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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid42243963,
year = {2026},
author = {Zong, J and Luo, Y and Wu, M and Wang, N and Sui, Y and Yang, J and Zhang, B and Li, C and Zhou, X},
title = {Gut microbiota-derived Tryptophanol driven by N-Carbamylglutamate alleviates premature ovarian failure through inhibiting oxidative stress.},
journal = {Journal of ovarian research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13048-026-02152-4},
pmid = {42243963},
issn = {1757-2215},
support = {2023YFD1300501//National Key Research and Development Program of China/ ; 32172726,32272872//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Premature ovarian failure (POF) affects 1-5% of women under 40 years old and is characterized by granulosa cells (GCs) apoptosis and follicular atresia. However, the pathogenesis of POF is complex and lacks effective prevention and treatment strategies. N-carbamylglutamate (NCG), a bioactive substance known for its antioxidant properties; however, whether it can alleviate POF remains unclear.

METHODS: This study using the cyclophosphamide (Cy)-induced POF mouse model, and demonstrated that NCG, has beneficial effects in alleviating POF symptoms and restoring the intestinal mucosal barrier through gut microbiota-metabolite crosstalk. Integrated 16 S rRNA sequencing, untargeted metabolomics, and fecal bacteria transplantation (FMT) experiments revealed that NCG induced restructuring of gut microbial communities, with enrichment of Muribaculum intestinale and concomitant elevation of its associated Tryptophan-derived metabolite, Tryptophanol.

RESULTS: Mechanistically, Tryptophanol, supplementation alleviated POF by reducing mouse GCs apoptosis and oxidative stress via inhibiting Phosphatidylinositol 3-kinase/ Protein Kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) pathways, thereby restoring ovarian function and fertility, and the efficacy of NCG in alleviating POF relies on promoting Tryptophanol-mediated anti-oxidative stress.

CONCLUSIONS: Our findings, highlight the "gut microbiota-Tryptophanol-ovary" axis in POF pathogenesis, and propose a potential therapy for NCG to regulate gut microbiota to restore ovarian redox homeostasis to alleviate POF.},
}

@article {pmid42244285,
year = {2026},
author = {Chen, Q and Liu, J and Jin, Y and Gu, Y},
title = {[Gut microbiota dysbiosis in type 1 diabetes mellitus: Impacts, mechanisms, and interventions].},
journal = {Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences},
volume = {51},
number = {3},
pages = {387-396},
pmid = {42244285},
issn = {1672-7347},
support = {2023ZD0507400 and 2023ZD0507403//the Four Major/ ; },
mesh = {Humans ; *Diabetes Mellitus, Type 1/microbiology/therapy/immunology ; *Dysbiosis/microbiology/therapy/complications ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; Fatty Acids, Volatile/metabolism ; },
abstract = {Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease whose pathogenesis involves interactions between genetic susceptibility and environmental factors. Gut microbiota dysbiosis may participate in the onset and progression of T1DM. Dysbiosis of the gut microbiota in patients with T1DM is characterized not only by reduced microbial diversity but also by systemic functional disturbances, particularly the depletion of protective metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids. These alterations may aggravate pancreatic islet autoimmunity through mechanisms including molecular mimicry, disruption of immune homeostasis, and impairment of intestinal barrier function. Intervention strategies targeting the gut microbiota, such as fecal microbiota transplantation, probiotics, and dietary regulation, have shown potential in delaying disease progression and improving glycemic control in animal models and some clinical trials. However, the heterogeneity of therapeutic efficacy still requires further validation. Future studies should integrate multi-omics technologies with personalized medicine approaches to further elucidate microbiota-host interaction mechanisms, thereby promoting early prediction and precision intervention for T1DM. Regulation of the gut microbiota may become a novel therapeutic target for the prevention and treatment of T1DM and provide new strategies for its management.},
}

Humans
*Diabetes Mellitus, Type 1/microbiology/therapy/immunology
*Dysbiosis/microbiology/therapy/complications
*Gastrointestinal Microbiome/physiology
Fecal Microbiota Transplantation
Probiotics/therapeutic use
Animals
Fatty Acids, Volatile/metabolism

@article {pmid42245509,
year = {2026},
author = {Wang, Z and Li, L and Dong, Y and Zhang, Y},
title = {The microbiota-tryptophan-brain axis in neurodegenerative diseases: pathogenic mechanisms, disease-specific roles, and translational therapeutics.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1820111},
pmid = {42245509},
issn = {1664-302X},
abstract = {The pathogenesis of neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD) and Parkinson's disease (PD) is very complex. Recent studies have shown that gut microbiota and their metabolites play a key role in the progression of these diseases. Tryptophan (Trp) is an essential amino acid, which mainly produces a variety of biologically active compounds in the intestine through the metabolism of indole pathway, Kynurenine pathway (KP) and serotonin pathway, including indole derivatives, Kynurenine (KYN) and serotonin (5-HT). These metabolites affect the central nervous system (CNS) through the Microbiota-gut-brain axis (MGBA) and affect CNS in a variety of mechanisms, including immune regulation, neuroprotection and maintenance of intestinal barrier function. They are involved in key pathological processes such as neuroinflammation, oxidative stress and pathological protein aggregation. This paper systematically reviews the mechanism of the role of Trp metabolites derived from gut microbiota in NDDs, and explores their specific roles in AD, PD, Amyotrophic Lateral Sclerosis (ALS) and Huntington's disease (HD), and summarizes the potential therapeutic value of the current pathway strategy. These strategies include nutritional intervention, targeted microbiome therapy [such as probiotic and fecal microbiota transplantation (FMT)], and metabolite-derived drugs. Future research must clarify its dynamic mechanism in the human body, develop relevant biomarkers, and promote personalized prevention and treatment strategies through clinical transformation, so as to provide a new direction for early intervention and treatment of NDDs.},
}

@article {pmid42246001,
year = {2026},
author = {Chen, S and Liu, J and Ni, H and Zhu, F and Liu, H and Lin, R},
title = {Gut microbiota and the kidney-gut-skin axis in chronic kidney disease-associated pruritus: mechanisms and therapeutic implications.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1811786},
pmid = {42246001},
issn = {2235-2988},
mesh = {Humans ; *Pruritus/therapy/etiology/microbiology ; *Renal Insufficiency, Chronic/complications/microbiology/therapy ; Animals ; *Gastrointestinal Microbiome/physiology ; *Skin/microbiology/pathology ; *Kidney/microbiology ; Dysbiosis ; Probiotics/therapeutic use ; },
abstract = {Chronic kidney disease-associated pruritus (CKD-aP) is a highly prevalent and debilitating symptom in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD), severely impairing quality of life, sleep quality, mental health, and clinical outcomes. Its pathogenesis is multifactorial and remains incompletely understood, involving chronic inflammation, immune imbalance, abnormal neuro-opioid pathways, mineral metabolism disorders and skin barrier damage. The kidney-gut-skin axis has attracted increasing attention as a novel theoretical framework to elucidate the roles of gut microbiota dysbiosis, gut-derived uremic toxins, intestinal barrier impairment and systemic inflammation in the development of CKD-aP. This review summarizes the traditional pathogenic mechanisms of CKD-aP, reviews recent advances linking gut microbial alterations to pruritus-related pathways, and systematically evaluates gut-targeted and metabolism-targeted interventions, including probiotics, prebiotics, synbiotics, AST-120, fecal microbiota transplantation, phytochemicals, Uremia Clearance Granules, and vitamin D-related strategies. Current evidence is mostly associative and is mainly derived from general CKD/ESKD populations, animal models, and in vitro studies; specific clinical validation in CKD-aP cohorts remains limited. Accordingly, gut microbiome-related mechanisms and interventions remain hypothetical and adjunctive, without established causal relationships or validated standard therapies for CKD-aP. Future studies are required to identify CKD-aP-specific pathological alterations, adopt longitudinal design and multi-omics analysis, conduct mechanistic verification, and perform randomized controlled trials with pruritus as a predefined primary endpoint.},
}

Humans
*Pruritus/therapy/etiology/microbiology
*Renal Insufficiency, Chronic/complications/microbiology/therapy
Animals
*Gastrointestinal Microbiome/physiology
*Skin/microbiology/pathology
*Kidney/microbiology
Dysbiosis
Probiotics/therapeutic use

@article {pmid42246158,
year = {2026},
author = {Xia, R and Ge, J and Shuai, Y},
title = {The Prebiotic 2'-Fucosyllactose Ameliorates Colitis via an Akkermansia muciniphila-Mediated Prebiotic-Microbiota-Metabolite Axis.},
journal = {Journal of agricultural and food chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jafc.5c15443},
pmid = {42246158},
issn = {1520-5118},
abstract = {Recent studies indicate that 2'-fucosyllactose (2'-FL), a human milk oligosaccharide, alleviates inflammatory bowel disease (IBD) by modulating the gut microbiota, yet the underlying mechanisms and key functional bacteria involved remain unclear. This study employed fecal microbiota transplantation and an antibiotic-treated mouse model to investigate the role of 2'-FL-mediated gut microbiota in lipopolysaccharide-induced colitis, with a focus on Akkermansia muciniphila (A. muciniphila). Results demonstrated that 2'-FL intervention significantly enriched A. muciniphila in the gut and promoted the production of short-chain fatty acids (SCFAs). Fecal microbiota transplantation experiments confirmed that 2'-FL-modulated microbiota reshaped the gut ecosystem in recipient mice. Notably, monocolonization with A. muciniphila alone alleviated colitis, while coadministration of 2'-FL synergistically enhanced anti-inflammatory effects and SCFAs production. These findings reveal that 2'-FL operates via a "prebiotic-key bacterium-metabolite" axis, wherein A. muciniphila acts as a mediator to metabolize 2'-FL into SCFAs, orchestrating anti-inflammatory and barrier-protective responses.},
}

@article {pmid42246374,
year = {2026},
author = {Pauwels, A and Devolder, L and Falony, G and D'haeseleer, M and Nagels, G and Van Remoortel, A and Derrien, M and D'hooghe, M and Raes, J},
title = {Deconfounded, quantitative microbiome profiling identifies robust multiple sclerosis markers and clinical covariate associations.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2681876},
doi = {10.1080/19490976.2026.2681876},
pmid = {42246374},
issn = {1949-0984},
abstract = {Despite a wealth of gut microbiota studies in multiple sclerosis (MS), consistent results are lacking. Here, we study confounder effects and use of quantitative microbiome profiling (QMP) in 228 MS patients (103 untreated) and 2860 population controls (Flemish Gut Flora Project (FGFP)). Total bacterial load was lower in relapsing remitting (RR)MS, while strong fecal moisture effects, indicative of longer transit times, in MS vs. FGFP, were driven by primary progressive (PP)MS. Applying cell count and moisture in deconfounded QMP, we identified 21 differentially abundant genera in MS, with a.o. Lachnobacterium, Blautia enriched, and Clostridium, Bacteroides depleted. Deconfounded QMP across 10 published studies (1065 patients, 874 controls) did not confirm commonly detected markers (Akkermansia, Roseburia), yet lowered Bacteroides, and higher Blautia and Methanobrevibacter emerged as robust MS biomarkers. Lowered butyrate producers (Butyricicoccus, Butyricimonas) merit further investigation. Enterotype stratification linked the low cell count Bacteroides 2 enterotype to low-efficacy DMTs, and the Prevotella enterotype to lower disease severity. Serum glial fibrillary acidic protein (GFAP), a disease progression biomarker, was identified as a covariate of gut microbial variation and inversely correlated with Faecalibacterium and Roseburia abundance in PPMS. Overall, our study provides robust disease markers and emphasizes the importance of QMP and confounder control.},
}

@article {pmid42247160,
year = {2026},
author = {Palani Kumar, MK and Iyer, KS and Shahi, SK and Raygoza Garay, JA and Mangalam, A and Dayal, S},
title = {Age and sex dependent shift in murine gut microbiome reveals pathological links to host cardiovascular and metabolic pathways.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {42247160},
issn = {2509-2723},
support = {HL168630/HL/NHLBI NIH HHS/United States ; HL007344/HL/NHLBI NIH HHS/United States ; BX007087//U.S. Department of Veterans Affairs/ ; AI162778//National Institute of Allergy and Infectious Diseases/ ; 18IPA4180014//American Heart Association/ ; P30 ES005605/ES/NIEHS NIH HHS/United States ; 1I01CX002212//Iowa City Veterans Affairs Medical Center/ ; },
abstract = {The gut microbiome undergoes dynamic, sex-dependent changes across the lifespan. However, comprehensive studies examining the combined effects of age and sex are limited. This study investigated both compositional and functional alterations in the gut microbiome of young (4 months, n = 14) and aged (20 months, n = 20) C57BL/6 J mice of both sexes using 16S rRNA gene (V3-V5) sequencing. Microbial community structure and predicted functional profiles were analyzed via QIIME2 and PICRUSt2, with pathway annotation based on MetaCyc. Compared to aged mice, young mice exhibited higher alpha diversity, with the highest increase observed in young females. This sex-specific difference was lost in aged mice. Aging was also associated with an increased Firmicutes-to-Bacteroidetes ratio, and distinct shifts in key taxa, including increased Lactobacillus and Roseburia and reduced Bacteroides and Lachnospiraceae. Functional prediction revealed substantial age-related metabolic shifts, especially in females showing alteration in 45 pathways including upregulation of branched-chain amino acid (BCAA) metabolism, uric acid metabolism, and lipopolysaccharide biosynthesis. To directly link alterations in microbial BCAA metabolism with host metabolic outcomes, fecal abundance of the bacterial BCAA aminotransferase gene (ilvE) was quantified and found to be significantly increased in aged mice. Concurrently, aged mice exhibited higher plasma levels of BCAA, insulin, and random glucose, indicating age-associated metabolic dysregulation. Fecal ilvE abundance associated positively with plasma BCAA levels, and negatively with blood glucose in aged mice, suggesting a link between microbial BCAA metabolism and host glucose homeostasis. Our findings demonstrate that gut microbiome composition and function are influenced by both age and sex. We also showed that these alterations in microbial BCAA metabolism are associated with host metabolic parameters during aging. Our findings underscore the importance of incorporating both age and sex as biological variables in microbiome research and may inform development of age- and sex-specific microbiome-targeted interventions.},
}

@article {pmid42247892,
year = {2026},
author = {Yang, W and Chen, J and Zhang, Y and Ma, X and Sun, J and Xia, L and Zeng, J},
title = {From air pollution to lung cancer: Microbiota as a mediator in the malignant transformation of pulmonary nodules.},
journal = {Microbiological research},
volume = {311},
number = {},
pages = {128572},
doi = {10.1016/j.micres.2026.128572},
pmid = {42247892},
issn = {1618-0623},
abstract = {Air pollution contributes to the malignant transformation of pulmonary nodules and the development of lung cancer. Emerging evidence suggests that the lung is not a sterile environment, and that air pollution-induced dysbiosis may alter the composition and diversity of the lung microbiota. This review explores the pathway by which exposure to air pollution may contribute to respiratory tract dysbiosis, which in turn may alter the tumor microenvironment, disrupt immune homeostasis, and ultimately be implicated in the progression of pulmonary nodules. A model of "air pollution-microbiota dysbiosis-immune modulation-PN malignancy" is proposed. Regarding alterations in the tumor microenvironment and immune suppression, the roles of various cytokines (IL-1, IL-6, IFN-γ, TGF-β) and signaling pathways (PI3K/AKT, NF-κB, ERK) and the effects of immune suppression on T cells, natural killer cells, and macrophages were found. Additionally, the "oral-lung axis" contributes to the progression of PD-LC, with Porphyromonas gingivalis identified as a key biomarker and pathogenic driver. Additionally, treatment approaches such as immune checkpoint inhibition, antibiotic therapy, fecal microbiota transplantation, and probiotic therapy have all shown encouraging potential. This review highlights the pivotal role of dysbiosis in the air pollution-PN-LC axis, providing insights into novel pathogenic mechanisms and highlighting microbiota-targeted approaches for lung cancer prevention and treatment.},
}

@article {pmid42248097,
year = {2026},
author = {Li, S and Li, Z and Chen, C and Liu, M and Cui, Y and Zhu, X and Wang, Z and Sun, H and Li, D and Liu, B and Shi, Y},
title = {Alfalfa polysaccharides-driven Kineothrix alysoides alleviates deoxynivalenol-induced intestinal injury by regulating macrophage polarization.},
journal = {Journal of hazardous materials},
volume = {514},
number = {},
pages = {142588},
doi = {10.1016/j.jhazmat.2026.142588},
pmid = {42248097},
issn = {1873-3336},
abstract = {Deoxynivalenol (DON), as one of the common mycotoxins, is widely present in crops and poses a significant threat to host health. Alfalfa polysaccharides (APs), as novel prebiotics, exert significant immunoregulatory effects and can modulate gut microbiota (GM). However, it remains unclear whether APs can alleviate DON-induced intestinal injury. In this study, we demonstrated that APs attenuated DON-induced intestinal toxicity by reducing inflammatory responses, maintaining intestinal barrier integrity, and promoting M2 macrophage polarization. Fecal microbiota transplantation (FMT) assays showed that transplantation of DON-disrupted GM into healthy recipient mice recapitulated the intestinal pathological injury induced by DON, whereas transplantation of fecal microbiota from the control and APs-treated groups exerted no adverse effects in mice. APs treatment restored the disrupted GM and significantly upregulated the abundance of Kineothrix alysoides (K. alysoides). Gavage administration of K. alysoides effectively alleviated DON-induced intestinal injury and inhibited M1 macrophage polarization. The beneficial effects of K. alysoides were abolished when macrophages were depleted using clodronate liposomes. Collectively, these results indicate that APs can ameliorate DON-induced intestinal injury by regulating K. alysoides and macrophage polarization, providing an important scientific basis for the future application of APs in food and feed products.},
}

@article {pmid42233026,
year = {2026},
author = {Hu, N and Yang, Y and Chen, R and Guan, J and Gu, H and Zhang, L and Zhang, X and Wang, X and Zhang, L},
title = {Resveratrol ameliorates intrahepatic cholestasis of pregnancy by modulating the gut-liver axis and FXR-mediated bile acid homeostasis.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1819374},
pmid = {42233026},
issn = {1664-3224},
abstract = {OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder with limited treatment options. This study investigated the therapeutic potential of resveratrol (RES) and its underlying mechanisms, focusing on the gut-liver axis and bile acid metabolism in an estrogen-induced ICP rat model.

METHODS: Pregnant rats were randomized into Sham, ICP (induced by 17β-estradiol), and ICP+RES (15, 30, 60 mg/kg) groups. Systemic and hepatic inflammation, liver function, histopathology, and intestinal barrier integrity were assessed. Hepatic bile acid profiles were analyzed by UHPLC-MS/MS, and gut microbiota was evaluated by 16S rRNA sequencing. The role of gut microbiota was further examined via fecal microbiota transplantation (FMT) in pseudogerm-free rats. Key proteins in the FXR signaling pathway were analyzed by Western blotting.

RESULTS: RES treatment dose-dependently alleviated ICP manifestations, including reducing serum levels of total bile acids, total bilirubin, and liver enzymes (AST, ALT, ALP), while mitigating systemic and hepatic inflammation. It also restored intestinal barrier integrity and corrected gut microbiota dysbiosis. FMT from RES-treated donors recapitulated these therapeutic effects in recipient ICP rats. Furthermore, RES reversed the hepatic bile acid imbalance by reducing primary bile acids and increasing beneficial secondary bile acids. Mechanistically, RES upregulated the expression of FXR and its downstream targets, including SHP, BSEP, UGT2B4, and CYP1A1.

CONCLUSION: RES effectively ameliorated ICP through multi-faceted mechanisms involving the attenuation of inflammation, restoration of gut microbiota and intestinal barrier, and correction of bile acid homeostasis via activation of the FXR signaling pathway. Our findings highlight RES as a promising multi-mechanistic therapeutic candidate for ICP.},
}

@article {pmid42233032,
year = {2026},
author = {Zheng, H and Lai, C and Liu, F and Luo, H},
title = {Research landscape, thematic evolution, and translational insights of immune checkpoint inhibitor-induced colitis: a bibliometric analysis (2006-2025).},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1817557},
pmid = {42233032},
issn = {1664-3224},
abstract = {BACKGROUND: In recent years, immune checkpoint inhibitors have been widely adopted in cancer therapy. However, their use is frequently associated with the development of colitis. This study employs bibliometric methods to analyze the knowledge structure and current research trends in immune checkpoint inhibitors induced colitis.

METHODS: A systematic literature search was conducted within the Web of Science Core Collection database. Data analysis and visualization were performed using CiteSpace, VOSViewer, and the Bibliometrix package in R software.

RESULTS: The present study collated 1,010 papers on ICI-induced colitis from Web of Science Core Collection, encompassing literature from 62 countries/regions, 1,873 institutions, 7,385 authors, and 373 journals. The United States demonstrated leadership in two key metrics: publication volume, with a total of 470 publications, and total citations, with a total of 41,125 citations. The University of Texas MD Anderson Cancer Center produced the highest number of publications (n=83). Wang Yinghong (n=48) emerged as the most prolific author. The Journal for Immunotherapy of Cancer was the most widely disseminated publication in this field (n=60). An analysis of keywords identified research trends beyond ICI, colitis, and irAE, including Ipilimumab, immunotherapy, Nivolumab, melanoma, cancer, and Pembrolizumab.

CONCLUSION: This study performed a visual analysis of the fundamental knowledge structure underlying immune checkpoint inhibitors mediated colitis. The results indicate that future research should prioritize the exploration of combination therapies, clinical case management strategies, underlying pathogenic mechanisms, fecal microbiota transplantation, and the identification of predictive and diagnostic biomarkers for adverse events.},
}

@article {pmid42234773,
year = {2026},
author = {Sakamachi, Y and Wiley, E and Trempus, CS and Jacobs, H and Solis, A and Johnson, CG and Meng, X and Hussain, S and Roselli, A and Lipinski, JH and O'Dwyer, DN and Randall, TA and Malphurs, J and Papas, B and Wu, BG and Li, Y and Kugler, MC and Mehta, S and Scappini, E and Thomas, SY and Li, JL and Zhou, L and Karmaus, PW and Lih, FB and Fessler, MB and McGrath, JA and Gibson, K and Kass, DJ and Gleiberman, A and Andrianova, E and Walts, A and Invernizzi, R and Molyneaux, PL and Yang, IV and Zhang, Y and Kaminski, N and Segal, LN and Schwartz, DA and Gudkov, AV and Garantziotis, S},
title = {Toll-like receptor 5 protects against murine lung fibrosis through reduced dysbiosis, and TLR5 deficiency is associated with human IPF.},
journal = {Science translational medicine},
volume = {18},
number = {852},
pages = {eadw1028},
doi = {10.1126/scitranslmed.adw1028},
pmid = {42234773},
issn = {1946-6242},
abstract = {Idiopathic pulmonary fibrosis (IPF) is a devastating pulmonary disease with no curative treatment other than lung transplantation that results from maladaptive responses to lung epithelial injury; however, the underlying mechanisms remain unclear, and treatment options are limited. Here, we showed that deficiency in the innate immune receptor toll-like receptor 5 (TLR5) is associated with IPF in humans and with increased susceptibility to bleomycin-induced pulmonary fibrosis in mice and that activation of lung epithelial TLR5 through a synthetic flagellin analog protected mice from experimental fibrosis. Mechanistically, epithelial TLR5 activation induced antimicrobial gene expression and ameliorated lung dysbiosis after injury. In contrast, TLR5 deficiency in mice and patients with IPF was associated with lung dysbiosis. Elimination of the microbiome in mice through administration of antibiotics abolished the protective effect of TLR5, and reconstitution of the microbiome by fecal microbiota transplantation rescued the observed phenotype. In conclusion, these studies revealed that TLR5 protects against pulmonary fibrosis through effects on the lung microbiota, providing insight into therapeutic approaches that may ultimately benefit patients with IPF.},
}

@article {pmid42235389,
year = {2026},
author = {Niu, S and Du, Y and Liu, B and Feng, Z and Wang, G and Li, C and Wang, Y and Sun, Q and Yu, F and Zhou, G and Ba, Y},
title = {Fluoride-induced male reproductive toxicity: Dual-tissue pyroptosis in the gut-testis axis mediated by inflammatory cytokines.},
journal = {Journal of hazardous materials},
volume = {514},
number = {},
pages = {142537},
doi = {10.1016/j.jhazmat.2026.142537},
pmid = {42235389},
issn = {1873-3336},
abstract = {Excessive fluoride impairs male reproductive function, and the gut-testis axis is potentially an important pathway. However, the molecular mechanism remains unclear. This study aimed to investigate whether fluoride damaged the male reproductive system through the gut-testis axis and to identify the molecular pathways involved. We first established in vivo rat models that were treated with sodium fluoride (NaF) and underwent fecal microbiota transplantation (FMT), and then constructed in vitro indirect co-culture models. In NaF-treated rats, our results showed disrupted testicular tissue structure, significantly decreased sperm quality and serum testosterone levels, elevated estradiol, and downregulated expression of tight junction proteins (ZO-1 and Occludin). NaF damaged intestinal physical, chemical, and microbial barriers, characterized by decreased ZO-1, Occludin, and MUC2, increased relative abundances of Firmicutes and Proteobacteria, and elevated intestinal permeability. Higher levels of IL-1β and TNF-α were found in colon, testis, and serum of NaF-treated rats. Transcriptomic analysis revealed significant enrichment of the NF-κB signaling pathway in both the colon and testis. Quantitative analysis and immunofluorescence exhibited the alteration of NF-κB-mediated pyroptosis pathway, with upregulation of Cle-Casp-1, NLRP3, ASC, GSDMD, GSDMD-N in both the colon and testis. The elevation of LDH levels was observed in serum and cell supernatant. Critically, FMT alleviated these damages. Concurrently, in vitro experiments confirmed that NaF induced similar inflammatory responses and pyroptosis, and these effects were mitigated by shikonin. In conclusion, fluoride may impair male reproduction by activating the NF-κB-mediated pyroptosis pathway with the gut-testis axis.},
}

@article {pmid42237172,
year = {2026},
author = {Moon, JM and Kim, SE and Kim, J and Cho, YS and Kim, H and Gweon, TG and Kim, KO and Kim, KW and Kim, K and Kim, MC and Moon, HW and Park, SK and Bang, CS and Yang, YJ and Kim, Y and Oh, CK and Lee, YJ and Lee, JG and Chang, JY and Chong, YP},
title = {Clinical Approaches to Clostridioides difficile Infection Management: Insights From a Nationwide Survey of Korean Physicians.},
journal = {Journal of Korean medical science},
volume = {41},
number = {21},
pages = {e150},
doi = {10.3346/jkms.2026.41.e150},
pmid = {42237172},
issn = {1598-6357},
support = {HI19C0481/MOHW/Ministry of Health and Welfare/Korea ; HC20C0099/MOHW/Ministry of Health and Welfare/Korea ; },
abstract = {BACKGROUND: Clostridioides difficile infection (CDI) remains a significant public health challenge, with variable diagnostic and treatment practices. This study evaluated current clinical practices for CDI diagnosis and management in Korean physicians through a nationwide survey.

METHODS: An online survey was conducted among physicians treating CDI, including gastroenterologists and infectious disease specialists. The survey covered diagnostic approaches, treatment regimens, and management strategies, including differentiation based on disease severity and recurrence.

RESULTS: A total of 300 physicians responded. The most commonly reported indication for CDI testing was the occurrence of three or more diarrheal episodes within a 24-hour period. The majority of physicians (69.7%) preferred multiple diagnostic tests, favoring simultaneous testing (90.4%) over a stepwise approach. Preferred tests included nucleic acid amplification test (NAAT) (69%), glutamate dehydrogenase+toxin A/B combined assay (56%) and toxin enzyme immunoassay (EIA) (48%). Single-test users preferred toxin EIA (37.4%) and NAAT (29.7%). Treatment was primarily tailored to severity by 84.1% of physicians. For non-severe CDI, oral vancomycin (50.7%) and metronidazole (29%) were the main treatments, with 88% not recommending hospitalization. Severe CDI was treated with oral vancomycin (45.3%) or intravenous metronidazole in combination (44.9%), often for ≥ 14 days. For the first recurrence, 69.3% used oral vancomycin, with 22.6% opting for a tapered/pulsed regimen. Fecal microbiota transplantation use increased from 0.3% initially to 17.6% for multiple recurrences. In CDI with ileus, 64% preferred combination therapy, and 48% used vancomycin enemas. In inflammatory bowel disease patients, 99% underwent CDI testing for worsening diarrhea. Immunomodulators and biologics were continued in 79% and 73% of non-severe cases, respectively, but often paused during severe CDI.

CONCLUSION: Korean physicians generally follow the recently developed Korean guideline for CDI practice, but certain gaps and inconsistencies in choices were observed in clinical situations. Further efforts are needed to monitor guideline implementation and to analyze gaps between guideline recommendations and real-world clinical practice to optimize CDI management in Korea.},
}

@article {pmid42237178,
year = {2026},
author = {Zhang, Q and Khan, I and Lei, E and Chen, H and Tang, X and Ding, L and Hong, M},
title = {The gut-brain-gonad axis mediates salinity adaptation in an invasive turtle: causal evidence from microbiota transplantation and metabolite supplementation.},
journal = {Animal microbiome},
volume = {},
number = {},
pages = {},
doi = {10.1186/s42523-026-00583-4},
pmid = {42237178},
issn = {2524-4671},
abstract = {BACKGROUND: Preliminary studies have shown that salinity stress can impair the differentiation of spermatogonial stem cells (SSC) in red-eared slider (Trachemys scripta elegans) through the gut-brain-gonad axis, thereby affecting their reproductive ability. However, a direct causal link between salinity-induced gut microbiota alterations and reproductive suppression remains unclear. To test the hypothesis that gut microbiota and their metabolites mediate salinity adaptation by modulating the gut-brain-gonad axis, we conducted fecal microbiota transplantation (FMT) and metabolite supplementation experiments.

RESULTS: Results showed that the FMT group successfully recapitulated the donor's gut microbial profile and exhibited significant changes in intestinal metabolites. Both FMT and GABA supplementation mimicked the reproductive inhibitory phenotype observed under direct salinity stress: altered brain neurotransmitter levels (increased dopamine, decreased serotonin), downregulated expression of reproductive genes (e.g. GnRH1, FSHβ), and impaired SSC self-renewal and differentiation in testes, as evidenced by reduced marker gene expression (e.g. PLZF, Stra8) and disrupted testicular histology.

CONCLUSION: Our findings demonstrate that salinity stress reshapes the gut microbiota and metabolome. This leads to increased inhibitory signaling, notably via GABA, along the gut-brain-gonad axis. Ultimately, this signaling cascade suppresses reproductive function. This study provides novel mechanistic insights into the environmental adaptation strategies of an invasive species and highlights the potential of targeting the microbiome-metabolite axis for developing innovative, environmentally friendly biocontrol approaches against this invasive species.},
}

@article {pmid42237397,
year = {2026},
author = {Deiana, M and Veschetti, L and Reynolds, K and Hunt, VL and Padovani, N and Manfredi, M and Vezzelli, E and Rizzi, E and Degani, M and Malerba, G and Ursini, T and Ronzoni, N and Piubelli, C and Buonfrate, D and Tiberti, N},
title = {Molecular characterisation of extracellular vesicles released by Strongyloides stercoralis infective larvae isolated from a clinical sample.},
journal = {Parasites & vectors},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13071-026-07484-0},
pmid = {42237397},
issn = {1756-3305},
support = {MR/W006308/1//GW4 BioMed2 MRC DTP studentship/ ; "Fondi Ricerca corrente-L3P2" to IRCCS Sacro Cuore Don Calabria Hospital//Ministero della Salute/ ; },
abstract = {BACKGROUND: Extracellular vesicles (EVs) represent a key mechanism of host-pathogen crosstalk. Numerous helminth parasites have already been reported to shed EV-like structures carrying biomolecules, including small RNAs (sRNAs), with functional effects on target cells. However, the ability of Strongyloides stercoralis to release EVs has yet to be demonstrated.

METHODS AND RESULTS: Following the isolation of S. stercoralis infective larvae (iL3s) from faecal samples obtained from a patient with strongyloidiasis, we showed that iL3s maintained in vitro for up to 48 h release EV-like structures. Transmission electron microscopy and nanoparticle tracking analysis highlighted vesicular structures enclosed by a bilayer and with a diameter of 120 nm in range. Small RNA sequencing identified multiple EV-associated sRNA types, including miRNAs, only partly overlapping with the previously described somatic miRNome. Comparative analyses revealed that several EV-associated miRNAs were conserved amongst Strongyloides spp., whereas others appeared specific to S. stercoralis. Prediction analyses indicated that miRNAs and other sRNAs may target human genes associated with the regulation of gene expression and immune response, supporting a potential role in host-parasite interaction.

CONCLUSIONS: These findings provide the first experimental evidence that S. stercoralis iL3s release EVs carrying regulatory sRNAs and suggest that EV-mediated RNA delivery may represent an additional tool for host-pathogen interaction. More in-depth investigations of these EVs may provide novel insights into the pathophysiology of strongyloidiasis as well as novel targets for clinical applications.},
}

@article {pmid42238434,
year = {2026},
author = {Basson, AR and Katz, J and Nguyen, V and Singh, D and Menghini, P and Gomez-Nguyen, A and Sieg, J and Bell, M and Thamma, K and Ponzani, G and Osme, A and Rodriguez-Palacios, A and Cominelli, F},
title = {A Randomized Controlled Trial Comparing Soy-Pea Protein to Animal Protein in Adults with Crohn's Disease.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.05.20.26353678},
pmid = {42238434},
abstract = {BACKGROUND AND AIMS: Diet plays a critical role in managing Crohn's disease (CD) inflammation. We assessed whether dietary replacement of animal protein (AnimalP) by soy-pea protein (SoyP) decreases the pro-inflammatory potential of gut microbiota and intestinal inflammation in CD patients.

DESIGN: In an open-label, randomized controlled feeding trial at University Hospitals Cleveland Medical Center, CD participants and healthy controls were randomized (1:1) to a soy-pea or animal protein diet for 7-days. Primary outcomes were the absolute difference (Δd7-d0) in; Crohn's Disease Activity Index (CDAI) score and fecal myeloperoxidase (MPO). Secondary outcomes included fecal calprotectin (FC) and high-sensitivity C-reactive protein (hsCRP). Murine fecal transplantation experiments were performed to determine the inflammatory potential of diet-altered gut microbiota.

RESULTS: The study randomized 66 participants and 60 were included in the final analysis (n=31 CD, n=29 HC). After 7 days, CD-SoyP participants were more likely than CD-AnimalP to show reductions in HBI (RR=4.68, 95% CI: 1.22-17.98, P=0.009) and fecal MPO (RR=2.30, 95% CI: 1.04-4.85, P=0.032), with a similar directional trend for CDAI (RR=1.52, 95% CI: 0.89-2.58, P=0.135). No participants experienced worsening of CDAI. The rank-based composite CDAI-MPO score was lower in the CD-SoyP vs CD-AnimalP group (median [IQR]: 5 [4-6] vs 8 [7-9]; P=0.012). Stratified analyses showed significant reductions in fecal MPO among CD participants with lower baseline disease activity (CDAI <150; P<0.0001), but not in those with higher activity (P=0.799).

CONCLUSION: Short-term addition of plant-based soy-pea protein within a controlled diet exerted a beneficial, anti-inflammatory effect in CD, with evidence of greater effects among participants with lower baseline disease activity. ClinicalTrials.gov, Number NCT04065048 .},
}

@article {pmid42239536,
year = {2026},
author = {Singh, P and Saravanan, A and Seitz, J and Alkarzon, N and Medugu, N},
title = {A one health perspective on the intestinal microbiome's role in COVID-19 outcomes and recovery.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1763844},
pmid = {42239536},
issn = {2235-2988},
abstract = {Emerging infectious diseases, particularly zoonotic ones, remain major global health concerns. The Coronavirus Disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), highlights the interconnectedness of human, animal, and environmental health within the One Health framework. The intestinal microbiome plays a central role in host immunity and systemic homeostasis, and its disruption has been linked to altered disease severity and recovery patterns in COVID-19. Evidence suggests that SARS-CoV-2 infection induces intestinal dysbiosis, modifies immune signaling, and affects the microbiota-gut-brain axis (MGBA), contributing to neuropsychiatric and metabolic complications. This review synthesizes current findings on the intestinal microbiome's role in COVID-19 pathophysiology and recovery, explores emerging therapeutic strategies including probiotics, prebiotics, and fecal microbiota transplantation, and emphasizes the importance of integrating microbiome research into pandemic preparedness through a One Health approach.},
}

@article {pmid42240365,
year = {2026},
author = {Chen, B and Su, Z and Sun, Y and Shao, Z and Yu, X and Jiang, X and Xue, X and Yu, L and Wang, L and Zhao, W and Feng, Y and Ning, K and Zhang, M and Cao, A and Zhang, L},
title = {Gut microbial culturomics identifies autism-associated Shigella and reveals species-level remodeling during fecal microbiota transplantation.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0079726},
doi = {10.1128/spectrum.00797-26},
pmid = {42240365},
issn = {2165-0497},
abstract = {Autism spectrum disorder (ASD) has been repeatedly linked to gut microbiota alterations, yet mechanistic insight remains limited by the scarcity of ASD-specific cultured isolates. Here, we performed large-scale gut microbial culturomics on fecal samples from 41 children with ASD and 12 typically developing (TD) controls, generating 1,724 isolates across six phyla. Longitudinal culturomics profiling was further conducted in 17 ASD children undergoing a 9-week fecal microbiota transplantation (FMT) intervention. All isolates underwent 16S rRNA sequencing and non-redundant clustering to assess species-level diversity, ASD-TD differences, and microbial dynamics associated with clinical response. ASD children harbored a distinct culturable microbiota enriched for Shigella flexneri and Shigella boydii, whereas TD children were enriched in beneficial taxa, such as Bifidobacterium catenulatum subsp. and other health-associated species. Notably, 20 species isolated from ASD children and 20 from TD children were absent from major existing gut microbiota biobanks, thereby expanding the cultivable repertoire. Among FMT participants, clinical responders exhibited increased alpha diversity, progressive enrichment of TD-associated beneficial taxa, such as Bacteroides fragilis, Anaerostipes hadrus, Parabacteroides merdae, and Turicibacter sanguinis, and a marked reduction of ASD-associated Shigella flexneri and Shigella boydii, whereas non-responders showed minimal shifts. Acquisition of TD-enriched strains at week 9 was strongly correlated with clinical improvement, suggesting that species-level ecosystem remodeling may contribute to FMT efficacy. This work establishes one of the first ASD-focused gut microbial culturomics resources, identifies Shigella as a potential ASD-associated taxon, and provides foundational evidence and testable mechanistic hypotheses for future microbiome-based interventions in ASD.IMPORTANCEMost autism spectrum disorder (ASD) microbiome studies rely on sequencing, which identifies associations but lacks live strains needed for mechanistic tests. We cultured 1,724 isolates from ASD and typically developing (TD) children, providing an ASD-focused, strain-level resource. ASD samples showed a significantly higher prevalence of Shigella flexneri. Longitudinal profiling during fecal microbiota transplantation (FMT) showed that clinical responders gained TD-enriched taxa and lost Shigella spp., and these shifts correlated with symptom improvement. This resource enables functional assays and gnotobiotic studies with ASD-relevant strains and provides a foundation for rational microbiome-based interventions.},
}

@article {pmid42240746,
year = {2026},
author = {Hu, Z and Yan, J and Wang, X and Liu, Z},
title = {Gut-bone axis in rheumatoid arthritis: microbiota-driven barrier dysfunction, immune crosstalk, and therapeutic strategies.},
journal = {Antonie van Leeuwenhoek},
volume = {119},
number = {7},
pages = {},
pmid = {42240746},
issn = {1572-9699},
support = {2023RC105, 2023KY1235//Medical Health Science and Technology Project of Zhejiang Province/ ; 2024USXH287//Shaoxing University enterprise important horizontal topic/ ; },
mesh = {Humans ; *Arthritis, Rheumatoid/immunology/microbiology/therapy ; *Gastrointestinal Microbiome ; Intestinal Barrier Function ; Animals ; Dysbiosis/immunology ; *Bone and Bones/immunology/metabolism ; },
abstract = {Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive bone destruction in which immune dysregulation plays a central role. Recent evidence has highlighted the gut-bone axis as a critical framework linking gut microbiota to skeletal and immune homeostasis. Gut microbiota dysbiosis disrupts intestinal barrier integrity by altering tight junction proteins and increasing intestinal permeability, facilitating microbial translocation and triggering systemic inflammatory responses. Microbiota-derived metabolites, including short-chain fatty acids, bile acids, and tryptophan metabolites, act as key mediators along the gut-bone axis. These metabolites regulate multiple signaling pathways and immune cell functions, particularly by modulating the balance between T helper 17 and regulatory T cells, suppressing B-cell hyperactivation, promoting macrophage M2 polarization, and inhibiting dendritic cell maturation. These actions may contribute to immune homeostasis and bone metabolism associated with RA. This review systematically summarizes the role of gut microbiota dysbiosis, intestinal barrier dysfunction, and microbial metabolites in RA pathogenesis within the framework of the gut-bone axis. Furthermore, microbiota-targeted therapeutic strategies, including probiotics, prebiotics, dietary interventions, fecal microbiota transplantation, and traditional Chinese medicine, are discussed as potential approaches to restore host-microbiota balance. However, most current evidence is derived from preclinical studies, highlighting the need for further clinical validation. Despite these limitations, a deeper understanding of microbiota-driven mechanisms along the gut-bone axis may provide novel insights into RA pathogenesis and facilitate the development of targeted and personalized therapeutic strategies.},
}

Humans
*Arthritis, Rheumatoid/immunology/microbiology/therapy
*Gastrointestinal Microbiome
Intestinal Barrier Function
Animals
Dysbiosis/immunology
*Bone and Bones/immunology/metabolism