@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

@article {pmid42241760,
year = {2026},
author = {Wang, G and Chen, Y and Xiao, Y and Sun, M and Li, X and Akhtar, M and You, Y and Zhou, X and Shi, D},
title = {Ostrich-derived Bacillus safensis O-6 enhances broiler growth performance by modulating gut microbiota and protein digestibility.},
journal = {Poultry science},
volume = {105},
number = {9},
pages = {107127},
doi = {10.1016/j.psj.2026.107127},
pmid = {42241760},
issn = {1525-3171},
abstract = {In broiler production, the inefficient utilization of dietary protein limits growth performance and wastes resources. Inspired by the high feed conversion efficiency of ostriches, which may host beneficial digestive microbes, this study investigated whether fecal microbiota transplantation (FMT) from ostriches could confer advantageous traits to broilers, and further sought to isolate and evaluate potential probiotic. In an initial FMT trial involving 54 one-day-old broilers, the FMT group exhibited significantly higher average daily gain (ADG) at 7 and 14 days of age compared to the Ctrl group (P < 0.05). From the fecal samples of ostrich donors, a bacterial strain, Bacillus safensis O-6 (O-6), was isolated and identified as a high producer of both protease and cellulase. In a subsequent feeding trial with 72 one-day-old broilers, supplementation with O-6 (4.74 × 10[7] CFU/mL/day in drinking water) increased the ADG by 7.16% by day 35 (P <0.01). The treatment also significantly enhanced the activities of protease, amylase, and lipase in the small intestine (P < 0.05), elevated serum immunoglobulins A and M (IgA and IgM) (P < 0.01), and improved immune organ indices (Spleen index and Bursa of Fabricius index, P < 0.05). Furthermore, O-6 supplementation significantly enhanced the alpha and beta diversity of the cecal microbiota (P < 0.05). This was accompanied by an enrichment of beneficial bacterial taxa, including Rikenellaceae and Alistipes, alongside a substantial reduction in cecal protein content by 28.23%, indicating improved protein digestibility. These results demonstrate that O-6 is a promising probiotic that enhances broiler growth by improving digestive enzyme activity, immune function, and gut microbiota structure. This study demonstrates that beneficial traits of ostriches can be transferred to broiler chickens through their gut microbiota (probiotics), offering a new avenue for the exploration of avian-derived probiotics.},
}

@article {pmid42242207,
year = {2026},
author = {Yasuma-Mitobe, K and Liao, C and Németh, T and Byrne, K and Billips, A and Faustino Ramos, RJJ and Salinas, CN and Chan, E and Perissinoto, M and Adami-Sampson, S and Salman, A and Sidebottom, AM and Plitas, G and Butler, G and Cross, JR and Pamer, EG and Gácser, A and Xavier, JB and Hohl, TM},
title = {Intracellular acidification by microbiota-derived valeric acid facilitates trans-kingdom ecology limiting Candida parapsilosis colonization.},
journal = {Cell host & microbe},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.chom.2026.05.008},
pmid = {42242207},
issn = {1934-6069},
abstract = {In hematopoietic cell transplant (HCT) patients, intestinal Candida parapsilosis expansion and translocation can cause life-threatening candidemia, yet whether commensal intestinal bacteria prevent Candida expansion remains incompletely defined. Here, we trained a machine learning model on supernatant metabolomic profiles of Lachnospiraceae to identify bacteria-derived inhibitors of fungal growth, identifying valeric and butyric acids as top hits. Fecal samples from HCT patients supported this association, with valeric and butyric acid levels inversely correlating with C. parapsilosis growth. In cell culture and mice, valeric acid inhibited C. parapsilosis growth by increasing intracellular acidification. Administration of glycerol valerate, or free or microencapsulated valeric acid, to release valeric acid along the entire intestinal tract blunted C. parapsilosis growth at murine intestinal sites where valeric acid was detected. Thus, machine learning identified a mechanistic driver of trans-kingdom ecology limiting C. parapsilosis intestinal expansion and may inform strategies to reduce patient risk of candidiasis.},
}

@article {pmid42242653,
year = {2026},
author = {Wang, Y and Zhang, J and Hou, X and Guan, T and Gong, J and Lin, J and Zhang, H and Xiao, J and Simal-Gandara, J and Wang, H and Cao, H},
title = {Soluble dietary fiber from Piper sarmentosum Roxb. leaves modulates gut microbiota-derived cis-11-eicosenoic acid to regulate lipid metabolism.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {152887},
doi = {10.1016/j.ijbiomac.2026.152887},
pmid = {42242653},
issn = {1879-0003},
abstract = {Obesity represents a critical global health challenge, significantly elevating risks for major chronic diseases. This underscores the urgent necessity to develop innovative prevention and therapeutic interventions. While Piper sarmentosum Roxb. has demonstrated antidiabetic and antihypertensive properties, its anti-obesity effects and underlying mechanisms remain largely uncharacterized. This study aimed to evaluate the anti-obesity effects of soluble dietary fiber from Piper sarmentosum Roxb. leaves (PSDF) and elucidate its molecular basis. PSDF was characterized as an acidic dietary fiber, predominantly composed of galacturonic acid (55.64%), galactose (21.74%), and arabinose (11.97%), exhibiting a triple-helical conformation and high thermal stability. In diet-induced obese mice, six weeks of PSDF administration significantly ameliorated glucose and lipid metabolic disorders (p < 0.05), an effect associated with modulation of gut microbiota. Untargeted metabolomics identified cis-11-eicosenoic acid (GA) as a key metabolite. In a 3 T3-L1 single-cell model, GA treatment did not affect adipocyte differentiation. However, in a co-culture model of 3 T3-L1 adipocytes and RAW264.7 macrophages, GA significantly downregulated pro-inflammatory cytokines (IL-1β, TNF-α) and SREBF1 expression, while upregulating anti-inflammatory markers (IL-4, IL-10) and fatty acid oxidation genes (CPT1A, PGC-1α). These results initially suggested that GA may exert anti-obesity effects primarily through modulating inflammation-associated lipid metabolism pathways. Fecal microbiota transplantation (FMT) confirmed both GA elevation and anti-adiposity effects were microbiota-dependent. These findings demonstrated PSDF alleviated lipid accumulation by modulating a gut microbiota-adipose axis centered on GA production, thereby improving inflammation-mediated lipid metabolism. This newly elucidated microbiota-GA axis establishes a theoretical basis for developing PSDF-based soluble dietary fibers into microbiota-focused anti-obesity nutraceuticals.},
}

@article {pmid42243132,
year = {2026},
author = {Hu, Y and Zhou, M and Xie, T and Wei, M and Wang, K and Wei, H and Zhang, F and Zhang, Z},
title = {Gut microbiota-associated N-Acetyl-L-leucine mediates fructose-induced hyperuricemia via the P300-URAT1 pathway.},
journal = {NPJ science of food},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41538-026-00917-1},
pmid = {42243132},
issn = {2396-8370},
support = {32560551//National Natural Science Foundation of China/ ; 20232BCJ23090//Training Program for Academic and Technical Leaders of Major Disciplines in Jiangxi Province/ ; 2025004//Project of Qian Xuesen Collaborative Research Center of Astrochemistry and Space Life Science/ ; },
abstract = {Hyperuricemia (HUA), a metabolic disorder characterized by elevated uric acid (UA), is marked by a rising incidence and trend toward earlier onset, both strongly associated with fructose intake. However, the roles of gut microbiota and their metabolites remain unclear. This study employed a fructose-induced HUA mouse model and fecal microbiota transplantation (FMT) to assess the impact of fructose-altered gut microbiota on the microbial community structure and UA degradation capacity in recipient mice. Non-targeted metabolomics was then utilized to identify key metabolites, and the HUA-inducing effects and underlying mechanisms of the metabolite were further validated. The results confirmed that microbiota from fructose-induced HUA mice promoted HUA development in recipients, significantly increasing the abundance of Bacteroidota and reducing microbial UA degradation ability. Specifically, recipient mice exhibited disordered amino acid metabolism, primarily characterized by elevated N-Acetyl-L-leucine. This metabolite was subsequently shown to induce HUA by promoting UA synthesis through enhanced adenosine deaminase and xanthine oxidase activity, as well as inhibiting UA excretion via upregulation of the reabsorption transporter urate transporter 1 (URAT1) through E1A binding protein p300 (P300) regulation. These results highlight N-Acetyl-L-leucine as a pivotal gut microbiota-associated metabolite in fructose-induced HUA and offer new insights and potential targets for future interventions.},
}

@article {pmid42243298,
year = {2026},
author = {Kunevičius, A and Gawlińska, K and Burokas, A and Gawliński, D},
title = {Efficacy of pharmacological and microbiota-based therapies in preclinical models of autism spectrum disorder: a systematic review.},
journal = {Molecular psychiatry},
volume = {},
number = {},
pages = {},
pmid = {42243298},
issn = {1476-5578},
support = {2021/43/B/NZ5/02552//Narodowe Centrum Nauki (National Science Centre)/ ; 2023/51/D/NZ5/02090//Narodowe Centrum Nauki (National Science Centre)/ ; },
abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental condition in which pharmacological and microbiota-targeted interventions are emerging as promising therapeutic avenues. Animal models are the main tool to investigate etiology, molecular mechanisms and screening for pharmacological therapies. Methodological differences, outcome measure variability, incomplete reporting, biological confounders, and overgeneralization of the results made evaluating innovative pharmacological agents challenging. These limitations in the field highlight a need for systematic and standardized research to reliably assess and translate pharmacological interventions from ASD animal models to human clinical relevance.

SUBJECTS: This systematic review synthesized efficacy evidence for pharmacological and microbiota-based therapies across established ASD animal models.

RESULTS: We identified 52 recent (2010-2025) studies that reported key ASD behavioral outcomes after pharmacological or microbiota-focused treatments. Interventions were grouped into therapeutic classes - including oxytocinergic agents, E/I balance therapeutic targets, metabolic drugs, cannabinoids, purine-based interventions and emerging targets - alongside microbiota-directed strategies such as probiotics, prebiotics, and fecal microbiota transplantation. By integrating effect directions and robustness across models, we identified most potential drug candidates, evaluated the efficacy of novel strategies, and recognized critical translational gaps. The reviewed studies demonstrate that ASD-like behavioral deficits in preclinical models can be modulated through interventions targeting diverse biological systems, including neurotransmission, neuroinflammation, metabolism, and the gut-brain axis.

CONCLUSIONS: These findings support the multifactorial nature of ASD pathophysiology which arises from a network of interacting systemic processes rather than a single molecular defect. It could explain the limited success of traditionally narrowly targeted interventions and suggest a paradigm shift into a more systemic approach.},
}

@article {pmid42001079,
year = {2026},
author = {Yang, Y and Kang, C and Pang, R and Huang, S and He, X and Gou, X and Yang, Y and Yan, Y and Ma, X},
title = {Dihydromyricetin exerts neuroprotective effects in acute spinal cord injury by inhibiting NLRP3/Caspase-1 inflammasome through gut microbiome modeling.},
journal = {Journal of inflammation (London, England)},
volume = {23},
number = {1},
pages = {},
pmid = {42001079},
issn = {1476-9255},
support = {2024060//Chengdu Municipal Health Commission Medical Research Project/ ; 25MSZX488//Sichuan Provincial Administration of Traditional Chinese Medicine Research Project/ ; },
abstract = {BACKGROUND: The gut microbiota is closely associated with spinal cord injury (SCI). Dihydromyricetin (DHM), a potent anti-inflammatory compound with neuroprotective properties, has been shown to improve outcomes in various diseases. However, the role of gut microbiota mediating the mechanism neuroprotective effects of DHM in SCI is unknown.

METHODS: Male Sprague-Dawley rats were randomly divided into three groups: SHAM, SCI, and DHM group. Motor function was assessed using the cylinder rearing test, and alterations in gut microbiota composition and metabolites were analyzed via 16S rRNA sequencing. Subsequently, Western blotting and immunofluorescence staining were employed to evaluate intestinal barrier integrity, as well as changes in proteins associated with the TLR4/NF-κB pathway and NLRP3/Caspase-1. Finally, fecal microbiota transplantation experiments were conducted to elucidate the necessity of gut microbiota in mediating the anti-inflammatory effects of DHM.

RESULTS: DHM exhibits a therapeutic effect by attenuating the severity of pathological SCI and promoting motor function recovery. Notably, DHM restored a balanced microbiota pattern by increasing the relative abundance of Actinobacteria and Bacteroidetes, while concurrently decreasing that of Proteobacteria. Furthermore, DHM promoted intestinal barrier recovery, reduced blood lipopolysaccharide (LPS) levels, and suppressed the activation of the TLR4/NF-κB pathway and reduced the activity of the NLRP3/Caspase-1 inflammasome, thereby effectively decreasing the subsequent release of inflammatory factors in spinal cord tissue. Furthermore, the results from the two FMT groups demonstrated that the gut microbiota serves as a critical target for DHM to exert its anti-inflammatory effects.

CONCLUSION: The results of this study demonstrate that restoring microbial balance, repairing intestinal barrier integrity, reducing serum LPS levels, and suppressing the TLR4/NF-κB pathway as well as NLRP3/Caspase-1 inflammasome activity constitute the key regulatory mechanisms underlying the neuroprotective effects of DHM following SCI, thereby opening up possibilities for a novel microbiome-directed therapeutic approach to SCI.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12950-026-00499-5.},
}

@article {pmid42230351,
year = {2026},
author = {Domagała, A and Kiecka, A},
title = {Gut Microbiota and Autoimmune Diseases: The Therapeutic Potential of Probiotics.},
journal = {Current microbiology},
volume = {83},
number = {7},
pages = {},
pmid = {42230351},
issn = {1432-0991},
abstract = {In recent years, increasing attention has been directed toward the role of gut microbiota in the pathogenesis of autoimmune diseases such as type 1 diabetes (T1D), rheumatoid arthritis (RA), and multiple sclerosis (MS). Numerous studies have shown that gut dysbiosis-an imbalance in the intestinal microbial community-can influence host immune responses by modulating inflammatory pathways, gut barrier integrity, and immune cell function. Patients with T1D, RA, and MS often exhibit a decreased abundance of anti-inflammatory bacteria (e.g., Faecalibacterium prausnitzii) and an overrepresentation of pro-inflammatory taxa (e.g., Prevotella copri). Probiotics and fecal microbiota transplantation have shown therapeutic potential by restoring microbial balance, enhancing short-chain fatty acid production, supporting regulatory T cell function, and suppressing pro-inflammatory Th1 and Th17 responses. Despite promising results, the efficacy and safety of these interventions remain uncertain, especially in immunocompromised individuals. The lack of standardization in probiotic formulations, limited large-scale clinical trials, and unknown long-term effects restrict their widespread application. Moreover, individual variability in microbiota composition and disease phenotype complicates the development of universally effective treatments. Further rigorous research is necessary to better understand the immunological mechanisms involved and to develop safe, personalized, and effective microbiota-based therapeutic strategies. Until then, probiotics and FMT should be considered as adjunctive therapies within comprehensive treatment plans for autoimmune diseases rather than standalone solutions.},
}

@article {pmid42230372,
year = {2026},
author = {Ram, E and Carter, D},
title = {Reframing loss of efficacy in sacral neuromodulation: a neurofunctional service model for coloproctology.},
journal = {Techniques in coloproctology},
volume = {30},
number = {1},
pages = {},
pmid = {42230372},
issn = {1128-045X},
abstract = {BACKGROUND: Sacral neuromodulation (SNM) is an established therapeutic option for fecal incontinence, low anterior resection syndrome (LARS), and selected bowel dysfunction phenotypes encountered in colorectal practice. Despite durable benefit in many patients, secondary loss of efficacy (LOE) remains a common long-term management problem and is often interpreted primarily through a mechanical lens.

OBJECTIVE: To refine a conceptual neurofunctional service model for LOE in SNM and to translate it into a more clinically applicable framework for coloproctological practice.

FRAMEWORK: For the purposes of this paper, LOE is defined as deterioration after a previously effective phase, operationalized by one or more of the following: loss of at least 50% of the initial clinically meaningful benefit; deterioration of five or more points on a validated symptom instrument (Wexner Continence Score, LARS Score, or equivalent), or documented worsening in a structured patient symptom diary; or sustained patient-reported decline over at least two consecutive assessments, after exclusion of technical failure. We propose a structured pathway comprising confirmation of LOE, systematic technical exclusion, minimum neurofunctional reassessment, phenotype-guided reprogramming, predefined reassessment intervals, and explicit thresholds for revision or explantation. Terms such as neuroadaptive drift and phenotype mismatch are presented as explanatory hypotheses rather than established mechanisms.

CLINICAL IMPLICATIONS: Viewing SNM as a dynamic network-modulating therapy rather than a static device intervention may reduce unnecessary procedural escalation and improve the consistency of long-term management. The proposed model is intended as an implementable service framework for structured follow-up and reprogramming in patients with suspected LOE.},
}

@article {pmid42230754,
year = {2026},
author = {Bethlehem, L and Bartu, L and Marke, G and Mar, P and Feldman, S and Eggers, J and Ruprecht, C and Britton, GJ and Aggarwala, V and Bongers, G and Li, Z and Yang, N and Hohmann, EL and Mogno, I and Faith, JJ and Grinspan, A},
title = {15-strain live biotherapeutic product or same donor fecal microbiota transplant for recurrent Clostridioides difficile infection: a randomized phase 1b trial.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {42230754},
issn = {1546-170X},
abstract = {Fecal microbiota transplant (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI) but has undefined composition and poor scalability. In vitro manufactured live biotherapeutic products (LBPs) enable both scalability and defined strain composition but with higher manufacturing complexity, resulting in few LBP clinical trials. Here we show how an accessible platform to produce human-grade LBPs could accelerate LBP development. We provide regulatory documentation and manufacturing protocols to facilitate translating microbiome advances to human trials. With this platform, we conducted the first direct comparison of the same bacterial strains from donor-sourced FMT compared to an in vitro manufactured 15-strain LBP drug product, MTC01, for the treatment of rCDI. In a phase 1b randomized controlled trial, 18 of 20 screened patients met eligibility and were randomized equally to one of four arms: low-dose FMT (n = 4), high-dose FMT (n = 5), low-dose MTC01 (n = 4) or high-dose MTC01 (n = 5), with a 5:1 female:male ratio. The primary outcome of safety was met with 10 adverse events across eight patients, evenly spread across MTC01 (five events) and FMT (five events) recipients and no treatment-related adverse events across all four groups. For secondary outcomes of efficacy and engraftment, rCDI was prevented 8 weeks after dosing in seven out of nine LBP patients, similar to eight out of nine FMT patients. Strain engraftment was high and durable for both FMT and MTC01 with a dose effect for the LBP. ClinicalTrials.gov: NCT05911997 .},
}

@article {pmid42231156,
year = {2026},
author = {Yang, Q and Liang, Y and Liu, J and Jia, R and Li, J and Yan, Z},
title = {Fecal microbiota transplantation from Hezuo pigs alleviates intestinal inflammatory injury in Clostridium perfringens type C-infected piglets via modulation gut microbiota and intestinal barrier.},
journal = {BMC microbiology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12866-026-05169-3},
pmid = {42231156},
issn = {1471-2180},
support = {23JRRA1422//Natural Science Foundation of Gansu Province/ ; 32460845//National Natural Science Foundation of China/ ; GSARS10//Pig Industry in Gansu Agriculture Research System/ ; 2023-QN-135//Lanzhou Youth Science and Technology Talent Innovation Project/ ; },
abstract = {Clostridium perfringens type C (CpC)-induced piglet diarrhea is a major challenge in the swine industry. This study aimed to investigate the protective effects of fecal microbiota transplantation (FMT) from Hezuo pigs against intestinal injury in Duroc×Landrace×Yorkshire (DLY) suckling piglets infected with CpC. Piglets were divided into two groups, including CpC-challenged control group and FMT-treatment group, which received fecal suspension from Hezuo pigs prior to infection. Morphological, immunological, microbiomic, and metabolomic analyses were conducted after post-infection. The results demonstrated that FMT significantly alleviated jejunal damage, leading to a significant increase in jejunal villus height and a significant decrease in crypt depth (P < 0.01). The intervention elevated the number of goblet cells (P < 0.05) and upregulated the expression of tight junction protein genes Occludin, ZO-1, Claudin-1 and the anti-inflammatory cytokine IL-10, while significantly reducing the levels of pro-inflammatory cytokines TNF-α and IL-6 (P < 0.05). FMT enriched beneficial genera such as Akkermansia, Rothia, Peptococcus, and Proteocatella, and increased the levels of the sphingolipid metabolite ceramide (d18:1/18:0). Correlation analysis further indicated that these microbiota alterations were positively associated with intestinal barrier repair and anti-inflammatory activity, and were strongly correlated with ceramide (d18:1/18:0) levels. In conclusion, FMT mitigates CpC-induced intestinal injury by modulating the gut microbiota and metabolome, thereby enhancing intestinal barrier integrity and regulating inflammatory responses. This study provides theoretical support and practical insights for the application of FMT as a promising microbiome-based strategy to control CpC-associated intestinal diseases in piglets.},
}

@article {pmid42232158,
year = {2026},
author = {Wang, H and Shao, S and Peng, Y and Xu, W and Zhang, J and Liu, X and Bian, X and Huang, K and Zhang, X},
title = {Pneumococcal Endopeptidase O Attenuates Colitis by Inhibiting the Macrophage-CCL2 Axis and Reshaping Gut Microbiota.},
journal = {Journal of inflammation research},
volume = {19},
number = {},
pages = {601434},
pmid = {42232158},
issn = {1178-7031},
abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease characterized by persistent immune activation and gut microbiota dysbiosis, for which current therapies remain limited by incomplete efficacy and substantial adverse effects. This study aimed to investigate the protective effects of pneumococcal endopeptidase O (PepO) on UC and its potential mechanisms of action.

METHODS: The efficacy of PepO was evaluated in a dextran sulfate sodium (DSS)-induced acute colitis mouse model. Clinical phenotypes were assessed using the disease activity index (DAI), colon length, histopathological analysis, and inflammatory cytokine levels. Macrophage infiltration and key inflammatory mediators were analyzed via immunofluorescence, flow cytometry, ELISA, and qPCR. Mechanisms were further validated by macrophage depletion using clodronate liposomes and recombinant CCL2 supplementation. In addition, gut microbiota composition was analyzed via 16S rRNA sequencing, and causality was confirmed through antibiotic-induced microbiota depletion and fecal microbiota transplantation (FMT) experiments.

RESULTS: PepO administration significantly improved disease activity, colon length, and ameliorated histopathological damage in the mice. Mechanistically, PepO directly inhibited macrophage CCL2 production, reducing macrophage infiltration and the release of pro-inflammatory cytokines in colitis. Additionally, PepO remodelled the gut microbiota and markedly increased the abundance of beneficial bacteria, such as Lactobacillus and Akkermansia. Antibiotic-induced microbiota depletion completely abolished PepO's protective effect, while FMT successfully replicated its protective actions, including suppression of CCL2 expression and macrophage infiltration.

CONCLUSION: This study shows that PepO exerts potent anti-colitic effects through a dual mechanism involving direct inhibition of the macrophage-CCL2 axis and microbiota-dependent enhancement of gut immune homeostasis.},
}

@article {pmid42232317,
year = {2026},
author = {Jakobsen, SS and Kousgaard, SJ and Cold, F and Halkjær, SI and Petersen, AM and Kjeldsen, J and Hansen, JM and Thorlacius-Ussing, O},
title = {The effect of fecal microbiota transplantation on quality of life in patients with chronic pouchitis: a post hoc analysis of the MicroPouch trial.},
journal = {Therapeutic advances in gastroenterology},
volume = {19},
number = {},
pages = {17562848261452497},
pmid = {42232317},
issn = {1756-283X},
abstract = {BACKGROUND: During surgical treatment for ulcerative colitis, an ileal pouch-anal anastomosis is often constructed. Pouchitis, the most common complication after this surgery, substantially reduces patients' quality of life (QoL). In chronic pouchitis, antibiotic treatment often proves ineffective. Fecal microbiota transplantation (FMT) has emerged as a potential treatment for chronic pouchitis.

OBJECTIVES: To determine the effect of FMT on QoL in patients with chronic pouchitis.

DESIGN: An exploratory post hoc analysis of data from the MicroPouch trial. A double-blinded, placebo-controlled study comprising a 4-week intervention period and 12-month follow-up.

METHOD: Thirty patients with chronic pouchitis were randomized 1:1 to receive either FMT or placebo. Treatment was administered by enema once daily for 2 weeks, then every other day for the following 2 weeks. QoL was assessed using three questionnaires-the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), the Pouch Dysfunction Score (PDS), and the 36-item Short Form Questionnaire (SF-36)-at baseline and at subsequent follow-ups.

RESULTS: At the 30-day follow-up, FMT-treated patients showed a significant decrease in QoL from baseline, measured by the SIBDQ (p = 0.03). Within the FMT group, the PDS did not change significantly from baseline to day 30 (p = 0.36). The placebo group reported higher SF-36 QoL scores at both baseline and day 30 (p = 0.02), although neither group showed significant within-group changes over time.

CONCLUSION: In patients with chronic pouchitis, FMT may temporarily worsen symptoms and reduce QoL, as indicated by three QoL questionnaires showing no improvement or poorer outcomes versus placebo. Trial registration: The study is registered at ClinicalTrials.gov (Trial number NCT04100291), date: 12 September 2019.},
}

@article {pmid42221589,
year = {2026},
author = {Song, D and Gao, H and Wang, T and Wei, Q and Liu, A and Ren, J},
title = {Gut microbiota dysbiosis-induced chronic inflammation as a driver of atherosclerosis: cellular crosstalk and host-microbe interactions.},
journal = {Frontiers in cellular and infection microbiology},
volume = {16},
number = {},
pages = {1789194},
pmid = {42221589},
issn = {2235-2988},
mesh = {*Dysbiosis/complications/microbiology ; Humans ; *Atherosclerosis/etiology/microbiology ; *Gastrointestinal Microbiome ; *Inflammation/microbiology ; Animals ; *Host Microbial Interactions ; Fecal Microbiota Transplantation ; Methylamines/metabolism ; Intestinal Barrier Function ; Fatty Acids, Volatile/metabolism ; },
abstract = {Gut microbiota dysbiosis is increasingly recognized as an upstream contributor to chronic low-grade inflammation and atherosclerosis (AS). Disruption of microbial homeostasis may impair intestinal barrier integrity, increase exposure to pro-inflammatory microbial products and metabolites, and reduce protective metabolites such as short-chain fatty acids (SCFAs), thereby activating innate immune signaling and sustaining vascular inflammation. Current evidence indicates that gut dysbiosis promotes atherosclerosis mainly through three interconnected processes: metabolite imbalance, barrier dysfunction with microbial translocation, and systemic immune reprogramming. Clinical studies have linked gut-derived biomarkers, particularly trimethylamine N-oxide (TMAO) and lipopolysaccharide (LPS)-related signals, to atherosclerotic burden and adverse cardiovascular outcomes, while experimental studies using fecal microbiota transplantation, probiotics, antibiotics, and gene-deficient models support a contributory role of the gut-immune-vascular axis. Emerging interventions, including dietary modulation, pharmacological repurposing, and microbiome-targeted therapies, may attenuate gut-derived chronic inflammation and offer new strategies for AS prevention and treatment. However, heterogeneity across studies and the limited causal evidence in humans warrant cautious interpretation. Overall, gut dysbiosis-driven chronic inflammation represents a biologically meaningful and potentially modifiable pathway in atherosclerosis.},
}

*Dysbiosis/complications/microbiology
Humans
*Atherosclerosis/etiology/microbiology
*Gastrointestinal Microbiome
*Inflammation/microbiology
Animals
*Host Microbial Interactions
Fecal Microbiota Transplantation
Methylamines/metabolism
Intestinal Barrier Function
Fatty Acids, Volatile/metabolism

@article {pmid42225253,
year = {2026},
author = {Singh, L and Bhullar, G and Shaik, S and Ganesh, V and Kesani, H and Rai, M},
title = {Gut Feeling: Microbiota as a Hidden Regulator of Hypertension.},
journal = {The Journal of nutrition},
volume = {},
number = {},
pages = {101623},
doi = {10.1016/j.tjnut.2026.101623},
pmid = {42225253},
issn = {1541-6100},
abstract = {Emerging evidence identifies the gut microbiota as a key regulator of blood pressure through its role in metabolizing dietary substrates into bioactive compounds that influence vascular, immune, and neurohumoral pathways. This review synthesizes recent mechanistic, preclinical, and clinical evidence linking gut microbial dysbiosis to hypertension, with particular emphasis on nutrition-dependent microbial metabolism and its translational implications. Experimental studies demonstrate that depletion of short-chain fatty acid (SCFA)-producing bacteria and enrichment of pro-inflammatory and trimethylamine-producing taxa contribute to endothelial dysfunction, immune activation, and renin-angiotensin-aldosterone system dysregulation. Fecal microbiota transplantation (FMT) and germ-free animal models provide causal evidence that hypertensive microbiota can directly elevate blood pressure. Human multi-omics and metabolomic studies further show that microbial functional capacity and metabolite production, rather than taxonomic composition alone, are strongly associated with hypertensive phenotypes and therapeutic responsiveness. Importantly, dietary interventions, including high-fiber diets, resistant starch, and the Dietary Approaches to Stop Hypertension (DASH) diet, modulate microbial composition and enhance SCFA production, providing a mechanistic basis for their antihypertensive effects. Microbiota-drug interactions have also emerged as a novel determinant of antihypertensive treatment efficacy. Collectively, these findings support a metabolite-centered framework in which diet-microbiota interactions influence blood pressure regulation. Targeting the gut microbiota through nutritional and microbiome-based strategies represents a promising adjunctive approach for hypertension prevention and personalized management. However, large-scale longitudinal and interventional human studies are needed to establish causality and optimize microbiota-targeted therapies.},
}

@article {pmid42225309,
year = {2026},
author = {Wang, W and Niu, X and Li, S and Cheng, B and Cheng, L and Yang, C and Xu, X and Chang, S and Wang, C and Liu, S},
title = {Efavirenz Mitigates Dyslipidemia and Attenuates Ulcerative Colitis through Gut Microbiota Modulation.},
journal = {ACS infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsinfecdis.6c00330},
pmid = {42225309},
issn = {2373-8227},
abstract = {Antiretroviral therapy (ART) is central to controlling human immunodeficiency virus (HIV) infection, yet it is frequently associated with dyslipidemia, a condition linked to the exacerbation of ulcerative colitis (UC) in people living with HIV (PLWH). The underlying mechanisms of ART-induced dyslipidemia and its contribution to UC progression remain incompletely understood. Here, we demonstrate that efavirenz (EFV), a widely used non-nucleoside reverse transcriptase inhibitor, mitigates ART-induced dyslipidemia and ameliorates UC symptoms. Our in vitro investigations reveal that palmitic acid (PA)-induced inflammation in human normal colorectal mucosal cells (FHCs) is mediated by the activation of the Akt phosphorylation pathway, triggered by the accumulation of 7-dehydrocholesterol (7-DHC), a substrate of 7-dehydrocholesterol reductase (DHCR7). While EFV did not directly modulate this inflammatory cascade in FHCs, in vivo studies using a high-fat diet (HFD)-induced dyslipidemia rat model demonstrated that EFV significantly attenuated elevated lipid levels and improved DHCR7 expression in dextran sulfate sodium (DSS)-induced UC tissues. Notably, fecal microbiota transplantation (FMT) from EFV-treated rats to HFD-fed recipients reduced dyslipidemia and restored DHCR7 expression, thereby suppressing 7-DHC-driven Akt phosphorylation and inflammatory responses in UC tissues. Our findings suggest a mechanism by which EFV mitigates dyslipidemia and UC progression, mediated through the regulation of lipid metabolism and gut microbiota. These findings provide compelling evidence for the potential of EFV to regulate dyslipidemia and associated comorbidities in HIV-infected individuals.},
}

@article {pmid42227044,
year = {2026},
author = {Singh, VK and Gupta, P and Jain, SK and Matreja, PS},
title = {The gut-brain axis in Alzheimer's and Parkinson's diseases: a systematic review of microbiota-derived biomarkers and novel therapeutic approaches.},
journal = {Journal of clinical and experimental neuropsychology},
volume = {},
number = {},
pages = {1-16},
doi = {10.1080/13803395.2026.2673084},
pmid = {42227044},
issn = {1744-411X},
abstract = {BACKGROUND: The altered gut microbiota substantially impacts the onset and progression of Alzheimer's disease (AD) and Parkinson's disease (PD), the two most widely studied neurodegenerative conditions. Microbiome-derived metabolites have been increasingly associated with disease onset, progression, and therapeutic targets in neurodegenerative disorders. Exploring the diagnostic and therapeutic implications of gut microbiome-derived biomarkers is critical to advancing our understanding and management of neurodegeneration.

METHODOLOGY: We systematically reviewed both clinical and preclinical studies published from 2010 to 2025. Studies examining gut microbiota composition, microbial-derived metabolites, or therapeutic interventions targeting the gut microbiome were included. Identification of gut microbiome alterations, discovery of microbial or metabolite-based biomarkers, association with disease onset or progression, and/or therapeutic effects on cognitive, neurological, or inflammatory outcomes were evaluated.

RESULT: Short-chain fatty acids(SCFAs) such as butyrate and acetate were found to be noninvasive biomarkers in patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), and Parkinson's disease (PD). Lower SCFA levels correlated with cognitive decline. Diagnostic accuracy improved when SCFA combinations were used, with AUCs ranging from 0.75 to 0.87. Trimethylamine N-oxide(TMAO) levels showed inconsistent associations, with both elevated and reduced levels linked to disease risk. Therapeutic approaches targeting gut microbiota, including probiotics, prebiotics, dietary changes, and fecal microbiota transplantation, demonstrated cognitive benefits and modulation of gut-brain signaling pathways.

CONCLUSION: Overall, gut-derived biomarkers offer a promising avenue for early diagnosis and novel therapeutic approaches in AD and PD, while acknowledging that evidence in other neurodegenerative diseases remains limited through modulation of the gut-brain axis.},
}

@article {pmid42227494,
year = {2026},
author = {Wang, JM and Wang, RQ and Wang, Y and Gao, XY and Liu, SY and Qi, SW and Hu, GL and Li, DL and Zhang, Y and Xu, XK and Feng, HL},
title = {Exploring the Influence of Circadian Rhythm Disorders in Metabolic Syndrome through Gut Microbiota.},
journal = {Combinatorial chemistry & high throughput screening},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113862073482277260412133043},
pmid = {42227494},
issn = {1875-5402},
abstract = {INTRODUCTION: Metabolic syndrome (MetS) is a chronic metabolic disorder whose global prevalence continues to rise, imposing a significant burden on public health. With the development of round-the-clock societies, shift work has become increasingly commonplace. A growing body of epidemiological evidence indicates that circadian rhythm disruption constitutes a predictable risk factor for MetS; however, the precise mechanisms underlying this relationship remain inadequately understood. This study employed golden hamsters as a model to investigate the effects of circadian rhythm disruption simulated by cyclic light (CL) exposure on MetS.

METHODS: Thirty-three male golden hamsters (7 weeks old, body weight 120-160 g) were randomly assigned to four groups for a 6-week intervention: the Control group (normal light + normal diet, ND), the high-fat diet group (normal light + HFD, to induce a MetS model), the cyclic light group (CL + normal diet, CL), and the CL + HFD group (CL + HFD). Outcome measures included metabolic indicators, hepatic histopathology, and gut microbiota (analyzed via 16S rDNA sequencing).

RESULTS: The stability of the MetS model was assessed through measurements of body weight, fasting blood glucose, and total cholesterol levels. The results indicated that CL exposure may further aggravate metabolic disorders associated with MetS. Furthermore, it was observed that CL exposure intensified MetS-related disturbances in gut microbiota, evidenced by an increase in α-diversity and distinct separation in β-diversity. CL exposure in the MetS model golden hamsters resulted in a reduced abundance of Bacteroidetes and Weissella, alongside an overgrowth of Helicobacter.

DISCUSSION: Circadian rhythm disruption is an independent risk factor for MetS. It further exacerbates metabolic indicators by inducing gut microbiota dysbiosis and promoting the growth of harmful bacteria. Future research should integrate functional metabolomics with faecal microbiota transplantation studies to validate causal mechanisms and explore clinical translational value.

CONCLUSION: Circadian rhythm disruption is an independent risk factor for MetS. It exacerbates the pathological progression of MetS by reducing beneficial bacteria and promoting the growth of harmful bacteria, thereby further damaging its metabolic indicators.},
}

@article {pmid42228606,
year = {2026},
author = {Waghmode, S and Viswanathan, R and Koligudde, V and Umare, P and Lavania, M},
title = {Microbial shifts in early life: the pediatric gut microbiome and its role in health and disease.},
journal = {Gut microbes},
volume = {18},
number = {1},
pages = {2681763},
doi = {10.1080/19490976.2026.2681763},
pmid = {42228606},
issn = {1949-0984},
abstract = {This review explores the pivotal role of the pediatric gut microbiome in shaping early-life development and influencing susceptibility to disease, emphasizing its impact on immune, metabolic, and neurodevelopmental processes. The neonatal period represents a critical window for host-microbiome interactions, beginning at birth when intestinal barrier function is still developing and immune responses remain immature. During this formative stage, rapid microbial colonization and ecological succession are influenced by delivery mode, infant feeding practices, antibiotic exposure, and environmental factors. Beyond bacterial populations, the early-life gut virome composed of bacteriophages and eukaryotic viruses evolves dynamically and contributes to microbial community structure, gene exchange, and immune system maturation. Microbially derived signals and metabolites support the development of mucosal integrity, immune programming, and host microbe equilibrium, with long-term implications for systemic immune function. Breastfeeding fosters the establishment of microbial communities and metabolic profiles associated with immune tolerance, whereas formula feeding and early-life antibiotic use may disrupt normal microbiome development. Alterations in early microbial trajectories have been associated with heightened risk of pediatric conditions, including allergic diseases, obesity, inflammatory bowel disease, and neurodevelopmental disorders. The review further evaluates emerging microbiome-directed strategies, such as probiotics, prebiotics, and fecal microbiota transplantation, considering both their therapeutic promise and current challenges. Collectively, current evidence underscores the early-life gut microbiome as a central determinant of host development and a compelling target for disease prevention strategies.},
}

@article {pmid42229822,
year = {2026},
author = {An, X and Li, C and Chai, Y and Wang, H and Yang, L and Qin, L and Soprun, LA and Gavrilova, NY and Weng, Z and Xu, J and Li, Q and Yang, D and Li, W and Guo, J and Li, Y and Wang, N and Yu, H},
title = {Luteolin rescues high-fat diet-induced hippocampal mitochondrial oxidative stress and cognitive decline by regulating gut microbiota-kynurenine-aryl hydrocarbon receptor axis.},
journal = {Free radical biology & medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.freeradbiomed.2026.06.002},
pmid = {42229822},
issn = {1873-4596},
abstract = {High-fat diet (HFD)-induced gut dysbiosis precipitates hippocampal mitochondrial oxidative stress, a pivotal driver of synaptic failure and cognitive decline. However, the molecular conduits linking intestinal microbial shifts to cerebral redox imbalance remain poorly defined, limiting therapeutic strategies. Here, we show that luteolin attenuates HFD-induced cognitive impairment in association with modulation of the gut microbiota-kynurenine (Kyn)-aryl hydrocarbon receptor (AhR) axis and improved mitochondrial redox homeostasis. Luteolin treatment ameliorated HFD-induced memory deficits and metabolic abnormalities in mice, effects that were markedly reduced after gut microbiota depletion and were transmissible via fecal microbiota transplantation. Consistent with this pathway, luteolin suppressed HFD-induced expansion of Proteobacteria (e.g., Escherichia coli), diminished intestinal lipopolysaccharide (LPS) leakage, and normalized colonic indoleamine 2,3-dioxygenase 1 (IDO1) expression. Consequently, luteolin reduced peripheral and hippocampal Kyn accumulation, thereby restricting AhR nuclear translocation and preventing the aberrant transcription of AhR-target genes implicated in mitochondrial respiratory chain disruption. Functionally, luteolin restored hippocampal mitochondrial bioenergetics, attenuated pathological reactive oxygen species (ROS) overload, and preserved synaptic long-term potentiation (LTP). The protective efficacy of luteolin against mitochondrial oxidative insult and cognitive decline was phenocopied by AhR inhibition and abrogated by exogenous Kyn supplementation. Collectively, our findings identify the gut Proteobacteria-Kyn-AhR signaling axis as an important contributor to hippocampal mitochondrial oxidative stress in HFD-challenged brains. Luteolin emerges as a promising microbiota-targeted antioxidant intervention that safeguards cognitive function by rectifying this gut-brain redox relay.},
}

@article {pmid42230119,
year = {2026},
author = {Alexander, JL and Mullish, BH and Thomas, L and Weersma, RK and Sokol, H and Roberts, LA and Edwards, LA and Emmanuel, A and Gerasimidis, K and Hall, LJ and Iqbal, TH and Kinross, JM and McIlroy, J and Monaghan, TM and Sergaki, C and Shawcross, DL and Stewart, CJ and Lamb, CA and Williams, HRT and Hansen, R and Hold, G},
title = {Recent advances in our understanding of the gut microbiome: an analysis from the Gut Microbiota for Health Expert Panel of the British Society of Gastroenterology.},
journal = {Gut},
volume = {},
number = {},
pages = {},
doi = {10.1136/gutjnl-2026-338252},
pmid = {42230119},
issn = {1468-3288},
abstract = {At around 10 years ago, at the time of the first publication by the Gut Microbiota for Health Expert Panel of the British Society of Gastroenterology, recognition of the gut microbiome's importance in health and disease was transitioning from fringe interest towards major global pursuit. A decade on, we appraise the considerable progress made in the field, while acknowledging ongoing challenges. Earlier human work characterising the 16S rRNA gene amplicon signature of particular conditions in small cohorts has been superseded by larger, multicentre studies with extensive metadata. Studies increasingly employ shotgun metagenomics and other 'omic' techniques-coupled with refined bioinformatic tools and disease models-to better characterise perturbation in gut microbiome functionality. The arrival of 'gold standard' pipelines for microbiome analysis and increased mechanistic validation of signals are key developments towards more clinically-translatable outcomes. Novel clinical areas where the gut microbiome has relevance have emerged, including early life and the efficacy of certain treatments (including immune checkpoint inhibitors and vaccination). Enthusiasm for 'microbiome diagnostics and treatments' has grown, but barriers to widespread adoption remain. Faecal microbiota transplant (FMT) is established for treating recurrent Clostridioides difficile infection, with donor-derived 'next generation' FMT products licensed for this condition in certain countries. Beyond FMT, other microbial therapeutic techniques-including nutritional, bacteriophage and probiotic therapies-show promise, but have not fulfilled their high expectations yet. Gut microbiome research is now well-established and shows significant translational potential; the future focus will be translational work to drive its utility in clinical diagnostics, prognostics and therapeutics.},
}

@article {pmid42218119,
year = {2026},
author = {Fessler, JL and Olm, MR and Engleman, EG and Sonnenburg, JL},
title = {Integration of donor microbiota following FMT correlates with anti-PD-1 response in melanoma.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-73465-7},
pmid = {42218119},
issn = {2041-1723},
support = {R21CA290426//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
abstract = {Fecal microbiota transplantation (FMT) has shown promise in improving anti-PD-1 therapy in melanoma, but the underlying microbial features remain poorly defined. We performed a strain-resolved metagenomic meta-analysis across three independent FMT plus anti-PD-1 melanoma trials (n = 41). Across cohorts, therapeutic benefit was linked to successful integration of donor microbiota, rather than increased diversity or engraftment of specific species. Responders acquired more donor-derived strains, exhibited greater post-FMT similarity to their donor, and maintained a more stable microbiome. Following FMT, non-responders' microbiomes showed greater taxonomic instability, larger fluctuations in estimated microbial load, and increased abundance of pathogen-associated secretion system genes, whereas responders showed enrichment for microbial functions involved in community-level metabolism and communication. Finally, shifts in tumor-infiltrating immune profiles tracked with clinical outcomes and microbiome changes. Together these findings highlight that distinct patterns of microbiome restructuring, including stable community transitions and altered functional capacity, are associated with anti-PD-1 response following FMT.},
}

@article {pmid42218700,
year = {2026},
author = {Zhang, Y and Wang, Y and Yang, Y and Mei, H and Liu, X and He, Y and Qin, S and Feng, B},
title = {Gut-Liver Axis Failure in Critical Alcohol-Associated Liver Disease: From ICU Secondary Hits to Microbiome-Targeted Therapy.},
journal = {Mediators of inflammation},
volume = {2026},
number = {1},
pages = {e3968719},
doi = {10.1155/mi/3968719},
pmid = {42218700},
issn = {1466-1861},
support = {82460373//National Natural Science Foundation of China/ ; 82560382//National Natural Science Foundation of China/ ; HZ (2025) 312//Zunyi Science and Technology Bureau, China/ ; HZ (2023) 366//Zunyi Science and Technology Bureau, China/ ; HZ (2025) 172//Zunyi Science and Technology Bureau, China/ ; QZYY-2024-137//Guizhou Administration of Traditional Chinese Medicine/ ; gzwkj2024-310//Guizhou Provincial Health Commission/ ; MTyk2024-55//Kweichow Moutai Hospital Research Project/ ; HZ202411//Traditional Chinese Medicine Hospital of Zunyi Medical and Pharmaceutical College/ ; },
mesh = {Humans ; Intensive Care Units ; *Liver Diseases, Alcoholic/therapy/microbiology/metabolism ; *Liver/metabolism ; *Gastrointestinal Microbiome/physiology ; Animals ; Intestinal Barrier Function ; Fecal Microbiota Transplantation ; Dysbiosis ; },
abstract = {Alcohol-associated liver disease (ALD) can progress to critical illness phenotypes requiring intensive care, including severe alcohol-associated hepatitis, acute decompensation, and alcohol-associated acute-on-chronic liver failure (ACLF). In these patients, short-term outcomes are driven less by the burden of fibrosis alone than by systemic inflammation, immune dysfunction, infection, and multiorgan failure. At the core of this process is gut-liver axis failure, which links alcohol-induced dysbiosis and intestinal barrier disruption to microbial translocation, hepatic innate immune activation, and systemic inflammatory amplification. In the intensive care unit (ICU), secondary hits such as broad-spectrum antibiotics, acid suppression, parenteral nutrition, shock, sedatives or opioids, and mechanical ventilation may further exacerbate these mechanisms and disturb microbial ecology and barrier integrity. Microbiome-targeted therapies (probiotics, postbiotics, and fecal microbiota transplantation) are biologically plausible. However, current evidence is mainly derived from non-ICU or relatively stable ALD populations. Therefore, their use in critically ill patients requires strict safety boundaries, including severe barrier disruption, invasive devices, uncontrolled infections, and profound immune dysfunction. This narrative review synthesizes the pathophysiological continuum from gut barrier failure to systemic inflammation and multiorgan dysfunction in critical ALD, with particular emphasis on ICU-specific secondary hits, safety-aware microbiome modulation, and future phenotype-informed precision strategies.},
}

Humans
Intensive Care Units
*Liver Diseases, Alcoholic/therapy/microbiology/metabolism
*Liver/metabolism
*Gastrointestinal Microbiome/physiology
Animals
Intestinal Barrier Function
Fecal Microbiota Transplantation
Dysbiosis

@article {pmid42218858,
year = {2026},
author = {Sun, Y and Xie, D and Fu, H and He, M and Li, J and Wu, C and Pan, S},
title = {Harpagide alleviates sepsis-induced acute respiratory distress syndrome via gut microbiota modulation.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {157},
number = {},
pages = {158329},
doi = {10.1016/j.phymed.2026.158329},
pmid = {42218858},
issn = {1618-095X},
abstract = {BACKGROUND: Sepsis-associated acute respiratory distress syndrome (ARDS) remains a leading cause of mortality in critically ill patients, with limited therapeutic options beyond supportive care. The gut-lung axis is critical in sepsis pathogenesis, yet effective targeting strategies remain scarce. Harpagide (HPG), an iridoid glycoside from Scrophularia ningpoensis, exhibits anti-inflammatory properties, but whether it protects against sepsis-induced ARDS through gut microbiota modulation remains unexplored.

METHODS: Sepsis-induced ARDS was established using the cecal ligation and puncture (CLP) model. Gut microbiota dependency was assessed via antibiotic depletion (ABX) and fecal microbiota transplantation (FMT). Ffar2[-/-] mice were used to verify receptor necessity. Microbial composition and SCFAs were analyzed by 16S rRNA sequencing and GC-MS. Lung signaling was assessed by RNA-seq, Western blot, and RT-qPCR. Plasma SCFAs were quantified in sepsis-induced ARDS patients (n = 12) and healthy controls (n = 12) by LC-MS/MS.

RESULTS: HPG significantly improved survival, attenuated lung injury, and suppressed cytokine storm in septic mice. These effects were abolished by ABX but transferable via FMT, confirming microbiota dependency. HPG enriched acetate-producing taxa, elevating fecal and plasma acetate. Transcriptomic analysis revealed simultaneous suppression of NF-κB signaling and excessive IFN-γ/STAT1 activation. HPG-mediated protection was completely abrogated in Ffar2[-/-] mice, and exogenous sodium acetate recapitulated these effects in a Ffar2-dependent manner. Clinically, plasma acetate was significantly depleted in ARDS patients and correlated with disease severity.

CONCLUSIONS: HPG alleviates sepsis-induced ARDS by reshaping gut microbiota to boost acetate production, which activates FFAR2 to orchestrate immune reprogramming via NF-κB and IFN-γ/STAT1 pathways, offering a novel microbial-metabolic therapeutic strategy.},
}

@article {pmid42219603,
year = {2026},
author = {Coiffard, B and Brodovitch, A and Mège, JL and Bardin, N and Cassir, N},
title = {IgM/IgA-Enriched Immunoglobulins: a Key to Breaking the Cycle of Clostridioides difficile Infection Recurrences in Patients with Hypogammaglobulinemia?.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiag291},
pmid = {42219603},
issn = {1537-6613},
abstract = {We present the case of a 57-year-old woman with secondary hypogammaglobulinemia who experienced Clostridioides difficile infection, with repeated recurrences despite transient clinical responses to standard therapies, including repeated fecal microbiota transplantation. Following the replacement of intravenous immunoglobulin supplementation with IgM/IgA-enriched immunoglobulin, no recurrence of CDI was observed during the 24-month follow-up period.},
}

@article {pmid42220281,
year = {2026},
author = {de Bruijn, CMA and Oorthuys, AOJ and Zeevenhooven, J and Davids, M and Levels, JHM and Vlieger, AM and Herrema, H and Nieuwdorp, M and Benninga, MA},
title = {Feasibility and efficacy of fecal microbiota transplantation in adolescents with refractory irritable bowel syndrome: A randomized clinical pilot trial.},
journal = {Journal of pediatric gastroenterology and nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1002/jpn3.70459},
pmid = {42220281},
issn = {1536-4801},
support = {//Stichting Dioraphte/ ; //For Wis(h)dom Foundation/ ; 09150182010020/ZONMW_/ZonMw/Netherlands ; 015.017.050//Aspasia Premium/ ; },
abstract = {OBJECTIVES: To assess the feasibility and efficacy of fecal microbiota transplantation (FMT) in adolescents (16-21 years) with refractory irritable bowel syndrome (IBS).

METHODS: Randomized controlled pilot trial. Thirty-two patients were included and randomized to receive two allogeneic or autologous FMTs. At baseline and after 6 weeks, two allogeneic or autologous FMTs were administered via a nasoduodenal tube. Feasibility outcomes included dropout rate. Clinical efficacy was evaluated by the proportion of responders (≥50 points reduction in total score of the IBS severity-scoring-system) at 12, 24, and 48 weeks follow-up. Secondary outcomes included health-related quality of life (QoL), depression and anxiety scores, and school/work absenteeism.

RESULTS: One patient (3%) withdrew after randomization, due to lack of effect after the first FMT. Response rates 12 weeks after allogeneic and autologous FMTs were 40% and 38% (p = 0.886). At 24 weeks, significantly more patients responded after allogeneic FMTs (60% vs. 25% autologous, p = 0.048), without significant differences at 48 weeks (60% vs. 50%, p = 0.576). Total QoL score was significantly better after allogeneic than autologous FMTs at 12, 24, and 48 weeks (p = 0.028, p = 0.007, p = 0.011). In the allogeneic FMTs group, school/work absenteeism was 7% at 24 weeks (vs. 41% autologous, p = 0.037).

CONCLUSIONS: Allogeneic FMTs were feasible and resulted in high response rates and better QoL compared to autologous FMTs. These results provide preliminary evidence for the use of allogeneic FMTs in adolescents with refractory IBS.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03074227 (https://clinicaltrials.gov/study/NCT03074227?id=NCT03074227&rank=1).},
}

@article {pmid42220621,
year = {2026},
author = {Kaiser Junior, RL and Piron-Ruiz, L and Tomiatti, RZ and De Castro, MLS and Quadros, LG and Ruiz, MA},
title = {Clinical Remission of Crohn's Disease and Closure of a Rectovaginal Fistula After Autologous Non-Myeloablative Hematopoietic Stem Cell Transplantation.},
journal = {International medical case reports journal},
volume = {19},
number = {},
pages = {550993},
pmid = {42220621},
issn = {1179-142X},
abstract = {BACKGROUND: Crohn's Disease is a chronic, heterogeneous, recurrent and remitting inflammatory bowel disease that can affect any part of the digestive system. To date there is no cure for this disease. Clinical treatment aims to reestablish a balance and avoid crises that are common in an immune-mediated disease that promotes intestinal dysregulation. Anti-inflammatory medications, corticosteroids, immunosuppressants and biologics are part of the therapeutic arsenal for the disease. Obstructions, strictures and intestinal fistulas are complications that require repeat surgery in most patients. Fistulas in the anal or perianal regions are common with rectovaginal fistulas being a serious and complex complication that is difficult to control. Autologous hematopoietic stem cell transplantation can be employed for select patients with severe, refractory autoimmune diseases that have failed to respond adequately to conventional treatments.

CASE PRESENTATION: A 31-year-old Brazilian patient underwent several unsuccessful perianal surgeries for a complex rectovaginal fistula during her twelve years with active Crohn's Disease. Stool elimination was mostly through the vagina as she had rectal stenosis. Consequently, rectal amputation and permanent colostomy implantation were recommended but refused by the patient. Instead, she underwent a non-myeloablative autologous hematopoietic stem cell transplantation. Four years later, she is without active disease, with no manifestation of a rectovaginal fistula. Previous descriptions of rectovaginal fistula closure with hematopoietic stem cell transplantation were not found in a review of the literature.

CONCLUSION: For patients who refuse radical surgery, the presence of a fistula is not a contraindication for hematopoietic stem cell transplantation. The procedure provided progressive improvement not only with apparent cure of the Crohn's disease but with no manifestation of the rectovaginal fistula four years after the transplantation.},
}

@article {pmid42220936,
year = {2026},
author = {Elbeltagi, YM and Abd Rab El Rasool, AO and Elkashlan, AM and Al-Beltagi, M},
title = {Medical treatment of autism spectrum disorder in children: Current evidence, controversies, and clinical challenges.},
journal = {World journal of clinical pediatrics},
volume = {15},
number = {2},
pages = {117274},
pmid = {42220936},
issn = {2219-2808},
abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition associated with debilitating comorbidities [e.g., aggression, irritability, gastrointestinal (GI) issues]. Medical management primarily targets these symptoms, as no drug is Food and Drug Administration-approved for core social-communication deficits.

AIM: To synthesize the efficacy and safety of five major pharmacological classes and evaluate the emerging evidence for biomarker-driven (precision medicine) interventions in pediatric ASD.

METHODS: Following PRISMA guidelines, we systematically reviewed randomized controlled trials (RCTs) for five classes: Atypical antipsychotics, stimulants, selective serotonin reuptake inhibitors, metabolic/nutritional, and microbiota-gut-brain axis agents. Quantitative meta-analysis for antipsychotics (n = 5 RCTs pooled) used the random-effects model, reporting I [2] to quantify heterogeneity.

RESULTS: Atypical antipsychotics are the only drugs with robust, established efficacy for severe irritability: Pooled analysis for risperidone (n = 3 RCTs) showed a significant mean difference of approximately -11.0 on Aberrant Behavior Checklist-Irritability subscale (I [2] approximately 72%). Risperidone carries a greater metabolic burden (e.g., weight gain) than aripiprazole. Stimulants and selective serotonin reuptake inhibitors, respectively. Emerging therapies demonstrate targeted potential: Microbiota transfer therapy significantly improved GI and behavioral symptoms in cohorts with GI disease. Similarly, the efficacy of High-dose folinic acid was concentrated in the subgroup with folate receptor-α autoantibodies.

CONCLUSION: The management of ASD demands a shift to a precision medicine model, as the efficacy of interventions is highly variable and concentrated in specific patient subgroups. Future research must prioritize the validation of biological biomarkers (metabolic, genetic, neurophysiological) to reliably predict treatment response, guiding the selection of targeted therapies, and addressing current evidence gaps.},
}

@article {pmid42221399,
year = {2026},
author = {Al Jnainati, M and Govindarajan, A and Tyagi, S and Iltaf, M and Al Jnainati, J and Ayoub, M and Shadab, HA},
title = {Harnessing Microbiome Therapy to Treat Metabolic Syndrome.},
journal = {AACE endocrinology and diabetes},
volume = {13},
number = {3},
pages = {463-472},
pmid = {42221399},
issn = {3050-9157},
abstract = {BACKGROUND/OBJECTIVE: Metabolic syndrome, a global health crisis marked by insulin resistance, obesity, and dyslipidemia, necessitates novel therapeutic approaches beyond conventional symptom management. Emerging research highlights the gut microbiome as a pivotal modulator of metabolic health, with dysbiosis-characterized by reduced microbial diversity and proinflammatory shifts-implicated in disease pathogenesis. This review synthesizes evidence from preclinical and clinical studies on microbiome-targeted therapies, including fecal microbiota transplantation, designer probiotics, and synbiotics, which aim to restore microbial balance and ameliorate metabolic dysfunction.

CASE REPORT: This review synthesizes evidence from preclinical and clinical studies on microbiome-targeted therapies, including fecal microbiota transplantation, designer probiotics, and synbiotics, which aim to restore microbial balance and ameliorate metabolic dysfunction.

DISCUSSION: Fecal microbiota transplantation transfers beneficial microbiota to enhance insulin sensitivity, while probiotics and synbiotics modulate inflammation, strengthen gut barrier integrity, and stimulate metabolic regulators like glucagon-like peptide-1 and short-chain fatty acids. Mechanistically, these therapies mitigate systemic inflammation, improve glucose/lipid homeostasis, and reduce intestinal permeability linked to endotoxin translocation. Clinical trials report improved glycemic control, lipid profiles, and weight management, underscoring their multitargeted potential. However, challenges such as donor variability, lack of standardized protocols, and long-term safety concerns hinder widespread application. Personalized approaches, informed by machine learning and microbial biomarkers, alongside innovations in Clustered Regularly Interspaced Short Palindromic Repeats-based engineering and encapsulation technologies, may address these limitations.

CONCLUSION: Despite promising outcomes, rigorous large-scale trials and interdisciplinary collaboration are essential to validate efficacy, optimize delivery, and ensure ethical compliance. In conclusion, microbiome therapies represent a paradigm shift in treating metabolic syndrome by targeting root causes, yet translating preclinical success into clinical practice demands further innovation and evidence-based standardization.},
}

@article {pmid42221483,
year = {2026},
author = {Yang, H and Liu, S and Chen, X and Yin, C and Xiao, L and Xu, W and Lv, S and Xie, L and Yin, C},
title = {Gut microbiota-associated immunomodulation contributes to the protective effects of fluvastatin against endometriosis in a mouse model, accompanied by increased Akkermansia muciniphila abundance.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1762444},
pmid = {42221483},
issn = {1664-302X},
abstract = {BACKGROUND: Endometriosis (EMs) is a chronic inflammatory disease characterized by tumor-like growth behavior and limited therapeutic options. Increasing evidence suggests that gut microbiota may contribute to EMs progression by promoting chronic inflammation and immune dysregulation. Fluvastatin, a lipid-lowering agent, exhibits anti-inflammatory, anti-tumor, and immunomodulatory effects and has also been reported to influence microbial homeostasis. However, the relationship among fluvastatin treatment, gut microbiota, and EMs progression remains unclear. This study aimed to investigate this relationship.

MATERIALS AND METHODS: A mouse model of EMs was established by autologous uterine tissue transplantation, followed by oral fluvastatin administration for 3 weeks. Lesion growth, inflammatory responses, and immune characteristics were evaluated by histology, quantitative PCR, flow cytometry, immunofluorescence, and immunohistochemistry. Gut microbiota involvement was assessed using antibiotic-mediated microbiota depletion and fecal microbiota transplantation (FMT). Microbial composition was analyzed by metagenomic sequencing. The role of Akkermansia muciniphila was evaluated by direct oral supplementation.

RESULTS: Fluvastatin significantly reduced the volume and mass of ectopic lesions and decreased the mRNA expression of pro-inflammatory cytokines. It was also associated with changes in macrophage polarization-related markers and reduced abnormal activation of splenic immune cells. Antibiotic-induced gut microbiota depletion attenuated the protective effects associated with fluvastatin treatment, whereas FMT from fluvastatin-treated mice partially transferred similar protective changes. Metagenomic analysis revealed that fluvastatin reshaped gut microbiota composition and increased the abundance of Akkermansia muciniphila. Moreover, oral supplementation with Akkermansia muciniphila attenuated EMs progression and was associated with anti-inflammatory and immune-related changes similar to those observed after fluvastatin treatment.

CONCLUSION: These findings suggest that the protective effects associated with fluvastatin treatment are accompanied by changes in gut microbiota composition, including increased abundance of Akkermansia muciniphila. Gut microbiota may contribute to the beneficial effects of fluvastatin in EMs. These results support the potential value of microbiota-informed therapeutic strategies for EMs.},
}

@article {pmid42221532,
year = {2026},
author = {Mishra, AK and Mishra, A and Vikal, A and Singh, H and Y Thajudeen, K and Khan, G and Ahmed, MM},
title = {Fecal microbiota transplant and its usefulness in hepatic disorders: a systematic review.},
journal = {Therapeutic advances in gastroenterology},
volume = {19},
number = {},
pages = {17562848261452504},
pmid = {42221532},
issn = {1756-283X},
abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an emerging therapeutic approach aimed at restoring gut microbial balance through the transfer of stool from healthy donors. It has gained significant attention for its role in managing gut dysbiosis-associated disorders, particularly hepatic diseases.

OBJECTIVE: This systematic review evaluated the therapeutic efficacy and clinical potential of FMT in the management of liver-related conditions, including recurrent Clostridium difficile infection (CDI), non-alcoholic fatty liver disease, liver cirrhosis, and hepatic encephalopathy.

DESIGN: A systematic review of existing literature was conducted to assess the clinical outcomes, mechanisms, and challenges associated with FMT in hepatic disorders.

DATA SOURCES AND METHODS: Relevant studies were identified from peer-reviewed scientific databases, focusing on clinical trials, observational studies, and experimental research investigating the role of FMT in gut dysbiosis and liver disease. Data were analyzed to evaluate efficacy, underlying mechanisms, and safety considerations.

RESULTS: FMT demonstrated high efficacy in recurrent CDI, with cure rates exceeding 80%-90%. In hepatic disorders, FMT was associated with improved microbial diversity, enhanced gut barrier integrity, and reduced systemic inflammation, contributing to better liver function and clinical outcomes. However, variability in donor selection, potential safety risks, and regulatory limitations remain significant challenges.

CONCLUSION: FMT represents a promising therapeutic strategy in hepatology, underscoring the critical role of the gut-liver axis. Advances such as synthetic microbiota and personalized microbiome-based therapies may further optimize its safety and efficacy, paving the way for innovative, microbiome-centered interventions in liver disease management.},
}

@article {pmid42214571,
year = {2026},
author = {Chung, HJ and Han, EJ and Kim, DH and Ahn, JS and Choi, YJ},
title = {Gut-derived commensal bacteria attenuate corticosterone-induced depressive-like behavior via regulation of oxidative stress and mitochondrial apoptotic signalling.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {108269},
doi = {10.1016/j.phrs.2026.108269},
pmid = {42214571},
issn = {1096-1186},
abstract = {Chronic stress and sustained glucocorticoid exposure disrupt intracellular signaling networks that regulate mitochondrial function and neurotrophic support, thereby increasing vulnerability to depressive disorders. Among these alterations, redox imbalance and mitochondrial dysfunction contribute to impairment of neuronal survival pathways, including TrkB-ERK-CREB-BDNF signaling. However, upstream biological modulators of these stress-responsive processes remain incompletely understood. Here, we investigated whether gut-derived commensal bacteria function as modulators of neuronal signaling under chronic stress conditions. Using a fecal microbiota transplantation (FMT)-based behavioral stratification approach, we identified Intestinimonas butyriciproducens and Parabacteroides merdae as species depleted in mice with increased depressive-like immobility. Functional validation showed that both strains attenuated oxidative stress, reduced intracellular reactive oxygen species, and suppressed mitochondrial apoptotic signaling in neuronal cells, accompanied by restoration of TrkB-ERK-CREB signaling and increased brain-derived neurotrophic factor expression. In a chronic corticosterone model, oral administration of these strains reduced depressive-like behavior and restored hippocampal BDNF levels. Collectively, these findings demonstrate that defined commensal bacteria act as biological modulators of intracellular signaling pathways, including redox balance and mitochondrial function, thereby preserving neurotrophic signaling. This study provides evidence linking specific commensal taxa to modulation of neuronal signaling under chronic stress conditions.},
}

@article {pmid42214609,
year = {2026},
author = {Yuan, S and Lin, L and Liu, J and Lin, Q and Wang, S and Wu, J and Xu, D and Liu, Y and Lee, JY and Qiu, L},
title = {Treadmill exercise attenuates neuroinflammation in APP/PS1 mice via gut microbiota remodeling: Evidence from fecal microbiota transplantation.},
journal = {Life sciences},
volume = {400},
number = {},
pages = {124500},
doi = {10.1016/j.lfs.2026.124500},
pmid = {42214609},
issn = {1879-0631},
abstract = {Alzheimer's disease is associated with gut microbiota dysbiosis, intestinal barrier dysfunction, lipopolysaccharide (LPS) translocation, and neuroinflammation. However, it is unclear whether exercise-induced gut microbiota remodeling causally contributes to the neuroprotective effects of exercise in AD. Herein, APP/PS1 mice underwent 12 weeks of treadmill exercise, and fecal microbiota transplantation (FMT) was used to determine whether exercise-related benefits could be transferred to the recipient mice. Behavioral performance was assessed using the Morris water maze and open-field test. Gut microbial profiles were analyzed by 16S rDNA sequencing. Intestinal barrier integrity was evaluated using histology, AB-PAS staining, and tight-junction protein expression, while plasma and brain LPS levels were measured by enzyme-linked immunosorbent assay. Neuroinflammation was examined with immunofluorescence and Western blotting. It was found that treadmill exercise improved spatial learning, memory, and anxiety-like behavior in APP/PS1 mice. These benefits were partly reproduced in recipients of microbiota from exercised donors. Exercise also restored gut microbial diversity and composition, increased the abundance of taxa including Dubosiella and UBA1819, alleviated colonic injury, enhanced mucus secretion, upregulated ZO-1, Occludin, and Claudin-1, and reduced plasma and brain LPS levels. In parallel, exercise and FMT from exercised donors decreased brain TLR4 expression, attenuated microglial and astrocytic activation, and suppressed TLR4/NF-κB signaling and downstream inflammatory cytokines. These findings indicate that treadmill exercise alleviates neuroinflammation in APP/PS1 mice, at least in part, through gut microbiota remodeling, improved intestinal barrier integrity, and reduced LPS-driven inflammatory signaling.},
}

@article {pmid42215979,
year = {2026},
author = {Li, X and Zhang, X and Yuan, S and Zhang, J},
title = {The gut-lung axis in ARDS: beyond microbial translocation.},
journal = {Respiratory research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12931-026-03752-w},
pmid = {42215979},
issn = {1465-993X},
support = {82272231//National Natural Science Foundation of China/ ; 82472223//National Natural Science Foundation of China/ ; 2021YFC2500800//National Key Research and Development program from Ministry of Science and Technology of the People's Republic of China/ ; 2025ZD01902600//Prevention and Control of Emerging and Major Infectious Diseases-National Science and Technology Major Project/ ; 2024ZD0529004//Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; },
abstract = {The gut-lung axis has emerged as a pivotal pathway in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Disruption of the intestinal barrier, a common event in critical illness, facilitates the systemic dissemination of live microbiota, their pathogen-associated molecular patterns (PAMPs), and bioactive metabolites. This process critically depends on the integrity of the gut vascular barrier (GVB). The GVB is the endothelial layer underlying the gut epithelium. It serves as the final gatekeeper, restricting microbial products from entering the systemic circulation. Concurrently, intestinal immune cells, such as γδ T cells and innate lymphoid cells (ILCs), migrate to the lungs and amplify the inflammatory cascade. Emerging evidence links regulated cell death, especially pyroptosis, necroptosis, and ferroptosis, to disruption of both gut and lung barriers, fueling a self-amplifying cycle of organ injury. This review synthesizes current evidence on the cellular, molecular, and metabolic mechanisms underlying gut-derived lung injury. Furthermore, we critically evaluate several emerging gut-targeted therapeutic strategies aimed at restoring microbial homeostasis and mitigating ALI/ARDS, including fecal microbiota transplantation (FMT), probiotics, synbiotics, and mesenchymal stem cell (MSC) therapy. Deciphering the gut-lung dialogue holds promise for developing novel treatments for this devastating condition.},
}

@article {pmid42205579,
year = {2026},
author = {Liu, Y and Gong, J and Wang, W and Li, X and Jia, H and Wang, R and Sun, Q and Zhang, R and Zhang, Y and Huang, L},
title = {The effects of filtration and centrifugation on the gut microbiota in fecal microbiota transplantation preparation.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1768356},
pmid = {42205579},
issn = {1664-302X},
abstract = {BACKGROUND: The preparation method of fecal microbiota suspensions is crucial for reliable fecal microbiota transplantation research. However, current protocols vary significantly in processing parameters, potentially compromising the comparability of studies. Systematic comparisons of how different preparation techniques affect the microbial community are still lacking.

METHODS: Fresh fecal samples from nine adult volunteers were processed via filtration and centrifugation at various speeds. Microbial viability was assessed via live/dead staining and colony forming unit enumeration. 16S rDNA sequencing was performed to analyze bacterial diversity and taxonomic composition.

RESULTS: The microbial composition and functional potential did not differ between the filtration alone group and the fresh fecal group, and filtration resulted in the lowest bacterial mortality. Mortality increased with increasing centrifugation speed. Centrifugation selectively affected the abundance of some genera (e.g., Delftia and Acinetobacter). High-speed supernatants presented markedly lower OD600 values than low-speed supernatants did, and differential centrifugation visibly reduced the amount of debris.

CONCLUSION: Filtration alone best preserved fecal microbial viability, composition and functional potential. Centrifugation enrichment becomes selective at high speeds. Differential centrifugation offered superior impurity removal. The preparation strategy should be tailored to the research or therapeutic goal.},
}

@article {pmid42206183,
year = {2026},
author = {Wang, Z and Cui, H and Huang, H and Zhang, P and Yin, L and Luo, G and Li, Q and Zhang, Y and Meng, L and Chang, W and Li, X and Yang, X and Ye, J},
title = {Therapeutic effect of Tripterygium hypoglaucum (H. Lév.) Hutch. extract on psoriasis-like skin inflammation correlated with gut microbiota homeostasis in mice.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1822819},
pmid = {42206183},
issn = {1663-9812},
abstract = {BACKGROUND: Tripterygium hypoglaucum (H. Lév.) Hutch. (THH) exerts anti-inflammatory and immunosuppressive effects against psoriasis. However, the extent to which and the mechanisms by which it ameliorates psoriasis-like dermatitis through modulation of the gut microbiota-metabolite axis remain unclear.

METHODS: This study investigated the therapeutic effects and underlying mechanisms of THH in a murine model by employing 16S rRNA gene sequencing, intestinal metabolomic profiling, fecal microbiota transplantation (FMT), and co-housing experiments.

RESULTS: Our results demonstrated that THH treatment significantly decreased PASI scores, alleviated epidermal hyperplasia and skin inflammation, and reversed IMQ-induced gut dysbiosis by restoring the Firmicutes/Bacteroidota ratio and modulating the abundance of beneficial and pathogenic bacteria. Metabolomic analysis revealed that THH normalized multiple metabolic pathways disturbed by IMQ, including arachidonic acid metabolism, sphingolipid metabolism, and primary bile acid biosynthesis. Correlation analyses further revealed significant associations among the altered gut microbiota, key metabolic pathways, and psoriasis-related phenotypic indices. Moreover, FMT from THH-treated mice conferred significant anti-psoriatic efficacy. Similarly, co-housing experiments resulted in the alleviation of skin lesions, reduction of spleen weight, and downregulation of inflammatory cytokines.

CONCLUSION: These findings demonstrate that THH attenuates psoriasis-like dermatitis partly by reshaping gut microbiota composition and regulating key metabolic pathways, supporting a potential gut-targeted therapeutic strategy for psoriasis.},
}

@article {pmid42206375,
year = {2026},
author = {Wang, J and Xu, J and Mai, H and Niu, G and Wu, S and Zhang, X and Zhu, J and Aschner, M and Meng, Q and Chen, R},
title = {Microplastic Exposure Aggravates Cardiomyopathy Under Hemodynamic Stress Through the Gut-Heart Axis.},
journal = {Circulation},
volume = {},
number = {},
pages = {},
doi = {10.1161/CIRCULATIONAHA.126.079820},
pmid = {42206375},
issn = {1524-4539},
abstract = {BACKGROUND: Bisphenol F (BPF) is a common substitute for bisphenol A and the most prevalent bisphenol compound in diverse plastic manufacturing applications. However, the potential toxicity of BPF remains largely unexplored. This study investigates the effects of BPF on the cardiovascular system and intestinal barrier.

METHODS: Germ-free mouse models and fecal microbiota transplantation techniques were used to confirm the role of gut microbiota in BPF-induced cardiovascular injury. Untargeted metabolomics and spatial metabolomics were used to identify the in vivo metabolic products of BPF. Single-cell sequencing was used to identify which cardiac cell types were damaged by BPF exposure.

RESULTS: BPF was detected in 90.5% of 285 human urine samples (median, 1.16 ng/μg creatinine). BPF exposure induced cardiomyocyte hypertrophy, cardiac dysfunction, and intestinal barrier damage, effects contingent on the presence of gut microbiota. Metabolomic analysis identified the microbial conversion of BPF to N-acetylputrescine (NAP). Mechanistically, we found that BPF stimulated intestinal epithelial cells to secrete spermidine/spermine N1-acetyltransferase 1 (Sat1), which catalyzed this conversion. Furthermore, NAP impaired the intestinal barrier by disrupting the Golgi-mitochondria axis and caused cardiac hypertrophy by activating the p53 pathway and inhibiting glycolysis in cardiomyocytes. Supplementation with Akkermansia muciniphila or its metabolite tryptophol mitigated BPF-induced cardiac and intestinal injuries by downregulating the Sat1-NAP axis. Clinical analysis further showed elevated serum NAP levels in patients with inflammatory bowel disease, positively correlating with cardiac injury markers.

CONCLUSIONS: BPF disrupts intestinal barrier function through microbial metabolism involving the tryptophol/Sat1 pathway, leading to NAP production. NAP damages intestinal organelles and enters circulation, inducing cardiac p53 activation and hypertrophy. This study delineates a novel gut microbiota-Sat1-NAP pathway underlying BPF-induced cardiotoxicity, offering new insights for risk assessment and therapeutic intervention.},
}