthma and is associated with microbiota-derived acetate, enhanced FFAR2-related signaling, and restoration of Th17/Treg balance. These findings suggest that microbiota-derived acetate and FFAR2-related immune regulation may contribute to the anti-asthmatic effects of Tri, although further loss-of-function studies are required to establish direct causality.},
}

@article {pmid42102900,
year = {2026},
author = {Hamerlinck, H and Boelens, J and De Looze, D and Messiaen, AS and Vandendriessche, S and Holvoet, T and Verhasselt, B},
title = {Seven years of stool banking: clinical and microbiological insights from the Ghent Stool Bank.},
journal = {International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases},
volume = {},
number = {},
pages = {108744},
doi = {10.1016/j.ijid.2026.108744},
pmid = {42102900},
issn = {1878-3511},
abstract = {OBJECTIVES: The Ghent Stool Bank (GSB) was founded in 2018 at Ghent University Hospital to provide safe, ready-to-use faecal suspensions for faecal microbiota transplantation (FMT), primarily targeting recurrent Clostridioides difficile infection (rCDI) and supporting clinical trials.

METHODS: This retrospective cohort study explores the relationship between donor characteristics and rCDI treatment outcomes following FMT.

RESULTS: Between 2018 and 2024, 12.0% of screened candidates qualified as donors after rigorous evaluation, resulting in 159 approved donations. Forty-four FMT procedures were carried out in forty rCDI patients, achieving a primary cure rate of 77.1%, which increased to 85.7% following a second treatment. Donor microbiome diversity did not show association with treatment outcomes, and no statistically significant differences in taxa abundance were observed. Notably, faecal suspensions stored for up to five years were as effective as those stored for shorter periods. Additionally higher donor age did not appear to negatively impact treatment success in rCDI patients.

CONCLUSION: These findings support the role of stool banks like the GSB in ensuring safe FMT procedures. Allowing higher donor age and longer storage periods may help sustain sufficient high‑quality donor availability. Future efforts should focus on improving safety, enhancing donor-recipient compatibility through microbiome profiling and increasing public awareness.},
}

@article {pmid41896437,
year = {2026},
author = {Jin, H and Zhou, W and Ying, R},
title = {Impact of ileostomy reversal on gut microbiome and metabolome in rectal cancer: a review of mechanisms and clinical consequences.},
journal = {Langenbeck's archives of surgery},
volume = {411},
number = {1},
pages = {},
pmid = {41896437},
issn = {1435-2451},
support = {2024S00023//the Social Development Science and Technology Project of Wenling City, Zhejiang Province/ ; },
abstract = {Prophylactic ileostomy is a critical measure for preventing anastomotic leakage after low rectal cancer surgery; however, the incidence of diarrhea following stoma reversal remains high, posing a major clinical challenge. Recent studies have revealed that the underlying pathophysiology involves not only anal sphincter dysfunction but also a comprehensive imbalance in the gut microbiota–metabolite–immune axis. This review systematically elucidates the dynamic evolution of the gut microbiome after stoma reversal and its interplay with host metabolism. It further delves into multidimensional pathophysiological mechanisms, including gut dysbiosis, reduced production of short-chain fatty acids, dysregulated bile acid metabolism, and impaired intestinal barrier integrity. In light of recent advances, this article analyzes the clinical characteristics and subtypes of postoperative diarrhea, summarizes precision diagnostic strategies based on multi-omics technologies, and provides an objective assessment of emerging therapies such as probiotics, fecal microbiota transplantation, metabolic interventions, and nutritional support. Finally, the necessity of establishing an integrated multidisciplinary management model is discussed, with the aim of offering new perspectives and a theoretical foundation for improving the quality of life in rectal cancer patients after surgery.},
}

@article {pmid42088511,
year = {2026},
author = {Smout, J and Lesker, TR and Hoenicke, L and Ortiz, D and Zou, M and Kruse, F and Pirr, S and Willers, M and Härtel, C and Falk, C and Torow, N and Viemann, D and Strowig, T and Huehn, J},
title = {Probiotic-conditioned microbiota from preterm infants modulate immune response to pathogen challenge in a microbiota-humanized mouse model.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1761680},
pmid = {42088511},
issn = {1664-3224},
mesh = {Animals ; *Probiotics/administration & dosage/pharmacology ; *Gastrointestinal Microbiome/immunology ; Mice ; *Infant, Premature/immunology ; Humans ; Female ; Infant, Newborn ; Disease Models, Animal ; Immunity, Innate ; Animals, Newborn ; *Escherichia coli Infections/immunology/microbiology ; Enteropathogenic Escherichia coli/immunology ; Feces/microbiology ; },
abstract = {Early-life host-microbe interactions critically shape immune development, lifelong homeostasis, and disease susceptibility. The PRIMAL trial (Priming Immunity at the Beginning of Life) demonstrated that multistrain probiotics shifted the gut microbiota of very preterm infants toward eubiosis without affecting sepsis incidence, yet the immunological consequences remained unresolved. To explore this, we colonized germ-free female mice with fecal samples from probiotic- or placebo-treated preterm infants from the PRIMAL trial. Microbiota composition was vertically transmitted and stable across generations. At steady-state, 3-week-old pups colonized with probiotic-conditioned microbiota exhibited markedly reduced populations of innate immune cells, particularly in the colon, with subtler effects in the small intestine and spleen, while adaptive immune subsets were less affected. Upon enteropathogenic Escherichia coli challenge at day 5, pups harboring probiotic-conditioned microbiota displayed reduced growth and impaired bacterial clearance, correlating with diminished numbers of key innate immune cell populations. These findings demonstrate that probiotic-driven shifts in human-derived microbial communities can attenuate immune cell development in mice and alter early-life infection outcomes. Our study underscores the complex, context-dependent effects of probiotics on the neonatal microbiota-immune axis and provides mechanistic insight into how interventions in preterm infants may influence susceptibility to infection.},
}

Animals
*Probiotics/administration & dosage/pharmacology
*Gastrointestinal Microbiome/immunology
Mice
*Infant, Premature/immunology
Humans
Female
Infant, Newborn
Disease Models, Animal
Immunity, Innate
Animals, Newborn
*Escherichia coli Infections/immunology/microbiology
Enteropathogenic Escherichia coli/immunology
Feces/microbiology

@article {pmid42088615,
year = {2026},
author = {Zhang, Z and Li, C and Tang, Y and Liu, B and Wang, J and Kong, L and Bao, W and Lai, H and Chen, T and Li, J},
title = {Indole-3-Carbaldehyde from Limosilactobacillus reuteri Boosts Chemotherapy Response in Diffuse Large B Cell Lymphoma by Blocking the Mechanistic Target of Rapamycin Pathway.},
journal = {Research (Washington, D.C.)},
volume = {9},
number = {},
pages = {1267},
pmid = {42088615},
issn = {2639-5274},
abstract = {Diffuse large B cell lymphoma (DLBCL) presents a critical clinical challenge due to declining chemosensitivity and difficult-to-manage dose-limiting toxicities. Although gut microbiota modulation shows potential for "toxicity reduction and efficacy enhancement", its mechanism in DLBCL remains unclear. Comparative analysis revealed a marked reduction of beneficial bacteria in patients with DLBCL versus healthy volunteers, with a marked decrease in the abundance of core probiotics, particularly Limosilactobacillus reuteri. Fecal microbiota transplantation from healthy donors into DLBCL mouse models reduced tumor burden, improved chemosensitivity, and alleviated intestinal toxicity. A core probiotic strain, L. reuteri HG001, was isolated and shown to replicate these effects alone, with the tryptophan metabolite indole-3-carbaldehyde (ICAld) identified as the key component responsible for its adjunctive antitumor activity. Mechanistic studies demonstrated that ICAld exerts significant adjunctive antitumor effects both in vitro and in vivo in a dose-dependent manner in mouse models; it acts by activating the aryl hydrocarbon receptor (AHR)/cytochrome P450 family 1 subfamily A member 1 (CYP1A1)/reactive oxygen species (ROS) axis, inhibiting the phosphatidylinositol 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) signaling pathway, promoting apoptosis, and synergizing with cyclophosphamide. An aryl hydrocarbon receptor antagonist reversed both the chemosensitizing and intestinal protective effects of L. reuteri HG001 and ICAld. This study elucidates a microbiota-mediated mechanism in DLBCL and supports L. reuteri HG001 as a probiotic adjuvant to enhance therapy while reducing toxicity.},
}

@article {pmid42090907,
year = {2026},
author = {Su, X and Li, A and Liu, J and Guo, Y and Yu, H and Yu, J and Wang, R and Garza, DR and Qu, J and Wen, B and Liu, B},
title = {From microbes to molecules: Gut microbiota as a prerequisite threshold determinant for cancer immunotherapy efficacy.},
journal = {Microbiological research},
volume = {309},
number = {},
pages = {128539},
doi = {10.1016/j.micres.2026.128539},
pmid = {42090907},
issn = {1618-0623},
abstract = {Cancer immunotherapy, represented by immune checkpoint inhibitors, adoptive cell therapy, and cancer vaccines, has revolutionized the clinical management of multiple malignant tumors, yet profound interindividual heterogeneity in treatment response and widespread primary/acquired resistance remain the most critical bottlenecks restricting its long-term clinical benefits. Accumulating preclinical and clinical evidence has unequivocally established the gut microbiota as a pivotal regulator of host anti-tumor immune responses. However, the vast majority of existing studies and reviews frame the gut microbiota as a mere adjuvant enhancer of immunotherapy efficacy, focusing solely on its role in boosting the upper limit of treatment effects, while neglecting its more fundamental role as a prerequisite for establishing a responsive immune baseline. In this review, we propose a unifying, evidence-based original core hypothesis: the gut microbiota is not merely an enhancer of cancer immunotherapy efficacy, but an indispensable prerequisite condition that sets the minimal baseline threshold for therapeutic responsiveness-a central thesis that distinguishes this review from previous descriptive work. Guided by this hypothesis, we systematically dissect the taxonomic and functional characteristics of threshold-determining gut microbiota, and clarify that microbial metabolites (e.g., short-chain fatty acids, bile acids, tryptophan derivatives) act as core molecular mediators translating microbial signals into host immune activation, which is critical for establishing the baseline efficacy threshold required for effective immunotherapy. We further perform a critical synthesis of clinical data from prospective cohorts, randomized controlled trials, and microbiota intervention studies, validating that threshold-based microbial signatures serve as non-invasive predictive biomarkers for immunotherapy outcomes, and propose mechanism-driven translational strategies targeting the gut microbiota (e.g., fecal microbiota transplantation, probiotic supplementation, dietary modulation) to reset the impaired immunotherapy efficacy threshold. This review provides a novel theoretical framework for understanding the microbiota-immunotherapy axis, which not only deepens the mechanistic insight into microbial metabolite-mediated immune regulation, but also facilitates the development of microbiota-guided personalized cancer immunotherapy and the overcoming of primary treatment resistance.},
}

@article {pmid42092466,
year = {2026},
author = {Gavini, CK and Raux, L and Labouèbe, G and Gornick, E and Mc Hugh, S and Elshareif, N and Calcutt, NA and Di Summa, PG and Gorostidi, F and Vonaesch, P and Mansuy-Aubert, V},
title = {A gut-adipose-nerve axis mediates inulin protection against Western diet-induced somatosensory dysfunction.},
journal = {Brain, behavior, and immunity},
volume = {137},
number = {},
pages = {106795},
doi = {10.1016/j.bbi.2026.106795},
pmid = {42092466},
issn = {1090-2139},
abstract = {Westernized diets (WDs)-high in fat and sugar and low in fiber-produce somatosensory deficits, chronic pain, and neuropathy, yet the mechanisms linking diet to peripheral nervous system (PNS) pathology remain incompletely defined. Emerging evidence implicates gut-derived metabolites in sensory homeostasis; for example, fecal microbiota transplantation (FMT) from lean donors to WD fed mice reduces hypersensitivity and attenuates PNS inflammation potentially via modifying short chain fatty acid (SCFA) levels, although FMT outcomes are variable. We therefore tested whether targeted modulation of the gut microbiota with fermentable complex carbohydrates (inulin) producing SCFA could reproducibly improve somatosensory function in WD-fed mice. Using an integrated pipeline-behavioral and physiological assays, peripheral nerve electrophysiology, and molecular and immune profiling-we show that inulin improved thermal and mechanical sensory function indirectly by improving metabolic health and remodeling immune cells in adipose tissue depots. Interestingly, in separate genetic experiments we found that deletion of the SCFA receptor FFAR2 (GPR43) in myeloid cells altered thermal sensitivity and adipose inflammatory gene expression, indicating that immune SCFA sensing can modulate pain-related behavior. These findings identify mechanisms by which dietary fiber indirectly preserves PNS function through effects on adiposity and systemic inflammation and provide a tractable alternative to FMT for mitigating WD-associated sensory neuropathy.},
}

@article {pmid42092473,
year = {2026},
author = {Liu, T and Zhao, Y and Wang, X and Ding, L and Yu, G and Lin, X and Wu, X},
title = {Comparative Pharmacodynamic Material Basis of Oral and Colonic Administration of Baitouweng Decoction in Experimental Ulcerative Colitis.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {121805},
doi = {10.1016/j.jep.2026.121805},
pmid = {42092473},
issn = {1872-7573},
abstract = {Baitouweng Decoction (BTWD) is a traditional Chinese medicine formula widely used in clinical practice for treating ulcerative colitis (UC). However, its precise therapeutic mechanisms remain unclear.

AIM OF THE STUDY: This study investigates the therapeutic effects of BTWD administered via colon and oral routes in a UC model induced by fecal microbiota transplantation (FMT) and dextran sodium sulfate (DSS). It further explores the distinct pharmacological mechanisms associated with each route of administration.

MATERIALS AND METHODS: Male rats with UC induced by human-derived FMT and DSS were treated with BTWD via oral or colonic administration. Therapeutic outcomes were evaluated through clinical indicators and histopathology. Drug metabolites in serum and colon contents were analyzed by Ultra Performance Liquid Chromatography-Q Exactive-Orbitrap Mass Spectrometer (UPLC-QE-Orbitrap MS). Serum and fecal metabolomics identified disease-related biomarkers. Potential active substances were screened by correlating serum and fecal biomarkers with BTWD-derived components. Key active substances and targets were identified through network pharmacology and molecular docking, clarifying the pharmacological basis of each administration route. Surface plasmon resonance (SPR) and Western blot were performed to experimentally validate the binding interactions and target protein expression.

RESULTS: Both administration routes of BTWD significantly alleviated UC symptoms. Compared to the model group, BTWD-treated rats exhibited reduced weight loss, lower disease activity index (DAI) scores, and recovered colon length. Serum levels of pro-inflammatory cytokines IL-6, IL-17, and IL-1β were decreased, while anti-inflammatory IL-10 was increased. Expression of Occludin and MUC2 proteins in colon tissue was significantly upregulated. In total, 82 serum and 70 colon components were identified following oral administration, while colonic administration yielded 73 serum and 78 colon components. Correlation analysis screened 36 active components associated with colonic administration and 25 with oral administration. Network pharmacology and molecular docking suggested that core components from colon administration (Anemoside B4, Betulonic acid) may act via targets such as EGFR, LCK, and MET, while oral components (Berberine, Oxyepiberberine) may target AURKA, MET, and PTGS2. SPR confirmed direct binding of anemoside B4 and berberine to EGFR with KD values of 9.47E-04 M and 2.96E-04 M, respectively. Western blot revealed route-dependent modulation of EGFR, PTGS2, LCK and AURKA expression, corroborating the predicted targeting.

CONCLUSION: BTWD is effective in treating UC through both colonic and oral administration. This study provides a comprehensive "efficacy-component-metabolism-target" analysis that reveals distinct pharmacological mechanisms underlying each administration route. These findings support the traditional use of BTWD and offer a theoretical foundation for developing optimized, route-specific therapies for UC.},
}

@article {pmid42093245,
year = {2026},
author = {Hamdan, A and Ziad, AN},
title = {Reframing obesity through the gut microbiota: functional dysbiosis and metabolic disease.},
journal = {Current opinion in clinical nutrition and metabolic care},
volume = {},
number = {},
pages = {},
pmid = {42093245},
issn = {1473-6519},
abstract = {PURPOSE OF REVIEW: Obesity and its metabolic complications remain major global health challenges. Beyond excess caloric intake, emerging evidence implicates diet-induced gut microbiota dysfunction as a modulator of metabolic homeostasis. This review examines recent advances in understanding how functional alterations of the gut microbiota contribute to obesity pathogenesis.

RECENT FINDINGS: Current data indicate that obesity is characterized less by specific microbial taxa and more by disruption of key microbial functions. Diet-induced dysbiosis alters short-chain fatty acid production, bile acid metabolism, tryptophan-derived signaling, and intestinal barrier integrity. These changes promote metabolic endotoxemia, impair enteroendocrine hormone secretion, and disrupt gut-brain and gut-liver communication, contributing to adipose tissue inflammation, hepatic steatosis, and insulin resistance. Experimental and clinical studies further suggest that microbiota-targeted interventions, including dietary fiber enrichment, prebiotics, synbiotics, and fecal microbiota transplantation, can partially restore microbial metabolic function and improve selected metabolic outcomes.

SUMMARY: Obesity is increasingly conceptualized as a state of diet-driven functional gut microbiota disruption. Targeting microbial metabolic pathways rather than individual taxa may offer a promising adjunctive strategy to complement established therapies for obesity-related metabolic disease.},
}

@article {pmid42093801,
year = {2026},
author = {Busmail, H and Weerakoon, S and Mandefro, BT and Sundara, SV and Lu, X and Avula, S and Mohammed, L},
title = {Fecal Microbiota Transplantation in Inflammatory Bowel Disease: A Systematic Review of Efficacy and Safety.},
journal = {Cureus},
volume = {18},
number = {4},
pages = {e106453},
pmid = {42093801},
issn = {2168-8184},
abstract = {Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory condition of the gastrointestinal tract associated with immune dysregulation and alterations in the gut microbiota. Growing evidence suggests that intestinal microbial dysbiosis plays an important role in disease pathogenesis, prompting interest in microbiome-targeted therapies, such as fecal microbiota transplantation (FMT). This systematic review aimed to evaluate the efficacy and safety of FMT in adult patients with IBD. A comprehensive literature search was conducted in PubMed, Embase, Scopus, and the Cochrane Library for studies published between 2020 and 2025 using keywords related to "fecal microbiota transplantation" and "inflammatory bowel disease." Eligible studies included randomized controlled trials (RCTs), cohort studies, systematic reviews, and meta-analyses involving adult patients with UC or CD. Due to clinical and methodological heterogeneity, a structured narrative synthesis was performed in accordance with Synthesis Without Meta-analysis (SWiM) guidelines. Nine studies comprising 1,847 participants met the inclusion criteria, including five RCTs, two systematic reviews, and two meta-analyses. In patients with UC, clinical remission rates ranged from 32% to 40%, with response rates between 44% and 52%. In CD, remission rates ranged from 24% to 31%, although evidence remained limited and heterogeneous. Multi-donor stool preparations and repeated FMT administrations were associated with improved clinical outcomes compared with single-donor protocols or single-dose protocols. Adverse events occurred in approximately 12-15% of patients and were predominantly mild gastrointestinal symptoms, while serious adverse events were rare (<2%). Current evidence suggests that FMT may induce clinical remission in a subset of patients with UC, while evidence in CD remains less consistent. Larger randomized trials with standardized protocols and long-term follow-up are needed to determine optimal donor selection, dosing strategies, and long-term safety.},
}

@article {pmid42094762,
year = {2026},
author = {Pan, Z and Zhang, T and Ren, Z and Zhang, H and Wang, J and Ma, Y and Man, R and Peng, J and Yu, Y},
title = {Microbiota-immune crosstalk in the regulation of intestinal motility in constipation.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1828926},
pmid = {42094762},
issn = {1664-302X},
abstract = {Constipation is a common functional gastrointestinal disorder with a complex pathogenesis. Traditional studies have primarily explained its development in terms of reduced intestinal motility or impaired defecatory coordination; however, these mechanisms alone cannot fully account for the multifactorial pathological processes underlying the condition. In recent years, increasing attention has been directed toward the roles of intestinal microbial dysbiosis and alterations in immune homeostasis in the development of constipation. The gut microbiota continuously interacts with the intestinal immune system through its structural components, metabolic products, and secreted molecules. These interactions modulate the mucosal immune microenvironment and participate in the regulation of intestinal motility by influencing the enteric nervous system, interstitial cells of Cajal, and smooth muscle function. Conversely, the immune system can reshape the composition and spatial distribution of the gut microbiota through mechanisms such as the mucosal barrier, immunoglobulin A, and antimicrobial peptides, thereby forming a bidirectional regulatory network. Accumulating evidence suggests that during the onset and progression of constipation, microbial dysbiosis, shifts in immune homeostasis, and abnormalities in intestinal motility may evolve through a progressively amplifying dynamic process, ultimately establishing a self-sustaining chronic cycle. In addition, microbiota-targeted interventions-including probiotics, prebiotics, and fecal microbiota transplantation-have demonstrated potential benefits in improving stool frequency and stool consistency in several clinical studies. However, the immunological mechanisms underlying these effects remain relatively underexplored. This review systematically summarizes the molecular mechanisms by which gut microbiota-immune interactions regulate intestinal motility. By integrating current evidence on disease progression and clinical studies, we propose a conceptual model of the "microbiota-immune-motility regulatory axis," aiming to provide a new perspective for understanding the pathogenesis of constipation and for optimizing microbiota-based therapeutic strategies.},
}

@article {pmid42094772,
year = {2026},
author = {Luo, H and Shen, Z and Jian, Y and Wang, M and Luo, S and Wang, J and Nan, L and Tang, L and Rehman, MU and Carbonero, F},
title = {Editorial: Unravelling the wildlife gut microbiome: the crucial role of gut microbiomes in wildlife conservation strategies.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1838495},
pmid = {42094772},
issn = {1664-302X},
}

@article {pmid42095982,
year = {2026},
author = {Răzniceanu, V and Țichindeleanu, A and Răducu, EV and Trella, ȘE and Nenu, I},
title = {Gut dysbiosis and nitric oxide dysregulation in cirrhosis progression: mechanistic insights and pathophysiological implications.},
journal = {Journal of physiology and biochemistry},
volume = {82},
number = {1},
pages = {},
pmid = {42095982},
issn = {1877-8755},
mesh = {Humans ; *Dysbiosis/metabolism/microbiology/immunology ; *Nitric Oxide/metabolism ; *Gastrointestinal Microbiome ; *Liver Cirrhosis/metabolism/microbiology/pathology/physiopathology ; Animals ; Disease Progression ; Liver/metabolism/pathology ; Hypertension, Portal/metabolism/microbiology ; Signal Transduction ; Nitric Oxide Synthase Type III/metabolism ; },
abstract = {Cirrhosis represents the end stage of chronic liver injury, characterized by progressive fibrosis and architectural distortion that precipitate portal hypertension and systemic complications. Recent evidence positions gut microbiota dysbiosis and nitric oxide (NO) dysregulation as central, interacting pathophysiological mechanisms in cirrhosis progression. Intestinal barrier dysfunction facilitates bacterial translocation and thereby exposes the liver to lipopolysaccharides and pathogen-associated molecular patterns that trigger hepatic inflammation via Toll-like receptor signalling, a phenomenon aggravated by dysbiosis. This immune activation stimulates inducible NO synthase in Kupffer cells and systemic endothelium, generating excess NO that drives splanchnic vasodilation and worsens portal hypertension. Paradoxically, intrahepatic endothelial NO synthase activity becomes impaired, reducing sinusoidal NO availability and increasing intrahepatic vascular resistance. These interconnected disturbances perpetuate inflammation and fibrogenesis, contributing to cirrhosis decompensation and spontaneous bacterial peritonitis. Despite substantial mechanistic insight into these pathways, therapeutic translation remains limited. Statins show promise by restoring intrahepatic eNOS function and reducing portal pressure, while microbiota-targeted interventions (antibiotics, probiotics, fecal transplantation) address gut-derived inflammation. This review synthesizes our current understanding of the gut-liver-NO axis in cirrhosis, highlighting how dysbiosis and aberrant NO signalling reinforce each other through inflammatory feedback loops, and identifies critical gaps between mechanistic knowledge and clinical application that warrant further investigation.},
}

Humans
*Dysbiosis/metabolism/microbiology/immunology
*Nitric Oxide/metabolism
*Gastrointestinal Microbiome
*Liver Cirrhosis/metabolism/microbiology/pathology/physiopathology
Animals
Disease Progression
Liver/metabolism/pathology
Hypertension, Portal/metabolism/microbiology
Signal Transduction
Nitric Oxide Synthase Type III/metabolism

@article {pmid42096120,
year = {2026},
author = {Wu, R and Yao, G},
title = {Research advancement on the correlation between gut microbiota and chronic kidney disease.},
journal = {Antonie van Leeuwenhoek},
volume = {119},
number = {6},
pages = {},
pmid = {42096120},
issn = {1572-9699},
support = {010086//the Beijing Major Epidemic Prevention and Control Key Specialty Intensive Care Medicine Construction Project under Grant/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Renal Insufficiency, Chronic/microbiology/therapy ; Dysbiosis/microbiology ; Probiotics ; Animals ; },
abstract = {Chronic kidney disease (CKD) represents a significant global health challenge, with its progression and complications associated with dysbiosis of the gut microbiota. Patients with CKD demonstrate stage-dependent alterations in the composition of gut microbiota and a reduction in diversity, which is characterized by a decline in beneficial bacteria (e.g., Bifidobacterium, Lactobacillus) and an increase in pathogenic species. This dysbiosis disrupts the gut-kidney axis, resulting in a depletion of protective metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids, while facilitating the accumulation of toxic metabolites including trimethylamine N-oxide (TMAO), indoxyl sulfate (IS), and p-cresyl sulfate (pCS). These toxins contribute to the progression of CKD and cardiovascular complications through mechanisms that involve oxidative stress, inflammation (e.g., NF-ĸB/NLRP3 activation), fibrosis (e.g., TGF-β/Smad signaling), and endothelial dysfunction. Therapeutic strategies aimed at modulating the gut microbiota encompass dietary interventions (such as increasing fiber and plant-based protein), microecological agents (including probiotics and prebiotics), fecal microbiota transplantation (FMT), and adsorbents (e.g., targeting uremic toxins). Although these approaches show promise in delaying CKD progression and alleviating complications, they necessitate further validation through large-scale clinical trials to confirm their efficacy, safety, and the development of personalized protocols. Investigating the gut-kidney axis may provide novel biomarkers and therapeutic opportunities for enhancing CKD outcomes.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Renal Insufficiency, Chronic/microbiology/therapy
Dysbiosis/microbiology
Probiotics
Animals

@article {pmid42097400,
year = {2026},
author = {Wang, H and Li, T and Yang, J and Zhang, W and Chen, S and Song, M and Wang, S and Liu, C},
title = {Drinking water temperatures modulate gut microbiota-L-cysteine axis to enhance adipose thermogenesis and alleviate obesity-related metabolic disorders in mice.},
journal = {Life sciences},
volume = {},
number = {},
pages = {124438},
doi = {10.1016/j.lfs.2026.124438},
pmid = {42097400},
issn = {1879-0631},
abstract = {AIMS: Although people living in different countries prefer to drink water at various temperatures, the influence of drinking water temperature on metabolic homeostasis remains largely unexplored. This study investigated how different drinking-water temperatures affect metabolic regulation and the underlying gut microbiota-metabolite interactions.

MATERIALS AND METHODS: High-fat diet (HFD)-fed mice were given water at 0 °C, 25 °C, or 40 °C. Metabolic alterations were assessed by histopathology, serum biochemistry, and body-composition analysis, with food intake and core temperature monitored. Gut microbiota causality was examined using antibiotic depletion and reciprocal fecal microbiota transplantation (FMT). 16S rRNA gene sequencing and metabolomics were performed to characterize fecal microbial and metabolite profiles. Adipose stromal vascular fraction (SVF) cells were used in vitro to examine the effects of L-cysteine on lipid metabolism.

KEY FINDINGS: Both 0 °C and 40 °C water ameliorated HFD-induced metabolic dysfunction through increased energy expenditure, reduced liver steatosis, and enhanced adipose-tissue thermogenesis, independent of differences in intake. Cold water selectively enriched Bifidobacterium pseudolongum and Adlercreutzia equolifaciens, whereas warm water increased Bacteroides acidifaciens, Alistipes inops and Alistipes obesi, indicating distinct microbiota configurations. Antibiotic ablation blunted these benefits, while cross-group FMT reproduced the metabolic and thermogenic phenotypes, confirming a microbiota-dependent mechanism. Despite divergent microbiota structures, both temperature regimens consistently elevated L-cysteine, which reduced lipid accumulation and enhanced thermogenic gene expression in SVF cells.

SIGNIFICANCE: These findings highlight drinking-water temperature as a simple, safe, and sustainable lifestyle factor with translational potential to mitigate obesity-related metabolic dysfunction, potentially via a gut microbiota-L-cysteine axis that enhances adipose thermogenesis and systemic metabolic homeostasis.},
}

@article {pmid42097699,
year = {2026},
author = {Xu, T and Lu, R and Oakland, DN and Estaleen, R and Rawlings, A and Montano, H and Diab, S and Michaelis, JS and Pop, M and Bankole, A and Reilly, CM and Luo, XM},
title = {Double humanised lupus mouse model with human immune system and faecal microbiota from patients with SLE.},
journal = {Lupus science & medicine},
volume = {13},
number = {1},
pages = {},
doi = {10.1136/lupus-2026-001982},
pmid = {42097699},
issn = {2053-8790},
mesh = {Animals ; *Lupus Erythematosus, Systemic/immunology/microbiology/therapy ; Humans ; Disease Models, Animal ; Mice ; *Fecal Microbiota Transplantation ; Female ; Feces/microbiology ; Immunoglobulin G/blood ; Gastrointestinal Microbiome ; Immunoglobulin M/blood ; Hematopoietic Stem Cell Transplantation ; T-Lymphocytes/immunology ; Terpenes ; Spleen/immunology ; Male ; },
abstract = {OBJECTIVE: We aimed to create a double humanised lupus mouse model with a human immune system and faecal microbiota from patients with SLE.

METHODS: We established the Double humanised SLE (DhuSLE) mouse by engrafting NSG immunodeficient mice with human CD34[+] haematopoietic stem and progenitor cells (NSG-hu mice) and performing faecal microbiota transplantation from patients with SLE (SLE-FMT).

RESULTS: While FMT in general transiently suppressed the development of human T cells in NSG-hu mice, SLE-FMT but not FMT from non-SLE donors promoted superficial skin lesions. Importantly, the combination of SLE-FMT and pristane in NSG-hu, now called the DhuSLE-P mouse, induced proteinuria although this clinical sign observed in mice did not reflect that of the microbiota donors. DhuSLE-P mice exhibited a higher level of human IgM in the circulation than NSG-hu mice, which was positively correlated with the frequency of plasma cells in the spleen. In the splenic sections of DhuSLE-P mice, nuclear BCL6 was minimally detected but CD138 expression was evident, suggesting that most plasma cells generated were not class switched and produced IgM. Some human IgG was detected in the kidney of DhuSLE-P mice with a trend towards increased total IgG in the serum. Analysis of the faecal microbiota revealed that the gut microbiota compositions were different between DhuSLE-P mice and NSG-hu mice due to SLE-FMT but not the injection of pristane.

CONCLUSION: Together, these results introduced the first humanised lupus mouse model combining the human immune system and gut microbiota from patients with SLE. However, limitations exist and the model may benefit from methods that promote antibody class switching. On further development, the DhuSLE model can be useful for elucidating mechanisms and/or evaluating SLE treatments.},
}

Animals
*Lupus Erythematosus, Systemic/immunology/microbiology/therapy
Humans
Disease Models, Animal
Mice
*Fecal Microbiota Transplantation
Female
Feces/microbiology
Immunoglobulin G/blood
Gastrointestinal Microbiome
Immunoglobulin M/blood
Hematopoietic Stem Cell Transplantation
T-Lymphocytes/immunology
Terpenes
Spleen/immunology
Male

@article {pmid42083540,
year = {2026},
author = {YuXuan, G and Iqbal, MK and Khan, B and Khan, H and Ud Din Shah, SS and Al-Hussain, F and Kiyani, MM and Bashir, S},
title = {The Gut-Brain Connection: Exploring the Connection Between the Gastrointestinal System and Parkinson's Disease.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273419693251206130059},
pmid = {42083540},
issn = {1996-3181},
abstract = {Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by motor and non-motor symptoms. Recent studies indicate that the gut-brain axis contributes to both the initiation and progression of PD, a disorder that primarily affects the central nervous system. This article reviews current research on the interaction between the central nervous system and the gastrointestinal tract in PD. The vagus nerve, areas of the enteric nervous system (ENS), systemic inflammation, and the microbiome are all involved in this interaction. For example, recent studies have shown PD-related effects such as abnormal distribution of gut bacteria, increased gut barrier permeability, and α-synuclein transport from the gut to the brain. A comprehensive evaluation of motor and non-motor symptoms was conducted. Additionally, we explored drugs that specifically target the gastrointestinal system, the possible gastrointestinal symptoms of PD, and how these symptoms may serve as early indicators of the disease. Our article also discusses dietary modifications, probiotics, and fecal microbiota transplantation as potential treatments for PD. By reviewing clinical and basic scientific research as well as translational applications, this article highlights the relationship between the central nervous system and the digestive system in PD. A better understanding of this complex connection may lead to improved detection and treatment of this debilitating disease and offer new opportunities for prevention and therapy. Finally, this paper suggests directions for further research in this area.},
}

@article {pmid42083785,
year = {2026},
author = {Wu, Y and Liu, J and Ren, Y and Zou, C},
title = {Unravelling the Gut-Skin Axis in Chronic Urticaria: Dysbiosis, Metabolites and Immunological Mechanisms.},
journal = {Experimental dermatology},
volume = {35},
number = {5},
pages = {e70261},
doi = {10.1111/exd.70261},
pmid = {42083785},
issn = {1600-0625},
support = {2025C02080//the Key Research and Development Plan of Zhejiang Province/ ; WKJ-ZJ-2409//the National Health Commission Scientific Research Fund/ ; },
mesh = {Humans ; *Dysbiosis/immunology ; *Gastrointestinal Microbiome ; Animals ; *Chronic Urticaria/immunology/microbiology/metabolism ; *Skin/immunology/metabolism ; Mice ; Fatty Acids, Volatile/metabolism ; Mast Cells/immunology ; },
abstract = {Although the core pathophysiological pathways of chronic urticaria (CU) are increasingly understood, the upstream triggers and factors contributing to disease chronicity remain poorly understood. Emerging evidence suggests that gut microbiota dysbiosis represents a potentially modifiable upstream factor, which has been predominantly investigated in patients with chronic spontaneous urticaria (CSU). Multi-omics and Mendelian randomization studies have provided convergent evidence linking gut dysbiosis to systemic inflammation and mast cell instability. This is characterized primarily by the depletion of short-chain fatty acid (SCFA)-producing taxa (e.g., Faecalibacterium, Roseburia and Bifidobacterium) and the relative enrichment of pro-inflammatory Proteobacteria (particularly Enterobacteriaceae). Mechanistically, these alterations may lower the mast cell activation threshold and promote systemic immune dysregulation through specific metabolic shifts, such as the depletion of SCFAs and unsaturated fatty acids, and the translocation of endotoxins (e.g., lipopolysaccharide) due to compromised intestinal barrier function. In this review, we discuss how the use of Mendelian randomization (MR) and germ-free mouse models can advance the gut-urticaria axis (with a primary focus on CSU) from mere correlation to causation, while highlighting the crucial need to account for clinical confounders. Finally, we evaluate the clinical translational potential and associated challenges of microbiome-targeted interventions (e.g., probiotics, faecal microbiota transplantation) as novel adjuvant therapies.},
}

Humans
*Dysbiosis/immunology
*Gastrointestinal Microbiome
Animals
*Chronic Urticaria/immunology/microbiology/metabolism
*Skin/immunology/metabolism
Mice
Fatty Acids, Volatile/metabolism
Mast Cells/immunology

@article {pmid42086265,
year = {2026},
author = {Bénard, MV and Van Der Spek, MJ and Davids, M and Visser, CE and Zoetendal, EG and Rethans, B and Zwezerijnen-Jiwa, FH and Visschedijk, MC and Ponsioen, CY and Oldenburg, B and Weersma, RK},
title = {Transfer of faeces in ulcerative colitis 2: improving efficacy - study protocol for a multicentre randomised controlled trial (TURN2 study).},
journal = {BMJ open},
volume = {16},
number = {5},
pages = {e107097},
doi = {10.1136/bmjopen-2025-107097},
pmid = {42086265},
issn = {2044-6055},
mesh = {Humans ; *Colitis, Ulcerative/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; Double-Blind Method ; Gastrointestinal Microbiome ; *Feces/microbiology ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Adult ; Male ; Female ; Enema ; },
abstract = {INTRODUCTION: The interaction between the gut microbiota and the host immune system is implicated in the pathogenesis of inflammatory bowel disease, including ulcerative colitis (UC). Targeting the gut microbiota with faecal microbiota transplantation (FMT) from a healthy donor has shown promise in inducing remission in patients with active UC. However, mixed results and protocol heterogeneity have limited its practical application. Our previous Transfer of Faeces in Ulcerative Colitis; Restoring Homeostasis (TURN) trial found a correlation of clinical response with specific strains and butyrate production. Since most gut microbes, including many butyrate producers, are anaerobes, anoxic processing of donor stool may be essential to increase efficacy of FMT in UC. This trial aims to enhance FMT efficacy by applying strict anoxic processing, selecting donors based on microbial composition and using repetitive dual-route administration.

METHODS AND ANALYSIS: This randomised, double-blind, placebo-controlled, multicentre study evaluates the efficacy of strictly anoxic prepared donor FMT compared with anoxic prepared autologous FMT in patients with mild to moderate active UC. An open-label extension option is available for non-responders in the autologous arm. Included patients will receive 4 weekly FMTs, comprising two double-route administrations (nasoduodenal administration combined with enema) and two single enemas. Donors are selected based on their microbiota profile, informed by our previous TURN trial and literature. A total of 76 patients evaluable for the primary endpoint will be included. The primary endpoint is steroid-free clinical and endoscopic remission at week 8, assessed by the adapted Mayo score. An interim analysis will be conducted midway through the study by a Data Safety Monitoring Board to monitor efficacy and safety. Other outcomes of this study include the evaluation of clinical, endoscopic and histological response. In addition to clinical results, this study aims to provide valuable insights into specific microbial strains, metabolites and mechanisms correlated with response, aiding in the development of future microbial therapies.

ETHICS AND DISSEMINATION: Ethics approval was obtained from the medical ethics committee of the Amsterdam University Medical Centre in the Netherlands (reference number 2018_057). All participants will provide written informed consent. The results of the trial will be disseminated through publication in a peer-reviewed journal and presentations at (inter)national conferences.

TRIAL REGISTRATION NUMBER: Prospectively registered in May 2018 in the Dutch Trial Register (NTR/LTR) as NL7770. Assigned NL-OMON52507 following the transition of the Dutch Trial Register to the Overview of Medical Research in the Netherlands. Also registered at ClinicalTrials.gov (NCT05998213).},
}

Humans
*Colitis, Ulcerative/therapy/microbiology
*Fecal Microbiota Transplantation/methods
Double-Blind Method
Gastrointestinal Microbiome
*Feces/microbiology
Multicenter Studies as Topic
Randomized Controlled Trials as Topic
Treatment Outcome
Adult
Male
Female
Enema

@article {pmid42088008,
year = {2026},
author = {Sgarbossa, C and Forth, E and Squires, S and Groth, A and Farid, M and Gallant, K and Desai, D and Redfearn, W and Milev, R},
title = {Neurobiological effects of microbial treatments within psychiatry: a systematic review.},
journal = {Frontiers in psychiatry},
volume = {17},
number = {},
pages = {1745964},
pmid = {42088008},
issn = {1664-0640},
abstract = {OBJECTIVE: Though microbial interventions such as probiotics and fecal microbiota transplantation have had a growing body of evidence suggesting their efficacy in alleviating the symptoms of psychiatric illnesses, their exact mechanisms of action and impacts on the brain are still not fully characterized. The aim of this review is to compile and summarize the current literature regarding neurobiological changes associated with microbial interventions targeting psychiatric symptoms in healthy and psychiatric populations.

METHODS: A systematic search of four databases was conducted using key terms related to neuroimaging, microbial interventions, and psychiatric illnesses and/or symptoms. All results were then evaluated based on specific eligibility criteria.

RESULTS: 10 studies met eligibility criteria and were included in this systematic review. Three of the five healthy control studies and all five of the studies conducted within psychiatric populations, observed significant neurobiological changes associated with probiotic intervention either in areas with psychiatric relevance, in the direction of a healthier profile, or correlated with improved psychiatric and/or affective symptoms. The interventions used in these studies consisted of probiotics with bacterial species primarily from the lactobacillus and bifidobacterium genera, at doses ranging from 1-900 billion CFU, taken for durations ranging from 4 weeks to 6 months.

CONCLUSIONS: The findings from this review suggest that probiotic intervention may be associated with neurobiological changes, and that these changes could play a role in ameliorating psychiatric symptoms. More research is needed to replicate these findings, explore other psychiatric populations and microbial interventions, and fully elucidate the mechanisms driving these promising neurobiological and clinical changes.},
}

@article {pmid41615004,
year = {2026},
author = {Tremblay, C and Edger-Lacoursière, Z and Schneider, G and Jean, S and Calva, V and Nedelec, B},
title = {Rehabilitation Evaluation and Treatment for Skin Graft Complications of the Genitalia.},
journal = {Journal of burn care & research : official publication of the American Burn Association},
volume = {47},
number = {3},
pages = {868-878},
doi = {10.1093/jbcr/irag016},
pmid = {41615004},
issn = {1559-0488},
mesh = {Humans ; Male ; *Skin Transplantation/adverse effects ; Adult ; *Fournier Gangrene/surgery/rehabilitation ; Aged ; *Fasciitis, Necrotizing/surgery/rehabilitation ; Perineum ; },
abstract = {Skin graft complications may include pain, contractures, hypertrophic scars (HSc), hypersensitivity, and recurrent wounds. Complications involving grafts to the genitalia, perineum, and/or buttocks can be particularly challenging, directly affecting walking, sitting, voiding, bowel elimination, sexual function, and intimacy, ultimately diminishing quality of life. Perineal and pelvic floor rehabilitation (PPFR) is commonly used to treat various pelvic floor disorders; however, its application following burn injury or necrotizing fasciitis has not been previously described. This manuscript presents the evaluation and treatment outcomes of patients with necrotizing fasciitis or Fournier's gangrene. Initial evaluation was conducted approximately 4 months postadmission by a certified pelvic floor physiotherapist and occupational therapist. Treatment included pelvic floor rehabilitation, patient education, sensory re-education, bladder and bowel training, use of adapted pressure garments, gel application, cutaneous and myofascial stretching, and manual therapy. This report details the outcomes of 2 male patients (37 and 69 years old) who underwent skin grafting and reconstructive surgery following necrotizing fasciitis and Fournier's gangrene. Both presented with complex wounds that closed approximately 4 months postadmission, accompanied by contractures, HSc, altered sensory perception, incontinence, and sexual intimacy dysfunction. Following PPFR treatment, improvements were observed in pruritus, urinary and fecal retention capacity, sexuality-related fear avoidance, penile deviation, lower extremity range of motion, satisfaction with sexual function, and sensory perception. This is the first description of a standardized PPFR protocol in this context, demonstrating that specialized interdisciplinary rehabilitation can enhance sexual function, body-image satisfaction, and overall quality of life in patients with genital, perineal, and/or buttock grafts.},
}

Humans
Male
*Skin Transplantation/adverse effects
Adult
*Fournier Gangrene/surgery/rehabilitation
Aged
*Fasciitis, Necrotizing/surgery/rehabilitation
Perineum

@article {pmid42079588,
year = {2026},
author = {Qie, RJ and Qin, JB and Wu, HY and Ji, ZH},
title = {Key messengers in the gut-nose axis: mechanisms of gut microbial metabolites in the immunomodulation of allergic rhinitis.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1796775},
pmid = {42079588},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Rhinitis, Allergic/immunology/metabolism/microbiology/therapy ; *Immunomodulation ; Animals ; *Nasal Mucosa/immunology/metabolism/microbiology ; },
abstract = {Allergic rhinitis (AR) is a common clinical chronic inflammatory respiratory disease, in which immune imbalance serves as a core component of its complex pathogenesis. In recent years, the gut-nose axis has emerged as a novel pathway mediating immune crosstalk between the intestinal tract and the nasal cavity, garnering significant academic attention. Gut microbial metabolites (such as short-chain fatty acids, tryptophan metabolites, bile acids, and polyamines) are profoundly involved in the pathophysiology of AR by reshaping the nasal mucosal immune microenvironment via systemic circulation and neural pathways and regulating the Th2/Treg balance, innate lymphoid cells (ILC2s), and mast cell functions. This article systematically reviews the immunomodulatory mechanisms of core gut microbial metabolites, explores their impact on nasal mucosal epithelial barrier function and immune cell activity, and summarizes metabolite-based clinical intervention strategies, including postbiotic therapy (bioactive compounds derived from microbial cells or metabolites), precision nutritional interventions, and fecal microbiota transplantation. Additionally, the paper analyzes current challenges such as heterogeneity and dose-response effects, aiming to provide a theoretical foundation for understanding the immunomodulatory mechanisms of the gut-nose axis and a reference for developing novel precision strategies for the prevention and treatment of AR.},
}

Humans
*Gastrointestinal Microbiome/immunology
*Rhinitis, Allergic/immunology/metabolism/microbiology/therapy
*Immunomodulation
Animals
*Nasal Mucosa/immunology/metabolism/microbiology

@article {pmid42079748,
year = {2026},
author = {Zheng, L and Jia, T and Li, Y and Zhang, Z and Su, H and Zhang, R},
title = {The interplay between gastrointestinal dysfunction and gut microbiota dynamics in sepsis.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1761536},
pmid = {42079748},
issn = {2235-2988},
mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Sepsis/microbiology/physiopathology/complications/immunology ; *Dysbiosis/microbiology ; Animals ; *Gastrointestinal Diseases/microbiology ; *Gastrointestinal Tract/microbiology/physiopathology ; Intestinal Mucosa/microbiology ; Multiple Organ Failure ; },
abstract = {Sepsis frequently involves early gastrointestinal dysfunction, in which intestinal barrier breakdown and microbiota dysbiosis amplify systemic inflammation and contribute to multi-organ failure. Emerging evidence indicates that the gut is not merely a bystander in sepsis but an active driver of pathogenic cascades through epithelial injury, mucosal immune dysregulation, ischemia-reperfusion stress, and impaired motility, collectively promoting microbial translocation and immune deviation. In parallel, sepsis is associated with profound remodeling of the gut microbiome, characterized by reduced commensal diversity, expansion of pathobionts, and functional shifts in key microbial metabolites, including short-chain fatty acids, bile acids, and tryptophan-derived products, which further compromise mucosal integrity and host immune tone. This narrative review synthesizes experimental, translational, and clinical findings to elucidate the bidirectional interaction gut barrier-microbiota interplay in sepsis and to summarize mechanistic links across epithelial, immune, and metabolic signaling pathways, including gut-liver and gut-brain axes relevant to sepsis-associated organ dysfunction. dysfunctional microbial community leads to systemic immune deviation, multi-organ dysfunction and sepsis-associated encephalopathy, a common and severe neurological complication of sepsis. We also discuss emerging therapeutic strategies targeting the gut-microbiota axis-such as early enteral nutrition, prebiotics/postbiotics, defined microbial consortia, fecal microbiota transplantation, and metabolite-based supplementation-and evaluate their potential and limitations in septic populations. Finally, we highlight key challenges, including unresolved causality, inter-individual variability, context-dependent responses, and safety concerns, underscoring the need for longitudinal multi-omic profiling, host-microbiome phenotyping, and mechanism-informed interventional trials to enable precision microbiome-based approaches for sepsis.},
}

Humans
*Gastrointestinal Microbiome/physiology
*Sepsis/microbiology/physiopathology/complications/immunology
*Dysbiosis/microbiology
Animals
*Gastrointestinal Diseases/microbiology
*Gastrointestinal Tract/microbiology/physiopathology
Intestinal Mucosa/microbiology
Multiple Organ Failure

@article {pmid42081036,
year = {2026},
author = {Yang, F and Liu, S and Liu, G and Luo, L and Lu, X and Lin, W and Chen, J and Lin, R},
title = {Fecal microbiota transplantation from different pig breeds alters fat deposition and gut microbiota in mice.},
journal = {Applied microbiology and biotechnology},
volume = {},
number = {},
pages = {},
doi = {10.1007/s00253-026-13823-z},
pmid = {42081036},
issn = {1432-0614},
support = {2023J01446//Natural Science Foundation of Fujian Province/ ; 2019-144//Fujian Modern Agricultural Pig Industry Technology System Project/ ; },
abstract = {Gut microbiota plays a vital role in nutrient digestion, energy metabolism, and immune regulation in pigs. However, the core bacterial species influencing fat deposition remain poorly defined due to the complexity and diversity of the intestinal microbial ecosystem. In this study, healthy Putian Black (PT) pigs and Duroc × Landrace × Yorkshire (DLY) pigs of similar ages were used as fecal microbiota transplantation (FMT) donors, with male ICR mice as recipients. A control group (CM) received saline, while the experimental groups were gavaged fecal suspensions from PT pigs (PM) or DLY pigs (DM). Results showed that intramuscular fat content, triglyceride levels, and adipogenic gene expression (PPARG, FABP4, LPL, ATGL) were extremely significant higher in the PM group than in the DM group (P<0.01). 16 S rRNA sequencing revealed that both PM and DM groups had lower Firmicutes abundance but higher Bacteroidetes abundance compared to the CM group (P<0.05). Notably, the PM group exhibited higher Firmicutes and lower Bacteroidetes abundance than the DM group (P<0.05). Correlation analysis identified S_uncultured_bacterium_g_Prevotella as negatively correlated with FASN and DGAT2 expression (P<0.01), while Lactobacillus species showed positive correlations with PPARG, FASN, and ATGL expression (P<0.05). These findings demonstrate that FMT alters gut microbiota composition and host gene expression, thereby influencing fat deposition, with Prevotella and Lactobacillus emerging as potential key genera. KEY POINTS: ∙ FMT resulted in extremely significant higher intramuscular fat content in the PM group compared to the DM group. ∙ Lactobacillus may be a key genus regulating fat deposition in PT pigs. ∙ Prevotella may be a key genus regulating fat deposition in DLY pigs.},
}

@article {pmid42083059,
year = {2026},
author = {Diop, K and Benlaïfaoui, M and Hunter, S and Méndez-Salazar, EO and Hakozaki, T and Richard, C and Prifti, DK and Kourtian, S and Proulx-Rocray, F and Naimi, S and Ponce, M and Messaoudene, M and Cauchois, F and Belkaid, W and Bataille, V and Lee, K and Mihalcioiu, C and Watson, IR and Elkrief, A and Routy, B},
title = {Metagenomics and culturomics reveal the dual role of the gut microbiome in the development of immune-related toxicities and the efficacy of immune checkpoint inhibitors in cancer.},
journal = {Microbiome},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40168-026-02419-4},
pmid = {42083059},
issn = {2049-2618},
support = {284894//Fonds de recherche du Québec/ ; },
abstract = {BACKGROUND: Despite their major impact on cancer treatment, immune checkpoint inhibitors (ICI) are frequently associated with immune-related adverse events (irAE). Growing evidence suggests that the occurrence of irAE may be correlated with enhanced ICI efficacy, although the underlying mechanisms remain unknown. Most studies investigating the role of the gut microbiome in oncology have relied on sequencing approaches, particularly shotgun metagenomics. Although microbiome profiling revealed strong associations between specific bacterial taxa and clinical outcomes, it has limitations, including an inability to detect low-abundance bacteria and to recover live cultivable bacteria. To overcome these limitations, we combined shotgun metagenomics and culturomics on fecal samples collected from patients with melanoma and non-small cell lung cancer (NSCLC), at baseline and at the onset of immune related (ir)-colitis.

RESULTS: We first validated across three independent cohorts of 589 patients with melanoma or NSCLC treated with ICI that grade ≥ 2 irAE were associated with significantly longer overall survival (OS) and progression-free survival (PFS). Complementary analysis using shotgun metagenomics and culturomics revealed that patients who developed grade ≥ 2 irAE had a lower alpha diversity compared to those who did not develop grade ≥ 2 irAE. Metagenomics results showed enrichment of Ruminococcus gnavus and Streptococcus vestibularis at baseline in grade ≥ 2 irAE patients, while Clostridium paraputrificum and Streptococcus spp. were isolated by culturomics from baseline stool samples from ir-colitis patients. Longitudinal analysis of paired stool samples revealed a shift in microbiome composition with enrichment of Paraclostridium bifermentans and Clostridium paraputrificum, lower lipopolysaccharide and higher flagellin concentrations at baseline compared with the time of ir-colitis. Fecal microbiome transplantation from a patient with ir-colitis into mice induced surrogate markers of colonic inflammation and enhanced the anti-tumor activity of combined anti-PD-1/CTLA-4. P. bifermentans isolated from this patient sample demonstrated direct epithelial barrier disruption in Caco-2 monolayers, characterized by decreased ZO-1 and Occludin immunofluorescence signal and increased TNF-α and IL-1β expression. Moreover, in the dextran sodium sulfate (DSS) colitis model, P. bifermentans worsened weight loss. In a separate tumor model, it amplified the anti-tumor effect of dual ICI. This beneficial effect was also maintained after treatment with P. bifermentans < 3 kDa filtered supernatant.

CONCLUSION: Altogether, our results suggest that P. bifermentans promotes subclinical colitis while increasing the efficacy of dual ICI. This provides a potential microbiome-derived link between irAE and improved anti-tumor responses. Video Abstract.},
}

@article {pmid42083117,
year = {2026},
author = {Helliwell, JA and Sciberras, P and Dosis, A and Burke, J and Chilton, CH and Wood, HM and Jayne, DG},
title = {Modulation of the gut microbiota as a novel strategy to prevent anastomotic leak after colorectal surgery: Systematic scoping review.},
journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland},
volume = {28},
number = {5},
pages = {e70472},
doi = {10.1111/codi.70472},
pmid = {42083117},
issn = {1463-1318},
mesh = {Humans ; *Anastomotic Leak/prevention & control/microbiology ; *Gastrointestinal Microbiome/physiology/drug effects ; Probiotics/therapeutic use ; *Colorectal Surgery/adverse effects ; Fecal Microbiota Transplantation ; Animals ; Female ; Male ; },
abstract = {BACKGROUND: Anastomotic leak (AL) remains a major source of morbidity following colorectal surgery. Increasing evidence implicates the gut microbiome in the pathogenesis of AL, with certain microbial species disrupting tissue repair through collagen degradation. Perioperative modulation of the microbiome may offer a novel strategy to improve anastomotic healing. This scoping review aimed to map available evidence on microbiome-targeted interventions, synthesise mechanistic insights, and identify translation gaps in relation to anastomotic outcomes.

METHODS: A systematic scoping review was performed. MEDLINE, Embase and Cochrane Central Registry of Controlled Trials databases were searched from database inception to 5th August 2025. Studies were eligible if they investigated perioperative interventions that modulated the gut microbiome and evaluated anastomotic healing or leak rates. Both clinical and preclinical studies were included. A narrative synthesis was performed by charting key findings.

RESULTS: Of 4209 records screened, 27 studies met the inclusion criteria: 9 clinical and 18 preclinical. Interventions included bowel preparation, probiotics, synbiotics, arginine/omega-3 supplementation, dietary modification, faecal microbiota transplantation (FMT), phosphate, tranexamic acid, morphine and infliximab. Among clinical studies, only oral antibiotics combined with mechanical bowel preparation were associated with a significant reduction in leak rates. Preclinical studies showed interventions such as high-fibre diets, FMT, rectal tranexamic acid and phosphate supplementation improved anastomotic healing via enhanced microbial diversity, suppression of pathogenic organisms, or inhibition of collagenolytic activity.

CONCLUSION: This review highlights a range of microbiome-targeted interventions with potential to reduce AL. While clinical evidence remains limited, several preclinical strategies demonstrate promise and warrant evaluation in early-phase human trials.},
}

Humans
*Anastomotic Leak/prevention & control/microbiology
*Gastrointestinal Microbiome/physiology/drug effects
Probiotics/therapeutic use
*Colorectal Surgery/adverse effects
Fecal Microbiota Transplantation
Animals
Female
Male

@article {pmid42083350,
year = {2026},
author = {Bashir, S and Shah, IM and Javeed, S and Rafiquee, A and Mir, B and Hassan Mir, R and Geer, MI and Ganie, MA},
title = {Beyond Conventional Therapy: A Comprehensive Review of Herbal, Traditional, and Emerging Interventions for Polycystic Ovary Syndrome.},
journal = {Current molecular medicine},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115665240406897251206074722},
pmid = {42083350},
issn = {1875-5666},
abstract = {Polycystic ovary syndrome (PCOS) is the most common and multifactorial endocrine disorder that leads to significant changes in the reproductive, metabolic, and psychological domains of women's health in their reproductive years. In addition, the conventional therapies (lifestyle modification, metformin, oral contraceptives, and ovulation-inducing agents) that are the mainstay of management of the syndrome may still not be able to fully address the diverse pathophysiology of PCOS as well as the long-term risks associated with it. This narrative review highlights clinical and mechanistic data from studies on various complementary and alternative medicine (CAM) modalities as first-line treatments for PCOS, in addition to conventional therapy. Correspondingly, herbal and botanical agents (berberine, cinnamon, licorice, Vitex agnus-castus, curcumin, and epigallocatechin gallate) modulate insulin signalling, androgen synthesis, inflammatory pathways, and oxidative stress, with initial clinical trials reporting improvements in metabolism and hormones to a similar extent as standard therapies in selected populations. Traditional Chinese Medicine (TCM), both multi-herb prescriptions and acupuncture, provides tailored formulas that might not only regulate ovulation and endocrine parameters but also lower metabolic indices, despite the high variability across studies. Stress reduction, physical fitness, and the quality of life are among the achievements of mind-body interventions (yoga, tai chi, qigong, and mindfulness-based stress reduction). Improvements in hyperinsulinemia, hypolipidemia, ovulation, and hyperandrogenemia, along with the related insulinresistant and vitamin D-deficient phenotypes, have been steadily reported with the use of the nutraceutical combinations of inositols, vitamin D, omega-3 fatty acids, Nacetylcysteine, coenzyme Q10, and resveratrol. New non-conventional methods, such as fecal and vaginal microbiota transplantation, platelet-rich plasma, and kisspeptin analogues, have been identified as potential therapeutic routes but are still in their infancy in terms of development. Although CAM therapies have multiple advantages in controlling many PCOS domains, the official integration into clinical practice would require standardization, rigorous randomized controlled trials, and continuous safety monitoring. If correctly and cautiously applied, CAM may be useful as an adjunct alongside established therapy, rendering PCOS management more holistic and personalized.},
}

@article {pmid42068877,
year = {2026},
author = {Liao, W and Gao, J and Zhang, J and Wu, Y and Jiang, Y and Liu, H and Chen, S and Xiu, L and Zhong, G},
title = {Haizao Yuhu Decoction alleviates goiter via the gut-thyroid axis: Microbiota-derived SCFAs promote hormone synthesis and restore apoptosis.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {156},
number = {},
pages = {158256},
doi = {10.1016/j.phymed.2026.158256},
pmid = {42068877},
issn = {1618-095X},
abstract = {BACKGROUND AND PURPOSE: Haizao Yuhu Decoction (HYD) is a classic Traditional Chinese Medicine for goiter, but its mechanism related to the "gut-thyroid axis" remains unknown. This study investigates whether HYD treats goiter via this axis and elucidates the underlying mechanisms.

METHODS: A rat goiter model was induced with propylthiouracil (PTU), followed by two weeks of HYD treatment. Gut microbiota was analyzed by metagenomic sequencing; fecal and serum short-chain fatty acids (SCFAs) were quantified by targeted LC-MS/MS analysis. Thyroid function was assessed via iodine content and hormone levels. Key proteins in hormone synthesis and apoptosis were evaluated by Western blot and immunohistochemistry. Fecal microbiota transplantation (FMT) supported microbiota causality.

RESULTS: HYD alleviated goiter and hypothyroidism. It restored gut microbiota diversity and enriched SCFA-producing bacteria (e.g., Bifidobacterium pseudolongum), coincident with increased SCFAs including butyrate. These SCFA changes correlated with reduced HDAC1/2/3/8 in thyroid tissue, consistent with enhanced histone acetylation, and were accompanied by upregulation of NIS, TG, TPO, and DUOX2. Concurrently, elevated SCFAs were associated with AKT/Mdm2 pathway inhibition, p53 stabilization, downstream activation of P21 and Caspase-3, and suppression of Bcl-2, supporting a model of promoted thyroid cell apoptosis. FMT supported that HYD-modulated microbiota alone reproduced these effects.

CONCLUSION: HYD alleviates PTU-induced goiter in rats in a manner associated with gut microbiota remodeling and increased SCFA production, which correlate with enhanced thyroid hormone synthesis and restored apoptosis-a relationship supported by FMT experiments. However, direct interactions between HYD and PTU cannot be fully excluded. These findings are consistent with a model in which HYD acts through the gut-thyroid axis, providing mechanistic insights into its therapeutic effects.},
}

@article {pmid42069299,
year = {2026},
author = {Meng, F and Xue, M and Li, H and Tao, G and Chen, W and Li, Y and Pei, H and Liu, Z and Yin, D and Qin, S and Xue, J and Liu, B},
title = {Consumption of hydrogen-rich water ameliorates atherosclerosis by modulating gut microbiota and enhancing short-chain fatty acid levels.},
journal = {Life sciences},
volume = {397},
number = {},
pages = {124418},
doi = {10.1016/j.lfs.2026.124418},
pmid = {42069299},
issn = {1879-0631},
abstract = {AIMS: Molecular hydrogen (H2) is a safe gaseous signaling molecule with anti-inflammatory properties. This study aimed to explore the anti-atherosclerotic effects of hydrogen-rich water (H2W) and clarify the underlying mechanism involving the gut microbiota and its metabolites.

MATERIALS AND METHODS: ApoE[-/-] mice were administered H2W to evaluate atherosclerotic plaque development and stability. Gut microbiota composition and short-chain fatty acid levels were analyzed. Antibiotic-induced microbiota depletion and fecal microbiota transplantation (FMT) were used to verify the mediating role of the gut microbiota. In vitro assays were performed to examine the effects of propionate on macrophage inflammation and polarization.

KEY FINDINGS: H2W consumption significantly attenuated plaque formation and enhanced plaque stability in ApoE[-/-] mice, accompanied by altered gut microbiota structure and short-chain fatty acid profiles. Antibiotic treatment abolished the protective effects of H2W, while FMT from H2W-treated mice transferred the anti-atherosclerotic phenotype. H2W notably increased propionate levels in cecal contents and serum. Propionate directly suppressed inflammatory responses and M1 macrophage polarization in vitro.

SIGNIFICANCE: This study demonstrates that H2W alleviates atherosclerosis by modulating the gut microbiota-propionate-macrophage axis. Our findings highlight H2W as a promising and safe intervention for atherosclerosis and provide new mechanistic insights into the crosstalk between gut microbial metabolites and vascular inflammation.},
}

@article {pmid42069657,
year = {2026},
author = {de Oliveira Andrade, F and Staley, C and Jin, L and Ozgul-Onal, M and McDermott, M and Kenanoglu, S and de Oliveira, KA and Verma, V and Hilakivi-Clarke, L},
title = {Gut microbiome modulates breast cancer risk in socially isolated mice.},
journal = {Breast cancer research : BCR},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13058-026-02292-x},
pmid = {42069657},
issn = {1465-542X},
abstract = {BACKGROUND: Breast cancer risk and mortality are associated with disrupted gut microbiome functions which in turn can affect tumor immune responses. One source of disruption could be stress. Social isolation (SI) stress consistently increases breast cancer risk and mortality in preclinical models and women, but whether SI promotes mammary tumor growth by affecting gut microbiome has not been studied.

METHODS: We investigated if increased E0771 mammary tumorigenesis in SI female C57BL/6 mice was associated with changes in their gut microbiome by treating mice with an antibiotic mix that suppresses bacterial abundance and by performing fecal microbiota transplantation (FMT) from SI or group-housed (GH) donors to GH host. The effect of SI on anti-tumor CD8 + T and immunosuppressive Foxp3 + Treg cells was also studied.

RESULTS: Fecal bacteria that were present at different abundances between GH and SI mice were short chain fatty acid (SCFA) producers, and the most consistent change across three replicate studies was decreased fecal abundance of Akkermansia genus in SI mice. In addition, fecal propionic acid levels were reduced in SI mice, compared with GH mice, in agreement with Akkermansia being propionic acid producer. SI reduced the activation of CD8 + T cells systemically and in the tumor microenvironment, while the levels and activation of immunosuppressive Foxp3 Tregs were increased. Antibiotic treatment reversed increased mammary tumorigenesis and immunosuppression in SI mice but did not affect GH mice. Further, FMT from SI donors increased tumor growth in GH host, compared with FMT from GH donor.

CONCLUSION: Gut dysbiosis caused by SI may be driving their increased mammary tumorigenesis, potentially through gut dysbiosis induced immunosuppression.},
}

@article {pmid42072400,
year = {2026},
author = {Lin, Y and Lu, P and Ding, Q and Liu, M},
title = {Current Perspectives on the Inflammatory Bowel Disease Pathogenesis of Microbiota and the Gut-Brain Axis, and Emerging Therapeutics.},
journal = {Biomedicines},
volume = {14},
number = {4},
pages = {},
doi = {10.3390/biomedicines14040859},
pmid = {42072400},
issn = {2227-9059},
abstract = {The pathogenesis of inflammatory bowel disease (IBD) is driven by an interplay among intestinal dysbiosis and aberrant mucosal immune responses. This review centers on the microbiota as a pivotal pathogenic hub, systematically dissecting how three hallmark features of dysbiosis-reduced microbial alpha diversity, depletion of immunomodulatory commensals, and expansion of pro-inflammatory pathobionts-collectively compromise epithelial barrier function, promote bacterial translocation, and sustain chronic mucosal inflammation. We further integrate emerging evidence implicating bidirectional gut-brain axis communication in amplifying both peripheral inflammation and central nervous system (CNS)-mediated behavioral comorbidities. Building on this mechanistic framework, we critically evaluate next-generation microbiota-targeted interventions: standardized fecal microbiota transplantation (FMT), rationally designed live biotherapeutic products (LBPs), precision phage cocktails targeting defined pathobionts, and microbiome-informed dietary strategies. Collectively, these approaches represent a paradigm shift-from broad-spectrum immunosuppression toward mechanism-guided, ecosystem-level modulation-thereby advancing the goal of precision medicine in IBD.},
}

@article {pmid42072403,
year = {2026},
author = {Shajahan, SR and Hamid, N and Okunsai, B and Shari, N and Ramli, MDC},
title = {Microbiota-Gut-Brain Axis in Alzheimer's Disease: Linking Oxidative Stress, Mitochondrial Dysfunction and Amyloid Pathology-A Systematic Review.},
journal = {Biomedicines},
volume = {14},
number = {4},
pages = {},
doi = {10.3390/biomedicines14040860},
pmid = {42072403},
issn = {2227-9059},
abstract = {Background: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β aggregation, tau hyperphosphorylation, oxidative stress, and mitochondrial dysfunction. Emerging evidence indicates that the gut microbiota plays a critical role in modulating neuroinflammatory, and metabolic pathways involved in AD pathogenesis through the microbiota-gut-brain axis. Objective: This systematic review aims to comprehensively evaluate the role of the microbiota-gut-brain axis in Alzheimer's disease, with a particular focus on its mechanistic links to oxidative stress, mitochondrial dysfunction, and amyloid pathology, as well as its therapeutic potential. Methodology: A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases, focusing on studies evaluating gut microbiota composition, metabolomic changes, oxidative stress markers, mitochondrial activity, and therapeutic interventions in AD models and patients. Results: Altered gut microbial composition in AD is associated with increased pro-inflammatory taxa (Escherichia-Shigella, Bacteroides) and depletion of short-chain fatty acid (SCFA) producing bacteria (Faecalibacterium, Roseburia). Dysbiosis contributes to systemic inflammation, disrupted intestinal permeability, and microglial activation, leading to oxidative damage and mitochondrial impairment in neurons. Preclinical and clinical studies indicate that probiotics, prebiotics, and fecal microbiota transplantation can restore redox balance, reduce neuroinflammation, and improve cognitive outcomes. Multi-omics and AI-based models are emerging as tools for identifying microbiome-derived biomarkers for early AD detection. Conclusion: The gut microbiota-mitochondria-oxidative stress axis represents a promising therapeutic target in Alzheimer's disease. Future research should focus on longitudinal human studies, standardized microbial profiling, and personalized microbiome-based interventions to translate these mechanistic insights into clinical benefit.},
}

@article {pmid42073392,
year = {2026},
author = {Yang, M and Chen, Q and Meng, Z and Gu, X and Bai, C},
title = {The Microbiota-Gut-Brain Axis in Insomnia: Mechanisms and Intervention Strategies.},
journal = {Life (Basel, Switzerland)},
volume = {16},
number = {4},
pages = {},
doi = {10.3390/life16040583},
pmid = {42073392},
issn = {2075-1729},
support = {82574999//National Natural Science Foundation of China/ ; zyyzdxk-2023264//National Administration of Traditional Chinese Medicine/ ; 2024-JYB-JBZD-038//The Fundamental Research Funds for the Central Universities/ ; },
abstract = {Insomnia is one of the most common sleep disorders. Traditionally, its pathophysiology has been interpreted mainly from the perspective of the central nervous system (CNS). However, accumulating evidence suggests that the microbiota-gut-brain axis (MGBA), a bidirectional communication network linking the gut and the CNS, may play an important role in the development, maintenance, and treatment of insomnia. This review summarizes the major signaling pathways of the MGBA and discusses its potential mechanisms in insomnia. Current evidence indicates that gut microbiota and their metabolites may influence sleep-wake homeostasis through neural, immune, endocrine, and circadian pathways. At the same time, insomnia-related stress responses, immune imbalance, and lifestyle disturbances may in turn affect the gut microbiota, thereby forming a bidirectional regulatory network. Animal and clinical studies further support a close association between gut microbial dysbiosis and insomnia. In addition, this review systematically summarizes factors that may affect the MGBA, including diet, lifestyle, psychosocial stress, medications, and medical exposures. On this basis, MGBA-targeted interventions, such as dietary modification, prebiotics and probiotics, lifestyle interventions, fecal microbiota transplantation, and natural medicines, may provide promising new strategies for the prevention and treatment of insomnia. Nevertheless, the current evidence still relies largely on animal studies and cross-sectional research, and further longitudinal studies and high-quality interventional trials are needed to clarify causality, long-term efficacy, and standardized therapeutic approaches.},
}

@article {pmid42073476,
year = {2026},
author = {Ichim, C and Boicean, A and Mihaila, R and Todor, SB and Anderco, P and Birlutiu, V},
title = {Effect of Fecal Microbiota Transplantation on Arterial Stiffness in Alcohol-Related Liver Cirrhosis: A Prospective Pilot Study.},
journal = {Life (Basel, Switzerland)},
volume = {16},
number = {4},
pages = {},
doi = {10.3390/life16040668},
pmid = {42073476},
issn = {2075-1729},
abstract = {BACKGROUND: Alcohol-related liver disease is frequently associated with systemic vascular dysfunction and increased arterial stiffness. This may contribute to adverse clinical outcomes. Modulation of the gut microbiota through fecal microbiota transplantation (FMT) has emerged as a potential therapeutic strategy in liver cirrhosis, but its influence on vascular stiffness in humans remains insufficiently characterized.

METHODS: This prospective study evaluated arterial stiffness in patients with alcohol-related liver cirrhosis undergoing FMT. A control group received standard care. Vascular stiffness was assessed non-invasively using an oscillometric arteriograph based on pulse wave analysis. Measurements were performed at baseline and at one and three months after FMT under standardized conditions. The main indices assessed included aortic pulse wave velocity, augmentation index, ejection duration and return time. Direct microbiome sequencing and metabolomic profiling were not performed.

RESULTS: At baseline, the study and control groups had comparable vascular stiffness profiles. Only minor differences in selected hemodynamic parameters were observed. At one month after intervention, no statistically significant differences in arterial stiffness indices were observed between groups. Longitudinal analysis within the FMT group also showed no significant changes in direct markers of arterial stiffness across the three-month follow-up period. A non-significant tendency toward reduced ejection duration was noted.

CONCLUSIONS: In patients with advanced alcohol-related liver cirrhosis, FMT did not produce measurable short-term improvements in arterial stiffness. These findings suggest that short-term vascular effects of microbiota modulation may be difficult to detect in patients with advanced alcohol-related liver cirrhosis. Larger studies including earlier-stage patients, longer follow-up and direct microbiome and metabolomic assessment are needed to clarify potential vascular effects of FMT.},
}

@article {pmid42073922,
year = {2026},
author = {Zheng, M and Wei, X and Chen, R and Wang, C and Xin, L},
title = {The Gut Microbiota and Autism Spectrum Disorder: Current Research and Therapeutic Insights.},
journal = {Behavioral sciences (Basel, Switzerland)},
volume = {16},
number = {4},
pages = {},
doi = {10.3390/bs16040559},
pmid = {42073922},
issn = {2076-328X},
abstract = {Autism Spectrum Disorder (ASD) is a collective term for neurodevelopmental disorders with core features of social communication impairment, restricted and repetitive behaviors, and narrow interests. These include classic autism, Asperger's syndrome, and pervasive developmental disorder not otherwise specified. ASD is currently managed with behavioral interventions, rehabilitation training, and family support, but there is no curative medication. Recent studies suggest that some patients with ASD may experience gastrointestinal symptoms. Perhaps this is associated with the disturbances of gut microbiota. Increasing evidence has demonstrated that the composition of gut microbiota in ASD individuals is different from that in normal population and may be associated with neurodevelopmental processes via the gut-brain axis. This article reviews the evidence for the association between gut microbiota and ASD, describes the characteristics of microbial changes, and analyzes the mechanism by which changes in the composition of the microbiota affect the occurrence and development of ASD. Finally, we review recent advances in microbiota-targeted therapeutic strategies, including probiotics, prebiotics, and fecal microbiota transplantation, which provide new approaches to alleviate and improve autism-related symptoms and point out the future research direction.},
}

@article {pmid42074015,
year = {2026},
author = {Papacocea, RI and Iliuță, FP and Papacocea, IR},
title = {Gut Microbiome Dysregulation Across Schizophrenia Spectrum Disorders: Bacteria-, Fungi- and Virome-Level Alterations with Molecular and Immunological Implications.},
journal = {International journal of molecular sciences},
volume = {27},
number = {8},
pages = {},
doi = {10.3390/ijms27083372},
pmid = {42074015},
issn = {1422-0067},
mesh = {Humans ; *Gastrointestinal Microbiome ; *Schizophrenia/microbiology/immunology ; *Virome ; *Bacteria ; Dysbiosis/microbiology ; *Fungi ; Animals ; },
abstract = {Schizophrenia spectrum disorders (SSD) are severe psychiatric conditions characterized by disturbances in cognition, emotion, and behavior, with increasing evidence suggesting an involvement of the gut microbiome in their pathophysiology. This PRISMA-informed structured review synthesizes 114 studies using a taxa-centered framework that maps microbial changes across SSD stages and phenotypes and serves as a structural basis for identifying cross-study patterns. Across heterogeneous cohorts, convergent alterations include depletion of short-chain fatty acid (SCFA)-producing taxa (including Faecalibacterium, Roseburia, and Coprococcus) and enrichment of potentially pro-inflammatory and fermentative taxa (such as Proteobacteria, Enterobacteriaceae, Streptococcus, Collinsella, and Desulfovibrio). These taxonomic patterns suggest potential functional alterations, including reduced SCFA availability. Reduced abundance of butyrate-producing taxa has been associated with impaired intestinal barrier function and increased microbial translocation (e.g., lipopolysaccharide), which may contribute to the activation of immune pathways, including Toll-like receptor 4 signaling and elevated inflammatory markers such as IL-6 and TNF-α. Additional alterations reported across studies include changes in lactate metabolism, bile acid profiles, aromatic amino acid metabolism, and the tryptophan-kynurenine pathway. These pathways may interact with neurobiological processes relevant to SSD, including glutamate-GABA balance, NMDA receptor function, microglial activation, and synaptic regulation, although much of the current evidence remains associative. Multi-kingdom studies and fecal microbiota transplantation models provide further support for the functional relevance of these observations, though causal relationships remain to be fully established. Overall, SSD-associated dysbiosis appears to reflect ecosystem-level metabolic alterations rather than isolated taxonomic abnormalities, supporting a Microbiota-Gut-Immune-Glia conceptual framework and highlighting the gut ecosystem as a potential therapeutic target.},
}

Humans
*Gastrointestinal Microbiome
*Schizophrenia/microbiology/immunology
*Virome
*Bacteria
Dysbiosis/microbiology
*Fungi
Animals

@article {pmid42074174,
year = {2026},
author = {Ratajczyk, K and Kaczorowska, E and Wyka, K and Tarasiuk-Zawadzka, A and Fichna, J and Gajos, A},
title = {Gut-Brain Signaling in Parkinson's Disease: A Narrative Review.},
journal = {International journal of molecular sciences},
volume = {27},
number = {8},
pages = {},
doi = {10.3390/ijms27083531},
pmid = {42074174},
issn = {1422-0067},
support = {Medical University of Lodz (#503/6-127-01/503-61-001 to AG and #503/1-156-04/503-11-001 to JF).//Medical University of Lodz/ ; },
mesh = {Humans ; *Parkinson Disease/metabolism/microbiology/therapy/pathology ; *Gastrointestinal Microbiome/physiology ; *Brain/metabolism ; Animals ; Signal Transduction ; *Brain-Gut Axis ; Neurotransmitter Agents/metabolism ; },
abstract = {The formulation of the gut-brain-microbiota axis (GBA) theory has led to new research directions that have expanded our understanding of the pathogenesis, phenotypic variability, and clinical course of Parkinson's disease (PD). Models of PD pathogenesis, based on the Braak hypothesis, suggest a subtype of the disease in which pathological changes begin in the gut many years before the onset of brain pathology and the manifestation of motor symptoms. Gut microbiota may influence nervous system function along the GBA by influencing intestinal permeability, chronic inflammation, and α-synuclein aggregation. Accumulating evidence suggests that the gut microbiota may also regulate the synthesis and metabolism of neurotransmitters, including dopamine (DA), serotonin (5-HT), acetylcholine (ACh) and γ-aminobutyric acid (GABA), both in the gut and brain, and indirectly stimulate central nervous system activity via the vagus nerve, which receives signals from the enteric nervous system. Research on the effects of microbiota on GBA has paved the way for the identification of novel treatment strategies, including probiotics, prebiotics, synbiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT), aimed at not only symptomatic but also disease-modifying treatment of PD. In this article, we propose a novel approach to GBA as a link between gut microbiota and gut and brain neurotransmitter metabolism in PD. We review the latest research on the gut epithelial barrier. We analyze and summarize the potential of therapeutic interventions targeting gut microbiota and their impact on neurotransmitter regulation in PD.},
}

Humans
*Parkinson Disease/metabolism/microbiology/therapy/pathology
*Gastrointestinal Microbiome/physiology
*Brain/metabolism
Animals
Signal Transduction
*Brain-Gut Axis
Neurotransmitter Agents/metabolism

@article {pmid42075006,
year = {2026},
author = {Zhang, X and Chen, F and Luo, Y and Li, D and Ji, J and Ma, L and Ma, C and Hu, X},
title = {Young Human-Derived Microbiota Ameliorates Cognitive Decline and Reproductive Senescence in Aged Mice.},
journal = {Nutrients},
volume = {18},
number = {8},
pages = {},
doi = {10.3390/nu18081193},
pmid = {42075006},
issn = {2072-6643},
support = {2023YFF1104005//National key research and development program/ ; },
mesh = {Animals ; Mice ; Humans ; Male ; Bifidobacterium/growth & development ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; *Cognitive Dysfunction/microbiology/therapy ; *Cellular Senescence/physiology ; Mice, Inbred C57BL ; Reproduction/physiology ; Dysbiosis/microbiology/therapy ; *Aging/physiology/psychology ; },
abstract = {Background/Objectives: Age-related gut microbiota dysbiosis leads to systemic oxidative stress, chronic inflammation, and multi-organ functional decline. However, there is limited evidence supporting microbiota-based therapies for aging. This study aimed to examine the effect of gut microbiota from young donors, particularly those with increasing Bifidobacteria levels through dietary intervention, on age-related declines in fertility, cognition, and reproduction. Methods: We conducted experiments using gut microbiota from young human donors, with or without pre-conditioning with barley leaves (BL), to transplant into aged male mice. Hippocampal metabolome and behavioral assessments were used to identify differences in recognitive regulation during aging. Moreover, testis tissue, semen quality, and offspring studies were determined to investigate the beneficial effects on fertility and underlying mechanism. Conclusions: This preliminary dietary treatment promotes the growth of Bifidobacterium in aged recipient mice. Aged male mice received young fecal microbiota transplants (yFMTs), BL-conditioned yFMTs (BLyFMTs), and a combined treatment of BLyFMT plus recipient BL supplementation. The combined approach significantly increased intestinal Bifidobacterium levels and effectively restored hippocampal metabolomic profiles and cognitive behavior. Additionally, yFMT-based treatments mitigated structural damage to the seminiferous tubules and prevented the germ cell depletion. Consistently, those interventions improved sperm quality and mechanistically enhanced hypothalamic-pituitary-gonadal (HPG) axis activity in aged recipients. These findings highlight Bifidobacterium as a key factor in microbiome-driven rejuvenation, enhancing the effectiveness of yFMTs in addressing aging-related declines.},
}

Animals
Mice
Humans
Male
Bifidobacterium/growth & development
*Fecal Microbiota Transplantation/methods
*Gastrointestinal Microbiome/physiology
*Cognitive Dysfunction/microbiology/therapy
*Cellular Senescence/physiology
Mice, Inbred C57BL
Reproduction/physiology
Dysbiosis/microbiology/therapy
*Aging/physiology/psychology

@article {pmid42075029,
year = {2026},
author = {Asayesh, M and Nazarzadeh, A and Jamshidi, S and Keramat, S and Ryszkiel, I and Stanek, A},
title = {Modulation of Gut Microbiota Through Dietary Fibers to Enhance Regulatory T Cell-Based Immunotherapy in GVHD Following Hematopoietic Stem Cell Transplantation.},
journal = {Nutrients},
volume = {18},
number = {8},
pages = {},
doi = {10.3390/nu18081216},
pmid = {42075029},
issn = {2072-6643},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology/drug effects ; *Graft vs Host Disease/therapy/immunology/microbiology/prevention & control ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Dietary Fiber/administration & dosage ; *T-Lymphocytes, Regulatory/immunology ; *Immunotherapy/methods ; Prebiotics ; Dysbiosis ; Fecal Microbiota Transplantation ; Probiotics ; },
abstract = {Graft-versus-host disease (GVHD) is one of the principal complications seen in the recipients of allogenic hematopoietic stem cell transplantation (allo-HSCT), and persists as a leading cause of post-transplant morbidity and mortality. Increasing evidence highlights the crucial influence of the gut microbiome (GM) on transplant outcomes. Microbial dysbiosis, characterized by reduced bacterial diversity and pathogenic overgrowth, is strongly associated with higher rates of complications and mortality. Patients with lower microbial diversity exhibit poorer overall survival (OS) and an increased incidence of acute GVHD (aGVHD). Conversely, restoration of beneficial commensal communities has been shown to enhance immune homeostasis, mitigate GVHD severity, and decrease infection risk. Emerging therapeutic strategies now focus on modulating the intestinal microbiome through dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation (FMT). It has been demonstrated that bacterial metabolites, such as short-chain fatty acids (SCFAs) from the diet, especially a diet rich in fibers, reduce the occurrence/severity of GVHD by inducing regulatory T cells (Tregs), which release anti-inflammatory cytokines and regulate the host immune system. Hence, the implementation of dietary fibers (DFs) could increase beneficial commensals, Treg induction, and improve outcomes such as GVHD and OS in recipients of allo-HCT. Hereupon, this review addresses how a fiber-rich diet modulates GM composition, reinforces epithelial barrier integrity, and improves the efficacy of Treg-based immunotherapy by stabilizing their regulatory phenotype and increasing their functional persistence, ultimately leading to a reduction in GI complications associated with GVHD. Unlike prior reviews that primarily cover the microbiome-GVHD axis or Treg therapies in isolation, this review emphasizes fermentable dietary fibers as a mechanistically grounded, clinically actionable strategy to support Treg stability and persistence via microbiota-derived metabolites. We integrate mechanistic evidence with emerging clinical feasibility data and ongoing trials of prebiotic supplementation in allogeneic HSCT.},
}

Humans
*Gastrointestinal Microbiome/immunology/drug effects
*Graft vs Host Disease/therapy/immunology/microbiology/prevention & control
*Hematopoietic Stem Cell Transplantation/adverse effects
*Dietary Fiber/administration & dosage
*T-Lymphocytes, Regulatory/immunology
*Immunotherapy/methods
Prebiotics
Dysbiosis
Fecal Microbiota Transplantation
Probiotics

@article {pmid42075307,
year = {2026},
author = {Burdette, RA and Whitt, CC and Cios Phillips, KJ and Worthington, MT and Behm, BW and Warren, CA},
title = {Treating Initial and Recurrent C. difficile: A Retrospective Analysis of 100 Referred Patients.},
journal = {Microorganisms},
volume = {14},
number = {4},
pages = {},
doi = {10.3390/microorganisms14040911},
pmid = {42075307},
issn = {2076-2607},
abstract = {Treatment guidelines for Clostridioides difficile infection (CDI) have been published by infectious disease and gastroenterology professional societies; however, adherence in clinical practice remains poorly characterized, particularly for recurrent disease. We conducted a retrospective chart review of 100 patients with CDI (350 episodes: 115 initial, 235 recurrent) referred to a tertiary complicated CDI clinic between 2018 and 2023. Guideline adherence was assessed by comparing treatment with IDSA/SHEA and ACG recommendations, and referring diagnoses were compared with final specialist diagnoses. Guideline adherence was significantly higher in initial compared to recurrent episodes (70.4% vs. 41.3%, p < 0.0001). Among guideline non-adherent recurrent episodes, 51.3% used standard antibiotic regimens inappropriate for the recurrence tier. Specialist review reclassified 12.0% of episodes, with colonization increasing from 2.6% to 8.9%. Misdiagnosed colonization cases had a 6.2-fold higher treatment failure rate than confirmed CDI (39.3% vs. 6.3%, p < 0.0001). Guideline non-adherence showed a non-significant trend toward treatment failure (10.0% vs. 6.7%, p = 0.31). Guideline adherence for recurrent CDI is inadequate in pre-referral settings, and diagnostic misclassification is common. Early specialist involvement may improve both diagnostic accuracy and treatment appropriateness for patients with recurrent CDI.},
}

@article {pmid42075777,
year = {2026},
author = {Lagos, I and Pérez de Arce, E and Faggiani, I and D'Amico, F and Zilli, A and Furfaro, F and Massironi, S and Cicerone, C and Solitano, V and Parigi, TL and Peyrin-Biroulet, L and Danese, S and Allocca, M},
title = {The Role of Microbiota and Fecal Transplantation in Inflammatory Bowel Disease.},
journal = {Pathogens (Basel, Switzerland)},
volume = {15},
number = {4},
pages = {},
doi = {10.3390/pathogens15040451},
pmid = {42075777},
issn = {2076-0817},
mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/therapy/microbiology ; Crohn Disease/therapy/microbiology ; Colitis, Ulcerative/therapy/microbiology ; Feces/microbiology ; Treatment Outcome ; },
abstract = {Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are consistently associated with alterations in gut microbial communities, although the extent and characteristics of these alterations vary across studies, supporting a potential role of the microbiota in disease pathogenesis and therapeutic modulation. We conducted a systematic review to synthesize current evidence on microbiota alterations in IBD and the clinical application of fecal microbiota transplantation (FMT). A total of 118 studies were included (76 focused on microbiota profiling and 42 evaluated FMT as therapy). Across heterogeneous study designs and microbial characterization methods, reduced microbial diversity was the most consistently reported alteration, generally more pronounced in CD than in UC. Depletion of Faecalibacterium prausnitzii-a key butyrate producer with anti-inflammatory properties-was commonly reported, often accompanied by functional impairment in short-chain fatty acid production. Microbial patterns were frequently associated with mucosal inflammation and varied across disease phenotypes; these patterns have been increasingly explored as predictors of treatment response and relapse, although mechanistic interpretation remains limited and causal relationships are difficult to establish. Evidence from randomized controlled trials suggests potential efficacy of FMT in UC, particularly with intensive or repeated protocols, whereas data in CD remain limited and heterogeneous, with signals of benefit often appearing transient. FMT was generally well tolerated, but long-term safety data remain scarce. Emerging multi-omic approaches are reshaping the field by integrating taxonomic and functional insights, with potential implications for risk stratification, diagnosis, prognosis, and therapeutic optimization. Further standardized, longitudinal, and mechanistically oriented studies are required to translate microbiome research into clinically actionable strategies in IBD.},
}

*Fecal Microbiota Transplantation/methods
Humans
*Gastrointestinal Microbiome
*Inflammatory Bowel Diseases/therapy/microbiology
Crohn Disease/therapy/microbiology
Colitis, Ulcerative/therapy/microbiology
Feces/microbiology
Treatment Outcome

@article {pmid42077461,
year = {2026},
author = {Wu, J and Qiu, Y and Deng, J and Li, Y and Jia, B and Cao, Z and Tao, J and Guo, J},
title = {Faecal microbiota transplantation and glucolipid metabolic disorders: the interventional role of gut microbiota.},
journal = {Frontiers in endocrinology},
volume = {17},
number = {},
pages = {1806638},
pmid = {42077461},
issn = {1664-2392},
mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Animals ; *Metabolic Diseases/therapy/microbiology/metabolism ; },
abstract = {Glucolipid metabolic disorders (GLMD) have emerged as a significant global public health issue, posing a significant threat to human health. With changes in modern social structures and an ageing population, the incidence of GLMD is on the rise and is increasingly affecting younger populations. Faecal microbiota transplantation (FMT) directly modifies the gut microbiota to reestablish its equilibrium and metabolites, consequently reinstating gut barrier integrity, mitigating chronic low-grade inflammation, and affecting the onset and progression of GLMD through the regulation of the gut-liver axis. This paper reviews the application of FMT in the treatment of GLMD, emphasizing research outcomes and efficacy assessments in clinical trials and animal studies. As a simple and secure intervention, FMT is anticipated to provide new therapeutic alternatives for GLMD patients in the future with the deepening of relevant research, the screening of specific probiotics and the revelation of functional mechanisms. This paper aims to clarify the potential mechanism of FMT in addressing GLMD, summarise recent research developments in this field, and anticipate the opportunities and challenges of FMT in clinical application.},
}

Humans
*Fecal Microbiota Transplantation/methods
*Gastrointestinal Microbiome/physiology
Animals
*Metabolic Diseases/therapy/microbiology/metabolism

@article {pmid42063504,
year = {2026},
author = {Yu, B and Zhao, WW and Tao, L and Li, K},
title = {The microbiota-gut-brain axis perspective: mechanisms and intervention strategies for the comorbidity of chronic constipation and depression.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1800520},
pmid = {42063504},
issn = {1664-302X},
abstract = {BACKGROUND: Chronic constipation and depression are highly prevalent worldwide. These two conditions frequently co-occur in clinical practice. Accumulating evidence indicates that gut microbiota dysbiosis mediates this comorbidity through the microbiota-gut-brain axis (MGBA).

METHODS: This narrative review systematically summarizes current research on MGBA bidirectional communication mechanisms, gut microbiota alterations in comorbid patients, and microbiota-targeted intervention strategies.

RESULTS: The MGBA facilitates bidirectional communication through four major pathways: neural pathways via the vagus nerve, immune pathways via cytokines, endocrine pathways via the HPA axis, and metabolic pathways via short-chain fatty acids and neurotransmitter precursors. Gut dysbiosis is associated with comorbidity and may contribute to its pathogenesis through multiple mechanisms. First, neurotransmitter metabolism becomes dysregulated, particularly in the serotonin and GABA systems. Second, chronic low-grade inflammation develops with elevated pro-inflammatory cytokines. Third, intestinal barrier dysfunction occurs, leading to increased permeability and bacterial translocation. Fourth, HPA axis hyperactivity emerges. Fifth, production of microbial metabolites is altered, including short-chain fatty acids and tryptophan metabolites. Comorbid patients exhibit characteristic microbiota signatures. These include reduced abundance of butyrate-producing bacteria such as Faecalibacterium, Roseburia, and Coprococcus. Microbial diversity decreases significantly. Pro-inflammatory taxa become enriched. Several evidence-based interventions show promise. These include psychobiotics, fecal microbiota transplantation, and dietary modifications such as Mediterranean diet and high-fiber intake. Exercise and integrative approaches including traditional Chinese medicine also demonstrate beneficial effects.

CONCLUSION: The gut microbiota represents a critical hub connecting gastrointestinal and mental health. Microbiota-targeted therapies offer promising strategies for managing chronic constipation-depression comorbidity. Future research should establish causal relationships and develop reliable microbial biomarkers. Precision medicine approaches based on individual microbiome profiles are needed to optimize therapeutic outcomes.},
}

@article {pmid42067917,
year = {2026},
author = {Fang, Q and Huang, S and Zhang, C and Li, M and Ye, Z and Guo, H and Xiao, M and Wang, S and Yu, L and Zhang, H and Zhao, J and Tian, F and Chen, W and Zhai, Q},
title = {Capsaicin ameliorates glycemic levels via gut microbiota-derived 5-aminolevulinic acid in mice.},
journal = {Microbiome},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40168-026-02415-8},
pmid = {42067917},
issn = {2049-2618},
support = {BX20250339//Postdoctoral Fellowship Program and China Postdoctoral Science Foundation/ ; U23A20259//National Natural Science Foundation of China/ ; JUSRP622013//Fundamental Research Funds for the Central Universities/ ; },
abstract = {BACKGROUND: Capsaicin, a natural alkaloid in chili peppers, regulates glycemic levels; however, its mechanisms and therapeutic potential remain unclear. This study aimed to elucidate the role of gut microbiota and their metabolites in mediating capsaicin's glycemic regulatory effects. We conducted experiments in specific pathogen-free (SPF) and germ-free (GF) mice, transient receptor potential vanilloid 1 (TRPV1) receptor ablation studies, and fecal microbiota transplantation (FMT) to demonstrate the involvement of gut microbiota in capsaicin-mediated glycemic control. Metagenomics and metabolomics analyses were employed to identify key microbial strains and metabolic pathways. Keystone strains and metabolites were supplemented in GF mice without capsaicin intervention to validate their effects on glycemic regulation. In vitro co-culture experiments were performed to investigate the mutualistic relationships among keystone strains under capsaicin treatment.

RESULTS: Gut microbiota constitute an important component of capsaicin-mediated glycemic regulation, acting in concert with but not solely dependent on TRPV1 signaling. Gut microbiota altered by capsaicin promote the production of 5-aminolevulinic acid (5-ALA), which contributes to heme synthesis and enhances glycemic control. Supplementation with Akkermansia muciniphila, Ligilactobacillus murinus, or 5-ALA in GF mice recapitulates the glycemic benefits of capsaicin. Furthermore, capsaicin enriches Akkermansia muciniphila, which in turn supports the growth of Ligilactobacillus murinus.

CONCLUSION: Capsaicin-induced changes in the gut microbiota promote 5-ALA synthesis, leading to improved glycemic control. These findings suggest that dietary or probiotic interventions targeting gut microbiota, particularly Akkermansia muciniphila and 5-ALA, may offer promising strategies for managing glycemic disorders, including type 2 diabetes (T2D). Video Abstract.},
}

@article {pmid42068031,
year = {2026},
author = {Chen, S and Feng, H and Wang, Y and Huang, J and Xu, S and Gong, Y and Liu, X and Ouyang, Y and Ye, Q and Zheng, D and Sun, K and Wang, A and Chen, Y},
title = {Intestinal epithelial Syndecan-1 maintains mucosal homeostasis in inflammatory bowel disease by enhancing Faecalibacterium prausnitzii biofilm formation.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2665870},
doi = {10.1080/19490976.2026.2665870},
pmid = {42068031},
issn = {1949-0984},
mesh = {Animals ; *Syndecan-1/genetics/metabolism ; *Inflammatory Bowel Diseases/microbiology/metabolism/genetics ; Mice ; *Intestinal Mucosa/microbiology/metabolism ; Gastrointestinal Microbiome ; *Biofilms/growth & development ; Mice, Knockout ; Humans ; *Faecalibacterium prausnitzii/physiology/genetics/growth & development ; Mice, Inbred C57BL ; Homeostasis ; Disease Models, Animal ; Dextran Sulfate ; Colitis/microbiology/chemically induced ; Male ; Fecal Microbiota Transplantation ; },
abstract = {Despite the rising global incidence of inflammatory bowel disease (IBD), curative therapies remain unavailable. While our previous work implicated the intestinal proteoglycan Syndecan-1 (SDC1) in IBD-associated barrier dysfunction and inflammation, the underlying mechanism was unclear. This study aimed to elucidate how SDC1 maintains intestinal barrier integrity through interactions with the gut microbiome. In DSS-induced colitis, global knockout of Sdc1 (Sdc1[-/-]) exhibited exacerbated inflammatory infiltration and greater impairment of barrier structure and function than wild-type (WT). Formation of intestinal organoids was independent of genotype, indicating that Sdc1[-/-] does not impair barrier function via disrupting epithelial development. The heightened colitis susceptibility in Sdc1[-/-] mice was abolished in the antibiotic-treated pseudo-germ-free models, and transmissible to WT mice via fecal microbiota transplantation. Similar results were reproduced in a germ-free mouse model. Metagenomic sequencing identified Faecalibacterium prausnitzii as the most significantly depleted species upon Sdc1 knockout. In vitro, SDC1-attached glycosaminoglycans (heparan sulfate (HS) and chondroitin sulfate (CS)) but not the SDC1 core protein promoted F. prausnitzii growth. Prokaryotic transcriptome profiling indicated that HS/CS induces cobalamin biosynthesis in F. prausnitzii. The critical role of cobalamin as a mediator was confirmed, as its synthetic inhibition significantly diminished the growth-promoting effect of HS/CS. Mechanism studies showed that HS/CS enhanced biofilm formation in F. prausnitzii, thereby facilitating cobalamin biosynthesis. Oral administration of HS ameliorated DSS-induced colitis and promoted mucosal colonization of F. prausnitzii, independent of the host genotype. Finally, human IBD biopsies revealed a positive correlation between epithelial SDC1 and mucosal F. prausnitzii, as well as an inverse correlation with bacterial translocation and the number of LPS‑positive cells. Our study elucidates a novel mechanism in which the glycosaminoglycan chains of SDC1 promote F. prausnitzii colonization and growth through enhanced biofilm formation and cobalamin synthesis, thereby highlighting the therapeutic potential of HS for IBD and offering a new basis for host-directed microbiota regulation.},
}

Animals
*Syndecan-1/genetics/metabolism
*Inflammatory Bowel Diseases/microbiology/metabolism/genetics
Mice
*Intestinal Mucosa/microbiology/metabolism
Gastrointestinal Microbiome
*Biofilms/growth & development
Mice, Knockout
Humans
*Faecalibacterium prausnitzii/physiology/genetics/growth & development
Mice, Inbred C57BL
Homeostasis
Disease Models, Animal
Dextran Sulfate
Colitis/microbiology/chemically induced
Male
Fecal Microbiota Transplantation

@article {pmid42068814,
year = {2026},
author = {Kanannejad, Z and Taylor, WR and Ghatee, MA and Mohkam, M},
title = {Microbial regulation of immune tolerance during embryonic implantation and pregnancy.},
journal = {Journal of reproductive immunology},
volume = {175},
number = {},
pages = {104898},
doi = {10.1016/j.jri.2026.104898},
pmid = {42068814},
issn = {1872-7603},
abstract = {Maternal immune tolerance is essential for successful embryo implantation and maintenance of pregnancy. The maternal microbiome, particularly in the gut, vagina, and possibly the placenta, has emerged as an important regulator of immune adaptation during gestation. Through continuous interaction with the maternal immune system, the microbiota influence key immune cell populations such as regulatory T cells, uterine natural killer cells, and dendritic cells. These cells promote a tolerogenic environment necessary for embryo acceptance and proper placental development. Microbial-derived metabolites, including short-chain fatty acids and tryptophan derivatives, play important roles in modulating cytokine production and immune cell differentiation. Disruption of microbial balance, or dysbiosis, has been associated with a range of pregnancy complications, including implantation failure, preeclampsia, gestational diabetes, and preterm birth. Additionally, the maternal microbiome may influence fetal immune development, with implications for the offspring's long-term health. Emerging translational research suggests that interventions targeting the maternal microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation, may beneficially modulate immune responses during pregnancy. While these approaches are promising, variability in individual microbiome composition and immune responses underscores the need for personalized strategies. In summary, the maternal microbiome is a dynamic and influential factor in shaping immune tolerance during pregnancy. A deeper understanding of microbiota-immune interactions may pave the way for novel, microbiome-based therapies to enhance reproductive outcomes and promote maternal-fetal health.},
}

@article {pmid42062271,
year = {2026},
author = {Jang, S and Kim, YJ and Park, J and Kim, D and Kim, TH and Lee, S and Kim, DJ and Ryu, CM and Seo, HW},
title = {A Muribaculaceae-enriched microbiota exacerbates TLR4-dependent Acinetobacter baumannii-induced hyperinflammatory sepsis.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-72435-3},
pmid = {42062271},
issn = {2041-1723},
abstract = {Host survival during sepsis depends not only on pathogen burden but also on inflammatory thresholds calibrated by the gut microbiota. Here, we show that different survival outcomes were observed in genetically equivalent female C57BL/6 mouse populations depending on their specific gut microbiota configuration. A Muribaculaceae-enriched gut microbiota, characterized by the dominance of Sangeribacter muris KT1-3, predisposed mice to fatal sepsis caused by Acinetobacter baumannii via TLR4-dependent hyperinflammation. This lethal phenotype, reproduced by colonization with S. muris strain KT1-3, was transferable by fecal microbiota transplantation and co-housing. Notably, fixed-dose LPS challenge and ex vivo stimulation assays demonstrated that this configuration induces a heightened TLR4-dependent inflammatory responsiveness independent of bacterial replication. Single-cell transcriptomics revealed that these microbiota-derived factors establish a transcriptionally pre-activated macrophage state, resulting in production of excessive pro-inflammatory cytokines upon challenge. Mechanistically, S. muris strain KT1-3 releases heat-stable and low-molecular-weight (<3 kDa) metabolites that are sufficient to potentiate systemic cytokine surges under a fixed-dose endotoxin challenge in vivo, effectively lowering the host's activation threshold for TLR4-driven signaling. Tlr4-deficient mice harboring the KT1-3-enriched susceptible microbiota survived despite persistent bacterial dissemination, demonstrating that the microbiota-TLR4 axis dictates hyperinflammatory A. baumannii-induced sepsis outcomes by modulating inflammatory magnitude rather than pathogen clearance. Our results provide a conceptual framework for how specific gut microbiota configurations modulate host susceptibility and drive infection resilience.},
}